+ ee Ogee oe we 4 ote joka hide bees Spm een em ay Sn ee ae - Sates." in Te Se A : aa ~ vee i ; és Pye i R “ — : ee dome 4 3 = \ =. Reg PS, ‘ . E . “rate vives : < ‘ x at <5 re cee arene c < oy 7 Po tn ty teed ae ed een OD eee me oo Aah ean ano ee een eos pe ee eee Se on penn aemeeomae ee OS EO Le ORES Wee Senet ate hater h ainek tet eae cereale khong eek a as ee eget yh? <3 o L " ‘“ - a \ ¢ \ ~~ \ ° ° a \ ‘ * C x > * “ X “ ° * - . A) 4 7, \ * o \ * ‘. é ® \ \ NF ‘ \ 4 \ 4 7 . P - , . ¥ , \ . R \ \ a - . & y * P A 3 , f < ' ‘ x Z : ; 7 - i i , x < ¥, , yy " . — : 3 ? g a x \ ‘ - ae. “se 7 te / “ 7 ‘ so . tg §N ” heat 7 ft ¢ . , a sO? . < ~ uy . ’ 7 nN ‘ X - . ‘ , y = Digitized by Google COLOR ADDITIVES HEARINGS BEFORE THE / COMMITTEE ON INTERSTATE AND FOREIGN COMMERCE, HOUSE OF REPRESENTATIVES EIGHTY-SIXTH CONGRESS SECOND SESSION ON H.R. 7624 A BILL TO PROTECT THE PUBLIC HEALTH BY AMENDING THE FEDERAL FOOD, DRUG, AND COSMETIC ACT SO AS TO AUTHORIZE THE USE OF SUITABLE COLOR ADDITIVES IN OR ON FOODS, DRUGS, AND COSMETICS, IN ACCORDANCE WITH REGULATIONS PRESCRIBING THE CONDITIONS (INCLUDING MAXIMUM TOLERANCES) UNDER WHICH SUCH ADDITIVES MAY BE SAFELY USED S. 2197 AN ACT TO PROTECT THE PUBLIC HEALTH BY AMENDING THE FEDERAL FOOD, DRUG, AND COSMETIC ACT SO AS TO AUTHORIZE THE USE OF SUITABLE COLOR ADDITIVES IN OR ON FOODS, DRUGS, AND COSMETICS, IN ACCORDANCE WITH REGULATIONS PRESCRIBING THE CONDITIONS (INCLUDING MAXIMUM TOLERANCES) UNDER WHICH SUCH ADDITIVES MAY BE SAFELY USED JANUARY 26, 27, 29, FEBRUARY 10, 11, MARCH 11, APRIL 5, 6, AND MAY 9, 1960 Printed for the use of the Committee on Interstate and Foreign Commerce UNITED STATES GOVERNMENT PRINTING OFFICE 56123 WASHINGTON : 1960 COMMITTEE ON INTERSTATE AND FOREIGN COMMERCE OREN HARRIS, Arkatisas, Chairman JOHN BELL WILLIAMS, Mississippi PETER F. MACK, Jr., Illinois KENNETH A. ROBERTS, Alabama MORGAN M. MOULDER, Missouri HARLEY O. STAGGERS, West Virginia WALTER ROGERS, Texas SAMUELN, FRIEDEL, Maryland JOUN J, FLYNT, Jk., Georgia TORBERT H. MACDONALD, Massachusetts GEORGE M, RHODES, Pennsylvania JOHN JARMAN, Oklahoma LEO W. O'BRIEN, New York JOUN E, MOsS, California JOHN D. DINGELL, Michigan JOE M. KILGORE, Texas PAUL G. ROGERS, Florida ROBERT W. HEMPHILL, South Carolina DAN ROSTENKOWSKI, Illinois LAWRENCE BROCK, Nebraska JAMES C, HEALEY, New York JOUN B. BENNETT, Michigan WILLIAM L. SPRINGER, Illinois PAUL F. SCHENCK, Ohio STEVEN B, DEROUNLAN, New York J, ARTHUR YOUNGER, California WILLIAM H. AVERY, Kansas HAROLD R. COLLIER, Illinois MILTON W. GLENN, New Jersey SAMUEL L, DEVINE, Ohio ANCHER NELSEN, Minnesota HASTINGS KEITIL, Massachusetts WILLARD 8. CURTIN, lennsyivania W. E. Wintiamson, Clerk KENNETH J. PAINTER, Assistant Clerk Professional Staff ANDREW STEVENSON Kurt BORCHARDT ll Saw G. Sra Manktin W, Cunsryenam CONTENTS Statement of — Dr. Harold, medical adviser, Consumers Union Aaron um, Dr. -) Nationa nstitute and department of biology, Princeton University—... 2.000. ..0.000.---2----- 406, 433, 465 Booras, Ann resident, 1 ‘ederation of Homemakers_....-.---...--. 153 > Division, Office of 364 at a Nerien _ Se ee _ B64 Ca wnon, Dr. Paul R., U hiversity of C hice y kOe 406, 4°3, 465 varney, Dr. Thotnas, vice president, ally TOL vee 253, 265 ‘ : ? at gricultural Research rvice, } ment of Avricuuture. . 00.2202 22 ee ee B64 Darby, Dr Witla J. departrent of biochemistry, Vanderbilt Uni- 433, 465 ment of Agriculture, “Western Utilization em mning, . mi tary eaith, Welfare 70-2 ene eens 38, 499 Forsythe yD ationa € nigrec ie nis : 329 Rensler, T . Charles J., department of Rarmacology, Boston Uni- versity School o' edicine_ ee eee eee ee 433, 465 King, Hon. David 8., a Representative in Congress from the State of 245 neaustry, Ne. 22 Le ee 2: Larrick, George P., Comnnissiontr Food and Drug Administration —_ 38 364 406, 433, 465 Levin, Dr. Morton L., Roswell Park Memorial Institute... _—- atson, Edw = director of scientific administration, Abbott Laboratories 20002 Mider, Tr. C. Burr: >ruhs, Associate Director in Charge of Research, . Iv CONTENTS Statement of—Continued Miller, A. R., Director, Meat Inspection Division, Seer of Page ——1 ——err eee ry eet Y OFT CONST 39 465 Mulford, Kenneth E., chairman, food additives committee, Manu- Bso0ciation, 1me...........-..-----.-----.-- 232 Noone, JA, vat adviser, x ational Agricultural Chemicals Association... .. 179 r. alter K., Sloan-Wettering Institute for Cancer Research, division of preventive medicine.......-..-_-_------- 406, 433 Peterson, J. Hardin, special counsel, Florida Citrus Mutual....2.__- 158 "kering, John ertined Color Industry Committee______-___._- 136 Popham, WL, Deputy Administrator, Crops Regulatory Programs, ; Ericuit 364 Riley, George D., Tegislative representative, AFL-CIO 145 Schramm, Arthur T., representing Certified Color Industry Com- mittee. 002 136 Starkey, Ione Dennis, homemaker_____....._-..--------------- eee 229 Pal Stewart, Dr. Harold L. National C Sullivan, on, Leonor Z r: Ab 0 > : issourie- ee 109 Tannenbaum, Dr. Albert, Medical Research Institute eese Hospital_ ~~~ ------ee 06, 433, 465 Williams, ivan Brown, Pharmaceutical Manufacturers Associa- ancer Institute_.._...--__- 406, 433, 465 —__see Additional information submitted for the record by— Letter from “anita Gerden secretary and eneral counsel. 2.222. OZ 4570 Recommendations-of 210 Scientific aa in law and regulation, by Edward J. Matson, director of scientific administration. . 2... ...0 22-22-02 22k 219 Agriculture Department, letter from True D. Morse, Acting Secre- TATV oo ee BOL 61 559 S551 EL. 582. rown, Eric V., letter from. —.- - wean eneeeeen------------- 552 Carney, Dr. Thomas, safety of diethylstilbestrol....-.------------- 295 Tentral Soya Co., statement of Harolc MeMillen....---------- 459 ertife olor Ta ustry Committee, etter rom— ickering, John H., attorney_____. lL lL _li.--------------- 595 Schramm, Arthur T., chairman.....-.----.-.-------+-+------ AYR Darby, Dr. « letter from... 22-22 - 2 ee eee 493 Doughboy Industries, Ine., letter from EB, J. Cashman, president... 553 General Federation of W ‘omen’s Clubs, statement of ____.--..------- 186 Health, Edueation, and Welfare Department: Estimate of cost of enforcement of proposed Color Additive Amendments of 1959, table... 2-22-22 eee 33 Explanation of principal features and purposes of proposed color additive amendments of 1959__ 2-02.02 23 Letter from Hon. Arthur 8. Flemming, Secretary, transmitting draft bill. -. ---_-__-.----------------------- 15 Letter from George P, Larrick, Commissioner of Food and Drugs, transmitting information with respect to lipstick colors_—.——— 130 Letters from Hon. Arthur 8, Flemming, Seeretary_—__—- _. °6, 37, 188, 217, 496, 497, 498, 539 CONTENTS Vv Additional information submitted for the record by—Continued Health, Edueation, and Welfare Department—Continued alams700 Spice . 61 502 president. ...---.-.--+----+---------------------------- +--+ Kansas State Board of Health: , Letter from Evan Wright, director, food and drug division, transmitting resolution... ....--.--.--------------------- 565 Letters from Dr. Geoffrey Martin, executive secretary —~ ~~~ -- 247, 249 Kensler, Dr. Charles J., curriculum vitae... ...-.--.------------- AOS 185 itives committee, transmitting Statement 2.202 eee ee e+ +--+ ---- 545 Mider, Dr. George Burroughs, curriculum vitae_.....-..--.------ 407 Missouri, University of, Jetter from J. H. Longwell, director, division of agricultural sciences, transmitting statement__..-_..---------- 565 National Agricultural Chemicals Association, letter from— 187 189 Martin, secretary-manager_............-.--------------------- 554 National Association of Margarine Manufacturers, statement of Siert F. Riepma, president..._.....---.-.-------.------------- 541 National Canners Association, letter from Carlos Campbell, execu- tive secretary. 20-00 + -- 598 National Paper Box Manufacturers Association, Ine., letter from Robert R. Hershman, executive assistant. ..222222-2---2 2 eee 184 National Starch and Chemical Corp., American Parboard Division, telegram from W. K. Grubman___ 549 Newton Paper Co.,, letter from W. W. Newton, president. .2.2.22-.--- 549 Nichols, Dr, Joe D., statement of... 2-20 ee eee 548 Nutritional Study Group of Cape Arthur, statement of Jane W. Hetrick -_-..2_ 222-2 eee 539 Pfizer, Chas., & Co., letter from Allan J. Greene, administrative vice president. .2 20-0000. ce eee ce ee ee 593 Pharmaceutical Manufacturers Association, letter from Edward Brown Williams, transmitting supplementary statement. . 2.22.0... .--__ 588 President’s Seience Advisory Committee, report of panel on food addi- dives eee +--+ BOL ao - 2-2 ---------- ~~ 2 eee 359 and “(2) the seope of judicial review of such order shall be in accordance with the third sentence of paragraph (2), and with the provisions of para- sraph (3), of section 400(¢). “Fees “(e) The udmitting to listing and certification of color additives, in accord- anes with regulations prescribed under this Act, shall be performed only upon parment of such fees, which shall be specified in such regulations, as may be necessary to provide, maintain, and equip an adequate service for such purposes. COLOR ADDITIVES 13 “Exemptions “(f) The Secretary shall by regulation (issued without regard to subsection (d) provide for exempting from the requirements of this section any color ad- ditive or any specific type of use thereof, and any article of food, drug, or cos- metic bearing or containing such additive, intended solely for investigational use by qualified experts when in his opinion such exemption is consistent with the public health.” CONFIDENTIALITY OF TRADE SECRETS Sec. 104. Section 301(j), as amended, of such Act, prohibiting disclosure of trade secrets, is amended by striking out ‘or 704” and inserting in lieu thereof “704, or 706”. CHANGES IN CROSS-REFERENCES AND TERMINOLOGY Sec. 105. Such Act is further amended by— (a) striking out, in section 301(i) thereof (relating to forgery or unau- thorized use of certain identification devices), “404, 406(b), 504, 506, 507, or 604", and inserting in lieu thereof “404, 506, 507, or 706” ; (b) (1) striking out, in clause (3) of section 303 (c) (relating to color manufacturer's guarantee), the word “coal-tar” wherever it appears in such clause, and (2) inserting after the word ‘color’, wherever it appears in such clause, the word “additive”; and (ec) striking out “harmless coloring” in section 402(d) (relating to non- nutritive substances in confectionery) and inserting in lieu thereof “au- thorized coloring”. TITLE II—EFFECTIVE DATE, TRANSITIONAL PROVISIONS, AND EFFECT ON OTHER LAWS DEFINITIONS Sec. 201. As used in this title, the term “basic Act’ means the Federal Food, Drug, and Cosmetic Act; the term “enactment date’ means the date of enact- ment of this Act; and other terms, insofar as also used in the basic Act (whether before or after enactment of this Act) shall have the same meaning as they have, or had when in effect, under the basic Act. EFFECTIVE DATE Sec. 202. This Act shall, subject to the provisions of section 203, take effect on the enactment date. PROVISIONAL LISTINGS OF COMMERCIALLY ESTABLISHED COLOKS Sec. 203. (a)(1) The purpose of this section is to make possible, on an in- terim basis for a reasonable period, through provisional listings, the use of com- mercially established color additives to the extent consistent with the public health, pending the completion of the scientific investigations needed as a basis for making determinations as to listing of such additives under the basic Act as amended by this Act. A provisional listing (including a deemed provisional listing) of a color additive under this section for any use shall, unless sooner terminated or expiring under the provisions of this section, expire (A) on the closing date (as defined in paragraph (2) of this subsection) or (B) on the effective date of a listing of such additive for such use under section 706 of the basie Act, whichever date first occurs. (2) For the purposes of this section, the term ‘closing date” means (A) the list day of the two and one-half year period beginning on the enactment date or (B), with respect to a particular provisional listing (or deemed provisional listing) of a color additive or use thereof, such later closing date as the Secre- tary may from time to time establish pursuant to the authority of this para- graph. The Secretary may by regulation, upon application of an interested person or on his own initiative, from time to time postpone the original closing date with respect to a provisional listing (or deemed provisional listing) un- der this section of a specified color additive, or of a specified use or uses of such additive. for such period or periods as he finds necessary to carry out the purpose of this section, if in the Secretary's judgment such action is consistent with the objective of carrying to completion in good faith, as soon as reason- 14 COLOR ADDITIVES ably practicable, the scientific investigations necessary for making a determi- nation as to listing such aditive, or such specified use or uses thereof, under section 706 of the basic Act. The Secretary may terminate a postponement of the closing date at any time if he finds that such postponement should not have been granted, or that by reason of a change in circumstances the basis for such postponement no longer exists, or that there has been a failure to comply with a requirement for submission of progress reports or with other conditions at- tached to such postponement. (b) Subject to the other provisions of this section— (1) any color additive which, on the day preceding the enactment date, was listed and certifiable for any use or uses under section 406(b), 504, or 604, or under the third proviso of section 402(c), of the basic Act, and of which a bateh or batches had been certified for such use or uses prior to the enactment date, and (2) any color additive which was commercially used or sold prior to the enactment date for any use or uses in or on any food, drug, or cosmetic, and which either (A) on the day preceding the enactment date was not a mate- rial within the purview of any of the provisions of the basic Act enumerated in paragraph (1) of this subsection, or (B) is the color additive known as synthetic beta-carotene, shall, beginning on the enactment date, be deemed to be provisionally listed under this section as a color additive for such use or uses. (ec) Upon request of any person, the Secretary, by regulations issued under subsection (d), shall without delay, if on the basis of the data before him he deems such action consistent with the protection of the public health, provi- sionally list a material as a color additive for any use for which it was listed, and for which a batch or batches of such material had been certified, under sec- tion 406(b), 504, or 604 of the basic Act prior to the enactment date, although such color was no longer listed and certifiable for such use under such sections on the day preceding the enactment date. Such provisional listing shall take effect on the date of publication. (d) (1) The Secretary shall, by regulations issued or amended from time to under this section— (A) insofar as practicable promulgate and keep current a list or lists of the color additives, and of the particular uses thereof, which he finds are deemed provisionally listed under subsection (b), and the presence of a color additive on such a list with respect to a particular use shall, in any proceeding under the basic Act, be conclusive evidence that such provisional listing is in effect : (B) provide for the provisional listing of the color additives and partic- ular uses thereof specified in subsection (c) ; (C) provide, with respect to particular uses for which color additives are or are deemed to be provisionally listed, such temporary tolerance limita- tions (including such limitations at zero level) and other conditions of use and labeling or packaging requirements, if any, as in his judgment are necessary to protect the public health pending listing under section 706 of the basic Act; (D) provide for the certification of batches of such color additives (with or without diluents) for the uses for which they are so listed or deemed to be listed under this section, except that such an additive which is a color additive deemed provisionally listed under subsection (b)(2) of this see- tion shall be deemed exempt from the requirement of such certification while not subject to a tolerance limitation; and (E) provide for the termination of a provisional listing (or deemed pro- visional listing) of a color additive or particular use thereof forthwith when- ever in his judgment such action is necessary to protect the public health. (2)(A) Regulations under this section shall, from time to time, be issued, amended, or repealed by the Secretary without regard to the requirements of the basic Act, but for the purposes of the application of section T06(e) of the basic Act (relating to fees) and of determining the availability of appropriations of fees (and of advance deposits to cover fees), proceedings, regulations, and certifications under this section shall be deemed to be proceedings, regulations, and certifications under such section 706. (B) On and after the enactment date, regulations, provisional listings, and certifications (or exemptions from certification) in effect under this section shall, for the purpose of determining whether an article is adulterated or mis- branded within the meaning of the basic Act by reason of its being, bearing, or COLOR ADDITIVES 15 containing a color additive, have the same effect as would regulations, listings, and certifications (or exemptions from certification) under section 706 of the basic Act. A regulation, provisional listing or termination thereof, tolerance limitation, or certification or exemption therefrom, under this section shall not be the basis for any presumption or inference in any proceeding under section 706(b) or (c) of the basic Art. (3) For the purpose of enabling the Secretary to carry out his functions under paragraph (1)(A) and (C) with respect to color additives deemed provisionally listed, he shall, as soon as practicable after enactment of this Act, afford by public notice a reasonable opportunity to interested persons to submit data rele- vant thereto. If the data so submitted or otherwise before him do not, in his judgment, establish a reliable basis for including such a color additive or par- ticular use of uses thereof in a list or lists promulgated under paragraph (1)(A), or for determining the prevailing level or levels of use thereof prior to the enact- ment date with a view to prescribing a temporary tolerance or tolerances for such use or uses under paragraph (1)(C), the Secretary shall establish a tem- porary tolerance limitation at zero level for such use or uses until such time as he finds that it would not be inconsistent with the protection of the public health to increase or dispense with such temporary tolerance limitation. EFFECT ON MEAT INSPECTION AND POULTRY PRODUCTS INSPECTION ACTS Sec. 204. Nothing in this Act shall be construed to exempt any meat or meat food product or any person from any requirement imposed by or pursuant to the Meat Inspection Act of March 4, 1907 (34 Stat. 1260), as amended or extended (21 U.S.C. 71 and the following), or the Poultry Products Inspection Act (21 U.S.C, 451 and the following). Passed the Senate August 24, 1959. Attest: FELTON M. JOHNSTON, Secretary. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, May 29, 1960. Hon, Sam Raygurn, Speaker of the House of Representatives, Washington, D.C. Drak Mr. SPEAKER: We are enclosing herewith a draft bill to protect the public health by amending the Federal Food, Drug, and Cosmetic Act so as to authorize the use of suitable color additives in or on food, drugs, and cosmetics, in accord- ance with regulations prescribing the conditions (including maximum tolerances) under which such additives may be safely used. The bill may be referred to by the short title “Color Additive Amendments of 1959.” We respectfully urge the prompt consideration and enactment of this bill by Congress. The bill is designed to meet a pressing need for replacing the inconsistent, and in part outmoded, provisions which now govern the use of different kinds of color for articles covered by the Federal Food, Drug, and Cosmetic Act, with a scien- tifically sound and uniform system for the listing of color additives of any kind which may safely be used in foods, drugs, or cosmetics, subject, when necessary, to appropriate tolerance limitations and other conditions of use and to official certification of batches of color so as to assure the safety of such use to the consumer. The principal reasons which give rise to the need for this legislation may be summarized as follows: 1. The law with respect to coal tar colors—and this comprises most synthetie colors—is not in consonance with modern concepts of consumer protection, in that it does not allow us to list a color for safe use under regulations which place a limit on the amount of a color that may be used on an article and to establish other conditions of use. For food, and for drugs and cosmetics other than those externally applied, we must ban the use of such a color completely, as not being “harmless,” if it is found to be toxic in the laboratory when fed in some concen- trations, even though its actual level and manner of use may be completely safe; for externally applied drugs and cosmeties the same principle applies if toxicity appears in the laboratory in some concentrations by any relevant type of test, even though its actual level and manner of use is wholly safe. 16 COLOR ADDITIVES The principle of allowing colors to be used under tolerance limitations was endorsed, in 1956, by a committee of recognized scientists appointed by the Na- tional Academy of Sciences to review the coal tar color research program of the Food and Drug Administration, as indicated by the following excerpt from the Committee's report: “This Committee feels compelled to indicate that certifica- tion of a compound as ‘harmless and suitable for use’ in food, drugs, and cos- metics as required under present law is unrealistic unless the level of use is specified.” 2. The theoretically “perfect” public health protection once thought to be accorded by the present law regarding coal tar colors has turned out to be in fact inadequate. While, theoretically, only “harmless” colors may be listed, a retesting program of the Food and Drug Administration, employing the most modern testing techniques, has led to the discovery that many, perhaps most, of the so-called colors on the list may in fact be toxic in some concentrations ; yet we cannot take a particular color off the list until we establish its toxicity by laboratory tests, a process which for the list as a whole may take as much as 20 years. Under the bill, there would, in general, be a maximum of 24) years during which the retesting process for the established colors would have to be completed—primarily by industry—and during which we could establish tem- porary tolerance limitations, at zero level if necessary, to protect the public health. This maximum period could be extended only where, in a particular ease, such extension is necessary to complete the required safety tests for a color and is found consistent with protection of the public health. 3. There is a need for making applicable to all color uses and all types of color—whether they be coal tar colors or others—the same pretesting require- ments and, where necessary for the protection of color users and consumers, the same requirements for certification of colors to assure their purity and identity with those listed as safe. At present, there are no provisions for the certification of non-coal-tur colors; there is, moreover, no pretesting requirement for nou- coal-tar color additives as such, other than food additives. 4. Unless the law, as proposed by the bill, is brought into conformity with modern methods of contrel by incorporation of the safe-for-use principle, it will become increasingly difficult, and may eventually became impossible, to find permissible colors to supply the demand for various important color uses on the part of consumers as well as the food, drug, and cosmetic industries. From the standpoint of the public interest there is no compensating advantage for the inflexibility of the present law in this respect. The scientifically sound principle that we must consider conditions of use when passing on suitability and safety of a color additive has recently been approved by Congress in temporary emergeney legislation (Public Law 86-2) with re- spect to one coal tar color, Le. citrus red No. 2 for use in coloring oranges, after previous adoption of the “safe for use” principle in the Food Additive Amendment of 1958 (Public Law 85-929). The only reason we had suggested to Congress that the emergency legislation for citrus red No. 2 have a termina- tion date was that color legislation limited to particular colors and articles of food is discriminatory and that permanent legislation on this subject should contain additional safeguards. Moreover, Public Law 86-2 on its face indicates the expectation that Congress will before long address itself to the problem of general color legislation. The bill—by permitting, for a reasonable period, the provisional listing and certification of heretofore commercially established colors, under temporary tolerances where necessary for public-health protection, pending the development of the scientific data required for a definitive determination as to the listing of these colors under the permanent provisions of the bill—would permit an orderly transition to the control procecures of the bill. At the same time, the bill would establish on a permanent basis a sound system of color regulation. fully protective of consumer interests. A more detailed explanation of the principal changes made in existing law. and the reasons therefor, is attached to the draft bill. There is also enclosed herewith a section-by-section analysis of the bill. The establishment of a tolerance system in this field requires, to an extent not involved in a system without tolerance limitations, a program of edueation of the user industries and public, and a program of enforcement activities by a thoroughly trained corps of inspectors and analysts. The fee provisions, which are the same as those under existing law for coal tar colors, would defray only the cost of maintaining the listing and certification service; additional costs COLOR ADDITIVES 17 would be incurred for the enforcement and informational activities required by the establishment of a tolerance system. Enclosed herewith, as required by Public Law 801, 84th Congress, are statements of cost estimates and personnel requirements which would be entailed. We should appreciate it if you would refer the enclosed draft bill, with the accompanying material, to the appropriate committee for consideration. The Bureau of the Budget advises that there is no objection to the presenta- tion of this proposed legislation to the Congress for its consideration. Sincerely yours, Artuur 8. FLEMMING, Secretary. A BILL To protect the public health by amending the Federal Food, Drug, and Cosmetic Act so as to authorize the use of snitable color additives in or on foods, drugs, and cosmetics, in accordance with regulations prescribing the conditions (including maximum tolerances) under which such additives may be safely used Be it enacted by the Senate and House and House of Representatives of the United States of America in Congress assembled, That this Act may be cited as the “Color Additive Amendments of 1959.” TITLE I—AMENDMENTS TO THE FEDERAL FOOD, DRUG, AND COSMETIC ACT DEFINITIONS Sec. 101. Section 201, as amended, of the Federal Food, Drug, and Cosmetic Act is further amended as follows : (a) Paragraph (s) of such section (defining the term “food additive’) is amended by redesignating clause (8) as clause (4), and by inserting immediately before clause (4), as so redesignated, the following new clause: “(3) a color additive; or”. (b) Paragraph (t) of such section is redesignated and otherwise amended to read as follows: “(u) The term ‘safe’, os used in paragraph (s) of this section and in sections 409 and 706, has reference to the health of man or animal.” (c) There is inserted, immediately after paragraph (s) of such section, the following new paragraph: “(t) (1) The term ‘color additive’ means a material which— “(A) isa dye, pigment, or other substance made by a process of synthesis or similar artifice, or extracted, isolated, or otherwise derived, with or with- out intermediate or final chunge of identity, from a vegetable, animal, mineral, or other source, and “(B), when added or applied to a food, drug, or cosmetic, or to the human body or any part thereof, is capable (alone or through reaction with other substance) of imparting color thereto; except that such term does not include any material which the Secretary, by regulation, determines is used (or intended to be used) solely for a purpose or purposes other than coloring. “(2) The term ‘color’ includes black, white, and intermediate grays.” COLORS OR COLORED ARTICLES--WHEN DEEMED TO BE ADULTERATED OR MISBRANDED FOODS, DRUGS, OK COSMETICS Food Seo. 102. (a) (1) Clause (2)(A) of section 402(a), as amended, of such Act (relating to food deemned adulterated by reason of unsafe additives) is further amended by striking out the matter within the parentheses and inserting in lieu thereof the following: “other than one which is (i) a pesticide chemical in or on a raw agricultural commodity; (ii) a food additive; or (ili) a color additive”. (2) Section 402(¢), as amended, of such Act (relating to food deemed adulterated by reason of uncertified coal-tar color) is amended to read as follows: “(ce) If it is, or it bears or contains, a color additive which is unsafe within the meaning of section 706(a).” (8) Section 403 of such Act (relating to the circumstances under which food is deemed misbranded) is amended by adding at the end thereof the following new paragraph: 18 COLOR ADDITIVES “(1) If it is a color additive, unless its packaging and labeling are in con- formity with such packaging and labeling requirements, applicable to such color additive, as may be contained in regulations issued under section 706.” Drugs (b) (1) Clause (4) of section 501(a) of such Act (relating to drugs deemed adulterated by reason of uncertified coal-tar color) is amended to read as follows: “(4) if (A) it is a drug which bears or contains, for purposes of color- ing only, a color additive which is unsafe within the meaning of section 706(a), or (B) it is a color additive the intended use of which in or on drugs is for purposes of coloring only and is unsafe within the meaning of section 706(a).” (2) Section 502 of such Act (relating to the circumstances under which drugs are deemed misbranded) is amended by adding at the end thereof the follow- ing new paragraph: “(m) If it is a color additive the intended use of which in or on drugs is for the purpose of coloring only, unless its packaging and labeling are in con- formity with such packaging and labeling requirements, applicable to such color additive, as may be contained in regulations issued under section 706.” Cosmetics (ce) (1) Section 601(e) of such Act (relating to cosmetics, other than hair dyes, deemed adulterated by reason of uncertified coal-tar color) is amended to read as follows: “(e) If it is not a hair dye and it is, or it bears or contains, a color additive which is unsafe within the meaning of section 706(a).” (2) Section 602 of such Act (relating to the circumstances under which cosmetics shall be deemed to be misbranded) is amended by adding at the end thereof the following new paragraph: “(e) If it is a color additive, unless its packaging and labeling are in con- formity with such packaging and labeling requirements, applicable to such color additive, as may be contained in regulations issued under section 706. This paragraph shall not apply to packages of color additives which, with respect to their use for cosmetics, are marketed and intended for use only in or on hair dyes (as defined in the last sentence of section 601(a) ).” REGULATIONS TO ASSURE SAFETY OF COLOR ADDITIVES FOR FOODS, DRUGS, AND COSMETICS Seo. 108. (a) Such Act is further amended by— (1) repealing subsection (b) of section 406 and striking out the sub- section designation “(a)” after “Src. 406.” in such section; (2) repealing section 504; (3) repealing section 604; and (4) amending section 701(e) by (A) striking out “406 (a) and (b)” and inserting in lieu thereof “406”; (B) striking out “504, or 604,”; and (C) inserting the word “or” after “501(b),”. (b) Section 706 of such Act is amended to read as follows: “LISTING AND CERTIFICATION OF COLOR ADDITIVES FOR FOODS, DRUGS, AND COSMETICS “When Color Additives Deemed Unsafe “Src. 706. (a) A color additive shall, with respect to any particular use (for which it is being used or intended to be used or is represented as suitable) in or on food or drugs or cosmetics, be deemed unsafe for the purposes of the ap- plication of section 402(c), section 501(a) (4), or section 601(e), as the case may be, unless— “(1)(A) there is in effect, and such additive and such use are in con- formity with, a regulation issued under subsection (b) of this section list- ing such additive for such use, including any provision of such regulation prescribing the conditions under which such additive may be safely used, and (B) such additive either (i) is from a bateh certified, in accordance with regulations issued pursuant to subsection (c), for such use, or (ii) has, with respect to such use, been exempted by the Secretary from the requirement of certification; or “(2) such additive and such use thereof conform to the terms of an exemption which is in effect pursuant to subsection (f) of this section, COLOR ADDITIVES 19 While there are in effect regulations under subsections (b) and (c) of this section relating to a color additive or an exemption pursuant to subsection (f) with respect to such additive, an article shall not, by reason of bearing or con- taining such additive in all respects in accordance with such regulations or such exemption, be considered adulterated within the meaning of clause (1) of sec- tion 402(a) if such article is a food, or within the meaning of section 601(a) if such article is a cosmetic other than a hair dye (as defined in the last sentence of section 601(a)). “Listing of Colors “(b)(1) The Secretary shall, by regulation, provide for separately listing color additives for use in or on food, color additives for use in or on drugs, and color additives for use in or on cosmetics, if and to the extent that such additives are suitable and safe for any such use when employed in accordance with such regulations. “(2)(A) Such regulations may list any color additive for use generally in or on food, or in or on drugs, or in or on cosmetics, if the Secretary finds that such additive is suitable and may safely be employed for such general use. “(B) If the data before the Secretary do not establish that the additive satis- fies the requirements for listing such additive on the applicable list pursuant to subparagraph (A) of this paragraph, or if the proposal is for listing such additive for a more limited use or uses, such regulations may list such additive only for any more limited use or uses for which it is suitable and may safely be employed. “(3) Such regulations shall, to the extent deemed necessary by the Secre- tary to assure the safety of the use or uses for which a particular color addi- tive is listed, prescribe the conditions under which such additive may be safely employed for such use or uses (including, but not limited to, specifications, hereafter in this section referred to as tolerance limitations, as to the maxi- mum quantity or quantities which may be used or permitted to remain in or on the article or articles in or on which it is used; specifications as to the man- ner in which such additive may be added to or used in or on such article or articles; and directions or other labeling or packaging requirements for such additive). “(4) The Secretary shall not list a color additive under this section for a proposed use unless the data before him establish— “(A) that such use, under the conditions of use to be specified tn the regulations, will be safe ; “(B) that practicable methods of analysis exist for determining the quan- tity of the pure dye and all intermediates and other impurities contained in such color additive ; and “(C) that practicable methods exist for determining the identity and quantity (i) of such additive in or on any article of food, drug, or cos- metic, and (ii) of any substance formed in or on such article because of the use of such additive. “(5) (A) In determining, for the purposes of this section, whether a pro- posed use of a color additive is safe, the Secretary shall consider, among other relevant factors— “(i) the probable cosumption of, or other relevant exposure from, the additive and of any substance formed in or on food, drugs, or cosmetics because of the use of the additive, “(ii) the cumulative effect, if any, of such additive in the diet of man or animals, taking into account the same or any chemically or pharmaco- logically related substance or substances in such diet; and “(iii) safety factors which, in the opinion of experts qualified by scien- tific training and experience to evaluate the safety of color additives for the use or uses for which the additive is proposed to be listed, are generally recognized as appropriate for the use of animal experimentation data. “(B) A color additive (i) shall be deemed unsafe, and shall not be listed, for any use which will or may result in ingestion of all or part of such additive, if the additive is found to induce cancer when ingested by man or animal, or if it is found, after tests which are appropriate for the evaluation of the safety of additives for use in food, to induce cancer in man or animal, and (ii) shall be deemed unsafe, and shall not be listed, for any use which will not result in ingestion of any part of such additive, if, after tests which are appropriate for the evaluation of the safety of additives for such use, or after other relevant exposure of man or animal to such additive, it is found to induce cancer in man or animal. 20 COLOR ADDITIVES “(6) The Secretary shall not list a color additive under this subsection for a proposed use if the data before him show that such proposed use would pro- mote deception of the consumer in violation of this Act or would otherwise result in misbranding or adulteration within the meaning of this Act. “(7) If, in the judgment of the Secretary, a tolerance limitation is required in order to assure that a proposed use of a color additive will be safe, the Secretary-— “(A) shall not list the additive for such use if he finds that the data before him do not establish that such additive, if used within a safe toler- ance limitation, would achieve the intended physical or other technical effect; and “(B) shall not fix such tolerance limitation at a level higher than he finds to be reasonably required to accomplish the intended physical or other technical effect. “(8) If, having regard to the aggregate quantity of color additive likely to be consumed in the diet or to be applied to the human body, the Secretary finds that the data before him fail to show that it would be safe and otherwise permissible to list a color additive (or pharmacologically related color additives) for all the uses proposed therefor and at the levels of concentration proposed, the Secretary shall, in determining for which use or uses such additive (or such related addi- tives) shall be or remain listed, or how the aggregate allowable safe tolerance for such additive or additives shall be allocated by him among the uses under consideration, take into account, among other relevant factors (and subject to the paramount criterion of safety), (A) the relative marketability of the articles involved as affected by the proposed uses of the color additive (or of such related additives) in or on such articles, and the relative dependence of the industries concerned on such uses; (8B) the relative aggregate amounts of such color addi- tive which he estimates would be consumed in the diet or applied to the human body by reason of the various uses and levels of concentration proposed; and (C) the availability, if any, of other color additives suitable and safe for one or more of the uses proposed. “Certification of Colors “(e) The Secretary shall further, by regulation, provide (1) for the certifica- tion, with safe diluents or without diluents, of batches of color additives listed pursuant to subsection (b) and conforming to the requirements for such addi- tives established by regulations under such subsection and this subsection, and (2) for exemption from the requirement of certification in the case of any such additive, or any listing or use thereof, for which he finds such requirement not to be necessary in the interest of the protection of the publie health. “Procedure for Issuance, Amendment, or Repeal of Regulations “(d) The provisions of section 701(e), (f), and (g) of this Act shall apply to and in all respects govern proceedings for the issuance, amendment, or repeal of regulations under subsections (b), (¢), or (e) of this section (including judicial review of the Secretary's action in such proceedings) and the admissibility of transcripts of the record of such proceedings in other proceedings, except that— “(1) the Secretary's order after public hearing (acting upon objections filed to an order made prior to hearing) shall be subject to the requiremnts of section 409(f) (2) ; and “(2) the scope of judicial review of such order shall be in accordance with the third sentence of paragraph (2), and with the provisions of para- graph (3), of section 409(g¢). “Fees “(e) The admitting to listing and certification of color additives, in accordance with regulations prescribed under this Act, shall be performed only upon pay- ment of such fees, which shall be specified in such regulations, as may be neces- sary to provide, maintain, and equip an adequate service for such purposes. “Exemptions “(f) The Secretary shall by regulation (issued without regard to subsection (d)) provide for exempting from the requirements of this section any color ad- ditive or any specific type of use thereof, and any article of food, drug, or cos- COLOR ADDITIVES 21 metic bearing or containing such additive, intended solely for investigational use by qualified experts when in his opinion such exemption is consistent with the public health.” CONFIDENTIALITY OF TRADE SECRETS Sec. 104. Section 301(j), as amended, of such Act, prohibiting disclosure of trade secrets, is amended by striking out “or 704” and inserting in lieu thereof “704, or 706”. CHANGES IN CROSS-REFERENCES AND TERMINOLOGY Sec. 105. Such Act is further amended by— (a) striking out, in section 301(i) thereof (relating to forgery or un- authorized use of certain identification devices), “404, 406(b), 504, 506, 507, or 604”, and inserting in lieu thereof “404, 506, 507, or 706”; (b) (1) striking out, in clause (3) of section 303(c) (relating to color manufacturer's guaranty), the word “coal-tar” wherever it appears in such clause, and (2) inserting after the word “color”, wherever it appears in such clause, the word “additive” ; and (c) striking out “harmless coloring” in section 402(d) (relating to non- nutritive substances in confectionery) and inserting in lieu thereof “author- ized coloring”. TITLE II—EFFECTIVE DATE, TRANSITIONAL PROVISIONS, AND EFFECT ON OTHER LAWS DEFINITIONS Sec. 201. As used in this title, the term “basic Act” means the Federal Food, Drug, and Cosmetic Act; the term “enactment date’ means the date of enact- ment of this Act; and other terms, insofar as also used in the basic Act (whether before or after enactment of this Act) shall have the same meaning as they have, or had when in effect, under the basic Act. EFFECTIVE DATE Sec. 202. This Act shall, subject to the provisions of section 203, take effect on the enactment date. PROVISIONAL LISTINGS OF COMMERCIALLY ESTABLISHED COLORS Sec. 203. (a) (1) The purpose of this section is to make possible, on an interim basis for a reasonable period, through provisional listings, the use of commer- cially established color additives to the extent consistent with the public health, pending the completion of the scientific investigations needed as a basis for mak- ing determinations as to listing of such additives under the basie Act as amended by this Act. A provisional listing (including a deemed provisional listing) of a color additive under this section for any use shall, unless sooner terminated or expiring under the provisions of this section, expire (A) on the closing date (as defined in paragraph (2) of this subsection) or (B) on the effective date of a listing of such additive for such use under section 706 of the basic Act, whichever date tirst occurs. (2) For the purposes of this section, the term “closing date” means (A) the last day of the two and one-half year period beginning on the enactment date or (B), with respect to a particular provisional listing (or deemed provisional list- ing) of a color additive or use thereof, such later closing date as the Secretary may from time to time establish pursuant to the authority of this paragraph. The Secretary may by regulation, upon application of an interested person or on his own initiative, from time to time postpone the original closing date with respect to a provisional listing (or deemed provisional listing) under this section of a specified color additive, or of a specified use or uses of such additive, for such period or periods as he finds necessary to carry out the purpose of this section, if in the Secretary's judgment such action is consistent with the objective of carrying to completion in good faith, as soon as reasonably practicable, the scientific investigations necessary for making a determination as to listing such additive, or such specified use or uses thereof, under section 706 of the basic Act. The Secretary may terminate a postponement of the closing date at any time if he finds that such postponement should not have been granted, or that by reason of a change in circumstances the basis for such postponement no longer exists, 22 COLOR ADDITIVES or that there has been a failure to comply with a requirement for submission of progress reports or with other conditions attached to such postponement. (b) Subject to the other provisions of this section— (1) any color additive which, on the day preceding the enactment date, was listed and certifiable for any use or uses under section 406(b), 504, or 604, or under the third proviso of section 402(c), of the basic Act, and of which a batch or batches had been certified for such use or uses prior to the enactment date, and (2) any color additive which was commercially used or sold prior to the enactment date for any use or uses in or on any food, drug, or cosmetic, and which either, (A), on the day preceding the enactment date, was not a mate- rial within the purview of any of the provisions of the basic Act enumerated in paragraph (1) of this subsection, or (B) is the color additive known as synthetic beta-carotene, shall, beginning on the enactment date, be deemed to be provisionally listed under this section as a color additive for such use or uses. (c) Upon request of any person, the Secretary, by regulations issued under subsection (d), shall without delay, if on the basis of the data before him he deems such action consistent with the protection of the public health, provision- ally list a material as a color additive for any use for which it was listed, and for which a batch or batches of such materia! had been certified, under section 406(b), 504, or 604 of the basic Act prior to the enactment date, although such color was no longer listed and certifiable for such use under such sections on the day preceding the enactment date. Such provisional listing shall take effect on the date of publication. (d) (1) The Secretary shall, by regulations issued or amended from time to- time under this section— (A) in so far as practicable promulgate and keep current a list or lists of the color additives, and of the particular uses thereof, which he finds are deemed provisionally listed under subsection (b), and the presence of a color additive on such a list with respect to a particular use shall, in any proceeding under the basic Act, be conclusive evidence that such provisional listing is in effect ; (B) provide for the provisional listing of the color additives and par- ticular uses thereof specified in subsection (c) ; (C) provide, with respect to particular uses for which color additives are or are deemed to be provisionally listed, such temporary tolerance limita- tions (including such limitations at zero level) and other conditions of use and labeling or packaging requirements, if any, as in his judgment are necessary to protect the public health pending listing under section 706 of the basic Act; (D) provide for the certification of batches of such color additives (with or without diluents) for the uses for which they are so listed or deemed to be listed under this section, except that such an additive which is a color additive deemed provisionally listed under subsection (b)(2) of this sec- tion shall be deemed exempt from the requirement of such certification while not subject to a tolerance limitation; and (E) provide for the termination of a provisional listing (or deemed pro- visional listing) of a color additive or particular use thereof forthwith whenever in his judgment such action is necessary to protect the public health. (2) (A) Regulations under this section shall, from time to time. be issued. amended, or repealed by the Secretary without regard to the requirements of the basie Act. but for the purposes of the application of section 70G(e) of the basic Act (relating to fees) and of determining the availability of appropria- tions of fees (and of advance deposits to cover fees), proceedings, regulations, and certifications under this section shall be deemed to be proceedings, regula- tions, and certifications under such section 706, (B) On and after the enactment date, regulations, provisional listings, and certifications (or exemptions from certification) in effect under this section shall, for the purpose of determining whether an article is adulterated or mis- branded within the meaning of the basie Act by reason of its being, bearing, or containing a color additive, have the same effect as would regulations, listings, and certifications (or exemptions from certification) under section 706 of the basic Act. A regulation, provisional listing or termination thereof, tolerance COLOR ADDITIVES 23 limitation, or certification or exemption therefrom, under this section shall not be the basis for any prestunption or inference in any proceeding under section 706 (b) or (c) of the basic Act. (3) For the purpose of enabling the Secretary to carry out his functions under paragraph (1) (A) and (C) with respect to color additives deemed pro- visionally listed, he shall, as soon as practicable after enactment of this Act, afford by public notice a reasonable opportunity to interested persons to submit data relevant thereto. If the data so submitted or otherwise before him do not, in his judgment, establish a reliable basis for including such a color additive or particular use or uses thereof in a list or lists promulgated under paragraph (1), (A), or for determining the prevailing level or levels of use thereof prior to the enactment date with a view to prescribing a temporary tolerance or tolerances for such use or uses under paragraph (1) (C), the Secretary shall establish a temporary tolerance limitation at zero level for such use or uses until such time as he finds that it would not be inconsistent with the protection of the public health to increase or dispense with such temporary tolerance limitation. EFFECT ON MEAT INSPECTION AND POULTRY PRODUCTS INSPECTION ACTS Sec. 204. Nothing in this Act shall be construed to exempt any meat or meat food product or any person from any requirement imposed by or pursuant to the Meat Inspection Act of March 4, 1907, 34 Stat. 1260, as amended or extended (21 U.S.C, 71 et seq.), or the Poultry Products Inspection Act (21 U.S.C. 451 et seq.). EXPLANATION OF PRINCIPAL FEATURES AND PURPOSES OF PRoposeD Cotor ADDITIVE AMENDMENTS OF 1959 The letter of transmittal briefly summarizes the general objectives of this legislative proposal, the principal reasons which gave rise to it, and previous amendments to the Federal Food, Drug, and Cosmetic Act which, in the case of food, show congressional endorsement of its key principle, ie, recognition of the scientific soundness of considering the level and other conditions of use in determining the safety of a color additive. A fuller explanation is, however, necessary to an adequate understanding of the major provisions of the bill and their purposes against the background of existing law. In addition, a section- difference between so-called coal tar colors and others, see the discussion under “Major Changes Proposed.” ) A. PRESENT LAW Under present law, the treatment of color additives differs radically as be- tween the so-called coal tar colors and others. (For explanation of the technical difference between so-called coal tar colors and others, se the discussion under “Major Changes Proposed”.) 1. Coal tar colors.—The act requires the Secretary to provide by regulation for listing and certifying batches of “coal tar colors which are harmless and suitable for use” in food, drugs, or cosmetics; and a food, drug, or cosmetic (other than a hair dye) is deemed adulterated if it bears or contains a coal tar color other than from a certified batch (except that in the case of drugs this provision applies only where the coal tar color is used for coloring purposes only). (See secs. 402(c), 406(b) ; 501(a) (4), 504; 601(e), 604; and 701 (e) and (f) of the act.) Under these provisions, we are without power to admit a color to listing under tolerance limitations. Flemming v. Florida Citrus Exchange, 358 U.S. 153 (1958). 2. Other colors —A coloring material not classified as a coal tar color is not subject to any pretesting, listing, or certification requirement in the case of cosmetics or drugs (except as pretesting may be required for a coloring compo- nent as an incident to official clearance of a new drug under the new drug provisions of the act). On the other hand, with respect to their use in food, non-coal-tar coloring materials which are classed as “food additives” under the recent Food Additives Amendment of 1958 (Public Law 85-929) are subject to a requirement of official safety clearance, and to the establishment of tolerance limitations and other conditions of safe use where necessary for public health protection, except that colors which were in commercial use before January 1, 1958, are allowed a grace period for compliance; this period will expire not later than March 6, 24 COLOR ADDITIVES 1961. Such food additive colors, however, are not subject to any requirement of batch certification even if, in our view, this would be desirable for the protec- tion of food processors and housewives using the color. B. MAJOR CHANGES PROPOSED The bill would change existing law in the following respects: 1. Uniform criteria of admissibility —It would do away with the differences in legal requirements and treatment as between the so-called coal tar colors and other color additives, and would establish an integrated and internally consistent basis for determining the admissibility of any coloring material for use in or on foods, drugs, or cosmetics (other than hair dyes). This would be accomplished by excepting color additives (as defined in the bill) from the term “food addi- tive’; repealing the present provisions for listing and certification of coal tar colors; enacting, as part of a single section (sec. 706), comprehensive provisions for the separate listing of any color additives suitable and safe for general or restricted use in foods, drugs, or cosmetics, and for their certification (or exemp- tion from certification) ; and making other amendments to the act to mesh with these provisions. The term “coal tar color” has been interpreted to apply not only to substances which are coal tar derivatives, but also to synthetic substances so related in their chemical structure to a coal tar constituent as to be capable of derivation there- from even when not actually so derived. The present bill would embrace all color additives whether or not synthesized and whether or not capable of deriva- tion from a coal tar constituent. From the point of view of determining safety of use, there is no sound scientific basis for distinguishing between a color additive extracted from a plant, animal, or mineral source and one which is synthesized with a chemical structure which will bring it under the term “coal tar color.” The bill would therefore establish common ground rules for all such colors. Doing away with the distinction between so-called coal tar colors and other coloring substances will have the incidental effect of establishing a pretesting and safety clearance requirement for the latter type of colors in the case of drugs or cosmetics. The lack of consumer protection inherent in the absence of such a requirement was forcefully brought to the attention of Congress by the investigations and recommendations of the House Select Committee to Investi- gente the Use of Chemicals in Foods and Cosmetics (Delaney committee) (see H. Rept. No. 2356, and H. Rept. No. 2182, 82d Cong.) and by the hearings cul- minating in the enactment of the Food Additives Amendment of 1958. 2. Safety-of-use principle—The bill adopts for all colors, and for all color uses covered by it, the basic principle of the Food Additives Amendment of 1958, by providing for the official listing of color additives for amy use in or on foods, drugs, or cosmetics, for which they are determined to be safe, subject to such ecnditions of use (including maximum tolerance limitations) as are determined to be necessary to assure the safety of such use. 3. Comprehensive lists.—The bill, however, retains the approach of the pres- ent coal tar color provisions in providing for comprehensive: lists of colors, in- stead of attempting to carve out an exception from listing for colors “generally recognized” by experts as safe for use. While there may have been justification in the case of the Food Additives Amendment of 1958 for placing the burden on the Government to prove that an additive is not generally recognized as safe before the safety clearance procedure applies—in view of the broad sweep of the amendment, which otherwise would have covered such additives as salt, vinegar and natural spices—we do not believe that such an exeeption is sound in the ease of color additives, whether they be extracted from a natural source of synthesized. To engraft such an exception on the bill would be retrogressive as compared with present law relating to coal tar colors, If a color is in fact generally recognized by competent experts as safe for unrestricted use in any kind of article, this ean be readily established and reflected in regulations list- ing such color. 4. Certification and exemptions from certification —While providing for certi- fication of batches of listed colors, as existing law does for eoal tur colors, the bill would permit the Secretary to grant exemptions from the requirement of certification where certification is not necessary to protect the public health. The present requirement of certification for coal tar colors is intended to assure food processors and bonsewives that the color is free from toxic impurities and otherwise complies with regulations refining the color's. identity: We believe - COLOR ADDITIVES 25 however, that power to exempt colors from the certification requirement is de- sirable, especially since the coverage of the law is broadened to include all types of substances capable of imparting color. 5. Effective date and transitional provisions.—The amendments made by the bill to the Federal Food, Drug, and Cosmetic Act, i.e., title I of the bill, would become effective as soon as the bill is enacted. However, in order to allow on an interim basis, for a reasonable period, the use of commercially established color additives to the extent consistent with the public health, pending completion of the scientific investigations needed as a basis for making determinations as to listing of such additives under the new permanent provisions of the bill, the bill provides for the provisional listing of such color additives, and their certification (or exemption from certification in certain cases). The “commercially established” color additives falling under these transitional provisions are (a) those coal tar colors of which a batch or. batches were actually certified prior to the date of enactment of the bill, and (b) those non-coal-tar colors, and synthetic beta-carotene, which were commer. cially used or sold prior to that date for food, drug, or cosmetic use. Provisional listings would be subject to appropriate temporary tolerance limi- tations and other conditions of use when deemed necessary for the protection of the public health during the period of provisional listing. The bill would permit establishment of a zero tolerance or removal from the provisional list at any time during this transitional period when the protection of the public health so requires. A provisional listing would be automatic, except that in the case of a coal tar color which was “delisted” prior to the enactment date of the bill, the color could be provisionally listed under these transitional provisions only upon re- quest to the Secretary. In order to enable the Secretary to compile and promulgate a list of colors which are deemed provisionally listed without specific request to the Secretary, and in order to enable him to determine temporary tolerances for such colors, the Secretary would, after reasonable public notice for submission of data, be required, for the time being, to fix temporary tolerances at zero level with re- spect to those colors and uses theresft for which the data available to him do not establish a reliable basis for inclusion in a list of colors deemed provisionally listed and for determining the prevailing levels of use thereof prior to the enact- ment date. In general, a provisional listing would terminate no later than the end of the 2\4-year period beginning on the date of enactment. However, where necessary to complete the scientific testing required for a particular addi- tive, the Secretary could extend this period with respect to a particular color additive or use, if this is consistent with the protection of the public health and with the objective of completing these tests as soon as prac- ticable. Of course, a provisional listing of a color additive for any use, if not sooner terminated, would cease upon listing of the additive for such use under the permanent provisions of the bill. Cc. NEED FOR THE BILL The interests of consumer protection and of the food, drug, cosmetic, and color industries combine to make urgent the need for enactment of this bill. 1. Consumer protection First: Under present law the Government has to perform extensive re- search to determine whether the colors now listed and being used are in fact harmless and suitable for use in food, drugs, and cosmetics. This testing may require up to 20 years. The bill would require industry to assume the burden of this testing, and would require the tests to be completed within 24% years or, in individual cases, such additional testing period as is shown to be required and to be consistent with public health protection. Further, it would allow the Department to place safe tolerance limitations on the amount of color that may be used and the products on which it may be used during this transition period ; the Department has no such authority under present law. Second: Other important aspects of consumer protection afforded by the bill are (a) that the pretesting requirement would be extended to those non- coal-tar colors, especially those used in cosmetics and drugs, to which it does 26 COLOR ADDITIVES not now apply, and (b) that the requirement of certification of batches of color, where necessary for the protection of the public health, would be extended to all colors. Third: The use of color in foods, drugs, and cosmetics, though largely of value from the point of view of enhancing the marketability of the articles involved, is, in many cases, also in the consumer's interest and affirmatively desired by consumers. This is obviously so not only in the case of cosmetics, many of which are designed and purchased for the very purpose of imparting color, but also in the case of certain foods, e.g., margarine, where consumers demand artificial color. Housewives also frequently purchase certified color for use in home-prepared foods. In drugs, color additives are much used for ready identification, thus helping the pharmacist, the physician, the nurse, and the patient to avoid dangerous mistakes in choosing the wrong bottle or box. Thus, it is in the interest of the consumer that the law be changed so as to make avail- able an adequate supply of colors of the safety of which, for particular uses, the consumer can be assured. 2. Commercial interests The food, drug, cosmetic, and color industries find themselves in a serious situation as the result of the removal of color after color from the lists under the present inflexible provisions of the law. Unless the law, by permitting the listing of colors under safe tolerances, is brought into line with present-day methods of control, the emergency will grow and deepen, an emergency which, we believe, could be relieved for most established colors on a sound and per- manent basis by enacting the provisions of this bill without in any way con- flicting with the need for adequate protection of the public health. There is no justification, from the point of view of the public interest, in driv- ing either color manufacturers or food, drug, or cosmetic producers, dependent upon the use of color, out of business where the particular use of color in- volved is one which can safely be admitted under proper conditions of use (including tolerance limitations and certification requirements) established by this Department. Hence, while, as a consumer protection agency, we are con- cerned first and foremost with the protection of consumer interests, equity to the commercial interests concerned is also a factor in the submission of this proposal. It should, however, be stressed in this connection that we could not agree to a dilution or relaxation of the limitations of the carefully designed transitional provisions of this bill with respect to color additives which have heretofore been in commercial use. The technical provisions and approach of this bill are summarized in detail in the section-by-section analysis enclosed herewith. Suffice it to say here that the bill includes, with necessary adaptations, the substantive safeguards for public health and consumer protection contained in the Food Additives Amend- ment of 1958 so recently considered and adopted by the Congress. SECTION-BY-SECTION ANALYSIS OF “COLOR ADDITIVE AMENDMENTS OF 1959” I. INTRODUCTION Under existing law, so-called coal tar colors are regulated under the Federal Food, Drug, and Cosmetic Act through similar sets of provisions in chapters IV (food), V (drugs), and VI (cosmetics). Food containing a coal tar color is deemed adulterated by section 402(c) of the act unless the color is from a batch certified by the Secretary under section 406; section 406(b) then directs the Secretary to provide for listing coal tar colors that are harmless and suitable for use in food, and to provide for certifying batches of such colors. A drug eontaining a coal tar color solely for coloring purposes is deemed adulterated by section 501(a) (4) unless the color is from a batch certified by the Secretary under section 504; section 504 then directs the Secretary to provide for listing coal tar colors that are harmless and suitable for use in drugs for purposes of eoloring only, and for certifying batches of such colors. A cosmetic (other than a hair dye (defined to exclude eyelash and eyebrow dyes)) containing a coal tar color is deemed adulterated by section 601(e) unless the color is from a batch certified by the Secretary under section 604; section 604 then directs COLOR. ADDITIVES 27 the Secretary to provide for listing coal tar colors that are harmless and suit- able for use in cosmetics, and for certifying batches of such colors. Food colors which are not coal tar colors are, when not generally recognized by experts as safe, regulated as “food additives’ under the Food Additives Amendment of 1958 (Public Law 85-929). Under section 402(a)(2)(C) of the act, a food which is, bears, or contains a food additive is deemed adulterated if the additive is unsafe within the meaning of section 409; and under section 409, the food additive is deemed unsafe unless it and its use (or intended use) conform to a regulation under section 409 announcing the conditions under which the additive may be safely used. The present bill takes color additives out of the scope of the Food Additives Amendment of 1958; repeals the present provisions for the listing and certifi- cation of “harmless” coal tar colors (sections 406(b), 504, and 604); enacts new, integrated provisions for the separate listing of suitable “color additives” safe for use in food, drugs, or cosmetics, under such conditions (including toler- ance limitations) as the Secretary may find necessary to assure the safety of the uses permitted; provides for the certification (or exemption from certifi- eation) of listed color additives for such permitted uses; adapts the adulteration and other provisions of the act to the substantive and other changes involved in the above-mentioned changes; and contains transitional provisions for commer- cially established colors. II. SecTIONAL ANALYSIS TITLE I—AMENDMENTS TO FEDERAL FOOD, DRUG, AND COSMETIC ACT SECTION 101 Amends section 201 (the definitional section) of the basic act as follows: Section 101(a) of the bill redesignates section 201(s) of the basic act, defin- ing the term “food additive,” by excluding color additives from the term “food additive.” While coal-tar colors are already, by implication, outside the scope of the operative provisions of the Food Additives Amendment of 1958 (Public Law 85-929), the express exclusion of “color additives” makes clear that, beginning with the date of enactment of this bill, all color additives (as defined in section 101(c) of the bill) will fall outside the scope of the provisions on food additives. Section 101(b) of the bill redesignates section 201(t) of the basic act as section 201(u) and extends the definition of “safe” to apply to the use of that term in section 706 of the basic act as amended by section 103(b) of the bill. Section 101(c) of the bill adds to section 201 of the basic act a new subsec- tion (t), which defines the term “color additives” as any dye, pigment, or other substance, either synthetic or extracted or otherwise derived, which is capable of imparting color to a food, drug, cosmetic, or the human body, but excluding any material that the Secretary, by regulation, determines is used solely for noncoloring purposes. (Black, white, and intermediate grays are expressly included in the term “color.” ) SECTION 102 Section 102(a). Paragraph (1) adds color additives to the exceptions from section 402(a)(2)(A) of the act, which now declares adulterated any food bearing or containing a poisonous or deleterious added substance which is unsafe within the meaning of section 406 of the act “except a pesticide chemical in or on a raw agricultural commodity and except a food additive.” This paragraph of the bill makes explicit, with regard to color additives, the interpretation of the Supreme Court in Flemming v. Florida Citrus Exchange, 358 U.S. 153 (1958), that section 406(a) of existing law—which authorizes the establishment of tolerances for poisonous or deleterious substances added to food where the addi- tive is required in the production of the food or cannot be avoided by good manufacturing practice—cannot serve as a basis for allowing the use of coal tar colors where marketability of a food depends on such coloring. Under the bill, section 706 of the act would (except during a transitional period) provide the exclusive procedure for the listing (with or withont tolerance limitations) and certification of color additives. Paragraph (2) amends section 402(c) to deem a food adulterated if “it is, or it bears or contains,” a “color additive” which is “unsafe within the meaning of section 706(a)” of the basic act as enacted by the bill. This would replace 56123—60 3 28 COLOR ADDITIVES the present requirement of section 402(c) that deems adulterated a food bearing a coal tar color which is not from a batch certified under section 406(b), and the provisos to section 402(c) with respect to the use of color on oranges (see Publie Law 86-2). (Section 406(b) of the act would be repealed under another section of the bill.) The effect of these changes would be to (a) make the new provisions applicable to all color additives, whether or not they are coal tar colors; (b) extend them to the color additive itself before being added to food; anand (c) use the technique of the Pesticide Chemicals Amendment and Food Additives Amendment by deeming the article adulterated if the additive is “un- safe” under another section (in this case the amended section 706) of the basic act which sets forth the criteria under which the additive shall be deemed unsafe. Paragraph (3) adds to section 403 of the basic act a new subsection (1), whereby a food which is a color additive is deemed misbranded unless packaged and labeled in accordance with packaging and labeling requirements, if any, con- tained in regulations issued under section 706 (as amended by the bill). (Under the basie act’s definition of “food,” a color additive intended to be added to food is itself considered “food” before it is so added.) Section 102(b). Paragraph (1) amends section 501(a) (4) of the basie act to deem adulaterated any drug containing a color additive solely for purposes of coloring, and any color additive which (with respect to its use in or on drugs) is intended solely for coloring purposes, if these are unsafe within the mean- ing of section 706(a) of the act. This would replace the present provision of section 501(a) (4), which deems a drug adulterated if it bears or contains, for purposes of coloring only, a coal tar color other than one from a batch that has been certified under section 504. (Section 504 of the act would be repealed by another section of the bill.) Paragraph (2) adds to section 502 of the basie act a new subsection (m) deeming misbranded a drug which is a color additive the intended use of which in or on drugs is for the purpose of coloring only, unless its packaging and label- ing are in conformity with packaging and labeling requirements, if any, con- tained in regulations issued under section 706. (A color additive is, under the definition of “drug” in the basic act, itself a drug when intended for use as a component of drugs.) Section 102(¢). Paragraph (1) amends section 601(e) of the basic act so as to deem adulterated a cosmetic (other than a hair dye) which is, bears, or contains a color additive which is unsafe within the meaning of section 706 of the act. This would replace the existing provision, which deems adulterated a cosmetie (other than a hair dye) which bears or contains a coal tar color other than one from a batch certified under section 604, (Section 604 of the act would be repealed by another section of the bill.) Paragraph (2) adds to section 602 of the act a new subsection (e) so as te deem misbranded a cosmetic which is a color additive (except a color additive for hair dyes) not packaged and labeled in accordance with packaging and label- ing requirements, if any, under section 706. (Under the definition of “cos- metic” in the basie act, a color additive which is intended for use as a compo- nent of cosmetics is itself considered a cosmetic.) SECTION 103 Subsection (a) repeals those sections (sections 406(b), 504, and 604) of the basic act directing the Secretary to provide for listing, and certification of batches, of coal tar colors which are “harmless and suitable’ for use in food, drugs, and cosmetics, respectively; it also repeals the references to these sec- tions in section 701(e) of the act. The saving provisions of 1 U.S.C., section 109, will, of course, apply to these repeals. Subsection (b) amends section 706 of the act to make more flexible and, inci- dentally, bring together within a single section of the act, the Secretary’s rule- making authority with respect to the use of color additives in or on food, drugs, or cosmetics, (Under present law, section 706 contains only a provision which conditions the admitting to listing and certification of coal tar colors upon the payment of fees. Cf. subsection (e) of section 706 as amended by the bill.) The major provisions of the proposed section 706 are: Section 706(a) The basic operative provision of the section, this subsection deems a color additive unsafe for a particular use (or intended use) in or on food, drugs, or COLOR ADDITIVES 29 cosmetics, for the purposes of the application of sections 402(c), 501(a) (4), and 601 (e), of the act as amended by the bill, unless the color additive is listed under section 706(b) and complies with the conditions of use prescribed by the regu- lations listing the additive, and unless the additive is from a batch certified pursuant to regulations under section 706(c) or is exempted from the require- ment of such certification. The single exception to these requirements is an exemption, to be provided by regulation (under sec. 706(f)), for color addi- tives intended solely for investigational use by qualified experts. Where a color additive is used in accordance with the Secretay’s regulations, it is also exempted from the general provisions that deem adulterated any food (sec. 402(a) (1)) or cosmetic (sec. 601(a)) bearing or containing a poisonous or deleterious substance that may render it injurious to health. This exempting provision does not apply to hair dye (other than eyebrow aand eyelash dye), since coal tar hair dyes are not covered by section 601(e) of the act. Section 706 (b) Paragraph (1): The Secretary is required to establish separate lists of color additives for use in respect to food, drugs, and cosmetics, to the extent that the additives are safe for use when employed in accordance with the regulations listing them. Paragraph (2): The listing of an additive may be for general use in respect to food, or drugs, or cosmetics, or it may be for a more limited use. Paragraph (8): The regulations listing the color additive must, to the extent deemed necessary to assure safety of use, prescribe tolerance limitations, other directions relating to the manner of adding or using the additive, labeling or packaging requirements for such additive, and other conditions, Paragraph (4): A color additive may be listed for use only where it affirma- tively appears that the additive may safely be used under the conditions to be prescribed by regulation; and that there are practicable methods for analyzing its contents, and for determining the identity and quantity of such additive in or on any article of foods, drugs, or cosmetic, and of any substance formed in an article because of the use of the additive. (Cf. secs. 409(b)(2)(D) and 409(c) (3) of the act, relating to food additives. ) Paragraph (5): In determining whether the use of a color additive is safe, the Secretary is required to consider a broad range of factors. In particular, however, a color additive may not be listed if it has relevant carcinogenic poten- tial. (This paragraph is modeled on see, 409(c)(5) and the proviso to sec, 400(¢) (3) (A) of the act, relating to food additives.) Paragraph (6): The Secretary may not list a color additive for a proposed use, if that use would promote deception of the consumer or otherwise result in a misbranding or adulteration within the meaning of other provisions of the act. (A similar provision is contained in sec. 409(c) (3) (B) of the act, for food additives. ) Paragraph (7): If a tolerance limitation is required to assure safety, a color additive may not be listed unless the data establish that, if used within a safe tolerance, the additive will achieve the intended physical or other technical ef- fect; and the permissible tolerance may be set no higher than the level neces- sary to accomplish this effect. This requirement is similar to that imposed on the Secretary by section 409(c) (4) of the act with respect to food additives, Paragraph (8): Where, because of the aggregate quantity of a color additive (or pharmacologically related additives) likely to be involved, the Secretary can- not list the color (or colors) for all proposed uses, he may select among those uses or may apportion the aggregate allowable tolerance among them, subject to the paramount criterion of safety. For the purpose of such selection or al- location, the bill provides for taking into account, among other relevant factors, the marketability of an article as affected by color, and industry dependence on the color uses involved; the quantities of color consumption involved in the various color uses; and the avuilability of other colors. Section 706(c) Directors the Secretary to provide for the certification of batches of color addi- tives, and for exemption from the requirement of certification where unnecessary in the interest of the public health. Under this subsection, the Secretary could provide for conditioning certification of batches of color additives on the keeping of records of disposal, as he does under existing law. 30 COLOR ADDITIVES Section 706 (d) This subsection, in general, incorporates by reference the procedures of section 701(e)-(g) which now govern coal tar colors, except that it adopts the provisions as to “fair evaluation on the basis of the entire record” enacted by the Food Ad- ditives Amendment of 1958. In discussing the provisions of the Food Additives Amendment of 1958 which the present bill incorporates by reference, Assistant Secretary Elliot L. Richard- son, in a letter to the chairman of the House Committee on Interstate and Foreign Commerce, dated August 8, 1958, and reprinted in the Congressional Record, stated: “The Secretary's action after hearing would have to be based upon a fair evaluation of the entire record at the hearing. On judicial review, the U.S. Court of Appeals would be required to sustain the findings of the Secretary if based upon a ‘fair evaluation of the entire record at the hearing’; it would have to reverse the order of the Secretary if it is not ‘based upon a fair evaluation of the entire record’ or if it fails to include a statement setting forth in detail the findings and conclusions upon which the order is based. The ‘fair evaluation’ provision is quite acceptable to the Department, because it is the standard to which we are accustomed to adhere.” (Congressional Record, 85th Cong., 2d sess., Aug. 13, 1958, p. 16016). The “fair evaluation of the entire record” standard thus is to govern the action of the Secretary after hearing, and to be used as a criterion by the review- ing court in passing on the validity of the Secretary's action, not merely as re- spects findings of fact but as respects his action as a whole. It, in effect, extends to rulemaking the approach to judicial review of administrative ad- judication taken in Universal Camera Corporation vy. N.L.R.B., 340 U.S. 474 (1951), and attempts to encapsule in a phrase the requirements of the Adminis- trative Procedure Act as to fairness as opposed to arbitrariness, caprice, and abuse of discretion. Section 706(e) This subsection contains the fee provision (with the reference to coal-tar colors amended to refer to color additives) contained in Section 706 under existing law. Under the amended act fees for admitting a color to listing would necessarily include the cost of setting tolerance limitations authorized by Section 706(b). Section 706(f) The Secretary is required to provide, by regulation not subject to the above- mentioned procedure, for exempting from the operation of Section 706 any color additive or use thereof intended solely for investigational use by qualified ex- perts, when such exemption is consistent with the public health. A similar exemption exists in Section 409(i) of the act for food additives. SECTION 104 Extends section 301(j) of the basic act, which prohibits the revelation and the personal use of trade secrets acquired under the authority of various sections of the act (including sec. 409, relating to food additives), so as to include information obtained under the proposed Section 706. SECTION 105 Contains appropriate changes of cross-references in, and other conforming amendments to, Sections 301(i) (false use of required marks), 803(c) (3) (guarantee that coal-tar color is certified), and 402(d) (non-nutritive substances in confectionery) of the basic act. TITLE Il--EFFECTIVE DATR, TRANSITIONAL PROVISIONS, AND EFFECT ON OTHER LAWS SECTION 201 Defines, for the purposes of title II, the term “basic act” as the Federal Food, Drug, and Cosmetic Act: the term “enactment date” as the date of enactment of the bill: and other terms, insofar as also used in the basic act (whether before or after enactment of the bill) as having the same meaning as they have, or had when in effect, under the basic act. COLOR ADDITIVES 31 SECTION 202 Makes the bill effective upon enactment, subject to the transitional provisions of Section 203. SECTION 203 Subsection (a)(1) declares that this section is intended to make possible, for a reasonable interim period, through provisional listings, the continued use of commercially established color additives to the extent consistent with the public health, pending completion of the scientific tests needed as a basis for making determinations with respect to the definitive listing of such additives under the basie act. Subsection (a)(1) also directs that a provisional listing (which, while in effect, has the same effect as a listing under sec. 706 of the basic act) shall, if bot sooner terminated, expire (i) on the “closing date” or (ii) on the effective date of the additive’s listing under section 706, whichever date first occurs. Subsection (a) (2) defines “closing date” as the last day of the 24-year period bezinning on the enactment date, except that with respect to a particular pro- visional listing, the Secretary could postpone the original closing date for such- period or periods as he finds necessary to carry out the declared purpose of this section, if consistent with the objective of completing in good faith, as soon as practicable, the necessary scientific tests needed to make a determination with respect to listing under section 706 of the basic act. Such postponements could be terminated if they should not have been granted, or on change of circum- stances, on failure to submit required progress reports or meet other conditions. Subsection (b): First, colors subject to those provisions of present law (sec. 406(b), 504, or 604, or the third proviso to sec. 402(c) which require the listing and certification of so-called coal-tar colors, are deemed provisionally listed for any use for which they were actually listed under these provisions on the day preceding the enactment date if a batch or batches of the color had been certified prior to that date. Second, a color additive which is either synthetic beta-carotene or which, on the date preceding the enactment date, was not within the purview of the so-called coal-tar provisions of the law, is deemed pro- visionally listed under the bill for any use of the color for which it was com- mercially used or sold prior to the enactment date. (It should be noted that the term “coal-tar color’—which under existing law is interpreted as including synthetic colors which, though not coal-tar derivatives, are so chemically struc- tured as to be capable of being derived from coal tar—is not used in the bill. Synthetic beta-carotene is separately dealt with in the bill because its classifica- tion with coal-tar colors under existing law is in dispute and has been the subject of a hearing.) Subsection (c) requires the Secretary, upon request, to list provisionally any color for any use for which it had been listed, and for which use a batch had actu- ally been certified, under the above-mentioned coal-tar color provisions of existing law prior to the enactment date, although it was not so listed on the day pre- ceding that date, if he deems such action consistent with protection of the public health. Subsection (d) (1). The Secretary is directed, so far as practicable, (a) to promulgate and maintain current a list of color additives deemed provisionally listed, (d) to provide for provisional listing of color additives upon request in accord ince With subsection (c), (¢) to prescribe, if needed for public-health protection, temporary tolerance limitations (including zero tolerances) and other conditions of use for color additives provisionally listed. (¢@) to provide for the certification of batches of provisionally listed color additives (except that a eelor additive deemed provisionally listed under subsection (b)(2) shall be deemed exempt from certification while not subject to a tolerance): and (e) to provide for the termination of a provisional listing forthwith where necessary to preteet the public health. Subsection (d) (2). Regulations under this section are not subject to the proce- dural requirements of the Federal Food, Drug, and Cosmetie Act, but fees shall be charged (and be available for use) as though the regulations and other pro- coedings under this section had been under section T06 of the basie act as amended by the bill. On and after the starting date. provisional listing and certification under this section have the same effect as listing and certification 32 COLOR ADDITIVES under section 706 for the purpose of determining whether an article is adulterated or misbranded, but provisional listings and other actions under section 203 of the bill shall not give rise to any presumption or inference in section 706 proceedings. Subsection (d)(3). In order that the Secretary may be able to promulgate and keep current a list of color additives deemed to be provisionally listed and to prescribe temporary tolerance limitations and other conditions of use with respect to those additives, he is directed to afford by public notice a reasonable opportunity to interested persons to submit data relevant thereto. If the data submitted or otherwise before the Secretary do not reliably enable him to in- clude a color in the published list of color additives deemed to be provisionally listed, or to ascertain the levels of use of such an additive prevailing prior to the enactment date, the Secretary is directed to fix a temporary zero tolerance for such colors or uses thereof until he deems a higher tolerance, or the absence of a tolerance limitation, consistent with the public interest. SECTION 204 Makes clear that the bill, when enacted, would not relieve any meat or meat food product or any person from any requirement under the Meat Inspection Act of March 4, 1907, as amended or extended (21 U.S.C. 71 et seq.), or the Poultry Products Inspection Act (21 U.S.C. 451 et seq.). 33 *yoasoq) SeYyoIwG BULA} 99 Pur Fup Is] OF SBA] PPC 10]09 AuPIYPUIpY 40) PPI9][OO eq OF S8aj OF UO] PPE UT ale SBIVUITIso asoyT, | 006 “Ys8 OO ul et *) 002 "y ie 006% OUF "8% , OO ‘8% ‘sto O08 ‘Sha O08 REO “OW Hs9UdaT AY “WUaTAOLAUTA ULj[Afo jo SaHaA-UB PY COLOR ADDITIVES 006 "9SSS rag 006 USS rane 006 ‘Yass rags “gass raat 000080 48 GE Pott terre rer sere ees EuO TI ppe WN xem pelvMypisg” qo) siees-uU yy 4509 suras-un py 09 suvad-uu yy pop SUUOAAIY FE wog SUAA-UR IY FO6E £901 2961 1961 0961 —ivat Wwost rbuoy yits ‘TOS avy o1qng fig pasinbas sv Gog] fo sjuaupuaumy aayippy 40j09 pasodosd fo yuauarsofua fo y8oo fo anus 34 COLOR ADDITIVES EXECUTIVE OFFICE OF THE PRESIDENT, BUREAU OF THE BUDGET, Washington, D.C., August 10, 1959. Hon. OREN Harris, Chairman, Committce on Interstate and Foreign Commerce, House of Represer.tatives, House Office Building, Washington, D.C. My Dear Mr. CuarnMan: This is reply to your request of June 11, 1959, for a report from the Bureau of the Budget on H.R. 7624, a bill to protect the public health by amending the Federal Food, Drug, and Cosmetic Act so as to authorize the use of suitable color additives in or on foods, drugs, and cosmetics, in accord- ance with regulations prescribing the conditions (including maximum tolerances) under which additives may be safely used. H.R. 7624 embodies the proposed legislation submitted to the Congress by the Department of Health, Education, and Welfare to establish safe tolerances for the use of color additives in foods, drugs, and cosmetics. The bill is patterned after the Food Additives Amendment of 1958 in which, after pretesting in accord- ance with controlled procedures, the amounts and conditions governing the safe use of food additives is established by regulation of the Secretary. Under the present law regulating the use of color additives, a given additive must be ex- cluded from use if it is found to be harmful under any circumstances even though it may be quite safe if used in more minimal quantities or under certain specific circumstances. The general purpose of the bill is to set aside the obsolete provisions now con- trolling the use of color additives and replace them with provisions which are more realistic and more scientifically sound. Accordingly, the Bureau of the Budget would have no objection to the enactment of H.R. 7624. Sincerely yours, (Signed) Puiu 8. HucHes, Assistant Director for Legislative Reference. EXECUTIVE OFFICE OF THE PRESIDENT, BUREAU OF THE BUDGET, Washington, D.C., April 13, 1960. Hon, Oren Harris, Chairman, Committee of Interstate and Foreign Commerce, House of Representatives, Washington, D.C. My Dear Mr. CuatRMAN: This is in reply to your letter of March 30, 1960, regarding your committee's urgent interest in information on the position of the administration on H.R. 7624, the color additive amendment to the Food and Drug Act. You make specific reference to the so-called Delaney amendment. In earlier testimony on the general subject of the Delaney amendment, the Secretary of Health, Education, and Welfare stated that in the present state of scientific knowledge, and unless otherwise required by law, he would not establish any tolerance for an additive which could enter the human diet if the substance had been found to cause cancer when fed to test animals. Since the Secretary's testimony, this matter has been intensively studied by the executive branch. These studies do not appear to provide the basis for any change at this time in the position expressed by the Secretary. This matter will, of course, be under continuous study, and if additional seientifie evidence indicates that fur- ther relaxation of the Delaney amendment is desirable, it will of course be proposed, The Delaney approach is unnecessarily stringent in one respect, however. Where an additive is used in animal food and leaves no residue in the animal after slaughter or in any food product and does not adversely affect the animal, there is no need to apply the proviso. The Secretary of Health, Education, and Welfare will submit language to modify the Delaney amendment in this regard in the near future. It seems apparent that the Secretary of Health, Education, and Welfare would in any event have the authority to apply the principle of the Delaney amendment to color additives administratively. However, shonld the Congress desire to explicitly require such action, we see no objection to the procedure. We under- stand that representatives of the Departments of Health, Education, and Welfare COLOR ADDITIVES 35 and Agriculture will be appearing further before your committee and can there- fore provide the committee with more detailed information on this matter, Our general comments on H.R. 7624 were presented to your committee in our letter of August 10, 1959. Sincerely yours, PHILLIP 8. HUGHES, Assistant Director for Legislative Reference. DEPARTMENT OF AGRICULTURE, Washington, D.C., August 11, 1959. Hon. Oren Harris, Chairman, Committee on Interstate and Foreign Commerce, House of Representatives. Dear CONGRESSMAN Harris: This is in reply to your request of June 11, for a report on H.R. 7624, a bill to protect the public health by amending the Federal Food, Drug, and Cosmetic Act so as to authorize the use of suitable color addi- tives in or on foods, drugs, and cosmetics, in accordance with regulations pre- scribing the conditions (including maximum tolerances) under which such addi- tives may be safely used. This Department would have no objection to enactment of the proposed legis- lation. The proposed legislation would enable the Secretary of Health, Edu- cation, and Welfare to take a realistic position with respect to the use of colors in food products, many of which are agricultural products. The bill would enable the Secretary of Health, Education, and Welfare to establish tolerance limitations and other conditions of safe use for all color additives in or on foods, drugs, and cosmetics, in a manner similar to that set forth in the Food Additives Amendment of 1958. Under existing law the said Secretary may not establish tolerance limitations for coal tar colors. A color additive would be deemed unsafe under the proposed bill if, among other things, it is found after tests which are appropriate for the evaluation of such additives to induce cancer in man or animals. The proposed legislation also contains a provision that its terms should not be construed to exempt any meat or meat food product or any person from any requirement imposed by or pursuant to the Meat Inspection Act or the Poultry Products Inspection Act. This provision is considered to be consistent with and in no way modifying the provisions of sec- tion 902(b) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 392) which exempts meat and meat food products from the terms of that act to the extent of the application thereto of the Meat Inspection Act. Section 18 of the Poultry Products Inspection Act contains an exemption with respect to poultry and poultry products similar to that contained in section 902(b) of the Federal Food, Drug, and Cosmetic Act for meat and meat food products. We believe that all dyes and colorings for use in or on foods, drugs, and cos- metics should be subject to the same principles presently applicable to food additives. The Secretary of Health, Education, and Welfare should be per- mitted to establish tolerances for these materials, Enactment of the proposed legislation will avoid such special legislation as that enacted recently permitting the addition of coloring to oranges (Public Law 86-2, approved Mar. 17, 1959). The Bureau of the Budget advises that there is no objection to the submis- sion of this report. Sincerely yours, E. L. Peterson, Acting Secretary. DEPARTMENT OF AGRICULTURE, Washington, D.C., April 14, 1960. Hon. Oren Harris, Chairman, Committee on Interstate and Foreign Commerce, House of Representatives. Dear ConaressMAN Harris: This is to supplement the Department's state- ment of March 11, before your committee on H.R. 7624 and 8S. 2197. These bills proposed amendments to the Federal Food, Drug, and Cosmetic Act concerning color additives. The Department, in its testimony, favored amending section 101 of Senate bill 2197 by adding before the period on line 10 of page 3 the following language: 36 COLOR ADDITIVES “or any soil or plant nutrient or any material subject to registration under the Federal Insecticide, Fungicide, and Rodenticide Act.” Dr, Clarkson stated at that time that the language suggested was preliminary and that discussions were being held with representatives of the Department of Health, Education, and Welfare. As a result of these discussions, we are now revising our proposal by recommending that section 101 of 8. 2197 be amended by adding a new paragraph 3 on page 3, as follows: “(3) Nothing in subparagraph (1) of this paragraph shall be construed to apply to any pesti- cide chemical, soil or plant nutrient, or other agricultural chemical solely because of its effect in aiding, retarding, or otherwise affecting, directly or indirectly, the growth or other natural physiological processes of produce of the soil and thereby affecting its color, whether before or after harvest.” I wish to thank you for the courtesies extended Dr, Clarkson in his appear- ance before your committee. Sincerely yours, E. L. Peterson, Assistant Secretary. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, August 7, 1959. Hon, Oren Harris, Chairman, Committee on Interstate and Foreign Commerce, House of Represent- atives, Washington, D.C. Deak Mr. CHarrMAN: We understand that representatives of some of the in- dustries that would be affected by H.R. 7624 (to be known as the “color additive amendments of 1959") have suggested an amendment to the bill, relating to the requirements concerning analytical methods for color additives. Under the bill in its present form (p. 9, lines 3-16), the proposed section 706(b) (4) of the Federal Food, Drug, and Cosmetic Act would preclude the Sec- retary from listing a color additive for any use in or on food, drugs, or cos- metics unless the data before him establish— “(A) that such use, under the conditions of use to be specified in the regulations, will be safe; “(B) that practicable methods of analysis exist for determining the quan- tity of the pure dye and all intermediates and other impurities contained in such color additive; and “(C) that practicable methods exist for determining the identity and quantity (i) of such additive in or on any article of food, drug, or cos- metic, and (ii) of any substance formed in or on such article because of the use of such additive.” The proposed amendment suggested by industry representatives would con- solidate the matter contained in the above-quoted paragraphs (B) and (C) and, with appropriate editorial revision, transfer it to section 706(b) (5), which be- gins on the same page and enumerates some of the most important factors which the Secretary must consider in passing on the safety of a proposed use of a color additive. As so amended, section 706(b) (4) and (5). beginning on page 9, line 8, and ending on page 10, line 10, of the bill, would read as follows: “(4) The Secretary shall not list a color additive under this section for a proposed use unless the data before him establish that such use, un- der the conditions of use specified in the regulations. will be safe. “(5)(A) In determining, for the purposes of this section, whether a pro- posed use of a color additive is safe, the Secretary shall consider, among other relevant factors— “(i) the probable consumption of, or other relevant exposure from, the additive and of any substance formed in or on food, drugs, or cos- metics because of the use of the additive; “(ii) the cumulative effect, if any, of such additive in the diet of man or animals, taking into account the same or any chemically or pharmacologically related substance or substances in such diet; “(iil) safety factors which, in the opinion of experts qualified by scientific training and experience to evaluate the safety of color addi- tives for the use or uses for which the additive is proposed to be listed, are generally recognized as appropriate for the use of animal experi- mentation data; and “(iv) the availability of any needed practicable methods of analysis for determining the identity and quantity of (I) the pure dye and all intermediates and other impurities contained in such color additive, COLOR ADDITIVES 37 (IL) such additive in or on any article of food, drug, or cosmetic, and (III) any substance formed in or on such article because of the use of such additive.” The net effect of the change would be to require the Secretary to determine whether, with respect to particular color additives and proposed listings, all of the analytical methods described both in the original bill and in the proposed amendment are needed and, to the extent that they are, to refuse a listing unless these methods exist and are made available to him, whereas, under the bill as originaally introduced, the Secretary must refuse a listing unless all of the de- scribed methods of analyses are available to him, without regard to whether, with respect to a particular proposed listing of a color additive, such methods are in his judgment actually needed. The proponents of the amendment believe that some of the requirements of the original bill, and in particular the requirement that there be practicable methods for determining the identity and quantity of any substance formed in or on food because of the use of a color additive, could not always be met in the present state of knowledge and that, in those cases in which there is no need for such a method of analysis for adequate public health protection, the requirement would unnecessarily bar the use of a color additive which would be perfectly safe. The purpose of the requirement of the bill that there be practicable methods of analysis for determining the quantity of the pure dye and all intermediates and other impurities contained in a color additive is to enable the manufacturer of the color, and also this Department where we are asked to certify batches of color, to determine that the color in actual practice meets the requirements for purity and the definitional standards of our regulations, and to facilitate enforcement. The purpose of the other requirements as to available practicable methods of analysis is to make possible effective enforcement of any conditions or limitations that may be put on the listing of a color for use in foods, drugs, or cosmetics. We, of course, regard practicability and facility of enforcement as essential elements of safety in determining whether a proposed use of a color additive is safe within the meaning of the bill, There are many circumstances where it would be necessary to have practicable analytical methods for all or most of the above-mentioned purposes. We can, however, visualize some situations in which these analytical methods, or some of them, would not be necessary for any of the purposes which we have men- tioned and would thus not be essential in the interest of sound public health protection. We therefore recognize that in requiring such analytical methods to be available in all cases without regard to actual need the original bill goes further than absolutely necessary for public health protection. Under the proposed change, we would consider ourselves bound to require those analytical methods specified in the bill for which, on the basis of our gen- eral knowledge or on the basis of the particular situation, we find that there is a need for the above-mentioned purposes, or otherwise in the interest of safe- guarding the public health, and we would therefore feel bound to refuse to list a color where such needed methods are not available. At the same time, the proposed amendment would relieve us of the necessity of imposing these requirements where they are not needed. We therefore would not object to the proposed change in the bill. The Bureau of the Budget advises that it perceives no objection to the submis- sion of this report to your committee. Sincerely yours, Extuiot L. RIcHarpson, Assistant Sceretary. DEPARTMENT OF HeALTH, EpvCcaTion, AND WELFARE, Washington, April 11, 1960, Hon. Oren Harris, Chairman, Committee on Interstate and Forcign Commerce, House of Representatives, Washington, D.C. Drak Mr. CHAIRMAN: The purpose of this letter is to recommend a correc- tion in the hearing provision in title I of the proposed Color Additive Amend- ments of 1959 (H.R. 7624 and 8. 2197) now pending before your committee. As drafted by this Department and submitted to Congress, and as contained in these bills, the hearing provision would, through an inadvertent cross-refer- ence to the subsection on fees, provide for hearing and judicial review not only with respect to the issuance, amendment, or repeal of regulations relating to 38 COLOR ADDITIVES the listing and certification of color additives, but also with respect to regula- tions establishing fees for such listing and certification. Under present law as consistently interpreted by us since its enactment, the issuance or amendment of regulations establishing schedules of fees for the listing and certification of coal tar colors is not subject to hearing or judicial review (sec. 706 of Federal Food, Drug, and Cosmetic Act). This likewise holds true in the case of fees for certification services for insulin or antibiotics, fees for the pesticide regulation service, and fees for seafood inspection (secs. 408(0), 506, 507, 702A). The establishment of such fees is purely a matter of cost accounting and, since the services must be self-sustaining, the fees are auto- matically kept at the appropriate level through auditing of expenditures by the General Accounting Office. To provide for hearing and judicial review with respect to the establishment of fees would thus serve no useful purpose and, on the other hand, might cause delay which could seriously impede or make impossible the performance of the services in question. We, therefore, recommend that the provisions of these bills be corrected by changing the phrase “subsections (b), (¢), or (e) of this section” (H.R. 7624, p. 13, line 6; S. 2197, p. 13, line 9) to read “subsection (b) or (c) of this section.” Sincerely yours, ARTHUR §S. FLemMMrine, Secretary. The Carman. The latest report from the Department of Health, Education, and Welfare in the form of a letter dated August 7, 1959, will be included with the original report. The first witness we have is the Honorable Arthur 5S. Flemming, Secretary of the Department of Health, Education, and Welfare. Mr. Secretary, we welcome you here this morning on this highly im- portant legislation, and we will be glad to have your testimony. STATEMENT OF HON. ARTHUR S. FLEMMING, SECRETARY OF HEALTH, EDUCATION, AND WELFARE; ACCOMPANIED BY C. BURROUGHS MIDER, M.D., ASSOCIATE DIRECTOR IN CHARGE OF RESEARCH, NATIONAL CANCER INSTITUTE, NATIONAL INSTI- TUTES OF HEALTH, PUBLIC HEALTH SERVICE; GEORGE P. LAR- RICK, COMMISSIONER, U.S. FOOD AND DRUG ADMINISTRATION; AND ROBERT A. FORSYTHE, ASSISTANT SECRETARY FOR LEGIS- LATION, DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE Secretary Firemaaine. Mr, Chairman and members of the commit- tee, I am very happy to have this opportunity to discuss proposed leg- islation dealing with the use of colors in foods, drugs, and cosmetics. This proposed legislation brings to the fore, it seems to me, certain basic issues bearing on the health of our people, It is appropriate for these issues to be reexamined periodically at a time when technological advances in diverse fields occur with such rapidity that it is difficult to keep pace with their impact on the health of all of us. Because of the nature of the issues involved, I have called upon the total resources of the Department, and particularly those of the Food and Drug Administration and the U.S. Public Health Service, to work with me in the development of the positions which I will place before you this morning. PROPOSED COLOR ADDITIVES AMENDMENT As you have indicated, Mr. Chairman, there are two similar bills pending before the committee; namely, H.R. 7624, which was intro- duced at our request, and S. 2197, which had been introduced by Senator Hill on behalf of himself and Senator Goldwater. COLOR ADDITIVES 39 H.R. 7624 embodies the legislative proposals submitted by the De- partment to the Congress on May 29, 1959. With your permission, Mr. Chairman, I should like to introduce into the record a copy of my letter to the Speaker transmitting the proposal, together with the en- closures explaining the principal features and details of the proposal. The Cuatrman. It will be included with the report referred to a moment ago, Secretary Fiemminc. Thank you, sir. S. 2197, as originally introduced, was identical with H.R. 7624 and our proposal which we submitted, except that the Senate bill omitted the anticancer provision. As reported out of committee and passed by the Senate, S. 2197 also incorporates minor amendments to the bill which are acceptable to us. Thus, if the anticancer clause of the House bill were inserted in S. 2197, we would support it in that orm. The purpose of these bills is to provide a scientifically sound basis for listing the colors that may be safely used in foods, drugs, and cos- metics; and to provide for other safeguards in the use of such colors, including, where necessary, appropriate tolerance limitations on the amount of color that may be used. The bills also would provide for a continuation of the present system of certifying the safety of indi- vidual batches of the so-called coal tar colors and would extend this system, where necessary, to natural colors not now covered by the cer- tification system. They would, on the other hand, permit us to exempt any listed color from the certification requirement where certification is not necessary for the protection of the public health. When the present law was enacted in 1938, it was thought that its coal tar color provisions represented the ultimate in consumer pro- tection. It provided for listing by the Food and Drug Administra- tion of coal tar colors found to be “harmless and suitable for use” in foods, drugs, and cosmetics; and for the testing of every batch of the rmitted colors in Food and Drug Administration laboratories be- Fore any color from the batch could be marketed for such use. But experience with this law and advances in scientific knowledge regarding the testing of compounds for safety have shown that the consumer is not in fact receiving adequate protection. The law as it stands arbitrarily divides all coal tar colors into two classes: Those that are considered “harmless” and which may be used without any limitation of the amount, and those considered not harm- less and which may, therefore, not be used at all. We now know that this arbitrary classification is not realistic— and that the amount of the color to be used must be taken into ac- count in determining whether the use will be safe, except for cancer- producing agents, which I shall discuss later. ; The crux of the matter with respect to the deficiency in_consumer protection under the law as it now stands is simply this: While the coal tar colors now permitted were originally listed on the premise that they were “harmless,” our own retesting program—using newer scientific knowledge—has shown this premise to be false with respect to most. of the colors retested so far. This makes it probable that the premise will also prove to be false on many of the remaining colors. Yet, under the present law, we must continue our tests and assume the burden of proving as to each listed color that it is not harmless before we can take that color off the permitted list. 40 COLOR ADDITIVES It would take many years for the Food and Drug Administration to complete this testing of the coal tar colors now in use. This burden, it seems to us, properly belongs on those who manu- facture the colors, just as you have place a comparable burden under the food additives law on those who manufacture the food additives. On the other side of the coin, however, is the fact that once we have shown a particular color to be not harmless, per se, we are obliged under the present law to remove this color from the permitted list, even though the amount of the color consumed under particular con- ditions of use would be completely safe. If the law is not changed, it, therefore, appears certain that many colors may have to be ruled out, even though they could be used without harm under proper re- strictions. The bill we have submitted provides that: (1) The burden of proof of the safety of colors now in use and proposed for future use would be placed upon the manufacturer. (2) Listing of a color for use would be forbidden if such use would promote consumer deception or would otherwise result in adultera- tion or misbranding in violation of the Federal Food, Drug, and Cos- metic Act. (3) The Government would be authorized to take into considera- tion, in determining whether a proposed use is safe, the amount of color which would be used and the manner of use; and it would be empowered to set safe limits on the amount and conditions of use as necessary to protect the public health. We have no authority to set tolerances under the present law even though we find that the use of a color in specified amounts would not be harmful. If it is harm- ful to use a color in large amounts, it cannot be used at all. We have recommended, however, that the law contain a provision that would prohibit the use of a color in any quantity if it is found by appropriate tests to cause cancer in either man or animal. At this point, therefore, I should like to discuss our reasons for believing that an anticancer proviso should be included in the color additives legis- lation. THE BROAD ISSUE Tn discussing this issue, I propose: First, to describe in rather broad terms the environmental factors involved in considering this subject. Second, to define the role of Government in the kind of situation we are discussing. Third, to discuss the role of certain chemical and physical agents in relation to cancer. Fourth, I am prepared to summarize the specific recent actions of the Department under the policy of the anticancer, or Delaney, clause of the Food Additives Amendment of 1958. Our changing environment Hippocrates, in the fourth century B.C., taught that man’s health depended on his living in harmony with his external surroundings. And he used the word “physician” to indicate that every practitioner of medicine must “strive to know what man is in relation to food, drink, occupation, and which effect each of these has on the other.” COLOR ADDITIVES 41 Man has learned a great deal about how to modify his environ- ment. The forward march of civilization reflects one success after another in his ceaseless effort to control, instead of being controlled by, the forces within him and the forces around him. It is to the external forces that affect man’s total health that we refer when we speak of environmental health. ‘These external forces may be bio- logical, chemical, physical, or social. They are closely interrelated. And they have multiplied at an incredible rate as technological ad- vances and population growth have had their impact throughout the world, The complex of health problems posed by our rapidly changing environment is well known: Pollution of air and water by new and increasing quantities of chemicals—the new hazards of radioactiv- ity—the spread of communicable disease by air transportation—the hazards of noise, other physical forces, and accidents—social and bio- logical problems inherent in the development of large metropolitan complexes. These are typical of the problems that threaten us and can jeopardize our sustained progress if they remain unchecked. Man adapts to some aspects of this complex external environment. Other aspects he changes to meet his needs. In changing the en- vironment for one purpose, however, he may knowingly or unknow- ingly create new hazards to his health. Technological advances have reduced some health hazards, intensified others, and introduced some entirely new ones. Many of these, man cannot adapt to. His only recourse is to control his environment. Water and air, food, wastes, insects, and rodents are among the channels through which man’s health may be endangered. Controls directed at these vehicles may eliminate or reduce not only known hazards, but unknown or little understood ones as well. Thus we see that the manmade hazards to man’s health are growing. A characteristic of the hazards of the external environment is that large numbers of people may be affected, and particularly by the total or cumulative effects of external forces, such as, for example, chemicals or radioactivity, over long periods of time. THE ROLE OF GOVERNMENT Next I would like to address myself to the role of Government in this type of situation. When the question arises as to whether limitations shall be placed on the fruits of technology for the protection of the people, the con- cept of Government acting to protect the public interest meets one of its sternest tests. This is a simple, straightforward matter when there is incontrover- tible scientific evidence that a control measure is necessary and war- ranted. It is when this situation does not obtain—when there is not incon- trovertible proof that a health hazard does exist but ample reason to think that it may—that the issues are joined. Here, it seems to me, are the guidelines for action that under such circumstances, government must follow: First, it must make an objective appraisal of the issue. It must seek out all the facts, assess them, and determine where the weight of scientific evidence lies. 42 COLOR ADDITIVES Second, on the basis of the evidence, it must pursue a course of ac- tion which best reflects the public interest. Third, it must maintain and demonstrate its respect for the point of view of others. In choosing its course of action, the Government has made a judgment. It must stand ready to modify that judgment if new evidence is obtained that warrants change. Fourth, in all of these actions, once a decision is reached, it should be made public and the reasons for the decision explained. But there is one thing that a responsible government cannot do. It cannot fail to place at the top of its list of priorities the health of all of the people even though by so doing it may be or may appear to be acting against the economic interests of a segment of our society. The Government’s paramount obligation to act in the interest of the health and safety of the people in administration of the food and drug laws was ably set forth by Justice Frankfurter of the Supreme Court in 1943. Speaking for the Court (United States v. Dotterweich, 320 U.S. 277), Justice 'rankfurter said: The Food and Drugs Act of 1906 was an exertion by Congress of its power to keep impure and adulterated food and drugs out of the channels of commerce. By the act of 1938, Congress extended the range of its control over illicit and noxious articles and stiffened the penalties for disobedience. The purposes of this legislation thus touch phases of the lives and health of people which, in the circumstances of modern industrialism, are largely beyond self-protection (emphasis supplied). Regard for these purposes should infuse construction of the legislation if it is to be treated as a working instrument of government and not merely as a collection of English words. Justice Douglas, also of the arpreme Court, speaking for the Court (Kordel v. United States, 335 U.S, 345) in a later case also involving the interpretation of food and drug laws underlined the same para- mount obligation of government when he said: The high purpose of the act is to protect consumers who under present condi- tions are largely unable to protect themselves in this field * * *. Judge Hastie of the third circuit court of appeals identified the high standard to which government must adhere in discharging this para- mount obligation. In speaking for that court in 1952 (Atlas Powder Company v. Federal Security Administrator, 201 F.(2d) 347), he said: One making a rule for the future which in practical effect will determine whether millions of people shall eat something every day may reasonably refuse to subject the general public to even slight risks and small deceptions. In these circumstances the fact that administrative action has been dominated by great caution but serves to emphasize the reasonableness of the Administrator's conduct. It seems to me that what these distinguished jurists have said in preparing opinions for their respective courts constitutes a sound re- statement of Abraham Lincoln’s conviction that the legitimate object of government is to do for the people what needs to be done, but which they cannot, by individual effort, do at all, or do so well, for themselves. And it is in the light of this concept of what seems to me to be the sound role of government that I believe we should consider the situa- tion that confronts us today in the field of cancer. Carcinogenesis in animals and man In framing laws relating to the problem of cancer-causing sub- stances in the environment and in carrying out administrative pro- COLOR ADDITIVES 43 grams under these laws, the legislative and executive branches of Government are dealing with a disease that is a major killer. There are many unknowns about cancer that are yet to be solved by medical research. But we do know that today cancer is second only to heart disease as a cause of death among the American people. We know that every year, approximately 250,000 people die of eancer in this country. We know that approximately 450,000 new cases of cancer are discovered each year. And we know that at any given time, about 700,000 persons are under treatment for cancer. We have on the one hand sobering facts. On the other hand, we also have this sobering evidence: Scientific inquiry into the incidence of cancer among certain specialized groups has been traced in several instances to specific substances involved in their environment. And laboratory experiments have shown that a number of substances when added to the diet of test animals have produced cancers of various kinds in the test animals. It is this latter fact, the incontrovertible evidence that small quan- tities of certain materials over a period of time will cause abnormal cell growth in animals, that gave rise to the Delaney or anticancer provi- sion in the food additives amendment of the Federal Food, Drugs, and Cosmetic Act. Early identification of carcinogens I consider the known scientific evidence bearing on the causation of cancer to be of such importance in considering the anticancer pro- vision that I asked the National Cancer Institute, which, as you know, is a part of the National Institutes of Health of the Pubic Health Service, to develop a statement summarizing scientific knowledge in this field. The Associate Director for Intramural Research of the National Cancer Institute, Dr. G. Burroughs Mider, in consultation with other members of the Institute staff, developed a careful and de- tailed statement which traces the key facts that have been illuminated by scientific study. Mr. Chairman, I have this complete study with me. I would like to request the inclusion of the full document in the record, but then I would like to read as a part of my statement a summary of the docu- ment which was prepared by Dr. Mider. Personally I feel that this constitutes a very important contribution on the part of Dr. Mider and his associates of the National Cancer Institute to an understanding of this very important problem. Copies of this are also available for members of the committee. The Cuamman. That will be received at this time and we will be glad to look it over and determine whether to include it in toto for the record, or have it in the files for the benefit and information of the committee. Secretary Fremmino. Thank you, Mr. Chairman. The summary to which I referred is as follows—I would like to make it clear, as I think that the document does, that this summary was prepared for me by Dr. Mider, and I am now quoting from the summary : THe Stupy or AGENTS CARCINOGENIC TO MAN A carcinogen may be defined as any agent that increases the risk of cancer to any population. Among the well-defined carcinogens that affect man are: ultraviolet rays, jonizing radiatiou, sodium or potassium arsenite, and three aromatic amines. 56123—60——4 44 COLOR ADDITIVES Sailors, farmers, and others whose occupations have required protracted ex- posure to sunlight have long been recognized as having a greater frequency of skin cancer than occurs in the general population. By 1910 the concept of sun- light as a cause of cancer of the skin was widely accepted by dermatologists. Several investigators have produced cancers of the skin of animals by exposure to ultraviolet rays, a major component of solar radiation. Dr. Harold F. Blum, physiologist with the National Cancer Institute and visit- ing professor of biology at Princeton University, reporting on his precise studies with ultraviolet irradiation, emphasized that cancerization is in some way cumulative—if dosage is stopped, development continues at a retarded pace but steps up with renewal of dosage. The ability of X-rays to produce cancers of the skin, leukemias, and highly malignant tumors of bone in man is well established. Ingestion of the radioactive chemical, mesothorium, has caused bone cancers in watch-dial painters, and injection of the radioactive chemical, thorium di- oxide, in man has been followed years later by malignant tumors of the liver and spleen. The occurrence of tumors of the urinary bladder was reported among workers in the German coal-tar dye industry in 1895. Many different compounds were suspected, but in 1988 Dr. W. C. Hueper, head of the Environmental Cancer Section of the National Cancer Institute, reported similar tumors in dogs after prolonged, i.e., 2 years, injection and ingestion of an important dye intermediate, beta-naphthylamine. The evidence of carcinogenic hazard from this agent has been so impressive that it is no longer produced in Great Britain or Germany, and its production has decreased in the United States. Moving from the specific to the general, it may be emphasized that: 1. Cancer can be caused by extraneous agents. 2. Not all members of the exposed population are expected to develop cancer, but those more susceptible to cancer production cannot be identified except by experience. 3. Even a powerful carcinogen requires weeks or months to elicit cancer in mice or rats and probably requires years in man. 4. No change need be recognizable in the organ or tissue destined to become cancerous before the cancer itself appears. EXPERIMENTAL EVIDENCE IN IMPLICATING AND UNDERSTANDING CARCINOGENS It becomes necessary to assay the degree of risk produced by uncontrolled and uncontrollable use of chemicals known only to produce cancer in laboratory species. Some considerations of the significance of findings among laboratory animals in relation to human experience are as follows: 1. Experience in the laboratory does not predict unequivocally the reaction of humans to the same agent, be it carcinogenic or otherwise. On the other hand, those few pure chemical and physical agents known to produce cancer in man, with the possible exception of inorganic arsenical compounds, have elicited cancers in animals. 2. The route of administration affects the carcinogenic property. 8. No one at this time can tell how much or how little of a carcinogen would be required to produce cancer in any human being, or how long it would take the cancer to develop. 4. The effect of certain chemical carcinogens can be markedly increased by other compounds with little or no carcinogenic power. Also, the accumulated evidence suggests the irreversibility of the cancerous response once it has been initiated and further suggests a cumulative effect. Tne IMPORTANCE oF StupyIna WEAK CARCINOGENS Thus far, this discussion has concerned principally the highly potent carcino- gens; yet the weaker ones are equally if not more important. The most potent carcinogens by their very strength are almost sure to be discovered clinically. It is assuredly the less potent carcinogens that seem most important in human eancer and provide the real problem for evaluation. A major objective of ex- perimental carcinogenesis is therefore the bioassay for the presence of weak carcinogens, CLASSIFYING AGENTS AS POTENTIALLY HAZARDOUS While chemical configuration alone cannot be used to predict the ability of a new compound to produce cancer, possession of a common biological effect known COLOR ADDITIVES 45 to be associated with a particular type of cancer production may be of the utmost importance. Three examples may be cited: 1. Female sex hormones known as estrogens are formed in the bodies of most mammals. Administration of synthetic or naturally occurring estrogens has increased the incidence of mammary and other tumors in susceptible animals of various species. 2. The discovery of specific, potent, and useful drugs that interfere with thyroid function has stemmed from the basic observation that ingestion of cer- tain foodstuffs in large amounts increased the size of the thyroid in some ex- perimental animals. Moreover, certain goiter-inducing drugs, such as thiourea, will produce cancers of the thyroid when fed for prolonged periods to mice or rats. No information exists on the carcinogenic properties of natural goitrogens, but it would not be surprising if they too produced cancer after adequate and prolonged ingestion. 3. A chemical compound which by itself produces cirrhosis of the liver might will produce cancer of that organ. FOOD ADDITIVES AND CONTAMINANTS AS POSSIBLE CARCINOGENS A symposium on the potential cancer hazards from chemical additives and contaminants to foodstuffs was held in Rome, August 10-15, 1956, under the aus- pices of the International Union Against Cancer. The participants, representing many countries, included distinguished scientists particularly experienced in re- search on the causation of cancer. They viewed the problem as a global one. Their resolutions refer to “general problems, biological experimental methods, purity standards and analytical methods, and special problems” such as food dyes and food contaminants. Their general conclusion follows: “The conference recommends that, as a basis for active cancer prevention, the proper authorities of various countries promulgate and exact adequate rules and regulations prohibiting the addition to food of substances having potential carci- nogenicity.” An even more cogent discussion—Problems in the Evalution of Carcinogenic Hazard From Use of Food Additives—is contained in the prepublication issue of a report by the Subcommittee on Carcinogenesis of the Food Protection Commit- tee, National Academy of Sciences-National Research Council. The concluding paragraph reads: “Because of the vagueness of present knowledge concerning quantitative as- pects of the carcinogenie process, use of any amount of a carcinogen as a food additive probably is justified only if (1) values to the public are such that ban- ning the use would constitute an important loss or hardship, and (2) there is no reasonably good noncarcinogenic alternative.” (The full prepared report on “The Role of Certain Chemical and Physical Agents in the Causation of Cancers” by G. Burroughs Mider, M. D. .5 is as follows :) Tue Rove or CERTAIN CHEMICAL AND PHYSICAL AGENTS IN THE CAUSATION OF CANCERS (By G. Burroughs Mider, M.D., Associate Director in Charge of Research, Na- tional Cancer Institute, National Institutes of Health, Public Health Service, Department of Health, Education, and Welfare) (Prepared at the request of the Secretary of Health, Education, and Welfare as part of his testimony before the Committee on Interstate and Foreign Com- merce, House of Representatives (86th Cong., 2d sess.) on H.R. 7624 and S. 2197, January 26, 1960) Research into the causation of cancer had its inception almost 200 years ago when the eminent British surgeon, Mr. Percivall Pott, described an extraordinary frequency of cancers of the scrotum among chimney sweeps which he related to their intimate and continuing contact with soot. A posthumous edition of his “Chirurgical Works,” liberally annotated by Sir James Earle, included two ex- tremely important observations: 1. Soot cancers occurred on other parts of the body than the serotum. 2. Not all persons continuously exposed to soot developed cancers. Cancer, then, could be caused by external influences which would not neces- sarily produce the lesion in all members of the population at risk. 46 COLOR ADDITIVES CAUSES OF CANCER IN MAN Other agents were identified which increased the risk to one or another specific kinds of cancers. Most of them were mixtures often associated with particular occupations, but sunlight was suspected of causing cancer of the skin long before experimentalists were able to produce cancers in laboratory species with mixtures or with pure chemical compounds. X-rays, in fact, were known to produce cancer of the skin before any other discretely definable agent was shown to have similar properties. Probably the first pure chemical suspected of eliciting cancers in man was potassium arsenite given as Fowler's solution to patients suffering from chronic dermatoses such as dermatitis herpetiformis and psoriasis, These people, benefiting from the medicine prescribed by their physicians, indulged in self-medication far beyond the period deemed prudent by competent medical authorities. Thus, our knowledge of the causation of cancer came from clinical observations by individual physicians who recognized a peculiar distribution of disease among their patients that could be related to some peculiarity of environment or habit. SCIENTIFIC APPROACHES Scientists, of course, were anxious to identify the specific causative factors responsible for the production of cancer and seized upon the observations of Mr. Pott as one point of departure for their experiments. Many attempts to produce cancers with tars and soots or extracts made from those mixtures failed until two Japanese scientists reported in 1915 the induction of cancers on the ears of rabbits which had been painted with extracts of tars for long periods of time. A complex study of fractions of tar extracts in relation to their can- cer-producing properties was guided by association of a particular measurable fluorescence with the ability of a fraction to elicit cancerous responses, as pioneered by British investigators. The fluorescence spectrum of dibenz [a, h] anthracene was quite similar to that emitted by cancer-producing tax extracts; consequently it was tested in mice by Kennaway in 1930 and proved to be the first pure chemical that produced cancer under experimental conditions. Di- benz[a,hJanthracene is a polycyclic aromatic hydrocarbon and the knowledge of its important biological property permitted isolation of benz[a]pyrene from the potent tar extracts, To date, it is the only substance known to occur in tars which has the power to produce cancer. Chemically similar substances are abundant in nature and include steroid hormones, some of which were soon implicated in the production of mammary eancers in mice through the brilliant researches of Lacassagne. Scientists directed their attention to search for other chemicals which might produce cancers in experimental animals in the hope that such compounds might share common chemical or physical properties that could be correlated with their ability to elicit cancers. They were unusually successful in their search for eancer-producing chemicals. Most of these were products of the chemist’s test tube, but some were explored because of their relation to events suspected of causing cancer in man. The list of chemical compounds which will elicit cancer in one or more species of experimental animals is long, and growing longer each year. It contains inorganic compounds and organie chemicals of both major classes—aliphatic and aromatic. Structurally related groups of compounds con- tain some which do and some which do not produce cancer. While some charac- teristics of internal structure, such as electron density in specific regions of the eancer-producing eyclopentenophenanthrenes which elicit cancerous responses, may be associated with that property, no generalization concerning relation of chemical structure to biological activity, is warranted other than to emphasize the absence of such correlation. Nor is the power to elicit cancer the exclusive prerogative of chemicals, since ultraviolet and ionizing radiations as well as microbiological entities have similar properties, Test animals Scientific testing of agents for cancer-producing potency had been rather un- satisfactory because responses were so erratic that quantification was practically impossible except for the most powerful agents. Interested geneticists pointed to the use of genetically controlled subjects as a means of improving greatly the uniformity and consistency of response. The tools immediately available were various strains of mice, inbred by brother to sister mating for 20 to 40 genera- tions, theoretically as alike as identical twins but actually somewhat less so. COLOR ADDITIVES 47 The use of inbred strains may be compared to a situation in which one is able to work over and over again on the same individual or his very close relative. Other animal species have not been neglected and, indeed, the general success in studying quantitative biology in the mouse has led to the production of in- bred rats and guinea pigs and an approach to the difficult problems of raising inbred rabbits. Just as the inbred strains of experimental animals may vary widely in their susceptibility to cancer production by a given agent, so do genetically mixed or heterogeneous populations of the same species. ‘The same is true of a number of infections, including tuberculosis, and drug action may vary considerably from individual to individual, strain to strain, or species to species. Were there not some degree of variation in susceptibility to disease, the human race should have disappeared during the great pandemics of plague that ravaged the world centuries ago. LABORATORY FINDINGS SUPPORT CLINICAL OBSERVATIONS Perhaps the most important fact to emerge from the study of the causation of cancer during the past 30 years is the support that laboratory experience has given for the principles established from the study of human cancer, With the possible exception of arsenical compounds, every chemical compound of physical agent known to produce cancer in man has produced cancer in one or more species of experimental animal, though not necessarily in the same site. Most of the mixtures which reasonable people have implicated in the causation of human eancers have likewise produced cancers under laboratory conditions. PURE CHEMICAL AND PHYSICAL CARCINOGENS A carcinogen may be defined as any agent that increases the risk to cancer of any population. It is the simplest and most inclusive definition possible, and many of the most sophisticated cancer experts might properly view it as too broad. It will serve the purpose, however, of illustrating some of the complexi- ties of cancer production learned from experience. Let us first consider what has been learned about the known carcinogens that affect man: 1. Ultraviolet rays. 2. Ionizing radiations, principally X-rays but emanations from naturally oc- curring or artificially produced radioactive isotopes as well. 3. Potassium arsenite as Fowler's solution, and perhaps other trivalent arsenical compounds. 4. A small group of aromatic amines: f-naphthylamine, benzidine, and 4- aminodiphenyl. CANCER AND SUNLIGHT Sailors, farmers, and others whose occupations have required protracted ex- posure to sunlight, have long been recognized as having a greater frequency of skin cancer than occurs in the general population. Dubreuilh was the first to study the problem systematically, at about the turn of the century. His idea was adopted by oher physicians, so that by 1910 the concept of sunlight as a cause of cancer of the skin was widely accepted by dermatologists. Although the evidence accumulated during the intervening years from clinical studies alone may be purely circumstantial, other data acquired from experimental and other fields form various parts of a picture which have been brought together in a satisfac- tory manner to make a composite whole. EXPERIMENTAL ULTRAVIOLET CANCER Findlay was the first to produce experimental cancers of the skin by exposure to ultraviolet rays, a major component of solar radiation. His first report in 1928 was followed rapidly by confirmatory studies conducted in widely separate parts of the world. Blum and his colleagues initiated a series of precise quan- titative studies of ultraviolet carcinogenesis In the mouse during 1940 which are summarized in his recent work “Carcinogenesis by Ultraviolet Light.” The wavelength dependence of the cancerous response has never been precisely de- fined. Penetration of ultraviolet light into mouse skin, however, is much greater than into human skin. A great deal passes through the thin upper layers of cells in the skin, the epidermis, into the connective tissues of the corium where sarcomas are produced. Virtually none of the carcinogenic wavelengths pass through the epidermis in man, so that the cancers arising from ultraviolet irradi- 48 COLOR ADDITIVES ation in man are characteristically derived from epidermal epithelial cells. The ability of ultraviolet to pass into the corium in the mouse and rat accounts in all probability for the high proportion of connective tissue sarcomas found in mice and rats, though these species do form some cancers microscopically com- parable to human ultraviolet cancers. Dose-response relationships Blum’s studies are probably the most precise that have ever been carried out on any carcinogenic agent and include descriptions of dose-response relation- ships. He has summarized his findings as follows: * “* * * By treating the quantitative description as empirical, one may arrive at certain conclusions regarding this kind of carcinogenesis. “It seems clear that whatever the process of cancerization, it is continuous throughout the whole of the development of the cancer and cannot be separated into distinct periods. “Cancerization is in someway cumulative—if dosage is stopped, development continues at a retarded pace but steps up with renewal of dosage. “Although there is evidence of a small degree of recovery, this is slight in over- all effect, and carcinogenesis may be regarded as essentially irreversible. “Since there is recovery—and we may take particular account of this in the failure of reciprocity at very low dose rates—it seems necessary to conclude that there is a threshold dosage at which recovery just balances cancerization. But this threshold is certainly very low, and is not directly measurable because of the limited lifetime of the animals. Thus in any practical sense, carcinogenesis by ultraviolet light may be considered as essentially nonthreshold.” Individual susceptibility This important information does not tell us why all persons exposed to intense sunlight do not develop cancers on the exposed surfaces. Cancer of the skin in white residents of the United States shows a marked latitudinal distribution, being much higher in the South than in the North, as could be expected if the incidence followed a strong north-south distribution of sunlight. Most other cancers show no such tendency, nor does cancer of the skin in Negroes, These data and other considerations lead to the proposition that intensity of skin pigmentation as determined by heritable factors is inversely related to sus- ceptibility to ultraviolet cancer of the skin. It is commonly held that people with fair complexions are more susceptible to this type of cancer, and, indeed, the utmost in susceptibility is found in a small group of persons with xeroderma pigmentosum. These unfortunate people develop cancers of the skin during childhood and, in contrast to most people whose sunlight cancers appear much later, seldom live to adult life. While Blum regards this condition as an heredi- tary cancer in which ultraviolet radiation plays only a minor role, the concensus tends to consider xeroderma pigmentosum as a genetically determined predispo- sition to the formation of multiple actinic cancers. Thus, the human population exhibits a wide spectrum of sensitivity and resistance to the carcinogenic action of ultraviolet light. CANCERS PRODUCED BY IONIZING RADIATIONS The ability of X-rays to produce cancers of the skin, leukemias, or Iymphosar- comas and highly malignant tumors of bone in man, is accepted. Dose-response relationships are obscure, but a considerable variation in the ability of a given dose of X-irradiation to cause reddening of the skin and, for that matter, to produce X-ray burns has long been recognized. During recent years an inordi- nately large proportion of children suffering from cancers of the thyroid gland has been found to have a history of irradiation delivered some years earlier to the general area of the head and neck or upper thorax, usually given to reduce the size of the thymus gland. No adequate study of the true incidence of thyroid eancers in irradiated and unirradiated children has been reported, so that the suspected cause and effect relationship can be neither affirmed nor denied with complete scientific objectivity, though the inference is strong indeed. Ingestion of mesothorinm has caused osteogenic sarcoma in wateh-dial painters. Injection of thorium dioxide as thorotrast has been followed years later by the appearance of peculiar malignant tumors of the liver and spleen. 1From Harold F. Blom, Ph. D.. “Carcinogenesis by U Princeton University Press, 1959. Dr. Blom ts physi Institute. National Institutes ef Health, Publie Health professor of biology at Prinecton University. vielet Licht.” Princeton. NT, ist with the Nationol Concer Service, and is presently visiting COLOR ADDITIVES 49 Dose-response relationships A wealth of experimental data confirms the qualitative effects of ionizing ra- diations described in man as equally significant for laboratory species. Quan- titative aspects of the research have been argued intensely in scientific circles and even before legislative committees. It will serve no useful purpose to delve into the experimental details. The argument of those who have studied the biological effects of ionizing radiations in populations of fruit flies points to increases in the mutation rate as a direct function of dose of ionizing radia- tions, the curve passing through the origin. These scientists seem to regard cancer as a mutation and propose that any increase in mutation rate will increase the frequency of cancer, especially lukemia. The mammalian experimentalist unable to study the extraordinarily large numbers of mice that would be needed to fill in the bottom part of the curve can find doses of ionizing radiations which do not seem to increase the risk of leukemia and other cancers to a statis- tically significant degree. He may propose that some threshold must be reached before X-rays or their equivalents will cause cancer. These scientists would have little difficulty in detecting an effect that increased the incidence of a specific type of cancer by as much as 10 percent, but they might find it ex- tremely hard to establish a significant difference at the 1 percent level. The techniques are known, but the cost is terribly high and the information may or may not be worth the effort. Precisely the same problem is pertinent to studies of chemical carcinogens. ARSENICAL CANCERS Some of the reasons for implicating certain arsenical compounds in produc- tion of cancer in man have been cited above and will not be repeated here. The use of arsenical sprays as pesticides is alleged to have produced cancers of the skin, and a series of papers in the German literature has implicated arsenicals in production of cancers arising in the liver and the lungs. These problems are extremely complex, and an all-inclusive judgment is impossible on the basis of known facts. Certainly the number of occupational cancers of the skin considered to have been caused by arsenicals is far less than the numerous cases of chronic arsenicism unrelated to cancerous changes. AROMATIC AMINE CANCERS Rehn reported the occurrence of neoplasms of the urinary bladder among workers in the German coal tar dye industry during 1895, B-naphthylanine Many different compounds were suspected of causing these tumors, but in 1938 Hueper, Wiley, and Wolfe described the appearance of similar tumors in dogs after injection and ingestion of the important dye intermediate §-naphthyl- amine for approximately 2 years. British workers had attempted unsuccess- fully to produce cancers in mice, rates, and guinea pigs with this same com- pound. Extensive research conducted by Bonser and coworkers indicates that a simple chemical change in the molecule occurs within the body and the re- sulting compound is carcinogenic when excreted into the urine. The relative abilities of various species to produce the chemical transformation correlates well with the production of bladder tumors in the species by feeding 8-naphthyl- amine. Man, dog, and rabbit, unfortunately, excrete greater amounts of the metabolite than do other species studied, hence develop bladder neoplasms most readily. The evidence of carcinogenic hazard from B-naphthylamine has been so impressive that it is no longer produced in Great Britain or West Germany, and its production has decreased in the United States. Benzidine Elimination of S-naphthylamine from some chemical plants focused atten- tion on the carcinogenic properties of benzidine—as sulfate or base. Although benzidine elicits neoplasms of the urinary bladder in man and dog, it produces tumors of the liver and large intestine of rats. 4-aminodiphenyl Interest in 4-aminodiphenyl (xenylamine) as a potential carcinogen was stimu- lated by the information that the compound had been isolated from mixtures formed during the manufacture of triphenylmethane dyes and also the demon- stration of carcinogenic potency of chemically related substances. As 4-amino- 50 COLOR ADDITIVES diphenyl produced a variety of tumors in rats, and bladder tumors in dogs, Walpole, Williams, and Roberts forecast in 1952 that bladder tumors would develop in men exposed to it. In 1955, Melick and others reported bladder tu- mors in 19 men engaged in the manufacture of 4-aminodiphenyl in the United States since 1938. It had taken about 17 years for the carcinogen to manifest its potential, during which time 171 men had been exposed to risk. Manufac- ture of 4-aminodiphenyl was never started in Great Britain because of the ex- perimental evidence for its carcinogenicity. NEW GENERAL PRINCIPLES These studies permit two more generalizations: 1. Even a powerful carcinogen requires weeks or months to elicit can- cer in mice or rats, years in man, constituting a highly significant though variable fraction of the total life span of the particular species. 2. No change need be recognizable in the organ or tissue destined to be- come cancerous before the cancer itself appears, although in some cases a predictable sequence of structural changes characterizes the precancerous interval. JUDGMENT NEEDED Just as important is the experience gained from such work to guide the test- ing of other compounds for carcinogenic activity. Many judgmental decisions are required which relate to: 1. Validity of experimental design and its adequacy.—This must be guided by known quantities of a chemical compound and its relatives. It must be “bio- logically available” in order to produce any effect. Solubility is one extremely important factor, but too much of a compound may mask its carcinogenic prop- erty by eliciting specific or general toxicity which of itself reduces the life span of the subject and prevents a cancerous response. 2. Reasonable interpretation of results —No short cuts which would reduce the time of testing by evaluating something other than the ability of an agent to produce malignant neoplasms are now available to the experimentalist. The eancers produced by the experimental procedures must possess recognizable biological attributes of the malignant neoplastic state. As in man, pathologic diagnosis requires skill and must be based on correlations between structural change and biological behavior no matter what species is being studied. 3. Cancerous responses must be reproducible -—This can be shown by repeated experiments conducted by the same or different individuals or by reference to known qualities of an agent which permit accurate forecast of carcinogenic properities to be discussed later in some detail. Many isolated experiments, re- corded in the literature, which attribute carcinogenic properties to certain chemicals remain unsubstantiated and are of questionable validity. A large number of chemical compounds are available which cause a wide variety of cancers in one or more species but have not been shown conclusively to produce cancer in man. Many of them, in fact, have never been introduced into the human environment beyond the experimental laboratory. Others, how- ever, are proving useful in various enterprises, so that some degree of human exposure is inevitable. To deny the use of these materials in limited and con- trollable operations in commerce and industry would deny their ability to con- trol the use of many poisons that are used daily without substantial risk to the personnel engaged in the operation. Moreover, it would deny the use of many medicinal preparations with which the medical profession effectively controls many diseases. The uncontrolled use of the same agents can represent serious hazards. ESTIMATING RISK TO MAN OF CARCINOGENS FOR ANIMALS It becomes necessary to assay the degree of risk produced by uncontrolled and uncontrollable use of chemicals known to produce cancer only in some laboratory species. Carcinogenie property is not equivalent to a physical or chemical prop- erty of a compound which goes with it under all circumstances and is lost only when the molecule ceases to exist. The carcinogenic property can be modified in some cases by comparatively simple manipulations of the diet, change in the vehicle in which the agent is administered, or even change in the route of ad- ministration. Such considerations have led some to question the significance of the scientists’ findings among laboratory animals in relation to human experi- ence. Some of the more important points will be amplified. COLOR ADDITIVES 51 1. Experience in the erperimental laboratory does not predict unequivocally the reaction of the human species to the same agent, be it carcinogenic or other- wise——A chemical that produces cancer in the rat may be inactive in the mouse. Guinea pigs, rabbits, dogs, and monkeys are often alleged to be more resistant or even completely resistant to some compounds highly carcinogenic for the mouse and rat. Research has clearly defined the probable reason for the dif- ferent reactions of various species for the carcinogenic aromatic amines. Less detailed information is available for other classes of cancer-producing chemicals, and, indeed, judgments on species variation may be premature. The question has been examined by Shubik and Hartwell,’ who write: “Two of the most debated issues in carcinogenesis as applied to the human may be commented on from surveying this material. The first concerns the matter of species variation and with it the effects of different routes of entry. It is remarkable that so little investigation has been undertaken on various species. A large proportion of the positive results reported refer to mouse in- vestigations and of those the vast majority refer to experiments on the skin or in the subcutaneous tissues. The survey therefore provides but little data with which to form opinions on the matter of species variation. It is, however, notable that with the potent polycyclic hydrocarbons all the species adequately tested have eventually yielded tumors; notably in this supplement the induction of tumors in the monkey is recorded. A comparison of the data in various species obtained with the aromatic amines, particularly beta-naphthylamine, introduces the second important issue, the significance of the induction of benign tumors. Although the dog is recorded as the only animal developing carcinoma of the bladder following feeding with beta-naphthylamine, it is notable that the rabbit and the rat are repeatedly recorded as developing bladder papillomas. In the instance of the arsenicals, implicated repeatedly as a carcinogen in man, animal studies again repeatedly record the induction of a small incidence of benign skin lesions. Such correlations certainly make a clear evaluation of the significance of the induced benign neoplasm necessary. Gross variations in species re- sponses are exceptional in this material; carbon tetrachlorid stands out parti- eularly, inducing hepatimas in the mouse, but not in the rat or several other species tested extensively. In other instances adequate studies of species vari- ation and variations in routes of entry have been accorded little attention, and data recorded to this time do not provide the basis for many views on this sub- ject.” 2. The route of administration affects the carcinogenic property, as would be expected.—A compound carcinogenic for skin or subcutaneous tissue if destroyed by the ferments of the stomach could not exert its characteristic effect when fed, but in its altered form might take on additional and unexpected properties. Similarly, a chemical that is not absorbed from the gastrointestinal tract cannot affect tissues or organs with which it has no contact, and the rate of absorption of soluble chemicals may influence the cancerous response if concentration of the agent in the blood is a primary determining factor in carcinogenicity. The objective of carcinogenesis research has been to identify causes of cancer in man through direct approaches and through the discovery of pertinent broad principles to be learned from the study of cancer production in experimental ani- mals. Topical application and parenteral injection have been used much more extensively than feeding in most experiments, partly for economic reasons, but more importantly for the greater degree of control afforded the scientist, hence the greater ability to quantify his results. The alimentary canal is an important portal of entry to the organs and tissues, but it is not the only one. Contaminated atmospheres are equally important. and some carcinogens, notably §-naphthylamine and benzidine, are readily ab- sorbed through the intact skin in adequate quantity to produce cancer in man. 8. Perhaps the greatest debate concerns dose-response relationships in chemi- cal carcinogenesis.—Pitifully few good studies are available. As stated above, not all members of a genetically heterogeneous species are expected to develop cancer when exposed to an optimal dose of a potent carcinogen. The inbred strains of mice represent varying degrees of susceptibility and resistance, thongh 2From Philippe Shubtk. M.B.. B. Ch.. Ph. D.. and Jonathan LL. Hartwell. Ph. D.. “Survey of Compounds Which Have Been Tested for Carcinogenic Activity,” supp. I, Wash- ington, D.C.. U.S. Government Printing Office, 1957. Dr. Shubik {s professor of oncology and enncer coordinator at the Chicago Medical School. Chicago, Il., and Dr. Hartwell ts a chemist on the staff of the National Cancer Institute, National Institutes of Health, Public Health Service. 52 COLOR ADDITIVES resistance must be considered in a relative sense because a massive dose can overwhelm native resistance, all other things being equal. If one is searching for a carcinogenic effect, the use of the most susceptible experimental subject seems advisable. No-effect levels might well be found, but they would pertain to only the particular experimental conditions under which they were determined. It makes a great difference whether the detectable response in an experiment represents a 10 percent increase or a 1 percent increase in cancer or some other manifestation of toxicity. In any case, some arbitrary decision must be made as to the margin of safety to be used in translating data obtained from animal experimentation to man, taking into consideration all known facts concerning the carcinogen in relation to its proposed use in the human environment. Ex- actly the same type of problem confronts physicians who introduce new drugs into patients. The risks must be weighed against the anticipated benefits. A single application of a powerful carcinogen to the skin of mice can pro- duce malignant tumors weeks or months later. In the absence of quantitative data, no dose-response relationship can be defined for this situation. It would not be the least bit surprising if a single dose of carcinogen administered by mouth did elicit cancer in some part of the body. y Some experimental evidence suggests that the size of the dose of a carcinogen ‘ required to produce a cancer is more important than the period of time over which it is given. Hueper has recently observed an interesting effect of dose response on the production of subcutaneous tumors in mice by benz[a]pyrene. Two series of mice received single injections of the carcinogen or repeated in- jections at monthly intervals. When the total dose was low the tumor frequency was approximately the same in both groups. Single large doses in increasing amount produced a plateau in the dose-response curve, but multiple individual doses to the same total dose revealed a steadily progressive increase in car- \cinogenicity. No one at this time can tell how much or how little of a carcinogen will be required to produce cancer in any human being. 4. Age factors assume increasing importance.—Some experiments have sug- gested a greater susceptibility of weanling mice to the carcinogenic action of specific chemicals than of mice just a few weeks older. The differences have not been great. W. E. Smith and H. S. N, Greene independently devised a test for earcinogenicity in which the suspected compound in extremely small concentra- tion was added to embryonal mouse tissue and the whole implanted sub- cutaneously in adult mice. The embryonal tissue responded much more rapidly than most adult tissues, but little attention was paid to the fundamental im- port of this observation until Gross demonstrated the exquisite sensitivity of mice less than 1 day old to the carcinogenic action of certain viruses which would not produce cancer in older mice. The sensitivity of newborn mice to chemical carcinogenesis is now being tested. ) (7) is found in the Food Additives Amendment of 1958. But whatever may be said to support the inclusion of such a provision in the regulation of food additives designed to achieve a myriad of functional purposes, there seems to us no conceptual justification for its adoption in color additive legislation. The intended “physical” or “technical” effect of a color additive is to impart color. Whether or not that color is a desirable one is a ques- tion to be determined in the first instance by the manufacturer and, in the final analysis, by the consumer. It requires no administrative prejudgment of any complex question of utility. Third, the next section of the law, proposed section 706(b) (8), seems to us to confer upon the Secretary vast power to decide which articles are marketable and which are not, and to decide which indus- try needs a color and which does not, and to change his mind from time to time without any recourse from the industries affected or from the hapless consumer. In our society, such decisions of economic prefer- ence belong solely to the interaction of buyers and sellers in the market- lace. P Under subsection (A) of the provision as proposed, however, the Secretary would be charged with allocating an allowable tolerance for a color on the basis of such commercial criteria as the relative marketability of the articles involved, and the relative dependence of 56123—60——14 204 COLOR ADDITIVES the industries concerned upon the color. Moreover, the section as worded would permit the Secretary to revoke a tolerance previously granted for a particular coloring use in favor of some subsequent applicant for a purpose which, in the Secretary’s sole judgment, is more desirable, A tolerance for a particular use once allowed should not thereafter be canceled and allocated elsewhere unless the use of the color sub- stance for that purpose is voluntarily abandoned. Indeed, the revoca- tion of a listing for a particular use—because the Secretary thinks some new proposed use may be more deserving—could subject drug manufacturers, whose marketing programs had been developed in reliance on a color’s continuing availability, to serious financial loss. Any decision as to the relative importance of proposed uses or as to how badly particular industries may need a coloring substance are matters, In our opinion, beyond the competence of a public health agency. "Accordingly, the specific changes which we advocate in this respect are set forth in the chart which is attached to this statement. And I might add, parenthetically, the chart which is attached covers all the changes which we are suggesting. Fourth, I would like to direct attention to the cancer clause con- tained in section 706(b) (5) (B) of H.R. 7624. In our opinion, cancer should not be singled out for special legisla- tive attention distinct from the many other diseases that afflict man- kind. The Secretary is given adequate authority under the general provisions of the proposed color additive legislation to prohibit the use of color additives that present actual cancer hazard. We recognize, however, the many pressures created by the wide- spread fear of this dread disease. It 1s no doubt for this reason that a number of witnesses before your committee, in addition to advocat- ing the elimination of the clause from H.R. 7624, have proposed in the alternative its modification to alleviate the serious administrative difficul‘ies that have developed from the interpretation of the clause in the food additives amendment. In considering our own position as to the minimum acceptable modification to the cancer clause as proposed in H.R. 7624, we have taken into account the fundamental premise of Secretary Flemming, as stated at page 63 of the transcript, that— * * * no one knows how much or how little of a substance will induce cancer when added to the diet of man if it has been demonstrated that it will induce cancer when added to the diet of a test animal. ‘ This statement by the Secretary is attractive in its simplicity, but it istoo simple. It 1s not a valid reason for opposing all modifications to the cancer clause. For example, it does not distinguish between substances which di- rectly cause cancer and those which at known levels lead to condi- tions which in turn may cause cancer. In the latter case, science is capable of recognizing a threshold below which the cancer-causing condition will not be created. The remoteness of a substance from carcinogenesis should be taken into consideration in the evaluation of scientific data on chemical substances. An illustration of this distinction is potassium arsenite, referred to by the Secretary at page 22 of the transcript as a known carcino- COLOR ADDITIVES 205 gen. Potassium arsenite is itself an admittedly toxic substance long used in large doses for humans under medical supervision. It is true as the report of the Subcommittee on Carcinogenesis of the Food Protection Committee of the National Research Council states, that potassium arsenite has been “associated with cancer” in man. However, the same report indicates that there is no adequate evi- dence that this substance has induced cancer in experimental animals, Its association with cancer in man derives entirely from reports in the medical literature of some cases in which massive long-term potas- sium arsenite therapy produced a characteristic thickening of the skin of the palms of the hands and the soles of the feet, and abnormal pigmentation of the skin. These patches of thickened skin even- tually became cancerous. It is thought by scientists that about 20 percent of those who show skin thic kening may develop cancer. In other words, potassium arsenite is sometimes the proximate cause of skin thickening, which is medically termed hyperkeratosis, but only when administered at so high a level of ingestion that it is essentially arsenic poisoning. It is the hyperkeratosis which is the pre- sumed cause of cancer. But a threshold level for potassium arsenite may readily be established below which no hyperkeratosis will be caused, Thus, though it may be assumed that no threshold level can be established for direct carcinogenic action, safe levels can be deter- mined for substances that are not in or of themselves carcinogenic. Therefore, we feel that the cancer clause should be modified at the very least to apply only to substances which proximately induce cancer. The term “proximately” should be added to the law. Furthermore, we think the cancer clause should be revised to make clear that it is applicable only when data establish reliably that a substance has caused cancer. ‘This clarification is necessary because experience under the food additives amendment indicates a disposition on the part of the Food and Drug Administration to apply the cancer clause contained therein to compounds not shown to induce cancer. A specific example of this misapplication involves a number of organic arsenical compounds which, since 1951, have been widely used in animal feeds. Though chemically related, these organic com- pounds have chemical attributes that differ from those of inorganic forms of arsenic such as potassium arsensite. The organic arsenicals have contributed importantly to the efficiency of food production and to lower costs of food production by helping to insure survival and top condition of food animals from birth to market. Some of these compounds have for years been considered by the Food and Drug Administration as generally recognized as safe under the conditions of their use. Because of their safety, certain organic arsenicals are exempt from the food additives amendment when “used as the sole medicament and in some medicated combinations in animal feeds. The Food and Drug Administration, however, has taken the posi- tion that the cancer clause does not permit it to grant additional clear- ances for any organic arsenical, and, therefore, in those limited situ- ations where its approval is necessary, it has refused to grant any ap- plication or petition for any product containing an organic arsenical as an ingredient. 206 COLOR ADDITIVES Yet, there is absolutely no evidence that any organic arsenical com- pound has ever induced cancer in man or animal, despite widespread use and despite extensive animal experimentation. The Food and Drug Administration admits that it has not been demonstrated that all arsenic compounds are carcinogenic, but contends only that certain inorganic arsenic compounds, suc has potassium arsenite, produce cancer in man, and that their chemical relationship to organic arseni- cals raises a que ion as to whether these compounds may cause cancer. The position of the Food and Drug Administration, as stated in an official letter, is: * * * our scientific advisers cannot say that arsenic compounds (referring to organic arsenicals) used in feed * * * are safe until it is demonstrated that such compounds do not have this carcinogenic potential. Thus the statutory language contained in the cancer clause has been administratively distorted to require manufacturers to attempt to prove that a compound which has not been found to induce cancer in fact cannot cause cancer. This is not possible to prove scientifically. In other words, as the cancer clause in the food additives amend- ment has been interpreted, any substance can be rendered suspect on the basis of inconclusive reports, even reports concerning different sub- stances, and its manufacturers then given the impossible task of “prov- ing” that the substance is not a carcinogen. W e should bear in mind that the organic arsenicals now rest in this unhappy position chiefly because of a tenuous relationship to potas- sium arsenite which itself is the proximate cause only of hyperkera- tosis, and that only at levels of ingestion which have no reasonable relationship to those levels of arsenicals used in food and feed. The relationship of organic arsenicals to cancer is even more tenuous. We believe that the cancer clause should not be responsible for the con- demnation of established substances with a long history of safe use solely on the basis of a chemical relationship to compounds that at worst are suspect as indirect carcinogens. The proposed cancer clause constitutes a departure from construc- tive inquiry as to what evidence is necessary to demonstrate the overall safety of acompound. Therefore, it should be limited to demonstrated carcinogens, lest we create a widespread fear of ingredients ordinarily considered safe, to the detriment of the public interest. As the chairman of this committee has recognized, this legislation “extends enormous authority to a Federal agency.” (T ranscript, 110.) The responsibility entrusted to the Secretary by a speci ic cancer clause is a weighty one. As the chairman has also stated : * * * we also have to be a little careful that we do not go so far as to make everybody think they may or may not have cancer. (Transcript, p. 111.) If the flat ban of a cancer clause is to be applied on the basis of remote implications from inconclusive scientific reports, the follow- ing substances might have to be excluded from our food supply as carcinogenic: ¢ coffee, tea, milk, cream, cocoa, claret, fat, vitamins, eggs, and sugar, to name only a few. In his testimony on January 26, Secretary Flemming appeared to endorse the principle for which we are contending. He asserted on page 32 of the transcript: COLOR ADDITIVES 207 The conclusion that an additive “is found to induce cancer when ingested by man or animal” is a scientific one. The conclusion is reached by competent scientists using widely accepted scientific testing methods and critical judg- ment. An isolated and inexplicable tumor would not be a basis for concluding that the test substance produces cancer. In answer to a question from the chairman, the Secretary said on pages 114-115 of the transcript : * * *T am not saying that no one knows whether it induces cancer when in- cluded in the diet of an animal. We do know that. And once we know that, and once it has been established, then we are simply contending that man should not be subjected to the risk that is involved in including the same substance in his diet. To implement these comments by the Secretary, we believe it is essential to write 2 phrase into the cancer clause concerning the quality of the evidence which is required. If Congress considers that special reference to cancer is necessary in the proposed legisla- tion, I would urge that section 706(b) (5) (B) of H.R. 7624 be deleted, and that the following proviso be added to section 706(b) (4) of 2197: Provided further, That a color additive shall be deemed unsafe, for the purposes of this subsection, if the data before the Secretary establish that such additive has been found, by evidence considered reliable by experts qualified by scien- tific training and experience to evaluate the safety of color additives, to proxi- mately induce cancer in man or animal (a) in the case of any use which is likely to result in ingestion of all or part of such additive, when ingested by man or animal or after tests which are appropriate for the evaluation of the safety of the additive for its intended use, or (b) in the case of any use which will not result in ingestion of any part of such additive, after tests which are appropriate for the evaluation of the safety of additives for such use, or after other relevant exposure of man or animal to the additive. Our suggested amendment would be designed to insure the sound scientific judgment alluded to both by the chairman snd by the Sec- retary on the first day of these hearings. The chairuan voiced his hope that people would realize: * * * we are trying to meet what we know and what we have found through the effective work of our scientists in the laboratories. (Transcript, p. 111.) And the Secretary stated : * * * T would want to stress the fact that we do not suggest that we should bar the use of a Substance unless we know that it will induce cancer * * *. (Transcript, p. 116.) Our proposed amendment would do no more than write into the law this statement of the Secretary’s understanding. We feel that it is essential to do so because operating policy under the cancer clause of the food additives amendment has departed from this kind of scientific standard. In order to permit full exercise of sound scientific judgment, a fur- ther amendment would be required. The Pharmaceutical Manufac- turers Association has recommended a phrase which would cause the second part of (a) of our proposal to read: When ingested by man or animal in an amount and under conditions reason- ably related to the intended use * * *. We believe the Pharmaceutical Manufacturers Association will de- velop amply the basis for this proposal. 208 COLOR ADDITIVES The important and essential ingredient in the drafting of a can- cer clause is that it will cause regulatory action to be initiated only with regard to substances shown by properly evaluated evidence to be the proximate cause of cancer within, but only within, the scope of sound scientific judgment. Any departure from these require- ments will not add to the protection of public health, but will de- tract from it by undue suspicion and by the possible withholding of safe substances which may be necessary to food technology. With respect to the scope of the bill, we see no justification for the imposition of controls over all subtsances that are capable of impart- ing color to foods, drugs, or cosmetics. There appears to be no valid reason to include all materials or ingredients, regardless of their chemical composition, that have any effect on the color of foods, drugs, and cosmetic products to which they may be added. Under the sweeping definition of “color additive” set forth in sec- tion 101(c) of both bills, products such as tomato juice, orange juice, molasses, or butter and eggs would come within the jurisdiction of the proposed legislation. Their exclusion would reside wholly with- in the discretion of the Secretary and would require him affirmatively to determine that their use is “solely for a purpose or purposes other than coloring.” The only warrant for prior-licensing control over the processing of foods, drugs, and cosmetics is the necessity of this type of control to protect the public health. The kinds of products that are to be sub- ject to this system of administrative licensing should therefore be determined on the basis of their own chemical nature and characteris- tics, not on the basis of what the Secretary conceives of as their func- tional value. It should be noted, in this connection, that to the extent that food ingredients do not come under the definition of “color addi- tives” they would of course remain subject to the coverage of the food additives amendment. In order that the legislation may be limited to the area of its legiti- mate concern, we believe that the following changes should be made in its coverage. In section 101(¢) of both bills, the proposed definition of the term “color additive,” should be amended by revising subsection (A) to read as follows: (A) is a dye, pigment, or other substance made by a process of synthesis or similar artifice or manufactured by extracting a natural dye or natural pigment from a plant or other material in which such die or pigment was naturally produced, This would conform to the definition of “artificial coloring” in sec- tion 1.12(a) (2), of the regulations promulgated by the Food and Drug Administration (21 Code of Federal Regulations). Subsection (B) should be changed to read: (B) is added or applied to a food, drug, or cosmetic, or to the human body or any part thereof primarily for the purpose of imparting color thereto, As presently drafted, this legislation would be applicable even to substances that are universally conceded to be wholly nontoxic and even nutritious. Though generally recognized as safe, any coloring substance would receive no more than the benefit of a “deemed” provi- sional listing which, under title II of the bill would be subject to ter- COLOR ADDITIVES 209 mination at the will of the Secretary without any recourse either in the nature of a public hearing or by petition for judicial review. This approach comes perilously close to violating our traditional concepts of equity and justice. The harsh impact can readily be avoided. The first step in so doing would be to delete the ‘ ‘except” clause in the “color additive” definition and to replace it with a new paragraph (C), reading as follows: (C) is not generally recognized among experts qualified by scientific training and experience to evaluate its safety, as have been adequately shown through scientific procedures or common use to be safe under the conditions of its intended use. In our view, certain provisions of section 203 of title II of the pro- posed bills, relating to provisional listing, are inconsistent with its stated purpose to make possible the use of commercially established color additives to the extent consistent with the public health pending the completion of needed scientific investigations. On the one hand, section 203(b)(1) provides that certain colors shall be deemed to be provisionally listed. On the other hand, sec- tion 203(d) (2) (A) would authorize the Secretary to issue, amend, and repeal regulations without regard to any of the procedural safeguards that are applicable to his other actions. Furthermore, section 203(d) (3) might possibly be construed to con- tradict the concept that established colors are automatically entitled to be provisionally listed. The best way of resolving this difficulty is, I believe, the deletion of proposed sections 203(d) (: 2) ( A) and (d) (3), and the inclusion of a section as indicated in our chart, to nrovide for normal administrative and judicial review. In conclusion, I would like to state that we of Abbott recognize the sincerity involved in the drafting of this legislation and that we are acutely aware of the extreme caution Congress must exhibit in con- sidering any changes that might be regarded as weakening its control. We feel, however, that none of the changes that we have proposed will in any way lessen the eflicacy of this measure in assuring the safety of our supply of foods, drugs, and cosinetics. To the extent that the coverage of the bill is limited in the respects I have suggested today, we believe that it will be possible for the Secretary and for the Food and Drug Administration to concentrate their efforts in areas where there is legitimate apprehension rather than to be forced to dilute their attention by consideration of matters which do not reasonably protect the public health. Thank you, sir. (The chart referred to in Mr. Gerden’s statement is as follows :) 210 COLOR ADDITIVES Color additive bill—Recommendations of Abbott Laboratories Page reference to bills Page Title I see- reference to [tions of Food, Statement of | Drug, and Paui Gerden | Cosmetic Act Marked up copy of S. 2197 unless otherwise indicated (deleted matter in black brackets; added matter in italic) -§. 2197: p. 2, line 19 to p. 3, line 10. TL.R. 7624: p. 2, line 18 to p. 3, line 7. §, 2197: p. 8, lines 4to9. H.R. 7624: p. 7, line 23 to p. §, line 3. “8. 2197: p. 8, lines 10 to 20. H.R. 7624: p. 8, lines 4 to 14, S. 2197: p. 9, lines 9to 19, TER. 7624: p. 9, lines 3 to 16. -S. 2197: p. 9, line 20 to p. 10. line 20, H.R. 7624: p. 9 line 17 to p. line 22. -S. 2107: p. 11, lines 3 tol. HR, 7624: p. 11, lines 4 to 15, The term “color additive” means a material which— (A) is a dye, pigment, or other substance made by @ process of synthesis or similar artifice, or [extracted, tsolated, or otherwise derived, with or without inter- mediate or final change of identity, from a vegetable, animal, mineral, or other source,) manufactured by ertracting a natural dye or natural ptgment from a plant or other material in which such dye or pigment was nafur- ally produced, and (B) [when] ts added or applied to a food, drug, or cosmetic, or to the human body or any part thereof (, is capable (alone or through reaction with other substance)) primarily for the purpose of imparting color thereto [; except that such term does not include any moaterial which the Secretary, by regulation, determines is used (or intended to be used) solely for a purpose or purposes other than coloringJ , and (C) is not generally recognized among erperts quali- fied by scientific training and experience to evaluate its safely, ax haring heen adequately shown through scientine procedures or common use to be safe under the condifions of its intended use. The Secretary shall, by regulation, provide for sepa- ratelv isting Color additives for use in or on food, color additives for use in or on drugs, and color additives for use in or on cosmetics, if and to the extent that such additives are (suitable and] safe for any such use wheo employed in accordance with such regulations. (A) Such regulations may list any color additive for use generally in cr on food, or in or on drugs, or in or on cosmetics, if the Secretary finds that such additive [is suitable and] may safely be employed for such general use, (1) If the data before the Secretary do not estab- lish that the additive satisfies the requirements for listing such additive on the applicable list pursuant to subparagraph (A) of this paragraph, or if the proposal is for listing such additive for a more limited use or uses, such regulations may list such additive only for any more limited use or uses for which [it is suitable ana] may safely be employed. The Secretory shall not list 2 color additive under this section for a proposed use unless the data before him establish that such use, under the conditions of use specified in the reculations, will be safe: Provided, however, That_a color additive shall be deemed to he Lsuitable and) safe for the purpose of listing under this subsection for use generally in or on food, while there is inetfeet a published finding of the Secretary declaring such substance exempt fram the term “food additive” because of its being generally recognized by qualified experts as safe for its intended use, as provided in sec- tion 2O1(s) ; Provided further, That a color additive shell he deemed unsafe, for the purposes of this subsection, if the data hefore the Secretary estahliah that snch additire has teen found, hy eridence considered relinhle by experts qualified by scientific training and experience to evaluate the safety of color additires, to prorimately induce cancer in manor animal (a) in the case of any use which is likely fo result in ingestion of all or part of such additire, when ingested hy man or antmal or after tests which are appro priate for the evaluation of the safety of the additire for its intended use, or (b) in the case of an use tohich will not resilt in ingestion of any part of such additive, after tests which are appropriate for the craluation of the safety of additives for such use, or after other relevant exposure of man or animal to the additire, Same ay 5, 2197, 706(b) (1)... } 5-6....-. ~+--| 706(b)(2)__.. 706(b) (4)... 706(b) (5)... 706(D) (7)... Delete. COLOR ADDITIVES 211 Color additive bit—Recommendations of Abbott Laboratories—Continued Page Title I see- Page reference reference to |tions of Food,| Marked up copy of S. 2197 unless otherwise indicated to bills statement of | Drug, and Paul Gerden | Cosmetic Act 8. 2197: p. 11, line 15 706(b) (8)... to p. 12, line 13, H.R. 7624: p. 11, line 16 to p. 12, line 13, 8. 2197: p. 19, line | 21-23........ 203(d)(2)(A) 24 to p. 20, line 7. H.R, 7624: p. 19, line 22 to p. 20, line 5. 8. 2197: p. 20, line | 21-23........ 203(d) (3)... 21 to p. 21, line 16. H.R. 7624: p. 20, line 19 to p, 21, line 11, (deleted matter in black brackets; added matter in italic) If, having regard to the aggregate quantity of color additive likely to be consumed in the diet or to be applied to the human body, the Secretary finds that the data before him fail to show that it would be safe and otherwise permissible to list a color additive (or pharmacologically related color additives) for all the uses proposed therefor and at the levels of concentra- tion proposed, the Secretary shall, in determining for which use or uses such adilitive (or such related addi- tives (shall be Cor remain] listed, or how the aggregate allowable safe tolerance for such additive or additives. shall be allocated by him among the nses [under con- siderntion,) for which such additive has not already been listed, take Into account, among other relevant factors fand subject to the paramount criterion of safety) ((A) the relative marketability of the articles involved as affected by the proposed uses of the color additive (or of such related additives) in or on such articles, and the relative dependence of the industries concerned on such uses;} ((B)) (4) the relative avgregate amounts of such color additive which he estimates would be consumed in the dict or applied to the human body by reason of the various uses and levels of concentration proposed; and €(C)] (7) the availability, ifany, of other color additives [suitable and) sufe for one or more of the uses proposed, Delete. Delete; substitute the following: “The provisions of section 701(e), (D, and (@) of the basic Act shall apply to and in all respects govern proceedings for the issu- ance, amendiment, or repeal of regulations under, this section (including judicial review of the Secretary's action in such proceedings) and the admissibility of transcripts of the record of such proceedings tn other Proceedings, exeept that—(1) the Secretary's order after public hearing (acting upon objections filed to an order made prior to hearing) shail be subject to the requirements of section 409(f)(2) of the basic Act; and (2) the scope of judicial review of such order shall be in aceordance with the third sentence of paragraph (2), and with the provisions of paragraph (3), of section 409 (g) of the basic Act.” Mr. Witurams. Mr. Younger. Mr. Roserrs. I have no questions. Mr. Wituiams. Mr. Younger. Mr. Youncer. Just one question, Mr. Chairman. You make the statement that once an ingredient has been approved, there would be no authority for the Secretary to recind the approval ; that is, a tolerance for a particular use, once allowed, should not therefore be canceled. Can you conceive of a case where the Secretary might give a certain tolerance and then later on it was found that it was injurious and his hands would be tied and for public safety he could not exercise that power? Mr. Grroen. Mr. Congressman, I believe my statement refers to- the establishment of a tolerance for a particular use. Mr. Youncer. Yes. 212 COLOR ADDITIVES Mr. Gerpven. And assuming a hypothetical situation, if a drug manufacturer has established a tolerance for use of a certain color, and perhaps that tolerance was then used up, but it was a safe product. The bill as now written would permit the Secretary—let us say if a lipstick manufacturer came in to revise our use of that color, and perhaps allocate part of it or all of it to another manufacturer. That 1s the point we make. We do not propose under any circumstances that any product which is not safe should not be discontinued im- mediately. Mr. Youncer. Well, as I understand it, under the present law, ac- cording to what the Secretary gave in his evidence, if he issued a tolerance to one applicant and that was granted and then they found that it was injurious, they could deny it to a new applicant but they could not rescind it for the previous applicant. Mr. Grrven. I think under these bills—— Mr. Youncer. Under existing law? Mr. Gerpven. I think under these proposed laws, if a color additive is found at any time not to be safe, the Secretary would have the authority to ban its use. I believe that is amply covered in the bill, sir. Mr. Youncer. I cannot coincide that with your statement on page 7: A tolerance for a particular use once allowed should not thereafter be can- celed. Mr. Gerpen. Well, we are thinking there, sir, in the allocation of these colors, that if a certain manufacturer has been given permission under this act to use a color within a certain tolerance, that the Secre- tary should not have the authority to remove the tolerance—let us assume it is safe—and allocate that to another manufacturer. That is all we are proposing. We are not proposing that if there is a safety question that the color should not be banned. We are merely propos- ing that once a manufacturer has a color which he is using, that the Secretary should not have the arbitrary power to withdraw from one in whole or in part and give it to somebody else. Mr. Youncer. You did not intend to say just because he does establish a tolerance which later develops to be a mistake, that he could not rescind the approval ? Mr. Gerven. Absolutely not. He could rescind that. Mr. Youncer. That is all, Mr. Chairman. Mr. Wiuurams. Mr. O'Brien. Mr. O’Brien. No questions, Mr. Chairman. Mr. Wiiitams. Mr. Nelsen. Mr. Netsen. No questions. Mr. WittiaMs. Mr. Rogers. Mr. Rocers of Florida. Just a question or two. If the Secretary did decide to rescind such an order, you would want a hearing before that was done; would you not? Mr. Gerven. That is correct, sir, Mr. Rocers of Florida. Which is not now provided in the proposed legislation ? Mr. Gerven. It is provided in title I but not in title II. Mr. Rocers of Florida. Yes. Now, also, I wondered about your statements that begin on pages 13 and 14. I get the implication there that the Secretary or the Food COLOR ADDITIVES 213 and Drug Administration has recently or in the past opposed the use of certain compounds without actually proving that through their testing that these substances did cause cancer in animals. Mr. Gerven. Yes, sir. Mr. Rocers of Florida. Even though they might not be able to prove that it causes cancer in man, at least they usually have proof in the animals. Do I understand they are now doing it without some proof along those lines? Mr. Gerpen. That is my understanding but, with your permission, I would ask Dr. Matson to comment on that. Mr. Matson. Yes; this seems to be the situation. Mr. Rocers of Florida. Have you any specific example of that ? Mr. Matson. The illustration given here in the presentation is on the organic arsenical drugs, which are used in animal feeds, and where the Administration feels itself unable to extend further ap- provals under the food additive law. Mr. Rogers of Florida. Now, were these tests not conducted on animals to show this Mr. Matson. No. This is merely on the basis of an association with the inorganic arsenic compounds which, it was felt, do have some record in the medical literature of having been associated with cancer. Actually, there is absolutely no record anywhere in the scientific literature that we know of that any of these organic arsenic com- pounds themselves have ever caused cancer. In fact, I just refreshed my memory by looking at a review by Neubauer, which is probably the most authoritative thing and most comprehensive thing that has been written that I know of. He has a brief statement here which specifically touches on one of these or- ganic arsenical compounds. It used to be used very widely in medical practice under the name Atoxyl, and his sentence there is: Some pentavalent organic arsenicals as cacodylates, Atoxyl and Arsacetine are—or were—frequently used as medicaments; but it seems that they never have proved as carcinogens. But the Administration seems to feel that just because there is some- thing of a chemical association that these compounds contain the element arsenic, that they therefore are unable to give further approvals. Mr. Roaers of Florida. Do you know if there were hearings held on this particular subject? Mr. Matson. No; there have been no hearings on this subject. Mr. Rocers of Florida. Has there been any challenge in the courts on that particular decision? Mr. Gerven. No, sir, we have not. Mr. Rogers of Florida. I wonder, because you also quote the Secre- tary’s testimony on page 16, where he says: ** * T am not saying that no one knows whether it induces cancer when included in the diet of an animal. We do know that. And once we know that, and once it has been established, then we are simply contending that man should not be subjected to the risk that is involved in including the same substance in his diet. It is my understanding of his testimony, that when they give these tests to animals and it is shown that there is a cancer-producing sub- 214 COLOR ADDITIVES stance then these compounds would be ruled out. But you say it is being done before that has happened ? Mr. Gerpen. Yes, sir; it is. Mr. Roerrs of Florida. Thank you. Mr. Gerpen. We agree with the Secretary’s statement. We are merely trying to write what he says into law. Mr. Rocers of Florida. But the present practice is not what the Secretary is saying? Mr. Gerven. That is correct, sir. Mr. Roerrs of Florida. Thank you, Mr. Chairman, Mr. Witurams. Mr. Keith. Mr. Keirn. Mr. Chairman, I would like to compliment the witness on his testimony and say, in my opinion, he has contributed greatly to the effort of this committee to enact legislation which will be reason- able. In the absence of legislation which is reason: ible, the pure Food and Drug Administration has a very difficult time administering the law, and the public loses confidence in the edicts of that division. The end result is lack of respect for the pronouncements of an agency of government, and in the long run the public interest would be ‘adverse- ly affected. We must not cry “wolf” unnecessarily because when the wolf shows at the door, we would not believe he is there. And the Secretary of Health, Education, and Welfare would, under the terms of the legis- lation we have before us today, have to unnecessarily alert great segments of our industry to dangers that are not in fact present. That is all. Mr. WintsaMs. Mr. Rhodes, do you have any questions? Mr. Ruopes. No questions. Mr. Witutams. Mr. Brock. Mr. Brock. Mr. Chairman, I would like to address myself to the witness along the lines of my colleagues, Mr. Rogers, on the potassium salts. Mr. Gerpen. You mean potassium arsenate ? Mr. Brock. If we would go along with the reasoning of the agency then, and think of sodium chloride and think of sodium chlorate, with the addition of a couple of molecules of chlorine, then we could have a toxic salt of sodium, just as we can with potassium arsenite. So I feel we should thoroughly study this subject of the different elements and their relationship to the health in human beings, and also animals. That is all I have, Mr. Chairman. Mr, Witztams. Mr. Hemphill. Mr. Henri. No questions, Mr. Chairman. Mr. Winiirams. Mr. Gerden, on about page 5 of your statement you testified about the functional value of the additives and you appar- ently register objection to the use of the words “suited” and “safe” or the word “suitable” in the phrase “suitable and safe.” Is it your contention that that imposes upon the Department or on the Govern- ment an obligation to determine whether the additive has a functional value and, if not, to deny the use of that additive if it has no fune- tional value, even though its safety is not in question ? Mr. Gernen. That, generally, is correct, Mr, Chairman, that the term “suitable” is a functional concept and we are not certain what COLOR ADDITIVES 215 it means, but if it does not mean safe, in our opinion, it should not be in the law. Mr. Wiuurams. As I recall, in our work on the food additive legis- lation of 1958, the question of whether the Secretary can be given au- thority to determine functional value in addition to the safety of the additive, was rather controversial and we had a great deal of dif- ficulty with it. I confess that I do not recall just exactly how it was resolved in the legislation. Do you remember ? ‘Mr. Gerven. I think most of the functional value tests were elimi- nated from the—— Mr. WituraMs. If I recall correctly the legislation was compromised to some extent, and I know the functional value authority was re- moved. Mr. Gerven. Yes. Mr. Wuurams. Do you feel that the Secretary should be given the power to determine whether or not an additive has a functional value and to contro] its use in that respect ? Mr. Gerven. No, sir, he should not. He should determine its safety but not whether or not a certain color might be of value in his opinion. The safety, yes; the functional characteristics, no. Mr. Wiuuiams. May I say, I agree with you completely in that premise. I feel that that is a prerogative of American business to determine whether or not the use of a color or an additive in their product is functional or nonfunctional or without functional value. The responsibility, in my opinion, of the Food and Drug Admin- istration is to deal with the safety of the ingredient used for public consumption or consumption by the public, and to that extent I agree with you completely. Are there any further questions? Mr. Avery. Mr. Avery. In furtherance, Mr. Chairman, of the observation you just made, those same thoughts were going through my mind. When we examine that philosophy, whether choice should be left entirely to the discretion of the consumer, or whether factor other than health be taken into account by a Government agency, I am thinking in that same connection in terms of the Federal Security and Exchange Com- mission, Now, we do not leave to the consumer (or buyer) in that case to decide whether or not a share of stock is a creditable issue. We as- sume that it is a rightful function of Government to decide whether a certain security should be put on the market. We are assuming the responsibility to make that decision for him, and so I am not so sure that I can agree with you in every respect, Mr. Gerden, that it has been established when or where should an agency not intervene in the public interest. To quote from your statement here, on page 6: Whether or not that color is a desirable one is a question to be determined in the first instance by the manufacturer and, in the final analysis, by the con- sumer. “Desirable” should be defined clearly. Just from a philosophical standpoint, of course, I would like to agree with you, but it seems to me we have developed and accepted the doctrine of intervenor in the 216 COLOR ADDITIVES consumer decisions here in the last 25 years and maybe we have inter- vened to the extent that the Government is expected to make some further—take some further responsibility in that area. Now, one other instance or one other place in your statement, you drew my attention to, and this is completely unrelated to the question or observation I just made, on page 18, if you would turn to your statement, page 18, and in that last paragraph you summarize by stating that— this decision of whether or not the additive was going to be harmful should be based strictly upon a scope of sound scientific judgment. Well now, is that not just what we are discussing actually, who is going to decide what constitutes scientific judgment? Is not that the ifference between the part of the industry and the part of the Ad- ministrator of Health, Education, and Welfare? Mr. Gerven. Our position is—now, we, as I have mentioned, some of the statements that the Secretary made, we are in complete agree- ment with. Now, however, as Dr. Matson mentioned, and as our tes- timony points out, under the Delaney clause in the food additives amendment, there has been deviation from, let us say, sound scientific judgment. Now, in our opinion, in our opinion, matters pertaining to any disease should be decided, as they have in the past, by the best scientific evidence available, and reliable scientific evidence, and that is all we are asking for. Mr. Avery. Well, do you not think the Secretary feels that he is asking for authority to make his decisions upon scientific evidence ? Is it not the definition of scientific evidence that we do not agree on? I say “We,” I mean all parties to this legislation. Mr. Gerven. I think that might be correct, but I think it might be a little more accurate to say that in some cases scientific evidence has not been considered, rather than a difference between the evaluation of scientific evidence. Now again, referring to the example we placed in here on organic arsenicals, in my opinion, as a layman—and I would let Dr. Matson amplify this—but in my opinion as a layman, I think the scientific people have been pushed aside. Lawyers have no place in a deter- mination of a given disease. We might have a place in another phase of society. But as far as the determination Mr. Avery. Was that lawyers, you said, had no part in that decision ? Mr. Gerven. I said lawyers should have no part. Mr. Avery. Yes. Mr. Gerpen. In determining matters pertaining to disease or that. Mr. Avery. Iam in full agreement with you on that. Mr. Gerven. And I am sure the medical men are, too. Mr. Avery. I do not want to let your point of view go without com- ment; that the Secretary has acted arbitrarily and not upon evidence presented to him by what he considers, anyhow, to be reliable scien- tists, and Iam not a lawyer or scientist. When we reduce this down to the final points of difference here, it seems to be on definition of what constitutes a scientific decision and what you might construe as being one arbitrarily arrived at by counsel for the Secretary. Perhaps you have come to the right conclusion, I am not saying that you are wrong in what you have suggested here in the way of amendments, COLOR ADDITIVES 217 but I am not willing to let the record stand without comment that it is a matter of nonscientific, nonsupportable position on the part of the Secretary, as it is a matter of judgment of what is in the public interest, how much and what kind of scientific evidence is necessary and should be relied upon in making a decision. Mr. Gerven. In that respect, sir, we disagree. Mr. Avery. That was the conclusion that only I could come to. [Laughter. ] Mr. Rocerrs of Florida. Mr, Chairman, would you yield? I think it would be helpful and I certainly as one member of the committee would desire it, and I hope the committee would, to have the Sec- retary comment on this specific example which I think would clear this up for us to a great extent. Since Mr, Freeman, I believe, is here from the Department, if he could either get a written comment on this or else let us recall the Secretary and go into this, I think it could be fairly important. Mr. Avery. Yes. Mr. Gerpen. We would, of course—— Mr. Wiuturams. Let me ask Mr. Freeman. Mr. Freeman, do you think the Secretary would be willing to submit a memorandum giv- ing us his views on this particular item ? Mr. Freeman. I am sure he would. I have no reason to doubt that he would not. Mr. Witiiams. Would you take care of that? Mr. Freeman. Yes, sir, I would be glad to. Mr. Gerven. We would appreciate the opportunity to be able to comment, if necessary, on the Secretary’s comments. Mr. Writs. I think the record will probably be kept open for some weeks after the hearing to receive rebuttals or re-rebuttals. Mr. Rocers of Florida. I think that would be proper, Mr. Chair- man. (The following letter was later received in connection with the above matter :) Tue SeckeETARY OF HEALTH, EDUCATION, AND WELFARE, Washington, April 18, 1960. Hon, Oren Harris, Chairman, Committee on Interstate and Foreign Commerce, House of Representa- tives, Washington, D.C. Dear Mr. CHAIRMAN: Dr. Kenneth A. Freeman, in charge of the Color Certi- fication Branch of the Food and Drug Administration, who attented the color additives hearings on February 10, has advised me of your request for a state- ment outlining the status of arsenic-containing compounds under the food addi- tives amendment to the Federal Food, Drug, and Cosmetic Act. Six arsenic-containing compounds are used in poultry feed to stimulate the growth of poultry or to control disease in the flocks. Certain of these com- pounds may be used also in swine feed for gowth stimulation and disease. While the Department of Agriculture has the responsibility for inspection of meat and poultry at the point of slaughter, the Food and Drug Administration is responsible for the safety of new drugs for veterinary use and of feed for meat animals and poultry. Before the enactment of the food additives amendment, some of these arsenic- containing compounds were allowed in animal feed under the provisions of the new-drug and antibiotic sections of the Federal Food, Drugs, and Cosmetic Act. The compounds were allowed in stated concentrations and with the understand- ing that they would be marketed with label directions requiring treated animals to be maintained for 5 days before slaughter on feed that does not contain added arsenic. The evidence before the Food and Drug Administration indicated that 218 COLOR ADDITIVES this 5-day withdrawal period would allow the elimination of added arsenic from tissues of the treated animals and thus would insure the safety of the use of the arsenic compounds, A very preliminary survey made some time ago by the Food and Drug Adminis tration indicated that some poultry raisers are not withholding arsenic-containing feeds from their flocks 5 days before slaughter, and we have information that in some parts of the country, hog raisers maintain their animals on arsenic- containing feed within the 5-day period that the arsenic is supposed to be with- held. It is evident that such disregard of the directions for safe use could lead to added arsenic residues in poultry and pork on the retail market and thus could frustrate the public health safeguards upon which the original approvals were granted. It is our purpose to look into this situation further, but our investiga- tion has been delayed pending a search in the laboratories of the Food and Drug Administration for suitable analytical methods to support the investigation. In September 1958 the food additives amendment to the Federal Food, Drug, and Cosmetic Act became law. This provides, as you know, that a person who proposes to promote an additive for use in food must first present evidence of the safety of the use to our Department and secure approval through the issuance of an appropriate food additives regulation. It provides also that we may not sanction the addition of a substance to food if it has been found to induce cancer when fed to man or animal, or if it has been found to induce cancer by other appropriate tests. (Food, as defined in the law, includes food for animals as well as for man.) The specific uses of arsenic-containing compounds on the basis of applications that were approved by the Food and Drug Administration under the new-drug or antibiotic sections of the law before enactment of the food additives amend- ment are exempt from the application of the food additives amendment. Thus, many uses of arsenic-containing compounds in animal feeds may continue as before. Whether other uses of these and other arsenic-containing compounds in animal feeds would be subject to the food additives amendment depends upon whether appropriately qualified experts generally recognize such uses as safe. If they do, then the chemicals are not included in the definition of food additives. There was some question in our mind as to whether these uses were generally recog- nized by experts as safe and we brought this to the attention of the Animal Health Institute, Des Moines, Iowa, and the American Feed Manufacturers As- sociation, Inc., in June and July 1959. It was our understanding that one or both of these organizations, perhaps with the assistance of some of the veterinary drug manufacturers whom they had contacted, would canvass a number of scientific experts in the country to determine whether the additional arsenicals were generally regarded as safe under their intended conditions of use. So far as we know, this has not been done, Consequently, it is our purpose in the near future to make such an investigation without waiting further for industry action. If the proposed uses of the arsenicals in animal feeds are subject to the food additives amendment, then one part of the showing of safety that is required under the amendment will be to determine whether the cancer clause of the amendment applies. The Food and Drug Administration tells me that the or- ganic arsenic compounds used in animal feeds have not been shown to produce cancer when fed to test animals. On the other hand, we do need more advice from the scientists who are most knowledgeable in the arsenical field. We are taking steps to get this advice. As you know from the testimony I gave before your committee on January 26, we expect to propose an amendment to the food additives law that wonld allow us to sanction the use of a chemical in animal feed, even though it may have been shown to produce cancer in test animals if the proposed use could leave no resi- dues in edible products derived from the animal for which the feed was intended and were without harm to the animal itself. Such an amendment, together with the further studies that we are undertaking, may well resolve a number of qnes- tions that have arisen about the arsenic compounds since the food additives amendment was enacted about a year and a half ago. Sincerely yours, ARTHUR S. FLEMMING, Secretary. Mr. Wititams. Thank you very much. Mr. Grrpen. Thank you, Mr. Chairman. (The following paper was submitted for the record by Mr. Matson :) COLOR ADDITIVES 219 ScrentTiric JUDGMENT IN LAW AND REGULATION Presented before the American Association for the Advancement of Science, Sec- tion on Pharmacy, December 30, 1959, by Edward J. Matson, Director of Scientific Administration, Abbott Laboratories, North Chicago, Ill. Just 16 months ago the Congress placed on the statute books a new Federal food additive law. Congress considered it necessary because of the greatly increased speed of development of food technology. The law reversed the whole pattern of enforcement by requiring in effect that a general license be granted by the enforcement agency prior to putting into use any new additive developed through food research. This new responsibility demands of the Food and Drug Administration administrative judgment of a different order than before. If sound policy is not developed and followed consistently, business and the public both can suffer needlessly. Certain events of the last year have disturbed many, events which indicate an uncertain administrative striving for the soundest scientific judgment. BUSINESS RESPONSIBILITY Let me say clearly that I would not oppose the imposition on the food industry of any law soundly conceived and necessary for the protection of public health. Several generations ago it began to be understood that business cannot be a law unto itself, but will prosper only as it responds to public need. In this connection, I am reminded of a chapter in the recent book by Mr. A. A. Berle, entitled “The 20th Century Capitalist Revolution.” * In the chapter, “The Conscience of the King and of the Corporation,” Berle says: “Deep in human consciousness is embedded the assumption that somewhere, somehow, there is a higher law which imposes itself in time on princes and powers and institutions of this terrestrial earth. We must leave doctrine to the theologians; but as students of legal history we have to take account of the persistent fact of this huge assumption. Keepers of the tradition of this higher law—medicine men in primitive times, magicians or sybils in the ancient world, or divines today—are regularly listened to with respect. They have power, though it is not the power either of purse or sword. Throughout Western history a priest could commonly intimidate a policeman; the Cross could quite frequently stop the king * * *. “It is here suggested that a somewhat similar phenomenon is slowly looming up in the corporate field through the mists that hide from us the history of the next generation. There is beginning to be apparent a realization of a counter force which checks, and remotely acts on, and in time may modify in certain areas the absolute power of business discretion. In our system it emerges in time as law; and good lawyers watch for it.” My only comment on Mr. Berle’s statement is that, in the food and drug industries at least, the moral responsibility he speaks of has already been as- sumped. And the restrictive laws are already in force. The question is there- fore appropriate as to how well the enforcing agency is able to act under the law to exercise its power even-handedly in the public interest. JUDGMENT AFFECTED BY EMOTION I spoke of an uncertain striving for sound scientific judgment in the han- dling of regulatory problems. Let me say at once that this uncertainty is not restricted to regulatory officials: lapses in judgment occur all too frequently among scientists. Let me give an example—one to which I shall return later for further discussion. The Congressional Record of August 27 carries a letter? by an eminent phys- iologist, Dr. Harold F. Blum, to Congresswoman Leonor K. Sullivan. he letter answers her request for information on the establishment of tolerances for chem- ical substances added to foodstuffs. Having pointed out that our knowledge is limited of how to determine the “threshold dose” of a cancer-producing agent in man, Dr. Blum concluces: “* * * it would seem that the only practical answer would be to beep any substance known to induce, or suspected of inducing cancer at as low levels as Rerle, A. A. “The 20th Century Canitolist Revolntion.” p, 69, 1954, Harcourt. ? Extension of remarks of Hon. Leonor K. Sullivan, Congressional Record Appeudix, vol. 105, A7482 (Aug. 27, 1959). 56123—60——_15 220 COLOR ADDITIVES feasible. The assigning of tolerance limits—which must necessarily be arbi- trary—can only give a false sense of security.” It is the last four words—“false sense of security”—which disturb me. Ad- mittedly the desire for security is a powerful motivating agent. It has great power to involve our whole emotional makeup. The same thing might be said at the present time of the word “cancer.” It is something from which we would like to be separated by an absolute guarantee. But we cannot forget that complete security, from cancer or from any other state which may befall mau, is not absolutely attainable in human life. To say, therefore, that the setting of a tolerance for a chemical used in food, on the basis of the best scientific judgment, would give a “false sense of security” is really to transfer the false sense of security elsewhere. For it suggests that, if no tolerances are established for a substance known to cause, or even sus- pected of causing cancer, say, in experimental animals, all tolerances which are set for other substances are entirely free of question or of hazard, For example, does the establishment of a tolerance for a new antioxidant mean that nowhere among the 170 million people in the United States might the antioxidant produce a skin reaction, or some other unexpected response? It is impossible to guarantee with absolute certainty that any substance is inca- pable of some unexpected effect. WHAT IS SCIENTIFIC JUDGMENT? I used the term “scientific judgment.” What does the term mean? In the first place, it is based on belief. Belief is an all-or-none proposition. A young man doesn’t say, “I probably believe Susie Brown loves me.” He might say, “I believe Susie Brown probably loves me.” Daisy petals give only two choices of belief : “she loves me”; “she loves me not.” On the other hand, one may properly speak of degrees of reasonableness of belief. One appraises the probabilities that a belief is true and arrives, more or less formally, at an idea of how firm is the evidence on which his belief is based. One expects to watch for further evidence affecting his belief. If it continues favorable, his belief is strengthened; if the trend is adverse, there comes a point at which he abandons his belief, and that is that. What then is “scientific judgment’? It is the concept that reasonableness as applied to belief may properly be related to reasonableness in acting upon the belief. In other words, when enough data are obtained to support taking an action which has desirable practical consequences, it is foolish to delay action for more stringent evidence. That was not my COLOR ADDITIVES 321 which were carcinogens whether, as or if the Delaney amendment were included or not. Mr. Witutams. Of course, I cannot—— Mr. Dincety. That was my understanding of the matter previous to the time that H.R. 12354 was enacted. Mr. Witi1ams. I do not understand it, Mr. Dingell. I do not know what it was. Mr. Drncetx. I would appreciate your assistance in construing the statutes, and I would like to see that my understanding perhaps either matches or conflicts with your understanding of these things, so that we can achieve intelligent approaches. Apparently you are construing these statutes, and I am very ap- reclative of your help, but I was on the committee at the time, and 4 was on the subcommittee that reported these matters out, and I had some pretty definite understandings as to what these things ap- plied to, and I now find that maybe my understanding was not cor- rect, and if I am incorrect, I would like to be corrected right now. Mr. Witu1aMs. Well, I cannot add to what I have said. Mr. Dincetu. There are some things which you have said which concern me, the first of which is you talk about the establishment of threshold levels, and so forth. I am sure you will agree with me that there is substantial medical evidence that there is no proper way of establishing thresholds on these things with existing testing methods; ain I correct on this? a Wiuiams. I would prefer to leave Dr, Carney’s testimony on that. Mr. Drncett. As you recall, Dr. Carney and I had some extensive discussion. Mr. Witxtams. Yes. Mr. Dinceti. But you want that discussion with me to stand in the record as it is. But, as you recall in your testimony you made some rather pro- found statements as to the scientific merit of the Delaney amendment, and so forth and so on. Now I am asking you for some other state- ments, and I would like to see you not take refuge in Dr. Carney’s statement, but to now stand on your own feet and give me some an- swers of your own on this. Mr. Witu1ams. The only statements I have made are those which I have been advised are sound, and I have no way of going beyond that. Mr. Dincetx. You have been advised of these things and have no knowledge of your own on them ? Mr. WitxtaMs. I have been advised that they are sound and, of course, I will support all of the statements which I make with respect to the statute and the legislative background and the logical deductions which have been made as to the meaning of the Delaney clause. But I do not have any competence in the field of cancer. Mr. Dincety. Well then, you would say that we should give con- siderable credence to what you say with regard to interpretation of the statute, but that we probably should not pay any attention to your scientific conclusions? Mr. Wrx1ams. I think my scientific conclusions were based on very sound advice. 322 COLOR ADDITIVES Mr. Drycex. Sufficiently sound so that you can stand on that, but not be examined further ? Mr. W iL1AMs. Well, I do not think that you and I would get far, frankly, in an argument on that point, Mr. Dingell, as much as I would enjoy it. [Laughter.] Mr. DINGELL. “You talked about strontium 90, and whether or not, it should be construed as being subject to the Delaney amendment. You also said that the fact that strontium 90 is in foods is also a basis for us to consider that there is a threshold level for safety. Have you read some of the scientific works on this subject ? Mr. Wituiams. Now, just a minute. I did not say what you said I said, Mr. Dingell. Mr. Dinorne. Well, I refer you to page 11 of your statement, and then ask you what you did say. Mr. Wituiams. All right, I will tell you what I said. I said that the Department, through the releases of Mr. Flemming and, perhaps, the Food and Drug Administration Mr. Dixerit. Were these releases directly construing the Delaney amendment ? Mr. Wititams (continuing). Have recognized threshold levels of strontium 90 which is an admitted carcinogen. I merely used that as an example of the inconsistencies to which you are led when you apply a per se construction to the Delaney clause. Mr. Dineen. Were these constructions of the particular statute, these press releases or these statements that you have referred to? These were not constructions of the Delaney clause or of the Food and Drug Act at all, were they? Mr. Wut1aMs. No, they were merely recognitions of threshold levels. Mr. Dincet. Well, now I intend to go into that. Further, as a matter of fact, these statements merely were that, as T recall them, and I am sure recollection is about the same as yours, they were merely statements my the Department that they could not show that there was any harm coming from these substances; is that correct? And they did not come out ‘and say that the milk was safe. They Just said they cannot prove the milk was not safe; isn’t that correct / Mr. Witi1aMs. No, sir. Mr. Dixcrtt. Then there was another body Mr. Witu1ams. Do you care to hear what they said ? Mr. Dincety. Yes, i would like to hear it. Mr. Witu1ams. This is the release of January 12, 1960: Analyses of single samples of wheat, cabbage, and potatoes from 12 States, and one sample of soybeans from one of these States showed levels of stron- tium 90 to be within the limits recommended by the National Committee on Radiation Protection and Measurements as permissible for lifetime exposure. Mr. Dincetu. This does not say they cause cancer or did not cause cancer, does it ? Mr. Witiiams (reading) : The Food and Drug Administration noted that the total radioactivity in the dried fruits above referred to was below the levels which would indicate a need to determine strontium 90 levels, It is all in terms of levels, Mr. Dingell. COLOR ADDITIVES 323- My only point was that they are recognizing there are levels below which there is no danger. Mr. DINGELL. They did not say though this was a level below which or above which cancer would be created. They made no mention of cancer in those releases, did they ? Mr. Wiuiams. I think it would have been even more embarrassing if they had, than it was. Mr. Dincetn. But they made no mention of it, did they ? Mr. Wittrams. No, they did not. Mr. Drvcett. And. as 2 matter of fact, there are a number of other things that you can determine from analysis of strontium 90, that it destroys bone marrow, it inhibits growth, it has a number of other toxic effects, including attacking the red blood cells and many, many other things; am I correct? Mr. Wirt1ams. T do not know. Mr. Dincetu. Well, these are true. Now, you made one statement on page 12 that I wanted to point to. You said: We want to avoid any misunderstanding of our position. We do not advocate the addition to the carcinogenic materials normally in our food supply. That would imply that much—it would imply that you would sup port the Delaney amendment which says, “We don’t allow the addition of any additional carcinogenic materials.’ > “Am I correct ? Mr. Wituiams. Perhaps you did not read the whole sentence. Mr. Dinceut. Well, as much as I just want to see whether our under- standings are clear as far as we have gone. Mr. Witutams. Then the answer is I did not intend that because I state at the end a qualification which may increase the incidence of cancer among the population, That is the whole point. Mr. Diners. Then you goon: Of the additional substances which may increase the incidence of cancer among the population. We desire sitmply to establish the proposition uniquivoe- ally in the statute that the regulatory agency, the Food and Drug Administra- tion. shall be empowered to determine whether the addition of a particular sub- stance will have that effect. Are you familiar with the work of the International Union Against Cancer, and more specifically the remarks of Dr. G. Burroughs Mider, M.D., on this subject ? Mr. Wiiiiams. I have a vague familiarity with those things. Mr. Drxcers. I wondered if you drew from that some of the same things I drew, where he said that carcinogenic substances can have accumulative effect, both insofar as repeated exposure to the same sub- stances, and so far as esposures to different substances at reasonably contemporaneous times, having accumulative effect ¢ Mr. Winiaams. I under stand that is true or many toxic drugs, Mr. Dincen., And he reported out that, as I underst: and, different persons would react. differently to different carcinogenic substances, Did you draw that? Mr. Witirams. Did I what? Mr. Dtncetx. Did you draw that inference, too? Mr. Witurams. That persons—— Mr. Dincevu. Did you draw the same inference that I did that different. persons would have different reactions? 324 COLOR ADDITIVES Mr. Wiuu1aMs. I would assume different persons would react dif- ferently. That is true in many fields. Mr. Divcent. I wonder if you derive from that the same thing I did, where he says—— Mr. Wituiams. But there is nothing new—— Mr. Dincetu. Where he says that: If a substance is shown by adequate tests to be carcinogenic for one mam- malian species, it is probable that it is carcinogenic for many, but not neces- sarily for all others, although quantitative differences between species may be marked. Did you get that inference from his work ? Mr. Witxrams. I have not read that particular part of his work. All I know is—— Mr. Dincetx. I would recommend it very highly. It might be that you would want to change your statement after you read it. Mr. Wuu1aMs. I listened to Mr. Flemming, and I read what Mr. Flemming quoted, but I assure you that our people have read it very carefully. Mr. Dincett. The last thing he said is this: There are nontumorigenic levels of exposure to carcinogens for given experi- mental conditions, but threshold levels may be affected by a number of factors associated with carcinogenic process. The burden of his remarks in this portion was that we cannot always fix levels; in fact, we cannot fix levels at all. Would you take any issue with that, I wonder? Mr. Wituiams. The fact that you cannot always fix levels? Mr. Dincety. That you cannot. Mr. Wituiam. I would assume you could not always. I do not know for a fact. Mr. Dincetu. Would there be agreement between you and me as to this point all through your testimony here today ? Mr. WituraMs. No, sir, Mr. Dingell; because all we are advocating is that this whole matter be returned to a scientific basis; that the Department of Health, Education, and Welfare, through the Food and Drug Administration, be permitted to use its scientific facilities to determine in each case, in each specific case, whether a given sub- stance, whether it is a carcinogen or some other toxic substance, is safe for use under the conditions under which it is to be used. We are not trying to—we are perfectly willing to face the problem of convincing the Department in individual cases. That is a matter of evidence and scientific judgment. Mr. Dinceti. What would you say about the substantial volume of scientific opinion, and informed scientific opinion, of capable, com- petent people, who say that any exposure to any one of these carcino- genic substances creates an irreversible change within the cell, which can never be changed, and which can never be reversed ? Mr. Witutams. Well, asa layman, I would doubt it. Mr. Dincett. You would doubt it, as a layman ? Mr. Witttams. Asalayman. Afterall, we are Mr. Dincevt. After all, we, in ignorance, could agree or disagrea Mr. Witttams. Weare exposed to them all the time. Mr. Dincett. These are scientific people. COLOR ADDITIVES 325 Mr. Witutams. We are exposed to them all the time we eat these. Mr. Divcexy. Iam awareof this. Do you want totake on any more of these substances than you have in your lifetime? Mr. WutuaMs. No, sir. I think that I explained my position. I wanted the Food and Drug Administration to decide what we should take on or what we should not. Mr. Drncety. Let me just ask you one or two more questions. As a general premise, would i be correct in this, that if we err in the field of cancer and carcinogens, any error which is made in leg- islating in this field should be made on the side of safety of the con- sumers who will have to take this substance more or less unknowingly, unwittingly, and unintentionally; is that a correct statement ? Mr. Wiu1aMs. If there is an error? Mr. Dincexz. Yes. It should be made on the side of safety of the consumers. Mr. Wuutams. Yes. I think, in general, that is true. But I think that whether Mr. Dincetu. But here we ought to make a specific exception ? Mr. Wiiu1ams. But I should think it should be evaluated by a scientific agency, not by Congress. The way you did it before, when you passed this bill originally, you left it up to the scientific agency, the Food and Drug Administration. And then suddenly this clause was inserted, and now it becomes a great thing for some reason, I do not know why, just since last summer so far as I can figure. Mr. Dincety. Should not any error which is made in this field be made on the side of safety for the consumer, and I am talking about legislatively as well as scientifically ? Mr. Wituiams, If there is an error, naturally you would want to make it on the side of safety. But to my mind it would not be an error to give the decision to the qualified agency involved. Mr. Dincetzt. Thank you very much. Thank you, Mr. Chairman. The Cuarrman. Mr, Keith? Mr. Kerru. No questions. The Cuairman. Mr. Nelsen? Mr. Netsen. No questions, The Cuarmman. Mr. Williams, I would like to turn to the last page of your statement for just one moment. As I understand, under present law the burden is on the indust to show that there is nothing present in a particular additive that will produce carcinoma? Mr. Wru1ams. I believe it amounts to that; in effect, proving a negative, which, of course, is impossible. The CHamman. Now, under the proposal of the language here, would the burden be shifted from the indust ry to the Food and Drug Administration ? Mr. Wituiams. No, sir. The Cuaman. The burden would still be on the industry then to show that such material were not present ? Mr. Wituiams. To the satisfaction of the Food and Drug Adminis- tration. The Cratrman. To the satisfaction of the Food and Drug Ad- ministration. Mr. Wiu1ams. That is correct. 326 COLOR ADDITIVES The Cuairman. Now, the procedure by which a final decision would be made would be under the provision for a public hearing, and so forth; is that right? Mr, Winitams. W ell, conceivably the matter could go to a public hearing. But se ientific matters of this nature have very rarely, if ever, gone to a public hearing. The Cuamman. In other words, a decision could be made without a public hearing? Mr. Wiiurams. Oh, yes. Theoretically the industry can insist on a public hearing under certain circumstances. But the history of these dealings between industry and Food and Drug is that if the Food and Dr ug Administration announces or tells the industry in- formally that “We think that you have not given us enough ma- terial to justify our giving you a tolerance” or “that we think that there i is some suggestion of carcinogenicity involved with this prod- uct,” then the industry withdraws its application, That happens time and time again. The Cuairman, I call your attention to page 13 of the bill referred to, H.R. 7624, paragraph (d), The provisions of section 701 (e), (f), and so forth, and followi except that (1) the Secretary's order after public hearing (acting upon ob- jections filed to an order made prior to hearing) shall be subject to the re- quirements of section 409(f) (2) and so forth. You do not think that would require a public hearing for the Sec- retary to take such action under the suggested modification ? Mr. Witiiams. As I said just a» moment ago, under certain cir- cumstances the applicant is entitled to a hearing. He is entitled to a hearing under certain circumstances. But, as a matter of practice, so far as I know, there has never been a food additive hearing; in fact, I am sure there has not been. The Cuataan. I note the Commissioner is sitting behind you, and shaking his head, so it must be that there have been some. Mr. Wuu1ams. There have been some? Mr. Larrick. We have got a color additive hearing scheduled for February 17. Mr. WitiiMms. I was thinking of food additives. That is not under this legislation. Mr. Larrick. You see, he used to be our General Counsel. [Laughter. ] The Cramman. Well, with you backing him up he should know what he is talking about, What you propose here would not deprive the Secretary of any of the authority that he has now to prevent. the use of any suc h materials that may have cancer-producing material in it? Mr. WittrAms. Correct. The Cuarrman. In other words, it has been construed by the De- artment under present law that they have no alternative than to volist 2 ? Mr. Winutams. That is right. COLOR ADDITIVES 327 The Cuamman. And under the suggested modification here the Secretary would have the authority, if he determined that they were safe, to permit the use, On the other hand, the Secretary would also have the authority and duty and responsibility in the protection of the public health and welfare of the American people, to prevent such use? Mr. WituraMs. Yes, sir, that 1s correct. The Cuamman. And you think that should be a fair proposition ? Mr. Wuuiams. Well, that is the one that your committee unani- mously reported out in 1958, The CuairmMan. That is the reason I cannot understand why there is so much difference in this thing because, as a matter of fact, as I stated before, I recall a statement that was made by the Secretary which said that he would have taken the same action that he did take even if he did not have the Delaney amendment. Mr, Winuiams. What wasthat, Mr. Chairman? I did not hear that. The Cuarrman. He said he would have taken the same action that he did take even if he did not have the Delaney amendment. Maybe he was misquoted in the press. I think it was in the press. Mr. WuuiaMs. I think he did say that and, as I said in this state- ment, if his approach is a sound approach from the scientific stand- point, then he does not need the Delaney amendment to do what he has said he would do, The Cuairman. I have a feeling that we have reached a stage in all of this where there have been so many questions raised on the terrible disease of cancer, that perhaps. the Delaney amendment, if applied correctly, to permit those things that are in the interests of the Amer- ican people and the health of ‘the people, and to prevent those things where there is any chance of being harmful, probably would serve a worthwhile purpose. Mr, WitviAms. If properly drawn. The Cuamman. Ilad it never been brought up, probably the health and welfare of the people would have been protected just as well. But now everyone, it seems to me, and there are so many people that I say almost everyone, is so conscious of cancer as a dread Fisease, and I think rightly and justifiably so—I know out of my own exper ience, only recently I had a little substance removed from my lip, a little sebaceous cyst on my back, and well, I know I felt a whole lot easier about 2 weeks after that when I was told that it was all right. I feel that I am just an ordinary American citizen. People are sO conscious of this deadly disease when it gets hold of them, that it seems to me arbitrarily to throw out the Delaney amendment would create so much fear in the mind of the American people in their reaction against industry that it might be pretty bad. Mr. Wititams. Do you think that such fear would be created if it were left in as an emphasis upon this problem, with the amendment which we propose ? The Cuatrman, No,I do not. In other words, I have a feeling that, it ought not to be so construed, and if it is so construed, that it should be modified, to permit the regu- lar delegated administrative officers to deal with it practically, and in the best. interests of the health of the American people. 328 COLOR ADDITIVES I think, I have a feeling, that there is some danger, and it may be greater than we think, that there will arise a cancer scare as a result of knowledge that so many of our common foods do contain carcinogens, Mr. Wiut1ams. These are just a few we have mentioned here today, and if this thing is agitated as it has been in the past, and then the facts are going to come out sooner or later, and I think it would be much better if we had a reasonable approach to the thing and put it back where it belongs with the Food and Drug Administration. They are perfectly capable of handling it. They have been handling it for years. The Cuarrman. It seems to me that could be done in a way to main- tain the intent and purposes—— Mr. Wituiams. Yes. The CuairmMan (continuing). Of the amendment itself without de- stroying or deleting the amendment. The way conditions are today I hope nobody will take milk away from us, but somebody will say that we cannot grow alfalfa hay any more or feed clover as a pasture. It seems to me like getting down to the fine points, but it is a fact if the law is not changed within a matter of a few months some permanent law on color additives will be adopted, and it is going to be a lot more rigid than it is today. Mr. WituraMs. They tell me, Mr. Chairman, that there are a great many more chemical substances than you would think even from what you have heard, which will, when ingested or injected in animals cause cancer under certain conditions and in certain strains of animals, and we do not know how many of these coal tar colors may do that. We do not know how many other food additives may do that. We have never tested them, and we do not know how many other food additives may do that. The Cuarrman. I would agree with that, as little as I know about it. Mr. WuutaMs. We just have no idea yet. But if we are going to put it on the basis that it is going to be put on, since the Delaney clause has been interpreted as it was by the Department, I do not know where we are going to come out, but it is not going to be good. The Cuarman. I think it should not be so rigid that the public would be deprived of something it should have. On the other hand, it appears to me that we are living in an age when there are so many synthetics that are being used and additions to this or that or the other, for one purpose or another, that perhaps it is necessary to extend some rather drastic authority or power within the proper agency in order to deal with it, and it is no reflection on industry at all, but I do know that there is a constant growth of the use of additives whether we use it or whether we eat it. ; Mr. Wituiams. I assure you they have plenty of power under these ills. The CHamman. You mean under the bill? Mr. WittiaMs. Yes. The Carman. I know that is what you are complaining about. At. Wuutams. No; I mean other than and aside from the Delaney clause. COLOR ADDITIVES 329 The Cuaman. I would not argue that question at all, but I still say that since it has already been included, to then try to eliminate it completely, I think, would bring on a lot more difficulty than it would be to try to adjust it in a way that makes it workable. That is my belief. , Mr. Witi1ams. We made a suggestion for adjusting it. The Cuarrman. Yes; and I want tocompliment you on it, too. I would be interested in analyzing it further in order to see if we can come to the same conclusion that you have come in presenting it. Let me thank you again for your testimony that you have given to tho committee. Mr. Witurams. Thank you, sir. The Cuairman. Mr. Peter Janss. Mr. Janss. Thank you, sir. By your leave, Mr. Chairman and members of the committee—— The Cuairman. You are Mr. Janss? STATEMENT OF PETER W. JANSS, ATTORNEY REPRESENTING NATIONAL FEED INGREDIENTS ASSOCIATION Mr. Janss. My name is Peter W. Janss, and I have lived and prac- ticed law in Des Moines, Iowa, since 1927. Since 1945 I have represented the National Mineral Feeds Associa- tion, and its successor trade association, the National Feed Ingredi- ents Association, comprised of some 70 member firms who manufac- ture and sell animal feed ingredients, and sometimes also manufac- ture and sell animal feeds. Mr. Chairman, with your leave, may I interpolate here and then file this statement ? The CuatrmMan. We will be very glad to let your entire statement be included in the record, and you can give a brief explanation of it. Mr. Janss. I am grateful to you and grateful to the committee for bearing with me while the great Midwest was under a terrific storm these last 3 days, resulting from a low-pressure area, and it was so intense as to break all records in Kansas City, some 19 barometic pressure. I simply could not get here on time, and I am still very grateful for your giving me this opportunity. Rather than read the statement or interpolate other remarks, I shall be very pleased to endorse almost entirely the philosophy and state- ments of Mr. Williams which he just made, on behalf of my association or, the association, rather, that I represent. The Curatrman, You represent the National Feed Ingredients Association ? Mr. Janss. Yes, sir; and with that I think it would be well to not take more of your time because these points I have made in here too concisely of pressure of time are the same that have been made by other witnesses, so I am cumulative in what I say from a different source of persons testifying, but I think it would serve no purpose, and unless you wish to simply have me read what I have said, and I will thus save your time. If there are any questions, I will be glad to answer them. 330 COLOR ADDITIVES The Cnamrman. Mr. Janss, let me on behalf of our committee thank you for your appearance here. I know you have been snowbound. Mr. Janss. Yes, indeed. . The Cuatrman. You came here after great effort and certainly you are entitled tomake your statement to the committee. Mr. Janss. I understand that, but they have been made for me. The Cuarrman. We appreciate having your statement. As we _look over it rather hurriedly we do see that it takes the same posi- tion and line as testimony previously presented Mr. Janss. That is right. The Cuarrman. By Mr. Williams. Mr. Janss. That is right. The Cuarrman. Are there any other questions of Mr. Janss? Mr. Dincett. Mr. Chairman, I was just wondering if Mr. Janss’ organization colored the feed that it sells to the feeders ? Mr. Janss. I did not quite get that. Mr. Dinaett. Do feed manufacturers color the feed that they serve, that they package and sell ? Mr. Janss. Only in specialized situations such as, for instance, min- eral feeds are often colored by the use of iron oxide which gives a reddish color to it, but it is also a nutrient. It is also classified as a sified as an essential nutrient, but is carbon, at least, and is utilized by the body. But ordinarily we do not color it in the sense that you are talking about. It is true, however, that under the definition of the color additive amendment practically everything we put in our feeds does impart some color and does qualify as a color additive under its definition, practically everything, including corn. Mr. Dincetu. Perhaps you are not familiar with the letter of the Food and Drug Administration which was inserted in the record of the hearings yesterday which went a long way to clarify that, but I would suggest that you direct your attention to that letter at your ealiest. convenience. Mr. Janss. I should be very glad to. Mr. Drncexu. How it affects your people. It affects your people ina way that you might have reason to think——— Mr. .Janss. I would be very pleased to do so. Mr. Dincext. If you would refer to page 4 of your statement, as I read it here, it refers to, I believe, the Delaney amendment. You specifically endorse, as I understand it, the amendment that has been suggested by the witness who preceded you; is that correct? Mr. Janss. Yes, I do. Mr. Drnceti. As a matter of fact you urge really that when a sub- stance is fed, according to its intended -use, it leaves no residue, car- cinogen, in the tissue of the animals—rather let me say this: As I read your statement, it would satisfy your organization if it would not be a violation of basic food and drug law or proposed amend- ments, if the substance when fed according to its intended use leaves no residue of carcinogen in the tissues of the animals, at least if that situation would result in no violation; is that correct 2 ° mineral nutrient. —— We also sometimes color it by use of carbon black which is not clas- ‘COLOR ADDITIVES 331 Mr. Janss. As far as carcinogens are concerned, that would seem to me to be adequate. Mr. Dincexy. That would satisfy you? Mr. Janss. Yes; it would. Mr. Dincetu. In other words, if no residue is left in the tissues, then the substance is proper for feeding. Now, as I read the situation with regard to stilbestrol, that is pre- cisely what is done today. In other w ords, they say as long as there are no carcinogens and no remains in the tissues, it is all right to feed to human beings. Mr. Janss. Their difficulty lies in the prior sanction situation. Diethylstilbestrol is being fed now and because I endorse the position of diethylstilbestrol as permitted in new drug applications because it does not leave carcinogens in the tissues, their difficulty lies in the fact that because it is a new drug status, they must now take off the market, by virtue of the amendment any new application for the use of diethylstilbestrol however it may be formulated in a feed, a new feed, or a formula. For instance, to illustrate, one of my members uses diethylstilbestrol in the feed now. If he would change the percentage, for instance, of soybean meal in that particular feed, he would have to come down to Food and Drug Administration and obtain a new application for that changed formula. The position of the Food and Drug Administration is that he can- not so obtain such a new application with that formula. He is frozen with such prior sanctions as they have already issued with reference to diethylstilbestrol. Mr. Dincety. But this is not because of the Delaney amendment. Mr. Janss. Yes, sir. Mr. Dinecett. It is? Mr. Janss. It is my understanding it is; yes. You see, before the Delaney amendment was passed, they had approved a number of uses of diethylstilbestrol in animal feeds. As it was passed and as it was interpreted by the Food and Drug Administration, their counsel there said no more. That meant that no change in the existing feed could be made and approved, because that would require what they call a new, or an extension of the new drug application. So they said what is out now is out, nothing more. And this causes, incidentally, a very difficult situation in the feed trade, because some people are using diethylst ilbestrol in their feeds and others cannot. This is because of the interpretation of the De- laney amendment to the food additive amendment, not to the color additive amendment. But that is the reason it is so. Now, whether that be right or not, I am not here to say. But this is the reason I say, or suggest, on behalf of my people, that the test should be in the residues in the tissues of the animals that are fed our animal feeds, Now, I am not talking about human foods. I agree with what Mr. Williams has said, from what I know about it through information given to me, that there are any number of carcinogens that are eaten by all of us every day in our normal foods, human foods. 56123—60——— 22 332 COLOR ADDITIVES And so all I say here, as far as diethylstilbestrol is concerned, and other such carcinogens, is that if they leave no evidence in the tissues of the animals that are eaten by man, then they should be permissible, permitted under the guidance of the Food and Drug Administration. I go exactly with him in saying let them decide. They are more competent than perhaps the Congress, more competent, perhaps, than anyone else to do just that job, and give them that power and let them do it. That is what I say. Mr. Dinceti. Thank you. Thank you, Mr. Chairman. The Cuamman. Mr. Nelsen? Mr. Netsen. Do I understand stilbestrol, for example, that is pres- ently under the existing law, under the Delaney amendment that is now approved for use in feed, may continue to be used in feed? Mr. ess. Yes, sir. Mr. Nevsen. The permits have been issued ? . Mr. Janss. Those that were issued before the Delaney amendment became effective. Mr. Neusen. Yes, and new applications would, under the Delaney amendment, be denied ? Mr. Janss. Yes, sir. Mr. Nesen. Therefore, under the circumstances that we now deal with, those who may fear the use of stilbestrol still have the problem before them, right or wrong, it isa situation that does exist. Mr. Janss. Your observation is true. I don’t know whether you can balance it out or not. But then your observation is accurate. Mr. Netsen. What I mean by that is some may use it and some may not. Mr. Janss. That is right. Mr. Nevsen. As I understand it, industry is not objecting to the fact that all of these additives need be examined. They merely are asking for clarification of the law so a uniform application may be made. Mr. Janss. I think that is part of our request, part of my request, let's put it that way. I think I would agree with that, but I want to go one step further. I want to do what Mr. Williams said, give the power of determina- tion as to whether or not this particular drug or food additive or color additive, or carcinogen, whatever you may want to call it, that may have some potential danger to animal or man, leave it to them, whether or not it is safe, as distingiushed from putting in an adamant clause that says if it is found to induce cancer in man or animal in any cir- cumstances, or under any conditions, that it cannot be used anywhere. That is the potential difficulty. We are also faced—this is inci- dental to this, but I stated, if you will permit me, incidental to this is a thing that is faced by some of my people. We have already under the food additives amendment a classification of certain other mate- rials, not carcinogens as far as we are told, unless they might be unknown to us, are classified now as to limits which may be used. They are ordinary mineral nutrients, such as iron sulfate, cobalt sulfate, and a number of others, cobalt, iron, manganese, and copper. They are now saying that they can be limited, used only in certain limited areas. COLOR ADDITIVES 333 Whether or not they have authority to do that under the Food and Drug Act, the food additives amendment, I am not sure. But this is again one step further and I am not complaining about this. I think they are doing what they should do. We have to find out whether they have the authority or whether it is right. But it does indicate that the Food and Drug Administration is very active, very active in taking care of the people of the United States. They are doing their best. We may have to fight them on some of the limitations they are placing upon us now. But I don’t have any doubt at all but what they are doing a fine job, and that they are trying to do the best thing. I think their feeling must be, or is, rather, that we put them in a legal straitjacket here where they, themselves, must do things they don’t want to do and injure the people in the doing. We must inci- dentally, I think, keep alive a very, very strong, virile and significant activity in the land grant colleges all through the country in experi- mentation with animals and in bringing out new things. True, I am sure, it is commercialized to some extent but I think they are doing a magnificent thing through industry for the building of more food and better food. And if, parenthetically, the population exprosion is real, why we will need that. fr. Nevsen. I rather join with the chairman in the fear of alfalfa being barred, because I would be in a bad way with my dairy cows if I couldn’t feed them alfalfa. Mr. Janss. Those are but one of a few, I guess. The Cuatrman. Thank you very much. Mr. Janss. Thank you, Mr. Chairman and gentlemen. The Cuarrman. I hope you have better luck trying to get back home than you did coming up. (The prepared statement of Mr. Janss is as follows:) STATEMENT OF THE NATIONAL FEED INGREDIENTS ASSOCIATION Mr. Chairman, my name is Peter W. Janss and I have lived and practiced law in Des Moines, Iowa, since 1927. Since 1945 I have represented the National Mineral Feeds Association and its successor trade association, the National Feed Ingredients Association, comprised of some 70 member firms who manu- facture and sell animal feed ingredients and sumetimes also manufacture and sell animal feeds. Our members have a more immediate and direct interest in the food additive amendment to the U.S. Food, Drug, and Cosmetic Act, but have asked me to express to you on their behalf an objecton to some of the provisions contained in H.R. 7624, commonly referred to as the House color additive amendment. Stated very concisely these ingredient and feed manufacturers wish to clearly separate the color additive amendment from the food additive amendment so that the provisions of the one cannot be interpreted as being applicable to the other, Section 101(n) of H.R. 7624 effectively excludes a color additive from the definition of a “food additive” set out in section 201(s) of the Food, Drug, and Cosmetie Act. But section 101(b) of H.R. 7624 in lines 18 to 25 inclusive on page 2 and lines 1 to 9 inclusive on page 3 defines a color additive among other things as including “(A) * * * a substance * * * derived, with or with- out intermediate or final change of identity, from a vegetable, animal, mineral, or other source, and (B) when added or applied to food, drug, or comestic, * * * is capable (alone or through reaction of other substance) of imparting color thereto * * *.” The term “color” includes black, white, and intermediate grays (lines 11 and 12, p. 3, H.R. 7624) Such a definition will clearly include substances which fall within the defini- tion of “a food additive” as set out in section 201(s). Practically any ingredient 334 COLOR ADDITIVES placed in animal feedstuffs will impart some measure of color thereto, and practically every such substance falls within the meaning of the definition of - “food additive” unless it be exempted by the provisions of section 201(s). The proposed color additive amendment as set out in H.R. 7624 is, of course, substantially different than the food additive amendments already enacted into law and it is our present desire that the provisions of the color additive amendment be not invoked by the Food and Drug Administration as a part of their administration of the food additive provisions of the law. To state it simply we agree that the food additive amendment should not include a “color additive” all as provided in section 101(a) of H.R. 7624, but we also believe that the definition of a color additive should comparably exclude a “food additive” so that a substance must fall in one or the other of the two categories and be there alone controlled. Without the suggested amendment it is not only possible, but probable, that the Food and Drug Administration will be constrained to utilize the rather stringent provisions of the proposed color additive bill to exercise control over feed ingredients which are now exempted from the food additive amendment because they are shown to be safe through experience based on common use in food under conditions of their intended use for a period long preceding January 1, 1958. While this may seem a somewhat tenuous legal argument, yet experience has shown that the department literally follows theh language of the law and in this instance both can and will, where necessary, interpret the color additive amendment so as to include practically all food additives because each of them impart some measure of color to animal feeds, and yet at the same time exclude all color additives from the effect of the exemptions set out in the food additive amendment (201(s)). We respectfully submit this possibility can and should be forestalled by the adoption of the following rather simple committee amendment : Amend line 4 of page 3 of H.R. 7624 by adding after the word “include” the words “a food additive or’. We also respectfully submit that the particular language of section 108(b) lines 11 to 22 inclusive, page 10 (proposed sec, T06(a) (5) (b) of H.R. 7624) is substantially different in context and meaning than a comparable clause in sec- tion 409(¢)(8)(A) of the Food, Drug, and Cosmetic Act relating to food addi- tives. The National Feed Ingredients Association here registers earnest resistance against form of the provision for the reason that it places beyond any possible use very valuable color compounds and perhaps nutrients simply because under extreme conditions and in extreme amounts the particular substances might in- duce cancer in either man or animal. The same interpretation has already been placed upon similar language in section 400(¢) (3) (A) of the act. This subcommittee will likely hereafter receive testimony from witnesses technically competent to discuss the impact of this conclusion upon the agricul- tural economy of United States and who may also have suggestions for the com- mittee concerning the restatement of the subject language in H.R, 7624. For our purposes we here quickly state that we believe that the livestock industry of United States and the agricultural economy of the United States, while com- pletely sympathetic with all legitimate measures against the biological induction of cancer in man, still very properly insist that cancer as such in animals can and will be adequately protected under existing adulteration provisions of sec- tions 402 and 401 of the Food, Drug, and Cosmetie Act. This subcommittee should also consider what is known as the Delaney amendment to the food addi- tive amendment appearing in section 409(¢) (3) (A) and amend the same by at least deleting the language which impels the banishment of any substance as a food ingredient (unless otherwise exempted) which under any circumstances and under any amounts mny induce cancer in an animal. Another possible amendment of both the food additive law and the color addi- tive law with reference to carcinogenic materials would encompass a permis- sion for use, if the substance when fed according to its intended use left no re- sidues of the carcinogen in the tissues of the animals. We speak to these philosophies with respect to food additives because the color additive amendment seems to be even more restrictive than the food addi- tives provision of the aet and also because, as aforesaid, our interpretation of its language would permit the use of more arbitrary restrictions against poten- tial carcinogens in food additives which technically qualify as a color additive under the present language of the H.R. 7624. COLOR ADDITIVES 335 The National Feed Ingredients Association through me extends to this commit- tee sincere thanks for the privilege of appearing before it and extending the fore- going comments on H.R. 7624 on the public records of the committee. The CuHarrman. For the final witness this afternoon we have Dr. Harold Aaron. ; ; Dr. Aaron, will you identify yourself for the record ? STATEMENT OF DR. HAROLD AARON, MEDICAL ADVISER TO CONSUMERS UNION Dr. Aaron. I am Harold Aaron, a physician and medical adviser to Consumers Union. I regret, Mr. Chairman, that I have not prepared copies for the members of the committee. As a practicing physician I just barely was to make a train to get down here. The Cuarrman. Will you give us your address. Dr. Aaron. My home ‘address is 190 Leonia Avenue, Leonia, N.J. I am medical adviser to Consumers Union, a nonprofit member- ship organization and publication with some 850,000 member sub- scribers. Since its founding in 1936, Consumers Union has played an effec- tive part in education of the consumer in problems of the wholesome- ness and safety of foods, drugs, and cosmetics. It has also contributed to legislative efforts intended to fill gaps in consumer protection, in the Federal Food, Drug, and Cosmetic Act, the Poultry Inspection Act, and other consumer “legislation. Consumers Union welcomed the work of this committee of the House during hearings and subsequent enactment of the Food Addi- tive Amendment of 1958. We considered the food additive amendment the most important consumer protection legislation since the passage of the Federal Food, Drug, and C ‘osmetic Act of 1938. We believe that the principle that the safety of an additive should be proven by a manufacturer prior to marketing is sound public health and administrative policy, and should be extended to all color addi- tives. We also believe this principle should be extended to materials in cosmetics and to theraputic devices. At the moment, however, we are concerned only with the use of colors in foods, drugs, and cos- metics. The test upon which the present coal tar colors depend for their acceptability are acknowledged to be outmoded. They date back, many of them, to half a century. In 1950, when many children w ere made sick by an unusually hard concentration of FDC orange No. 2 in Halloween candy, it became clear that the early tests had not heen adequate. Using improved methods, the FDA began to recheck its colors. A substantial proportion of the colors restested so far proved to be not harmless within the meaning of the law. We believe that a bill to deal effectively with the problem of color additive should have the following features: 336 COLOR ADDITIVES It should require industry to prove that its use of the color will be safe from the point of view of acute or chronic toxic and carcinogen effects. It should allow the FDA to set tolerances for color in amounts that will not produce toxic effects. It should forbid the use of any color in any amount that causes cancer in man or animal, distinguishing, of course, between the exter- nal and internal use of such colors. It should extend the new color relations to synthetic colors, to colors extracted from vegetable and other natural sources, as well as to coal tar dyes, so that all coloring agents will be under one law. And it should forbid the listing of any color for a use that will pro- mote deception of a consumer. We support H.R. 7624 introduced by the chairman, a bill S. 2197 with essentially these provisions, excepting for the absence of the- Delaney clause as passed by the Senate last year. Last fall’s cran- berry episode illustrated the value of the Delaney cancer cause in bolstering the FDA’s ability to deal effectively for consumer protec- tion. Consumers Union considers such a clause in the color law essential to the proper protection of a consumer. As Arthur Flemming, Secretary of the Department of Health, Education, and Welfare, pointed out, a scientist cannot establish a safe tolerance for humans for chemicals which cause cancer in animals. On the basis of previous experience with carcinogens, on the basis of experimental data provided by experts in carcinogenisis, it is im- possible to state what 1s a safe dose of a carcinogen for humans. Sound public health policy demands, if there is any evidence that a substance is carcinogenic for any animal, in any dosage when taken by mouth, that that substance be considered a human carcinogen and that it should be excluded from the food supply before harm to a single human being has been demonstrated. To deny the carcinogenic properties of a material on the grounds that no case of cancer in humans has been proven to be caused by the chemical is neither good scientific logic, nor consistent with good public health policy. : As has already been mentioned at the hearings, a comprehensive statement on the role of certain chemical and physical agents in the causation of cancer was prepared by Dr. Mider and presented to this committee. I should like to quote from page 29 of this statement, articularly Dr. Paul Kotin’s observation on weak carcinogens. Dr. Lider quotes Dr. Kotin: Conservatism necessitates a virtually all or none concept in utilizing experi- mental data for humans, A large number of workers in the field of experimental earcinogenisis have erroneously tended to deprecate the clinical importance of experimental weak carcinogens. To implicate a potential experimental carcinogen as representing a greater human hazard is perhaps understandable, and, indeed, numerous clinical and epidemiological studies have shown such relationship to exist. To minimize the importance of, or to dismiss a weak experimental carcinogen in terms of human significance is wholly unsupportable. The impossibility of establishing a tolerance for carcinogenic ma- terials, a threshold level for such materials is accepted by leading and unbiased cancer investigators. When there is some evidence of COLOR ADDITIVES 2, 337 carcinogenic action in any experimental animal, it cannot be con- cluded that very low doses would produce no cases in the human population. Hence the question really is not whether certain chemi- cals or colors do or do not produce cancer in humans because the only way to fully prove this is to deliberately expose people for 20 years. and to wait for 20 years after they have been exposed. . The question is, shall we err on the side of safety or on the side of the commercial use of a chemical or color additive. Doubt as to the freedom from toxic effects of many colors employed in food, drugs, and cosmetics has already been established by tests of the Food and Drug Administration and by actual clinical episodes in the population. In 1950, as I already pointed out, many children were made sick by a heavy concentration in Halloween candy of a certified orange dye, F.D. & C. Orange No. 1. In October 1955, children were made sick by the same dye present in a popcorn con- fection. In December 1955, nearly 200 people, mostly children, were made ill after eating popcorn colored with F.D. & C. dye No. 32. So. there is no question that colors employed in foods can be toxic; that colors used in foods, drugs, and cosmetics have carcinogenic prop- erties is more difficult to establish, since tests have to be carried on during many years in several species of laboratory animals, But @ number of such food colors are listed in the report by Dr. Shubic and Dr. Howell, I believe, of the U.S. Public Health Service in a com- pilation of carcinogenic substances published by the Public Health ervice. Tests on the carcinogenic properties of food colors should be per- formed as well as on those colors used in drugs or cosmetics or on any color that eventually gains access to the digestive tract. A spokesman for the certified color industry objects to the cancer clause in H.R. 7624 because— it singles out for special and prohibitory treatment an element cancer poten- tiality which is but one of the many complex factors which bear on the basic test of safety, and it really adds nothing to that test. This spokesman, I am afraid, underestimates the importance of cancer control in this context. Cancer potentiality is not just one of many complex factors. It is in Consumer Union opinion the heart and soul of this legislation, the most important of the factors bearing on the basic test of safety. Consumers do not underestimate the im- portance of cancer potentiality of color additives, and if there is a single test by which the American consumer will apprise the merits of a color additive bill such as H.R. 2794, it is by the presence or absence of the cancer clause. The fact that carcinogenic materials are found naturally in certain foods as emphasized by spokesmen of the pharmaceutical industry is no justification for adding to the burden of carcinogens to which the population is exposed. It is justification for additional study of these foods or other nat- ural substances to determine the full carcinogenic potential of these foods. We all consume butter and eggs, cream, and other fatty foods, and these are natural products. And yet there is a significant medical opinion in this country that for some sections of the popu- lation these natural foods in excess may be harmful, and the fact that weak carcinogens are present in natural foods is no justification, 338 COLOR ADDITIVES it seems to me, for the establishment of the principle that a threshold of tolerance is possible for carcinogens that are added to the foods, to the drugs, or to our cosmetic materials. In the light of present knowledge of threshold effects of carcino- genic substances, the per se doctrine expressed in the Delaney clause is the only doctrine that is scientifically and morally justified. If and when it is discovered that a tolerance or threshold level for a useful chemical can be established as free of carcinogenic danger, then it is reasonable, proper, and possible for the FDA to request and obtain an amendment from Congress permitting the establishment of toler- ance levels for carcinogens. There are many other features in the House bill that deserve discussion and emphasis, but I shall not take the time to do this since it has already been done so well by Secre- tary Flemming in his statement of January 26 before this committee. Consumers Union fully and enthusiastically endorses Secretary Flemming’s statement. It is a statement that fairly balances the requirements of public health with the proper interests of private industry. The passage of H.R. 7624 would strengthen the conviction of consumers that. our food and drug laws are primarily concerned with protection of the public health, and not with commercial inter- ests. Ultimately the commercial interests of food, drug, and cosmetic manufacturers will be advanced when the public has confidence that our laws safeguard the wholesomeness and safety of these products, and that the Food and Drug Administration has the integrity, dedica- tion, and the resources to enforce these laws. During recent years the American consumer has come to trust the integrity and dedication of the Food and Drug Administration. They do not have the same trust and confidence in our Federal laws governing food, drug, and cosmetic products. Passage of H.R. 7624 without any weakening amendments and with the Delaney cancer clause intact will go far to strengthen the confidence of consumers in the wholesomeness and safety of our foods, drugs, and cosmetics. Thank you, Mr. Chairman. The Cruamman. Thank you very much, Doctor. We appreciate having your interesting and informative statement. Mr. Mack, any questions? Mr. Mack. Doctor, are you an officer in Consumers Union ? Dr. Aaron. No, sir. Mr. Mack. Where is the headquarters of this organization? Dr. Aaron, Mount Vernon, N.Y. Mr. Mack. Yousay you have almost a million members? Dr. Aaron. Subscribers and members combined. I think we have about 400,000 members and the rest are subscribers or new stamp pur- chasers. Mr. Mack. It is principally a publication? Dr. Aaron. It 1s principally a publication that reports tests on materials that the consumer uses, on services that the consumer makes use of, Mr. Mack. Is it similar to Consumer's Guide? Dr. Aaron. It publishes Consumer's Reports. There is another organization called Consumer's Research, our rival and competitor, that publishes a consumer publication. I think it may be called Con- sumer’s Guide, but I am not sure. T shall be glad to send you copies, Mr. Congressman. COLOR ADDITIVES 339 Mr. Mack. I am not very familiar with your organization. I have heard of various consumer organizations, but I was wondering if this was an organization which actually had members. Dr. Aaron. Yes, it does, Mr. Mack. Is this the largest one with membership ¢ Dr. Aaron. That is right. Mr. Mack. It has members in all the States of the Union ? Dr. Aaron. Members in all the States of the Union, in Canada and possibly in some foreign countries, although I am not sure about whether we permit foreigners who subscribe to become members as well. Mr. Mack. What are the dues of your organization ? Dr. Aaron. $5 a year. Mr. Mack. And that includes the publication ? Dr. Aaron. That includes the publication. It is a nonprofit organ- ization. Mr. Mack. How much is a subscription to the publication without membership ? Dr. Aaron. The same fee, $5. Mr. Mack. Then it would appear to me that you would have 8,000 members. Dr. Aaron. Some subscribers do not wish to participate in the vot- ing and other obligations of membership. They prefer simply to sub- scribe to the publication. Mr. Mack. So you have two classes of subscribers. Dr. Aaron, That is right. Mr. Mack. Thank you, Mr. Chairman. The Cuarrman. Mr. Younger. Mr. Younger. Doctor, earlier in your testimony you used the ex- pression that something was “found not harmless.” Can you pick that out of your testimony. Dr. Aaron. Something was found not harmless? Mr. Younger. Yes, you used the expression “not harmless” earlier in your statement. Dr. Aaron. I think it is— Hence the question is not whether certain colors or chemicals do or do not produce cancer in humans, because the only way to fully prove this is to delib- erately expose people for 20 years. But the question is shall we err on the side of safety? Mr. Youncer. No. Are you reading from something you have written ? Dr. Aaron. Yes, that is something I have written. Mr. Youncer. Or are those quotations from a paper? You had some printed things there. Dr. Aaron. Yes; that is what I published in Consumer Reports. I am including some portions that appeared in last month’s issue of Consumer Reports. Mr. Younger. You are not quoting from somebody else? Dr. Aaron. No, sir. Mr. Younger. You cannot find that expression that you used, “not harmless” ? In other words, it sounded as though you were advising that these carcinogenic substances were not harmless if used in a certain manner. That is the way the testimony sounded when you read it. 340 COLOR ADDITIVES Dr. Aaron. No; I had no intention of conveying that meaning, Mr. Younger. Mr. Youncer. That is all, Mr. Chairman. The CHarrman. Mr. Dingell. Mr. Dinceiu., Thank you, Mr. Chairman. Doctor, are you familiar with this substance stilbestrol ? Dr. Aaron. Yes, sir. Mr. DincEtu. You area doctor of medicine, are you not ? Dr. Aaron. Yes, sir. Mr. Dincety. You have been practicing medicine for how long ? Dr. Aaron. Twenty-five years. Mr. Dincetu. Do you prescribe stilbestrol ? Dr. Aaron. I do prescribe stilbestrol, but with caution, because I consider it a powerful hormone. I have heard some of the testi- mony about stilbestrol here, and I would be identified with the point -of view that Dr. Mider took about the precautions required in the administration of stilbestrol. It is very difficult to connect the ad- ministration of a drug or a hormone with the subsequent development of cancer or injury to a human being. There are so many factors that contribute to the evolution of a single disorder, particularly of -one like cancer, so many factors that are involved, that it is very diffi- -cult to isolate one factor and say that is responsible. Particularly in the development of cancer there is the concept of multiplicity of fac- tors which has been emphasized by all cancer investigators. If fac- tors A, B, and C are necessary to produce a cancer, and if you eliminate factor C, the cancer does not develop, then that factor C is of great importance in the evolution of the cancer. Now, it is possible that in some individuals stilbestrol can cause cancer, and I now personally gynecologists who will refuse to prescribe stilbestrol if there is a history of breast trouble in the family, or if there is a history of cancer in the uterus in the family. They will prohibit the use of stilbestrol in their patients irrespective of the medical indications for the use of stilbestrol. Mr. Dixcetu. These are sound men. Dr. Aaron. These are well-known investigators in their field or specialists practicing medicine who, in the light of researches in this field are convinced that for some individuals stilbestrol can be harm- ful if not a dangerous drug. Mr. DincEt. Possibly because of cancer producing-—— Dr. Aaron. Because of the possible effect it may have on susceptible segments of the population. I do not know whether I am in order in quoting from my own consultant, but my wife has a cystic mastitis -of the breast, and we consulted with Dr. Hagenson, who is professor of surgery at Columbia University, and the consultant in breast. cancer for the American Cancer Society, and he warns her against using stil- besterol, because of the possibility that it may have, and he can’t be sure, nor can anyone else be sure, it may be a significant factor in the evolution of cancer of one or more organs, and that is why most doc- tors are very cautious in their administration and prescription of stil- strol. Mr. Dincety. I wonder—you have been sitting here very patiently, Doctor, and you have listened to the testimony of a number of previous witnesses. You favor the language of the Delaney amendment as it appears in the original bill; am I correct on that ? COLOR ADDITIVES 341 Dr. Aaron. Yes, sir. Mr. Dincerx. You do not favor any watering down of it Dr. Aaron. No, sir. Mr. Drngeui. (continuing). To include “in an amount and other conditions reasonably related to its intended use.” Dr. Aaron. No,sir. I believe there should be no discretion involved in the enforcement of a regulation dealing with a cancer or carcino- genic agent, that discretion may sometimes be converted into whim, and whim has no place, whim or discretion have no place in public health policies, particularly when it concerns problems of epidemic importance. When the water supply of a city is polluted and there is a danger of a typhoid epidemic, we do not leave it to the discretion of the commissioner of health to announce this to the population. By law the commissioner of health, at least in my city, is compelled to take immediate and strong action to prevent harm to the population. Well, I contend, and I think many other doctors do contend, that we are faced with an epidemic, an epidemic of cancer, a chronic disease, and that all measures that will protect the public health should be taken, even at the cost of discomfort or sacrifice, financial sacrifice, to some segments of industry. Mr. Dinceii. Let me ask you this question, Doctor. How is the medical knowledge on cancer? Is it as extensive as let’s say the knowl- edge on heart disease or rheumatism or arthritis or let’s say some of the -other diseases like typhoid or even polio? Dr. Aaron. Our knowledge of the diagnosis of these diseases is con- siderable. Our knowledge of the causes of these diseases is fragmen- tary, to put it charitably. Mr. Dincext. Are you referring to cancer ? Dr. Aaron. I am referring to cancer, arthritis, heart disease, and other chronic disorders. We know very little about the causes of these disorders. We have some clues, we have some evidence, we have some directions, but these fragmentary pieces of evidence have not been brought together into a comprehensive view of the causation -of any one of these chronic disorders. Therefore, I think in the absence of definite knowledge, we must use whatever information we have to protect the population, and that information dictates, it seems to me, that any substance that is carcinogenic in any species, by a route that is natural to human consumption, that substance should ‘be suspected of being carcinogenic and should be banned from not only foods, but drugs and cosmetics, since, as you know, a wide variety of drugs are now colored. The extent of consumption of drugs in this population I think is very considerable and has been brought out in recent hearings and publications, and as far as cosmetics go, I think it has been established that the colors in lipsticks frequently are swallowed in significant amounts. But how significant remains to be established by further tests. Mr. Dinceti. Would you say our knowledge is sufficient to deter- mine whether or not these substances, when ingested, will cause cancer ‘over a long period? Dr. Aaron. For some of the colors there is sufficient knowledge. For others, more work is required to be done. Mr. Dincett. Thank you very much, Doctor, you have been most helpful. $42 COLOR ADDITIVES The Cuatmman. Mr. Nelsen? Mr. Nevsen. Mr. Chairman, in view of the testimony, for example in earlier statements, we have been told that, for example, hens’ eggs, milk, beef, soybeans, corn, lettuce, alfalfa, have certain factors in them that create cancer. By that criteria’ that you cite, would we bar the use of these products? Where do we draw the line? How do we do it? Dr. Aaron. I know the statement. has been made, but I would like to see the evidence for the statement. Several months ago a report appeared that feeding hens’ eggs to mice caused carcinomas to de- velop. Now, it is well known that certain strains of mice and rats spont: aneously develop carcinomas. When I brought this experiment to the attention of a cancer investigator, he pointed out that there were not adequate controls, that is a yopulation of that species of experimental animal, the rat under study had not been observed par- allel with that group of rats that were fed the eggs to determine the incidence of spontaneous development of carcinomas. The suscepti- bility of various animal species to cancer development varies widely, and it requires a substitute experimentation, a knowledge of the spon- taneous evolution of cancers in these animals, to draw conclusions about the effects of certain natural foods on these experimental ani- mals. And so I do not know the facts about these hens’ eggs. I do not know the facts upon which were based these other statements about the carcinogenic effects of other natural foods. One would have to examine the specific evidence. And I would not be the person to examine it. Such evidence should be examined by specialists; investigators in cancer. Mr. Newsen. Then if in your findings you found, then, that hens’ eggs did contribute toward this situation, then according to your statement you then would want to bar the use of hens’ eggs? Dr. Aaron. If hens’ eggs were known to produce cancer in human beings, I would certainly ask that it be barred, or that whatever ele- ment in hens’ eggs caused cancer should be excluded, Mr. Netsen. Thank you. The Cramman. Mr. Rogers. Mr. Rocers of Florida. I just want to ask two or three questions, Doctor. As I understand it now, you were talking about cancer, heart, arthritis and so forth, diseases for which we have about the same scientific knowledge as far as what causes them. I understand you to say that this is true generally. Dr. Aaron. That we are yonly at the threshold of our knowledge as to the causation. Mr. Rogers of Florida. Yes. Now, I notice that in your recom- mendations you say first that industry must prove the substance they want to add would not be harmful; secondly, that the Food and Drus Administration should be able to set certain tolerances. Dr. Aaron. For toxic. Mr. Rocers of Florida. For toxic. But when it comes to cancer alone, then you say, as I understand your statement. you want them to have no discretion at all. Dr. Aaron. No discretion and no tolerance. COLOR ADDITIVES 343 Mr. Rocers of Florida. Yes, and no tolerance. Now, in my mind I wonder if your position is consistent when, for instance we know that heart disease is responsible for more deaths than cancer. Now, you would allow them to set tolerances in those situations, and yet you do not want to have them use any discretion in setting any tolerances when cancer is involved. Now, why is that? Dr, Aaron. Well, heart disease is not caused by toxic materials. Mr. Rocers of Florida. Well, we know about materials that cause heart disease, do we not? Dr. Aaron. No. Mr. Rogers of Florida. We have no knowledge of any materials that cause heart disease—like fats ? Dr. Aaron. We are not certain that fats are the significant factor or what component of fats, whether saturated or unsaturated, nor what quantity. There is a growing body of evidence that suggests that nutrition may be one factor in the evolution of one type of heart disease, arteriosclerosis. Mr. Rocers of Florida. I know our doctors here tell us that if the level of cholesterol in the human body gets to a certain point it must. be brought down by cutting out fats. Dr. Aaron. If your cholesterol is very high and you have a bad family history of heart disease, it might be a good idea. But the doctor would not do it with great conviction. It might be a good idea to cut down on those foods that influence the cholesterol level. Mr. Rocers of Florida. But you do not feel that this has gotten to the point where Food and Drug could act? Dr. Aaron. No, sir. Mr. Rocrrs of Florida. All right, now what about liver diseases? I understand certain foods affect the liver. Dr. Aaron. Yes, certain foods do. Mr. Rocers of Florida. Are you going to give them any discretion in that? Dr. Aaron. What foods do you know of that affect the liver? Mr. Rogers of Florida. I have just heard testimony here. I presume you heard it, too. Maybe you haven't heard it all along, but I under- stand Dr. Aaron. No, I have been here only today. Mr. Rocers of Florida. I understand that as you said there were certain foods that would affect the liver. In other words, suppose there is some additive that would affect the liver. Under your proposi- tion here you would allow the Food and Drug Administration to set tolerances for that, and yet when it comes to cancer, then you allow them no discretion. It just seems to me a little inconsistent. Dr. Aaron. No, there is no inconsistency because there is a dose rela- tionship to toxic effects. In other words, if you take one gram of salt, you will get a seasoning. If you take 100 grams of salt, you have a poison. Mr. Rocrers of Florida. Yes. I understand. Dr. Aaron. But the same relationship does not exist yet with car- cinogenic materials. If you have one microgram of a carcinogen, that may be just as dangerous for a significant section of the population as a thousand micrograms. Mr. Dinceri. Or 10 pounds. 344 COLOR ADDITIVES Dr. Aaron. Or 10 pounds. Mr. Rogers of Florida. Or perhaps if we get to, say, 6 percent of cur diet—I understand if you feed 6 percent of a diet of salt to a rat, that that will be toxic. Dr. Aaron. That is right, sure. It depends on the dose in toxic effect. Mr. Rocers of Florida. Now, may I go further? We say we haven't been able to really test for cancer on humans in amounts sufficient to get results, and testimony today was that only certain strains of mice and rats were affected by stilbestrol, and many animals were not even affected then. But if we are going to judge everything on the effect it may have on animal, then the salt test certainly would demand that we cut out all salt in our diet because it could be harmful. Dr. Aaron. We have better tests for salt than the results that one sees in experimental animals. Humans have consumed salt, and we know by manipulation of the quantity of salt what effects small and large doses will have, just as we know what effects small and large doses of alcohol will have. But we do not know that there is a dis- tinction between small and large amounts of carcinogenic substances, and it is possible that some day a level can be established, a threshold of tolerance level can be established for a carcinogenic material. It is possible. But when that time occurs, there is no reason why the law cannot be changed. Mr. Rocers of Florida. For instance, now you feel that lipstick is in the position where it is harmful, although the testimony was that to get, as I recall, two parts out of a million a woman would have to actually consume approximately 100 lipsticks a day. Dr. Aaron. No. You see, it is impossible to translate dosages in experimental animals to dosages in humans. It may be that one gram of a carcinogen will produce a tumor in a mouse, but it may be only one-tenth of a gram will produce a cancer in a human a hundred times the size of a mouse. There is no relationship between dosage in ex- perimental animals and dosage in humans. This is not my opinion. Mr. Rocers of Florida. Yes, I understand. Dr. Aaron, This is the opinion of cancer investigators. Mr. Rogers of Florida. If there is no relationship, why are we still using the test that we are making on animals to apply to humans? Dr. Aaron. We are using the tests only qualitatively for carcino- gens. That is, once a substance is known to be carcinogenic by a route that is conceivable for humans, that is by ingestion, if it is es- tablished that it is carcinogenic, and that effect can be reproduced by other investigators, confirmed by other investigators Mr. Rocers of Florida. Confirmed? How ? Dr. Aaron. Confirmed by other investigators in other laboratories, I mean. A single investigator finding a cancer in one animal in a brood does not prove that that substance is carcinogenic. In other words, to establish a single scientific fact, you have to do a number of experiments. They have to be checked, counterchecked and con- firmed. Then you have a fact established. When that fact is estab- lished, that a chemical produces a cancer in an experimental animal, then that substance should be suspected of being cancerous for hu- mans until proven otherwise. Mr. Rocers of Florida. Yes. COLOR ADDITIVES 345- Dr. Aaron. And we should err on the side of safety. Mr. Rocrrs of Florida. Now, for instance, I believe that in the testimony which you heard today about stilbestrol, and I am just using that as an example, they said that in most of the animals in which it was tested there was no result with cancer, but simply in a highly narrow field where there had been certain breeding. This field was restricted to a very few strains of mice or rats and these were the only animals where cancer developed at all, and no amount of it developed it in other animals. Now, do you feel that no discretion should be used in cases of this type by the scientists as to whether or not a drug should be used? Yr. Aaron. Of course judgment should be used by the scientist, but we must define what we mean by “scientist.” A man who—— Mr. Rocers of Florida. I presume the tests are conducted by scien- tists or they would not be any good. Dr. Aaron. Well, there are scientists and scientists. Mr. Rocers of Florida. Well, there are doctors and doctors. Dr. Aaron. Exactly, and there are scientists who have a bias and there are scientists who have less of a bias. Mr. Rocers of Florida. Yes, I agree, but I am certainly giving them the benefit of the doubt that they are going to try to do what is best. Dr. Aaron. Right. Mr. Rocers of Florida. And I am sure that they could determine the biases. It is not very difficult to, and I am sure you and I could. But I think there is an instance where you say even you use stilbestrol because you use judgment. Dr. Aaron. No, I use stilbestrol when the risk of therapeutic gain outweighs the risk of harmful side effects. I am willing to accept the risks of possible cancer if I know it is going to help my patient, and the help to the patient far outweighs the possibility of armful side effects. But if the risks of side effects including cancer are too great, I will find a substitute for the stilbestrol. Mr. Rogers of Florida. Of course that comes down again to a matter of judgment. Dr. Aaron. Precisely. Mr. Rocers of Florida. Whether we are willing to, as you say, submit a person to certain risks. I cannot argue with you on that ground. It is up to the doctors to decide and it is not the point of Government, I think, to come in and say, “Doctor, you should not have the right of judgment to use this substance if you feel it will do more good than harm.” Dr. Aaron. Right. Mr. Rocers of Florida. And we are not asking the Food and Drug Administration to come in and tell you you cannot, because it may be better for humanity that you use it. I am simply saying that even where it has been stated that this would not be harmful, yet you won’t give the scientist in FDA the right to make this determination, that because of this amendment which says that even if there is no residue in meat to be eaten, it cannot be used. Dr. Aaron. Oh, not, I did not say if there is no residue it cannot be used. Mr. Rocers of Florida. You said the feed could not be used if it contalms a carcinogen. 346 COLOR ADDITIVES Dr. Aaron. The feed? Mr. Rogers of Florida. Whatever we would eat or consume, did younot? Youdo not take that position, then ? Dr. Aaron. Oh, yes, I do take the position that any food, drug, or cosmetic containing a ‘substance th: aut Aas produced cancer in experi- mental animals should not be used in that food, drug, or cosmetic. Mr. Rocers of Florida. That is the point I am making. Dr. Aaron. Yes. Mr. Rocers of Florida. Now, feed for animls. Dr. Aaron. Feed for animals, yes. Mr. Rocers of Florida. If it has this element in it, you would not want. it used under this amendment, is that. not true? Dr. Aaron. If it leaves a residue of that carcinogen or potential carcinogen in any part of the food that is consumed. Mr. Rowexs of Florida. Then you do not: want this to just be barred. You want to let them see and set a tolerance. Dr. Aaron. No, sir. Mr. Rocers of Florida. You are willing to let them set a certain amount if it leaves no residue, is that your position ? Dr. Aaron. I am willing to let them, to allow the Food and Drug Administration to use stilbestrol in animal feeding in an amount that is safe. Mr. Roaers of Florida. Where tolerances may be set. Dr. Aaron. Safe for both the animal and for the human that will consume the products of that animal. Mr. Rocers of Florida. Yes, and which means there would be no residue. Dr. Aaron. Now, there will be no residue whatsoever of a potential carcinogen. Mr. Rocers of Florida. I think we see eye to eye because that is my position, too, that we must set a tolerance, and it must be based on scientific judgment. I thank the gentleman. Mr. Dince.u. If the gentleman will yield, that is not what the doctor said at all. Mr. Rocers of Florida. I do not mean to be putting words in your mouth. You explain it, then, Doctor. I thoug ht I understood you to say that they may put a certain amount of it in the feed, as long as it is not harmful and the test is whether there is residue in the meat to be eaten by the human. In this case, you have no objection to it? Dr. AARON, The test is whether it is harmful from the point of view of toxic or carcinogenic effects to the animal and to the human that consumes any part of that animal. Mr. Rocers of Florida. And what is the test, whether there is residue in the animal or what ? Dr. Aaron. The test for a carcinogen is that there should be zero tolerance in any part of the animal that is consumed by a human. Mr. Rocers of Florida. And if there is no residue is that zero tolerance? Dr, Aaron. If there is no residue then there is no residue and there is no need to consider a tolerance. Mr. Rocers of Florida. I thought I had understood you to say exactly that. . COLOR ADDITIVES 347 Dr. Aaron. That is right. Mr. Rogers of Florida. I did understand the gentleman correctly. Mr. Dince.u. That happens to be present law, as a matter of fact. Mr. Rogers of Florida. I am ind, then, that you are willing to have that apply or continue to apply and change the complete bearing of any judgment in setting of any tolerances which would be done by thisamendment. Thank you, Mr. Chairman. The Cuarrman. Mr. Younger? Mr. Youncer. I have just one question. As I understand the present law the manufacturer must furnish the evidence to the Food and Drug as to the product. Dr. Aaron. As to it? Mr. Youncer. As to their product, whether it is safe. Dr. Aaron. Under the food additives amendment ? Mr. Younger. Yes. Dr. Aaron. That is right, sir. Mr. Youncer. All right, who shall furnish the proof about the egg? Dr. Aaron. About the egg? Mr. Youncer. Yes, is that the hen’s duty ? Dr. Aaron. The chicken, probably. Mr. YounGer. You said you wanted proof. Now, who is going to furnish the proof ? Dr. Aaron. Well, there is no proof that the egg is harmful. I think the burden is on the chicken. Mr. Youncer. That is all, Mr. Chairman. The Cnairman. Doctor, thank you very much. We appreciate your testimony here. We have a request from Mr. Fred W. Burrows that he be permitted to file a statement. Mr. Burrows is the executive vice president of the International Apple Association, Inc., 1302 18th Street N.W., Washington, D.C. Mr. Burrows’ statement may be included in the record at this point. (The statement referred to is as follows :) INTERNATIONAL APPLE ASSOCIATION, INC., Washington, D.C., Febraury 15, 1960. Subject : Color additive legislation. Hon. OreEN Harris, House Office Building, Washington, D.C. Dear CONGRESSMAN Harris: I was scheduled to testify on the proposed color additive legislation (H.R. 7642 and S. 2197) on Thursday, February 11. How- ever, due toa certain development, I relinquished my time. The reason for my desiring to testify on this proposed legislation was to make one point—and one point only; namely, we strongly urge that the pro- posed legislation be amended so as to exempt pesticide chemicals trom the requirements of the proposed color additive legislation. As you know, a similar exemption for pesticide chemicals was provided in the food additive amendment. While attending the hearings on Thursday morning. February 11, [ learned that a letter from Secretary Flemming had been read into the record the pre- vious day which clearly stated that the definition of the term “color additive” would not include pesticide chemicals and, therefore, these chemicals would not be subject to requirements of the proposed color additive legislation. In view of this letter I felt, at that time, that the legislative history would be clear and therefore gave up my allotted time relative to testimony, However, I have been giving the matter some further thought and believe it would be advisable that a specific exemption for pesticide chemicals be placed 56123—60-———-23 348 COLOR ADDITIVES in the color additive legislation. Certainly there can be no opposition from Health, Education, and Welfare in view of the letter already placed in the rec- ord. Also such a specific exemption would leave no doubt in the minds of any- one in the future relative to the status of pesticide chemicals as they might be related to color additives. Mr. J. A. Noone of the National Agricultural Chemicals Association has already testified before your committee on this matter. He suggested an appropriate amendment concerning pesticide chemicals and the reasons for the exemption. We strongly urge that your committee adopt the proposed amendment and provide a specific exemption in the color additive legislation for pesticide chemicals, In any event, we urge that the committee report clearly show that the com- mittee concurs with Secretary Flemming’s position as stated in his letter that pesticide chemicals are not color additives. The legislation would be much clearer if the specific exemption were carried in the legislation itself. Kindest regards. Sincerely, Frep W. Burrows. The Crrarrman. We have a request from Mr. Frank R. Schell, of 1602 Richardson Place, Tampa, Fla. His statement may be included in the record at this point. (The statement referred to is as follows :) AFFIDAVIT County or York, Province of Ontario, Dominion of Canada, 88: Before me, a notary publie in and for the county and Province aforesaid, personally appeared, this 8th day of February A.D. 1960, one Frank R. Schell, who, being first duly sworn deposes and says that he personally prepared the following (hereto attached) : (1) Statement of 20 pages, titled “Statement of Frank R. Schell Before the Committee on Interstate and Foreign Commerce, House of Representatives, in Hearings on H.R. 7624 and 8. 2197, January 28, 1960,” which statement was not presented on January 28, 1960, because the hearings on that day were canceled ; and (2) Letter of six pages, dated February 4, 1960, addressed to Hon. Oren Harris, chairman of that same committee, being a supplemental statement on the same subject matter. The said Frank R. Schell further swears that he prepared each of said state- ment and letter for the uses and purposes therein recited; that the statements of facts therein recited are true and correct and the statements made on in- formation and belief are based on information bad from persons whom he has heretofore found to be reliable and are verily believed to be truth and fact. Frank R. ScHELL. Sworn and subscribed to before me in the city of Toronto, of the county, Province and Dominion aforesaid, this 8th day of February A.D. 1960. [SEAL] F. F. CUNNINGHAM, Notary Public for Ontario. My commission is for life. Toronto, ONTARIO, February 4, 1960. Re H.R. 7624 and 8. 2197. Hon, Oren Harris, Chairman, Committee on Interstate and Foreign Commerce, House of Representatives, Washington. My Dear Mr. CHAIRMAN: I was scheduled to appear as a witness in the above matter, before the committee, on Thursday, January 28. After arrival in Wash- ington, however, I learned of an emergency situation adverse to our interests here in Canada, requiring my immediate presence. Therefore, when hearings for January 28 were postponed, I went to Mr. Painter and Mr. Williamson, re- questing that I be rescheduled for February 10 or 11, I regret to advise that it has become impossible for me to finish my work here in time to be in Washington on either February 10 or 11. Therefore, I am COLOR ADDITIVES 349 enclosing a sworn statement comprehending my previously prepared statement, of which 75 copies were supplied to Mr. Williamson, and am also enclosing the same munber of copies of this letter, reciting further comments which seem re- quired by some of the testimony that has been brought in, and I request that my prior statement and this letter and its statements be made a part of the record presented at these hearings as the sworn statements of this witness, I am particularly concerned with the fact that loose statements are being made that tend to unjustifiably enhance consumer distrust of our food supplies, Which distrust, if not corrected, will eventually destroy our agricultural economy. For example, the sale of Florida oranges, as fresh fruit, have been declining for the past 5 years, until, for the season 1958-59, these shipments aggregated less than 9 million boxes out of a total production of some 85 million boxes, as against 14 million boxes utilized as fresh fruit out of a total of 16.5 million boxes produced in 1933-34. ) Phe Federal Insecticide, Fungicide, and Rodenticide Act of 1947 pro- vided for USDA preexamination of economic poisons including labeling to insure safety and effectiveness in use. (c) The “Miller amendment” to the Food, Drug, and Cosmetic Act in 1954 provided more workable procedures for HEW preclearance of pesticide chemicals in or on raw agricultural commodities by authorizing the establish- ment of tolerances when needed—legai levels—of such chemicals in these products. The directions for use on labels registered by USDA for pesticides are gaged to meet such tolerances in or on the raw agricultural commodities. (d@) The Poultry Products Inspection Act of 1957 provided for extension of the meat inspection type of preclearance to poultry products by USDA. (¢) The Food Additives Amendment of 1958 to the Food, Drug, and Cos- metic Act provided for preclearance of chemicals and other additives to foods. In each ease the Congress provided the mechanism which permits the exer- cise of scientific and professional judgment in arriving at determinations of safety of use and wholesomeness of the products. These are good provisions. This Department fully supports them, ‘The legislative histories show the neces- sity for the exercise of such judgment to cope with the complexity of the prob- lems and the rapidly advancing slate of knowledge concerning them. The anticancer clanses contained in the Food Additives Amendment of 1958 and in HLR. 7624 on page 10, lines 11 through 22, are flat prohibitions against the exercise of scientific and professional judgment in the determination of safety. That such a flat prohibition may present problems is well exemplified in the case of selenium, a known carcinogen. Normal amounts (0.1 p.pau.) in the diet ap- pear to have no measurable effect upon animal health. Sheep on diets with sub- hormal amounts (0.05 p.p.m. or less) are not thrifty and show abnormalities of the muscular and internal organs. Excessive amounts (5 p.p.m. and above) in the diet produce poisoning. Here we have a chemical, a carcinogen, a toxicant, which in proper amount is essentinl to animal health. The law should not pre- vent proper use of such a chemical as an additive or otherwise. In view of the above and since we understand that the Secretary of Health, Edueation. and Welfare has adequate authority to withhold from use any addi- tive that he is nnable to find would be safe in regard to cancer as well as in re- COLOR ADDITIVES 393 gard to toxicity and other factors, it is our opinion that the anticancer provi- sions in lines 11 through 22 on page 10 of H.R. 7624 are unnecessary. This is equally true of the anticancer provisions in the Food Additives Amendment of 1958. We fully agree that the Secretary of Health, Education, and Welfare should withhold from use any additive which in his judgment would be unsafe, but we urge that the decision on safety be left to him rather than being deter- mined by law. In the event the committee should desire to retain an anticancer clause in the color additive legislation, the following language is submitted for its considera- tion: In H.R. 7624 on page 10 at the end of line 22, before the period, insert the fol- lowing proviso: “Provided, That this subsection shall not apply with respect to the use of an additive, if the Secretary finds, upon the basis of evaluation by experts qualified by scientific training and experience, that, under the proposed conditions of use, reasonably certain to be followed in practice, there is no rea- sonable basis to conclude that such use of the additive will involve a hazard of causing cancer in or resulting in harm to man or animal.” Similar language should be provided fur the anticancer clause in the food additives amendment. We are attuching a copy of the report of the President’s Science Advisory Comunittee released on May 14, 1960, which supports our position on this matter. If the above proviso is not acceptable and the committee wishes to retain an anticancer clause in H.R, 7624, it is recommended that the following proviso, which is being suggested by the Secretary of Health, Education, and Welfare, be included before the period at the end of section 706(b)(5)(B) (p. 10, line 22, of H.R, 7624); “Provided, That clause (i) of this subparagraph (B) shall not apply with respect to the use of a color additive as an ingredient of feed for animals which are raised for food production, if the Secretary finds that, under the conditions of use and feeding specitied in proposed labeling and reasonably certain to be followed in practice, such additive will not adversely affect the animals for which such feed is intended, and that no residue of the additive will be found (by methods of examination prescribed or approved by the Secretary by regulations, which regulations shall not be subject to subsection (d)) in any edible portion of such animals after slaughter or in any good yielded by or de rived from the living animal.” . This proviso contemplates that the Secretary of Health, Education, and Wel- fare will prescribe or approve methods of examination that would determine whether significant residues of additives romain in any edible portion of slaughtered animals that have consumed such feed or in any food yielded by or derived from the living animal. Similar language should then be added to the anticancer clause contained in the food additives amendment. In addition, the Department of Health, Education, and Welfare is proposing a modification of the prior sanction (grandfather) clause contained in section 201(s) of the Food, Drug, and Cosmetic Act as follows: “The last numbered clause of section 201(s) of the Federal Food, Drug, and Cosmetie Act (which clause is redesignated as clause (4) by section 101(a) of this Act) is amended by inserting in such clause, before the period, a colon and the following: ‘Provided, That, with respect to any sanction or approval granted pursuant to this Act, this clause shall be inapplicable, and the provisions of this Act (other than this clause) relating to food additives shall apply, to any such previously sanctioned or approved use of a substance if, on the basis of the information then available, the Secretary finds that, for the reasons set forth by him, there is reasonable doubt as to its safety. Except when the Secretary finds that there is an imminent hazard to public health, he shall take such action only in conformity with section 4 of the Administrative Procedure Act if such prior sanction or approval hud been made public, and only after sending reason- able notice of his proposed action and the reasons therefor to any person on whose application such prior sanction or appreval had been granted and any other person who had been officially advised thereof unless such personal notice is impracticable.’ " We have no objection to this proposal since it deals only with sanct‘ons or approvals granted by the Secretary of Health, Education, and Welfare under the Food, Drug, and Cosmetic Act and would not affect the authority of this Department or the impact of actions taken by it under programs which it ad- ministers. ~~. Science and 394 COLOR ADDITIVES The Bureau of the Budget advises that there is no objection to the submission of this report. Sincerely yours, TRUE D. MORSE, Acting Secretary. May 14, 1960, Anne Wheaton, Associate Press Secretary to the [Immediate release, President] Tue WHITE House The White House today made public the report of a study of certain aspects of the use of chemicals and drugs as food additives, which the President re- uested to be made by the Departments of Agriculture, and Health, Education, and Welfare, and the president’s Science Advisory Committee. In making this study, the Science Advisory Committee convened a special panel of experts and consulted scientists from the Agriculture and Health, Edu- cation, and Welfare Departments and also outside Government circles. Findings of the study were approved by the President's Special Assistant for Technology, Dr. George B. Kistiakowsky, and also concurred in by and Health, Education, and Welfare. The report describes the complex nature of the scientific issues involved in protecting the food supply from added eancer-producing substances. It suggests areas of research and also recommends improved administrative procedures. the Departments of Agriculture, THE PRESIDENT’S ScreNCE ADVISORY CoM MITTEE, Washington, D.C., May 9, 1960. Report OF THE PANEL ON Foop ADDITIVES INTRODUCTION ‘ans today are better fed and in better health than at any time in This fortunate position derives from the rational exploitation of national resources through manifold applications of scientific research, The integrated eontributions of the engineering, agricultural, and chemical sciences have resulted in increasing quantities of uniformly high quality and pure foods which have contributed demonstrably to the physical well-being of the Nation. Greatest strides have been made during the past 50 years, partly as a result of the use of a broad spectrum of chemical substances in support of the entire pattern of food production, processing, and preservation. These include: Chemical fertilizers, insecticides, herbicides, antibiotics, preservatives, larva- cides, fungicides, and hormones, among others. Some are essential to the effi- cient production of erops and livestock, others are vital in assuring adequate and continuing supplies of pure, nutritious, and appetizing foods. Paralleling modern developments in food production have heen those in safe- guarding the purity of foods. A variety of Federal and State agencies have been established for the purposes of assuring that foods which reach the con- sumer have been produced, handled, and processed under such conditions that they are wholesome and safe for human consumption. Producers and processors of foods have cooperated in this endeavor in the recognition that they, too, have a responsibility for public heulth and welfare. Recently there has been public preoccupation with reports that certain chem- ical food additives have been shown to be earcinogenic (cancer producing) under laboratory conditions when ingested by experimental animals. Several such compounds have been withdrawn from the market; and new legislation has been enacted specifically dealing with carcinogenic food additives. Asa result of this legislation, many questions of interpretation have arisen. The Presi- dent’s Science Advisory Committee has been asked to convene a special panel es and problems in relation to public policy. to review the scientific issu The panel had the opportunity to discuss the varied aspects of carcinogenic food additives with representatives of the Department of Health, Education, and Welfare, including the Public Health Service and Food and Drug Adminis tration, and with the Department of Agriculture as well as with experts outside of Government. The panel has also studied prepared statements pertinent to the subject, congressional committee reports, monographs, and published scien- tifie literature (app. A). Consumers expect safe, wholesome food of good quality and they rely on Government, as set forth in the laws, to maintain sufficient controls to meet this COLOR ADDITIVES 395 expectation. Government must, can, and does act in maintaining this objective. Careful regulations have been provided to guard the health of the public from unwitting exposure to toxic chemicals in foods, through the Federal Food, Drug, and Cosmetic Act, the Federal Insecticide, Fungicide, and Rodenticide Act and the Federal Meat Inspection and Poultry and Poultry Products Acts (app. B). These protections are implemented by the staffs of the Department of Health, Education, and Welfare and the Department of Agriculture. Under the food additives amendments of the Federal Food, Drug, and Cos- metic Act, the Secretary of the Department of Health, Education, and Welfare may establish regulations prescribing, with respect to one or more proposed uses of the food additive involved, the conditions under which the additive can be used. The act provides, however, that no such regulation shall be issned if a fair evaluation of the data before the Secretary fails to establish that the proposed use of the food additive, under the conditions of use to be specified in the regulation will be safe. Accordingly, the Food and Drug Administra- tion has an area of administrative discretion in determining the safety of food additives under conditions of proposed use. This area of administrative discretion has recently been greatly narrowed in those cases where a new food additive is possibly carcinogenic. In 1958, Con- gress enacted the food additives amendment of the Food, Drug, and Cosmetic Act. Section 409(¢c)(3) (hereinafter referred to as see. 409(c)) of the amend- ment states that “no additive shall be deemed to be safe if it is found to induce cancer when ingested by man or animal, or if it is found, after tests which are appropriate for the evaluation of the safety of food additives, to induce cancer in man or animal.” The panel has focused attention on this proviso which, under the language of the food additives amendment, is concerned chiefly with new substances." The emphasis on new substances considerably narrows the effect of the proviso on industry and the public. The panel subscribes to the intent of the Congress in approving this section of the food additives amendment to protect the public from increasing cancer risks through the diet. However, there are certain difliculties in its practical application—difliculties which give rise to many uncertainties both on the part of the public and those whose responsibility it is to administer the law. SCIENTIFIC ISSUFS Several scientific problems raised by section 409(c) have been examined in detail by the panel. These are: 1. Problem of recognition of a carcinogenic food additive Section 409(¢c) of the food additives amendment under consideration classifies as unsafe any new substance or one not previously evaluated for its safety “if it is found to induce cancer when ingested by man or animal * * *,.” It is to be noted that a finding of cancer induction in man or animal must be made as a prerequisite to banning of the additive in question. This recognizes the fact that the present state of scientific knowledge does not permit an a priori assumption of the carcinogenicity of a chemical. Since tests on animals or observations on man must be carried out to determine the capacity of an additive to induce cancer, it is pertinent to examine the procedures in current usage to recognize a carcinogen for man and/or animals. (a) Recognition in man.—The recognition of chemically induced cancer in man is based on circumstantial evidence. Although cancer morbidity may be in part related to environmental carcinogens, these have not been specifically identified in most instances because of the numerous, varied, and often un- recognized environmental factors to which man has been exposed. When, how- ever, certain limited populations have had, through their specialized occupation, a concentrated exposure to specific environmental factors, it has been possible in a number of instances to obtain evidence indicative of a causal relationship between the specific environmental factor and the induction of cancer. Examples ‘Congress, in defining “food additives” In the Food, Drug. and Cosmetic Act, expressly provided that the entire food additives amendment does not apply to: (a) Any substance which under the conditions of its intended use is generally recog- nized as safe by competent scientific experts on the basis of scientific procedures (or for substances used in food before Jan, 1, 1958, on the basis of either scientific procedures or experience based on common use in food), (b) Any substance previously sanetioned or approved under the Food, Drug, and Cos- metic Act, the Poultry Products Inspection Act, or the Meat Inspection Act. 56123—60——26 396 COLOR ADDITIVES of this include urinary bladder cancer among. workers in the dye industry ex- posed to 2-naphthylamine, lung cancer among chromate industry employees, and skin cancer among those engaged in the paraffin pressing operation in oil refineries. The recognition of the relationship between an environmental factor and an increased frequency of a particular type of cancer in these examples rested on a marked difference between exposure of the individuals involved and the general population. Since, by contrast, exposure to food additives is general throughout the population, it is unlikely that carcinogenic properties would be recognized from examination of data obtained on man. From a practical stand- point, therefore, the indication of possible carcinogenicity to man of chemical additives must come from observations on laboratory animals or on persons exposed to unusual amounts of these chemicals during their manufacture or use, or in the treatment of disease. (b) Definition of induced cancer in animals.—The recommended procedure for testing the possible carcinogenicity of a chemical additive calls for its incorporation into the diet of several animal species, at several dosage levels, and for the duration of the animals’ lifespan where feasible. Like all biological assay methods, this procedure has more inherent variables than do procedures involving physical and chemical methods. Further, the recognition of a carcino- gen by the bioassay technique presents greater difficulties of interpretation than are usually encountered in assaying the effects of other pharmacologically active substances, These difficulties of interpretation are related to the identification of the tumor as a cancer, and to the way in which the experiment is designed. The criteria for detining whether or not a “cancer” has been induced in the experimental animal are varied. They include the microscopic appearance of the tumor (histopathology), its ability to metastasize, its transplantability to other animals of the same species or inbred strain and its local invasiveness. The most commonly employed criterion is the histopathological diagnosis. However, this depends on the judgment of pathologists and diversity of opinion among them is not uncommon, A further difficulty emerges from the fact that not all tumors are cancers and that there is difference of opinion regarding the possible, subsequent malignancy of at least certain benigu tumors. (Appendix C.) The design of the experiment is important in the recognition of a carcinogen by laboratory methods. The chapter on carcinogenicity screening in the mono- graph of the Food and Drug Administration’? clearly presents factors which may influence the results of tests. These include the dose levels which may be too high as well as too low, thereby masking carcinogenic potentiality through nonspecific toxicity; the necessity to conduct tests in several species and in the same species in more than one inbred strain in order to avoid drawing general conclusions based on species or strain-specifie susceptibility or resistance to the induction of cancer; the need for careful biometric planning so that appropriate numbers of animals are included in beth experimental and control groups to allow precise statistical interpretation of the results. 2. Problem of the relation of dose to cancer production in man Section 409(c) of the food additives amendment of the Food, Drug, and Cosmetic Act prohibits the approval of a food additive regardless of the amount that is found to be required to increase the incidence of cancer in test animals. A literal interpretation of the seetion must lend to the prohibition of such a sub- stance even though present in trace amounts. Since new substances will be evaluated by animal tests, in practice the prohibition is based 6n the assumption that a substance which increases the incidence of cancer when included in the diet of animals at any dose level may increase the incidence of cancer when included in the diet Of man even when present in amounts detectable only by the most sensitive analytical techniques. + For a number of carcinogens that have been studied, however, there is evidence for the existence of a level of ingestion at which no carcinogenesis occurs during the life of the animals when tested in limited numbers. Also, dose-response Curves for certain potent carcinogens in animals have been worked out from which can be reliably predicted the proba- bility of an individual, in a given-sized population, developing a tumor from a given dose of carcinogen, Such curves lead to the conclusion that dietary levels of carcinogenic agents exist at which the probability of cancer induction in animals is near zero. *“Anpraisal of the Safety of Chemicals in Foods, Drugs, and Cosmeties,” F a Drug Administration, 1959, pp, 79-82. 6 osmetics,” Food and COLOR ADDITIVES 397 The conclusion derived from animal studies has relevance to certain common components of the diet of man. In foodstuffs, as they occur in nature, one finds traces of chemicals which in larger amounts are generally accepted as carcino- genic, such as certain inorganic arsenic compounds, radium. and selenium. It can be shown by methods of analysis now available that ordinary table salt derived from rock salt contains trace amounts of radium and that foodstuffs con- taining iron salts are contaminated by minute quantities of arsenic. Although it cannot be stated absolutely that these traces of carcinogenic materials have never induced cancer in any human, the available evidence has not directed suspicion to these trace amounts as significant to the overall cancer morbidity. There is additional evidence which indicates that a dose-response relation for earcinogens exists in man. Thus, the bladder cancer incidence rate in those exposed to 2-naphthylamine (to which reference was made earlier in this report) was highest among those most intensely exposed among several groups of work- ers in the dye industry. Another example of the existence of the relation of dose of a carcinogen and duration of exposure to cancer production is creosote to which there is widespread exposure of workers in several trades. Although it has been demonstrated that creosote can produce skin cancers in mice and men, the frequency with which this has been observed in man is very low and only in those persons exposed to high amounts of the material over prolonged time periods. Finally, there is some indication in the literature that the frequency of cancer induction in man might be decreased by reduction of the amount of ex- posure to a particular carcinogen. Examples of this are the absence of reports of skin cancer in paraffin pressing operators in oil retineries following the intro- duction of hygienic practices, and the reduction of nose cancer in nickel industry workers following the introduction of dust control measures, In these examples, it can reasonably be assumed that there has been a reduction in the exposure to the carcinogen rather than a complete removal of the cancer-producing substance. From the experience obtained in animal experiments and study of humans who have been exposed to carcinogens in the course of their work such as cited above, the panel believes that the probability of cancer induction from a par- ticular carcinogen in minute doses may be eventually assessed by weighing scientific evidence as it becomes available. 8. Problems in the administration of scction 409(c) (a) Special problems might arise when substances useful in trace amounts but carcinogenic ip large doses are considered : (i) Selenium consumed for long periods in considerable amounts by ani- mals will produce liver cancer. Selenium is reported on the other hand to be an essential nutrient element (at a level of 1 part per million) in the diet of lambs; (it) Certain inorganic arsenic compounds have been indicated as carcino- genic. When organic arsenicals are added as chemotherapeutic agents to animal feed, some inorganic arsenic is released ; (iii) Polyoxyethylene stearate fed to rats at a level of 25 percent of the diet (but not at lower levels) produced urinary bladder stones which induced bladder tumors, some malignant. Since the cancers are always associated with the presence of stones, minute traces in the human diet are not likely to produce bladder cancer, and can be treated as any other toxic material. This list of examples may be expected to lengthen and each case requires scientific judgment to determine the issues involved. (b) A different problem arises when carcinogenic substances are permitted to be used in agriculture and food industry under such conditions that they are absent from human food products. Any assay method used to determine the presence or absence of particular substances in human food has only a finite sen- sitivity of course. In the effort to improve the sensitivity of the assay, resort may be had to modern indirect methods, such for instance as bioassay or radio- active tracers. A large gain in sensitivity is sometimes obtained partially at the cost of certainty that the substance detected is indeed the original carcino- gen. Scientific judgment as well as the rule of reason are required to decide what is a proper and adequate assay method. CONCLUSIONS AND RECOMMENDATIONS The rapidly increasing number of new chemicals potentially useful in agri- enlture and food production demand vigilant and careful scrutiny of the com- 398 COLOR ADDITIVES pounds offered in order to safeguard the consumer from those that may present carcinogenic and other toxic hazards. In applying the provisions of section 409(c) (3) of the food additives amend- ment of the Food, Drug, and Cosmetic Act, the enforcing agency must employ the “rule of reason” * based on scientific judgment in order to carry out the intent of the Congress to protect the public from the possibility of increasing cancer risks through the diet. The definition of a carcinogen implicit in the language of section 409(c) re- quires discretion in its interpretation because so many variables enter into a judgment as to whe: her a particular substance is or is not carcinogenic. It is to be emphasized that the present difficulty in establishing whether there are permissible levels for certain possibly carcinogenic food additives is accen- tuated by the limited relevant scientific information available. From the experi- ence obtained in animal experiments and study of humans who have been exposed to carcinogens in the course of their work such as cited above, the panel believes that the probability of cancer induction from a particular carcinogen in minute doses may be eventually assessed by weighing scientific evidence as it becomes available. The special emphasis placed by the Congress on the protection of the public from the dangers resulting from the addition of possible carcinogens to food calls for prudent administration of section Ate) of the food additives amend- ment of the Food, Drug and Cosmetic Act. Since an area of administrative discretion based on the rule of reason is unavoidable if the clause is to be workable, it is essential that this discretion be based on the most informed and expert scientific advice available. Until the causes of carcinogenesis are better understood, each situation must be judged in the light of all applicable evidence. In this way the protection of public health can best be assured. Accordingly, the following recommendations are made: 1. That the Secretary of Health, Education, and Welfare appoint a Board ad- visory to him to assist in the evaluation of scientifie evidence on the basis of which decisions have to be made prohibiting or permitting the use of certain possibly carcinogenic compounds. The advisory Board should be composed of scientists from the National Cancer Institute, the Food and Drug Administration, the U.S. Department of Agricul- ture, and the scientists outside of Government from a panel nominated by the National Academy of Sciences. It would be the function of the Board to weigh evidence and to make recom- mendations to the Secretary of the Department of Health, Education, and Wel- fare on the basis of available scientific data, both on applications for approval of new food additives and in all cases where the withdrawal of a prior approval or sanction is under consideration, The Board would consider among other matters: (a) Whether or not the tests for carcinogenicity are appropriate and reasonable, (b) Whether the substance is or is not in reality carcinogenic as deter- mined histopathologically or by other criteria, (c) Whether addition of the substance to agricultural products would result in a concentration of the substance above the natural background level of such substance. (d@) What assay techniques are appropriate to determine whether a specific carcinogen is present in food. It would also be the function of this Board to review from time to time its recommendations and to modify them in the light of new scientific knowledge. Further, the Board would assume the responsibility of recommending to the Secretary of Health, Education, and Welfare specific research problems to be undertaken to provide necessary scientifie data. 2. Iftexisting legislation does not permit the Secretary of Health, Education, and Welfare to exercise discretion consistent with the recommendations of this report, it is recommended that appropriate modifications in the law be sought. 3. Because of the limited scientific information available relevant to the ef- fects of possible carcinogenic food additives, it is recommended that: (a) Proportionately greater emphasis be placed by Government agencies on the study of representative carcinogens in a variety of animal species *“Every statute must be interpreted in the light of reason and common understanding to reach the results intended by the legislature.” Opinion handed down by Chief Justice Warren in Rathburn vy. U.S, (355 U.S. 107 at 109), COLOR ADDITIVES 399 in an attempt to define dose-response relations. It must be recognized from the very nature of such research that definitive answers useful in extra- polation to man may not be expected for many years to come. The applica- bility of such research to the problems discussed in this report will be fur- thered by studies carried out on large groups of animals. (b) Studies be increased on the possible carcinogenic action of sub- stances to which numbers of individuals have been regularly exposed and that these studies be related to the incidence of cancer in the exposed in- dividuals. Restrospective studies should also be made of patients who have received a variety of chemical compounds, in the course of treatment of disease, which are subsequently suspected of being carcinogenic. 4, Research be expanded also by the Department of Agriculture, by the State agricultural experiment stations, and by industry to discover additional safe and effectiveness materials for the production and processing of foods. Dr. Detley W. Bronk, chairman, president, Rockefeller Institute and president, National Academy of Sciences. Dr. Robert F. Loeb, vice chairman, Bard professor of medicine, Columbia University, on leave. Dr. Edwin B. Astwood, professor of medicine, Tufts University School of Medicine, New England Center Hospital. Dr. Alfred Gellhorn, director of the Institute of Cancer Research and professor of medicine, Columbia University. Dr. J. George Harrar, vice president, the Rockefeller Foundation. Dr. Harold C. Hodge, professor of pharmacology and toxicology, Uni- versity of Rochseter. Dr. James G. Horsfall, director, the Connecticut Agricultural Experiment Station. Dr. C. N. Hugh Long, Sterling professor of physiology, Yale University. Dr. C. Chester Stock, scientific director, Sloan-Kettering Institute for Cancer Research. ‘Consultant, Mr. Charles S. Rhyne, Rhyne & Rhyne, Washington, D.C. Technical assistant: Dr. Frederic Holtzberg, the President's Science Ad- visory Committee, the White House. APPENDIX A SELECTED REFERENCES ON FOOD ADDITIVES “Progress in Clearing Safe Food Additives,” a statement !y» Arthur S. Flem- ming, Secretary of Health, Education, and Welfare, January 26, 1960. “Proposed Color Additives Amendment,” a statement by Arthur 8, Flemming before the House Committee on Interstate and Foreign Commerce, U.S. House of Representatives, Tuesday, January 26, 1960. “Aminotriazole in Cranberries,” a report presented by Arthur S, Flemming to the Committee on Interstate and Foreign Commerce of the House of Repre- sentatives on actions taken with respect to aminotriazole and stilbestrol. “The Role of Certain Chemical and Physical Agents in the Causation of Cancers,” by G. Burroughs Mider, M.D., Association Director in Charge of Re- search, National Cancer Institute, National Institutes of Health, Public Health Service, Department of Health, Education, and Welfare, January 26, 1960. “Chemicals and Food Safety,” a statement by E. L. Peterson, Assistant Sec- retary of Agriculture. “Insignificant Levels of Chemical Additives in Food,” reprint from the July 1958 issue of Food, Drug, Cosmetic Law Jourual, the Scientists’ Forum, edited by Bernard L, Oser. Reports of the National Academy of Sciences, National Research Council : “Problems in the Evaluation of Carcinogenic Hazard From Use of Food Additives,” Food Protection Committee, Food and Nutrition Board, Decem- ber 1959. “Principles and Procedures for Evaluating the Safety of Intentional Chemical Additives in Foods,” a statement prepared by the Food Protection Committee of the Food Nutrition Board, November 1954. “Food-Packaging Materials Their Composition and Uses,” a report of the Food Protection Committee, November 1959. “Hormonal Relationships and Applications,” publication 714, a report of the Committee on Animal Nutrition, 1959. 400 COLOR ADDITIVES “Safe Use of Pesticides in Food Production.” 4 report by the Food Protec- tion Committee on the Food and Nutrition Board, November 1956. “Statement on What We Know About Possible Relationships Between Cancer and Food Additives,” Food Protection Committee, December 1956. “Regulations for the Enforcement of the Federal Insecticide, Fungicide, and Rodenticide Act,” issued March 1948, U.S. Department of Agriculture. “Interpretation of the Regulations for the Enforcement of the Federal Insecti- cide, Fungicide, and Rodenticide Act,” issued August 1948, U.S. Department of Agriculture. “Federal Food, Drug, and Cosmetic Act—as Amended,” U.S. Department of Health, Education, and Welfare, Food and Drug Administration “Appraisal of the Safety of Chemicals in Foods, Drugs, and Cosmetics,” edited and published by the Editorial Committee, Association of Food and Drug Officials of the United States, Food and Drug Administration. APPENDIX B The various bureaus of the Departments of Agriculture and Health, Education, and Welfare have long worked in close association with each other and with corresponding State and local government agencies to guard the food supply. The highly trained scientific and technical manpower in these bureaus work in unison. The Departments of Agriculture and Health, Education, and Welfare administer laws that regulate the purity of food. The Department of Agriculture administers: (a) The Federal Insecticide, Fungicide, and Rodenticide Act which requires the registration of economic poisons (pesticide chemical formulations such as insecticides) shipped interstate. Before registering an economic poison, the Department determines, among other things, that its label bears directions for use which, if followed, are adequate to protect the public. The Department investigates interstate shipments of economic poisons to insure compliance with the requirements of the act. In case of violations, it may seize the merchandise and prosecute the responsible party. (b) The Federal Meat Inspection and Poultry and Poultry Products Acts which gives the Department authority to determine, by regulation, what chemicals are safe and may be used in establishments producing red meat, poultry, and products containing them for interstate commerce. Under the continuous inspec- tion of meat, poultry, and their products produced for interstate commerce, the Department has authority to condemn and prevent the movement of any such materials found to be unwholesome. In addition, the Department may cause prosecution of any person shipping meat, poultry, and their products in interstate commerce which have not been inspected for wholesomeness in compliance with the requirements of the act. The Department of Health, Education, and Welfare: (a) Approves labeling of new drugs and drugs containing antibiotics for veterinary use; in this way it determines that when shipped these drugs bear directions for use that guard against contamination of food from treated animals with hazardous drug residues (secs. 505 and 507 of the act). (b) By regulation establishes tolerances for the residues of toxic pesticides (insecticides, fungicides, herbicides, etc.) that may safely remain on crops when they are marketed in interstate commerce (sec. 408 of the act, also known as the pesticide chemicals amendment). (c) By regulation establishes safe conditions for use of food additives in food processing or handling, including chemicals for use in or on meat or poultry (sec. 409 of the act, also known as the food additives amendment). In general, the person who wishes to promote a toxic chemical for uses that may leave small amounts in food must establish the safety of the proposed uses. He does this under the Federal Food, Drug, and Cosmetic Act by conducting appropriate laboratory tests to determine: (i) How much of the chemical or toxic materials resulting from its use will remain in food. It is essential in this connection to have an analytical method, usable for enforcement purposes, for detecting excessive amounts should they occur in food in commercial practice. (ii) What the effect of various dosages is on test animals. (iii) That there is an adequate margin of safety between the toxic level of the chemical and the level proposed in food. COLOR ADDITIVES 401 The promoter then furnishes these tests results to the Department of Health, Education, and Welfare with a request for approval of his proposed use. Only when the Department grants approval may the product be employed legally. (The detailed procedures for approval vary depending upon whether the product is, by definition in the law, an antibiotic, a new drug, a pesticide chemical, or a food additive.) If the chemical is an antibiotic veterinary drug or new drug or a pesticide to be used on animal or plant crops so that no residue remains on food as it is marketed, the promoter must show the Department of Health, Education, and Welfare (for antibiotics or veterinary drugs) or the Department of Agriculture (for pesticides) that under the proposed directions there will be no residue. Evaluating the safety of chemicals added to food is extremely complex. In- tensive scientific exploration in numerous laboratories develops new information almost daily. Inevitably there will be occasions in which the Government must rescind some of the authorizations it has granted for use in chemicals. APPENDIX C EXTRACTS FROM “APPRAISAL OF THE SAFETY OF CHEMICALS IN FOODS, DRUGS, AND COSMETICS,” FOOD AND DRUG ADMINISTRATION, 1959 Page 79 “For the purpose of this discussion, carcinogens are those substances which produce a significant increase in tumor incidence when administered at any dosage level by any route of administration in any species of animal as com- pared to controls. Obviously, carinogenic (perhaps tumorigenic would be more correct since not all tumors are malignant) potency may range from very weak to very strong; on a mg/Kg dosage basis, 10,000 or more times the quantity of one chemical may be needed than of another * * *” Page 82 “Tumor-producing action is not something that either ‘is or is not present’ in acompound. In other words, this action is not all black or all white but incor- porates a lot of gray. At one end of the scale we have compounds which have not been known to cause any increased incidence of neoplasia in any species by any route of administration with any dosage. And, at the other end, there are the compounds that are readily detectable as potent carcinogens. How should we evaluate the compounds that fall in the ‘gray area’? Some cancer workers con- sider that carcinogenic stimuli are cumulative and irreversible. We have previ- ously defined a carcinogen as a substance that produces a significant increase in tumor incidence when administered at any dosage by any route of adminis- tration in any species of animal as compared to controls. We have also indicated that carcinogenesis in one species or by one route of administration does not imply carcinogenesis in another species or by another route of administration. It should be kept in mind that mouse and rat tumor production is greatly influ- enced by dietary factors. These dietary factors may be either qualitative, as in the case of increased tumor incidence with choline deficiency, or quantitative, such as the pronounced decreases in tumor incidence (in the presence of an equal life span) with caloric restriction. The selection of test animals and the reasons for those chosen have been discussed earlier. What we are principally con- cerned with is the tumor-producing potential for man. Carcinogenesis is one manifestation of chronic toxicity; but since mechanisms of carcinogenesis are understood less well than the more frequently encountered toxic alterations of the usual chronic experiment, it is prudent to err on the side of caution. Evalua- tion of the significance for man and tumorigenicity or carcionogenicity in experi- mental animals when the results are in the borderline area (that is, not negative but not distinctly positive) is most difficult and complex, and demands the com- bined talents of people in many biological specialties.” (Whereupon, at 12 noon, the hearing was adjourned. ) COLOR ADDITIVES TUESDAY, APRIL 5, 1960 House or Representatives, CoMMITTEE ON INTERSTATE AND Foreign COMMERCE, Washington, D.C. The committee met, pursuant to call, at 10 a.m., in room 1334, New House Office Building, Hon. Oren Harris (chairman of the committee) presiding. Present: Representatives Harris (presiding), Williams, Moulder, Flynt, Macdonald, Dingell, Rogers (Florida), Bennett, Schenck, Younger, Avery, Devine, Keith, Hemphill, Healey, and Curtin. Also present: W. E. Williamson, chief clerk. The Cuarraan. The committee will come to order. In resuming consideration of what is referred to as color additives proposed legislation, H.R. 7624 and S. 2197, we are indeed pleased to welcome this morning a most distinguished group of scientific experts, if you gentlemen don’t mind my using that term, who will greatly as- sist the committee in discussing scientific problems involved in this proposed legislation, and with particular emphasis on one provision of the House bill which has caused so much concern in the minds of the American people, namely, the Delaney anticancer clause. You gentlemen will recall that in the consideration of the Food Additives Amendment of 1958, this provision became a part of that law. Out of the experience we have had with it since that time, it has become necessary in connection with this particular proposed legisla- tion to give further consideration to the problem. The nationally recognized scientists who have favored us with their presence this morning for the discussion of this problem, and whom we are very glad to welcome, are Dr. William J. Darby, of the de- partment of biochemistry, Vanderbilt University School of Medicine, Nashville, Tenn. I think you might raise your hand, gentlemen, when I call you so the members of the committee can get you placed. Dr. Darby is to act as the chairman of this distinguished panel. Dr. Harold F. Blum, Department of Biology, National Cancer In- stitute and Princeton University, Princeton, N.J. Dr. Paul R. Cannon, of the University of Chicago and of York- ville, Tl. Dr. Floyd De Eds, of the U.S. Department of Agriculture, Western Utilization Laboratory, Albany, Calif. Dr. Charles K. Kensler, Department of Pharmacology, School of Medicine, Boston University, Boston, Mass. 403 404 COLOR ADDITIVES Dr. Morton L. Levin, Roswell Park Memorial Institute, Buffalo, N.Y. Dr. G. Burroughs Mider, Associate Director of the National Cancer Institute, National Institutes of Health, Bethesda, Md. I might interpolate that Dr. Mider has been before the committee already on this problem when he accompanied the Secretary of Health, Education, and Welfare at the previous hearings. Dr. James A. Miller, McArdle Laboratory, University of Wiscon- sin, Madison, Wis. Dr. Walter E. O’Donnell, Sloan-Kettering Institute for Cancer Research, division of preventive medicine, New York, N.Y. Dr. Philippe Shubik, division of oncology, Chicago Medical School, Chicago, ll Dr. Darsy. Dr. Shubik is unable to be here, sir. We received a telegram yesterday that it would be impossible for him to attend because of some family increases which are occurring. The Cuatrman. Dr. Harold L. Stewart, National Cancer Institute, National Institutes of Health, Bethesda, Md. Dr. Albert Tannenbaum, Medical Research Institute, Michael Reese Hospital, Chicago, Ill. Dr. Mitchell R. Zavon, Kettering Laboratory of Industrial Health, Cincinnati, Ohio. I say to my distinguished colleagues you can very well see that we have a most distinguished panel here today, and I know you join me in giving them a welcome. I might say that these gentlemen were named by Dr. Bronk, Presi- dent of the National Academy of Sciences, pursuant to my request for assistance in establishing a representative panel of expert scien- tists qualified to discuss the scientific aspects of color additive legis- lation, particularly the Delaney clause, pending before this committee. I would like to say that some of the members of this committee were tremendously concerned with the problem as developed in the cranberry incident last year. Some of us are equally concerned with the problem that developed in connection with the poultry business, and many industries in this country are quite concerned with this problem because of the effect it had on that industry in providing food substance to the American people. So I would like to take the opportunity in behalf of the committee to express our thanks to Dr. Bronk, Dr. S. D. Cornell, executive offi- cer of the Academy; and Dr, Paul E. Johnson, Chairman of the Food Protection Committee of the Academy, for their fine cooperation. The procedure the committee would like to follow during these hearings will be somewhat similar to that which was used in con- nection with the Salk vaccine, when we had a panel discussion on that problem in 1955, and then with the food additives panel in 1957. The chairman and members of the panel will introduce themselves and each give a brief statement of his particular qualifications with respect to the scientific aspects of the problem facing the committee. Then we shall have a brief statement from Dr. Darby, the Chairman, and from each of the panel members who will present his views. Following these statements we will have a question period, under the COLOR ADDITIVES 405 direction of Dr. Darby, during which the members of the panel will be able to ask questions of each other. Of course, the members of this committee probably will want to ask some questions of the members of the panel. However, if the subject matter gets too deep for us, why, we will sit back and let you make the record, The committee has held extensive hearings on the legislation during the past several weeks. The point of controversy which I have in- dicated and the question on which the committee seeks particular information from you gentlemen is whether or not it is possible to establish safe tolerances for food or color additives known to induce cancer in man or animal. On page 10 of H.R. 7624—and I hope the clerk has provided each of you with a copy—lines 11 through 22—there appears the followin language, which I have said is referred to as the Delaney clause, an I quote: (B) A color additive (i) shall be deemed unsafe, and shall not be listed, for any use which will or may result in ingestion of all or part of such additive, if the additive is found to induce cancer when ingested by man or animal, or if it is found, after tests which are appropriate for the evaluation of the safety of additives for use in food, to induce cancer in man or animal, and (ii) shall be deemed unsafe, and shall not be listed, for any use which will not result in ingestion of any part of such additive if, after tests which are appropriate for the evaluation of the safety of additives for such use, or after other relevant exposure of man or animal to such additive, it is found to induce cancer in man or animal. Now, the Senate has approved a bill S. 2197, which does not con- tain this language or any reference to it. However, the Food Addi- tives Amendment of 1958, Public Law 85-929, contains similar language. Much controversy has developed during our hearings over this clause. You can readily appreciate that the question of retaining, modifying, or eliminating this provision is one of vital importance to the health of our people. Views of this panel on this question, therefore, will be of tremendous help to us in determining legislative policy. Now, I would like to introduce Dr. Darby, the chairman of the panel. Doctor, we are pleased to welcome you back. I recall that you were chairman of a previous panel before this committee in 1957. You may proceed as I fave outlined, 406 COLOR ADDITIVES STATEMENTS OF DR. WILLIAM J. DARBY, DEPARTMENT OF BIO- CHEMISTRY, VANDERBILT UNIVERSITY SCHOOL OF MEDICINE, NASHVILLE, TENN.; DR. HAROLD F. BLUM, NATIONAL CANCER INSTITUTE, DEPARTMENT OF BIOLOGY, PRINCETON UNIVER- SITY, PRINCETON, N.J.; DR. PAUL R. CANNON, UNIVERSITY OF CHICAGO; DR. FLOYD DE EDS, U.S. DEPARTMENT OF AGRICUL- TURE, WESTERN UTILIZATION LABORATORY, ALBANY, CALIF. ; DR. CHARLES J. KENSLER, DEPARTMENT OF PHARMACOLOGY, SCHOOL OF MEDICINE, BOSTON UNIVERSITY, BOSTON, MASS. ; DR. MORTON L. LEVIN, ROSWELL PARK MEMORIAL INSTITUTE, BUF- FALO, N.Y.; DR. G. BURROUGHS MIDER, ASSOCIATE DIRECTOR, NA- TIONAL CANCER INSTITUTE, NATIONAL INSTITUTES OF HEALTH, BETHESDA, MD.; DR. JAMES A. MILLER, McARDLE LABORATORY, UNIVERSITY OF WISCONSIN, MADISON, WIS.; DR. WALTER E. O'DONNELL, SLOAN-KETTERING INSTITUTE FOR CANCER RE- SEARCH, DIVISION OF PREVENTIVE MEDICINE, NEW YORK, N.Y.: DR. HAROLD L. STEWART, NATIONAL CANCER INSTITUTE, NA- TIONAL INSTITUTES OF HEALTH, BETHESDA, MD.; DR. ALBERT TANNENBAUM, MEDICAL RESEARCH INSTITUTE, MICHAEL REESE HOSPITAL, CHICAGO, ILL.; AND DR. M. R, ZAVON, KET- TERING LABORATORY OF INDUSTRIAL HEALTH, CINCINNATI, OHIO Dr. Darpy. Thank you indeed, Mr. Harris. First, I should like to express my appreciation for the opportunity of again discussing with you and your committee the scientific considerations which are basic to legislative action aimed at improving and providing our Na- tion with an ab:indance of the most wholesome and nutritious food obtainable. As you know, I have long been interested in many aspects of nutri- tion. “My background started in your own home State, Arkansas. From the University of Arkansas I received an M.D. degree, and subsequently from the University of Michigan a Ph. D. in bio- chemistry. At the present time, as you indicated, I am professor and head of the Department of Biochemistry at Vanderbilt University, and direc- tor of the division of nutrition of that medical school. I have since the formation of the Food Protection Committee of the National Academy of Science been on that committee, and at the pres- ent I am chairman of the food protection committee, and I am also a member of the Food Nutrition Board of the Academy. T have for a number of years been a member of the council on foods and nutrition of the American Medical Association. Asa result of interest and attention to some of the questions relative to food additives, T have served as a member—in fact, as chairman of the first joint FAO-WHO Expert Committee on Food Additives. T wonder if IT might ask whether it would save time if in giving the individual statements we had the members of the panel qualify them- COLOR ADDITIVES 407 selves at that time, or would you prefer the qualification all at one moment? The Cuaman. I think, doctor, it would be proper and much better for the record if you could have them listed all together. Dr. Darpy. All right,sir. We shall do that. The Cuarrman. In order to save time, I think each one of you should file such a statement for the record, and it will appear in the record at this point, if that procedure is all right with you. Dr. Darsy. Yes, it is perfectly all right. We shall proceed then as you suggested. The Cuarman. I knew you had an interesting background, Dr. Darby, and for that reason you would be highly qualified for this purpose. Dr. Darsy. Thank you. (The statements of background which were furnished are as follows :) CURRICULUM VITAE GEORGE BURROUGHS MIDER Date and place of birth: August 9, 1907, Windsor, N.Y. Education: A.B., Cornell University, 1930; M.D., Cornell Medical College, 1933. Professional training and positions held: Intern, Albany Hospital, Albany, N.Y., 1983-34. Assistant resident surgeon, Albany Hospital, Albany, N.Y., 1934-35. Resident surgeon, Albany Hospital, Albany, N.Y., 1935-36. Assistant in surgery, Albany Medical College, 1935-36. Assistant resident in surgery, Strong Memorial Hospital, 1936-37. Assistant in surgery, University of Rochester School of Medicine and Dentistry, 1936-37. Fellow in surgery, University of Rochester School of Medicine and Den- tistry, 1937-38. Instructor in surgery, University of Rochester School of Medicine and Dentistry, 1938-39. Research fellow, National Cancer Institute, 1938—41. Instructor in pathology, Cornell Medical College, 1941-42. ssistant professor of pathology, Cornell Medical College, 1942-44. stant pathologist, New York Hospital, 1941-44. Assoviate professor of pathology, University of Virginia School of Medi- cine, 1944-45. Kesearch associate in surgery, University of Rochester School of Medi- eine and Dentistry, 1945-48. Professor of cancer research, University of Rochester School of Medicine and Dentistry, 1948-52. Associate director in charge of research, National Cancer Institute, 1952-, Board certification: American Board of Pathology, in pathologic anatomy. Memberships : American Association of Pathologists and Bacteriologists. American Society for Experimental Pathology. Harvey Society. James Ewing Society. American Association for Cancer Research; director, 1952-55; chairman, Program Committee. 195: chairman, Finance Committee, 1956—. Editorial Advisory Board of Cancer Research, 1944-56, Scientific Advisory Committee, Detroit Institute of Cancer Research, 1952-60. Gordon Research Conference on Cancer: chairman, 1952, vice chairman, 1951. Panel on Clinical Investigations, Committee on Growth, National Re- search Council, 1951-62. Tumor Registry Committee, American Academy of Pediatrics, 1952-55. 408 COLOR ADDITIVES Committee on Occupational Cancer, Council on Industrial Health, Ameri- can Medical Association: chairman, 1954-. American Cancer Society ; board of directors, 1944-45; board of directors, Monroe County branch, 1950-52; board of directors, New York State divi- sion, 1951-52; Advisory Committee on Institutional Research Grants, 1056— 58; chairman, Survey Committee, 1958-59. Editorial Advisory Board, Cancer, 1957-. American Association for the Advancement of Science. AAAS Selection Committee for AAAS-Anne Frankel Rosenthal Memorial Award for Cancer Research, 1955-59. Committeeman-at-large, Section AAAS, 1957-. Washington Academy of Medicine; Clinico-Pathological Society of Wash- ington. Cancer Control Committee (National Cancer Institute), and Subcommit- tee on Environmental Cancer, 1958-. Advisory Board of the Biomedical Division, the Samuel Roberts Noble Foundation, Ardmore, Okla., 1958-. CHARLES J. KENSLER Education : Columbia College, A.B. Columbia University, M.A. Cornell University, Ph. D. Research and teaching appointments: Chemical assistant, Rockefeller Institute, New York, 1938-39, Research associate, Memorial Hospital, New York, N.Y., 1930-43. Research for OSRD, 1942-43. U.S. Army, Edgewood Arsenal, toxicologist POA, 1948-46. Research fellow, Cornell (Department of Pharmacology), 1946-48. Instructor, Cornell (Department of Pharmacology), 1948-50. Assistant professor, Cornell (Department of Pharmacology ), 1950-53. Associate professor, Cornell (Department of Pharmacology), 1953-54. Head, biological laboratories, A. D, Little, Inc., Cambridge, 1954-57, Lecturer in pharmacology, Harvard Medical School, 1954-57. Professor and chairman, department of pharmacology and experimental therapeutics, Boston University School of Medicine, 1957- Fellowships: U.S. Public Health Service, 1947-48. National Research Council, 1948-49, Traveling fellow, Oxferd University, England, 1949-50. Sloan Foundation scholar, 1951-54. Professional society membership: American Society for Pharmacology and Experimental Therapeutics, American Association for Cancer Research, Harvey Society, Society for Experimental Biology and Medicine, Biochemical Society (England), fellow AAAS. fellow New York Academy of Sciences, New York State Society for Medical Research (president 1952-53), Sigma Xi. Member of: Ejjitorial board, Journal American Society for Pharmacology and Experi- mental Therapeutics, 157-59. Drug Evaluation Panel, Department of Health, Education, and Welfare, Oancer Chemotherapy National Service Center, 1957- . Chairman, Phar- macology Comittee, 1959-—, Subcommittee on Carcinogenesis ef the Food Protection Conimittee of the Na- tional Research Council, National Academy of Sciences, 1947— Scientitie Advisory Committee on Lung Cancer, American Cancer Society, 1957-59. Scientifie Advisory Committee on Aetiology of Cancer, American Cancer Society, 1959- Dr. Darsy. In introducing this subject, I think there are certain objectives which we might try to keep in mind. First, there is that objective which I have jus. indicated of the need to provide an abun- dant, wholesome and nutritious food supply for our Nation. To ob- tain this objective today and in the future we must assure that proper COLOR ADDITIVES | 409 use is made of the many important and effective means at our dis- posal for the continued enhancement of agricultural production, of improved food preservation, of improvement in food distribution and improvement in nutritional quality of foodstuffs. It is essential that the complex of agriculture and industry combine for fulfillment of this objective and that they do so within a regulatory framework which assures maximum benefit and maximum health of the consumer, and at the same time permits the introduction of new improvements as these improvements are developed or become possible as a result of scientific progress, whether, indeed, we are thinking of improvements such as new varieties of crops, new methods of culture or new process- ing procedures. ; It was this philosophy which led, in fact, to the establishment of the Food Protection Committee of the National Academy (FPC) in 1950, and this Committee, as you know, has given attention to many aspects of the use of food additives and food additive problems. I have here only three of the several publications of the FPC which I might call your attention to. One is the so-called green book, “The Use of Chemical Additives in Food Processing,” which report of the Food Protection Committee discusses the reasons for use of additives. It lists a large number of additives which either have been used, are in use, or have been proposed for use or possibly could be used. Not all of these are used. More recently, in 1958, the Food Protection Committee published a report entitled “Food Packaging Materials, Their Composition and Uses,” dealing with the matter of food packaging. Then in December 1959, especially pertinent to the point of this panel, there appeared a report from the Food Protection Committee which is Publication No, 749, of the National Academy of Sciences- National Research Council, “Problems in the Evaluation of Carcino- genic Hazard From the Use of Food Additives.” I have brought a number of copies of this, and I hope that they will be distributed to any members of the committee who would be interested in brousing through this publication. The Cuatrman. Do you have copies of this which you can distribute to members? Dr. Darsy. Yes. The Crarrman. What is the other one, Dr. Darby ? Dr. Darsy. The other one is “The Use of Chemical Additives in Food Processing.” I do not believe we brought copies of this, nor of the food packaging material report, but if you should like copies we will be glad to supply them. The Cuamman. Very well, we will receive them for the files, and then we will look it over and see whether any part of it should be included in the record, but we will have them in the files and by reference. Dr. Darsy. The present panel contains some of the members of the Subcommittee on Carcinogenesis of the Food Protection Committee, responsible for developing this report. However, the present panel has a variety of persons who had not been concerned directly with the development. of this report and who were not members of the Food Protection Committee. I think you recognize that the panel 410 COLOR ADDITIVES has representatives from Health, Education, and Welfare. In fact, it has three such representatives. Dr. Blum, who is listed from the Biology Department at Princeton, is actually from the National Cancer Institute and is visiting scientist at Princeton at present. We also have a scientist from agriculture, we have scientists from several universities, and research institutes. We do not, I should point out, have on the Committee a repre- sentative who is directly from industry. Now, with this background of the Committee, I think we might proceed with asking each member of the panel to introduce themselves riefly and then present whatever statement they should like to make. I should say that the members of this Committee, although selected by the Academy, are appearing as individuals and not as a Committee of the Academy. Nor are they appearing as representatives of their respective agencies, but as individuals. Dr. Stewart, would you be willing to identify yourself? Dr. Srewart. Mr. Chairman and Dr. Darby, my name is Harold L. Stewart. I am from the National Cancer Institute at Bethesda. Dr. Darby, I have a short summary statement, and then I have a little longer presentation of my views, and I was wondering which you would like me to read. The summary may not mean too much without the longer statement of my views or without the presenta- tion of this point of view. I would be glad to read either one. Dr. Darsy. I think if you could adjust it timewise to approximately 10 minutes or so, why, that will enable you to choose how much of your long statement you can read. Dr. Srewart. Thank you very much, Dr. Darby. Mr. Avery. Could I ask you to speak up, Dr. Stewart? It is hard to hear in this room. I couldn’t hear your colloquy with Dr. Darby, and I would like to hear your statement. Dr. Srewart. It is not possible to establish a safe dose of carcinogen to be added to food for fuman consumption. That is my premise. These following comments present my personal views on the legisla- tion presently before the Committee on Interstate and Foreign Com- merce of the House of Representatives which is considering two bills; namely, H.R. 7624 and companion bill S. 2197. I favor the inclusion of the so-called Delaney clause which appears in House bill H.R. 7624, as stated earlier this morning. T shall summarize my comments under four headings: 1. As I have stated, it is not possible to establish a safe dose of a carcinogen to be added to food and human consumption. The effect of carcinogen is cumulative and irreversible which pre- vents the determination of a threshold dose of any one carcinogen for man. Publication 749 entitled “Problems in the Evaluation of Carcinogenic Hazard From Use of Food Additives,” published by the National Academy of Sciences-National Research Council, Wash- ington, D.C., dated 1960, contains a good deal of useful information on carcinogensis but it also contains some misstatements and insecure conclusions with which I disagree. The NAS-NRC publication 749 lists two justifications for using carcinogens as food additives: They are stated to be (1) values to the public are such that banning the use will constitute an important loss COLOR ADDITIVES 411 or hardship and (2) there is no reasonable good noncarcinogenic alternative. Justification No. 2 depends on justification No. 1. Justification No. 1 is composed of such abstract words, “important loss,” “hardship,” that it conveys no meaning. These words sound like reasons to save money or to save work, neither of which are valid excuses to deliberately expose human beings to the risk of cancer. They cannot be considered serious justifications for the introduction of carcinogens into food for human consumption. If justifications are to be stated they should be concrete, detinite, positive, and im- portant and be overriding considerations. While, as stated in NAS-NRC publication No, 749, it has been pos- sible in a few experiments to determine a so-called “safe dose” of a carcinogen for animals, this so-called “safe dose” has not been tested under a variety of experimental models in which co-careinogens, dif- ferent vehicles, different solvents, and diiferent strains of dilferent species of animals are employed, all of which may modify the effect of a carcinogen. It may be argued that since minute doses of chemicals that are toxic but not carcinogenic for animals are permitted as food additives, the same plan should be followed by adding carcinogens to food. With- out passing judgment whether or not it is justified to add toxie chem- icals to foods, I can point out that toxic effects of a chemical differ from carcinogenic effects of a chemical. If not too badly damaged, cells may recover from the toxic effects of a chemical and may thereafter be more resistant to the effects of the same toxic chemical. The ef- fects of carcinogens on the other hand are definitely long lasting, if not permanent, and the likelihood of cancer increases with repeated exposure of tissues to carcinogens. Furthermore, while it has been possible, under carefully controlled iaboratory conditions to administer a single known carcinogen in a dose insuflicient to induce cancer ina group of animals, say 10 animals or 50 animals, this would hardly apply to the inclusion of numerous carcinogens in foods to be eaten by the people of the United States indiscriminately. On the same day, and day after day a person might well ingest the same carcinogen in numerous different foods and many different carcinogens in the same and different foods so that it is likely that an individual would end up after a period of time having ingested total doses of carcinogens large enough to induce cancer in him. Added to such exposure to carcinogens in food would be the exposures that the individual sustains from the carcinogens already present from other sources in his environment. In considering the danger of low doses of carcinogens in human food it is important to consider the response of the human organism in its embryonic and young, immature states. The offspring of fe- male mice that are treated with urethane during their pregnancy will develop lung tumors. The administration of 20-methylcholanthrene to a lactating rat results in the onset of leukemia in her offspring which as pups nursed such a mother. Lung tumors and subentaneous sarcomas are more readily induced in mice that are treated with a carcinogen during the first day or first few days of life, than they are if treated with the carcinogen at a later age. All of these points to the extreme danger that may result from the exposure of human beings to carcinogens during the embryonic, fetal and infantile peri- ods of life and adult life. 56123—60——27 412 COLOR ADDITIVES Thus, if carcinogenic food additives are permitted, the human population may be exposed to the same and different carcinogenic agents from single foods and from several food sources. To these must be added the environmental carcinogens. All of these carcino- gens may exert synergistic actions on each other so that human beings are therefore exposed to a degree of contact with carcinogenic agents that can neither be quantitatively or qualitatively determined nor effectively controlled as long as present. 2. Repeated minute does of mixtures of carcinogens may operate through the mechanisms of addition, summation, potentiation, and synergism. By the administration of a mixture of two carcinogens to animals it 1s possible to markedly increase the yield of tumors over that induced by either carcinogen given alone. Thus, two weak carcinogens injected together may show definite summation of car- cinogenic effects if not synergistic action. The tumor yield from the combined carcinogens may be greater than the sum of their individual yields despite the halfing the dose of each compound injected. Two powerful carcinogens mixed together and injected may show an ad- ditive effect. 3. The results of animal tests for carcinogenic potency of agents or substances are significant for human beings just as are toxicity, microbiologic, and pharmacologic tests in animals significant for human beings. Animal experimentation provides the only known method avail- able for determination of carcinogenic nature and potency for chemi- cal substances or other agents suspected to be carcinogenic for human beings. The results of animal experiments are widely used in human medicine. If tissues from 2 human being suspected to have tubercu- losis produce tuberculosis upon injection into guinea pigs, a diagnosis of tuberculosis is made in that individual. Monkeys are used to de- termine the safety of different batches of the Salk vaccine for inocula- tion of human beings against poliomyelitis. Chemicals toxic for hu- man beings are toxic for animals also; bichloride of mercury kills an animal just as it kills a human being. So that before suspected toxic agents are added to food or used as a drug they are first tested in animals, and their use in food or as a drug is determined by the results of the experimentation in animals. The pharmacologic actions of drugs are the same in animals as in man. Substances known to pro- duce cancer in man can produce cancer in animals. All the types of tumors known to occur in man from radiations occur in animals and more too. Not only ionizing radiations, but ultraviolet radiation, soot, coal tar, shale oil, aromatic amines, creosote, chromates—all carcino- gens for human beings, also produce cancer in experimental animals. And so it is fully justifiable to regard the results of animal tests for sarcinogens as being significant for the human problem. Other experimental models should be added to those described in NAS-NRC publication 749 and these are: (1) The administration of suspected carcinogens to pregnant animals to determine whether the offspring of such mothers will develop cancer in a higher than ex- pected incidence—some children are born with tumors and so it can be concluded that human fetuses and embryos are exposed to car- cinogens in utero; (2) the administration of suspected carcinogens to lactating mothers to determine whether the pups that nurse such COLOR ADDITIVES 413 mothers will develop a higher incidence of cancer when they grow up; (3) 24-hour-old baby animals and adolescent animals should also added as experimental test objects. Day-old mice are more suscepti- ble to carcinogens than are mice 1 week old or 3 weeks old and mice of all three ages are more susceptible to carcinogens than are mice 1 year old. An example of the importance of experimental information from animals on the problem of human carcinogenesis is exemplified by the studies of the radioactive substance thorium dioxide in thorotrast. Thorotrast injected subcutaneously in mice induces sarcomas but ex- trovosated subcutaneously in man is not apt to; however, thorotrast injected intraveneously into man produces multiple sarcomas at dif- ferent sites. The NAS-NRC publication 749 is too conservative in the animal! models it recommends for the experimental testing of agents for carcinogenesis. It recommends, for example, that dogs under test be kept only for a period of 4 years, that is only one-third of their life span. Experience has taught us that dogs exposed to potent car- cinogens may not develop tumors unless they are maintained under exposure for periods of 7 or 8 years. This has been found to be true following the administration of benzidine and 2-acetylaminofluorene. Benzidine is doubtlessly highly carcinogenic for man but seems to be rather weakly carcinogenic for dogs, and 2-acetylaminofluorene which is a highly potent carcinogen for rats needs to be given in massive doses to dogs to induce tumors in them after a latent period of 7 to 8 years. I would recommend the intravenous injection of the suspected car- cinogen into experimental animals because it was by this method that the carcinogenicity of beryllium was first demonstrated in rabbits. I would further recommend the repeated injection of the suspected carcinogen by the subcutaneous route for two reasons: The suspected agent may be absorbed from the tissues and needs to be replenished and, furthermore, it has been shown that the same dose of a carcinogen administered subcutaneously may be considerably more potent if given as repeated small doses than it is if given as a single dose. Some test animals exposed to suspected carcinogens should be maintained on different types of poor dietary regimens. It has been shown in experi- ments that the potency of a carcinogen can be considerably enhanced by the maintenance of experimental test animals on inadequate diets, such as diets composed of poor quality protein or low in thiamine or Jow in protein. After all, not all human beings who ingest food that might be contaminated with carcinogens enjoy a complete nourishing diet. Many human beings suffer from malnutrition because of inade- quate diet or because of chronic illnesses. It is therefore important to reduplicate in the animal test studies, conditions which actually exist inthe human population. We are inclined to think that carcinogens always act directly on the tissues exposed to them but we need to remember that carcinogens ad- ministered by the gastrointestinal tract may produce cancer in many sites besides the gastrointestinal tract. Some of these sites are lung, pancreas, mesenteric lymph nodes, salivary glands, brain, thyroid gland, ear duct, liver. kidney, and uterus. Just whv this is so we do not know but the probabilities are that the mechanism of carcinogen- 414 COLOR ADDITIVES esis is not always as direct as that of skin cancer induced in man whose skin is splashed with carcinogenic shale oil. In addition to the experimental test models described in NAS-NRC publicaticn No. 749 suspected carcinogens should be administered in a variety of solvents because the vehicles in which carcinogens have been administered have been shown to be of great importance in the deter- mination of the site and incidence of induced cancers. A variety of cocarcinogenic agents should also be employed in connection with the suspected carcinogen under test. The philosophy should be to use every possible means to enhance the carcinogenic potency of a chemical under test because such situations will obtain when human popula- tions ingest or are exposed to carcinogens in food. NAS-NRC publication No. 749 discuses briefly the use of the epi- demiological method to study environmental carcinogens. Methods in addition to those discussed in this publication might be considered such as epidemiologic comparison with populations outside the United States of America, and between industrial and nonindustrial popula- tions. Whereas in the United States roughly 25 percent of spontan- eous tumors occur in the gastronintestinal tract, principally in the stomach and colon, this is not true in some other populations. In the Negro populations of the native townships in the environs of Johan- nesburg, South Africa, the South African Bantu has considerably less cancer of the stomach and intestine than U.S, nationals, white or Ne- gro. Of 331 tumors collected over a 3-year period from a population of 100,000 Negroes in Lourenco Marques, Mozambique, only 5 tumors in- volved the following sites: Bronchus, lung, esophagus, stomach, and intestine. A useful type of epidemiological study that could be ap- plied in the United States would be the study of men and women who are exposed to suspected carcinogenic agents in industry. In women so exposed it would be of the greatest importance also to study their offspring for possible carcinogenic effects on the embryo and on the nursing child. 4, The importance of the avoidance of the deliberate introduction of additional carcinogens into man’s environment depends upon the fact that they add to the total carcinogenic load to which human beings are exposed in their environment. Human beings are, under ordinary cir- cumstances in their environment, exposed to a variety of carcinogenic hazards including ultraviolet light, radiation from radioactive fallout, or from radioactive substances in water or food contaminated by de- posits of radioactive substances, industrial wastes, exhausts from gas- oline and diesel engines, tarred roads, medicines, cosmetics, arsenic, estrogens, DDT, industrially produced consumer goods, environmental industrial pollutants, and exposures of persons through hobbies to aints, pesticides, herbicides, cleaning fluids, and the like. If to these iazardous exposures are added a new variety of carcinogenic food additives, the incidence of cancer that is due to exogenous carcinogens may be expected to rise in the human population of this country. Dr. Darby. I hope, Mr. Williams, that your committee will ask questions at any time of our panel and I hope that the members of the panel will feel quite free to participate through discussion, questions, disagreements, or agreement, either immediately after a speaker or at the time that you give your statement. COLOR ADDITIVES 415 Mr. Wiuu1ams. Dr. Darby, I don’t know about your panel, but I don’t think that you will find the committee unusually bashful in that respect. Dr. Darby. Unless somebody has a question—Mr,. Younger ? Mr. Youncer. Dr. Stewart, 1s tobacco carcinogenic ¢ Dr. Srewarr. I don’t know whether tobacco is, but tobacco tar is. Mr. Youncer. Are cigarettes? Dr. Stewart. The tar from cigarettes is carcinogenic. Mr. Hemp... Mr. Chairman Mr. Wittrams. Mr. Hemphill? Mr. Hemeniny. I enjoyed the presentation, Dr. Stewart. I would like to ask you one question. In the progress we have been making in this country in preventive medicines and antibiotics, is there any relationship between that progress and the growth in the number of people having cancer? Dr. Srewarr. Well, cancer—certain cancers are increasing in this country. It is said that cancer of the lung is on the increase; and certain cancers appear to be decreasing. It is said that cancer of the stomach is decreasing. It is always possible to relate changes like these to certain assurances. For example, the increase in the use of radios or televisions, the increase in the use of automobiles, increase of cigarette smoking, and so forth, but to relate them to a certain event and have that mean any- thing you must have proper controls. For example, wearing dentures may be related to these things, or changing the type of footgear from a high type of shoe to a low type. Mr. Hempuinn. I was trying to find out if there was any relation bet ween the increase in any type of cancer or cancer generally and the progress we have made in preventive medicine such as antibioties and the myacines and sulfa drugs, and so on. Dr. Stewart. Oh, yes; the longer people live the more cancer they develop, and if you save lives and have people living into an old age, whereas formerly they died, say, at ages 30 and 40, there will be much more cancer. Most cancers rise toward the end of life. Mr. Hempuinn. But except for the fact that the life expectancy and life realization, the longevity has been increased of mankind, it has no other relation that you know of ? Dr. Stewart. Yes. For example, people who have studied lung cancer relate this to the year people were born. For example, they take all the people who were born, let’s say, in 1885, 1886, 1887, and so on, and they show that taking those groups that. are called cohorts, and following those groups throughout their lives, the ones who were born later developed more lung cancer, suggesting that they have been exposed more to some carcinogen that produces lung cancer than the ones who were born earlier. Mr. Hempnine. And that tendency is congenital ? Dr. Stewarr. Not congenital; no; it is due, we think to the exposure to carcinogens in the environment. Dr. Darsy. Dr. Levin, would you like to speak at this point ? Dr. Levin. I think the Congressman is referring to the post-effect of improvements in medical and preventive care, so that greater num- bers of people reach an older age than would be true 20 or 30 years 416 COLOR ADDITIVES ago. Now it is quite possible to show, sir, that if that effect is taken into account by considering the number of cases of cancer per 1,000 persons of each age group that there has been a net increase mn cancer over the last 30 years in males and a net decrease in females. That is in the mortality chiefly. The increase in cancer which has been ob- served from the standpoint of the number of cases per 1,000 popu- lation has been chiefly in the following forms of cancer: cancer of the lung, cancer of the bladder, cancer of the pancreas, cancer of the kidneys, and in females cancer of the ovary. There seems to be a real decrease of cancer of the stomach, both in the males and females. With the exception of cancer of the lungs, which is definitely tied up with the use of tobacco, there are not very good explanations for these increases in cancer in the human population, but they cannot be ex- plained as entirely due to ine reased longevity. Mr. Hemeniny. Thank you, Mr, Chairman. Mr. Wiuutams. I would like to ask Dr. Stewart a question to follow up Mr. Younger’s question. You made the statement that the tars, tobacco tars, are carcinogenic. Does it follow that you are in a posi- tion to state that smoking can be the approximate cause of cancer ¢ Dr. Srewarr. No, Lean’t. Mr. Wiir1ams. Then in what manner are these tobacco tars ap- plied? In other words, what manner of application is required in order to prove they are carcinogenic Dr. Srewarr. That is quite a difficult thing. You find people in this country, some of whom believe that smoking cigarettes is a cause of cancer, others who don’t believe they are a cause of cancer of the lung, and some people who don’t know for sure. I don’t know the answer to that. I have read a good deal of this. I have done some ex- periments on it myself. Cigarette tar is certainly carcinogenic if it Is painted on the skin of mice. Mr. Witurams. That is the point I wanted to make. Is there any proof that tobacco sinoke inhaled by mice will induce lung cancer? Dr. Srewarr. I did an experiment on that a number of years ago in which mice were exposed to cigarette smoke in a chamber for many months and, as a matter of fact, the experimental animals had less lung cancer than the control animals, so you can understand my natu- ral reluctance to accept the statement of many of my colleagues that cigarette smoking is the cause of lung cancer in human beings. Of course, one person is working with human beings and one with mice. Dr. Darsy. Don’t you think this is an example of one of the things that plagues us in work of this sort: That is the difliculty of trans- lating studies or findings froin one species to another? What is car- cinogenic in one species is not always carcinogenic in another, just as you have indicated here. And sometimes that which is not car- cinogenic in one species is carcinogenic in another. Dr. Srewarr. I didn’t say that tobacco smoke is carcinogenic in one species and not in another. I said I am not sure that cigarette smok- ing is the cause of lung cancer. I said that tar from cigarettes caused cancer when painted on the skin of mice, but when inhaled doesn’t cause cancer of the lung in mice that I tested. Now whether cigarette smoking may be carcinogenic on the human lungs, as I say, I don’t know. COLOR ADDITIVES 417 Dr. Darsy. Without judging this, though, is it not true that you have great variation between species in testing, not just tobacco smoke, but other things? Dr, Srewart. You mean for testing carcinogens? Dr. Darsy. Yes. Dr. Srewarr. You can paint methylcholanthrene on the skin of mice or rats and get cancer and tumors in 100 percent of the mice but none in the rats. ‘if you inject the methylcholanthrene subcutaneously in rats and mice both species develop sarcomas. You have to consider the species, the tissue affected, the solvent, the general condition of the animal and so forth. There is a great deal of variation in experi- mental carcinogens, Mr, Youncer. I think you brought up a rather interesting point there that has puzzled some of us. I would judge that in your tests, if you were testing smoke from tobacco, you would probably get some coal tar in it, some small particle, probably. Isn't that true? Dr. Stewart. In the lungs of these mice that I tested you could see tarinthem. I could demonstrate it. Mr. Youncer. All right. Now if that was controlled by the De- laney amendment, then you would have to prohibit that, wouldn’t you, even though you say that it is safe? Dr. Srewart. I can’t say it was safe. No, I didn’t say it was safe. Mr. Youncer. I understood you to say that it was safe. Dr. Srrwarr. No, I didn’t say that it was safe. I said it didn’t produce cancer in those mice and I said that I don’t know whether cigarette smoking is a cause of human cancer or not. That is my posi- tion. I wouldn’t say that smoking cigarettes is safe for human beings or for mice. As a matter of fact, it made mice pretty sick. They didn’t look very good. Mr. Younerr. The point that I make is that you test tobacco and you find coal tar, a test. of coal tar even though in a very minute quan- tity, and you say that, at least as far as you know, it didn’t breed can- cer. Dr. Stewart. In the lung. Mr. Youncer. But you take cranberries and if you test and get a very minute sample—one in a million, one in a billion—of a carcino- genic substance, there under the Delaney amendment it is thrown out. I was wonderi ing where the difference lies? Where our responsibility to the people is # Dr. Srewart. I answered your first question, Your first question was in tobacco carcinogenic and I said tobaceo is carcinogenic because you can take tobacco tar and paint it on the skin of mice and you can get cancer. Now I said further that I exposed mice to the inhalation of tobacco smoke and got less lung tumors in my experimental animals than I did in mye ontrolled animals. Well, if cigarette smoke is to be tested carefully it should be tested in a great many species. I did some tests in mice and some other people have done some tests, but not many. There has really been no real serious effort to attempt to produce lung cancer by exposing animals to cigarette smoke, It could be that, as Dr. Darby said, you may find a species in which that species is suspectible to the car- cinogenic effect of cigarette smoke on the lung and it could be that 418 COLOR ADDITIVES human beings are susceptible. I don’t know that answer, whether cigarette smoking is carcinogenic for human beings. Mr. Kerri. Mr. Chairman? Mr. Witntams. Mr. Keith. Mr. Kerri. You said that you found tar in the lungs of these mice that had been inhaling smoke. Dr. Srewarr. That is correct. Mr. Kerrn. And tar on the lung tissue more exposed than skin, which is conditioned to exterior exposure, didn’t cause cancer of the inside of the body, where it did cause it on the outside of the body? Dr. Srewarr. That is correct. Mr. Kerru. It seems very inconsistent. Dr. Srewarr. Well, mice are sometimes inconsistent. This is bio- logical experimentation, you see, and we are products of biology, the human being. Mr. Kerru. You made reference to the impact of television on the human being as a factor to be considered in weighing your experi- ments. What did you mean by that? Dr. Stewart. I didn’t say that. You didn’t express it the way I expressed it. No, I said several things can happen at the same time in a country, as, for example, in the United States in the last several years or in ancient Rome and ancient Greece, and associated with those very same happenings may be other happenings. For example, there has been an increase in hing cancer, according to my friend, Dr. Levin. Now during the time there has been an increase in lung eancer, there has been an increase in the sale of radios, an increase in the sale of television; we have had a small depression, the price of whiskey has increased. Now how do all these things affect the increased inci- dence of lung cancer? That is all I meant to say, you see. Mr. Screncx. Mr. Chairman? Mr. Winntams. Mr. Sehenck. Mr. Science. May I point out, Dr. Stewart, that there has also been a tremendous increase in automobile traflic, a lot of increase in exhaust gases into the air. Isn't that maybe a part of your progress? Doesn't that become a part of vour analysis? Dr. Srewarr. Of course the exhaust from the automobiles are carcinogenic. Mr. Avery. Dr. Stewart, I don’t like to belabor this point, but I am a little confused on this matter. In your experimentations, just what were you able to establish with your experimentation on cran- berries that is carcinogenic which you did not establish as to the carcinogenic effect of tobacco tar? Dr. Srewarr. Tnever experimented with cranberries, Mr. Avery. Apparently somebody did in your shop, did they not? Dr. Srewarr. Not that [have heard. Dr. Miner. No, sir, Mr. Avery, not at the National Cancer Insti- tute. We have used 3-amino 1:2:4-triazole to interfere with the oxi- dative enzymes in the liver, but we have not tested its carcinogenic potency in experimental animals, There is one experiment under- way at the present time. Mr. Gienn. Dr. Stewart, did I understand you to say that DDT has some effect in the growth of cancer? Dr. Srewartr. DDT has been shown to be a carcinogen for animals. COLOR ADDITIVES 419 Mr. Grenn. Does that mean then the use of DDT in these sprays throughout agriculture and the many other uses it may have some effect on animals? Dr. Srewarr. It may have some effect on animals, Mr. Drnceit. And on humans, too. Dr. Srewarr. And on humans. Mr. Guenn. Has any safe limit been arrived at as to the use of DDT? Dr. Srewart. I don’t know whether a safe tolerance for DDT in animals has been shown or not. Dr. Darpy. Dr. ‘Tannenbaum, would you like to speak to that? Dr. TANNENBAUM. From the discussion that has been taking place, one might get the impression that the whole field of carcinogenesis is in a state of confusion. This is not true. Some of the misunder- standing arises from not taking into account the varied responses due to the differences in species, tissues affected, potency of agents studied, time of exposure, and so forth. If the agent that induces cancer is potent, effects may be elicited in more than one species and in a number of tissues. On the other hand, if the agent is potent but utilized in extremely small dosage, or if it happens to be very mild or weak, it is more difficult to demonstrate a cancer-producing effect. This morning, certain questions and comparisons failed to consider these and other facts. For example, the same agent (cigarette smoke) may produce a cancer of the ling in man after acting for 20 to 30 years, but may not in the mouse exposed for only 6 months to 1 year. The relative size of the nasal passages, and the rate and depth of respiration, may make a difference in the amount of agent that reaches the bronchial epithelium. Tissue susceptibility may differ between species. These and other factors and conditions must be considered before accepting a view that different events have occurred following identical exposures. Mr. Wituiams. Let me ask Dr. Darby this question before we go any further. Do I understand that each of these gentlemen has a brief statement to make? Dr. Darby. Yes. Mr. Witiiams. The time is passing rather rapidly. I am certain that the members of the committee could keep you here all day on the points raised in Dr. Stewart’s statement, but I am inclined to think that maybe we better move along as fast as we can. I believe you were seeking recognition, Dr. Levin. Dr. Levin. Mr. Chairman, I simply wanted to comment on an im- plication which Dr. Stew art has made which members of the com- mittee apparently took up, that the evidence regarding the relation- ship between cigarette smoking and lung cancer “rested “merely on the association of time between these two characteristics. This is not true at all. The evidence rests on the fact that people who smoke to- day or at any given time when they have been studied show a greater incidence of lung cancer than people who do not smoke, This is not merely a temporal association, but an association in people who do or do not. Dr. Darsy. I think these points will be elaborated on in the subse- quent statements because of the various interests of the panelists. I 420 COLOR ADDITIVES think we might follow your suggestion, sir, and go on with the next statement. Mr. Wiuutiams. I think it would be advisable to move along as fast as we can. Dr. O’DonnEtu. Members of the committee, Iam Walter E. O’Don- nell, assistant, Division of Preventive Medicine, Sloan-Kettering In- stitute, assistant professor of preventive medicine, Sloan-Kettering Division, Cornell University Medical College, and assistant director, Strang Cancer Prevention Clinic, Memorial Center, New York, N.Y. As I understand the role of this panel, it is primarily to provide back- ground to the members of the committee in order that they may reach the proper decisions. However, I also understand that there are two principal questions which are involved here, and I think it would be unrealistic and probably not very helpful if we were to concern our- selves only with principles, rather than specifics, which obviously you men are concerned with. The two questions, as I understand them, are actually one question. First of all, should the so-called Delaney amendment be retained, modi- fied, or eliminated, and, secondly, is it possible to set safe tolerances for food or color additives known to induce cancer in man or animal. Now the first question having to do with retention, modification of elimination of the so-called Delaney amendment seems to me is primarily a concern of the legislators. It is not really up to us as people concerned with the scientific aspects of the matter to advise you specifically. Tlowever, I think we would not be fulfilling our responsibility—at least I would not—were I not to make my feelings known on the matter. In my opinion, I believe that the Secretary of Health, Education, and Welfare should not only have the authority but the responsibility to evaluate the carcinogenicity of and possibly ban the use of certain color additives when in his judgment and that of his advisers a significant cancer threat is posed. So that if this clause under discussion charges the Secretary with the responsibility he does not now have or grants him power he does not now possess, then in my opinion it should be retained. If not— if, as I suspect, he already has this responsibility and power and is exercising them, then the clause would seem to be superfluous and unduly inflexible. The Secretary should, of course, have full authority to take any appropriate course of action, but it would appear unwise, in my judg- ment, to attempt to spell this out in advance too rigidly or to single out cancer for special consideration. However, this is primarily a matter of interpretation of the clause as it is worded. Now the second part, having to do with the establishment of safe tolerance levels, is more of a scientific question. I think, first of all, there is need to define what is meant by a “safe tolerance level.” With- out going into that specifically here—and this will undoubtedly come out in the later discussion—I think one must say that if you mean that by reducing the dosage of a laboratory carcinogen to a certain minimum level, one could be absolutely 100 percent sure that no human would ever develop cancer no matter how long the exposure, the answer must be “No.” But one should hasten to flank this statement with one which emphasizes that by the same token it is virtually impossible to declare any substance absolutely safe. It is inherent in the very COLOR ADDITIVES 421 nature of such biological testing schemes that there will be false posi- tives and false negatives. That is to say, certain substances will be declared free of cancer hazard which in fact do not appear to be free of cancer hazards and others will be declared carcinogenic which do not appear to be. In general, I would oppose any attempt to set tolerance levels for the more potent carcinogens and Dr. Tannenbaum’s point is well taken that it is important to distinguish between strong and weak carcino- ns. I would also oppose setting tolerance levels for weak carcinogens, not because I do not think it could be done with considerable ac- curacy and safety much of the time, but in the vast majority of cases it seems unnecessary to assume even the small risk of miscalculation involved. I feel sure in most instances, as Dr. Stewart has implied, a substitute additive, noncarcinogenic by all laboratory tests, could be found which would do the job just as well. I would rather have the decision to set tolerance levels one of judgment, not of legislation. However, although I am opposed to tolerance levels in the ordinary scheme of things, I do believe the Secretary should be given the op- portunity to exercise flexibility discretion and judgment in certain rare instances. I certainly can conceive of situations in the future in which a compound of very unique and important capacities, one for which there is no substitute and which when used in miniscule amounts plays an important role in our economic and industrial life, might suddenly and inexplicably be found to have weak carcinogenic properties. As I understand it, under the proposed legislation such a substance would have to be banned without any consideration of its known benefits as opposed to its hazards. In such a situation I be- lieve that the mature scientific judgment and discretion is called for. If, then, the Secretary's decision were to ban the substance, I would respect his judgment. Thank you. The Cuairman. Thank you very much, Doctor. If you will excuse me just a minute, the Chair would like to go off the record. (Discussion off the record.) Mr. Wiuurams. Proceed, Doctor. Dr. Darsy. Thank you, sir. Are there comments or questions on Dr. O’Donnell’s statement ? Mr. Dineevi. Mr. Chairman, could I be recognized ? Mr. Wituiams. Mr. Dingell. Mr. Dincett. Doctor, you made the statement that it is conceivable that some food additives would at some future time have an enormous impact on the economy which would justify the fixing of tolerances fora carcinogen. Is that a correct summary of your statement ? Dr. O’Donnewt. Well, I think—yes, but—— Mr. Dinceii. Do you know of any such situation that prevails? Dr. O’Donxuti. No, I do not at the present. However, I must immediately disavow any pretensions to being an expert on food additives as such and the various ones which might involve a situa- tion such as I speculated upon. Mr. Dixeeii. Now under the circumstances, you say you know of no situation where this would be justified as of this particular time. Now let’s go on. You say that this should be a matter of judgment 422 COLOR ADDITIVES in the Secretary. Is that correct? Your statement that this would be a matter of judgment does not raise an inference that the Secretary has not been behaving promptly in his actions in banning of certain carcinogenic substances from the foods? I don’t want to embarrass you and I don't want to entrap you; I want to know, Doctor. This is not to embarrass you, but you don’t want to raise any inference that. he has been acting on improper scientific evidence, do you? Dr. O'Donnetx. No, I certainly do not. In a sense it seems to me that the Secretary is empowered to set tolerance levels at the present time. Mr. Dinceu. For things other than carcinogens? Dr. O’Donne.t. Well, because of the nature of the wording of the clause, as I understand it. In other words, it would seem to me he is empowered to decide when tests are appropriate for the testing of a substance and when they are not appropriate, and if he is confronted with evidence which would appear to the average person, let’s say, to demonstrate that a substance is carcinogenic, it is his prerogative to declare this an inappropriate test. Mr. Dinceti. So, in etleet, the Secretary does not fix tolerance levels. In effect, what the Secretary does is exercise an intelligent judgement as to whether or not the tests are appropriate to determine whether this substance actually happens to fall within the bane of the so-called Delaney clause and actually determine whether or not they induce cancer, whether these substances induce cancer in humans or in test animals; isn’t that correct? Dr. O'Donnetn. Yes, this is his role. Mr. Dincrtn. So, in effect, the Delaney amendment as of this mo- ment, as applied in existing law, does not ban mature scientific judg- ment in terms of whether or not a substance is carcinogenic or not, does it? I say does not ban mature judgment. Dr. O'Donneti. No, it does not. However, it specifies something that we assume is being exercised now and would appear to give him power which he already has, as far as IT am able to determine. Mr. Dincert. I see. Thank you very much, Mr. Chairman, The Cuamman. Any further questions? Thank you very much. Proceed. Dr. Danny. Tf there are no other questions, we shall proceed to the next panelist, Dr. Mider, National Cancer Institute. Dr. Miner. Mr. Chairman, gentlemen of the committee, in the in- terest. of saving time, I will be glad to associate my views with those of my distinguished colleague, Dr. Harold Stewart, insofar as the general tenor of his prepared statement is concerned. 1, too, believe that the language in House bill, TLR. 7624, often referred to as the Delaney clause, is necessary for the optimal protec- tion of the public interest in the light of our present knowledge. The current controversy over the Delaney clause is intensified perhaps by rapid advances in our technology. We are now able to measure some chemicals in extremely small amounts that only a short time ago could not even be detected in such low concentrations, or, if detectable, could not be quantified. One can understand the reluctance to accept an hypothesis that millimicrogram quantities of a compound may produce cancer when the only existing data relate to the cancer- producing activity of doses measured in milligrams, 1 million times larger. On the other hand, some vitamins essential to our well-being COLOR ADDITIVES 423 are active in micromilligram quantities and probably some of the hormones produced by cer’ rtain endocrine glands are equally potent. The Delaney clause has been criticized as rigid and allowing for no scientific judgment of the results of research. I submit that the clause requires a finding that a chemical does in fact produce cancer when ingested by man or animal and also requires that tests be appropriate for evaluation of the safety of food additives. These requirements ean only be met through scientific judgment relating to adequacy and validity of experimental design and the reproducibility and reason- able interpretation of the results. The Secret: ary of Health, Educa- tion, and Welfare has also emphasized this point. Finally, Lam deeply concerned about our ability to control the con- sumption ‘of any food additive. A poisonous drug can be used ex- tremely well by the medical profession, and much good accrues in the public interest. The same compound used indiscriminately may kill. A drug or chemical introduced in the food supply will be eaten in various degrees of susceptibility to its pharmacological effects. The ability to produc e cancer is but one of many noxious setfects. I believe the current uncertainties concerning quantitative factors in the ear- cinogenic process as initiated by chemicals require the safeguards included in the Delaney clause of House bill H.R. 7624. Mr. Winuiams. Thank you for your statement. Mr. Younerr. Dr. Mider, will you read that statement back where you mentioned the responsibility of the Delaney amendment ? Dr. Miner. The first statement I made about it, Mr. Younger? Mr. Youncer. No. As I understood it, you said that it is neces- sary to prove that this particular food is eancer producing. Now you have something in there about it, which under the Delaney amendment it is required thi if you must make tests. Dr. Miper. I submit that the clause requires a finding that a chemi- eal does, in fact, produce cancer when ingested by man or animal and also requires that tests be appropriate for evaluation of the safety of food additives. Mr. Youncer. Well, that isn’t the understanding which I person: ally gathered from Mr. Flemming. If they discovered a carcinogenic substance of any quantity, without any further test as to its appli- cation to mice or anything else, then it is thrown out. Dr. Miper. That is correct, sir, providing the evidence is adequate to support such a judgment that it is in fact carcinogenic. It is then thrown out. Mr. Youncer. In any quantity? Dr. Miner. Correct. Mr. Youncer. And you do not have to have tests to prove whether or not this particular chemical produces cancer ? Dr. Miver. That is correct. Mr. Dincenn. Just a minute. That is not a correct answer to that uestion. Once the tests establish that a substance is a carcinogen, then it is banned, but let’s say the establishment of a tumor in a single mouse or rat or in a single strain of mice would not be suf- ficient on which to base a proper judgment that the substance is a carcinogen, Dr. Miver. Other things being equal, that would be true. I can think of circumstances, however, in which the appearance of one tumor in a small group of mice might require additional experimenta- tion before one could give a good judgment. 424 COLOR ADDITIVES Mr. Dince.u. This is precisely the point that I was talking over with Dr. Stewart, or rather, with Dr. O’Donnell to the effect that this is a matter of mature judgment. Dr. Mmer. Yes, sir. Mr. Drncett. It is tested scientifically as to whether or not the sub- stance does create a cancer in a test animal or human being and then it is banned. Dr. Zavon. Mr. Chairman. Mr. Fiynvr. Dr. Zavon. Dr. Zavon. Would it be possible for the chairman of the committee to give the members of the panel, one might say, an official interpreta- tion of this Delaney clause, because, as I read it, the first part of the clause says flatly— shall be deemed unsafe and shall not be listed for any use which will or may result in ingestion of all or part of such additive, if the additive is found in amounts and under conditions reasonably related to the intended use to induce cancer when ingested by man or animal, or if it is found— That is an “or” clause, and my previous experience would indicate that “or” legally has a great deal of significance and therefore this is a flat prohibition without any judgment involved. Is this correct, or is there another interpretation ? Mr. Fiynt. Dr. Zavon, let me say that the present occupant of the Chair could take the easiest way out and say the permanent chairman has just returned. However, I think that would be manifestly unfair to the chairman. Let me say this, as a practice the present occupant of the chair or any person who might be occupying the chair at the given time, would attempt to give a definitive statement on any phase of proposed legislation or inactive legislation because this particular section of which you have asked a definitive interpretation, 1s capable of as many diiferent interpretations as there are members of a com- mittee or a panel. Mr. Witi1ams. And as someone said, our Supreme Court. Mr. Fiynr. And I do not, of course, Dr. Zavon, mean to give you a short answer on that, but it is impossible to give a definitive answer. Dr. Zavon. The reason I ask the question is that apparently the Secretary has interpreted it to mean that judgment can be used, but apparently a succeeding Secretary, someone else, could equally well take the same words and say, “No, I cannot use my judgment, this is a flat’ prohibition irrespective of the validity of the test involved.” This is what disturbs me just a little bit in reading this wording. Mr. Fiynt. What you have stated is substantially true, that under the phraseology of the language that you just read the Secretary by his exercise of his own independent judgment which would be binding until overruled by a proper court ruling or by his successor in office. Mr. Rocers of Florida. Mr. Chairman, I just wanted to ask Dr. Mider a question. As I understood it, you feel that there is an element. of judgment as far as the Delaney amendment is concerned in determining what is a carcinogenic substance. That is where the judgment comes in? Dr. Mivrr. Yes, Mr. Rogers. ; Mr. Rogers of Florida. But once that has been established, then there is no judgment to determine what level might be safe, is that trie? COLOR ADDITIVES 425 Dr. Miper. That is correct. Mr. Rocers of Florida. Now, is it true that, for instance, feeding or injecting a tannic acid, which is in, say, tea, has been shown b scientific studies to produce cancer. Are you familiar with any suc studies? Dr. Miver. I am superficially familiar with it, Mr. Rogers. I believe that tannic acid does produce damage to the liver and tumors do arise in the liver. Mr. Rocers of Florida. Would that constitute a carcinogen ? Dr. Mier. I am not familiar enough with the details of the experi- ment to pass judgment at this time. Mr. Rocers of Florida. I wonder if any of the members of the panel are. Dr. Munter. Korpassy, in Hungary, has definitely shown that when large amounts of tannic acid are injected subcutaneously in rats liver cancer will develop. There is no evidence yet that feeding of tannic acids, which are present in many of our foods, will induce cancer in exper ‘imental animals. Mr. Rocers of Florida. What about the feeding of eggs? Dr. Munier. That is a very important point. There is an investi- gator who has fed boiled egg yolk repeatedly to mice for their lifespan and claims to have an incre: ised incidence of cancer in these mice. Now, many of us in the field of chemical carcinogenesis and nutri- tion realize’ that these experiments are thoroughly inadequate to support the conclusions that this investigator has made. He has used small groups of animals. He has not controlled them from the stand- point of caloric intake and so forth, So astatement to the effect that egg yolk or eggs are carcinogenic is at present indefensible. Mr. Rocrrs of Florida. Does not stand up under scientific judg- ment ? Dr. Mutter. It certainly doesn’t. Mr. Rocers of Florida. How about salt in the diet ? Dr. Mitirr. The only hint that I can think of that this has been associated with carcinogenesis are experiments in Japan on the subcu- taneous injection of hypertonic—that is strong solutions of salt—for 1 year to rats. these rats then developed about a 20-percent incidence of sarcomas; i.e., tumors derived from subcutaneous tissue. An iso- tonic level of sale did not produce any tumors when so injected. This is at the level found in our blood. So I think the route is highly abnormal, and there is no reason to believe that salt is carcinogenic by ingestion. Mr. Rocens of Florida. Is it toxic? Dr. Miturr. Any substance can be toxic if supplied to an animal in sufficiently large amount. Mr. Rocers of Florida. Is salt toxic to an animal if it is 6 percent of its diet ? Dr. Muuter. It certainly is. If you feed enough salt you can kill an animal off easily. Dr. Darsy. As a matter of fact, Mr. Rogers, you can increase blood pressure very significantly in rats ‘ond i increase the number of animals that die of the consequences of hypertension by increasing sufficiently the amount of salt in the diet over a long period of time. In fact, excessive amounts of any nutrient can be harmful. Any essential nutrient if given in sufficiently large quantities can be judged to have 426 COLOR ADDITIVES toxic effects. If we give any one of the vitamins in sufficient quan- tities, we can get toxic effects, although if we do not have them we die for a lack of them. Mr. Rogers of Florida. So you have used scientific judgment to de- termine the level of intake? Dr. Darby. Exactly. Mr. Rocers of Florida. Now, what I wanted to know about these tests that, are made by Dr. Mider, for instance—are all of the tests done by ingestion or are the tests made by injection as well ? Dr. Miner. Mr. Rogers, in most cancer research laboratorise we have done most. of our testing by injection or by painting. There has been comparatively little testing for carcinogenic action by oral administra- tion, especially of those things which might conceivably be used as food additives. We have fed compounds which have no probability of ever entering the human environment outside of the laboratory, but we are woefully ignorant of dose response relationships or of carcino- genic effects obtained from feeding of some of the things that are of interest in relation to food additives. Mr. Rocers of Florida. I wonder if the tests then are consistent. I am asking for my own knowledge. Are the tests inconsistent? Can results of our intake by ingestion be proved by tests by injection? You see what I mean? What I am trying to drive at, there are tests of ingestion and injection. Will they bring about the same result ? Dr. Miper. Not necessarily, Mr. Rogers. For example, one can pro- duce an inerease in the frequency of breast tumors in mice by the in- jection or ingestion of the estrogen diethylstilbesterol. One can do it also by the injection of naturally occurring estrogens, but we do not anticipate we will be able to feed these estrogens and get the same effect because generally speaking they are destroyed by the gastro- intestinal juices. Mr. Recers of Florida. In determining what materials are carcino- genie do you make your determinations from your tests by injections to determine what the human should ingest 7 Dr. Miver. Mr. Rogers, most of the things that we have been in- terested in, we were interested only because they produced cancers. For that purpose we can define a carcinogen as any material which will produce a cancer by any route of administration. This is ac- ceptable in some circles. Whether or not this broad definition is appropriate to the interpretation of the Delaney clause I think is open to very considerable question. Mr. Rogers of Florida. I wondered what basis there should be for making tests to come to a scientific judgment, which is the only judg- ment, I understand, that would be permitted under the Delaney amendment, the judgment of determining what is carcinogenic. What is the test that should be used? Dr. Miver. I would prefer, Mr. Rogers, that anything to come under the Delaney clause should have been tested by feeding. I would find it most difficult to say that since sodium chloride has been found to cause cancer by injection subcutaneously in large quantity that this has any real pertinence to the use of sodium chloride in our diet, especially when body fluids contain a measurable concentration of sodium chloride without which we couldn’t live. Mr. Rogers of Florida. Is it possible under the Delaney amendment. to show that by injection salt could become a carcinogenic material COLOR ADDITIVES 427 or could be—I think the tests show that perhaps under some circum- stances it could be. Is it possible under the Delaney amendment that some future Secretary would have the authority then to say that this would be banned from the diet ? Dr. Miper. Mr. Rogers, I can’t answer that, sir. I am sorry, be- cause I believe most of the judgments are made by the extremely competent scientists of the Food and Drug Administration, and the scientific judgments are then taken to the Secretary for aflirmation. Mr. Rogers of Florida. Iam not saying that I am questioning any- one’s abilities, and Iam not. I am saying under the interpretation of the Delaney amendinent since you say that the only judgment is. whether material is or is not carcinogenic—a test by injection could bar materials to be ingested. Dr. Miper. Within the meaning of this act. Mr. Rogers of Florida. Now, if you make tests by injection and use an injection testing method to determine whether material is cancer forming, then it is possible, is it not, under this Delaney amend- ment for some future Secretary, if they tell him, well, now, we have made tests by injection and it has caused cancer, would it not then be possible for some future Secretary under the Delaney amendment to say there will be no salt sold for humans? Dr. Miver. Theoretically, sir, it is possible, Mr. Rogers of Florida, Thank you. Dr. Darny. Mr. Rogers, I believe some of the other panelists will give some attention to this question of the method of tests and the interpretation and the nicety of judgment as to the appropriateness of a given test in relation to the use or possible use of an additive. Now, I think even possibly Dr. Kensler may have something to say on it and perhaps we may let him at the same time make his statement. Mr. Fiynr. I would like to ask Dr. Mider one question: Is it sub- stantially true that nearly every element of food known at the present time if either injected or ingested in large quantities is capable of producing cancer first or toxicity secondly 4 Dr. Miner. No, Mr. Flynt, I don’t believe it is possible to produce cancer with most foodstuils. It is, however, possible to produce toxicity with most of them, some type of toxicity. Mr. Avery. Mr. Chairman, I would like to ask a question before we get into the next statement. I think I will direct it to Dr. Stewart. We have used the pronoun “they.” They conduct these tests to de- termine whether or not a certain chemical is carcinogenic or not. Who isthey? Who finally makes that determination ? Dr. Srewarr. I don’t do it, but I think this is done by Food and Drug Administration. Mr. Avery. Does anybody here know? Dr. Larrick. In general, if a new article is to be introduced into the diet it is incumbent upon the manufacturer to bring to the Food and Drug Administration the evidence showing that it is not harm- ful to them and also evidence dealing with this carcinogenicity, and then our scientists are empowered to use just these judgmental de- cisions that Dr. Mider spoke of. Ordinarily the tests are made in the universities or in the commercial laboratories and are brought to us by the firms that want to use the food additives. Mr, Avery. Thank you. I will read your statement again after a while. 56123—60——28 428 COLOR ADDITIVES Mr. Keiru. Mr. Chairman, I would like to ask a question of Dr. Stewart. Mr. Frynt. Mr. Keith. Mr. Kerrnu. In your opinion, Dr. Stewart, would fluoride in 1 part per 1,000 cause cancer in test animals? Dr. Srewarr. I don’t know. Mr. Kerru. Is it possible that it could? Dr. Stewart. I really don’t know the answer to that. Mr. Keir. Thank you. Dr. Darrny. Dr. Kensler. Dr. Kenster. Charles Kensler, professor of pharmacology and ex- perimental therapeutics, Boston University School of Medicine. I think the committee has available to it—or I know it has the docu- ment which was prepared by a subcommittee of the Food Protection Committee of the National Academy of Sciences. This is the docu- ment entitled “Problems in the Evaluation of Carcinogenic Hazards From Use of Food Additives.” There are seven members of this com- mittee, four of whom are present today. I think in this report you will find in moderately detailed fashions most of our collective scien- tific knowledge and evaluations of this problem, although we as in- dividuals may differ with particular statements of opinion expressed init. In contrast to what Dr. Stewart said about it as being too con- servative, I think actually he meant it is not conservative enough. It is in reality too liberal. I think in terms of Dr. Stewart's state- ment, concerning possible synergistic effects of carcinogens that he is using a different definition of synergism than I would use. Syner- gism means to me that you get more from the combination of two things than simple addition. I am not aware of experiements which clearly prove synergistic effects. I am aware of experiments which show that one carcinogen can prevent the action of another in the same animal. I would like to read three sentences from this report. These were some generalizations which the committee found it possible to agree on. The first is one—— Mr. Ketrn. What pages are you reading from ? Dr. Kenster. Iam reading from page 19: 1. If a substance is shown by adequate test to be carcinogenic for one mam- malian species, it is probable that it is carcinogenic for many, but not necessarily for all others, although quantitative differences between species may be marked. 2. Carcinogens are likely to be active when administered by any of several but not necessarily all routes, although noteworthy quantitative differences asso- ciated with route of administration are evident. 3. There are nontumorgenic levels of exposure to carcinogens for given experi- mental conditions, but threshold levels may be affected by a number of factors associated with the carcinogenic process. I think this last point is really the erux of the issue; namely, while T think most would agree that carcinogens, certainly weak ones, can be administered to animals without any increase in the resulting spon- taneous level of cancers to which the population is exposed. Tt is difficult to extrapolate from species to species, from route to route, to arrive at quantitative evaluations of any safety level for man. How- ever, I do believe as a pharmacologist that carcinogens represent not a unique category of materials but represent compounds at one end of aspectrum. Carcinogens have a slower onset of action than many other drugs. They have a longer duration of action, which may or COLOR ADDITIVES 429 may not prove to be irreversible. There is evidence suggesting that it is not truly irreversible, but at this point it is controversial. The area which I would like to mention, an example in terms of the amounts required to produce cancer, which I think is an important consideration, which is automatically excluded by the Delaney amend- ment, which, in my opinion, prevents an expression of scientific judg- ment on this matter could be illustrated by a compound which when fed to rats at a 25-percent level in the diet products an incidence of bladder cancer, which is statistically significant in animals fed at that level. This occurrence is associated with the production of bladder stones. Insofar as we know this compound does not produce bladder cancer unless it first produces stones. There is obviously, as has been shown in these experiments, levels at a 10-percent-of-lifetime intake of an animal in the diet where neither stones nor cancer were produced. Now, I think that it is problems such as this that scientific judg- ment should be permitted to be exercised under the law, and that it would seem to me that. the Delaney amendment might be modified from its present all-inclusive ban to a statement which would involve the scientific judgment of the problem as a whole, including the ex- perimental evidence, and that this might be handled by having the Food and Drug Administration make its decision as to whether a compound would be permitted for use or not than if the users or the potential users would like to challenge the—we will assume they will just challenge adverse decisions—that a panel of experts, both Gov- ernment, such as Dr. Stewart and Dr. Mider, and outside competent individuals, be appointed to express an opinion as to the extent of the hazard. The information on which the decision was based should then be made public at the same time that the decision is made public so that other scientists and interested people would have knowledge of the basis on which the decision was made. Thank you. Mr. Fuynt. Dr. Kensler, I was impressed with the last statement you made about the necessity for some exercise of judgment. Don’t you think that that discretion is authorized by the power given in the language of the amendment for the Secretary to determine which testsareappropriate? I will read this: * * * or if it is found, after tests which are appropriate for the evaluation of the safety of additives or use in food, to induce cancer in man or animal. The example that you just gave about giving a substance in doses of 25 percent and then comparing it with an amount equal to less than 10 percent of the lifetime intake, I think, was your expression ; wouldn't that very fact give to the Secretary at least a latitude of discretion that he could exercise ? Dr. Kenster. Not in my judgment, sir, as I read this law. It lists material fed at the 25-pereent level produced these effects and the amount at the 10-percent level did not. According to the law, the first part here, before you get to the “or,” “if the additive is found to induce cancer when ingested by man or animal,” it seems to me this clause is overriding, but then I don’t know the answer to these legal problems, Mr. Frynt. You have brought forth the point right there that I wanted to go in the record here. Mr. Keirn. This is what caused all the trouble in the cranberry incident, in my opinion. 430 COLOR ADDITIVES And the Secretary said before the committee that he did not want to have responsibility to establish a threshold, and if he had that responsibility or if ite had resorted to a panel as I requested the President to do at the time this thing came up, in my opinion, we would not have had the extensive difliculties that we did. Mr. Fuynr. Thank you, Dr. Kensler, for including your statement for the record. Dr. Darny. Are there any other comments? Dr. Srewarr. I want to defend myself against the attack made upon me by my good friend, Dr. Kensler. He questioned my use of the word, “synergistic effects,’ and I would like to call his attention, and I will be glad to insert this in the record, to the experiments done by Dr. Steiner and Dr. Falk at Chicago and published in Cancer Re- search in the January 1951 issue. These two scientists took two so- called weak carcinogens, chrysene and 1:2 benzenthracene. They gave each of these two carcinogens in a certain dose and they got tumors that appeared at a certain time, and they got a certain number of tumors in their experiment. Then they combined these carcinogens. They gave half the dose of each carcinogen combined, so that according to Dr. Kensler, they shouldn’t have gotten any more tumors than they did with the most powerful of these two weak carcinogens. Look what they got. The tumors appeared somewhat earlier and they got many more than could be accounted for by the combined carcinogenic effect of these two carcinogens. : Now, I read you what Dr. Steiner and Dr. Falk said about this: 1. 1:2 benzanthracene and chrysene were carcinogenic, inducing sarcoma on subcutaneous injection. The former was stronger than the latter, having both a shorter induction time and a higher tumor yield. The significance of these results with regard to the relation of chemical-physical characteristics of hydro- earbons to their carcinogenicity is discussed, 2. 1:2 benzanthracene and chrysene injected together showed definite sum- mation of carcinogenic effects if not actually a synergistic action. The tumor yield was greater than the sum of their individual tumor yields, despite the halving of the dose of each compound injected. This observation is significant, because it cannot be explained by the existing theories of inhibition or sum- mation effects of carcinogenie compounds, 3. The carcinogenic effects of 1:2-benzanthracene and 1:2:5:6-dibenzanthra- cene injected together were not those of summation but apparently of inhibition. 4. The carcinogenic effects of 1:2:5:6-dibenzanthracene and 20-methylcholan- threne injected together were additive, although imperfectly so. I would say with respect to this other carcinogen that Dr. Kensler mentioned, which produces bladder tumors and which he would like to sce introduced into the diet of the people of the United States, it is such combinations of so-called weak carcinogens of this type plus other weak carcinogens that may produced bladder cancers, that makes the problem so difficult because it is impossible to quantitate for the individual citizen how much of these various combinations of car- cinogens he may get, and he is up against the problem which acts biologically of the synergistic action of one carcinogen upon another. Dr. Kenster. If J may clarify my position and answer the attack of Dr. Stewart, I would like to point out that it is impossible to arrive ata decision as to whether you have a synergistic effect or not unless you have established the dose response curve to both of these materials alone and together. Dr. Srewarr. Here they are. Read the book. 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(que. sem jaorm 920101 ord peormayo prise? punodmoy emty = BUTI WOT] aad) aad) -09188 18107 18707 jo "ON jo‘"7my Gorjonp = -onput Spars tppark = paonpur aary aary aay una aomny sounyp = jocOoN “2294 297 “ON SNOMUVIOUCAH AO SLOAIIY NOILVNIGHOD ANV ALIQINADONIOUV) 432 COLOR ADDITIVES 8 1:2:5:6—dibenzanthracene a + 20-methylcholanthrene & 1:2:5:6-—dibenzanthracene 20-methyl cholanthrene 4° __ 1:2-benzanthracene ar + Chrysene 30 ’ ra 1:2-benzanthracene ; / o———— +: 1:2:5:6—dibenzanthracene PER CENT OF MICE INJECTED DEAD WITH TUMOR § e 1:2-benzanthracene Fia. 1.—Cumulative mortality from induced tumors. Shows the effective total mice in each experiment was the number cumulative percentage of the mice injected witheachcompound surviving at 4 months. dying of tumor im each month. For calculating these figures COLOR ADDITIVES 433 Dr. Kenster. Is that dose or time? Dr. Stewart. Here are the raw data. Dr. Kenster. This is not a dose response curve. This is a time course in the occurrence of incidence. Mr. Kerry. Excuse me, Mr. Chairman. Dr. Kenster. I would like to clarify one other matter. I did not recommend or mean to imply that I recommended that this emulsifier be included in the diet. What I recommend is that a panel consider whether or not they would recommend it in any amount, and that they have the right to do this and not be automatically banned by Jaw from even considering this problem. The Cuairman. Gentlemen, this discussion has reached a most in- teresting stage. I am wondering, in view of the time and no doubt the demands made on a good many members of the committee, since we have a great many of our constituents here for various reasons, it would not be advisable to recess until 2 o’clock. I think the business of the House will have been accomplished by that time. We can come back and resume, as I understand several members of the panel have not yet presented their statements; is that right, Dr. Darby ¢ Dr. Darsy. Right. The Cuatrman. That would indicate that we are getting along, and if you gentlemen would accommodate us by returning at 2 o’clock, we will resume. (Whereupon, at 12:10 p.m., the committee recessed to reconvene at 2 p.m., of the same day.) AFTERNOON SESSION STATEMENTS OF DR. WILLIAM J. DARBY, CHAIRMAN, DR. HAROLD F. BLUM, DR. PAUL R. CANNON, DR. FLOYD DE EDS, DR. CHARLES J. KENSLER, DR. MORTON L. LEVIN, DR. G. BURROUGHS MIDER, DR. JAMES A. MILLER, DR. WALTER E. O’DONNELL, DR. HAROLD L. STEWART, DR. ALBERT TANNENBAUM, AND DR. M. R. ZAVON— (Resumed) The Cuamman. The committee will come to order. Dr. Darby, you may proceed. Do you want to take up where we left off, with a lively discussion? If so, that is all right with me. Maybe the committee is enthusiastic. Dr. Darsy. Thank you, Mr. Harris. I think in order to get back into the spirit of the discussion we might start with the statement from the next panelist. Knowing this panel, seeing its performance this morning, I am sure we will immediately get back to the spirit of the discussion at the time we had the break for lunch. So I would like to introduce Dr. Paul Cannon. Dr. Cannon. Mr. Chairman, with reference to my qualifications for service on the panel, let me say that I have the M.D. degree from Rush Medica] College and the Ph. D. from the University of Chicago. For the past 40 years I have been a pathologist, the last 20 of which have been as chairman of the department of pathology at the Uni- versity of Chicago, until my retirement in 1957. At the present time I am the chief editor of the Archives of Pathology of the American Med- ical Association. I am a member of the Food Protection Committee 434 COLOR ADDITIVES and of the Carcinogenesis Committee of the National Research Coun- cil, and I am chairman of the Studies Section on Toxicology of the National Institutes of Health. I might add that I was a member of the group that worked out. the problem of the elixir of sulfanilimide tragedy of 1988 in which we established diethyleneglycol as the toxic agent. As you will recall, this episode stimulated the passage of the Food, Drug, and Cosmetic Act of 1938. As to my accompanying statement, since most of the discussion this morning was essentially theoretical, I would like to make a few remarks of a practical nature with reference to the prob- lem of testing. The details of this problem are handled in the bro- chure that has been mentioned this morning, but I don’t know whether all the Members of the Congress or even all the members of this com- mittee are completely aware of the complexities of the testing problem from the standpoints of time and expense involved, numbers of ani- mals required, facilities demanded, and, particularly, the availability of personnel competent to determine the question of carcinogenesis of selected agents. I think Dr. Stewart and Dr. Hueper and I esti- mated about 3 years ago that at that time there might not be more than 12 persons in the entire country competent to do this job, and that, furthermore, probably of those 12 not more than 6 would be interested in doing it. There is unquestionably a tremendous dearth of toxicologists, and also of experimental pathologists. We estimated at that time that it might cost something in the order of $200,000 to test adequately a single substance. I mention these facts simply because many are unaware of them. Furthermore, one of the objectives of our Toxicology Study Section is to promote interest in methodology in the field of food additives in order to find ways whereby some of these problems can be solved more rapidly and less expensively. It is a tremendously complex problem. I notice in the act of 1958 that there was a time interval allowed for certain chemical substances that might be added, a testing period of 1 year which could be extended to 2 years. Now the time period of March 5 has passed and I under- stand that many of these have had to have another period of extension, In consequence we now have the so-called white list and the black list. In relation to these time periods Jet me recall that in our recom- mendation of the Carcinogenesis Committee, we suggested that a mini- mum of 4 years may be necessary in the dog for the testing of possible carcinogenicity, and Dr. Stewart has suggested this morning that in some instances it might take 7 or 8 years. And yet if we are going to legislate on this, we can’t avoid the above hard facts unless we can discover more rapid methods. It is true that in H.R. 7624 there is more leeway with respect to time of its becoming effective; viz, a 21-year period, with the Secre- tary of HEW being allowed to give a further extension if necessary. I am sure, however, that there will be situations in which even 314 years will not be adequate for the proper testing of certain substances for carcinogenicity. To me the most hopeful thing about this legislation is the fact that more persons are becoming interested in the problem of carcinogenesis and the prevention of cancer rather than in trying to cure cancer after it has developed. COLOR ADDITIVES 435 In any case, no matter how hopeful we may be, we must look forward to many years of intensive investigation of the problems of carcino- genesis. I offer these suggestions on the assumption that some may not be completely aware of the extreme technical difficulty of the prob- lem and the great scarcity of manpower in this field. There is one other item I would like to mention, because I think many people are also unaware of this. We have been studying this problem i in the Food Protection Committee of the National Academy of Sciences for at least 5 years. Dr. Stewart, Dr. Hueper, and I were on the first ad hoe committee that started the study, and that led to the present committee from which this report has come. I would like to emphasize this point: The entire impetus for the study came from the industry members of our group. I say this because I think they are entitled to great credit for asking that ‘a detailed study be made of the entire problem of chemical carcinogenesis. They have cooperated with us in every way in our studies, Thank you. The Cuarman. Thank you, Doctor. Dr. Darny. Do members of the committee have any questions or points you would like particularly to put to Dr. Cannon? The Cuaman. Mr. Rogers? Mr. Rooers of Florida. Mr. Chairman, on the testing, Dr. Cannon, is there any agreed method or is there disagreement on the methods used for testing for the carcinogens? Dr. Cannon. I think there are others on this panel who will talk to that. However, it was obvious in this morning’s discussion that there are disagreements as to methods of testing, and I suppose there always will be. I think that is a good thing, in the interests of prog- ress. The important question is: When you legislate, you have to be sure, as I am sure you realize, of the nature of these disagreements. I think every member of this panel would be free to admit how much is not known, and indeed many have already admitted that. In short, we have to develop new methods and continue to try to get better methods. It is a pretty severe kind of test which may require 7 or 8 years and then even have to be extended to the offspring of animals, as Dr. Stewart brought out this morning in connection with the transmission of some of these materials through the mother’s milk. It is just another problem for which we have no answer. Mr. Rocers of Florida. Yes, I realize the difficulty, and what IT was wondering now, is there some basis of agreement that the scientific community could come to to decide on testing in order to be helptul to the Secretary of Health, Education, and Welfare in coming to a conclusion as to what should be pr ohibited 2 Dr. Cannon. I think there has been a reasonable basis of agree- ment between our report and the members of the Food and Drug Administration, for instance. Asa matter of fact, one member of the Food and Drug Administration was on our committee, and there has been quite good agreement, I should say, on methodology. I think the thing we are all unhappy about is the fact that the methodology is so complicated. 436 COLOR ADDITIVES Dr. Darsy. I think if you should like this might be a point for several members of the panel to comment on your question, because this is a very important question, and as Dr. Cannon has emphasized, it is one which has very real practical considerations in terms of resources required for study, and returns on invested resources after a certain degree of investment. I believe, “if I might predict what the general nature of the dis- cussion may be here, that there would be a large area of agreement up to a certain point, on the kinds of investigations which would be informative. That where the major disagreement will arise is in the extent of study beyond a certain basic program which will prove informative. I don’t want to influence the nature of the discussion, but I think that this is what one will see as the discussion evolves. I would like if I might to call on two or three members of the panel to comment on this. Dr. Miller, would you like to speak to this? Dr. Mier. Briefly, yes. Certainly there is very good agreement, T believe, amongst this ‘subcommittee and Food and “Drug ‘Adminis- tration that testing by ingestion is necessary in every case. That is, when you have substances new to man’s experience, that are being roposed for use in foods, they must be tested by this partic ular route. Yow practical considerations limit the type of animal in this case. We have to get these tests done in some reasonable leneth of time, and we have to have animals that are readily available in large numbers, and this for all practics! purposes brings it down to using the rat and the mouse for their lifetime. This is of the order of 2 to 3 years. This is what we on the subcommittee have proposed, that these substances be tested at several levels for the lifetime in rats and in mice. We also have suggested, because of the fact that large species dif- ferences exist amongst various animals and their response to carcino- gens, that these substances be tested in one other species, a nonrodent species. Here again you are limited to practical considerations. The dog is for all practical purposes the only other species that we can turn to at the present time on which we have any real information, on how this species responds to carcinogenic substances. We have proposed that these animals he tested for ‘approximately 4 years. Now I know that Dr. Stewart feels that this is not long enough, but there have to be some practical limitations. If we tested each substance in the detailed way that Dr. Stewart outlined, this morning, we would never get done with testing one substance in the next 20 years. We have also suggested that these materials be tested by painting on the skin of mice. Now to my knowledge this is not required at present by Food and Drug Administration, but we feel this is a site observation that is always available to the experimenter. He can pick up early lesions. It is a site on which we have a great deal of information on the mechanism of carcinogenesis, such as it is. We have also suggested a very limited use, at least in some cases, of the subcutaneous route. Now, there is a lot of argument about this, and we have suggested that this test be used in certain cases in a very limited sense, that is a single injection of a fairly large amount of material. COLOR ADDITIVES 437 This is to prevent false positives. Now, we have mentioned this morning how salt or sugar solutions in high concentration when re- peatedly injected produce tumors in a very sensitive site, the sub- cutaneous tissue of a rat. Now what is involved there? What is involved is not only the in- jection of these materials every day, but every day you have to put a sharp needle in there. You are destroying cells. You have regenera- tion of cells. You can’t tell at the end whether this effect, the tumor that you got, had anything to do with the continued regeneration of tissue or whether it was really due to the material that you injected. Mr. Dincexx. Doctor, at this point perhaps maybe your statement about injection of salt under the skin might not have so much to do with the salt being there as with the sticking of the needle. Dr. Miter. You do it with water and you won't find tumors, but together you do. So it is very difficult to separate these two things. Therefore, our reason for suggesting that a single injection be made was to eliminate as far as we could the repeated trauma and regen- eration with repeated injection. Mr. Rocers of Florida. Did I understand you to say that when in- jections were made with water there was no— Dr. Mitier. Nothing happens then or with iosotonic salt, that is, salt that is present in the same concentration as in our body fluids. So you see the tests that this subcommittee have proposed go beyond the present requirements that the Food and Drug Administration requires to show whether a compound is carcinogenic. Now they are limited by practical considerations obviously. There is a limit to what you can expect a manufacturer to come in with in terms of data, so it Is an extremely difficult problem, and one in which further re- search needs to be done. I am gratified to see that the Food and Drug Administration is turning more and more to research in this field and I certainly hope that they can continue to get more appropriation for this sort of work. We need more information on this. Mr. Rocers of Florida. Mav I ask one question there? As I under- stood some of the discussion this morning, they felt that there was a level of application of scientific knowledge as to testing the amount of the item to be tested, and that is where the scientific judgment came into play in the testing, to determine whether something is bad or good for the diet. But as soon as that had been established, then under the Delaney amendment as I understand it, that item would be barred if it were found to have carcinogenic properties. Now do you think we are at the point where we can generalize in this area where judgment would be put into eifect to the extent that we can get the result that we want now? Dr. Mitier. I certainly don’t think we can generalize in such a way as to take care of the testing of all kinds of substances that may come along. There are some very big surprises, at least they are to me, that have come up in terms of what will produce a tumor in an animal. I think we have to make it possible that the merits and demerits of a particular substance in question are examined by as competent a board of scientific experts as we can get. 438 COLOR ADDITIVES Let them exercise the judgment. Mr. Rogers of Florida. Are you in agreement with Dr. Cannon that there are perhaps only 12 people of adequate competency now to fully conduct these tests and perhaps only 6 who wish to be available ¢ Dr. Miter. Perhaps in terms of directing these tests, but I believe that these people certainly could direct many more people. Mr. Rocers of Florida. But you are in agreement. with Dr. Cannon? Dr. Minter. There certainly are not many people particularly con- cerned with research on chemical carcinogenesis. Mr. Rocers of Florida. Thank you. Thank you, Mr. Chairman. The Cratirman. Mr. Younger? Mr. Youncoer. I would like to have each of you speak on the ques- tion of pure foods, to express your own view as to whether in your opinion Food and Drug ought to have any discretion whatsoever in these cases. I think that is the point that we have to decide, as to whether in your opinion any latitude, any setting of standards should be allowed the Food and Drug. I would like that in the case of each one of vou. Dr. Darsy. You have heard this request. Dr. Miller, would you like to comment on this? Dr. Minter. Certainly they should be allowed discretion. These people are extremely competent in their field, but they can’t be ex- pected to know all the ins and outs of every new type of compound that comes up before them. Tere is where I believe they have to have the opportunity to go out and seek, perhaps through the National Acadeiny of Sciences, a competent board to help them in making these decisions. Obviously, they have to make the decision. Mr. Youncer. In regard to the Delaney amendment, that is what is confusing. Now right within Government we have differences of opinion. Mr, Clarkson, who is the Associate Administrator of the Agricultural Research, who came up before the committee and stated category that he did not believe that Food and Drug ought to be hamstrung with any kind of amendment that did not allow them to set some kind of standards. Dr. Mitier. Might I just point out something? T have been quite interested in reading through this food additives collection of all the past hearings. You will recall that before the present. food additives amendment was passed, that the Department of Health, Education, and Welfare was of course asked for their opinion, and they spon- sored a bill. This bill did not have any statement in it about cancer producing substances. It is very interesting that the testimony of Mr. Larrick given there stated this, and I am quoting Commissioner Larrick: This bill bars the use of an additive unless it is established that it is without hazard to health. Thus the bill would prohibit the addition of any chemical ad- ditive to the food supply unless adequate evidence acceptable to competent scientists shows that it will not produce cancer in man under the conditions of use proposed. It is obvious that they felt that they had the complete authority to do what needed to be done without having it spelled out in so many words, with the possibility of a restriction occurring that was not intended perhaps in the bill. COLOR ADDITIVES 439 The Cuairman. Doctor, I understand, however, that you take the position that there is no tolerance at all under the language in the food additives amendment. Dr. Miuier. Yes. The Cuatrman. And under the language that is now in this bill? Dr. Mutter. There is no tolerance. It comes under the statement as I see it in the first part of (b), line 11, “is found to induce cancer when ingested by man or animal.” I, for example, do not feel that this emulsifier that we heard about this morning that produced blad- der tumors when fed in 25 percent of the diet, an astounding level, is a carcinogen. I mean this happened indirectly. At the 10 percent level nothing happened. At the level it would be used in human food, I cannot believe it would have this effect. I am looking for the report by the Food Protection Committee on the subject of the emulsifier. It certainly strikes me that this compound has been tested extremely well. The only thing against it is that when tested at 25 percent of the diet, it produced this syndrome. In some animals in a more limited test at 20 percent of the diet nothing happened. If the decision had not been made to test the emulsifier at 25 percent, as far as I can see this question would never have arisen. The point is where do you stop? The Cuatrman. Are you in a position to state, Doctor, as to whether or not in your opinion the Food and Drug Administration should have the authority to establish any tolerance at all? Dr. Mituer. Well, as I was planning to state in my comments, I think it should in very dubious cases of carcinogenicity, “as for ex- ample this compound that produced these bladder tumors when fed 25 percent of the diet.” I think they should have that discretion. Mr. Dinceti. Mr. Chairman, may I ask a few questions at this point ? The CHamman. Yes. Mr. Dincewu. Doctor, your last statement, in cases of very dubious carcinogenicity, I believe those were your words Dr. Miuter. Yes. Mr. Divert. You say that discretion ought to be given. What you are really saying is that they ought to be given a scientific dis- cretion to determine whether or not these substances are actually cancer producers. Dr. Mitter. Right. Mr. Dincrii. And it is to this discretion that you have been ad- dressing yourself ? Dr. Minver. Yes, Mr. Dincetn. And not the discretion let us say as to the fixing of tolerance levels for known carcinogens, isn’t that it ? Dr. Mitier. That’s right. Mr. Dincett, And as a matter of fact you do not advocate the fixing of a tolerance level for any known carcinogen weak or strong, do you 4 Dr. Mitrer. On which there is good scientific agreement that it is a carcinogen. Mr. Dinceti. So we then resolve ourselves to this premise and not to the other premises, and to this precise point: That scientific judg- ment should prevail as to the first point. One, whether the substance 440 COLOR ADDITIVES is a carcinogen in fact, and that this should be a question of sound scientific judgment and discretion, is that correct Dr, Miter. Yes. Mr. Drvcexx. You do not address yourself to or support the thesis that judgment or discretion should be given in the fixing of tolerance levels for known carcinogen, do you ? Dr. Minter. In human food. Mr, Dineett. In human food ; yes? Dr. Minier. Yes: that’s right. Mr. Drncetu. In fact you “vould very strongly oppose the fixing of a level of tolerance for a known carcinogen in human food, is that correct ? Dr. Miter. On the basis of our present information in carcino- genesis, that 1s correct. Mr. Drxcevi. And you say on the basis of our known information on carcinogenesis. Your reason for saying this, Doctor, is simply that presently we do not have sound scientific know ledge upon w rich we may base a transfer of information let’s say on test animals to human, except in very narrowly isolated cases and then possibly not too good at that point; am I correct ? Dr. Miuier. Yes. Mr. Drvcety. Now let me ask: Is there any member of the panel who says that tolerance levels can be fixed and should be fixed for known carcinogens ! ¢ I notice Dr. Zavon over there. Do you make that statement? Dr. Zavon. I would like to go into this in detail in my statement if you will permit me to delay until that time. The Cuarrman. I think asa matter of fact that we probably should move on to let each one of these gentlemen have their say. That will be a more orderly method of srocedure in making a record on this. Mr. Dixcet. Thank you, Mr. Chairman. Dr. Darsy. Dr. Kensier? Dr. Kenstrr. I would like to ask Dr. Miller a question or two. It is my understanding that the definition of a carcinogen is a chemical which has been shown to produce a significant, a statistically signifi- cant incidence of cancer, and that therefore this material which “he is talking about is by definition a carcinogen, and is covered by the Delaney amendment. I would then like to ask him the second question: Would you be willing to eat or have in your food a few mictograms of this material ? Do you think this would represent any hazard to you or to anyone else? Dr. Minter. There is the area where we just don't have any infor- mation, I am personally not. very concerned about these extremely tiny amounts, but it is the difference between knowing that a particu- lar compound is in food and knowing that it is a strong carcinogen when you test it experimentally, and it is a difference of knowing whether at the tiny amount that is in food, does it constitute any hazard? Now my personal feeling is that. in very tiny amounts it does not constitute any hazard. Dr. Kenstrr. May I say if we accept your definition, that it is not a carcinogen, then you would be willing to eat it, is that right ? Dr. Minter. Are you talking about this emulsifier? Dr. Kenser. Yes. COLOR ADDITIVES 441 Dr. Mriter. Yes. I have no question about that subject. Dr. Darsy. I think part of this problem, Mr. Dingell, lies in what you mean by a carcinogen and what I mean and what Dr. Miller, Dr. is true, is no larger than five in a hundred * [3] [6] [8]. General adherence to such a rigid strategy is interesting by itself but might have no further consequences on the decisions reached. However, when a fixed level of significance is used as a critical criterion for selecting reports for dissemination in professional journals it may result in embarrassing and unanticipated results. 1The author wishes to express his thanks to Sir Ronald Fisher whose discussion on related topics stimulated this research in the first place, and to Leo Katz, Oliver Lacey, Enders Robinson, and Paul Siegel for reading and criticizing earlier drafts of this manuscript, 2The fact that some tables present only the 0.05 and 0.01 levels of significance encour- ages the use of these two levels of significance [8, p. 202]. COLOR ADDITIVES 473. TAaBLe 31.—Outcomes of tests of significance for 4 psychology research journals: Number of research Number of] Number of | Number of} reports Total research research research that are number reports reports reports | replication: Journals, all issues from January to of research | using tests} that reject | that fail to| of pre- December reports of signiti- Ho with reject He viously cance | Pr( Ej ito) <.05 published experi- ments (ly (2) (3) (4) (5) Experimental Psychology (1955) ....--.-. 124 106 105 1 0 Comparative and Physiological Psy- chology (1956) 118 4 a1 3 0: Clinical Psychology (1955, 8! 2 59 3 0 Social Psychology (1955) 39 2 31 1 o Total....--.2-.. avensccevevesoce 362 204 286 8 0- Table 31 shows that for psychological journals a policy exists under which. the vast majority of published articles satisfy a minimum criterion of signifi- cance. The table summarizes the number of research articles in four publica- tions. The journals were selected at random from four major areas of psy- chology. The table gives the distribution for the number of reports that used: tests of significance to test Ho and either rejected H» or failed to do so at Pr (£ | H.)=.05. In addition the table gives the number of experiments that were replications of previously published investigations, Column 1 gives the number of experimental research reports and column 2 gives the number of those reports that used tests of significance to choose among possible alternative: hypotheses. Column 3 shows how many of the reports of column 2 managed to- reject Ho and column 4 counts the number of reports that failed to reject Ho. (either for the major hypothesis tested or for the majority of hypotheses under investigation.)* Finally, column 5 gives the number of experiments representing a replication of work previously reported in the literature. Table 32 shows the same distributions as proportions of columns 1 and 2, A glance at the tables is sufficient to show that most articles published during: the year by the journals in question used tests of significance as aides in choos- *Some explanatory remarks concerning table 81 are in order. Almost all of the 294 studies that used tests of significance were of a multivariable design. All evaluated ob- served differences against the assertion of Ho, however, Ho was sometimes not rejected for all variables tested. The following rules were adopted in compiling table 31: (a) The attempt was made to determine the major variable or prediction tested by the research design. Such was usually clear from the author's preliminary remarks; the multivariable design was most frequently used to contro! for conditions not covered by the experimental procedure. The level of significance for which Ho was rejected for the major prediction was noted (if He was rejected at all). (b) If the design tested two or more variables for which no unambiguous decision as to major importance conld be made, the lowest level of significance for which at least half the- variables rejected Ho was noted, If Ho was not rejected for at least half the variables, the article was placed in the class of studies for which Ho was not rejected. {c) Where results from more than one research design were reported, an attempt was: made to determine the one study deemed most crucial by the author and the level of sig- nificance for that study was recorded if it rejected Ho. (d) If all studies seemed of equal importance, the lowest level of sienifieance for which at least half the reported studies rejected Ho was recorded. If Ho was not rejected for at least half the studies reported, the article was placed in the class of studies for which He was not rejected. (This special provision in 2 and 4 was not really necessary since for no single article were less than half of the quoted results fn the stenificant category.) (e) Two studies that obtained Pr(F|He)—0.1 were Included beeause the authors had expressly pointed out that they rejected Ho since the obtained significance level was close enough to the conventional 0.05 to suit their purposes, Since the Psychological Abstracts essentially attempt to present an outline of the major- olnts made in almost all research articles of interest te psychologists the procedure used ere could be checked for reliability with that publication. Of 100 research articles selected at random from volumes covering 1952 to 1957, 94 reported positive results, 5 reported negative results, and one was a replication of a previous study. These propor- tions agreed by and large with thhe total proportions in table 31. No comparison for use of tests of significance were made since that journal seldom reports results of statistical tests. However, the words “significantly different” were applied to most of the reported: results. 474 COLOR ADDITIVES ing among alternative experimental hypotheses and, at the same time, that nearly all managed to reject Ho at the recommended level of certainty. It need not be assumed that the observed distributions are due to explicit edi- torial rules. The single factor contributing most to the selection of articles in which H, is rejected may be implicit agreement among authors. The term “publication policy” will be used here largely as a matter of convenience. In fact, the distribution of articles in psychological journals in general appears to be similar to the ones shown in the table and it seems likely that the authors selection rather than editorial policy accounts for the observed profession-wide selection. Whatever the reasons, the tables indicate what gets printed with a high probability; namely, research reports that use tests of significance and at the same time reject H» for the effects of treatments in the design.‘ To state the above more concisely : TABLE 32.—Percent of articles using tests of significance and percent of articles rejecting Ho Percent of Percent of Percent of - articles using | articles re- articles not Journals, all issues from January to December tests of all | jecting Hoof! rejecting Ho articles walarticles | of all articles published using tests using tests (2/1) (3/2) (4/2) Experimental Psychology (1955)... .- wee ee eee 85. 48 99.06 0. OF Comparative and Physiological Psychology (1956) .- 70. 66 96. 81 3.19 Clinical Psychology (1055)... ....-.--.-.-------.-- 76. 54 5. 16 4s4 Social Psychology (1055)_........2..-.-2-2---+-2-------+------ 82.05 16. SS 12 0 6 81, 22 97. 28 A, Experimental results will be printed with a greater probability if the relevant test of significance rejects H. for the major hypothesis with Pr, (E\ H,)=.05 than if they fail to reject Ho at that level. A; The probability that an experimental design will be replicated becomes very small once such an experiment appears in print. With respect to Ax, it is not known how many research results either reject Hy, or do not do so, or, are submitted or not submitted for publication. How- ever, it does seem clear (2) that pressure exists which leads to the selection of a very small number of publications from a large number of submitted mann- scripts. From a commonly admitted tendency to acknowledge only the most significant findings, and from perusal of statements concerning publication pres- sures (2) one could infer another reasonable assumption : A; A great many more experiments are performed than appear in the pages of professional journals, With respect to As, the lack of replication of experimentation in psychology has been noted elsewhere (5). Replications are sometimes reported at profes- sional meetings. Since such papers are rarely used as references unless they have been published they may be ignored as sources for widespread professional or scientifie information. The three assumptions are admittedly substantive in nature and strong sup- porting evidence for them, beyond that given here, is hard to come by. They may be taken as a fair statement of the prevailing conditions in which the scientific community is not equally aware of all experimental results. As a con- sequence, experiments for which Pr( | H) is large may well have a high fre- queney of replication by individuals who do not know that this particular com- parison bad been made previously, and that previous tests of significance had failed to reject Ho at acceptable levels of significance. Once a study does result in a level of significance that meets this criterion, not only will it be published, but the likelihood of its ever being repeated appears to become very small. A picture emerges for which the number of possible replications of a test between 4It-is interesting that the Journal of Experimental Psychology appears te set the pnee for the use of statistical tests as well as for the selection of articles that reject Ho. Some years ago the same journal wis used [4] to show that 7? was consistently misused by psychologists. The authors noted at the time that analyses in this journal would be typical fer psyehologieal publications in general and that the expectation of finding sound statistical treatments would be better in that journal than in others. COLOR ADDITIVES 475 experimental variates is related inversely to the actual magnitude of the differ- ences between their effects, The smaller this difference the larger may be the likelihood of repetition. This chain is terminated apparently by an observation for which the relevant statistical test can reject Ho with reasonable certainty. For any set of observed differences that are randomly variable (and which ex- perimental observations are not?) a difference of some substance should then appear in print—irrespective of the actual state of nature. What credence can then be given to inferences drawn from statistical tests of H. if the reader is not aware of all experimental outcomes of a kind? Perhaps even more pertinent is the question: Can the reader justify adopting the same level of significance as does the author of a published study? Two points are worth noting with respect to the last two questions. Both refer to the expectations a reader may form when he picks up an article in one of the journals of table 31 (or in a journal following like practices). First the reader's best expectation is that the author will reject Ho. The probability that he will commit a type II error (accepting the null hypothesis when it is false) if he adopts the author’s conclusion is, in consequence, extremely small. In fact, from table 31 it appears that this risk is scarcely more than zero, One may therefore conclude that any and all tests used by authors are of equally high power for the reader. This obviously was not true for the individual investigator who attempted fo choose the most powerful test in the first place. There is also another side to this problem. ‘The reader's expectations are that H. will be rejected. What risks does he take in making a type I error by rejecting H> with the author? The author intended to indicate the probability of such a risk by stating a level of significance. On the other hand, the reader has to consider the selection that may have taken place among a set of similar experiments for which the one that obtained large differences by chance had the better opportunity to come under his serutiny. The problem simply is that a type I error (rejecting the null hypothesis when it is true) has a fair oppor- tunity to end up in print when the correct decision is the acceptance of H, for a particular set of experimental variables. Before the reader can make an intel- ligent decision he must have some information concerning the distribution of outcomes of similar experiments or at least the assurance that a similar experi- ment las never been performed. Since the latter information is unobtainable he is in a dilemma. One thing is clear however. The risk stated by the author eannot be accepted at its face value once the author's conclusions appear in print. It may be safe to conclude that pursuing statistical analyses under the conditions outlined here may have considerable less merit than psychologists like to ascribe to statistics in experimental design. It would be unfair to close with the impression that the malpractices discussed here are the private domain of psychology. A few minutes of browsing through experimental journals in biology, chemistry, medicine, physiology, or sociology show that the same usages are widespread through other sciences. Some onus appears to be attached to reporting negative results. Certainly such results occur with lesser frequency in the literature than they may reasonably be expected to happen in the laboratory—even if it is assumed that all experimenters are outstandingly clever in selecting hypotheses, Perhaps the trend of our time is exemplified by the editors of a cancer journal who in a recent announce- mrent took action to change the name of their yearly supplement from “Negative Data... to"... Screening Data” [1, p. 619].° BIBLIOGRAPHY (1) American Association for Cancer Research, “Cancer Research 18,” Uni- versity of Chicago Press, 1958, (2) American Psychological Association, Publication Manual (1957 Revision), Washington, D.C., Psychological Association, 1957. (3) Edwards, A. L., “Experimental Design in Psychological Research,’ New York, Rinehart & Co., 1950. (4) Lewis, D. and C. L. Burke, “The Use and Misuse of the Chi-Square Test,” Psychological Bulletin 46 (1949) 433-489. (5) Lubin, A., “Replicability as a Publication Criterion,” American Psychol- ogist 8 (1957) 519-520. * This was pointed out to me by Charles Stevens of the Kettering Laboratory, University of Cincinnati, 56123 --60-———31 476 COLOR ADDITIVES (6)McNemar, “Psychological Statistics’ (2d ed.), New York, John Wiley & Sons, 1955. (7) Savage, L. J., “The Foundations of Statistics,” New York, John Wiley & Sons, 1954. (8) Walker, H. M., “Elementary Statistical Methods,” New York, Henry Holt & Co., 1947. PusiicaTion Decisions AND TESTS OF SIGNIFICANCE—A COMMENT (Gordon Tullock, University of Virginia) The custom of only publishing research when it reaches a certain degree of significance is likely to lead to errors, not through repetition of the same experiments, but over many different experiments The purpose of this comment is not to criticize Sterling’s important article,* but to suggest that it has somewhat wider application than he implies. The specific type of error to which Dr. Sterling refers (p. 33) is the repetition of some given experiment by different investigators until one of them obtains a significant result, which is then published. I do not think this is at all a fre quent occurrence. If an hypothesis had been tested by a number of independent investigators, all but one of whom had obtained negative results, the publication of the positive results of the single investigator who had had the good fortune to obtain a “significant” result would normally bring the others out in the open. A man who has devoted a good deal of time to testing a hypothesis with a given experimental design and has been forced to conclude that the hypothesis is incorrect will normally simply file his results. If, however, he sees an article reporting a similar experiment with significant results, he will at least write the editor of the journal in which it appears. Since this type of comment on articles is rare, I judge that the publication of experimental designs is rare. But while this indicates that investigators have minds sufficiently independent that they seldom duplicate others’ experiments by accident, it does not reduce the importance of Sterling’s basic point. The necessary restrictions imposed on articles by the scarcity of publication resources does result in greatly reducing the confidence we can put in statistical tests of significance as reported in the literature. There is little difference, statistically speaking between the likeli- hood of a false correlation from 20 investigators all investigating independently the same false hypothesis with the same experimental design, or from the same 20 investigators investigating 20 false hypothesis. The same number of results of a given level of significance would be expected from either “design.” The moral of these considerations would appear to be clear. The tradition of independent repetition of experiments should be transferred from physics and chemistry to the areas where it is now a rarity? It should be realized that re- peating an experiment, while not necessarily showing great originality of mind, is nevertheless an important function. Journals should make space for brief reports of such repetitions, and foundations should undertake their support. Academics in the social sciences should learn to feel no more embarrassment in repeating someone else’s experiment than their colleagues in the physics and chemistry departments do now. Dr. Levin. I would like to point out, Mr. Chairman, this whole question of statistical evaluation of carcinogenic tests is discussed in our report to the Food Protection Committee in considerable length— the evaluation of these 5-percent errors and so forth. Dr. Srewarr. I would like to take Dr. Zavon up on another point he made. You said—— 1“Publication Decisions and Their Possible Effects on Inferences Drawn From Tests of Significance—-or Vice Versa,’ Theodore D, Sterling, Journal of the American Statistical Association, March 1959, p. 30. 2A good illustrative example of the Practice in the physical sciences is A. B. Mah’s “Heats of Formation of Alumina, Molybdenum Dioxide, and Molybdenum Trioxide,” Jour- nal of Physical Chemistry, 61 (1957), p. 1573. Dr. Mah repeated a series of careful measurements made by several other scientists. Since his work simply confirmed their's it was reported in the form of a brief note rather than in a full article. COLOR ADDITIVES 477 The Cuairman. Doctor, if you are going to another point, I prom- ised Mr. Dingell I would let him ask his question. Mr. Drncett. I just want to ask this question of Dr. Zavon: Doctor, aren’t you comparing apples and oranges? You are saying that there is a 5-percent probable error because on a statistical basis perhaps 5 percent of the cases might not be reported, and you might get a 5- percent error in evaluating a whole series of experiments, because per- aps an occasional erroneous experience will be reported. But you are not saying that this 5-percent error means that there is a 5-percent chance that any specific experiment is going to give a false report? And this is the precise point I want you to discuss. Dr. Zavon. That in essence is correct. As I understand the statis- tical theory, the statistical reasoning which Dr. Sterling has presented, it is this.’ If you test 100 substances—we are not talking about any one specific material—100 substances, or the same material 100 times, there is a 5-percent chance that irrespective of your original assump- tion—you might assume that they are not carcinogens—5 percent of those 100 tests he points out can come out positive under presently accepted statistical procedures irrespective of whether or not the material is a carcinogen. Now, Dr. Levin disagrees with me. And, as I said, I don’t want to attempt to qualify myself as a statistician. I am merely presenting work that the statistician in our laboratory has developed for your consideration as one of the points to be considered. I suggest that I am not competent to argue it. I question whether many of the members of the panel are competent in this particular area of statistical theory. Dr. Levin may well be the only member here who can discuss it. Mr. Drnceut. I notice Dr. Tannenbaum, sitting next to you, has been nodding his head in disagreement. Dr. Tannenbaum. It would be better to have this problem dis- cussed by Dr. Levin, as I am not a statistician. However, it does not seem reasonable or logical to expect a compound completely noncar- cinogenic to result in the formation of tumors in about 5 percent of test experiments. Nor would one expect a potent carcinogen, tested under proper experimental conditions, to appear to be noncarcinogenic in about 5 percent of the studies that were made. On the other hand, with weak cancer-producing agents, it is statistically expected that a smal] percentage of experiments will not indicate their carcinogeni- city—in other words, they will give negative results. One should not implicate statistical methods as the cause of the difficulties that arise in evaluating the biological significance of such borderline findings. Dr. Zavon. Mr. Dingell—may I answer one further point in regard to your question as an example of why I disagree with Dr. Tanne- baum’s answer? Not too long ago I had occasion to take a very potent chemical, one which is widely used and try to duplicate some work that had been reported in a foreign medical journal. I took 40 animals, and ad- ministered this material by injection. I gave a dose that by calcula- tion should have killed close to 100 percent of the animals involved. The animals were then divided into groups on a random selection basis, and treated with various types of antidote. Now, in the ordi- nary course of events, and intuitively I would have said if I gave them a dose that could be expected to kill close to 100 percent of the animals, 478 COLOR ADDITIVES out of 10 animals so treated I would have expected at leaast 1 to die, and more probably close to 10. I was rather chagrinned to find that all those animals that should have died, didn’t. This is despite the fact. that those who got a dose—but not. the antidote—they all got the same dose, a dose that. would have been expected to kill 100 percent of the animals—none of those died. Therefore, I say, if you need an example of how your intuitive reaction can lead you astray, this is an example. Mr. Dixcety. Just one more question. This 5-percent error— isn’t this all the more argument for erring on the side of safety, rather than throwing the bill open, or throwing the law open to additional error? In other w ords, isn’t our purpose here to err on the side of safety, or should we say because there is a probability of error, we should throw the whole thing out the window and not use any special care in the case of cancer? Dr. Zavox. No. I think we have to clarify—— Mr. Drxcey. That is the inference I get from your statement. Dr. Zavon. No, your inference is wrong in this sense; one, I don’t think any member of this panel has remotely implied that we want to toss out all regard for screening for cancer. I think some of us, my- self certainly —I won't speak for anyone else, although Dr. Darby mentioned it this morning—have contended that the law adequately sets up protection against cancer without the special mention in the Delaney clause. But the particular point I am attempting to make here, and the inference I would like to draw from it, is that if you test. a large number of materials, and you keep on testing them, you can show that every one of the materials may be judged a carcinogen unless you review your data very carefully and interpret in proper fashion what is being shown experimentally. And I predict, and I know that—I won’t put words in anyone else’s mouth, but in private conversation with at least one other member of the panel, I know we were in agreement—we anticipate that there is a reasonable prob- ability that in years to come there will be experimental evidence re- ported time after time showing, as Dr. De Eds did yesterday, that there are common items of our diet, which under certain conditions can cause an increase in cancer. Mr. Dincetu. Let’s not go into that again. Dr. Zavon. Well, this is the point, sir. Mr. Dixcext. Let's address ourselves to the narrow specific point. The thing I get now from your statement is that you feel that the Food and Drug i is not competent to properly apply the so-called Delaney eancer clause, or the Delaney cancer clause, is that correct ? Dr. Zavon. No, sir, you are putting words in my mouth which I did not say. Mr. Dincett. If I am doing so, just be free to tell me. The Cuamman. Well, I think, ‘Mr. Dingell, you can ask him the question. But I have observed that you are telling the panel what they say and what they believe. Mr. Dixcenr. All he has to do, Mr. Chairman, is say Iam erroneous, and I will be delighted to be corrected. Now, then, would I be fair in inferring that the Food and Drug Administration—that you do have some faith in Food and Drug— and that they have done a competent job in clearing these substances COLOR ADDITIVES 479 which are carcinogenic, or they hold to be carcinogenic, with the scien- tific community gener: ily. Dr. Zavon. Not enough information has been published for me to evaluate whether or not “they have done a competent job. Dr. Darsy. Mr. Harris, I wonder if it might not be helpful The Cuarrman. I am wondering x, Doctor, if we are going to com- plete the statement of Dr. Stewart ultimately. Dr. Darsy. I think it might be helpful if we permitted Dr. Stewart to continue. And I know there are a number of members of the panel have comments they would like to make. And since our time is limited—if we might get from the panel these points bearing on the scientific questions, I think it would give you the greatest assistance that we could provide. Dr. Srewarr. Well, Dr. Zavon made a statement that a chemical once tested for its induction of cancer, that that experiment is not re- peated, or not likely to be repeated. Now, Dr. De Eds said yesterday that acetylaminofliorene, w Rich he and Dr. Cox and his associates discovered some years ago, has been retested, how many times would you say, Dr. De Eds? Dr. De Eos. W ell, at least—I wouldn't hazard a guess on the num- ber, but it isa great many times. Dr. Srewarr. Up to 1953 it had been retested 85 times, and there are another 7 y ears of retesting to add to that. Dr. De‘Eps. I would have guessed close to 100 times. But I think I should also add that this is a rather special situation, I believe. The nature of the compound, the fact that it was a useful tool in cancer research, has stimulated this repetition. It has stimulated investiga- tions into the effect of diet, the effect of change in hormone balance and even taking a look at what the effect would be if certain chemica modifications were made in the chemical composition of the compound. Dr. Srewart. Well, yes. What you say is true. Now, I read from this NRC publication that butter yellow has been retested over 200 times, and betanaphthalamine over 30 times. If you tuke, for example, the polieye lic hydrocarbons, including the dimethyl and the trimethyl 1,2 benzanthracene, they have been retested for ‘arcinogenicity over and over again, Tam Just offering this evidence to show, that your (Dr. Zavon's) statement is not entirely correct— that once a substance is shown to be a carcinogenic everybody forgets about it. That is not quite so. Dr. Darsy. Dr. Stewart, may I suggest a possible explanation of this difference in statement? I believe that the implication was that if one were considering a sub- stance as a possible food additive, that if it is shown to be a car- cinogen then one would back off of promotion of further testing. One would not pursue this. Now, I am certain, as Dr. De Eds has just pointed out, and as you are far better aware than I, because of your vast and long interest in the subject of the mechanism of carcinogenesis, and the study of carcinogenic process, that when a substance is a powerful carcinogen or it has unusual properties which are valuable to us in elucidating the scientific nature of cancer, then there will be a concentrated use of that substance as a tool. And I think that you are both right. But you are perhaps looking at it from a different viewpoint here. 480 COLOR ADDITIVES Dr. Stewart. Is that offered as a compromise? Dr. Zavon. I am in full agreement with Dr. Darby’s statement. This is absolutely correct. Dr. Kensier. It would seem to me that one of the problems here that hasn’t been mentioned is where the particular dose lies in terms of the dose response curve to this compound. And that the probability of getting a wrong answer will differ, depending on where you are on this dose response curve. If this is a very steep curve, and—then you would expect big differences in incidence as a result of small errors in the administered concentration. If it is a nonsteep curve Dr. Zavon. Will you explain what “steep curve” means? Dr. Krenster. By “steep curve” I mean where you get a rapid change in incidence of response with a small change in dose of the material you are administering. In this sort of a situation, you could expect marked variations in incidence within a population, because you have a very steep dose response curve. If you have a flat dose response curve, then changes in this direction will not be as apt to occur in any single experiment. This applies to any test of drug activity, be it for carcinogenesis or something else. Dr. Darsy. Dr. Blum has been asking for the floor. I think he has a pertinent comment. Dr. Blum. Dr. Bium. I simply would like to point out that I am perfectly in agreement with Dr. Zavon that we need more careful measurements, and we need our evidence more completely presented, as is not always the case in the literature. However, each problem that one solves statistically is a different problem in this field. What I was worried about in putting my ques- tion was a statement which might be taken as a blanket statement for all cases. I would like to give you an example. In the case of ultraviolet carcinogenesis, one has a very nice distri- bution curve, the kind of curve we are all acquainted with. In this case plotting the logarithm of the time to cancer appearance gives a normal curve which does not change its shape with the dose of the carcinogen. Itsimply moves along, on the time scale. If, on the other hand, we work with chemical carcinogens, we find that the shape and slope of this curve does change. And I believe this is quite to be expected from the data, or from what we know about the process. Now, if you are going to do statistics, this becomes a more difficult problem, because you have different statistics for each dose level, and your dose response curve will be quite different if you work, say, at 50 percent incidence, or if you work at 10 percent incidence, or 80 percent incidence. So that one has to be careful in what one means by a dose response curve, because it has to be based on some kind of 2 statistical evaluation. And I believe that we will have to have a little more theoretical knowledge of this before we can get practical answers. Dr. Levin. I think for the record it would be well to point out there are two types of error in this kind of situation recognized, known as type 1 error and type 2 error. Type 1 error is the error involved in assuming that a given difference is real when in fact it is not real. In other words, in this case, assuming that a substance actually does pro- duce cancer, when actually it does not. This is a chance variation, That is type 1 error. The other type error is the opposite error. That COLOR ADDITIVES 481 is the error of assuming there is no difference when there is a difference. And this, of course, can occur also on the basis of chance. Now, which error you make larger depends, of course, on the impor- tance of of the two decisions. I think that everyone will agree that if the decision involves admitting a carcinogen to the human food supply, or keeping it out. we would want to maximize the type 2 error. In other words, we want to make it as unlikely as possible that we will admit a carcinogen. Now, with respect to the type 2 error, I would like to point out that if the true incidence, in other words, the true effect of a substance, were 3 percent, then there is a 5-percent chance of finding zero in samples of a hundred. And thisisa more important area than the type 1 error to which you have been referring, Dr. Zavon, and this is the point I think we wanted to make in our report—that in a matter of this type of significance, where the alternatives were admitting a can- cer compound or not, it is the type 2 error that should be given the greatest evaluation, and not the type 1 error. You have been talking about the type 1 error, and the error of saying a compound is carcinogenic when in fact it is not, which would mean we would exclude a useful compound. We have pointed out that the more important error is the type 2 error, which would mean, if we made it, we would include a carcinogenic compound. Dr. Zavon. I would like to refer back to Dr. Stewart, so he can complete, before going into this area again. Dr. Kenster. I would like to comment that as I listened to what Dr. Blum said, that I had the impression he was talking about a time incidence curve, rather than what pharmacologists call a dose response curve. Is that right? Dr. Bium. Yes and no. The dose response curve of the pharma- cologist must in this case—must be dependent upon the time incidence curve. Dr. Kenster. You would have to take an end point, 2 years, 1 year, or something, and you calculate your dose response curve in terms of your end point which you select, as a function of dose. Dr. Brum. The end point in the cancer study is the volume of a detectable tumor. And the time at which you arrive at this volume is your measurement. Now, no matter how you make the measurement, this is what you are measuring. Dr. Kenster. Providing you use the same time to evaluate all doses. Then you get a dose response curve. Dr. Brum. Oh, no. Then you get something which I think may be fictitious and uninterpretable. Dr. Kenstrr. I disagree with Dr. Blum. Dr. Darsy. I think perhaps we should move on. This is a technical disagreement at a level which perhaps doesn’t directly pertain to the question before us. Dr. Srewarr. Well, I just want to make one other point. When we are talking about a safe dose of carcinogen and extrapolating from a safe dose in animals to a safe dose in human beings, we are really not talking about one carcinogen; but we are talking about many, maybe 1,000, maybe 2,000 carcinogens, I don’t know. The Food and Drug Administration in this country, and I think the British have come up with some sort of a statement that there are somewhere be- 482 COLOR ADDITIVES tween 900 and 1,000 substances added to food. So when we are talk- ing about adding carcinogens in low doses to food, we are not talking about one carcinogen, but we are perhaps talking in terms of hundreds or even thousands. And I think that is a point that is wise to bear in mind when we are talking about safe doses of carcinogens to be added to food. I yield now, Mr. Chairman. Dr. Darsy. Thank you, Dr. Stewart. I certainly think that you and I are both against cancer. Dr. Srewart. I knew we could agree. You would have to come around to my point of view. ; Dr. Kenster. I would like to comment on one of Dr, Stewart's earlier remarks this morning when he mentioned that it was his im- pression that during the discussion yesterday, that the results ob- tained with sodium chloride solutions injected and sugar solutions injected were used as reasons for throwing out the Delaney amend- ment. Now I don’t think they were at all. The issues where the Delaney amendment is involved is where a compound produces can- cer by ingestion, and in the instances which were mentioned, the emulsi- fier, bladder stones, bladder cancer, the selenium, and so on, not sodium chloride or glutens. Dr. Stewart. I must say I have to defend myself against this. With this surface acting agent, with this substance that causes bladder cancer, you are actually recommending the addition of a substance that: causes bladder cancer in animals to human food. And with that I disagree, of course. Dr. Kensuer. Sir, we went through this yesterday. Iam not recom- mending this. I am recommending that legislation permit compe- tent expert judging as to whether this should or should not be admitted in any amount into the food. I am not recommending that it be ad- mitted. And this judgment is prevented under the present clause. Dr. Miver. Mr. Chairman, it would appear that some of my col- leagues are interpreting the Delaney clause to mean that nothing may be introduced into the food supply or used in drugs or cosmeties which produces cancer by any form of test. I have not so interpreted that clause. Perhaps I am inerror. It seems to me that we have two large classes of materials that we have been talking about. One is the compound that is new to human experience, and has been found to produce cancer by adequate tests appropriately designed in experimental animals. However, a con- siderable amount of our discussion has centered about materials, chemi- eal compounds, that we have known about for a long time. The selenium problem, for example. We have known a lot about selenium, but our information has improved materially in the past. I doubt that it was the intent of the Delaney clause to prevent the correction of a nutritional deficiency. In that regard, I would eall to your attention the change in the act proposed by the Secretary of Health, Education, and Welfare, which as I recall it, would permit the feeding of a compound to an animal, providing—even though it were carcinogenic, providing it did not produce a residue in the meat after slaughter, or in any byproducts from the animal during its life which were to be used for human consumption. : COLOR ADDITIVES 483 I think that Dr. Darby made a very significant statement this morn- ing when he said that our ignorance requires protection from minimal exposures, I think that we do require that protection. For example, among the carcinogens that are known, there are a few chemicals which will produce cancer from a single dose. There are others which will pro- duce it from a dose that can be determined, and once that dose has been given, even though administration of the compound be stopped, the risk of cancer is still there, and the animals do in fact develop cancer, We also have some compounds which must apparently be admin- istered until the cancer appears, and if we stop before the cancer ap- pears, we may not get any cancer. It has also been said that in this legislation pending before your committee, it would be appropriate that the test for c arcinogenicity include feeding. And I would suggest that if the compound is to be used in cosmetics, it would also be appropriate for it to be painted on the skin. I do not believe we have sufficient experience at this time to make the judgments which some of my colleagues on this committee are willing to make. Under those circumstances, I believe that the interest. of the public is best protected by the Delaney clause or some modification thereof. I am not entirely familiar with the way in which the Food and Drug Administration conducts its business. I am aware, however, that “they seek consultation on many knotty problems that confront them, not only from Government scientists, but from scientists throughout the United States, I believe that they administer this law well. And I would not object to any advisory committee, but I would point out, that if we want to look at each one of these cases and judge each one on its own merit, it would be very difficult to form one committee of specialists that could look at all the multiple problems relating to cancer that are likely to be brought up before the Food and Drug Administration. Thank you, sir. The CHairman. Mr. Rogers wanted to ask a question on that point, if you don’t mind. Mr. Rocers of Florida. I would appreciate it, Mr. Chairman, if the committee could discuss this phase of this problem, and it is this. As I understand it, from the definition, a carcinogen is a substance or chemical that will—forms cancer. It is cancer forming. Now what I cannot clear up in my mind from the discussion thus far is how we determine what is a carcinogen, what it tests. Is there agreement on a test? Is there a standard for testing? And until, it seems to me, there is some set form for testing, there is no telling what is or what is not a carcinogen, as far as we are concerned or the public is concerned. Now, if you are going to give doses of, say, 40 percent or 10 percent, if there i is no way of testing, how can we tell really what a carcino- gen is, and how can we legislate, unless we have some understanding of the very basic problem of determining what it is? Now I wondered if the panel could develop for us what you do use as testing, and what is a standard, or if there isn’t any, how can the problem ever be solved. It would be helpful to me, and I hope to the committee, to have something developed along that line. 484 COLOR ADDITIVES Dr. Darsy. Mr. Rogers, we discussed this at one point. I would suggest that this is discussed in considerable detail in this publica- tion of the Food Protection Committee. However, very briefly, to illustrate the judgment required, may I review the following. When one asks whether cancer is produced and puts this question to the animal—will administration of this pro- duce cancer ?—then your answer will depend on the animal which you use, the dosage level, the nature of the compound, the route of ‘ad- ministration, “how long you administer the compound, and so on. There is not complete agreement in every detail of the method of study. But there is, I think, a large area of agreement that you would use a rodent species and a nonrodent species, and you would administer the substance at a variety of levels, with a sufficient number of animals that you would reduce to the minimum practi¢al errors— experimental errors which have been discussed as inherent in experi- mental design. Now I think that our disagreement here is toa considerable extent. in whether, then, if you administer something subeutaneously, and you find a reaction which is cancer, whether this substance is ‘termed a carcinogen. We are really interested in the utilization of this sub- stance by another route of administration, an oral route of adminis- tration. I think that if you got clear evidence of cé urcinogenic activ- ity, most of us would say, “Yes, this is a carcinogen,” even if it were by subcutaneous, or painting on the skin. However, if the effect of this subcutaneous injection appeared to be that sort of effect which Dr. Stewart was referring to this morning for sodium chloride, an effect. probably not inherent in sodium chloride itself, there is room for debate, When one says not. a property of the sodium chloride itself it is perhaps puzzling. But it is probably the hypertonic solution being repeatedly injected subcutaneously, and the constant irritation of this that is responsible for the injury—not necessarily a property of this compound itself. Then judgment would tell me that—just as I believe Dr. Stewart Dr. Stewarr. Hold on now. Dr. Darsy. My judgment would be that this is not a carcinogen in practical terms. Mr. Rocers of Florida. Now may I say this: Dr. Stewart might say it is. ‘Dr. Darsy. Yes, he might very well. Mr. Rocrrs of Florida. And so we don’t have any basis of deter- mining yet what is a carcinogen. Mr. Dixertt. If the gentleman will yield. I think we ought to ask Dr. Stewart that. Dr. Srewarr. Finally I have a chance to speak here. Let me put it this way: The important thing about the Delaney clause that. is emphasized i is that the substance that is suspected should be fed. I think that is a good idea. It is written right in the law. Mr. Rogers of Florida. To write it into the law, you say ? Dr, Srewarr. It is written in the proposed amendment, as I have read it.in the letter that Representative Harris sent to me. Now, then, I can name a carcinogen, beryllium, one of the most potent carcinogens as we know, So far as I know, and I may be mis- taken, I don’t think that has ever been tested by feeding. If I am COLOR ADDITIVES 485 wrong, I hope I will be corrected. But if it is injected intravenously into rabbits, it produces bone sarcomas in multiple bones of that animal, and if it is inhaled by rats, it produces multiple lung cancers all through the lungs. Now that is an example of a carcinogen shown to be a highly potent carcinogen by inhalation and by intravenous injection Sue to my knowledge not by feeding. I would say that substance should not be added to food. And I would like to see the Delaney amendment broad enough, which it is now, to include subcutaneous injection, painting, intravenous injection, inhalation, the administration of sus- pected carcinogens to pregnant animals and to lactating animals. Suppose you come up with an agent which you feed repeatedly and it does not produce cancer in an animal, but by painting and sub- cutaneous injection you get 100 percent cancers in those animals, I wouldn’t add that substance to food, even though it does not produce cancer in animals that ingest it. Now that is my point, Representative Rogers. The CHarrman. Doctor, on that point, the important thing is that whoever proposes to use such substance has got to show positively, under the Delaney clause, that the additive 1s found not to induce cancer. Now many have brought to our attention the statement that they know that such additive does not induce cancer, but they are unable scientifically to prove it. Now I agree with you that the Delaney clause does what you said it would do. But, as has been developed during this panel discussion, there is no way of showing positively the effect of the use of the addi- tive. How we overcome that is a problem. Mr. Sprincer. I think that is the erux of this whole thing we are talking about. That is, what you are doing by this amendment—that is what this committee wants to know about—is where you are putting the burden of proof. The burden of proof is not upon the Depart- ment down here. It is upon these people to show that this is not dan- gerous. In effect, that is what they are saying—just to put this on the record broadly. Now the question is, Do you people have anything by which you can make a standard of proof and convince the administration down here, whoever is administering the law, that that is not dangerous ?¢ The Cuamman. If the gentleman will permit, that was very clearly developed here yesterday. Some contend that it takes not only a year or 2 years or 3 years to test certain additives, but that it would take 7 years to develop the data on which to make a finding. And that seems to be the dilemma. I would say the gentleman from Florida put his finger on the point. Dr. Stewart brought it up to right where we come into this picture. I agree with what you said up toa point. But when it gets to that point where the burden of proof is, then the Department locks every- ody out, because there is no known way to prove it. Mr. Sprtncer. Would the gentleman yield? May I say this is not new to this committee. For 8 years we have been working with pesti- cides, and that is a field which has been tremendously developed. Even as long as they have been working on pesticides, there are pesti- 486 COLOR ADDITIVES cides that they are unable to prove to the satisfaction of the Depart- ment are safe. Mr. Dincetxi. Which department is that? Mr. Sprincer. Food and Drug. Mr. Dincete. I beg to differ, because that particular amendment is administered by the Department of Agriculture. Mr. Sprincer. There has been an amendment to transfer it. But put it either way. This, it seems to me, is a far more nebulous propo- sition. I am not saying it is right or wrong, the amendment. I am just saying that is the ‘problem with which this committee is faced. 3ut we are making an impossible situation for the people administer- ing the law. ‘The Cramman, Now, gentlemen, we would like to get the most out of this discussion in the time we have. I wonder if it might not be advisable, in the 30 minutes left, to give each one of you an opportunity tosummarize. Would that procedure be agreeable, Doctor # Dr. Darpy. Certainly. Mr. Youncer. Mr. Chairman, we all recognize that there is a matter of judgment as to w hether the compound, by experiment, is going to be carcinogenic—that judgment rests now with the Food and Drug as to the experiment. Will each of the witnesses state whether or not after that judgment the Pure Food and Drug should be allowed to set tolerances; I think they should say, as you go around, yes or no on that question, so that we have a poll of the panel on that one question, The Crairman. Well, several of them expressed their views on that yesterday afternoon. It isall in the record. Mr. Youncer. I was here. But they have not, said definitely yes or no on that question. Our question is color additive. Most of the con- versation has been on food additives. Now, the bill that is before us is not solely restricted. We are de- bating ‘today a bill on color additives for food, drugs, and cosmetics. Whatever your judgment is, you are going to have to determine as to whether your statement applies to cosmetics and drugs. And I think we have already passed the food additive, and that is on the books. We are talking about color additves today. And I think we ought to confine our remarks to that. Mr. Guenn. Mr. Chairman, may I have one comment from Dr. Stewart as to something that. was said yesterday, and which follows through on the discussion which we just had. as to ‘pesticides. I think that you said that the use of DDT has been shown to have some effect on animals in the way of cancer producing. Now, last night I was thinking of that, and I recalled that. we had previous hearings, and I have here a question and an answer by Mr. Larrick, Commissioner of Food and Drugs, and I would like to have you comment. The question was this: On the evidence presently available, do you regard DDT cancer-producing chemicals when fed to animals? The answer was: “No.” Now, can you comment on that? Dr. Stewart. IT would be glad to comment. on that. After my testimony yesterday, I talked to Dr. Nelson, of the Food and Drug Administration, who is in the audience today. I based my COLOR ADDITIVES 487 answer on a paper published by Dr, Nelson some years ago—I have the reference right here—in which he got some liver tumors in rats fed DDT. And this is in the literature—DDT—as being a carcinogen for animals. Now, Dr. Nelson told me yesterday, and I don’t want to put words in his mouth, I think he ought to speak for himself—but my impres- sion of what he told me yesterday was that after he had gone over all his material, he didn’t think DDT was a carcinogen, but that it was a weak tumorigen. Now, that is about what I got from Dr. Nelson yesterday. And he is here, and I am sure he can speak for himself. Mr. Guenn. Thank you. Dr. Darsy. Would you like for us to proceed ? The Crrairman. Yes. Dr. Miner. Mr. Chairman, I think the panel could agree, within a reasonably short time, on an appropriate series of tests for any chemi- cal compound that was presented to it. If we had three or four com- pounds, we might not come up with the same tests. But given the structure of a compound, some knowledge of its solubility, some of its general toxicological properties, I think we would have little difficulty getting substantial agreement on testing procedures. Mr. Youncrr. How about the other question ? Dr. Miper. You want me tostart that? Mr. Youncer. Yes, I think each one of you ought to say whether or not you believe that the Pure Food and Drug should have any right or power to set tolerance. The Cuamman. Well, I think the gentlemen should be given leeway if they are not ina position to assert that. Mr. Youncer. Well, that is all right. At least, they ought to address themselves to it. Dr. Miver. At the present. time, Mr. Chairman, I would prefer that the Food and Drug Administration not have that responsibility, until we have additional information. I do not hold that this is a decision that is binding forever. But as we acquire more experience, I think we should reexamine the question. Dr. Darsy. Dr. Stewart, would you like to speak to this? Dr. Srewarr. I don’t believe it is possible to set tolerances for carcinogens to be added to food at the present time, or cosmetics. Dr. Kenster. In my opinion, the Delaney clause, as written, pre- vents the application of proper scientific judgment to this problem, In my opinion, it should be modified in such a way that the current scientific judgment be brought to bear on the problem whenever such judgments are appropriate, and when such information is available, not necessarily having to wait for the passage of another piece of legis- lation. 7 Dr. Darny. Do you wish to speak to the tolerance question ? _ Dr. Kenster. In terms of the tolerance question, I think that there is no final answer that can be given to this, except possibly in the ex- ceptional case where compounds have been found by one test or another to produce an effect in what might be considered unreasonable concentrations, And I think we have an example of physical factors, of course, which ean do this. . Dr. Cannon. I find a little difficulty in answering that. question specifically. I think it has been brought out very clearly that the 488 COLOR ADDITIVES only disagreement among the panel members with reference to the Delaney clause is the question of modification in terms of permitting the exercise of judgment. I think your specific question, Mr. Younger, was: Do we think the Food and Drug Administration should set tolerances for carcinogens? Is that the question ? Mr. Youncer. Yes. Dr. Cannon. I think all of us who have had experience with mem- bers of the Food and Drug Administration have great confidence in their ability. I would say, also, that they have never been reticent about going afield to get help in any of these technical matters. I assume, furthermore, that there is nothing in this bill to prevent that, inasmuch as it has been brought out, for instance, in the Senate bill, that the clause is not there, and it is assumed, nevertheless, that they have the power of adequate enforcement anyway. SoI see no hazard whatever in entrusting the decisons to the Food and Drug Depart- ment, I would like to say one other thing, though. You all, as lawyers, are familiar with the problem of legislative disagreement in matters of judgment. But you have a Supreme Court that you can carry things to, even though you may get a five to four decision. We have no court to appeal to except the scientific judgment of our peers. You are seeing illustrated today the way in which we arrive at judgments. Sometimes it may take 50 years. ; It is a little surprising to me that there is so much concern about the possibility that a matter of judgment is precluded by legislation. I am sure that the members of the committee would not accept the conclusion that your proposed bill denies the exercise of judgment. Nevertheless, that is the only point of disagreement that has been brought up by us with reference to the Delaney clause, and it is only the question of scientific judgment which we have been talking about. Does that answer your question ? Mr. Youncer. Yes. Dr. Buum. Mr. Younger remarked and used the term “set toler- ances.” And I find this is a rather difficult thing to define. If you mean by this tolerance levels which are going to be accepted, then I think this is a procedure that has to be taken—considered very care- fully, because we may set a limit on the basis of some test, and under any circumstances it becomes a pretty arbitrary limit, and it should not be taken too seriously, because it may have to be revised up or down, probably down, as in the case—we have seen this happen with radiation limits over and over again, within the last 20 years. On the other hand, we are setting a tolerance limit in one way or another if we forbid the use of a compound. And it seems to me that this is clearly a question which requires consideration from a number of points of view, including the question of whether the substance is really necessary, as an additive—I mean what is the value of it to the public in general—and these are problems for which I see no exact answer at the present time. And I think we must put the judgement in the hands of someone. As far as I am concerned, the Food and Drug group is qualified as anyone I know. COLOR ADDITIVES 489 Mr. Rocers of Florida. Mr. Chairman, I just want to ask whether it is possible for the panel just to say whether they feel the Delaney amendment should be modified some to allow for greater scientific judgment. Dr. Bium. I would say that I see no—I think the Delaney amend- ment, or a similar amendment, is necessary. But I see no particular reason for modification. It seems to me to cover the situation. Dr. Dr Eps. In the first place, let me say that I know the personnel of the Food and Drug Administration, and I have confidence in their ability. Nevertheless, they, like everybody else, are human beings. There may arise special occasions when they would desire to have con- sultation with people on the outside. I realize that they actually do this. Nevertheless, the mere fact that we are all here indicates that there is a decided feeling that cancer is a particularly important sub- jcet, and I, therefore, think that it would be advisable to have a specific requirement in the act to the effect that whenever the toxicological data suggest carcinogenic properties, that then the Food and Drug would have their decision supplemented, if they so desired, by experts in the field of cancer. This is particularly true, I think, in certain borderline cases. I made no mention yesterday of the fact that we studied a compound, thioactamide, which would have been useful on Florida oranges for the prevention of rot at the stem of the orange. We discovered that this compound produces an enlargement of the nuclei of the liver cells, and that it was a potentialy dangerous sub- stance. We never even consulted the Food and Drug about this. We reported the facts to the Bureau of Plant Industry, and suggested that this would not be a safe compound. I think that the investigators themselves who study the compounds are in many instances going to recognize that a compound per se is carcinogenic, and that is that. But, at the same time, they will be confronted with certain instances where it is not so clearcut, particularly where, as has been pointed out in the discussions yesterday, we are dealing with a situation where the compound is not necessarily carcinogenic per se, but can indirectly result in cancer because of metabolic products resulting from unusually high dietary levels which would never be encountered under practical conditions of usage. This is an entirely different situation, and this is where, I think that there is a need for the exercise of scientific judgment. Mr. Dinceti. As a matter of fact, Doctor, the Food and Drug now does consult with industry, and they have consulted with you on many problems? Dr. Dr Eps. That is correct. Mr. Dinceti. And they have gone afield to seek scientific judgments of reputable people in the scientific brotherhood, as to whether or not these things are in fact carcinogenic, isn’t that a fact ? Dr. De Eps. That is right. Mr. Dincetx. So there is really no requirement for additional au- thority for them to go and seek this scientific information, since they are presently consulting with members of the scientific brotherhood on many points? Dr. Dr Eps. That is right. I do not deny that, Mr. Dingell. It is because of the special importance that attaches to the subject of cancer, I think there is a definite, let us say, psychological value, in having in 490 COLOR ADDITIVES the legislation a specific requirement. I think this is something that will be appreciated by the public. Dr. Darsy. Do you wish to speak to the question of tolerance? Dr. De Ens. I think that the question of tolerance is of much greater importance in connection with these situations that are borderline. A compound like acetylaminofluorene, or like the thioacetamide, which we didn’t even refer to the Food and Drug, I wouldn’t even consider for a moment that there should be a tolerance there. But in these borderline cases, particularly where there is some evidence that the carcinogenic action is an indirect mechanism and not due to the com- pound per se, and present only when these unrealistic high dosages are required to demonstrate the carcinogenic action, that this is where it is reasonable to set a tolerance limit. Dr. Levin. Mr. Chairman, I should like to say that after listening to the testimony of this panel, and considering it as carefully as I can, I feel that the principle of the Delaney amendment should be retained in the publie interest. I feel, also, that as a principle, it would be undesirable to allow tolerances for recognized carginogens as a prin- ciple. I do recognize the possibility of exceptional instance to which we might want to make an exception to that rule. And if a workable arrangement could be devised which would allow for an exceptional review of such exceptional instances, I would be in favor of that. But if the alternative is to keep tolerances or not to keep tolerances, I would be entirely in favor of refusing tolerances to carcinogens in the language of the amendment as it now stands, It is my understanding that there is ample authority for the Food and Drug Administration to seek scientific review of scientific ques- tions, and that they make full use of this authority. In fact, there is no need to modify the amendment accordingly. If that is not correct, I would favor such a modification as would make it mandatory upon the Food and Drug Administration to seek scientific review of scientific problems, The Cuarrman. Well, would you go further? If they sought such review and judgment could they use that in accordance with whatever judgment they received? Would you go that far? Dr. Levin. Yes: if there is an exceptional instance in which there is good reason to think there should be an exception made to the prin- ciple of tolerance for a substance suspected of being carcinogenic, then I think that the judgment of a special board of scientists should be permitted to prevail. Mr. Avery. Doctor, what would be the difference between an excep- tion and setting up a tolerance ? Dr, Levin. As I understand the question which is asked is whether we should permit the Food and Drug Administration to exercise its own judgment. in the ordinary course of events on the basis of evidence submitted to it—whether it should set a tolerance. And this I do not favor. Mr. Avery. That you do not favor. But you went on to say you thought there should be certain exceptions. _ Dr. Levin. If there is an exceptional instance, in which the public interest. is at stake, and this can be shown Mr. Avery. Then they should set tolerance ? COLOR ADDITIVES 491 Dr. Levix. Then they should call in a special scientific board of review to review the adequacy of their contention that there is a special situation which calls fora tolerane e. Mr. Avery. All right, that is what I wanted to wrap up. Thank you. Dr. Minter. We have seen unusual situations have occurred where the carcinogenic hazards from the use of a substance are at serious dispute on scientific grounds. Therefore, I feel the law should direct the Secretary to seek the opinion of a board of experts when such a dispute arises with the petitioner. The final decision must be made by the Secretary, and he should be directed to publish without delay the evidence upon which this decision was made. Dr. Tannennacm. It is my opinion that the Delaney clause should be retained, but that it should include provisions for review of Food and Drug Administration decisions on exceptional controversial prob- lems. In these instances the specifie problem, and experimental con- ditions and findings, should be reviewed with regard to their bearing on the probability of hazard, by a qualified panel. Only for special borderline problems should the F ool and Drug Administration give consideration to tolerances. Dr. Zavon. By chance, I assume the spectrum of opinion goes from Dr, Stewart to myself. Just as Dr. Stewart has stuck his neck out. I will stick mine out again. On page 8 of House bill 7624, line 15 and thereon, there is, in my opinion, ample basis for any regulations which the Secretary w ishes to promulgate for the protection of the public. Therefore, [ wou!d be in favor of. eliminating what to me—and I have had some experience in writing legislation—w hat to me is a redundant and unnecessary phrase or portion of the legislation, and tends to highlight the current hysteria regarding cancer. If, for reasons not scientific reasons, but if for other reasons it is impossible to eliminate this clause, I would suggest its modification, and would suggest at the very least the elimination on page 10 of por- tions of lines 11, 12, 13, and 14, up to and including the word “or.” The remainder of it would, of course, have to be rewritten somewhat. But the first phrase which, as was brought out yesterday—no one is willing to interpret for me, should indicate that it does not preclude the operation of all subsequent phraseology. Third, I must say that I am in almost complete agreement with Ir. De Ed’s statement. I was very sorry that no one “took up my chal- lenge in my statement yesterday that we are now setting tolerances for c arcinogens, that we do this on the basis of scientific judgment, on the basis of the evaluation of a panel of experts. We have set toler- ances, maximum allowable limits for radioactive materials in drink- ing water and other ingestibles. And, therefore, I conclude that we can set. tolerances. I agree with Dr. Mider’s last statement, but I wonder whether this panel, or any other panel, could agree on the dosage level at which we must test these materials if we are agreed on the experimental design other than dosage level. I think this isa ver Vy important point which this panel, and probably no other panel, will fully agree on, 56123-—-80——-32 492 COLOR ADDITIVES Furthermore, I would say that health is a broader concept than just cancer protection. I would point out to you, in connection with DDT, and many other materials, if research in color additives or food additives or any other area ‘that we are discussing is brought to a halt, or significantly impaired in this country, it means that one of the major areas of such research in the free world will be eliminated, and that the development of materials which might significantly benefit the world at large in extending its inadequate food supply may be seriously jeopardized. I think at the present time this is a very important point in determining our entire future Thank you. Dr. Darsy. Mr. Harris, I will attempt to summarize my own feel- ing about this. I think T have already done so. But, very briefly, I am of the opinion that the section—paragraph on page 10, beginning line 11 to 22, is really unnecessary in order to provide the authority for protection of the public health in this bill. I believe that that portion referred to by Dr. Zavon, and then the portion beginning on line 16, page 11, adequately give the Secretary the authority to review and evaluate data before him, and should evidence presented fail to show that it would be safe and otherwise permissible to list a color additive for all purposes proposed, and so forth, that he may doso. If it were unsafe, fre would not do so, T believe that it would be impractical to adopt the suggestion which has been made this morning that you make exceptions in the law to certain substances (sugar, salt), because repeatedly, as science prog- resses, it will be necessary to add to this list of exceptions and have additional legislative action. Accordingly, I would prefer to trust the scientific | judgment of a responsible agency, such as the Food and Drug ‘Administration, rather than having a firmly predeter- mined legislated decision. Any decision so legislated, as I am sure this panel has illustrated—would be legislated with a certain lack of the desired scientific knowledge. Finally, one point has not previously been mentioned. It is late, but I really feel obligated to call attention to it. On page 10, line 13, of the bill the statement is made— If ingestion of all or any part of such additives is found to induce cancer. This certainly is subject to a considerable amount of scientific ques- tion, because it is conceivable that an additive would have one portion which is a nonnutrient, another portion which might be a perfectly harmless nutrient. This statement could legally “be interpreted, J believe, as preventing the addition of even a portion of an additive which is perfectly he urmless. As far as tolerances are concerned, I feel, again, that in those exceptional situations, such as I interpret Dr. Levin to have indi- cated, that we should permit tolerances, and that those tolerances should be based on the best. judgments, the best appraisals, which could be afforded, the best advice which can be affor nee to the Secre- tary. And this would be the advice which he could get from his sci- entists in Food and Drug, from other scientists that he might wish to eall in. And I should like to see that this includes the possibility of calling in scientists from outside of the Government agencies through such body as the National Academy of Sciences. COLOR ADDITIVES 493 In closing, I should like very much to thank you and the com- mittee, for the panel, for your very kindly and patient handling of us in our moments of controversy. I can assure you that there has been in these controversial moments nothing but scientific differences. This is a panel, each member of which has great respect for the others. Everybody-—except they don’t have much respect for the chairman. The Cuatrman. Which chairman are you talking about ? Dr. Darsy. The chairman of the panel, sir. We all have great re- spect for the chairman of the committee. The Cuairman. Gentlemen of the panel, let me say that the hour of 12 has arrived. We will have to conclude this very helpful and highly instructive and beneficial discussion. On behalf of the committee, let me thank each one of your for your willingness to come here and discuss with the committee these prob- lems that are so disturbing. I personally have gotten a great deal out of it. One fact that I have learned is that outstanding and distinguished scientists can ver definitely draw lines and disagree. I also can understand how, with the knowledge and the experience and background that you have, you can contribute to the welfare of the public. Each one of you can certainly be justified in feeling that you have made such a contribution. I am not sure whether I will ask the Secretary of HEW to come back and try to unravel and analyze what you have put into this record. I am sure that it will not only be helpful to this committee as it strives for a resolution of this problem, but it will also be help- ful to the Department, the Food and Drug Administration, and the Agriculture Department as well, as they continue to administer these important laws in the interest of the public. Thank you very much for the 2 days that you have given of your time and of your knowledge to this record. I wish there were some other way in which the committee could show its respect and appreciation for you taking the time to come here and give us the benefit of your knowledge and information, The committee will now adjourn. (The following letter was later received from Dr. Darby :) VANDERBILT UNIVERSITY, ScHoOL OF MEDICINE, Nashville, Tenn., April 25, 1960. Representative OreEN HArgIs, Committee on Interstate and Foreign Commerce, House of Representatives, Congress of the United States, Washington, D.C. Dear Mr. Harris: I have had an opportunity to reread the transcript of the hearings on April 5—6, 1960, before the Committee on Interstate and Foreign Com- merce on the subject of H.R. 7624, color additives amendment to the Food and Drug Act. This testimony was that of the panel of scientists selected by the National Academy of Sciences to discuss with the committee scientific informa- tion and knowledge pertaining to the possibility of establishment of safe toler- ances for food and color additives known to induce cancer in man or in animals, It is evident from the testimony that the panel of scientists agree that tests in animals can provide some useful basis for appraising the degree of hazard which may be associated with a given use of a substance. It is equally evident that such tests are not infallible and that scientific judgment must be the basis for decision as to the hazard or safety for use of any substance. In the discussions of the panel much time and attention was given to the different interpretations of the word, carcinogenesis. It might have been more helpful to your committee had the panel addressed itself more to the question 494 COLOR ADDITIVES of hazard from cancer as a result of use of a substance or degree of safety in- volved in the use of the substance. It is clear from reading of the testimony that when they spoke of carcinogenesis different members of the panel had in mind different degrees of certainty that a compound could produce cancer. The evidence upon which judgment such as this is based includes a vast array of considerations, tunny of which were brought out in the testimony of the panel, Consideration of these factors and the interpretation of their significance is that element repeatedly referred to by the panel as scientific judgment. There seemed to be a unanimous opinion of the panel that scientific judgment must enter into a decision pertaining to the hazard which might be presented by the use of a given substance. Some members of the panel felt that the evidence at present is such that one should limit or restrict by legislative action the type of evidence upon which one might make a scientific judgment. Others felt this limitation unwise. The record reveals that the type of evidence upon which scientific judgment bas and is being based at present has undergone change and is likely in the future to un- dergo further change. From the record sincere differences of opinion exist as to the degree of limi- tation imposed by the wording of the so-called Delaney clause. Some of the panel members arguing for the retention of the present wording of the Delaney clause appeared to feel that there was considerable restrictiveness of the clause and it wis even suggested that certain legal exceptions be written into the clause to take cognizance of controversial evidence for some specific food sub- stances (for example, evidence relative to common salt). This would seem most unwise because of the impossibility of identifying or predicting the ex- ceptions which should be made in face of existing and future knowledge. The oceurrence of cancer is but one of many undesirable reactions which may be induced by a given material and which might be judged to render the use of a substance unsafe. Without the Delaney clause the Secretary of Health, Edueation, and Welfare is charged with the responsibility for decision as to the safety for use of a given substance. It is my opinion that the legislative action should continue to charge the Secretary with this responsibility for decision as to safety for use of any pro- posed food additive, regardless of the kind of hazard. If it is deemed useful by the Congress to call especial attention to the potential hazard from cancer, I be- lieve this could in the best interest of the health and welfare of our people be accomplished by the simple device of instructing the Secretary that in reaching a decision as to safety he is to consider evidence bearing upon the possible hazard from eancer which might result from the use of a given substance in the manner proposed. Such charge would then assure that he take into account all evidence obtained by methods presently available or which might be developed in the future for judging the safety or hazard for use of a given substance, and that he not only could seek but, in fact, exercise the best scientific judgment in the administra- tion of the law. When a decision of the Secretary made on such a basis is appealed it would again be my considered judgment that a mechanism for review by a competent scientific group selected for the particular case at hand would be desirable, Finally, legislative requirement of publication of the evidence considered in reaching judgments would greatly promote confidence on the part of the pub- lic and scientists as to the degree of protection and safety afforded by our food supply. At the present time evidence submitted other than at public hear- ings must be kept as confidential information by the Food and Drug Administra- tion until it is released by those who have presented the evidence. Members of both panels from the National Academy of Sciences who have testified before your committee or its subcommittee on food additives legislation have urged a change in this requirement. I believe this desirable. Sincerely yours, WirrtamM J. Darry. (Whereupon, at 12 o’clock noon, the committee recessed, subject to the call of the Chair.) COLOR ADDITIVES MONDAY, MAY 9, 1960 Howsrt or REPRESENTATIVES, ComMirresE ON INTERSTATE AND ForEIGN COMMERCE, Washington, D.C. The committee met, pursuant to call, at 10 a.m., in room 1334, New House Office Building, Hon. Oren Harris (chairman of the com- mittee) presiding. Present: Representatives Oren Harris (presiding), W illiam S. Mack, Dingell, Rogers of Texas, Bennett, Springer, Schenck, Younger, Avery, Nelsen, Keith, Hemphill, and Brock. Also present : Dr. Arthur S. F lemming, Secretary of Health, Edu- cation and Welfare; Dr. G. Burroughs Mider, Associate Director in Charge of Research, National Cancer Institute ; George P. Larrick, Commissioner, F ood and Drug Administration ; Theodore Ellenbogen, legislative attorney, Department of Health, Education, and Welfare; W. FE. Williamson, chief clerk. The CHairman. The committee will come to order, The committee is meeting again today to resume hearings, and hopes to conclude the hearings today on color additives proposed legislation, H.R. 7624 and S. 2197, It. will be recalled that the committee conducted hearings on this subject some time ago. We are very glad to welcome again Dr. Arthur S. Flemming, Secretary of the Department of Health, Edu- cation, and W elfare, who will present a statement—should I say an- other staterment—on this particular subject. matter. It will be recalled, also, that we held a panel discussion on April 5 and 6, at which time we heard a group of distinguished scientists discuss the scientific aspects of the legislation with particular em- phasis on the Delaney clause. When Dr. Flemming was here before, it was indicated then that he probably would have a subsequent report to make to the committee. Mr. Clerk, I believe we have the report from the Bureau of the Budget, dated April 13, 1960, which I think should go in the record at this point. (The report referred to appears on p. 34.) The Cramman. Before we ask you to proceed, Dr. Flemming, I should like to take the occasion to welcome a distinguished and fine group of girls who are visiting with us today. I do not know if it is because they heard that you were coming here that brought them to visit. It could very well be. We have classes from various institu- tions throughout the country who visit this committee, and we are 495 496 COLOR ADDITIVES always glad to welcome these groups here, because we feel that the work of this committee is of such importance that it would be very helpful to you during the course of your education. It indicates the interest that you have in the important problems of the day, be- cause you are to be our citizens of tomorrow. So it is a pleasure to welcome the senior class of the Academy of the New Church at Bryn Athyn, Pa. ; May I say that we are very glad to have you with us. We appre- ciate your taking the time to visit this committee on your trip to Washington. We, of course, hope you can stay as long as your time permits, and wish you the best on your trip to the Nation’s Capital. I observe that we have a supplemental letter from your Department, Mr. Secretary, under date of April 11, 1960, and also one dated April 18, 1960, and I have just been handed one that was sent to us April 21, 1960, transmitting comments on amendments proposed by nongovern- mental witnesses, I assume these are the comments you are going to give today? Secretary Fremaana. In substance, Mr. Chairman. The Cuamrman. They can go in the record, if you like, or you can proceed. Secretary Fremane. I would be very glad to have the letters go in the record at this point. (The documents referred to are as follows :) DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, April 11, 1960. Hon. Oren Harris, Chairman, Committee on Interstate and Foreign Commerce, House of Representatives, Washington, D.C. Dear Mr. CHatkMan: The purpose of this letter is to recommend a correction in the hearing provision in title I of the proposed “Color Additive Amendments of 1959” (H.R. 7624 and S. 2197) now pending before your committee. As drafted by this Department and submitted to Congress, and as contained in these bills, the hearing provision would, through an inadvertent cross-refer- ence to the subsection on fees, provide for hearing and judicial review not only with respect to the issuance, amendment, or repeal of regulations relating to the listing and certification of color additives, but also with respect to regulations establishing fees for such listing and certification. Under present law as consistently interpreted by us since its enactment, the issuance or amendment of regulations establishing schedules of fees for the listing and certification of coal-tar colors is not subject to hearing or judicial review (section 706 of Federal Food, Drug, and Cosmetie Act). This likewise holds true in the case of fees for certification services for insulin or antibiotics, fees for the pesticide regulation service, and fees for seafood inspection (sections 408 (0), 506, 507, T02A). The establishment of such fees is purely a matter of cost accounting and, since the services must be self-sustaining, the fees are auto- matically kept at the appropriate level through auditing of expenditures by the General Accounting Office. To provide for hearing and judicial review with re- spect to the establishment of fees would thus serve no useful purpose and, on the other hand, might cause delay which could seriously impede or make im- possible the performance of the services in question. We therefore recommend that the provisions of these bills be corrected by changing the phrase “subsection (b) (¢), or (e) of this section” (H.R. 7624, p. 13, line 6; S. 2197, p. 13, line 9) to read “subsection (b) or (¢) of this section.” Sincerely yours, Arrnur S. FLEMMING, Secretary. COLOR ADDITIVES 497 Tue SECRETARY OF HEALTH, EpUCATION, AND WELFARE, Washington, April 18, 1960. Hon, Oren Harrts, Chairman, Committee on Interstate and Foreign Commerce, House of Representatives, Washington, D.C. Dear Mr. CHarkMAN: Dr. Kenneth A. Freeman, in charge of the Color Certifi- cation Branch of the Food and Drug Administration, who attended the color additives hearings on February 10, has advised me of your request for a state- ment outlining the status of arsenic-containing compounds under the food addi- tives amendment to the Federal Food, Drug, and Cosmetic Act. Six arsenic-containing compounds are used in poultry feed to stimulate the growth of poultry or to control disease in the flocks. Certain of these com- pounds may be used also in swine feed for growth stimulation and disease, While the Department of Agriculture has the responsibility for inspection of meat and poultry at the point of slaughter, the Food and Drug Administration is responsible for the safety of new drugs for veterinary use and of feed for meat animals, and poultry. Before the enactment of the food additives amendment, some of these arsenic- containing compounds were allowed in animal feed under the provisions of the new-drug and antibiotic sections of the Federal Food, Drug, and Cosmetic Act. The compounds were allowed in stated concentrations and with the understand- ing that they would be marketed with label directions requiring treated animals to be maintained for 5 days before slaughter on feed that does not contain added arsenic. The evidence before the Food and Drug Administration indicated that this 5-day withdrawal period would allow the elimination of added arsenic from tissues of the treated animals and thus would insure the safety of the use of the arsenic compounds. A very preliminary survey made some time ago by the Food and Drug Ad- ministration indicated that some poultry raisers are not withholding arsenic- containing feeds from their flocks 5 days before slaughter, and we have informa- tion that in some parts of the country hog raisers maintain their animals on arsenic-containing feed within the 5-day period that the arsenic is supposed to be withheld. It is evident that such disregard of the directions for sufe use could lead to added arsenic residues in poultry and pork on the retail market and thus could frustrate the public health safeguards upon which the original approvals were granted. It is our purpose to look into this situation further, but our investigation has been delayed pending a search in the laboratories of the Food and Drug Administration for suitable analytical methods to support the investigation. In September 1958 the food additives amendment to the Federal Food, Drug, and Cosmetic Act became law. This provides, as you know, that a person who proposes to promote and additive for use in food must first present evidence of the safety of the use to our Department and secure approval through the issnance of an appropriate food additives regulation. It provides also that we may not sanction the addition of a substance to food if it has been found to induce cancer when fed to man or animal, or if it has been found to induce eancer by other appropriate tests. (Food, as defined in the law, includes food for animals as well as for man.) The specific uses of arsenic-containing compounds on the basis of applications that were approved by the Food and Drug Administration under the new drug or antibiotic sections of the law before enactment of the food additives amend- ment are exempt from the application of the food additives amendment. Thus, many uses of arsenic-containing compounds in animal feeds may continue as before. Whether other uses of these and other arsenie-containing compounds in animal feeds would be subject to the food additives amendment depends upon whether appropriately qualitied experts generally recognize such uses as safe. If they do, then the chemicals are not included in the definition of food additives. There was some question in our minds as to whether these uses were generally recognized by experts as safe, and we brought this to the attention of the Animal Health Institute, Des Moines, Iowa, and the American Feed Manufacturers Association, Inc., in June and July 1959. It was our understanding that one or both of these organizations, perhaps with the assistance of some of the veterinary drug manufacturers whom they hud contacted, would canvass a num- 498 COLOR ADDITIVES ber of scientific experts in the country to determine whether the additional arsenicals were generally regarded as safe under their intended conditions of use. So far as we know, this has not been done. Consequently, it is our purpose in the near future to make such an investigation without waiting further for industry action. If. the proposed uses of the arsenicals in animal feeds are subject to the food additives amendment, then one part of the showing of safety Chat is required under the amendment will be to determine whether the cancer clause of the amendment applies. The Food and Drug Administration tells me that the organic arsenic compounds used in animal feeds have not been shown to produce cancer when fed to test animals, On the other hand, we do need more advice from the scientists who are most knowledgeable in the arsenical field. We are taking steps to get this advice. As you know, from the testimony I gave before your committee on January 26 we expect to propose an amendment to the food additive law that would allow us to sanction the use of a chemical in animal feed, even though it may have been shown to produce cancer in test animals if the proposed use could leave no residues in edible products derived from the animal for which the feed was intended and were without harm to the animal itself. Such an amendment, together with the further studies that we are undertaking, may well resolve a number of questions that have arisen about the arsenic compounds since the food additives amendinent was enacted about a year and a half ago. Sincerely yours, ARTHUR 8S. FLEMMING, Secretary. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, Washington, D.C., Aprit.21, 1960. Hon. OREN Harris, . Chairman, Committee on Interstate and Foreign Commerce, House of Representatives, Washington, D.C. Deak Mr. CHAIRMAN: On January 29, you indicated during the hearings on pending color additive legislation (H.R. 7624 and 8, 2197) that you would like to have our views on the various amendments proposed by witnesses other than those representing this Department. Accordingly, we have reviewed the record of the hearings and are glad to offer the following comments. The amendments proposed by the witnesses fall into four principal cate gories: 1. There are a number of suggestions for change in the scope of the bills. 2. There are several recommendations with respect to the substantive criteria for listing colors, including a number of adverse comments on the anticancer clause in the Department's proposal as contained in H.R. 7624. The criticisms of the bill’s anticancer clause also extend to the clause from which it is de- rived, i.e., the so-called Delaney proviso in the Food Additives Amendment of 1958, 3. A number of suggestions are made on procedural points, both with respect to the permanent part (title I) and the transitional part (title II) of the bill. Additionally, one individual, Mr. Frank Schell, of Florida, has written to the committee proposing an entirely new bill to be substituted for the De partment's bill. Our comments on these various items, except the anticancer clause are en- closed herewith (enclosure I). I expect to testify further on the anticancer clause, There is enclosed herewith (enclosure IT) a draft of a provision which would accord an opportunity for hearing with respect to certain regula- tory actions under the transitional part of the bill, under the conditions stated in my testimony. There is enclosed (enclosure III) a draft amendment to the proposed section 706(d) of the bills, to incorporate time limits in the rulemaking procedure of the legislation if the committee should wish to do so. Also there is enclosed (enclosure IV) a draft amendment to section 203(d)(2) (A) of the bill to make it clear that funds and regulations dealing with the cost of certify- ing coal-tar colors under section 706 of the basic act, shall continue to be avail- able and in effect, respectively, for the purposes specfied in section 706 as amended by the proposed bill. In summury, we are opposed to all the amendments proposed by the witnesses, except (1) a clarifying amendment on agricultural chemicals, in the form con- COLOR ADDITIVES 499 tained in enclosure I agreed upon by us with the Department of Agriculture, and (2) the amendments set forth in enclosures II and III. As between the respective versions of S, 2197 and H.R. 7624, we have already advised that the changes contained in S. 2197 as passed by the Senate are acceptable to us, ex- cept that we recommend inclusion of the anticancer clause of H.R, 7624 with a modification relating to animal feed similar to the one we are developing for the Delaney proviso to the Food Additives Amendment of 1958. We have also recommended, by letter dated April 11, 1960, a technical correction in section 706(d). Sincerely yours, ArtHURS. FLEMMING, Sccretary. The Cuatrman. I also observe that the committee has a report from the Department of Agriculture which will be included in the record, (The report referred to appears on p. 35.) The Cyamrman. I hope that we are getting somewhere toward resolving this very difficult and important issue. We are very glad to have you back with us, Mr. Secretary, and I believe you have a statement which you would like to present. STATEMENT OF ARTHUR S. FLEMMING, SECRETARY, DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE Secretary Ftemmine. Mr. Chairman, thank you very much. I am very happy to appear before the committee again and appre- ciate the courtesy that you have extended to me in giving me the op- portunity of commenting on some of the testimony that has been pre- sented to the committee since I appeared the last ‘time. As the members of the committee will recall, when I appeared be- fore your committee on January 26 to discuss proposed legislation dealing with the use of colors in foods, drugs, and cosmetics, I par- ticularly urged that the anticancer provision “of the food additives amendment be included in any legislation to assure the safety of color additives. In the intervening months you have heard the issue of the anti- cancer clause discussed further by a great many witnesses, including a panel of distinguished scientists. I appreciate, therefore, the oppor- tunity which you have extended me to review the position of the Department of Health, Education, and Welfare on this issue in the light of the testimony which has been presented to you. “The panel disc ussed in considerable detail the scientific problems that. confront us in connection with determination of the cancer- producing potential of chemicals. They pointed out the difficulties of designing and conducting an experiment to determine whether a substance is a cancer producer for man and the difficulties in evaluat- ing the test data after it is obtained. Scientists in our Department who were present during the panel discussion and who have since reviewed the transcript of the testimony tell me that the scientific views expressed by the panel and those ex- pressed earlier by our Department are basically in accord. The panel also gave you its views about the administrative pro- cedures that could be employed in applying the accepted scientific principles in the cancer field. There is an area here in which we do not find it possible to agree with the recommendations of some of the scientists. 500 COLOR ADDITIVES A number of the panel members have suggested that despite the difficulties, in extraordinary cases, our Department should have the authority to decide that a minute amount of a cancer-producing chemical may be added to man’s food after a group of scientists sit down and consider all the facts and conclude that the quantity to be tolerated is probably without hazard. . The Department's position is that the proposed color additives leg- islation should include an anticancer clause that makes illegal the use of any color that will induce cancer when tested by appropriate methods. We believe this position to be the only sound public policy in view of the fact that our experts tell us present scientific techniques do not permit them to state unequivocally how much or how little of a substance that induces cancer when administered to animals will induce cancer when administer to man. This means, of course, that we would oppose any change in the Delaney anticancer clause of the food additives amendment other than the proposal I incorporated in my January 26 testimony. At that time I stated that we believe the Delaney clause should be modified to provide that additives used in animal feed which leave no residue either in the animal after slaughter or in any food product obtained from the living animal be exempt from the provisions of the clause. Let us look for a moment at the practical effect of the anticancer clause: I believe it is significant that in all the testimony you have heard on the color additive bills since last January 26, no witness has given you a single example of a cancer-producing color additive that he thinks should be allowed. And no witness has stated what he would regard as an extraordinary situation that would justify approval of a cancer-producing color additive. Certainly we know of no cancer-producing color additive that should be permitted, nor are we able to visualize a situation that would justify the addition of any amount of a carcinogenic color additive to foods, drugs, or cosmetics in the present state of our scientific knowledge, Four chemicals, not color additives, were mentioned during the hearings as compounds that might be permitted in small amounts in food. I have here a supplemental statement prepared by the Food and Drug Administration commenting on these compounds and on certain other phases of the testimony you have heard on cancer, It is a brief statement, Mr. Chairman, and I would be glad to go over that. after I finsh my opening statement, which, as you will note, is short: or I would be glad to have the Food and Drug memorandum included in the record of the hearing, whichever vou desire. You will note from this statement that the Food and Drug Ad- ministration finds that not one of these four compounds has been established as a necessary ingredient in the diet of man, I would like to state, however, that in my opinion the facts pre- sented to your committee about these four componds, for which some people believe a small tolerance level could be established without great risk, do not add up to a compelling or even a persuasive argu- COLOR ADDITIVES 501 ment for abandoning or weakening the principle of the anticancer clause. The rallying point against the anticancer provision is the catch phrase that it takes away the scientist’s right to exercise judgent. The issue this made is a false one, because the clause allows the exercise of all the judgment that can safely be exercised on the basis of our present knowledge. The clause is grounded on the scientific fact of life that no one, at this time, can tell us how to establish for man a safe toler- ance for a cancer-producing agent. . . Until cancer research makes a breakthrough at this point, there simply is no scientific basis on which judgment or discretion could be exercised in tolerating a small amount of a known carcinogenic color or food additive. As I pointed out in my original testimony, the opposition to inclu- sion of an anticancer clause arises largely out of a misunderstanding of how this provision works. It allows the Department and its scien- tific people full discretion and judgment in deciding whether a sub- stance has been shown to produce cancer when added to the diet of test animals. But once this decision is made, the limits of judgment have been reached and there is no reliable basis on which discretion could be exercised in determining a safe threshold does for the estab- lished carcinogen. So long as the outstanding experts in the National Cancer Institute and the Food and Drug Administration tell us that they do not know how to establish with any assurance at all a safe dose in man’s food for a cancer-producing substance, the principle in the anticancer clause is sound. I want to emphasize the statement I made on January 26 that the Food, Drug, and Cosmetic Act, as it now stands, will be enforced to prohibit the addition of cancer-producing substances to food unless a law should be passed directing us to follow another course of action. Even though we have this authority in the law, we urge the Con- gress to join with the executive branch to give added assurance to the consuming public by directing the anticancer clause in the proposed color-additives amendment. Whenever a sound scientific basis is developed for the establishment of tolerances for carcinogens, we will request the Congress to give us that authority. ; Again, we say, however, that we believe the issue is so important that the elected Representatives of the people should have the oppor- tunity of examining the evidence and determining whether or not the authority should be granted. As I have indicated, Mr. Chairman, there is attached another rather brief memorandum which is headed, “Comments on Testimony on the Cancer Clause in H.R. 7624.” ‘This was prepared for me by the Food and Drug Administration. If you so desire, I would be glad to go through that now. It is brief. But, as I indicated earlier, I would also be very glad to simply make it available for the record. The Cuarmman. You may proceed just as you like, Mr. Secretary. Secretary FiremMine. I think it would probably be helpful, because this is a brief memorandum—and, as I say, this memorandum was fur- 502 COLOR ADDITIVES nished me by the Food and Drug Administration commenting on thie testimony on the cancer clause. Four specific compounds were mentioned during the hearings as substances for which safe tolerances might be established. One was an emulsifier that produced bladder stones and cancer when included as 25 percent of the total diet, but did not. produce stones and cancers when fed at a level of 10 percent of the total diet. Some wit- nesses criticized the test on the ground that the chemical was fed at too high a percentage of the total diet. The level at which the emulsifier was tested was appropriate. This emulsifier was being used in bread. It was being added at one-half pound of emulsifier per 100 pounds of flour; allowing for other in- gredients and moisture present in bread, this amounted to approxi- mately 0.3 percent of the weight of the finished bread. When the Food and Drug Administration learned that the product was being used, it started tests to determine its effect on laboratory animals, In accordance with accepted pharmacological procedures, the chemical was tested at higher levels than were being employed in man’s food. This is necessary because man does not always respond to added poisons in his diet exactly like test animals—a healthy man may be less sensitive or he may be more sensitive than the animals. It should be remembered, too, that food is consumed by the weak, the sick, and the aged, who may be much more sensitive than others. Combining these sources of possible error in translating animal- test results to safe tolerances for man has led the Food and Drug Administration over the years to follow a policy of requiring a safety factor of 100 for new chemicals, foreign to man’s food. That is, animals should show no adverse effect when they consume 100 times as much of a chemical as is proposed for man’s diet. Now let us apply this policy to the question of the validity of the test on the emulsifier. Ffad 25 percent of the emulsifier in the ani- mals’ diet been proved safe, this would have justified the assumption, applying the safety factor of 100, that 0.25 percent would be safe in man’s diet. Bread contained as much as 0.3 percent of the emulsi- fier, and the 25-percent level did not prove safe for animals. There- fore, the amount fed is reasonably relevant to the safety question. When you consider the fact that animals fed 25 percent of the emulsifier got cancers, we believe the decision that none of this chemi- sal could be used in bread was proper. Furthermore, what is the significance of this compound in food, drugs, or cosmetics? There are a number of other emulsifying agents on the market today that can be used in place of this chemical. It is not essential for nutrition. It is not essential for the manufacture of food. Tt is not. essential for the manufacture of drugs. It is not essential for the manufacture of cosmetics. So why should the Government take action to allow this chemical to be used when there are other materials that will adequately per- form the function it is supposed to accomplish and when these other materials have not been found to produce cancer upon feeding? An industry lawyer suggested that it would be possible to establish a safe tolerance for potassium arsenite by determining a feeding level COLOR ADDITIVES 503 at which it fails to produce the characteristic changes in palms of the hands and soles of the feet. Why should we establish a tolerance for potassium arsenite which has been found to induce cancer when consumed by man? It is not used in food today. So far as we know, there is no technological pur- pose that its use would serve that cannot be served adequately by non- carcinogenic chemicals. Another industry witness spoke in favor of allowing stilbestrol to be used in the production of poultry. We are adv ised that the use of stilbestrol was economically important in the production of about 1 percent of the total poultry supply of the country. Its use yielded caponettes, birds quite similar to those produced after surgical castration, at less cost. But the use has been shown to le ave residues in some edible tissues of the treated birds, and the chem- eal has produced cancers when fed to laboratory animals. We do not know of scientific procedures that would permit us to determine how much or how little of a substance that produces cancer by feeding to test animals would be required to produce cancer when fed to man. In view of this, why should we take a risk with the public health, just to permit. a very small segment of the poultry in- dustry to use production methods somewhat cheaper than others already available? Some witnesses addressed their comments to selenium, a chemical which some believe is an essential nutritional factor in young lambs and young calves. There has been no showing that the use of quanti- ties of selenium needed for nutritional benefit would leave a residue of selenium in the meat of treated animals at time of slaughter. I have testified that the Department would favor an ‘amendment. to the food-additives amendment exempting from coverage of the cancer clause substances to be used in animal feed which leave no residue either in the animal after slaughter or in any food product obtained from the living animal. Moreover, I have stated that if a situation should develop which in the public interest would indicate the need for further modification of the anticancer clause, we wonld present the facts to the Congress with a request for appropriate action, The Food and Drug Administration knows of no situation in this country at the present time which suggests the need for modification of the anticancer clause other than that already proposed in my testi- mony of January 26. There was indication during the hearings that some believe the anti- cancer clause requires every additive to be tested for 7 years before a decision can be reached as to its safety. This is not correct. Safety of a food additive is ordinarily determined by feeding the chemical to test animals for 2 years. This feeding period permits observations to be made on any changes in the test animal that would indicate any type of hazard, of which cancer is but one. If the chemical passes the 2-year test, it may then be allowed in food. Tf it fails to pass because the 2-year test raises some question that still needs to be explored, then the decision as to whether further testing should be undertaken is an economic one to be reached by the promoter of the additive. In the vast majority of cases the 2-year test permits a final decision on the chemical. But if it does not, public health considerations cer- 504 COLOR ADDITIVES tainly would require that the chemical not be used until its safety is fully established. One industry witness objected to any anticancer clause. Another witness argued that it is possible to establish safe tolerance levels for substances that produce cancer when fed to test animals. Some suggested that the cancer clause be modified to apply only to substances that “proximately” induce cancer. Some would have the ban on cancer producers apply only to colors that induce cancer when ingested in an amount and under conditions reasonably related to their intended use. And another witness proposed that the cancer clause be taken out of its present position in the bill and added with material language changes to section 706(b) (5) so that it would be- come simply one of the factors for the Secretary to consider in evaluating the safety of a color additive. It is evident that these changes are intended to give the Secretary the right to establish tolerances for presumed safe levels of colors that produce cancer when tested under appropriate laboratory condi- tions. Thus, any of the proposals, if adopted, would weaken the present cancer clause in H.R. 7624. For this reason all of the pro- posed changes should be rejected. In his supplemental statement of April 25, 1960, which was mailed to the committee, Dr. William J. Darby, chairman of the scientific panel, stated: Finally, legislative requirement of publication of the evidence considered in reaching judgments would greatly promote confidence on the part of the public and scientists as to the degree of protection and safety afforded by our food supply. At the present time evidence submitted other than at public hearings must be kept as confidential information by the Food and Drug Ad- ministration until it is released by those who have presented the evidence. Members of both panels from the National Academy of Sciences who have testi- fied before your committee or its subcommittees on food additives legislation have urged a change in this requirement. I believe this desirable. We concur in this recommendation. The Cuamman. Does that conclude your statement, Mr. Secretary ? Secretary FLemsana. It does, Mr. Chairman. The Cuarrman. Mr. Williams, do you have any questions? Mr. Wituiams. Mr. Secretary, I am sorry that I didn’t get a chance to hear all of your statement. However, I have hastily scanned over it. Is it not a fact that certain ingredients in tobacco smoke have been proven to induce cancer in animals? Secretary Fremmine. Mr. Chairman and Congressman Williams, you doubtlessly know this is Dr. Mider, of the National Cancer Insti- tute, and I would appreciate it, if it is satisfactory with you, if he would respond to that question. Dr. Miner. Mr. Williams, condensates made from tobacco smoke have produced cancers when applied to the skin of mice, repeatedly, sir. Mr. Witu1aMs. Is it the position of the Department that no toler- ance should be allowed in the case of tobacco, and that tobacco will hereafter be banned because it has been proven to induce cancer in animals $ Secretary Freaminc. Mr. Congressman, it isnot. Of course, as you know, first of all, we have no authority in this particular area under existing law, nor would I recommend at this particular point that we be given authority in this particular area. COLOR ADDITIVES 505 It seems to me that the responsibility that rests on the Department in this area as of the present time—and I don’t think we should go beyond this—is to evaluate the kind of evidence to which you have called attention, Mr. Wiiuiams. Mr. Secretary, I don’t recommend that you do ban the smoking of tobacco because that is the only way I can figure that I can quit. Secretary FLemmine. Congressman, could I just complete. My feeling is that the Public Health Service does have a definite obligation to take the evidence that has been developed in what I know is a controversial area, present that evidence both pro and con to the public, evaluate it for the benefit of the public so that the pub- lic can then make up their own mind as to just what they are going to do. Now, this the Public Health Service, as you know, has done, and I feel that the Surgeon General and those who are associated with him are to be commended for the way in which they have handled it. But it seems to me this is quite a different proposition as contrasted with a proposition where people are asked to consume food, some- times knowingly, often without their knowing it, that contains a substance that has been demonstrated to be a substance that induces cancer when included in the diet of an animal. Mr. Wituiams. How does that differ, Mr. Secretary ? Secretary FremMinc. Well, 1 think the individual is in quite a different position, The consumer goes to the market to buy food, and under the philosophy that the Congress has followed since 1906, the Federal Government is trying to do everything possible to see to it that when the consumer buys that food, he can buy it with the understanding that it is safe. Mr. Witui1ams. The same thing applies to tobacco; doesn’t it? Secretary Fremmine (continuing). But as far as—and the con- sumer, I think, on the basis of the action that has been taken by the Congress, has the right to indulge in that particular assumption, and he certainly has the right to feel that he is not buying food that includes in it a substance that has induced cancer when included in the diet of an animal. As far as tobacco is concerned, the individual is perfectly free to buy tobacco or not, to buy cigarettes or not buy them. Individuals do feel that it is necessary to buy food in order to sus- tain life, but the individual is in a position where he can decide whether he is going to smoke or not smoke on the basis of the evidence that has been made available to him by the Government. As Dr. Mider can point out better than I can, the whole question of the correlation between the increase and the incidence of lung cancer and smoking is a debatable issue. Mr. Wiuiu1aMs. I understand that. Secretary FLemmine. There are those who take the other position on it. But, as I say, I think the Public Health Service has done what the Government should do in this particular instance. Personally, I don’t see any reason why at this point the Government should go further than it has gone. 506 COLOR ADDITIVES Mr. Witirams. Mr. Secretary, I will accept that, of course, but I have some difficulty in reconciling the difference, as you have indicated, as between food and tobacco, and as between tobacco and cosmetics. You have in your suggestions been very careful to suggest that we ban the use of cosmetics which contain any carcinogenic substances that will produce cancer in animals. Yet, you do not suggest that tobacco, which has already been proven, so I am told, to induce cancer in animals be banned from the market. There is no compulsion on anyone to use cosmetics; there is to use foods. So let’s compare the case of cosmetics with the case of tobacco. Secretary Fiexrmine. Here, again, Mr. Congressman, the Congress some years ago added cosmetics to the Pure Food and Drug Act, and in so doing said, in effect, to the consumer again: We are going to do everything within our power to insure the fact that when you use cosmetics, you will use them under conditions that can be regarded as safe. And, certainly, we feel that that being the case, that the Congress should not, that certainly the Food and Drug Administration should not permit, under the authority given to it by the Congress, the inclu- sion of a substance which has been shown to induce cancer in animals. As I indicated in my testimony, with or without a Delaney amend- ment on the food additives, with or without a Delaney amendment on the color additives, this is the policy that we would follow under the basic authority that has been conferred on us by the Congress. We know of no other way of discharging that authority in a man- ner that would be fair to the consumer. Let me put it this way. As far as the manufacture of cigarettes is concerned, I assume that if the time ever comes when the scientists can identify something that goes into the manufacture of cigarettes that, in and of itself, induces cancer, that the Congress will be very much interested in receiving that testimony and would be very much interested in considering legislation which would confer additional authority on our Department. But I assume that that particular time has not yet come. But as far as cosmetics are concerned, we feel that the evidence is clear that if a substance, if a color in this case, does induce cancer in animals, that because no one knows how much or how little of that substance will induce cancer in man, it is sound public policy to ban the use of that substance. Mr. Wiiu1ams. Well, I would refer you to paragraph 3 on page 2 of your statement respecting the Department’s position in regard to this, which is very clear, in my opinion. You confine that to proposed color additives legislation. Assum- ing that tobacco should fall within the jurisdiction of your agency, the position which you have taken with respect to color additives would have to be the same with respect to tobacco, wouldn’t it, if the same test is applied and the same yardstick used ? Secretary Presta. Congressman, and Mr. Chairman, I wanted to talk with Dr. Mider about this before I make this statement, and I will make it now subject to further verification. Mr. Wirttams. Let me say this, Mr. Secretary. I am not attempt- ing to embarrass you with these questions at all. TI am attempting to find out the scope of this amendment in its application. COLOR ADDITIVES 507 Secretary Fremmine. Congressman Williams, I appreciate your questions because I can assure you that whenever T meet with a group of citizens and talk about this particular problem, the type of ques- tion that you have raised is raised with me, and it is a very natural and normal question for people to raise. But let me put it this way. As far as I know—and I am talking as a layman, as you appreciate; and, as I say, this is subject to verifi- cation by the sclentists—as far as I know, no one has yet identified a substance that is included in the processing of tobacco or in the manufacture of cigarettes that, in and of itself, does induce cancer in test animals. Dr. Mider has responded to the question that you addressed in the first instance. From that point on—I don’t know whether I should make it as a sweeping generalization, but certainly to a considerable degree from that point on, the evaluation of the situation on smoking in relation to the increase in incidence of lung cancer is based on statistical correlation. Mr. Wuiams. But the test that is required under this bill is: Will it produce cancer in animals; and that has already apparently been conceded by your people, that it does produce cancer in animals. Using the same yardstick that you used with respect to these other chemicals, if that were construed literally, wouldn’t it also be in- cumbent upon you to ban the use of tobacco? ” Secretary FLemminc. Let's make perfectly clear—and I am sure you agree with me on this—there is no authority in law at the present time—— Mr. Wiutams. I understand that. Secretary Fiesmine (continuing). Which would authorize us to ake any action whatever with regard to tobacco. I assume that your question is directed to the point of whether or not there should be au- thority in law. Mr. Wittrams. Yes. Secretary FLemmina. Which would make it possible for us—— Mr. WitutaMs. It is on the assumption that you should be given authority under law Secretary FLremmine (continuing). To act in this particular area. As I indicated earlier, on the basis of present research insofar as tobacco is concerned, it is my own judgment that such authority should not be given to us, because I do not believe that research has reached the point where that authority could be discharged in a sound manner. Mr. Wittrams. Wouldn’t the same thing apply, however, to many of these chemicals which fall within the scope of this amendment, which, when applied to animals, induced cancer, but there is no proof that they would induce cancer when consumed by man? Secretary FLemmine. Congressman Williams, we go back to the basic point that what we are talking about are additives. We are talking about additives to food. We are talking about color addi- tives in this particular instance. The scientists tell us that when they do induce cancer in animals, that no one knows how much or how little of this substance is needed to induce cancer when included in the diet of man, thinking in terms now of the moment in-——— 56123—-60——-33 508 COLOR ADDITIVES Mr. Wiir1ams. We can debate this all day long. Secretary Fremmine. But my only point is this: That we do not feel that it is sound public policy to add to the risk that the consumer must undergo in his daily life by adding these substances either to food or colors. when we know that they have induced cancer whea., included in the diet of an animal. ; ; Now, going to your basic, fundamental point, I still feel that there is quite a distinction between saying to the American people, “Iiere is all of the evidence that we have as far as the relationship between smoking and lung cancer is concerned, here is our evaluation of that evidence,” and on the basis of that evaluation the individual citizea can decide whether or not he wants to continue to smoke. ; Now, we have had some experience as a nation—going over into a related area—in saying we do not think that drinking under certain circumstances is good for the health, and, therefore, we will ban the use of intoxicating liquors. After all, the Congress amended the Constitution so as to make that possible. And on the basis of the experience the Congress and the States de- cided to repeal that particular amendment to the Constitution. — We have an obligation as a public health agency in that particular area to make available to the American people the evidence that we have which we feel has a bearing on the health of the individual, and then the individual has a responsibility for making up his own mind. I think that the same thing is true in the field of smoking. That is one thing. But it is another thing to say to the consumer, as he goes to the market to purchase food, “You may or may not be purchasing food that has had added to it some substances that we know induce cancer when included in the diet of test animals.” We do not feel—and I feel that that is the policy of the Congress— the Congress does not feel that the consumer should be put in that position, because the consumer under those circumstances has no real choice. He doesn’t know whether or not he is buying food that includes some of these substances or doesn’t include some of these substances. Now, I suppose you could get a roughly parallel situation by re- quiring that the food be labeled to the effect that it includes a sub- stance that has induced cancer when included in the diet of a test animal. Then the individual would have the choice. But I don’t think that anyone would advocate that course of action. Rather, it is the basic policy of Congress that as a Government we have the responsibility of seeing to it that the individual does not involuntarily, in effect, consume a substance that we have discovered induces cancer when included in the diet of an animal. I appreciate your line of questioning; and I do think that there is a basic difference between the consumption of food, the use of cosmet- ics, the use of drugs, and the question of whether or not a person is going to smoke; and I think it is somewhat comparable to the ques- tion of whether or not a person is going to drink. In these two areas I think the Government, as I say, has got an obligation to take the evidence, analyze it, evaluate it without fear or favor, make it available to the public, and then let the public make COLOR ADDITIVES 509, its own decision. But when you include it in food or in cosmeties, really, the public is not being given the opportunity of making its own decision, because they go in and innocently buy food or buy cosmetics that include these substances that will induce cancer when tested on animals. . If they knew that those substances were there, in many, many in-. stances they just wouldn’t want to touch that particular item. But not knowing it one way or another, they go ahead and buy. And we feel that we have an obligation as a Covernment—I mean I think this is an obligation shared by the Congress and the executive branch— to do everything we can to see that they are not involuntarily exposed to an additional risk in this area. Mr. Wiiu1ams. Mr. Secretary, I can appreciate your explanation and certainly I can appreciate the position which this controversy would place your agency in. But to be perfectly frank, and this would conclude my questions, I have no other questions, but I would like to make the observation that I personally fail to see the distinc- tion or the differentiation between the use of cancer-producing tobacco and the use of cancer-producing cosmetics or additives to food. However, you have expressed your position and there is no need in asking you to do it again. The Cuairman. I suppose that would be just about as highly controversial a subject 1 it were to be brought to a vote, Doctor; as it was with the prohibition amendment. Secretary Fremmine. It seems to me, Mr. Chairman, that it in- volves the same basic issue, and as I have tried to point out, I think it is a different issue than the issue that confronts us in the area of food, drugs, and cometics The Cuarrman. I don’t know whether that would be one way of finding out whether there are more smokers than nonsmokers. I doubt that it would be the same situation as to whether there are more drinkers than nondrinkers. Secretary Fremmine. But, Mr. Chairman, I do want to emphasize again that although I feel that the Government’s role is a different one, I nevertheless feel that it does have a role, and I think the Public Health Service has discharged its responsibility on the smoking side very effectively. The Cuatrman. Mr. Schenck. Mr. Scuencx. Mr. Chairman, I appreciate this opportunity, and I have greatly enjoyed this colloquy between our colleague and the Secretary. As I understand Dr. Mider’s statement, it was that the concentrates from tobacco produced this cancer-forming or carcinogenic type Dr. Miner. I think I said, Mr. Schenck, that the condensates of the tobacco smoke produced a tar which would produce cancer when applied to the skin of mice. fr. Scuencx. You were referring to the fact that these were the condensates from the entire tobacco leaf and it was not something that was added to tobacco? Dr. Miper. That is correct. Mr. Scnenck. So we do have that difference here concerning cosmetics, from the standpoint that colors are additives, and the to- bacco, in itself, is the culprit in this case; is that true? 510 COLOR ADDITIVES Secretary Firmuinc. That is certainly true, Congressman Schenck, and I think it is a very important distinction to be kept in mind, because what the Congress has been dealing with here all the way along the line is the question of additives. I mean arbitrarily adding something to food or to cosmetics or to drugs as the case may be. Mr. Scnencr. Recently I had in my office the owner of a small canning factory who was quite perturbed over the possibility of the banning of such things as red beet juice used in coloring certain vegetables, and also the possibility of banning of a substance called turmeric, I believe, which is used to make mustard yellow. Other- wise, ordinary table mustard would be sort of a putty gray, I under- stand. Now, are those substances presently being considered ? _ Dr. Larrick. We have already considered the turmeric and have put it on a list of articles that may be used, and we have no objection what- soever to the use of beet juice to color materials in food. I don’t think your constituent has any real reason for any con- cern whatsoever. Mr. Scuenck. That is all the questions I have, Mr. Chairman. The Cuarrman. Mr. Mack? Mr. Mack. Mr. Secretary, in the case of tobacco, so far as you know, these cancer-producing substances were not a result of spraying the tobacco or treatment in tobacco? Secretary FLemmine. Not insofar as we know, that is correct. Mr. Mack. It is my understanding that some of the cigarette com- panies formerly used a chemical to retain moisture in the tobacco, is that correct ? Secretary Fremmrina. I wouldn’t know that of my own knowledge, but Commissioner Larrick Dr. Larrick. They have used some of the glycols, I understand, to retain moisture in tobacco. Mr. Mack. That would not be the cancer-producing agent, is that correct ? Dr. Larrick. We don’t know that that is a fact, sir. We don’t think that it would be. Mr. Mack. That has never been determined? Dr. Larrick. That is my opinion. It has never been determined. We don’t have any responsibility in Food and Drug to do research on tobacco. The things we know about that we just know quite casnally without having done any work on it ourselves. Mr. Mack. Considerable research has been done in that field, Mr. Secretary, on cancer-producing agents in cigarette smoke? Secretary Fremaane. Dr. Mider could possibly comment on that. Dr. Mier. There is considerable effort, Mr. Mack, on the part of the tobacco industry scientists and scientists throughout the United States in defining the composition and the biological characteristics of compounds obtained from tobacco smoke, but I would like to say, sir, that. burning any carbonaceous material in the absence of a completely adequate supply of oxygen is likely to provide or to produce small amounts of a chemical 3,4-benzpyrene, which we can collect in the dust of many cities, which has been part of our environment for years, which does produce cancer in animals, and for good circumstantial reasons we believe could produce cancer in man as well. COLOR ADDITIVES 511 Mr. Mack. You have, then, done some research in this area? Dr. Mwer. Not myself, personally, Mr. Mack. We have done some work at our Institute, and we are familiar with other work going on in the rest of the country. You see, there is a popular assumption that because the tobacco tar will elicit cancer of the skin in mice, that it is the collection of these tars within the lungs that really elic its the cancer in the lungs. Now this is the one that has been spoken of by most people and dis- cussed at great length, but it isn’t the only other possibility. There are several other possibilities. Mr. Mack. It is just one possibility ? Dr. Miner. No, sir; there are other possibilities. And I, myself, am a smoker. I hare been smoking for 35 years. I am convinced that the excess smoking of cigarettes is causally related to pulmonary cancer, but I don’t know in exactly what. way it does it. I don’t know that it is through the deposition of tar in the lungs. Mr Mack. Then, to the best of your knowledge, it has not. been determined whether this is the result of the actual burning of the to- bacco or whether it might be the burning of the chemicals? Dr. Miper. That is right, sir. Mr. Mack. It might be the burning of the chemical instead of the tobacco? Dr. Miner. If you mean the chemical in the sense of an additive, I don’t know of any such additive, although there may be humectant. But, after all, tobacco itself is a collec tion of chemical compounds, and through the burning of those it is conceivable that this might be important ‘in enhancing the carcinogenic effect of the tars that result. Mr. Mack. Mr. Secretary, aren’t there some foods today which are believed to produce canc ert Secretary FLemaine. I didn’t get the first part of your question, I am sorry. Mr. Mack. I said are there not some foods today that are being con- sumed that are believed to produce cancer; that. is, untreated food ¢ Secretary FLremsine. Here, again, I would like Dr. Mider to re- spond to that, Mr. Congressman, Dr. Miver. Mr. Congressman, I don’t know of any in the United States. Mr. Mack. Has the Department or the Institute done any research on certain types of food ¢ Dr. Miper. In what sense, Mr. Mack? Looking for carcinogenic potency ? : Mr. Mack. That is right. Dr. Miner. No, sir; we have not in a systematic way. But we are greatly interested in this problem at the present time, because the mortality from cancer of the stomach in the United States fell more than 50 percent between 1930 and 1955. Work which is currently being done by one of our associates, Mr. Hanso, would suggest that the risk to foreign-born Americans, some ethnic groups, of gastric cancer is higher than it is in native-born Americans. Now if this change takes place within a period of 25 years, and we ean show that this occurred within one generation, it would be strong 512 COLOR ADDITIVES circumstantial evidence that something in the environment was re- sponsible for this benefit, as it were, to the people. Now we would like to identify. it. Of course, one of the logical] things to assume is that something going into the stomach not so ‘much ‘in America, but in some other country, may be responsible for some of the cancers of the stomach. But whether this be a natural food- stuff or what it may be, we have no knowled ge at this time. There have been surveys conducted in the past by a number of physicians attempting to identify dietary constituents that might be associated with the risk of many different types of diseases including cancer. For the most part, these have not produced the type of evidence that we need. Mr. Mack. Thank you very much. Secretary Fiemmine. Mr. Chairman and Mr. Congressman, could I just make two observations growing out of our recent discussion. May I go back for a moment to smoking tobacco, and I think in order to round out that picture, I should make this additional state- ment, which Dr. Mider tells me is correct from a scientific point of view. That no cancer has been produced in animals when they have been subjected to conditions comparable to the conditions to which man is subjected when he smokes. I think in the light of our discussion about this point that in all fairness I should get that into the record in order to keep the record balanced. In other words, we have, just to sum it up, the point that Dr. Mider made in response to Congressman Williams’ question and which Con- gressman Schenck has also commented on, we have got these statistical correlations about which I appreciate the fact that there is an honest difference of opinion. But as far as the Public Health Service is concerned, they have come to the conclusion that it is the principal causative factor in the in- crease in incidence of lung cancer. But, on the other hand, and this has always been underlined as they have talked to me, and I think it has been underlined in their articles, it is also fair to say, to keep it in balance, that no cancer has been induced in animals when they have been subjected to con- ditions comparable to the conditions to which man is subjected when he smokes. At this particular point, of course, the evidence differs from the kind of evidence that we are talking about in connection with food additives and color additives where cancer has been induced in ani- mals when these substances have been included in their diet. The Cuatrman. Mr. Secretary, that brings on another question. Mr. Witttams. Excuse me, I just want to ask one question. Is that the same test that is applied to color additives and to food additives? Secretary FLemaine. Is it the same test ? Mr. WituraMs. In other words, when the same chemicals are pres- ent in foods or cosmetics, is the same yardstick applied? Is it the same thing under the Delaney amendment, the fact that they may induce cancer, but not under the conditions — Secretary Fiemuine. I get your point now, Congressman Williams. COLOR ADDITIVES 513 The policy that we have followed, the policy that we advocate as sound public policy, is that when it has been demonstrated that a sub- stance will induce cancer—I will stay with the food additive at the moment—when included in the diet of an animal, that then this sub- stance should be banned as far as its use in the diet of man is con- cerned. As I have indicated both times when I have come before the com- + mittee, our scientists feel that this is the only sound public policy to follow. Right at that point I would like just to comment on the last one ‘or two questions of Congressman Mack by calling attention to one pamgraph in my testimony on January 26, when I said that the popu- ation is inadvertently exposed to certain carcinogens. We accept this, of course. Ultraviolet light occurs in sunlight. The burning of most fuels produces some minute quantities of chemi- cal compounds that elicit cancer in experimental animals, and some ‘of the same agents can be identitied in soot, tars, dusts, and similar residues even from the atmosphere. . In view of these facts, it becomes all the more imperative to protect the public from a deliberate introduction of additional carcinogenic ‘materials into the human environment. This is the conviction that we have in dealing with this problem. Pardon me, Mr. Chairman. The Cramrman. Well, now, Mr. Secretary, you have raised a second important question. Did I understand you to say just now that the policy of the Depart- ment and the position you take is that when any substance is included which is shown to produce or induce cancer, then, of course, that sub- stance should be abandoned 2 Secretary FLemacina. I said when included in the diet of an animal, when fed. The Cuamman. Yes. And that is the position the Department takes, and that is your policy ? _ Secretary FLemuine. In our judgment, in dealing with these addi- tives, either food or color, we see no reason at all why the individual should be subjected to an additional risk by permitting the addition of either food or color additives that will induce cancer when included in the diet of an animal. _ The Carman. Now, Mr. Secretary, I have been under the impres- sion that these hearings all along, as highly technical and important as this subject is, that the interpretation that had been placed on the Delaney clause was that there had to be an affirmative showing that it would not induce cancer, and that is a most important point in the con- sideration of this whole matter. It is one thing if it is shown that it induces cancer when included in the diet, and no one would argue with you about that. But then the question arises: Does the industry have to show beyond any doubt or convince the Department that an additive will not induce cancer? Now I would like to know what is the policy of the Department. I think it will help clear up this matter. . Secretary FLemaine. All right, Mr. Chairman. Let me see if I can state it as we understand it. As you know, the law. 514 COLOK ADDITIVES The Cuatman. One is an affirmative showing and the other isa negative showing. Secretary Fiemmina. Yes. The Cuatrman. Now which is true? Secretary Fieminc. As you know, the law places upon the com- pany that proposes to use a particular substance as an additive to food the responsibility of coming to the Government, and on the basis of tests that it has conducted, demonstrating to the Government that its use under the proposed conditions would be safe. And under our basic policy, as well as under the Delaney clause, we have said that where those tests show that a substance will induce cancer when included in the diet of a test animal, that it will be banned. Tt cannot be used under those conditions. This is our interpreation of the Delaney amendment, and it is our conviction as to sound public policy. Now as I pointed out in my statement, Mr. Chairman, I don’t want to suggest again, as apparently maybe we have inadvertently on other occasions, that this does not allow for any exercise of judgment. There is provision made there for the exercise of scientific judgment. The Cuamman. Where is it? Secretary FLemmrinc. As to whether or not the substance will induce cancer when included in the diet of an animal. Certainly, that is a determination that can be made only by scientists, and on the basis cf scientific evidence. But once that determination has been made, then we do not feel that anybody in the executive branch should be able to exercise judgment, because we don’t think that there has been any showing made to the effect that there is any reason at all for adding that additional risk to what all of us are already subjected to in this area. The Cuatrman. Will vou point out the language to me? Secretary FLemmine. The Delaney amendment language? The Cuairman. No, the language that you just mentioned which gives you the authority to exercise judgment. Secretary Firemmine. You mean the language in the Delaney amendment that gives us authority to determine whether or not it is, in fact, a cancer-inducing substance ? The Cratraan. I am just taking your own statement, Mr. Secre- tary. You have just said that there is some misunderstanding. Secretary Freamrne. About the Delaney clause? The Craman. That there was in this provision authority to use judgment as to whether or not it was cancer-producing. Secretary Fremine. All right. I now have in front of me H.R. 7624, Mr. Chairman. The Craimman. Yes. Mr. Dixcett. Which, incidentally, is sponsored by the chairman of this committee. The Cuarman. And introduced at the request of you, Mr. Secretary. Secretary Fremnine. That is correct, Mr. Chairman. I can as- sure you that Iam very happy to acknowledge the fact that we did make such a request. COLOR ADDITIVES 515 First of all, I am going to read the Delaney clause in the food addi- tives amendment. I will read that first. It says: Provided, That no additive shall be deemed to be safe if it is found to induce eancer when ingested by man or animal, or if it is found— and I emphasize the word “found”— after tests which are appropriate for the evaluation of the safety of food addi- tives, to induce cancer in man or animal. Now, that finding has got to be made on the basis of scientific evi- dence. The evidence has to be weighed by component scientists and a conclusion reached as to whether or not this evidence establishes the fact that the substance does induce cancer. I am not sure who was the original author—I mean who worked up the language originally as far as the Delaney clause is concerned. But Tam sure that the person who drafted it originally certainly had in mind that this finding would have to be made on the basis of care- fully evaluated evidence. Now, if I may turn to the color additive proposal that is pending before this committee, it says : A color additive, (1) shall be deemed unsafe and shall not be listed for any use which will or may result in ingestion of all or part of such additive if the additive is found— and I emphasize the word “found” again— to induce cancer when ingested by man or animal, or if it is found, after tests which are appropriate for the evaluation of the safety of additives for use in food, to induce cancer in man or animal. Certainly, no responsible public official could make such a finding except on the basis of a careful weighing and evaluation of evidence pointing in this particular direction. It is my understanding, Mr. Chairman, that scientists are not always of one mind as to w hether or not the evidence that is presented does point to the conclusion that it has induced cancer when included in the diet of an animal; that this is something on which scientists can and do disagree from time to time. Am I correct, Dr. Mider? Dr. Miver. Yes, sir. The Cuarrman. That is the big problem that we have here, because there are so many that have diss ugreed on this thing. Secretary Fremaine. And this is w hy I think, Mr. Chairman, and T am glad that you press me on this point, because I think this is why it is important to—. The Cramman. But you haven't satisfied me on the other point, Mr. Secretary. Secretary Fremoine. Which other point, now? The Cuairman. The other point is: Do you, as a matter of policy, require industry to show that it will not induce cancer in order for it to become safe ? Secretary Firemoine. I will ask Commissioner Larrick to reply. Dr. Larrick. Our practice, Mr. Chairman, is to require the manu- facturer of a new chemical additive to present ordinarily 2 years of experimental feeding. Two years in the rat. is comparable to the life- span of a man. 516 COLOR ADDITIVES We like a second animal to be used in addition to the rat, so that we will pick up species variation. Now, if in that first 2 years of feeding any serious suspicion of carcinogenicity is raised, then we do not allow the chemical because we can’t honestly make a finding that it is safe, because we don’t know. But in the vast majority of cases—and I only know of a very few exceptions since you have given us the pesticide law and the chemical additive law—the 2-year feeding has satisfied it, and the material either goes into the food supply or is put out of the food supply on the basis of the 2-year feeding. Now, the only time when you might approach the necessity of a negative finding would be when your 2-year work or some other scien- tific work makes the scientific fraternity grossly suspicious that if this material were fed to man, it might cause cancer. And only then does that come into the picture; and, as I have said, it has rarely come into the picture. The CuHamman. You remember during the course of the hearings we had some weeks ago there were various representatives of the industry in the package business that were meeting with your De- partment. I think the last report I had was that some of their fears were resolved, ina way, but Iam not sure about that. I don’t think that I was satisfied. I don’t know if that was worked out completely or not. Dr. Larrick. No, I wouldn’t say it is worked out completely. The substances that they brought to us—and this included the paper manufacturers, the container manufacturers, and the other people that make things that foods go into—the materials that they presented to us fell into three categories: (1) A category where we could on the basis of our present knowl- edge say there is no migration of this material into the food, so it isn’t a food additive; or (2) There is migration, but we know it is in an amount and of a kind that is safe, so those we clear; (3) Then there was another class where we don’t know. But the probabilities are that there is no harm, and that legislation gives us the right under those circumstances where we can make a finding that the possibility of harm is quite remote, to give them a year’s time within which to complete their testing. So we have allowed some things in without hesitation. We have put the others in this list where they have an additional year. And then there were some materials which we and they decided would best be discontinued. And that is where the matter stands, and they are working energetically to complete their testing procedures. The Cuamaayn. Then it is not a fact that the policy of the Depart- ment in the interpretation of this language, requires the industry to show that an additive does not induce cancer in order for it to be safe. Dr. Larrick. That is quite correct. The Cuairman. I am glad to get that cleared up, and I think industry will have probably a different viewpoint on this thing, if it can be cleared up. Now, I understood the issue at that time was that some of these containers that have been used a long time—and, as you said, there COLOR ADDITIVES 517 were some that were recognized as safe without any question—but that the producers of these containers were placed in the position that they could not convince, or prove, to your Department that there was no cancer-producing element in connection with it. That is what I understood the big controversy was about. They knew they were safe, but the scientists had not developed a technique yet where they could say beyond all question of a doubt. If you interpret this language the way you have just said, 1 think it lessens somewhat. the controversy. Secretary FLemmine. Mr. Chairman, could I put it this way. Commissioner Larrick has indicated that when a person files ap- plication for the use of either a color or a food additive, that under the law he must then file with the Department the results of his test- ing program. The Department ordinarily requires a feeding program of 2 years, and, as he indicated, ordinarily would require that the testing be carried on with two types of animals, not just one, but two. This they must do. If those tests The Cuarrman. And I don’t think anybody in industry has quar- reled about that, have they? Secretary Fiemmine. I wouldn’t think that they would, because certainly, it seems to me, that this is a duty that they owe the con- suming public. Now, if these tests show that these substances have induced cancer when ingested by these animals—and, as I said earlier, this question of whether they do or do not show is a matter for scientific determina- tion and the exercise of scientific judgment—but if they show that they have induced cancer when included in the diet of one or both of these animals, then under the law we must ban the use of that particular substance. Mr. Chairman, I think part of the misunderstanding has developed, as I have discussed it with our people, out of what happens after that, I mean, here they have carried on the 2-year test. They have sub- mitted their results of the tests. In the judgment of competent scientific personnel these tests demonstrate that cancer has been in- duced in one or more of these animals, or raises serious question. Then the question is: Does that shut the door once and for all? This is just a 2-year test. ow, the Department, because the manufacturer may come back and say, “Well, I think if there were longer tests, that maybe you would arrive at a different conclusion,” the Department is perfectly willing to have them carry on longer tests, and present the results of those longer tests to the Department for evaluation. As I understand it, under those conditions, I mean having arrived at this first result after the 2-year study, under those conditions the Department would normally ask for about 5 years of additional test- ing. But this has happened in only one or two situations, Out of that has grown the feeling that we would require a 7-year testing program, whereas, basically, the length of the test is ordi- narily 2 years. It is only when the results of the tests that they, themselves, have carried on raise real question as to carcinogenicity that we use—and 518 COLOR ADDITIVES we think properly so—our discretion; that in view of the question then we say it can’t be used. Then they come back to us and say, “Well, we think if we carried on additional tests, maybe you wouldn’t arrive at that particular conclusion.” And, of course, we don’t deny them the right to carry on additional tests, and we shouldn’t. We will evaluate those when they are over. The Cuairman. Mr. Younger, I apologize for utilizing your time. Mr. Youncer. That is perfectly all right, Mr. Chairman. I have enjoyed it. There are two points that I would like to clear up. If I understood the testimony a while ago, it was that cancer of the stomach has been on the decrease ; is that correct ? Dr. Miver. That is correct, Mr. Younger. Mr. Youncrr. Cancer of the lung has been on the increase ? Dr. Miper. Yes, sir. Mr. Youncrr. The only substance that goes into the lung is air, isn’t it, or is it? Dr. Miner. Iam afraid not. Tt isan important organ. Mr. Youncer. Then it could possibly be something else even in the diet ? Dr. Miprr. Yes, sir. Mr. Youncer. That produces lung cancer? Dr. Mmer. It could be. Mr. Youncer. Other than smoking. You have no tests, no infor- mation on that subject yet ? Dr. Miner. No, sir. Mr. Younaer. Now, one other question that bothers me of your testimony, Mr. Secretary. I wonder if this is true. Should you conduct tests of some foods, say carrots, and you found that by testing those with animals that carrots produced cancer, you have no authority under the law to take food off the market even though it is proven by your tests to produce cancer; is that true? Dr. Larrick. No, sir. If it is proven positively to be a dangerous substance, under sections of the law that have been in effect since 1906 the Federal court has the right to seize it and remove it from the market. Mr. Youncer. Well, now, that is different than what you said a while ago, because you said you had no authority over anything except that which was an additive to food. Secretary FLremminc. Mr. Chairman, I think whatever misunder- standing may have developed on that grew out of the discussion with Congressman Williams on tobacco and on smoking. Of course, that is not classified as a food. Mr. Younarr. No. Secretary Fremmina. And, consequently, the Department never has had any jurisdiction over that. I think once somebody alleged that by smoking a particular brand of cigarettes, you could reduce your weight, and I think that the Department regarded that as a claim over in the drug area and did move in and take some action. But outside of some action of that kind, the Department has no authority in that particular area. COLOR ADDITIVES 519 I am sorry, you and I were talking back and forth about additives, so that my stress was on that. But, certainly, as Commissioner Larrick has pointed out, since 1906, if it can be demonstrated that a food would have the kind of results that he indicated, the Department does have authority to take action. But tobacco and smoking does not come within any definition of the law under which we operate. Mr. Youncer. I have a resolution that was sent to me by the berry growers of California called the California Berry Advisory Board. The substance of their resolution is this: Be it resolved, That the boysenberry growers and processors, meeting at the University of California at Davis, November 18, 1955, urgently recommend action be taken to authorize public regulatory agencies to condemn food products only on the basis of a proven scientific fact. Are you in any way condemning food products other than on the scientific facts ? Secretary FLemmine. I certainly hope not. Mr. Youncer. Then you would concur with this resolution ? Dr. Larrick. Mr. Younger, the Food and Drug Administration has no authority of its own to condemn anything. Any punitive action that we take, either a criminal action, an injunction, or seizure of mer- chandise, has to be done by our taking the facts to the U.S. Depart- ment of Justice; getting it into the hands of the U.S. attorney; a libel or other legal document is presented to the Federal judge; he signs it; the merchandise is confiscated or the action is started; and if any- one disagrees with the facts we allege, he is entitled to a trial by a jury of 12 people. I think the procedures are completely fair in that respect, sir. Mr. Youncer. I just have one other question. The Cuamman. On that point, will the gentleman yield? Mr. Youncer. Yes, sir. The Cuarrman. Is that the procedure you took when you took all the cranberries off the market ? Dr. Larrick. Yes, sir; we seized the cranberries. The Cuarrman. How? Dr. Larrick. By libel filed in the Federal courts. The Crratramanx. In Washington, Wisconsin, Massachusetts ? Dr. Larrick. We didn’t seize them until they moved in interstate commerce, but the ones that we found on the market contaminated with aminotriazole were seized pursuant to libels of condemnation filed with the Federal courts. The Cuatrman. I am glad to have that information. The news- papers, of course, gave the indication that your Department just went m and seized them wherever you found them, on the shelves, im whole- sale houses, and everywhere else. Dr. Larrick. We have no power to do that, and we don’t want that power, The Cuamman. And you did not just go in on your own in your own Department ? Dr. Larrick. No. The Cuarrman. And seize all this? Dr. Larrick. No, sir. We filed libels with the Federal court. The U.S. marshal seized them. 520 COLOR ADDITIVES The Cuarrman. That is certainly interesting. Secretary FLesouine. Mr, Chairman, I think that the detailed state- ment that I The Cuarrman. You got the credit; the U.S. marshal didn’t. Secretary Fiemmine. I can testify to that, Mr. Chairman. Mr. Chairman, I think that the detailed statement that I filed with the committee, when I appeared on January 26, regarding that partic- ular matter, bears out definitely what Commissioner Larrick has said. Mr. Youncer. Just one question. As I understand it, where stilbestrol is used in the preparation of food for animals, it is permitted in a number of cases, isn’t that true? Secretary FLemmine. Yes. Mr. Congressman, this illustrates one of the points that I have been making in my testimony. Where we have found that its use in con- nection with the feed for cattle does not leave any residue in the food that is consumed by man, we have taken no action; and we are sug- gesting that the Delaney amendment be amended to make that doubly clear: that that is the policy of the Congress. Mr. Youncer. Now, you have a certain food for cattle that has that substance in it. Now, the chemical industry develops another chemi- cal and they prove to your satisfaction that it is not carcinogenic in any way. Do you permit them to use that chemical with stilbestrol in the mixing of food ? Dr. Larrick. This question becomes very complicated because the food additive amendment says that any previous permissions that have been given to use substances in food shall be continued. We had allowed a number of firms to add stilbestro] to the feed of animals and you have these permissions still in etfect—as you have described. But the law further says that if an article is capable of causing cancer when consumed by mouth by man or animals, then no further permissions shall be granted. Now, that brings about the very bad situation where a small feed manufacturer or a large feed manufacturer on one side of the street can continue to merchandise his feed containing stilbestrol, but be- cause we are not allowed by the statute to issue any new permits, if the man across the street makes his application to us we have to turn it down. So, if the man who has the effective application for stilbestrol wants to add something new to it and he thereby has to file a new petition, we are not. permitted under the statute to make his petition effective. That is why the Secretary is recommending that if the substance does not go into the food that human beings eat, and if the substance does not. harm the animal, that that excep‘ion to the Delaney amend- ment should be permitted. And we would then be relieved of an administrative problem that I think is unfair. Mr. Youncer. Then the food manufacturer could proceed with an added chemical provided it was safe? Dr. Larrick. Right. Mr. Youncrr. And the amendment would cure that defect ? Dr. Larrick. That would cure that defect. Mr. Youncer. That is all, Mr. Chairman. The Cuarrman. Mr. Dingell. COLOR ADDITIVES 521 Mr. Drncett. Mr. Chairman, I look at the clock and I note that it is 10 minutes to 12. I was wondering if we could have some thought from the Chair as to how long we will meet today. ; The Cuarmman. We want to proceed until we get through with this witness. Mr. Drnecett. I would like to have every other member have a chance to ask a couple of questions. The CHamman. You may proceed, and we will see how we get along. I do hope wecan get through before we have to adjourn, unless there are many questions by the other members. Mr. Dincett. Thank you, Mr. Chairman. I was particularly interested in this business of new drug applica- tions that we have been discussing. Under the so-called new drug sections, would you be precluded from removing stilbestrol from the market if you were to suddenly find that there was some new hazard or some tremendous hazard that requires the cancellation of the out- standing permits, so to speak, of the outstanding licenses to persons who have been using it under preexisting license from Food and Drug? Secretary Friemminc. Mr. Congressman, there is a procedure set for'h in the new drug section of the law under which we could pro- ceed under these circumstances. As you know, it is a more formal and a more involved procedure than the procedure that we would follow under comparable condi- tions dealing with a pesticide or dealing with a food additive; am I correct on that? Dr. Larrick. Yes; I might add, sir, that the action that was taken with respect to stilbestrol was a voluntary action. But three of the firms who agreed to temporarily discontinue the distribution of stil- bestrol] disagree basically with the Department’s position, and so they have asked for their rights under the statute. We have set a hearing, a date for a hearing, and a hearing has been in progress now for some weeks whereby the Government presents its evidence and the other side is presenting its evidence. Then, after that, that record is compiled and it is a private hear- ing; the aggrieved party is entitled to appeal to the Secretary. If the Secretary rules against him, then he has an appeal to the U.S. district court, a very good process, but it is not a quick process. Mr. Drncetu. In the event that this proceeding is adverse to the applicants who desire to begin or to continue using stilbestrol, what impact will this have on other stilbestrol users on the market now ? Dr. Larrick. It would be our obligation, if we revoke the applica- tions for stilbestrol, to revoke them for each of the parties involved individually. Most of them agreed to having their permits canceled, but three did not. And after that, if we were to prevail and they would still continue to merchandise it, it would be an illicit article in commerce. And, as you know from your experience in Detroit, we would file a libel, prob- ably a criminal action, too. Mr. Drncett. Mr. Secretary, I want to commend you and compli- ment you for your statement this morning, for the very fine statement which was also made by Commissioner Larrick and by Dr. Mider. 522 COLOR ADDITIVES I have been very much impressed by the work of Commissioner Larrick and Dr. Mider, and also by the testimony you have given here. I would like to conclude by just asking one thing. Will you again comment on the judgment that the Delaney amendment, as in the resent law and as in the bill before us, confers on you and on the Food and Drug Administration with regard to whether or not a sub- stance is a cancer producer in an animal or a human being? Secretary Fiemmine. I will be very happy to, Congressman Dingell, because, it seems to me, that at times the Delaney clause has been unfairly characterized on that particular point. As I indicated in reading the clause as it appears both in the pro- posed color-additive legislation and also in the food-additive legis- lation, there must be a finding that the substance has induced cancer when ingested by man or animal, or there must be a finding after tests which are appropriate for the evaluation of the safety of additives for use in food that they have induced cancer in man or animal. This finding is a scientific judgment based on the weighing of scientific evidence, and it is certainly never, as I understand it, just open and shut, necessarily. Let me put it this way. There certainly are situations where scientists differ as to how the evidence should be weighed and what the conclusions should be. But, as I see it, we have the responsibility under our general au- thority and under the Delaney clause to weigh that evidence and to arrive ata conclusion. As Commissioner Larrick has pointed out a number of times, cer- tainly, if people want to take issue with the way in which the evi- dence has Neen weighed and the conclusion that has been arrived at, there are ways of doing so. Mr. DinceEtu. This is, in effect, then, the exercise of scientific judg- ment by scientific people as to whether or not this substance creates cancer In a test animal or in a human being. Secretary Frexminc. That is right. It must be, as I see it. Mr. Dincety. Furthermore, Mr. Secretary, you have authority to eall in independent scientists not employed by the Department ? Secretary FLemmine. We certainly do. We have ample authority along that line both in the Public Health Service and in the Food and Drug Administration. Mr. Drnceti. And with specific emphasis on determinations under the so-called Delaney amendment, or the cancer clause ? Secretary FLemuinea. We certainly do, ample authority. Mr. Dincett. And, as a matter of fact, you have done this in the past, have you not, Mr. Secretary ? Secretary Ftemaine. Yes. Take aminotriazole which, as you probably recall, is under the pesticide amendment. If the manufacturers of that particular pesti- cide had not agreed with the determination that was made by the Food and Drug Administration, they had the right either to appeal or had the right to request us to set up a scientific panel on the rec- ommendation of the National Research Council. This is written into law. Mr. Dincett. Did they choose to do so? COLOR ADDITIVES 523 Secretary Ftemmine. They did not. We recommended, of course, that a similar provision be inserted in the food-additive law. That recommendation was not accepted. We would have no objection to a similar provision being in the color-additive law. Mr. Dincett. Excepting you can do it as of now ? Secretary FLEmMinG. We can do it and will do it. Mr. Dincett. And have done it in the past ? Secretary Ftemming. That is right. Mr. Dincett. Whether by law or not ? Secretary FiemMrna. The fact of the matter is, Mr. Congressman and Mr. Chairman, I think I should point this out to the committee: that we have, or I have, taken action under which, before a final deter- mination is made by us as to whether or not a substance induces cancer, the evidence will be considered by a panel made up of representatives of the Food and Drug Administration and the Public Health Service, with the assistance of a scientist or scientists from the Department of Agriculture, and with the assistance of scientists nominated by the National Research Council. Mr. Dincexy. One last question along this line. In the tests that are run by which the industry tests a certain sub- stance for safety, the tests are actually performed by industry under the guidance and approval of the Food and Drug Administration; isn’t that true? Dr, Larrick. I would say that a great many of them are performed by universities that are employ ed by industry. There are some indus- tries that have their own testing facilities. But they are not required to come to us ahead of time and get approval of their proposed testing. Most. of them do that, but as a legal matter they are not required to submit their data or their plans to us until the work is completed. But at that stage we have plenty of authority to decide whether or not it is valid work honestly done. Mr. Drncetu. So the exercise of judgment under the food additives and pesticide law and under the proposed bill before us actually would be largely in the hands of the industry concerned rather than exclu- sively in the Food and Drug’s hands, as they seem to indicate? Dr. Larrick. We would certainly say that, in part, they participate very ex‘ensively in the scientific judgment, but we have the final re- sponsibility of appraising their data, and being sure that we give the public the protection that the Congress has intended. Mr. Dinceizt. Now, while you do run independent tests within the framework of the Food and Drug and within the framework of its responsibility, nevertheless, the bulk of these tests probably are per- formed by industry acting under the supervision of Food and Drug or in consultation ‘with Food and Drug, with final approval of the tests invested in the hands of the Food : and Drug Administration in the Office of the Secretary ? Dr. Larrick. You are quite right. Mr. Dixcetx. Gentlemen, I certainly thank you for a very fine exposition. I compliment you, Mr. Secretary, for the fine work you are doing in consumer protection through the Food and Drug Ad- ministration, and other agencies under your leadership. Secretary FLEMMING. Thank you. The CHarrman. Mr. Nelsen? 56123~-—-60-——-34 524 COLOR ADDITIVES Mr. Neusen. It is my understanding, Mr. Secretary, that there has been a Presidential Scientific Committee that has made a study. Have you any knowledge as to whether or not that study is complete # Secretary ftemminoc. As a White House statement indicated some weeks ago, the Pr esident did request information from the scientists in the Department of Agriculture, in the Department of Health, Edu- cation, and Welfare, and from his own Science Advisory Committee, which is located in the White House. That information has been supplied. I do not know as to whether or not a report has actually been made to the President, and, of course, consequently, I do not know what action, if any, he may take. Mr. Nersen. You have not studied the report in your office to this date, or have you seen the report ? Secretary Ftemmine. We have had the opportunity of consulting with the President’s Scientific Adviser, Dr. Kistiakowski, and also the Chairman of the President's Science Advi isory Committee. We have commented on various points that have been raised. But, as I say, I do not know what the final content or form of the report may be; nor, obviously, do I know what may be the Presi- dent’s reaction. Mr. Nersen. Could I suggest that this committee have this report before we finally take action? This is a very complicated process, obviously, and it would seem that we should have that report and your observations relative to the report before we take action. Secretary Fremminea. Of course, this is information that was re- quested by the President, and, obviously, it wouldn’t be appropriate for me to comment on what the President may or may not do with the information. Mr. Netsen. Thank you. No more questions, Mr. Chairman. The Cuarrman. Mr. Hemphill? Mr. Hemrniuy. Mr. Secretary, I would like to direct your atten- tion to the last paragraph of your statement on page 4. Secretary FremMina. Yes, sir. Mr. Hempuitt. Including the first four lines of page 5. Am I to assume from that statement that this legislation, if it is passed—that you are not going to have any authority that you do not now have? Secretary Firamine. In respect to this particular matter that we have been talking about; not in respect to the color additive situation generally. I mean the color additive bill does, of course, confer additional au- thority on the Department. But in respect to determining that we will not permit a cancer-inducing substance to be used—we feel that we do have that kind of authority under the broad delegations that have been made to the Department over the years by Congress. Mr. Hempnity. Then, so far as your Department is concerned, the Delaney amendment w ould not give you any authority that you do not now have ? Secretary Fiemmine. As I understand it, when Commissioner Lar- rick appeared before this committee in connection with the Delaney clause as it was proposed for the food additives amendment, he made the point that we had that authority and would exercise it along the line of the Delaney amendment. €OLOR ADDITIVES 525 Mr. Hempams. Then can I assume the Delaney amendment would just be window dressing insofar as legislation is concerned ? Secretary Fremmine, No, Mr. Congressman, I do not so interpret it. As I indicated in my testimony on J anuary 26, and as I tried to em- phasize again today, I think that in view of the seriousness of this problem, a great deal can be gained by the Congress joining with the executive branch to give added assurance to the consuming public that this is the kind of policy that they can count on being followed. In other words, I see a lot to be gained by the executive and legis- lative branches pr resenting a united front on a matter of this kind. Mr. Hempuut. I certainly subscribe to that. I just don’t want to be put in the position, as a ‘representative of the people, of perhaps passing some amendment which might give rise to a belief that here we have taken care of this situation which is continuously being eriticizd in our Nation. I don’t want the Congress, nor the Reresentative of my district, being said to be put in a position of having done something that we haven’t. That was the reason for my question, Do you think there is any possibility of our saying to the public, if we adopt the Delaney amendment, that we are giving assurance now that we are not going to have these’ cancer- causing ingredients in the foods which are shipped i in interstate commerce ? Secretary Fremmine. Of course, any action that is taken by the Congress in this general area—and I am not just talking about the cancer area now, but I mean in the whole area of food, drug, and cosmetics—has to be subject to certain qualifications: namely, the ability of the Department to keep up with situations as they develop, whether or not it has sufficient resources to do that, and so on. So I think that it would be unfair to create the impression that because this was included that no one has got to worry about it at all any more. I think the impression that would be created is that the Congress and the legislative branch, working together, are determined to do ev erything that it is possible to do in order to cut down on the risks that people may be up against in this particular area. I think, for example, Mr. Congressman—and I wasn’t here when the food additives legislation was—well, it was passed just after I took office, and I didn’t participate in the hearings at all—but as I look back on it, it seems to me that it was a very w *holesome thing for the Commissioner of Food and Drugs to say to this committee this is the policy that we will follow. And then for the Congress to, in effect, say, “Well, we certainly agree with you that this is a sound public policy, and because we agree with you and because of the importance of this par‘icular issue, we are going to state our conviction and our belief affirmatively b including the clause that Congressman Delaney suggested should be included.” And T feel the same way as far as the color additive legislation is concerned. I think this is particularly true in view of the discussion that has taken place revarding it. The only reason I included this statement was I wanted to make it perfectly clear that if this clause were not included, we would still feel that as public officials this is 526 COLOR ADDITIVES the policy that we should follow in the discharge of the overall duties and responsibilities that have been placed on us by the Congress. In other words, I wouldn’t want any misunderstanding on that to develop in the public mind. Mr. Hempuity. I have in mind last year you issued some ruling or authority. As a result of it some industry—I won’t name it—down in my part of the country called on me. We got in touch with the people, and they assured us that the situa- tion wouldn’ t arise. So the industry asked if I would issue a press release on it, and I refused to do so. I said to issue a press release would give the public, depending upon my supposed knowledge, the wrong information, or at least arouse suspicion of the product, or something of that nature. And I thought that it best be handled just as it was handled be- tween your Department and the industry through my office. I thank you for it. But I didn’t want us to get into that same sort of posi- tion with the Delaney amendment by saying we have got it all taken care of and now you can eat what you want to and the food is not going to be a cancer-causing agent. That is my reason, Thank you very much. Secretary FLemmrne. I think a fair statement would be that we are headed in the right direction and that we are doing everything we can to give you protection, as we talk to the consumer. Mr. Hempniuy. I subscribe to that. Thank you, Mr. Chairman. The Cuarrman. Mr. Keith? Mr. Kerrn. Thank you, Mr. Chairman. Mr. Secretary, on page 2 of your statement, “Comments on Testi- mony on the C: incer C lause in FIR. 7624,” dated May 9, 1960-——— Secretary Fremmine. The Food and Drug memorandum, you mean ? Mr. Kerrn. Yes. You commented that it has led the Food and Drug Administration over the years to follow a policy, of requiring a safety factor of 100 for new chemicals foreign to man’s food. That is, animals should show no adverse effect. when they consume 100 times as much of a chemical as is proposed for man’s diet. Now, was this the factor that was used in the case of aminotriazole? Dr. Larrick. Well, the facts there were that when rats were fed 10 parts per million of the chemical they developed a cancer of the thyroid. Mr. Kerra. In 10 parts per million? Dr. Larrick. Ten parts per million was the lowest dose at which cancer was produced. We never did feed it at a level where there was no effect. But producing cancer would outlaw it regardless of a 100 to 1 tolerance that we applied to other tvpes of injury to the animal. Mr. Kerru. Who conducted the tests that found cancer at 10 parts per million? Dr. Larrick. The laboratories that were employed by the firms that were merchandising the weed killer. Some of it was done in Amer- ican Cyanamid Laboratory ; some of it was done in a commercial lab- oratory out here in Virgina; very good laboratories, both of them. Mr. Kerra. Within your Department, who reviewed this particu- Jar chemical analysis ? COLOR ADDITIVES 527 Dr. Larrick. Dr. Lehman, the chief of our Division of Pharma- cology, and his associates in his division and other scientists in the Department. We have a routine whereby we review it pharmacologically, medi- cally, if necessary, chemically, and we pass the document around among the various scientists so that the fina] decision is an institutional decision, rather than an individual decision. Mr. Kerrn. What role did Dr. Stewart play in all of this, if any? Dr. Larrick. I don’t think Dr. Stewart made any—played any role in it. He isascientist at the National Cancer Institute. Dr. Miper. You mean Dr. Harold L. Stewart ? Mr. Kerru. Yes. The one that was on the panel. Dr. Larrick. He played no part. Mr. Kerru. It was pointed out by someone here that the cranberry people didn’t have the advantage of the panel in the case of deter mining whether or not this course of action was sound. I might say that there is no opportunity for the third party, the injured party, in this instance to have the advantage of the panel. It was the American Cyanamid that Dr. Larrick. There were two chemical firms involved. Both of them were petitioners, and either of them, under the statute, could have applied for and been entitled to the panel. I do not think that a third party under the Jaw as it is written would be entitled to the panel. Mr. Kerru. Do you know why they didn’t request such? Dr. Larrick. I don’t know that, sir. Secretary FLemmine. Could we just check your point, Congress- man Keith, on the third party law? Dr. Larrick. The w ay we have administered it is that anyone who has registered the substance w ith the Department of Agriculture and applied to us for a tolerance is entitled to have this committee ap- pointed and anyone else is not. Mr. Kerrn. What is the proper time to ask for such a panel? Dr. Larrick. There are time limits in the statute. I have for- gotten exactly what they are. I think it has to be done within 90 days after the Department of Agriculture certifies to us that the chemical is useful to agriculture. The section of the law that applies, Mr. Keith, is section 408(d) (3) of the Federal Food, Drug, and Cosmetic Act. It says: In the event that the person filing the petition requests within 90 days after certification of usefulness by the Secretary of Agriculture under subsection 1 with respect to the pesticide chemical named in the petition, that the petition be referred to an advisory committee, or in the event the Secretary of Health, Education and Welfare within such period otherwise deems such referral neces- sary, the Secretary of Health, Education, and Welfare shall forthwith submit the petition and other data before him to an advisory committee to be appointed in accordance with subsection (g) of this section. That subsection (g) provides that the Secretary, or whoever he has delegated the responsibility to, shall ask the National Academy of Sciences to designate some indiv iduals that are knowledgeable in this field. Then the Food and Drug Administration appoints them. So the Food and Drug does not participate in the choice of the scientists who serve on this advisory panel. And the committee’s findings are not binding. They are simply advisory. 528 COLOR ADDITIVES Mr. Kerra. What role does such a panel, or a similar panel, play in the early decision, the fundamental decision whereby a subject 1s deemed to be a carcinogen so far as animals are concerned ? Dr. Larrick. It depends on the nature of the problem. But. if the problem ‘is so clean cut that we feel that our scientists can handle x without any outside consultation, they do so handle it, and they make a recommendation to the administrative officers, and we act on it. But if in the judgment of our scientists the question is sufficiently close so that they want the benefit of skills that are not contained within the Food and Drug Administration, they are at liberty to go to the Public Health Service, to go to the National Research Council, to go to the universities, or to go wherever the scientific information that we need exists and get that advice. Mr. Kerrn. Is there any place for a potential employer of the chemical or substance under question at that time to request that a panel’s action be taken ? Dr. Larrick. No, not at that stage. There is no authority in the statute whatsoever for the petitioner to have a panel under food addi- tives, and the time limits allowed there are so short that it really hurries us to get that sort of consideration. Tn the pesticide amendment they have it as an absolute right. They have to pay the costs themselves. The industry pays the costs, and it has been used on several occasions. Every time it has been used, we have followed the advice of the advisory panel. Under the law a user of the weedkiller, of the chemical, would not have the legal right to ask for a panel, but all he would have to do to acquire that legal right would be to file a petition. Actually, we have been very free to get outside advice at the sug- gestion of industry or at the suggestion of our own scientists, and we would welcome, if the Congress cares to do it, to see this advisory committee principle go through the entire Pure Food. and Drug Act. But we would have to change the time limits within which we must act on a petition so that we could give the panel time to consider the petition, and, secondly, I should think that if industry or anyone else wants to have the panel convene, they should pay for it. I don’t think it should be paid for out of the Treasury. Mr. Ketru. Thank you, Mr. Chairman. The Cratrman. Mr. Brock ? Mr. Brock. No questions. The Cuatrman. Mr. Springer? Mr. Sprincer. Mr. Secretary, just one or two questions about the cranberry matter. Are youa lawyer, Mr. Flemming ? Secretary Fremmine. All I can say in response to that is I am a graduate of a law school, but I have never practiced law. Mr. Sprincer. Mr. Larrick, are you a lawyer? Dr. Larrick. No, sir; I am not a lawyer. Secretary Fremminc. We have got some lawyers here. Mr. Springer. Did you handle this matter, the cranberry matter? Dr. Larrick. Yes. Mr. Sprincer. You are familiar with it 2 Dr. Larrick. Yes. I don’t know about all of it, but I am very familiar with it. COLOR ADDITIVES 529 Mr. Sprincer. I am going to direct this question at both the Secre- tary and you. Did the Department of Health, Education, and Welfare follow all of the legal prerequisites of the law and the regulations pursuant thereto prior to the seizing of the cranberries in the fall of 1959? Dr. Larrick. The answer to that is “Yes.” Secretary FLemmine. I concur in that. Mr. Springer. I ask this of the Secretary. Mr. Secretary, I have only read the newspapers, and, therefore, I am only acquainted that far. It was my understanding that you had presented a plan to the Ways and Means Committee which was sub- stantially the administration plan for health benefits for those above 65 years of age; am I correct? Secretary Fiemmine. Yes, sir. I presented a plan last Wednes- day and the testimony—at that time I presented to the committee a written statement, and that written statement was released to the press, and it was on the basis of that that the stories to which you refer were written. Mr. Sprincer. In that plan is there any provision for social security taxes? Secretary FLemminea. Not in our plan, no. There is, however, I should say, Mr. Congressman, if our plan were carried out—I mean were accepted and were carried out—it would re- quire,, in my judgment, some amendments to title I of the Social ecurity Act. Mr. Sprincer. Just in short, substantially what would those amend- ments provide? Secretary Fremmine. I would have to get into the whole plan. But let me put. it this way. The plan that we have presented, at least the basic part of the plan, rests back on the same basic philosophy that is reflected in title I, particularly as title I has been amended to include medical services for those who participate in the Federal-State public assistance program. One portion of our plan—in fact, an integral portion of our plan— would result in quite a major change in the way in which that partic- ular part of the public assistance program would be handled, Mr. Sprincer. You are talking about public assistance only? Secretary FLemminc. When I talk about title I, that has reference to old-age assistance; yes. Mr. Sprincer. Are you talking about old-age assistance? Secretary Firemmrina.-The part I am talking about is the old-age assistance category. ; Mr. Serincer. Another portion would provide for those on social security above the age of 65 years, or does your plan just encompass all those above 65? Secretary Ftemsine. Yes; we do not relate our plan to the old-age and survivors insurance program at all. Mr. Sprincer. That is what I want to find out. Secretary FLemmine. That is right. But our plan is related to the Social Security Act insofar as it relates to title I. But it has no refer- ence to the old-age, survivors, and disability insurance program. In fact, that is one of the positions that we have made, as you know, very emphatically : that, in our judgment, a program in this particular 520 COLOR ADDITIVES area should not be related to the old-age, survivors, and disability in- surance program. Mr. Sprincer. The reason I raise that is that all the health matters come within the jurisdiction of this committee, and there is one that used to be Health and Science. Secretary Fuemmrne. Right. Mr. Sprincer. It is now Health and Safety that comes before this committee. Have you talked with, or had any of your legal staff talk with, the Department as to where such a bill, if introduced, would go? Secretary Fremmine. No; we have not, Mr. Congressman. As you know, we have not proposed any bill for introduction. The Ways and Means Committee, as I think everyone knows, has had under con- sideration for a long period of time the question of what should be done in this area of the aged. About 10 days or 2 weeks ago, knowing that we were working on a program, the chairman of the committee, Mr. Mills, asked me whether or not I thought that by such and such a date I would be in a position where I could outline to the committee what we had in mind, I told him that I thought there was a very good chance of my being in such a position, and I would certainly work toward such a deadline. I did work toward such a deadline. I had to ask for an extension of 1day. But within the 1 day, I met the deadline. And so what I did was to outline to the full membership of the Ways and Means Committee our feeling as an administration as to the best way in which to deal with what we recognize is a very major problem. So that we have not transmitted any formal bill to the Congress either by letter to the Speaker or to the Vice President of the Senate, nor, in fact, have we drawn a formal bill up to the present time. We are continuing our discussions with the Ways and Means Committee. I will resume tomorrow. As you know, they have got under consideration a number of pos- sible approaches. Mr. Sprincer. May I ask you this last question? Do you in the foreseeable future—and I am going to limit that to 4 weeks—intend, or do you now plan, to present. a bill? Secretary Fiemmrne. I really don’t know on that as yet. I think a lot will depend on further discussions in the Ways and Means Com- mittee. But we are prepared, of course, to outline to any other com- mittee the basic approach that we believe to be sound. Mr. Sprincer. Mr. Secretary, I think it would be extremely im- portant in view of what has already gone before in stated opinion around the Congress that your legal counsel get an opinion insofar as he can at this time from the Parliamentarian or the Assistant Par- liamentarian as to where that bill is likely to go. If it indicates that that bill is most likely to come before this com- mittee, I think it will be well, then, to talk with the chairman of this committee, so that there is some resolving of this between Mr. Mills and the chairman of this committee as to what should be done. I think this will save a lot of time not only for you, but this com- mittee is going to be very busy if what the chairman tells me is true, and I think it is, until the end of this Congress. COLOR ADDITIVES 531 So I merely make that statement because I think it is well to keep in mind. May I say last, having asked all these questions, I thought your statement was excellent this morning. In the first place, it was short and concise, and we could understand it, and I like that kind of state- ment. Secretary Fiemminc. Thank you. I appreciate that. The Cuarrman. I don’t want any misunderstanding of the record in view of the comment made by Mr. Springer and “the request he made of you. In the first place, I will say you and I have previously discussed this question and the jurisdiction problem, and I raised with you the same question earlier this morning. We were going to bring that out. But before I ask you another question on this, there is what is referred to as rule 40 of the Rules of the House of Representatives that provides a proper procedure for the departments and agencies of the Government to present legislation to the Congress. There have been some questions raised about. whether or not that rule has been strictly complied with in the past, but in view of the fact that the Speaker a year or two ago raised it, I must say that inso- far as I know, all agencies and departments of the Government have been comply ing strictly therewith since. The rule requires you to submit your proposals and recommenda- tions to the Speaker of the House and the President of the Senate and it then bee: “omes the responsibility of the Speaker and the Presi- dent of the Senate, with the advice from the Parliamentarian, to refer such proposals. Now, that is the rule, and you or your lawyers can’t do anything about it, Mr. Secretary. Secretary FLemmMina. That is right. The Cuarrman. The Speaker has made it very clear that he expects that rule to be followed. But it does present a rather unusual type of a situation where the Ways and Means Committee—and I don’t want to get into any fracas with my own colleague Mr. Mills—as you told me a while ago Arkansas has been keeping you pretty busy recently. Secretary Fremine. That is right. The Cnatrman. IT guess maybe. that is true; but, nevertheless, as Mr. Springer said, it does pose a very important jurisdictional matter. And as members of this committee have discussed the matter with me in recent days, it is quite obvious that this committee cannot just sit idly by and see the jurisdiction of this important question taken away by such devious means as trying to propose something as a sub- stitute for a bill that is appropriately before another committee. Now, we had you scheduled to come here on that day, and the chair- man of that committee talked me into letting you come before him, and you expressed that you wanted to be there. Yet, we find that we released vou to them and you went down there and presented the problem to them which you ought to have presented up here, because, as I understand, this is a health insurance plan on a grant-in-aid basis, is that right ? 582 COLOR ADDITIVES . Secretary FLemmine. Well, it is certainly a Federal-State program I mean a program under w hich the Federal Government would make grants to the States in order to enable the States to give assistance to the aged under the terms that would be prescribed in the bill. But, as I indicated in my exchange with Congressman Springer, without trying to get into the middle of any jurisdictional dispute between committees of the Congress, I should in all fairness point out that it would involve some amendments to title I which is the public-assistance title of the social security. The Crarrman. It involves some amendments to title I only be- cause of compliancee—— Mr. Kerra. Incidentally The Cuarrman. Actually, it is a health insurance plan provided for the States to administer; isn’t it? Secretary I'xemmine. The only thing that makes me hesitate is the use of the technical term “insurance.” The basic proposal, as you probably have noticed, is a proposal under which the individual who is not on public assistance could enroll in the plan. If he did, that certain costs over and above a deductible figure, or 80 percent of certain costs over and above a deductible figure, would be taken care of for him by the State, and the State would draw on a fund that would be set up by Federal-State matching. The Cuairman. But w hen he enrolls, he pays so much doesn’t he? Secretary FLemmine. Under the proposal that we submitted, he would pay what we call an enrollment fee of $24. Now, this does not apply to the public-assistance recipients. “They would get all of the benefits of the plan without paying any fee, without being in- volved in any deductible, and also without being involved in any pro- vision for paying 80 percent of the costs of the benefits, So that they would be treated differently than the others. This is the part that, of course, would—the fact of the matter is that it represents a considerable step-up in the medical service benefits pro- vision of the Public Assistance Act, so that, as I see it, it probably would involve matters that might very well be within the jurisdic- tion of both committees, and how that is resolved by a Parliamen- tarian, I don’t know. I agree with you, Mr. Chairman, I don’t think that we should at- tempt. to get the Parliamentarian to resolve it. The Cuamman, It isn’t your responsibility. Secretary FLemmina. That is right. The Cuarrman. And we will take care of that ourselves. I would like to get back to this bill here, if we can, before we get too far away. Mr. Sprincer. May I just say this one thing. Mr. Secretary, you weren't here in Washington in 1954? Secretary Fremminec. I was here, but I was over in another area. Mr. Sprrncer. A subcommittee from this committee traveled in some 15 countries over a period of some 3 or 4 months to get all the information with reference to the Health Insurance Act of 1954, and I am pretty sure—as I was on the subcommittee at that time and saw these other health acts in all these countries—just about everything that you have in this bill, I am sure, which was encompassed in the 1954 act in a slightly different way to cover all the people mentioned COLOR ADDITIVES 533 :in_ your bill, although not in quite the same way, so I am almost pos- itive this is a bill before this committee. I am talking about the principal portion. It might take some -amendments, but I think it is one that will be found to be with this . committee. Thank you, Mr. Chairman. The Cuarmman. Did you want to say anything on that score, Mr. Dingell ? Mr. Drineext. I just wanted to ask a couple of questions as long as that issue has come up, and I thank the Chair very much for this. Mr. Secretary, I was very much concerned about the rather slow process of the administration in evolving something along the lines that you were discussing today. The Forand bill was introduced in the Congress a matter of some 4 year or 5 years ago, and I had sponsored a similar bill previous to the Forand bill. Secretary Firemmine. I think the Forand bill was introduced in 1957, if my memory is correct. Mr. Dincett. And previous to this time, at any rate, reports of this have been requested from the administration for better than 4 years that I know of and, actually, considerably previous to that, because my dad sponsored a bill that was not too much different. . Secretary Fremainc. That is right. That was back in 1949, I think. Mr. Drncetu. His bill was first introduced in the early 1950's, or it may go back into 1949. What I am interested in is this: Here we have a problem that has needed meeting for some while. We have jurisdiction in one committee which has “been considering legislation. You folks downtown come up with a proposal that goes now to— that comes to a very different committee—and I am satisfied it does, because I have legislation not. vastly different than yours that comes to this committee. Don’t you think it would be a wise idea for the Department to get some kind of legislative proposal up here to Congress so we can find out just who does have jurisdiction on this matter # Secretary Fremmine. Mr. Chairman and Congressman Dingell, may I say this: I don’t want to suggest by anything I have said that we will not follow the formal procedure. I have tried to outline just the exact position that I find myself in as far as the Ways and Means Committee is concerned. In other words, the chairman did not request me to come up with a formal draft of a bill, but he did not ask me to present to the com- mittee the outline of any plan that we might decide on. We were able to reach agreement on a plan, and I did come up, and T have discussed it with the Ways and Means Committee in response to that request. Of course, we are working on getting our proposal into legislative language, and certainly, at the appropriate time, that would be made available, and, I would assume, would go through the kind of a process The Cuarrman. Will you yield? Mr. Secretary, will you submit to this committee the proposal that yon submitted to the Ways and 534 COLOR ADDITIVES Means Committee together with any additional information that you submit here in the Congress regarding this matter ¢ Secretary Ftemmrne. I will be very ha Mr. Dince.y. Mr. Chairman, I would TR te to point out to you, Mr. Secretary, that the clock is a very, very harsh master. The present indication is that the Congress intends to adjourn sometime very early in July. If the administration does not move with the greatest speed in getting some kind of concrete legislation up here that they intend to back, we may very well find, instead of concrete legislation, we are going to have just another campaign issue next fall. This problem of health insurance for our aged will be removed from the question of accomplishing something concrete into a heated political forum. I hope that you folks down in the department will act diligently, and see to it that we get something that we can act on rather than to resolve ourselves into a rather bitter partisan wrangle during the fall. Secretary FLemmina. Mr. Congressman, might I say that this is the kind of an objective toward which I am personally working. Might I also say that I am spending a great deal of time before the committee that is now considering this matter, and we are responding to all kinds of requests for additional information—for backup mate- rial and so on—and responding to it literally almost overnight at times. We have a staff that is literally working morning, noon, and night, and literally working around the clock and Saturday’ s and Sunday s, in order to put before the committee that is now considering the matter all of the information that they feel they need in order to act on it. I appreciate the issue that has been raised here, but I think you can also appreciate my position that this is the committee that is con- sidering the matter at the present time; and this is the committee to which Lam presenting this information. But I will certainly be very happy to respond to the chairman’s re- quest and present comparable material to this committee. The Crarrman. Mr. Secretary, I would not want any implication to go by that the mere fact that you submitted your plan up here and got it accepted would eliminate it asa campaign issue, Mr. Dincett. I happen to be one man who is interested in getting something done here rather than running around the country cam- paigning c on this issue, and I would like to see something come up here as soon as possible from you folks downtown, Apparently rather extensive consideration has been given to this, and it would appear to my mind that having given extensive con- sideration, the actual draftsmanship of a proposal of this sort is a relatively simple matter. The Cuatrman. I think we have discussed this matter with the Secretary. I would like to get back to this legislation because it is getting late. Mr. Dineen. I didn’t open the question, Mr. Chairman. The Cuarrmman. I know, but I don’t intend that it go on and on. Mr. Sprincer. Mr. Chairman if you would—could T ask, Would you send mea copy of the statement made before the Ways and Means Committee ? COLOR ADDITIVES 535 Secretary FLemmrine. Yes. Mr. Chairman, suppose we make copies available to the clerk of the committee for distribution to all members of the committee. The Cuairman. That is precisely what I had in mind when I asked you the question a moment ago. Secretary FLremminc. We will be very happy to do that and do it immediately. The Cuarmman. I would like to get back to this subject matter here which is of great concern to us. I want to ask you the same question with reference to your action against the chicken people on abandoning the use of stilbestrol that was asked by Mr. Springer a moment ago with reference to the banning and seizure of cranberries. Did you follow the same procedure as he outlined to you as required by law? 2 Secretary Fiemmina. Certainly, Mr. Chairman, I feel that every- thing we have done in connection with that is in conformity with the law. Now we did follow a different procedure, as you know, and as I outlined to the committee the last time. In the first place, in the one case we were dealing with a situation where there was some use of a substance in violation of the law en- forced by the Food and Drug Administration. In this particular instance no one was in violation of the law or any of our findings or of any of our rulings. But some evidence had been made available to us which made us realize that it would be necessary for us to take action. As I indicated the last time I was here, we asked the interested rep- resentatives of the interested parties to come in and discuss the matter with us, and asked them whether or not they would be willing to take some action informally prior to our instituting the formal action. Commissioner Larrick has referred to that, “and of course they did agree, and since then in three instances the formal action has” been taken and } is now underway. I don’t know just when that will be com- ete P The CuHatrman. Yes. I think the great complaint was not in doing that. It was the manner in which it was done according to the reports which I got from the people involved. They have advised me that they had people here who pleaded with you and your department not to make the announcement as you did at that particular time because of the effect it would have—that they would voluntarily and were glad to comply with whatever you wanted them to do. But in making the announcement as it was made at that particular time, it wasa blow to the chicken industry. Secretary FLemuine. Mr. Chairman, ‘of course I recognize that it is a matter of judgment, and I recognize that some took issue with the final judgment that we exercised. But in view of the fact that the information had become available, in view of the fact that the information was going to be made public, we felt that being able to say to the public that the manufacturers of the product, the industry, and the retailers had agreed to stop the use of the product in the way in which it was being used—had agreed totake the birds that were involved off the market so that the consumer 536 COLOR ADDITIVES could be assured of the fact that what he or she was purchasing was absolutely OK: The Cuarrman. But they did agree voluntarily to take them off the market? Secretary FLemminc. There is no question about it, Mr. Chairman. The Cuairman. And they did so take them off the market ? Secretary FLemminc. They did, and we so stated, and as you know, I have so stated. I stated then at the time of the initial announcement and repeated it a number of times afterward, in order to make per- fectly clear to everybody concerned that what they were buying on the market was OK. The Cuatrman. I might say that I was at that particular time on a duck shoot in Arkansas, and when you made your announcement on television, I was just getting ready to eat a choice chicken that they were serving. Mr. Kerru. I gather you hadn’t shot any duck ¢ The Cuarrman. Well, I want to say, it did not keep me from eating the chicken, even though the announcement was made. But I did want to raise the same question with reference to the poultry business, because these gentlemen with cranberries up there can't have much luck selling their cranberries unless we have chicken and turkey to go with it. But back to the proposal in your statement this morning. In the first place you suggested an amendment to the Delaney amendment. Secretary Fremaina. That is correct. The CHarrmMan. What was that suggestion ? Secretary FLemuine. Mr. Chairman, as you know in my testimony, both today and January 26, I outlined the substance of that. Ap- parently the exact wording is not here. I will see to it that it is here so it can be included in the record at this point. The Cuarrman, That is referred to in your statement on page 2. Secretary FLemmrine. That is correct. The Cuamman, You said: At that time I stated that we believed the Delaney clause should be modified to provide that additives used in animal feed which leave no residue either in the animal after slaughter or in the food product obtained from the living animal be exempt from the provisions of the clause, Secretary Fitemmina. Right. The Cuarrman. I suppose you would apply that to chickens, too; wouldn’t you? Secretary Ftemmina. Yes, sir. The Cnarrman. You will then provide for the committee what you have in mind as language to meet this policy statement ? Secretary FLtemmina. That is correct. The Cuarrman. Now you also say that the Delaney amendment should not be amended in any other way; is that correct ? Secretary FLemmine. That is correct. The CHamman. Except with reference to Dr. Darby’s suggestion ? Secretary Fiemmina. Yes, Of course, that really wouldn’t be an amendment to the Delaney amendment. That would really be some- thing that would be included in the bill and would apply both to the Delaney clause or any other matter that might come up. COLOR ADDITIVES 537 _ The Cuamman. That is right. Does that reach the point that — Commissioner Larrick referred to a moment ago on a question by Mr. Keith about making information available to what you had called the third party or the injured party ? Dr. Larrick. No, that would be an entirely different matter than the advisory committees he is talking about. As it is now, if a manu- facturer comes to us with a petition in this area, his data would, un- less there is a public hearing, be regarded as a private matter, and we would not feel privileged to make it known to the world. The sug- gestion that Dr. Darby has would provide that we publish the. scientific basis upon which we reach these decisions. The Cuarrman. Now the Bureau of the Budget sent up a letter and referred to the fact, Mr. Secretary, that the Delaney approach is un- necessarily stringent in one respect. Where an additive is used in ani- mal foods and leaves no residue in the food after slaughter and does not adversely affect the animal, there is no need to have the proviso. The Secretary of Health, Education, and Welfare will submit language to modify the Delaney amendment in this regard in the near future. That is what you just referred to. Secretary FLemmine. That is correct. The Cuarrman. Then in your letter of April 11, you suggest that a correction in the provision in title I of the proposed color additive amendment be made. Secretary FLemmine. That is correct. The Cuatmrman. And you think that is necessary in order to make it conform. Secretary Fremmine. Yes. That was as indicated here in the sec- ond paragraph. This problem arose out of an inadvertent cross- reference to the subsection on fees and soon, This is simply designed to improve the bill technically. The Cuatrman. The letter of April 18 to the committee is merely along the lines of your statement this morning regarding the arsenic situation ? Secretary Fremmina. Yes, and this was in response to a request from the committee for background information on this. The Cuatmrman. The Department of Agriculture has submitted a letter of April 14. The Department favored, when it testified, amend- ing section 101 of the Senate bill 2197 by adding before the period in line 10, page 3, certain language. Or are you familiar with that? Secretary FLEMMING. Thave the letter in front me, yes. The Cuatrman (reading) : Or any soil or plant nutrient or any materials subject to registration under the Federal Insecticide, Fungicide, and Rodenticide Act. Do you agree with the recommendations of the Agriculture Depart- ment? Mr. Ettennocen. Sir, may I interpose. There is a later reeommen- dation that this Department and the Agriculture Department worked out jointly which appears in a letter from the Department of Agricul- ture to you, sir, dated April 14. The Cuarrman. That is what I am reading from. It goes on to say: 538 COLOR ADDITIVES Secretary Freamine. Yes; the chairman is reading from the letter of April 14. Pardon me, Mr. Chairman, what confused the lawyer there, that later on in this letter the language is suggested to which we have agreed. The Cuairman. In other words, reading further from the letter: Dr. Clarkson stated at that time that the language suggested was preliminary, and that discussions were being held with representatives of the Department of Health, Education, and Welfare. As a result of these discussions, we are now revising our proposal by recom- mending that section 101 of S. 2197 be amended by adding a new paragraph 3 on page 3 as follows: (3) Nothing in subparagraph 1 of this paragraph shall be construed to apply to any pesticide chemical, soil or plant nutrient, or other agricultural chemical solely because of its effect in aiding, retarding, or otherwise affecting, directly or indirectly, the growth or other natural physiological processes of produce of the soil and thereby affecting its color, whether before or after harvest. Now does this try to resolve the issue which was presented to this committee in hearings by our former colleague from Florida, Mr. Peterson ? Dr. Larrick. It is my recollection that that was one of his points. At the start of the hearings the people who were concerned with this thought that it could be handled as a matter of legislative history, and then there was some court decision that was handed down that gave them concern, and this simply would mean that you wouldn’t include within the color amendment these substances that are ruled out here, and that would take care of some of Mr. Peterson’s problem. The Crarrman. In the presentation to this committee, you have the bill before you, the House bill, on page 10 it was suggested that the first part of the amendment, that is lines 2, 3, and 4, and part of 1, and beginning on line 14: If it is found after tests which are appropriate for evaluation of the safety of additives for use in food to induce cancer in man or animal— and so forth, it has been recommended to us that the first part of that be left out and adopt the latter part. Have you got any com- ment on that suggestion ? Secretary FLemmine. Just a minute until I get the substance. The suggestion is that it would read now on page 10, line 11: A color additive shall be deemed unsafe and shall not be listed for any use which will or may result in ingestion of all or part of such additive if the additive— now what is it suggested that should be stricken ? The Cnamman. That that part be stricken, and as I understood it would read: A color additive shall be deemed unsafe if it is found after tests which are appropriate for the evaluation, safety— and so forth. Secretary Ftemminc. Mr. Chairman, we have looked at a number of suggestions that have been made on the change in the wording. This is one, however, that we haven’t looked at. I would like to have the opportunity of considering it with the lawyers before comment- ing on it, if I may. The Cuarrman. Yes; you may. Secretary FLemmina. I would appreciate it. COLOR ADDITIVES 539 The Cuatrman. Mr. Secretary, I have detained you entirely too long, but I thought it better to go ahead and try to get through in- stead of having you come back this afternoon. Consequently we have gone on through the noon hour as it is now 1 o’clock. Secretary Fremmine. I appreciate very much the opportunity of appearing again. I am very happy to stay until you have concluded. The Cuamman. We appreciate your cooperation and your presen- tation here this morning in further reference to this important problem. ; . It is going to be my intention after other hearings which are sched- uled for this week by some of the subcommittees are concluded—if we can get through those hearings, and I hope we can—it will be my intention to have a series of executive sessions at which I hope to get to resolving some of these issues, so any further information that is to be submitted to this committee is going to have to come within the next few days. Secretary FLemminc. We will see to it. The CuairmMan. In that regard I am going to hold the record open 5 days for any additional information to be submitted. With the thanks of the committee for your statement and your testimony today and your cooperation in the matter, the committee is now adjourned. Secretary Fremainc. Thank you very much, Mr. Chairman. (The following letter was later received from Secretary Flemming :) DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, Washington, May 18, 1960. Hon. OreEN Hakgris, Chairman, Committee on Interstate and Foreign Commerce, House of Repre- sentatives, Washington, D.C. Dear Mr. CHATRMAN: On May 9, 1960, when I appeared before your committee with regard to proposed color-additives legislation, you requested that we com- ment on a proposal that has been made for amending the anticancer clause of H.R. 7624. As we understand the proposal, it would change section T06(b) (5) (B) (i) so that it reads: “(B) A color additive (i) shall be deemed unsafe and shall not be listed, for any use which will or may result in ingestion of all or part of such additive. Cif the additive is found to induce cancer when ingested by man or animal,] or if it is found, after tests which are appropriate for the evaluation of the safety of additives for use in food, to induce cancer in man or animal, * * *.” (Brack- eted material present in original bill, but to be deleted.) The deletion of the bracketed language from the proposed color-additives bill, and deletion of comparable language from the anticancer clause of the Food Additives Amendment of 1958, in view of the past history of the anticancer clauses, is obviously designed to weaken the anticancer clause and to allow room for the contention that our Department should establish tolerances to permit chemicals in food even though they had been found to induce cancer when fed. This would serve no purpose except to lead to extended litigation on this issue in the courts. As you know from my testimony on January 26 and again on May 9, 1960, we believe there is no sound scientific basis at this time for establishing tolerances to allow carcinogens to be added to food. We recommend that the proposed change not be adopted. Sincerely yours, ArtHurR 8. FLEMMING, Secretary. (The following material was received for the record :) STATEMENT BY JANE W. HeETRICH ON THE BEHALF OF THE NUTRITIONAL StupYy Group oF CAPE ARTHUR, SEVERNA PARK, Mp. Mr. Chairman and members of the committee; it has been a privilege to sit in on some of the hearings of the Interstate and Foreign Commerce Committee 56123—60——35 540 recently held regarding proposed legislation dealing with the use of artificial chemical colors in foods, drugs, and cosmetics. The manner in which this has been conducted has reassured me that our fine Congressmen will not be deceived by false security regarding our national health. Certain industries with their cry of “no harm in a little bit,” as voiced at the hearings as well as in newspapers and magazines (such as Feb. 15, 1960. issue of Life magazine), prompts me to submit for the record the following observations of dangerous chemicals in foods: On an attached sheet I have listed a common menu for one day, just such as you or I might eat. For each food I have listed the chemicals contained therein as indicated on the labels of that food or as commonly known to be used in its production. You will note these 16 everyday food items contain at least 435 different artificial chemical colorings, flavorings, and preservatives. If our imaginary diner should augment his diet with, perhaps, a carbonated beverage or candy bar this would further increase the chemicals ingested. Also an expert in food preparation might know of even more chemicals used in today’s food production, but I am just a housewife and know only of those stated by the manufacturer or processor. Nor does this consider any insecticides or antibiotics, although we all know virtually every particle of food now available to us, including meat and milk, contains one or more chemical poisons or drugs of varying degrees of harmfulness. Now some might say these chemicals are (mostly) not harmful, but we must remember only a few years ago many chemicals were believed not harmful and are now recognized as definitely inciting to cancer and other degenerative di- seases. The oft-heard cry that just this “little bit” of chemical surely cannot hurt, even if it is carcinogenic, begins to sound hollow when we consider, on such a simple diet as I have submitted, this “little bit” in perhaps madam’s lip- stick, becomes not the first but the 44th “little bit” to be ingested in 1 day. As a representative of a group of intelligent housewives I ask that you please keep these observations in mind when considering this matter of colors in foods, drugs, and cosmetics. If we must be forced to ingest chemicals in our foods, and they are so prevelant it is almost impossibel to avoid all of them, the very least our Congress can do is forbid those know to be harmful. COLOR ADDITIVES Number of Food item chemical Type or variety of additive additives Breakfast: Tang breakfast drink... - 8 | 8 chemicals for coloring, flavoring, and preserving. Prepared cereal... 3 | Artificial favoring, preservative, coloring. Toast wo ae . 2 | Bleach; calcium propionate (retard spoilage). Oleomargarine...........-...-- 3 | Sodium benzoate; chemical preservative, artificial coloring. Total......---...2.-.-.-.---- 16 Lunch: - Lunch meat......--2.-.. aweeee 3 | Sodium nitrate; sodium nitrite; artificial coloring, Cheese... . 2 | Scorbic acid, preservative; artificial coloring. Bread... . 2 | Bleach; calcium propionate. Oleomargarine.........-...---. 3 Sodium benzoate; chemical preservative; artificial coloring. Relish... 2 Alum; citric acid (harmful when not in natural form). Cookies 3 | Artificial color, flavor, preservative. Orange... 2 | Artificial color; wax. Total....-..----------------- 7 Dinner: Ham. -.......2-22-----022----- 3 | Potassium nitrate; borax; boracie acid. PotatoeS........--.----2------- 1 | Red dye to make them aprew t> contain more miner- als, and therefore bring hig»er price. Mixed vegetables (canned) - -.- 1 | Artificial Mavoring (might also contain artificial color- ing). Mixed fruit salad...........--. 2 Artificial coloring; artificial flavoring. Frozen ple..........-.....-...- 3 | Artificial coloring; artificial flavoring; preservative. 0 COLOR ADDITIVES 541 STATEMENT oF Srert F, RiepMA, PRESIDENT, NATIONAL ASSOCIATION OF MARGARINE MANUFACTURERS My name is Siert F. Riepma and I am president and treasurer of the National Association of Margarine Manufacturers, a nonprofit trade association organized under the laws of the State of Illinois, with offices in the Munsey Building, Washington, D.C. The association, which is national in scope, is a typical trade association devoted to a single product—margarine. Its membership includes the following margarine manufacturers, some large and some small, which, collectively, market their product throughout the United States : Anderson, Clayton & Co. Foods Division, Gibraltar Life Building, Post Office Box 35, Dallas, Tex. Armour & Co., 401 North Wabash Avenue, Chicago, Ill. Blue Plate Foods, Inc., Box 13014, Broadmoor Station, New Orleans, La. The Carthage Creamery Co., 545 North Main Street, Carthage, Mo. The Cudahy Packing Co., 5002 South 33d Street, Omaha, Nebr. Durkee Famous Foods, Division of the Glidden Co., 900 Union Commerce Building, Cleveland, Ohio. J. H. Filbert, Inc., 3701 Southwestern Boulevard, Baltimore, Md. Kent Products, Inc., Wornall Road at 42d Terrace, Kansas City, Mo. Kraft Foods, Division of National Dairy Products Corp., 500 Peshtigo Court, Chicago, Il. Lever Bros. Co., 390 Park Avenue, New York, N.Y. The Merchants Creamery Co., 536 Livingston Street, Cincinnati, Ohio. The Miami Margarine Co., 5226 Vine Street, Cincinnati, Ohio. Osceola Foods, Inc., Box 389, Osceola, Ark. Shedd-Bartush Foods, Inc., 14401 Dexter Boulevard, Detroit, Mich. Sunnyland Refining Co., 3330 10th Avenue, North, Birmingham, Ala. Swift & Co., Union Stock Yards, Chicago, Ill. Vegetable Oil Products Co., 401 Canal Avenue, Wilmington, Calif. Wilson & Co., Inc., Prudential Plaza, Chicago, Ill. The National Association of Margarine Manufacturers endorses legislation of this type and, in this statement, we desire to point out why this legislation is considered by us to be both necessary and desirable and why we believe that the Congress should enact it into law without delay. I desire also to comment upon, and make some suggestions: with respect to, specific provisions of the pro- posed legislation. Except in one respect, S. 2197, as introduced in the Senate on June 17, 1959, was identical with H.R. 7624, which was introduced by Representative Harris on June 9, 1959, and referred to the House Committee on Interstate and For- eign Commerce. The exception relates to the provision appearing in section 706(b) (5) (B) of H.R. 7624 respecting the so-called cancer provision. No com- parable provision appears in S. 2197 either in the form in which it was intro- duced or in which it passed the Senate on August 24, 1959. Also, two amend- ments to the Senate bill as originally introduced were adopted by the Senate Committee on Labor and Public Welfare after consulations by the committee staff, by representatives of the industries concerned, and by representatives of the Food and Drug Administration of the Department of Health, Education, and Welfare. The first of these amendments, which were subsequently adopted by the Senate in passing S, 2197, has the effect of permitting those additives found “safe” by the Secretary of Health, Education, and Welfare, under the procedures set forth in the 1958 Food Additives Amendment, to be also consid- ered “safe” when used as color additives; and the second such amendment has the effect of relieving the Food and Drug Administration from the obligation of requiring the use of certain analytical methods with respect to color addi- tives when, in its opinion, they are not needed. Save in the respects mentioned, therefore, S. 2197, in the form in which it is now pending before this committee, is identical with H.R. 7624. The reasons why I believe that it is in the best interest of both manufac- turers and consumers of margarine for the Congress to enact this legislation may be suinmarized as follows: (1) Margarine manufactured and marketed by the members of the National Association of Margarine Manufacturers is produced and distributed in accord- ance with both Federal and State laws. 542 COLOR ADDITIVES The industry, of course, has a vital stake in a supply of suitable and ade quate colors for use in margarine. In 1950, the Congress enacted important new legislation with respect to the manufacture and sale of colored margarine in this country and established a national publie policy whereby, insofar as the Federal Government is concerned, the consumers of this country would be as- sured of a plentiful supply of colored margarine. In all but two of the States. Wisconsin and Minnesota, the laws also established a public policy at the State level whereby consumers may freely purchase and use colored margarine. The interest of both the manufacturer aud consumer in a continuous supply of suitable colors is well stated in the report of the Senate Committee on La- bor and Public Welfare, which accompanied 8S, 2197 (S. Rept. No. 795, 86th Cong., Ist sess., to accompany S. 2197, August 21, 1959, p. 11), where the com- mittee stated, in pertinent part, as follows: “The use of color in foods, drugs, and cosmetics, though largely of value from the point of view of enhancing the marketability of the articles involved, is, in many cases, also in the consumer's interest and affirmatively desired by con- sumers. This is obviously so not only in the case of cosmetics, many of which are designed and purchased for the very purpose of imparting color, but also in the case of certain foods, e.g., margarine, where consumers demand arti- ficial color, * * * Thus, it is in the interest of the consumer that the law be changed so as to make available an adequate supply of colors of the safety of which, for particular uses, the consumer can be assured.” For these reasons, the availability of suitable color additives for margarine is important both to the manufacturers and consumers of this product. (2) In order that, in the future, there may continue to be an adequate supply of suitable colors for use in margarine and in other foods, it is absolutely essen- tial for the Congress to enact remedial legislation such as that proposed in H.R. 7624 and 8. 2197. The fabrication of foods by the combination of ingredients for sale and ultimate consumption by consumers is an accepted fact in our economy. Last year, in the 1958 Food Additives Amendment to the Federal Food, Drug. and Cosmetic Act of 1938, as amended, the Congress dealt comprehensively with all food additives other than color additives to fabricated foods, such as margarine. In that important amendment, the Congress adopted the concept that food addi- tives must be pretested for safety before hey are used in foods and, moreover. authorized the Secretary of Health, Education, and Welfare to establish safe tolerances within which certain additives might be used in our food supply. H.R. 7624 and S. 2197 would, in substantial effect, adopt a similar concept with respect to color additives, thus placing all food additives on the same plane. Under the present law, a sharp distinction is made between so-called certified colors, which are undefined by the law, and other color additives. Certified colors may not be used in foods unless they have previously been listed by the Secretary of Health, Education, and Welfare as harmless and unless they come from batches of these colors certified by the Food and Drug Administration. But, under the present law, there is no provision for pretesting color additives used in foods which are not classified as certified colors. They may be freely used in foods by the manufacturer, and it is up to the Government to show that they are not safe after they have been used. Under the provisions of H.R. 7624 and S. 2197, this distinction between certi- fied colors and other colors would be eliminated and a uniform procedure would be adopted whereby no color additive may be used in a food except in accordance with regulations prescribed by the Secretary of Health, Education, and Welfare. The essential key to the proposed new law is that a color additive must be safe before it is used. H.R. 7624 and S. 2197 spell out, at great length, the criteria which must be followed in determining the safety of the proposed color additive and, like the 1958 Food Additives Amendment, would authorize the establishment of tolerances within the safe limits of which color additives might be used if tolerances are found to be necessary. It is generally recognized that, in the light of the present techniques in the preparation of manufactured food products, such remedial legislation is desirable, and that it would safeguard the public health more adequately than the present law and, at the same time, enable the food industry to utilize advancing scientific knowledge. There is no scientific or other reason for treating color additives differently from other food additives, (3) The basie provisions of the present law and regulations respecting colors to he added to the food supply were written at a time when the principal colors available for use were of coal-tar origin. However, following the 1958 decision of the Supreme Court of the United States in Flemming v. Florida Citrus Ex- COLOR ADDITIVES 543 change (358 U.S, 153), holding that, under the present law, there is no authority to establish tolerances respecting coal-tar colors which may be used in foods, the Food and Drug Administration of the Department of Health, Education, and Welfare changed its regulations so that certain yellow coal-tar colors theretofore used in the food supply of the Nation are no longer available. It is important to bear in mind that this action was not taken by the Food and Drug Administration on the basis of any evidence that these coal-tar colors were harmful within the infinitesimally small limits within which they have been used in food products for coloring purposes. Rather, the action was taken because, as a matter of law, the Supreme Court has announced that there is no authority in the present law for the establishment of safe tolerances insofar as coal-tar colors are concerned. Under H.R. 7624 and S. 2197, authority would be vested in the Secretary to establish such tolerances, where needed, just as he already has authority to establish tolerances, where necessary, with respect to the great variety of all other additives governed by the 1958 Food Additives Amendment. (4) In the years which have intervened since 1938, when the Congress en- acted into the law the present coal-tar color provision, giant strides have been made in the production of a variety of colors not then available. Regulation of the use of these newly developed colors, under the provisions dealing with coal-tar colors, is not realistic and is not in the publie interest. Under the pro- visions of H.R. 7624 and 8S. 2197, these new colors, as well as coual-tar colors, could be used in the food supply if they are found to be sufe by scientilic experi- ments and, where necessary, the Secretary would be authorized to establish tolerances for their use. Such a system of regulation is absolutely necessary if the best interests of American consumers are to be preserved. In this connec- tion, it should be pointed out that the Food and Drug Administration of the Department of Health, Education, and Welfare is experiencing considerable difficulty in determining whether some of these newly developed color additives are or are not to be considered “coal-tar colors” within the meaning of the present law. There is utter confusion which would easily be remedied by H.R. 7624 and 8S, 2197, It does not make sense to spend time and effort in attempting to classify a color as a coal-tar color or not, when the real question of paramount importance is the safety of the color regardless of its classification. (5) We desire to call particular attention to the desirability of including the provisions of section 203 in H.R. 7624 and 8S. 2197. In legislation of this im- portance and complexity, it is important for the Congress to provide for the orderly transition from the old system of regulation to the new system of reg- ulation so that the best interests of consumers in a continued food supply will be preserved and in order to avoid the disruption of orderly manufacturing proc- esses. The purpose of section 203 is to provide for the orderly transition from the old system of regulation to the new system of regulation. Thus, among other things, the Secretary would, during the transitional period of 242 years follow- ing the date of the enactment of H.R. 7624 and S. 2197, be specifically author- ized to provide for the continued use, during such period, (1) of any certified or coal-tar color previously listed as harmless and certifiable for use; (2) any other color additive heretofore commercially used and sold, and (3) the color additive known as synthetic beta carotene. The last is a yellow-coloring mate- rial used in the margarine industry as well as in the food industry in general. It is recognized as a healthful and nutritious product and is an important source of vitamin A. I feel that the transitional provisions, just mentioned, are wise and should be enacted without change into the new legislation. Before concluding this statement, we now desire to comment particularly with respect to specific provisions of the two bills under consideration by this com- mittee, (1) In the first place, we submit that the two amendments made by the Sen- ate Committee on Labor and Public Welfare to S. 2197 and adopted by the Sen- ate, as summarized above, are desirable and should be adopted. The first of these amendments, with respect to relieving the Food and Drug Administration from the obligation of requiring the use of certain analytical methods when, in its opinion, they are not needed, appears in section T06(b) (5) of S. 2197. The second of the two amendments, permitting those additives found “safe” under the 1958 feod additives amendment to be cousidered “safe” under the proposed eolor additives amendment, appears in the proviso in section 706(b) (4) of S. 2197. If the House bill rather than the Senate bill is to be reported by this 544 COLOR ADDITIVES committee, section 706(b) (4) and (5) (A) of the House bill should be amended to conform to the provisions found in section 706(b) (4) and (5). (2) Aside from the two amendments just noted, which were adopted by the Senate in passing S. 2197, and which this association favors, the only other difference in the two bills is that H.R. 7624 contains the so-called cancer pro- vision in section 706(b) (5) (B), while no such provision is found in the Senate bill. This association submits that, in this respect, S. 2197 is to be preferred, rather than H.R. 7624. This is true because the basic provisions of both the bills provide that a color additive may be used unless its safety has been proved and tolerances, if needed, are established. No one favors the using of any color additive which would induce cancer in man. Certainly, if there is any evidence whatever that a particular color addi- tive will induce cancer, its use may be proscribed under the basic provisions of either the House or the Senate bill, which permit the use of a color additive only if its “safety” is proven, Therefore, the so-called special cancer provision ap- pearing in section 106(b) (5) (B) of H.R, 7624 is unnecessary to protect the health of the Nation, and its only real effect actually is to mislead consumers into be- lieving that they secure some protection from this provision which they, in fact, do not. Aside from the foregoing, the provision is contrary to the whole philosophy of the remainder of the bill, which is to permit the establishment of safe tolerances, where necessary. Furthermore, the provision, as now written, might well be regarded as perpetuating the doctrine announced by the Supreme Court in 1958 in Fleming v. Florida Citrus Exchange. This doctrine is that the Secretary of Health, Education, and Welfare is without authority to permit the use of a coal tar color, even if the Secretary knows it is safe to permit its use under ordinary conditions of human ingestion, where there is any evidence that the color may be harmful if fed in enormous doses to experimental animals. To overcome such doctrine is one of the reasons why legislation upon the subject is necessary. I recognize that a similar provision is found in the 1958 food additives amendment, but we do not believe that this establishes a precedent for con- tinuing an undesirable and unrealistic provision such as that which now appears in H.R 724. I reiterate that no one desires to use any color additive or food additive which actually is unsafe under ordinary conditions of human usage, whether it causes cancer or smallpox, In all candor, I feel compelled to point out that the present so-called cancer provision appearing in the House bill accomplishes no real purpose not otherwise accomplished by the bill, and that, indeed, it provides a basis for potential confusion and deception to consumers. (3) Section 706(b) (6) of H.R, 7624 and S. 2197 provide, in effect, that the Secretary shall not permit a color additive to be used “if the data before him show that such proposed use would promote deception of the consumer in violation of this act or would otherwise result in misbranding or adulteration within the meaning of this act.” Obviously, this particular provision is not related to the “safety’’ of the use of a color additive in the food supply and, for this reason, logically does not belong in a proposed bill having, as its primary purpose, the adoption of a system of regulation based upon the safety of color additives. Therefore, the provision could be eliminated as not germane to the rest of the bill, and, on the additional ground that the subject is adequately covered by provisions of the Federal Trade Commission Act. However, I do not object to the inclusion of the provision in H.R. 7624 and $. 2197 but I do desire to call attention to the fact that the right of the consumers of this country to purchase colored margarine has already been established as a national publi¢ policy by the Congress, in 1950, and by the legislatures of all but two of the States. The quotation from the report of the Senate committee ac- companying S. 2197, set forth above in this statement, shows that the Senate committee specifically recognized the right of the consumers of this country to purchase colored margarine. Therefore, the provision under consideration should not be understood as giving the Secretary any authority to prohibit the use of colored margarine if the color additive proposed for use therein otherwise meets the standards of safety contained in H.R, 7624 and S$. 2197. (4) Seetion 706(b)(8) of both bills provides, in effect, that the Secretary may, under certain circumstances, decide that one industry may use a given color while another industry may not. This results from the fact that the bills authorize the Secretary to establish tolernnces, if he finds this to be necessary. Then, section 706(b) (8), in effect, provides that, to keep the use of a particular COLOR ADDITIVES 545 color additive within such safe tolerances, he may determine which use or uses may be made of the additive to the exclusion of other uses. Obviously, under this provision, an extraordinary power is conferred upon the Secretary which could result in discrimination among those who desire to use a particular color additive. We feel that the Congress should make it clear to the Secretary that special care should be taken by him in the administration of this provision so as to avoid potential discrimination among competing users of a particular color additive. I commend the Congress for the attention it is giving to this crucially important legislation, and I urge the Congress to enact it without delay. MANUFACTURING CHEMISTS’ ASSOCIATION, INC., Washington, D.C., May 18, 1960. Hon. Oren Harzis, House Interstate and Foreign Commerce Committee, U.S. House of Representatives, Washington, D.C. Dear Mr. Hargis: We have carefully studied Secretary Flemming’s May 9 statement to your committee reiterating the opposition of the Department of Health, Education, and Welfare to proposals for changes in the cancer clause as it would be incorporated in proposed color additives legislation. In view of Secretary Flemming’s continued support of such a clause, we would like to summarize below our position on this important matter. In our statement of February 10 to your committee, we opposed the inclusion in H.R. 7624 of an inflexible cancer clause which precludes the application of ‘diseretion and scientific judgment. We urged that questions concerning safety be resolved by the findings of a group of competent and representative scientists which would review all relevant data and make appropriate recommendations. It is apparent that the difference between the Secretary’s view and our own is not so much a consequence of differing appraisals of the cancer problem as it is the result of our differing views of the way in which scientific questions may best be administered. Once it is acknowledged—as it must be—that man’s understanding of carcinogenesis is continuously being improved; that is, that his knowledge is a changing thing, it follows as a necessary corollary that governmental regulation of questions of carcinogenicity should be flexible enough to permit adaptation to such advances in knowledge. The cancer clause is the antithesis of flexibility. This provision, hastily enacted into the Food Additives Amendment of 1958 without serious reflection, imposes absolute statutory bars where flexible administrative controls are needed. Only yesterday we had the opportunity to examine the report and recom- mendations of the study group convened by the President's special assistant for science and technology, Dr. George B. Kistiakowsky, The group's principal recommendation was that the Secretary of Health, Education, and Welfare ap- point an advisory board of scientists to assist him in the evaluation of scientific evidence on the basis of which decisions have to be made prohibiting or permit- ting the use of certain possible carcinogenic compounds. We believe that this recommendation is excellent and is entirely consistent with the suggestion we made on February 10 and we particularly commend to your attention the fact that such a board would be composed of scientists from the National Cancer Institute, the Food and Drug Administration, the U.S. Department of Agcricul- ture, “and the scientists outside of Government from a panel nominated by the National Academy of Sciences.” We respectfully urge that you incorporate this proposal in S. 2197, which has been passed by the Senate and which, with the changes we have recommended to your committee, would constitute an excellent basis for wise color additives legislation. Adoption of the recommendations contained in the report of the special panel convened at the request of the President would provide a means of settling many of the perplexing problems which have resulted from the arbitrary prohibition contained in the cancer clause. The rule of reason and scientific judgment would be advanced in this important area of Government regulation. Very truly yours, KENNETH E. MULrorn, Chairman, MCA Food Additires Committee, 546 COLOR ADDITIVES RESPONSE OF MANUFACTURING CHEMISTS’ ASSOCIATION TO HEW CoMMENTS oF ApRIL 21, 1960, ReGaRDING ProposkD AMENDMENTS TO S, 2197 orn H.R. 7624 I. SCOPE OF BILL 1. Nature, source, or type of action of the coloring material (c) Food additives—Along with other witnesses, the Manufacturing Chem- ists’ Association proposed that substances which are food additives, the uses of which have been approved by published regulations pursuant to the Food Addi- tives Amendment of 1958, and substances exempt from the food additives amend- ment because of prior sanction, be exempt from the pending color additives bill. The Secretary's answer to this proposal is that (1) this would prevent the publication of a complete list of approved as safe color additives and (2) that such substances could be listed by the Secretary promptly under the color addi- tives bill as it now reads. We do not know the reason for the emphasis by the Secretary on having a complete list of acceptable color additives. We know of no demand by the manufacturers or users of color additives for such a list. Furthermore, the Secretary has sufficient authority to publish complete lists of safe color additives as he has done in case of food additives which have prior sanction or are generally recognized as safe under the food additives amendment. We have reservations regarding the Secretary’s statement that he would list substances without procedural burdens upon industry. We are concerned that the administrators of the law may subsequently discover reasons why the color additive bill would prevent this. The proposed color additive bill contains re- quirements which vary from those of the food additives amendment. For in- stance there is a reference in the color additive bill for analytical methods to determine the identity of the color additive in food, which requirement is not present in the food additives amendment. As the Secretary has shown no substantial reason for the deletion of the proposed exemption and as we and others representing industry feel strongly that the failure to give such an exemption will result in useless duplication of effort by industry, we respectfully recommend inclusion of the exemption. 2. Purpose for which a dye material is used (a) In general.—The Manufacturing Chemists’ Association proposed limiting the color additives definition to include only those substances which are used “primarily for the purpose of imparting color,” leaving substances with other primary purposes under the food additives amendment. The Secretary makes three arguments against this proposal. First, he says this would be a step backward from the present coal tar color provisions of the Food, Drug, and Cosmetie Act. It is not clear what he means by the term “backward.” We are not proposing that additives used primarily for a purpose other than coloring be exempt from regulation under the act entirely, but that they be dealt with under the food additives amendment where they properly belong. Second, he repeats the argument for a complete list of color additives which we believe we have already shown to be without merit as (1) we doubt the need for such a complete list and (2) our proposal in no way prevents the Secretary from drawing up and publishing any list felt desirable by him. Third, the Secretary states that such a definition would impose a heavy ad- ministrative and enforcement burden upon the Government. We feel certain that there will be no serious administrative problem as the person who wants to clear a particular use for an additive to food will know the primary purpose of his use and will request action under the proper section of the act. In enforce- ment, fine lines of distinction will, of course, occur. However, this is always the case in law enforcement. We do not see how any public health hazard could be a consequence. Certainly this is true if the product in question is cleared as safe under either the food additives amendment of the color additives bill. And if it is cleared under neither, a defense to an enforcement action bronght under one amendment that the product, instend, was subject to the other amendment would obviously serve no purpose. 8. Substances generally recognized as safe The Mannfacturing Chemists’ Association and other witnesses proposed that substances generally recognized to be safe under conditions of intended use be exempt from the color additive bill. COLOR ADDITIVES 547 The Secretary again argues that this would prevent a complete list of safe color additives. Again we point out that, to the extent that such a complete list is desired, it can be had, just as the Secretary has listed “generally recognized as safe food additives.” Secondly, the Secretary argues that “generally recognized as safe colors” may, in fact, be unsafe. This is equally the case with regard to generally recognized as safe materials exempt under the food additives amendment. We do not see how the concept is any less sound for colors. Furthermore, we believe the Food and Drug Administration’s experience with the general recognition of safety exemption under the food additives amendment clearly indicates no grounds for serious concern. Industry has taken a responsible attitude toward this matter and, as the Food and Drug Administration has pointed out many times, if reason to doubt the safety of a color appears and such information is made known to the relevant scientific community, the generally recognized as safe status may be lost and the product then would be subject to the food or color additive amendment. We submit that this is just as reasonable for colors as it is for other additives to foods. Thirdly, the Secretary states that the question of what is a color additive can- not rationally be made to depend on whether the additive is generally recognized as safe. It is difficult to see why this provision was regarded as rational by Congress in the case of food additives and could not be so regarded in the case of color additives. The Secretary says that, although the food additives amend- ment exemption was all right because of the broad sweep with which the amend- ment would otherwise have covered “salt, vinegar, and natural spices,” it would be retrogressive to do the same thing for colors. But natural spices and other common materials may well be color additives and not food additives under the all encompassing definition of color additives in the pending bill, and thus, we believe, the argument is self-defeating. Finally, the Secretary agrees to automatic listing of substances which have been published as generally recognized as safe food additives. We do not be- lieve that such a listing is a reasonable substitute for our proposal. In the first place, probably more generally recognized as safe substances would thereby be left unexempt. The Secretary has made no effort to list obviously safe food addi- tives, such as sugar and vinegar, and many proposed generally recognized as safe food additives are currently pending. These and many others as yet un- proposed for listing will become color additives under the present color additive bill. None of these could thereafter become a “substance exempt from the term ‘food additive’ because of its being generally recognized by qualified experts as safe for its intended use.” Furthermore, we believe that, if a substance is, in fact, generally recognized as safe, it should be exempt whether or not the Secre- tary agrees that it is generally recognized as safe. II. SURSTANTIVE PROVISIONS AS TO LISTING OF COLORS (SEC. 7086) 1. Basic provision for listing The Manufacturing Chemists’ Association proposed that section 706(b) (1) begin as follows: “The Secretary shall, by regulation, separately list color addi- tives for use in or on food.” The Secretary agrees that this would be proper as long as “it is clearly under- stood that the Secretary may not and will not merely list colors by regulation, but, necessarily, also promulgate interstitial regulations providing for the listing, i.e., relating to the conditions and procedures for such listing, interpretations of the law, etc.” This is understood and we, therefore, recommend the adoption of our proposal for the purpose of clarity. 2. Analytical methods requirement The Manufacturing Chemists’ Association proposed the deletion of the words, “identify and” from section 706(b)(5)(D). The Secretary, in his comments does not give his reason why such language is needed in a color additives bill although it was not deemed necessary in the food additives amendment. He indicates concern over the Government's inability to be sure that color additives are not present in amounts in excess of the established tolerance. We feel that the Secretary should recognize that often it is impossible to determine the identity of a substance in food at the minute level of the established tolerance 548 COLOR ADDITIVES and that it should be wholly sufficient for enforcement purposes to be able to show that the additive itself is of such a character that no amount in excess of the tolerance could get into the food. We believe adequate enforcement tools are provided by the requirement for needed analytical methods, as stated in the food additives amendment, without the addition of the words “identity and,” which give us concern. II. PROCEDURAL CHANGES UNDER PERMANENT PART OF BILL (SEC. 706(d) ) 2. Time limits for action on petition The Manufacturing Chemists’ Association proposed time limits within which the Secretary shall publish notice of the regulation proposed by the petitioner and the order of the Secretary thereon. The Secretary agrees to such time limits and proposes slightly different lan- guage for such provision (see his enclosure III), with which language we concur. IV. CHANGES IN TRANSITIONAL PART 4. Proposal to delete section 203(d) (3) (title II) We feel that a provisional listing for the very purpose of enabling the manu- facturer or user to develop scientific data regarding the color should not be denied because the data is not available. There are adequate safeguards for termination of the listing if there is any public health hazard or if the scientific investigations are not pursued in good faith. Vv. MISCELLANEOUS Regarding the proposed cancer clause, the Manufacturing Chemists’ Associ- ation testimony referred to an article in a scientific journal and stated, “The work reported in this article appears to establish that hard-boiled eggs when fed to mice result in cancer.” The Secretary answered, in part, “Our experts, who are acquainted not only with this article but with the general research going on in the cancer field, advise us that the experiment to which Mr. Mulford refers does not prove that eggs contain a carcinogenic chemical.” (Emphasis supplied.) We believe the Secretary has thus emphasized the point that we were trying to make, namely, that the proposed cancer clause may well outlaw perfectly safe foods or food or color additives. This clause is not limited to situations in which there is proof that a carcinogenic chemical is present in the additive. In fact, the clause does not use the word “carcinogen” or “carcinogenic,” but rather the “if it is found to induce cancer” language, which is much broader because substances may be used in such a manner as to induce cancer without their being carcinogenic. The hard-boiled egg article was merely cited as an example of this. STATEMENT OF Joe D. Nicnuors, M.D., ATLANTA, TEx. I am a graduate of the University of Arkansas Medical School, having re ceived an M.D. degree in 1932. I own and operate a 30-bed general hospital in Atlanta, Tex. I am a past president of the Tri-State Medical Society and for 9 years was councilor of the Texas Medical Association. The increase in the incidence of cancer in America has reached an alarming rate. The chief cause of death in children under 14 years of age, after acci- dents, is cancer. Known cancer-causing chemicals are being added to food in this country. While it may be true that safe doses can be established for many poisons that are absorbed and excreted without residual effects, responsible bodies of cancer experts have repeatedly stated that safe doses cannot yet be established with any confidence for chemicals that produce cancer. Cancer-inciting substances (carcinogens) have a different pharmacological action from most other poisons. They have irreversible effects on cells. The Fifth International Cancer Congress in San Paulo unamiously adopted a resolution against the concept of safe doses for carcinogens. COLOR ADDITIVES 549 In 1956 the International Union Against Cancer convened at a symposium on food additives in Rome. This symposium was attended by cancer experts from 40 countries. Our Food and Drug Administration was represented. This meet- ing specifically concluded that any substance found to induce cancer in any species of animal in any dose should not be approved for use in food. The Delaney amendment to the food and drug law passed in 1958 prohibits the use of known cancer-causing chemicals in foods. It establishes the prin- ciple that a manufacturer must prove a chemical food addiitve safe before it can be used. This is a good and fair law. It is a result of many years of eareful study of this problem. The American people deserve the protection xiven them by the Delaney amendment. It must be kept in the law. ASHEVILLE, N.C., January 28, 1960. Hon. Davin McKee Hatt, Jr., House of Representatieva, Washington, D.C.: Re congressional hearings starting January 26 urge you to bring to the atten- tion of Oren Harris, chairman, Interstate and Foreign Commerce Committee, the need for a 2-year extension in the March 5 effective date of the food and drug amendment. The $18 billion packaging industry, of which we are a part, has been most diligent in its efforts to submit the necessary scientific data to the FDA, but it is physically impossible to complete this work by March 5. We also feel that packaging materials should be recognized as unintentional additives and should not be subjected to the same rigid standards as intentional food additives. We sincerely believe these necessary changes will permit more effective enforcement. We are heartly in support of the purpose of the food and drug amendment and continue to be primarily concerned with protecting the health of the American citizens. W. K. GrusMan, National Starch & Chemical Corp., American Parboard Division. NEWTON PAPER Co., Holyoke, Mass., January 26, 1960. Congressman S1rtvio O. Conte, House Office Building, Washington, D.C. Dear CoNnGRESSMAN: It is imperative that you use every influence to support H.R. 7624, which is being discussed by the House Interstate and Foreign Com- merce Committee this week. This bill covers an amendment on color additives in connection with the Food and Drug Additives Amendment of 1958. Newton Paper Co. is one of the most important sources of supply of Chocolate layer board used in the packaging of candy. So much confusion and uncer- tainty has arisen over the status of various colors and chemicals used in the manufacture of this board, that our position is being seriously jeopardized, It should be noted that our chocolate layer board has been put through extensive tests over the past several years by the Institute of Paper Chemistry and by many confectionery companies, and has been found free of any harmful sub- stances. It is vital, therefore, that proper time be given for further study and clari- fication of color additives by an extension of the March 5, 1960, deadline date covering materials, in use prior to January 1, 1958. We have done everything possible by working with our trade association and exerting pressure on our suppliers of colors and chemicals to obtain clear- ance of these materials as safe, so that we may in turn certify to our customers that our chocolate layer board meets the qualifications of the Food and Drug Additives Amendment of 1958, Tf an extension is not granted we may be forced to drastically curtail our production causing undue hardship to our employees. The confectionery in- dustry will also be seriously hampered without chocolate layer board to pack- age their products. We ask that you give this problem your most serious consideration. Sincerely, W. W. NewrTon, President. 550 COLOR ADDITIVES Sun CHEMICAL Corp., New York, N.Y., July 2, 1959. Hon. Oren Harris, Chairman of the House Committee on Interstate and Foreign Commerce, House Office Building, Washington, D.C. Dear Sir: I would like to urge your support of H.R. 7624 Color Additive Amendments of 1959. This bill would amend the Federal Food Drug and Cosmetic Act to authorize the use of suitable color additives in or on foods, drugs, and cosmetics, including maximum tolerances, under which such ad:i- tives may be used safely. We are the largest manufacturer of colors used in the cosmetic industry in this country and the passage of this bill is of paramount interest to us in the continuance of this important industry. Although heartily in favor of the objectives of the bill we respectfully submit the following minor changes designed to clarify and improve its administra- tion. Section 706(b) (4)C.—We believe this section to be unworkable. We axree with section B that we should be able to determine the quantity of pure pix- ment intermediates and impurities. However our customers use our pigment in (for example) a lipstick base of secret composition, using as one constituent purchased perfumes of proprietary composition. It is fantastic to believe that suitable analytical methods exist for determining the products of interaction of every constituent of our pigment with every constituent of the perfume. On this basis, eating bread would be suspect. Who knows what are the chemical reactions of every constituent of the lard with every constituent of the flour and yeast. We believe that if everything added to the final product has a history of being safe, and no known reactions produce anything harmful, the final product will be harmless. If any doubt exists, it should be resolved by safety tests of the final product and not by exhaustive analysis. Section 706(b)5(B).—We object to the emphasis placed on cancer. Of course a color should not be listed if it induces cancer or for that matter any disease or affliction. There is not a shred of evidence that D & C pigments induce cancer. Why cause the users of cosmetics undue anxiety by suggesting that they may be inducing cancer? In many sections of the bill the need for pharmacology is implied. Nowhere does it say who shall do it. We suggest that the Food and Drug Administration employ their existing facilities, augmented if necessary, for this purpose. We propose to finance this work by fees for the certification service. Thus the con- sumer would pay in proportion to his use of the pharmacology. We tremble at the thought of setting up scientific committees among units of the industry and in turn having them hire pharmacologists and set up laboratories. There would be times when Food and Drug Administration would feel the necessity of check- ing our results. They would have to duplicate testing and we would have to pay for the work twice; as manufacturers and as taxpayers. We hope that these improvements will not impede the progress of this bill toward final passage. Very truly yours, Eric N. BLACKSTEAD, Vice President. Sun Cremtear Corp., New York, N.Y., July 2, 1959. Hon. Kennetr A. Roperts, Chairman of the Subcommittee on Health and Science of the House Committee on Interstate and Foreign Commerce, House Office Building, Washington, D.C. Dear Str: T would like to urge your suport of H.R. 7624 Color Additive Amend- ments of 1959. As the largest manufacturer of colors used for the cosmetic in- dustry in this country we feel that it is essential to the continuance of this im- portant industry. Mr. J. W. Ingram, technical director of our Ansbacher-Siegle Division has already written you and included some minor changes which we feel would clarify the bill, however the objectives of the bill receive our wholehearted endorsement. May we have your support? Sincerely, Erto N. BirackstTeEan, Vice President. COLOR ADDITIVES 551 ANSRBACHER-SIEGLE CorP., Rosebank, Staten Island, N.Y., June 30, 1959. Subject : H.R. 7624 Color Additive Amendments of 1959. Hon. Kennetu A. Roperts, Chairman of the Subcommittee on Health and Science of the House Committee on Interstate and Foreign Commerce, House Office Building, Washington, D.C. Dear Sir: This bill would amend the Federal Food Drug and Cosmetic Act to authorize the use of suitable color additives in or on foods, drugs, and cos- metics, including maximum tolerances, under which such additives may be used safely. Our interest is that of the largest manufactures of colors used for cosmetic in the country. We are heartily in favor of the objectives of the bill and urge its speedy passage with several minor changes designed to clarify and improve its administration. Several of these changes are listed below. SECTION 706 (b) (4)C We believe this section to be unworkable. We agree with section B that we should be able to determine the quantity of pure pigment, intermediates, and im- purities. However our customers use our pigment in (for example) a lipstick base of secret composition, using as one constituent purchased perfumes of pro- prietary composition. It is fantastic to believe that suitable analytical methods exist for determining the products of interaction of every constituent of our pigment with every constituent of the perfume. On this basis, eating bread would be suspect. Who knows what are the chemical reactions of every con- stituent of the lard with every constituent of the flour and yeast. We believe that if everything added to the final product has a history of being safe, and no known reactions produce anything harmful, the final product will be harm- less. If any doubt exists, it should be resolved by safety tests of the final product aud not by exhaustive analysis. SECTION 706 (b)5(B) We object to the emphasis place on cancer. Of course a color should not be listed if it induces cancer or for that matter any disease or affliction. There is not a shred of evidence that D. & C. pigments induce cancer. Why cause the users of cosmetics undue anxiety by suggesting that they may be inducing cancer? In many sections of the bill the need for pharmacology is implied. Nowhere does it say who shall do it. We suggest that the Food and Drug Administration employ their existing facilities, augmented if necessary, for this purpose. We propose to finance this work by fees for the certification service. Thus the con- sumer would pay in proportion to his use of the pharmacology. We tremble at the thought of setting up scientific committees among units of the industry and in turn having them hire pharmacologists and set up laboratories. There would be times when FDA would feel the necessity of checking our results. They would have to duplicate testing and we would have to pay for the work twice; as manufacturers and as taxpayers. We hope that these improvements will not impede the progress of this bill toward final passage. Very truly yours, J. W. Incram, Technical Director, AMERICAN FEED MANUFACTURERS ASSOCIATION, INC., Chicago, Ill., March 1, 1960. Hon. OREN Harris, Chairman, House Interstate and Foreign Commerce Committee, House Office Building, Washington, D.C. Dear CONGRESSMAN Harris: There are certain aspects of the proposed color- additives legislation (H.R. 7624 and 8. 2197) that have considerable significance to the feed industry. The recently enacted food-additives amendment covers food for both animals and humans. It is true that many feed ingredients are not covered since they 552 COLOR ADDITIVES are generally recognized as safe because of common use over a long period of time. The feed industry does not use color additives, as such, to any extent. Any color additives that might be developed in the future for use in feeds would be subject to the food-additives amendment since they would be ingested by the birds or animals. It is possible, unless specific exemption is granted, that under the present broad definition of a color additive that certain feed ingredients could be considered both a color additive and a food additive. This is unnecessary, and could result in an undue burden and hardship. The food-additives amendment provides ample safeguards to prevent the use of unsafe additives in feed. As an agricultural industry, we are also very much interested in the long-range implications of the very stringent Delaney “cancer” clause as it is now written and interpreted. Unless some modification is made, progress in the development of new and better agricultural chemicals will be seriously threatened. If this is permitted to happen all segments of our population will suffer. We agree with the testimony presented to you and your committee on February 10 and 11, and trust that the Delaney amendment will be modified to allow for the exercise of scientific judgment and at the same time amply protect the public health. Yours very truly, W. E. GLENNON, President. Brown & CoLMAN, ATTORNEYS AT Law, Kalamazoo, Mich., February 11, 1960. Re proposed color-additives amendment. Hon. Aucust E, JOHANSEN, House of Representatives, Washington, D.C. Dear Mr. JoHANSEN: I am writing you in regard to the above amendment on behalf of my client, Kalamazoo Spice Extraction Co., which is engaged in grind- ing and extracting spices for the flavoring and/or coloring of food. It is our understanding that there are presently being conducted hearings on H.R. 7624, before the House Interstate Commerce Committee, of which the Honorable Oren Harris is chairman. My client has already written to the Honorable Mr. Harris and the purpose of this letter is to enlist your aid in presenting our thinking as effectively as possible, particularly to the committee in its hearing on this important bill. We are aware of the passage in the Senate of S. 2197. Under the 1958 Food Additive Amendments, colors derived from natural sources and not classified as coal tar colors come under the same provisions as other natural and synthetic additives. We believe the provisions of this law are intelligently designed to protect the public health, and certification is not required of synthetic or natural products under this law. Rather, it is required that they be recognized as safe by FDA. If manufacturing processes are such as to impart a hazard to health, the law provides for corrective FDA action. Among the substances which we manufacture, and which might require FDA certification under the proposed act, are paprika, red pepper, turmeric, saffron, and cinnamon. Similarly, chili, grape juice, tomato puree, or beets might require certification if one of the purposes of its use was to impart a color—and cer- tainly FDA could argue that these substances have, as one purpose, the ob- jective of coloring food. The problem which my clients face is that it would be very impractical to have “batch certification” for natural coloring materials. “Batch certification” is presently required for coal tar colors, and requires the following steps: (1) Submit a sample of the batch, with a fee to FDA. (2) Testing by FDA. (2) Certification of the batch, if the test of the sample is approved. (4) Sales could then be made. (5) Record purchases of each sale. (6) Purchaser must record source of each lot purchased. The above procedure takes a few months, tying up inventory and increasing market risks. For example, at present, paprika extract is sold during processing. My eclient’s business is, after all, essentially the processing of agricultural products, and the subject legislation, apparently proposed by the coal tar color manufacturers, attempts to impose the same burdens on agriculture which are COLOR ADDITIVES 553 placed on coal tar colors, substances not occurring in nature and potentially hazardous to public health. We are unaware of any evidence that natural coloring materials commonly used in food have presented any hazard to health, either by themselves, or through their process of manufacture. Certainly, tomato puree appears no more hazardous nor in need of certification than fresh tomatoes. Dried chili peppers or red peppers, when ground, do not appear more in need of batch certification than green peppers appearing in the market. Ground paprika does not appear to present a greater hazard than fresh pimentos; or paprika extract, made by essentially the same process as corn oil, and in no more need of certifica- tion than corn oil. I would be glad to furnish any information you might desire in addition to that set forth in this letter. I will very much appreciate any means which you could use to present the above views to the committee. Thank you for your help in this matter. Very truly yours, Eric V. Brown. DovecHsor INpustRIEs, INC., New Richmond, Wis., April 5, 1960. Hon. Lester R. Jounson, House of Representatives, Washington, D.C. Dear Mr. Jonnson: House bill 7624, concerning the use of additives to im- part color to food, drugs, and cosmetics, is of great concern to me. It appears that this color additive bill could be construed as to include feed ingredients used in formula feeds for nutritional reasons, but which also may impart a color to the feed. I feel very strongly that it is most important to clearly separate the color additives amendment from the food additives amendment. Certainly a food addi- tive already given the green light because it has been recognized as safe, or has had previous sanction or approval, should not have to be cleared under a color law. Furthermore, the Delaney amendment is, in the bill's present form, included as part of this legislation. Basically, we realize, this amendment is being considered to protect public health. However, it seems that imposing a flat prohibition on all substances than can be made to produce cancer when ingested by animals, even if the dosage is a million times that normally ingested by man, is certainly unrelated to actual use conditions. Our American farmer today is being penalized be- cause of the Delaney amendment already in the food additive amendment laws. Several feed additives have been put to severe disaadvantage in use (diethylstilbesterol and arsenicals) because of this amendment with lack of actual scientific proof. Some of our own suppliers of feed nutrients have closed and curtailed research activities because of the broad implications of the Delaney amendment. They are unwilling to spend years of research work as well as millions of dollars on feed additives only to have them kept off the market because of the in- flexible cancer clause. Our job, Doughboy’s job, as a formula feed manufacturer is to supply high quality feeds to help the farmer make more food to feed our exploding population and be able to make a living as he does it. Therefore, we do not want to be “hamstrung” in our attempts to do this by the type of legislation proposed. All I ask is (1) a return to the Food and Drug Administration of the full right to exercise scientific judgment in determining which food and color additives are safe when used under conditions reasonably related to their in- tended use. This is the system under which FDA operated successfully until the Food Additives Amendment of 1958 became effective; (2) all feed ingredients ingested by livestock and poultry be subject to review and clearance under the food additives amendment, not under both the color additives amendment and the food additives amendment. Very truly yours, Dovucnroy INpustrirs, Inc., E. J. CasuMan, President. 554 COLOR ADDITIVES NATIONAL ASSOCIATION OF FrozEN Foon PACKERS, Washington, D.C., February 17, 1960. Hon. Oren Harris, Chairman, Committee on Interstate and Foreign Commerce, The Capitol, Washington, D.C. Dear Mr. Harris: I appreciate the opportunity to comment on H.R. 7624, relating to the use of color additives in foods, drugs, and cosmetics, on behalf of the National Association of Frozen Food Packers. The association is a nonprofit trade association whose members pack more than 75 percent of the frozen fruits, vegetables, and concentrates marketed in the United States, and a major proportion of the prepared frozen foods produced in this country. We are deeply concerned that each new legislative proposal for dealing with additives to food has, in its field of application, extended governmental authority beyond that of the preceding proposal. Thus, the food additives amendment, enacted in 1958, was more comprehensive, insofar as Government regulatory powers were concerned, than was the pesticide chemicals amendment, which had been enacted in 1954. The proposed color legislation follows the same pattern of expansion. In the area of regulation of colors in foods, drugs, and cosmetics, the color bill, H.R. 7624, would confer authority upon the Department which exceeds in its scope that granted by the food additives amendment, and as a corollary, would place more restrictions upon the regulated industries than does the food additives amendment. It is difficult to appreciate why the Department of Health, Education, and Welfare feels that it requires more comprehensive power over business opera- tions in its regulation of color additives than it asked for and received under the pesticide chemicals amendment and the food additives amendment. It is our hope that your committee will examine H.R. 7624 to determine what regulatory jurisdiction is essential for the Department in order to carry out the legitimate purposes of the proposed legislation, in the light of the experience which the Department has had under the previously enacted additives legis- lation. It seems apparent to us that the authority which the Department may exercise under the earlier additive statutes is adequate for protection of the public health and, indeed, in some respects, goes beyond adequacy into a field with which the Department should not be concerned at all. I. THE DEFINITION OF “COLOR ADDITIVE” (a) The titles of the Senate and House bills state their purposes: “to protect the public health” by prescribing the conditions under which color additives “may be safely used.” This is also the purpose of the food additives amendment, which is of far greater scope and significance from the standpoint of public health protection than the proposed color legislation would be. Insofar as we know, nobody has suggested that the food additives amendment does not furnish an adequate basis for safeguarding the public in the vast field in which it operates. The Department is apparently satisfied that it is adequate. It is difficult to un- derstand, then, why many food additives—those which are also colors—are to be removed from coverage of the food additives amendment and transferred to the proposed color legislation; and why some colors which are excluded from the coverage of the food additives amendment because they are generally recognized by qualified experts to be safe for use under the conditions of their intended use, are now to be subjected to the burdensome and exceptionally complicated pro- cedural provisions of the color legislation. This, however, would be the effect of H.R. 7624 if it is enacted with the defini- tion of “color additive” contained in section 101(¢) of that bill. That definition includes as a color additive any substance derived from any source which, when added or applied to a food, drug, or cosmetic, or to the human body, is capable of imparting color thereto. There is no limiting factor in the definition other than the “except” clause following subparagraph (B) of the definition, which will be discussed hereinafter. We propose, therefore, that the definition be amended to exclude from juris- diction under H.R. 7624, any food additive. This could be accomplished by revis- ing the introductory phrase of section 101(t)(1I) so that it would read “The term ‘color additive’ means a material other than a food additive, which * * *.” Coal tar colors are not regarded by the Department of Health, Education, and Welfare as subject to the food additives amendment. It has long been assumed that many coal tar colors used in food, drugs, and cosmetics require special COLOR ADDITIVES 555 treatment by way of batch certification, to assure their safety. Even if we ac- cept that proposition we may nevertheless maintain consistently that colors other than those coal tar colors which require batch certification, should be dealt with like other additives. If batch certification is not necessary for additives other than color additives, it is not apparent why it should be required for the latter (again, granting the exception for coal tar colors). Surely, in the case of foods, color additives from mineral, plant, or animal sources offer no greater hazard to the public health than the vast numbers of other additives from such sources which are used in foods. Such additives would be effectively controlled by the food additives amendment. The effect of the change which we propose in the definition would be to place all food additives, other than coal tar colors, under the same regulatory scheme. Surely this is a legical approach. We know of no sound reason why colors (at least those other than coal tar derivatives) should be subject to different require- ments, such as individual batch certification, from those applicable to other food additives, If there is a problem of definition of the scope of the term “coal tar color” in the application of the food additives and color legislation, it could be resolved by a suitable provision in H.R. 7624. This course would be far more appropriate, in our opinion, than is that proposed in the bill as it now stands, (b) Even with the change herein proposed, there is no basis that we can see, in a bill offered for public health protection, for the inclusion of any color addi- tive (including coal tar colors), which is known to be safe under the conditions of its intended use. We, therefore, recommend the addition of the following subparagraph (C) to the definition of “color additive”: “(C) is not generally recognized, among experts qualified by scientific training and experience to evaluate its safety, as having been adequately shown through scientific procedures, or experience based on common use, to be sufe when added or applied to a food, drug, or cosmetic, or to the human body or any part thereof :". This change would be of particular importance if all color additives, includ- ing those now subject to the food additives amendment, are to be regulated under the proposed legislation, contrary to the recommendation which we have made. Even such common and harmless articles as fruit and vegetable juices, and eoncentrates and extracts of such juices, are comprehended within the term “color additive’ as defined in H.R. 7624, as are other concededly safe sub stances, including those listed by FDA as exempt from the food additives amendment because they are generally recognized as safe for use in foods. Under the Senate bill such substunces are deemed safe for listing for food “while there is in effect a published finding of the Secretary” declaring them exempt from the term “food additive” by reason of general recognition of their safety." This provision, however, will not affect color additives which are not designated as exempt from the food additives amendment before the effec- tive date of color additives legislation since, under both the Senate and the House bills, color additives cease to be “food additives” upon the enactment of the color bills. Very few commonly used substances about which there can be no question at all of safety are listed in the announcements of exempt substances published by FDA. Consequently, the provision of the Senate bill in question cannot be expected to give any substantial relief. In addition to fruit and vegetable juices, some of the other common colors which have not been found and announced publicly to be safe, are carbon black, charcoal, titanium dioxide, chlorophyll, xanthophyll, and annato. It is true that such colors would be deemed to be provisionally listed be- cause of prior commercial use and, as to such uses, would be exempt from certification requirements.? This seems to mean, however, that a concededly safe color used in a particular food prior to the enactment date of the pro- posed law would be deemed to be provisionally listed and exempt from cer- tification for use only in the particular food in which it was used prior to the enactment date and, presumably, only in the quantities in which it was used in such food. If occasion arises for its use in a different quantity or in another food, the color would be deemed unsafe unless it is listed for the new use by the Secretary and is certified or exempted from certification for such use by a certification regulation. 1See, TO6(b) (4), as added by sec. 103(b) of S. 2197. ?See. 203(b)(2) and see. 203(d)(1)(d). These provisions are considered below. 56123—60——36 556 COLOR ADDITIVES A formal petition under section 701 of the act would be required to obtain a listing and exemption from certification of any new use of such a color unless FDA should act upon its own initiative as provided in section 701. In any event, a regulation would have to issue listing and exempting the par- ticular use from certification, before the end of any period of provisional listing and exemption from certification: a proposal for listing would have to be published; and any interested person would have an opportunity to object. If there is any objection by a person adversely affected, the regulation would be stayed and a public hearing would be held; perhaps an appeal to the courts would follow. The person “proposing” the use—who in fact may have been using the color for many years—must anticipate that through these procedures costly delays, perhaps litigation, and even an eventual denial of the use of the color may result. The same procedural provisions would apply to new colors, even though they are recognized as safe. We can see no justification for the establishment of these onerous require- ments as a condition of marketing concededly safe colors. If it made sense to exclude safe, commonly used substances from the food additives amendment by the test of general recognition of safety, it makes equal sense to exclude them from color additives regulation by the same test. ec. We propose, also, that subparagraph (B) of section 201(t) (I), which would be added to that section by section 101 of the bill, be revised to read as follows: “(B) is added or applied to a food, drug, or cosmetic or to the human body or any part thereof, primarily for the purpose of imparting color thereto ;” and that the “except” clause following subparagraph (B), which authorizes the exemption of materials used solely for purposes other than coloring, be eliminated from the bill. If the incidental effect of the addition of a substance to food is to impart color, as, for example, where tumeric is used as a condiment, such use would be excluded under the suggested change. Any substance exempted would, however, be subjected to regulation under the food additives amendment, just as it has been since that amendment became effective, unless it were gen- erally recognized as safe by qualified experts. We cannot see how the factor of “capability” of imparting color has any relevance to the question of classification as between colors and other food additives, as provided in the definition as now written. Moreover, practically all substances are capable of imparting some degree of color. It will obviously be difficult in many situations, and probably impossible in others, to make a determination whether a material is used solely for a pur- pose other than coloring, as contemplated in the “except” clause of the definition. Such a determination would too often depend upon subjective factors which we doubt that the Secretary is equipped to evaluate or should be empowered to evaluate. The regulation by which the Secretary would determine his own jurisdication involves a matter of basic coverage of the legislation. If that matter cannot be resolved informally with the Food and Drug Administration, it should be left to the courts. We think these changes in proposed section 201(t)(I) should be made re- gardless of whether the legislation includes colors which are now food additives in the definition of “color additive.” The reasons stated for the changes are applicable to both situations. Il. ECONOMIC DECISIONS COMMITTED TO THE DEPARTMENT Section 706(b) of the bill contains authority for the Secretary to make deter- minations on economic matters which have no relation to the declared purpose of the bill of safeguarding the public from toxic ingredients in foods, drugs, and cosmetics. (a) Section 706(b) (1) provides for the listing by the Secretary of colors which are “suitable and safe” for use. No tests of “suitability” are estab- lished as they are for safety. Consequently the Secretary would be empowered to deny listing of colors for uses which he considers unsuitable without any prescribed restrictions upon the exercise of his authority. This extension of power has no counterpart under the food additives amendment. It is found in the existing provisions of law relating to certification of coal tar colors but, when added to the other extensive grants of authority under H.R. 7624. the scope which it will be given is difficult to predict. The test of “suitability” should be eliminated. COLOR ADDITIVES 557 (b) Under section 706(b) (6) the Secretary would be directed not to list an additive for a proposed use if the data before him showed that such use would promote deception of the consumer in violation of the act or would otherwise result in misbranding or adulteration. Here is a clear enough indication that the listing of concededly safe colors will not follow as a matter of course; and that each use of a color will be serutinized by the Food and Drug Administration to determine whether it ap- pears to be in conflict with any provision of the act other than the color ad- ditives amendment or whether it would “promote deception of the consumer in violation of the act,” whatever that generalized catchall may mean. If FDA refuses to list a color under this provision, the remedy of the manu- facturer or shipper of the color is to appeal to the appropriate U.S. Court of Appeals under section 701 of the act, after following the procedures for objection and hearing provided under that section. In such a judicial pro- ceeding the findings of FDA as to the facts are conclusive upon the court if based upon a fair evaluation of the entire record of the administrative hear- ing. Thus, the burden of proof which, under the basic structure of the statute, has heretofore been upon the Government in the enforcement of the adulter- ation and misbranding provisions of the act, would effectively be shifted from FDA to the person who proposed to use the additive, since FDA would no longer have to adduce proof of violation by a preponderance of the evidence. In prac- tice, opinion evidence of FDA experts may be expected to play a substantial role in such cases. Here then, is an effective extension of the licensing sys- tem to substantial areas of economic adulteration and misbranding of foods, drugs, and cosmetics, coupled with a significant lightening of the requirement of proof by the Government. A similar provision is, of course, found in the food additives amendment (sec. 409(c) (3) (B) of the act). It does not appear to be germane either to food additives or color additives legislation, which is designed fundamentally to assure the safety of those additives. We must object to such basic changes in fields unrelated to safety, which are contrary to the traditional philosophy of our system of law. (c) Section 706(b) (7) would authorize denial of the use of a color additive if the Secretary finds that the data before him do not establish that the additive would “achieve the intended physical or other technical effect.’ This provi- sion also requires that any tolerance be fixed at a level no higher than the Secretary finds to be reasonably required to accomplish such physical or other technical effect. It is not clear what the scope of the Secretary’s authority would be under the provision. Is the Secretary to determine whether the shade or tint obtained by the use of the substance is too bright, or not bright enough? If the processor maintains that the coloring achieved is just what he wants is the Secretary to decide whether that intensity of hue would be of no commer- cial value and therefore may not be used? Surely the exercise of such a busi- ness judgment should not be committed to the Secretary. As a practical matter, if a substance imparts to the articles in which it is used a color or hue satisfactory to the processor it has achieved is intended effect, unless its use was for a purpose other than coloring. In that event the definition of color additive contemplates its exemption from H.R. 7624 upon a determination by the Secretary to that effect. If it is not capable of impart- ing color at all, it is not a color additive and the Secretary would be with- out jurisdiction over its use under the terms of the bill as introduced. This, then, is an onerous and potentially mischevious provision, both in the proposed color legislation and in the food additives legislation, where it also appears. It is, in addition, inherently illogical in the proposed color legislation, for the reasons which we have stated. We, therefore, urge the deletion of proposed paragraph 7 of section 706(b) of the act. (d) Section 706(b) (8) contains authority for the Secretary, where he finds it necessary in the interests of safety to restrict the uses of an additive, to determine for which uses the additive shall be or remain listed or how the aggregate allowable safe tolerances for an additive or additives are to be al- located among the uses proposed. One of the factors which the Secretary is to take into account in determining what restrictions shall be placed upon the uses of an additive is “(a) the relative marketability of the articles involved as affected by the proposed uses of the color additive (or of such related ad- ditives) in or on such articles, and the relative dependence of the industries concerned on such uses,” 558 COLOR ADDITIVES We do not believe that the Department is in a position to make such far- reaching economic decisions or that, in any event, it should be granted author- ity to do so. The Department should be confined, as we have insisted, to the determination of questions of safety of additives. If the authority to be granted in section 706(b) (8) were appropriate in color legislation, it would be equally appropriate in general food additives legislation. It is not provided in the food additives amendment. It would be out of place there as it is in H.R. 7624. Westrongly recommend its elimination. Similar considerations apply to the factor to be considered by the Secretary of “the availability, if any, of other color additives suitable and safe for one or more of the uses proposed,” as provided in section 706(b) (8) (e). This clause, too, should be eliminated. III. PROVISIONAL LISTING The scheme of provisional listings and removals from the provisional list is remarkable for its grant of extensive powers to the Secretary without the traditional safeguards of hearings, findings, and judicial review, even when viewed in the light of some of the other broad authorizations of the bill which have been discussed. Section 203(d)(2)(A) provides that “Regulations under this section shall, from time to time, be issued, amended, or repealed by the Secretary without re- gard to the requirements of the basic act * * *.” This means that notice, hearing, and judicial review are not required for delisting color additives now in commercial use which are provisionally listed (or deemed provisionally listed) under other provisions of section 203. If, in the judgment of the Secretary such action is necessary to protect the public health, he may “forthwith” terminate a provisional listing (sec, 203(d)(1)(2)). Not only does this extreme grant of unencumbered authority depart from the basic pattern of the Food, Drug, and Cosmetic Act and the food additives and pesticide chemical amendments, but it is not consistent with the fundamental concepts of fairness in administra- tive regulation which are established in our legal system, It provides none of the protection against arbitrary action affecting substantial property interests in provisional listings, which are afforded by the provisions of section T06(d) of the bill with respect to new colors. Section T06(d) has the effect of in- corporating the procedural and judicial review provisions of the basic act and the food additives amendment. Those provisions should also be made applicable to regulations under section 203(d) (2) (A). IV. THE CANCER CLAUSE The so-called Delaney clause, which has been adapted for H.R. 7624 from the food additives amendment, is the final provision to which we shall refer. It is found in section 706(b) (5) (B) of the bill. We know of no substances used in the processing of frozen foods which might be affected by the cancer clause. We are certain that no freezer would know- ingly use in frozen foods a substance which might induce cancer in human beings. We are persuaded, however, that the presence of this hastily adapted provision in the food additives amendment, and its enactment in H.R. 7624, constitutes a disservice to the cause of basic and practical research in agricul- tural and other chemical agents which are today essential for use in foods, drugs, and cosmetics, There has been impressive testimony before your com- tmhittee to this effect. Moreover, the per se interpretation given to the Delaney clause by the Depart- ment of Health, Education, and Welfare deprives the Food and Drug Adminis- tration of the right to exercise scientific judgment in evaluating the safety of useful chemicals which, but for the Delaney clause, might be cleared for use in foods without any hazard to the public health. If there is hazard in the use of an additive, we are convinced from experience with, and observation of the operations of FDA over the years, that its use will not be permitted whether the danger which is involved is from cancer or any other disease condition. If it were necessary to ban from use, additives which induce cancer in animals, without regard to the concentrations or other conditions of their use, it would seem to us that it would also be necessary to prohibit, at the least, the use of muny other additives which induce diseases in animals whose causes in human beings we do not know or of which we are uncertain. The ultimate reach of such a doctrine could not be forseen, The food additives amendment was unanimously adopted by your committee in 1958 without the Delaney clause. The Senate passed the food additives bill COLOR ADDITIVES 559 without the Delaney clause and has adopted 8S. 2197, the companion bill of H.R. 7624, without that provision. The basic approach of both the color and food additives legislation cannot be squared with the Department’s concept of the cancer clause. Conditions of use in both cases, as well as under the pesticide chemicals amendment, are the basic element in the determination of safety and the cancer clause prohibits the consideration of any such factors. We urge that, in adopting color additives legislation, this committee return to the basic philosophy underlying this and the other additives legislation which has been enacted by the Congress, CONCLUSION We have recommended the following changes in the bill— (1) (a) The revision of the definition of “color additive” in section 101(c) of the bill to exclude any food additive as defined in section 201(s) of the Fed- eral Food, Drug, and Cosmetic Act. (b) The inclusion in the definition of a new subparagraph (C) to exclude from coverage of the bill substances which are generally recognized as safe under the conditions of their intended use. (¢) The revision of subparagraph (B) to limit the application of the bill to materials used “primarily for the purpose of imparting color,” and the elim- ination of the “except” clause following the present subparagraph (B). 2) The elimination of those provisions authorizing economic determinations by the Secretary, viz, (a) the test of “suitability” for use in section 706(b) (1); (b) section 706(b) (6); (c) section 706(b) (7); and (d) section 706(b) (8) (A) and (C). (3) Inclusion of procedural safeguards in the scheme of provisional listing, as provided for clearances for new color additives or new uses of such additives. (4) Elimination of section 706(b) (5) (B), the cancer clause. With these changes, the bill would, we believe, be fully adequate to protect consumers against hazards which may result from the use of color additives in foods, drugs, or cosmetics. Respectfully submitted. LAWRENCE S. MARTIN, Secretary-Manager. Views oF THE CENTRAL Sora Co. In principle, we respectfully request your careful consideration of these three points : 1. A return to the Food and Drug Administration of the full right to exercise scientific judgment in determining which food (feed) and color additives are safe when used under conditions reasonably related to their intended use. 2. Feed ingredients ingested by poultry and livestock should be subject to review and clearance under only the food additives amendment (not both food and color additives amendments). 3. If the Delaney clause must be included it should be changed to read: “A color additive (or food additive) shall be deemed unsafe * * * if the additive is found in amounts and under conditions reasonably related to the intended use to induce cancer when ingested by man or animal.” The addition of the italicized clause would permit scientific Judgment in evaluating new additives but would still protect the public. Finally, the Delaney amendment stifles research in agriculture and works against the general public. Properly used chemicals and additives developed through research have significantly contributed to feeding our people abundantly, economically and safely. Respectfully yours, Harotp W. McMILLen. ANIMAL HEALTH INSTITUTE, Des Moines, Towa, March 30, 1960. Hon, Oren Harris, House of Representatives, Washington, D.C. Dear Mr. Harris: Because of the overall significance of the current delibera- tions of the Committee on Interstate and Foreign Commerce, House of Repre- 560 COLOR ADDITIVES sentatives, which is considering color additives legislation, the Animal Health Institute wishes to express its views on H.R. 7624 and 8. 2197. The Animal Health Institute is a trade association whose members are en- gaged in the production and/or sale of biologics, pharmaceuticals, or allied products for veterinary use. The current list of members is attached hereto. The purposes of the Animal Health Institute include the encouragement of production of pure, safe, and efficacious products intended for use in animal health and nutrition, the encouragement of basic and applied research in the develop- ment of new and better products for animal agriculture, and the encouragement of safe and efficient methods in the production, packaging, transportation, and storage of such products. The Animal Health Institute is interested in color legislation to insure an adequate supply of colors for use in veterinary drugs. Among other things, colors are used in veterinary drugs which are sold to feed manufacturers as an aid in determining whether the drugs have been adequately and properly dispersed throughout finished feeds. Comments on the proposed color additives legislation will be limited to section 706(b) (5) (B) of H.R. 7624, the so-called cancer clause. No equivalent clause appears in S. 2197. A similar clause appears in section 409(c) (3) (A) of the Federal Food, Drug, and Cosmetic Act as amended by the food additives amendment of 1958. Ex- perience under the food additives amendment of 1958 indicates that the effect of this clause may be to seriously curtail research and the development of new products in the field of animal health, with resulting impairment of our ability to meet the food needs of a rapidly growing population. The Animal Health Institute is convinced that the use of additives at safe levels is essential to insure adequate production of high quality products from farm animals. One of the purposes of the food additives amendment of 1958, in fact, was to advance food technology by permitting the use of food additives at safe levels, Yet the cancer clause has already been invoked to bar additional approvals for valuable products long used in animal feeds and considered to be absolutely safe under conditions of use. The basis for these actions is totally unrelated to the use of these substances and constitutes a negation of scientific judgment in the evaluation of chemical additives. Furthermore, the cancer clause as presently worded inhibits the application of scientific judgment in evaluation of additives which are not even demonstrated earcinogens. Administrative decisions have already been made in the name of the cancer clause adversely affecting medicated animal feeds to the detriment of the farmer—even in the absence of any evidence that they have the capacity to produce cancer. The Animal Health Institute feels that the flat prohibitions contained in this clause should not be permitted to apply to products which have not been found by evidence considered reliable by qualified experts to proxi- mately induce cancer. However, to restore scientific judgment to the cancer clause, it is necessary to limit its operation so as to provide that approval for an additive shall be with- held if it is found to induce cancer when ingested by man or animal “in an amount and under conditions reasonably related to the intended use.” This amendment is consistent with the fundamental principle that substances which are without hazard to man or animal under conditions of use shall be permitted. The Animal Health Institute urges that such an amendment be added to section 706(b) (5) (B) of H.R. 7264. It is requested that this letter be inserted in the record and made part of the transcript of the hearings of the Committee on Interstate and Foreign Commerce pertaining to color additives legislation. Sincerely, D. L. Bruner, Evecutive Secretary. MEMBERSHIP LIST, ANIMAL HEALTH INSTITUTE Abbott Laboratories, North Chicago, Il. American Cyanamid Co., 30 Rockefeller Plaza, New York, N.Y. American Serum Co., 2117 Leech Avenue, Sioux City, Iowa. Anchor Serum Co., 2400 Frederick Avenue, St. Joseph, Mo. Anchor Serum Co. of Indiana, 1101 Kentucky Avenue, Indianapolis, Ind. Anchor Serum Co. of Minnesota, Shippers Club Building, South St. Paul, Minn. Armour Pharmaceutical Co., Box 511, Kankakee, Ill. Beckton, Dickinson & Co., Rutherford, N. J. COLOR ADDITIVES 561 Bio Ramo Drug Co., Inc., 325 West Baltimore Street, Baltimore, Md. Chemo Puro Manufacturing Co., 150 Doremus Avenue, Newark, N.J. Ciba Pharmaceutical Products, Inc., Summit, N.J. Colorado Serum Co., 4950 York Street, Denver, Colo. Corn States Laboratories, 1124 Harney Street, Omaha, Nebr. Cutter Laboratories, Fourth and Parker Streets, Berkeley, Calif. Dawe'’s Laboratories, Inc., 4800 South Richmond Street, Chicago, M1. Delaware Poultry Laboratories, Inc., Millsboro, Del. Dorn & Mitchell, Post Office Box 999, Opelika, Ala. Dow Chemical Co., Midland, Mich. Drug Topics, 155 East 44th Street, New York, N.Y. E. I. du Pont de Nemours & Co., Inc., Wilmington, Del. Farm Journal, Inc., Washington Square, Philadelphia, Pa. The Fox Co., Inc., Newfield, N.J. The Gland-O-Lac Co., 19th and Leavenworth Streets, Omaha, Nebr. Haver-Lockhart Laboratories, Post Office Box 676, Kansas City, Mo. Hazelton Laboratories, Box 30, Falls Church, Va. Hess & Clark, Ine., Ashland, Ohio. George H. Lee Co., 4175 Beck Avenue, St. Louis, Mo. Dr. LeGear, Ine., 4161 Beck Avenue, St. Louis, Mo. Eli Lilly & Co., Indianapolis, Ind. Magnus, Mabee & Reynard, Inc., 16 Desbrosses Street, New York, N.Y. Mallinckrodt Chemical Works, Second and Mallinckrodt Streets, St. Louis, Mo. Merck & Co., Inc., Rahway, N.J. New York Quinine & Chemical Division, 100 Church Street, New York, N.Y. Norwich Pharmacal Co., 17 Eaton Avenue, Norwich, N.Y. S. B. Penick & Co., 100 Church Street, New York, N.Y. Peters Serum Co., 1601 Genesee, Kansas City, Mo. Prentiss Drug & Chemical Co., Inc., 101 West 31st Street, New York, N.Y. Research Laboratories, Inc., Box 990, St. Joseph, Mo, I. D. Russell Co., 2463 Harrison, Kansas City, Mo. Dr. Salshury’s Laboratories, Charles City, Iowa. Smith Kline & French Laboratories, Philadelphia, Pa. E. R. Squibb & Sons, 745 Fifth Avenue, New York, N.Y. Sterwin Chemicals, Inc., 1450 Broadway, New York, N.Y. Successful Farming, 1716 Locust, Des Moines, Iowa. Vet Products Corp., 1522-24 Holmes Street, Kansas City, Mo. Vitamins, Inc., 809 West 58th Street, Chicago, Nl. Wallerstein Co., Wallerstein Square Mariners Harbor, Staten Island, N.Y. Watt Publishing Co., Mount Morris, Il. T. C. Wheaton Co., Millville, N.J. Whitmoyer Laboratories, Inc., Myerstown, Pa. Wilke Laboratories, Inc., Box 2494, Memphis, Tenn. Kaiamazoo Spice Exrraction Co., Kalamazoo, Mich., February 1, 1960. Hon. Oren Harris, Chairman, House Interstate and Foreign Commerce Committee, House of Representatives, Washington, D.C. Dear Mr. Harris: We are engaged in grinding and extracting spices for the flavoring and/or coloring of food. We therefore have a substantial interest in the legislation which you are considering as H.R. 7624, commonly referred to as the color additives bill. It is our understanding that the bill as originally presented to Congress was substantially that recommended and drafted by the coal-tar color trade associa- tion and that its key provisions remain unmodified, These provisions are designed to make all colors equal, regardless of source, and regardless of the potential hazards to the public, by authorizing FDA to require certification for any substance used to color food. Among the substances which we manufacture, and which might require FDA certification under the act, are paprika, red pepper, tumeric, saffron, and cinnamon. Similarly, chili, grapejuice, tomato puree, or beets might require certification if one of the purposes of its use was to impart a color—and 562 COLOR ADDITIVES certainly FDA could argue that these substances have, as one purpose, the objective of coloring food. Under the 1958 food additives amendment, colors derived from natural sources and not classified as coal-tar colors come under the same provisions as other natural and synthetic additives. We believe the provisions of this law are intelligently designed to protect the public health, and certification is not required of synthetic or natural products under this law. Rather, it is required that they be recognized as safe by FDA. If manufacturing processes are such as to impart a hazard to health, the law provides for corrective FDA action. The subject legislation proposes to draw a distinction between colors, regardless of source, and all other food components, because of some unsavory association with food colors in the past. We submit that any unsavory association is with the coal-tar colors and the policies followed by their manufacturers, and not with natural colors per se, or grapejuice, or tomato puree. We do not see any advantage, except to coal-tar manufacturers, in imposing added and pointless burdens upon natural coloring materials and foods. If the experience of FDA shows that some coal-tar colors are sufficiently safe and that certification is not required, it would be better to lighten the burden on them, by modifying the coal-tar color law to make certification discretionary, than to make a new law penalizing all colors for the benefit of those which may be unsafe. Although the argument is presented that a color, because of its natural source. is not per se safe, any lack of safety is adequately handled by the food additives amendment. If this amendment does not protect against an unsafe natural color, it cannot protect against other unsafe natural or synthetic additives. We are unaware of any evidence that natural coloring materials commonly used in food have presented any hazard to health, either by themselves, or through their process of manufacture. Certainly, tomato puree appears no more hazardous and in need of certification than fresh tomatoes. Dried chili peppers or red peppers, when ground, do not appear more in need of batch certification than green peppers appearing in the market. Ground paprika does not appear to present a greater hazard than fresh pimientos; or paprika extract, made by essentially the same provess as corn oil, any more in need of certification than corn oil, To apply certification procedures to any of the products mentioned in the above paragraph is a direct implication that any and all foods and food additives need batch certification to protect the public health. If such an assertion were made, it would be considered ridiculous. It is our opinion that certification provisions for any of the above substances are equally out of place. We cannot believe that your committee or the Congress believes that batch certification of certain spices or spice extracts, such as paprika, or any and all agricultural products, is necessary in the public health. We hope that you will not place a pointless burden on agriculture and agricultural processing industries for the sole purpose of aiding the coal-tar color manufacturers, If possible, I would appreciate your placing this letter in the record of your committee, and should be pleased to offer testimony at your convenience if anything might be gained by a fuller expression of the thoughts contained erein. Respectfully yours, KataMazoo Spice Extraction Co., Pau. H. Topp, Jr., President. KALAMAzZ00 SPICE EXTRACTION Co., Kalamazoo, Mich., March 28, 1960. Subject: Color additives bill (referred to herein as the color bill). Hon. Oren Harris, Member of Congress, House Office Building, Washington, D.C. Deak Mr. Harets: Thank you your letter of March 17 and the subsequent correspondence with our counsel, Mr. Erie V. Brown. In accordance with the suggestion contained in your letter to Mr. Brown under date of March 18, we would appreciate the incorporation of this statement in the committee record : COLOR ADDITIVES 563 1. PROPOSAL That the bill be rephrased to omit the part enclosed in black brackets. “See.101 * * * “(t) (1) The term ‘color additive’ means a material which— “(A) is a dye, pigment, or other substance made by a process of synthesis or similar artifice, [or extracted, isolated, or otherwise derived, with or without intermediate or final change of identity,] from a vegetable, animal, mineral, or other source, and * * *” and after paragraph (B) of this section, add the phrase printed in italic: “except that such term does not include any material which the Secretary, by regulation, determines is used (or intended to be used) solely for a purpose or purposes other than coloring or any material which is directly derived from a vegetable or animal source.” 2. REASONS FOR PROPOSED CHANGE (a) Background The 1958 Food Additives Amendment to the Federal Food, Drug and Cosmetic Act gives jurisdiction to FDA to control any substance which is a “food additive” within the meaning of that law. Among such substances are natural spices, extracts thereof, and other natural coloring materials such as extracts of car- rots and beets. It appears that, as to such substances, the publie health is adequately protected by the provisions of the food additives law, and that fur- ther restrictions are not required in the interest of public health. (b) Definition The color bill defines a “color additive” as any material capable of imparting a color to a food, except if the material is used solely for a purpose or purposes other than coloring. Under this definition, not only “food additives” such as spices, but foods themselves such as tomato puree and dried beets, would be con- sidered “color additives.” The 1958 Food Additives Amendment does not apply to foods, but only to “food additives.” We submit that the purpose of the color bill is similar and that food substances used to impart color to the products to which they are added are not intended to be covered. The color bill provides that a ‘color additive” shall be deemed to be suitable and safe if it is not a “food additive” as defined in section 201(s). Since a food such as dried beets or carrots is not a “food additive” under section 201(s), it will not be deemed suitable and safe for listing unless the requirements pro- posed by section 706(b) are fulfilled: such requirements appear to be intended as safeguards against toxic substances in synthetic colors and not as applying to natural foods. 3. DISCUSSION In view of the above considerations, we believe that the scope of the color bill would be improved by modifying the definition of the term “color additive” in section 101 as above provided. This modification would remove agricultural products or derivatives thereof from the scope of the color bill and leave them under the food additives amendment or as foods; they would not be listed as a “color additive” and batch certification would not be a potential requirement for such natural foods, It appears to us that these modifications would have the following effects: 1. Condimental substances such as ground red pepper and paprika, and extracts thereof, could not be included in the definition of a “color additive” and would remain under the food additives amendment. 2. Colors derived from agricultural products classified as foods, like carrots and beets, would not be considered “color additives” but would come under the food additives amendment, The term “color additive’ would not have to be a part of the label declaration of foods containing such substances, but the name of the food itself would be adequate to designate the source of the color. 3. It is not enough to say that under the color bill as proposed, FDA would have discretion to eliminate the requirement of batch certification from such natural foods. Whenever a Government agency has discretion to include or exclude a product from its scope, it tends to include rather than exclude such 564 COLOR ADDITIVES product. The interests of public health do not require this protection. The interests of the industry require that this possibility be eliminated. We greatly appreciate this opportunity of having our viewpoint considered by your committee. Very truly yours, KatamMazoo Spice Extraction Co., Pau. H. Topp, Jr., President. WALNUT Grove Propucts Co., INc., Atlantic, Lowa, April 6, 1960. Hon. Ben F. JENSEN, House of Representatives, Washington, D.C. Dear Ben: The Interstate and Foreign Commerce Committee of your House is considering legislation amending the Food and Drug Act with a bill known as the color additives amendment, H.R. 7624. Although you do not serve on this particular committee, Ben, we want to express our opinions to you in regard to this legislation and hope you will give them your due consideration and perhaps will pass them on to your fellow Congressmen. This bill is so worded that it can be applied to any substance added to animal feed regardless of whether or not it was so added to affect color. In the bill a “color additive” is defined as “a substance * * * when added * * * to a food * * * is capable * * * of imparting color thereto.” Color includes black, white, or intermediate grays. As virtually any substance when added to a feed imparts some degree of color to the final product, the scope of this amendment is extremely broad and, if passed as it is now worded, will be needlessly burden- some to the feed industry. It is suggested that the bill be amended to state that a color additive “does not include a food additive or any material which the Secretary, by regulation, determines is used (or intended to be used) solely for a purpose or purposes other than coloring.” H.R. 7624 contains a cancer clause more restrictive than the Delaney clause in the Food Additives Amendment of 1958, and like the Delaney clause it pre- vents the exercise of scientific Judgment by the Food and Drug Administration in the evaluation of all pertinent data. We believe the protection of the public health to be a paramount consideration; however, we do not believe that the interests of the public would be jeopardized by the exercise by the Food and Drug Administration of scientific judgment in evaluating all pertinent data. Therefore, we contend the cancer clause of the color additives bill should be amended to read in part as follows: “A color additive * * * shall be deemed unsafe * * * if the additive is found in amounts and under conditions reasonably related to the intended use to induce cancer when ingested by man or animal.” The italic portion is the only change we suggest in this clause. This would not take any power away from the Food and Drug Administration and would still require that the safety of the food additive be proven by the manufacturer. In addition, Ben, we urge this same amendment be made to the Delaney amend- ment to the Food Additives Act of 1958. However, the point to be made at this moment is to not allow the same mistake made in the Delaney amendment to be made in regard to the color additives amendment. Finally, the bill provides that the color additives may be listed for use if they are “suitable and safe.” If the bill is a public health measure, the determina- tion of safety should be sufficient, and questions of suitability should not be made matters of administrative determination but should be left up to the manufacturer. This color additives amendment is of great concern to us at Walnut Grove as it is, I am sure, to all well-informed feeders of livestock. New ideas in research and new theories of animal nutrition have been drastically thwarted because of the confusion existing after the adoption of the food additives amend- ment. The broad scope of the color additive amendment will only multiply the existing confusion to the damage of not only the feed industry but farmers here in the Seventh Congressional District and elsewhere. Your efforts in bringing COLOR ADDITIVES 565 these facts to the consideration of your fellow Representatives will be sincerely appreciated. Sincerely yours, Wabtnut Grove Propucts Co., INc., Dick L. JENSEN, General Counsel. THE KANSAS STATE BoArp oF HEALTH, Topeka, Kans., April 28, 1960. Hon. Oren Harris, Chairman, House Interstate and Forcign Commerce Committee, Washington, D.C. Dear Mr. Harris: Attached is a copy of a resolution adopted by the Kansas Board of Health relating to the subject of color additives for foods. We respectfully request that this resolution be made a part of the record of the hearings on color additive legislation now pending in the House. Yours very truly, Evan Waicut, Director, Food and Drug Division. A RESOLUTION ON CARCINOGENS IN Foops, ADOPTED BY THE KANSAS STATE BOARD or HeaLtu, Marcu 11, 1960 Whereas the problem of chemical additives in foods is one of the great public health issues of our times; and Whereas the interests of consumers were significantly compromised in 1959 when the Food, Drug, and Cosmetic Act was by amendment stripped of the so-called per se principle, which had since 1907 prohibited the setting of tolerance for toxic and deleterious substances in food unless they were actually necessary in processing or production ; and Whereas this loss was partially offset, at the 11th hour, by incorporation into the above amendment of an absolute prohibition on the setting of tolerance for substances known to produce cancer when ingested by man or animals, a prohibi- tion which has come to be known as the Delaney amendment ; and Whereas the Department of Health, Education, and Welfare has declared and made evident its intention to enforce the prohibitions of the Delaney amendment, and to press for inclusion of its principle in future food, drug, and cosmetic legislation, particularly as related to the use of artificial colors; and Whereas the directness and vigor of the Department's present approach are in refreshing contrast to its attitudes of recent years, which have appeared to be unduly sensitive to the financial interests of the food industry and somewhat callous to the health interests of the consumer ; and Whereas the present activity of the Department is of great assistance to the Kansas State Board of Health in the education of the public on matters dealing with the adulteration and contamination of foodstuffs, and in the enforcement of the Kansas pure food, drug, and cosmetic laws: Now, therefore, be it Resolwed, That we, the Kansas State Board of Health, go on record as approv- ing of an absolute prohibition of chemical additives known to be carcinogen in foods, drugs, or cosmetics, believing such a principle to be only common prudence in our present state of ignorance of the causative mechanism of cancer, and believing such a principle to be practical and enforcible within the existing struc- ture of Federal and State controls; and be it further Resolved, That we warmly commend the Department of Health, Education, and Welfare, and the Food and Drug Administration for their courage and integrity as shown in recent actions with regard to cranberries and other foodstuffs adul- terated or contaminated by carcinogenic substances. UNIVERSITY OF MISSOURI, DIVISION OF AGRICULTURAL SCTENCES, Columbia, March 15, 1960, Senator Trroomas C. HENNINGS, Jr., Senate Office Building, Washington, D.C. Dear SENATOR HENNINGS: Citizens of the United States are supplied regularly with the most abundant supply, the greatest variety, and most wholesome food of any nation, and as a consequence are the best nourished people on earth. 566 COLOR ADDITIVES This food supply is made possible by the combined efforts of industries which manufacture equipment and materials used by farmers in the production of crops and animals, and by other industries that process and distribute farm products to consumers. The combination of farm production with the manufacturing and processing industries has attained its highly effective state through applications of research and experience to the many complex problems involved. A substantial and essential segment of this complex food-producing structure consists of the contributions of the chemical industry. Chemical products essential to farm production include plant foods, hormones, enzymes, fungicides, herbicides, and insecticides, which enable a relatively small percentage of total population to produce the quantity and quality of farm products required by the people of the Nation. Many substances, whether occurring free in nature or produced by industry, are useful to man when properly controlled but may be dangerous when handled carelessly. The idea has developed that any substance which has been added to food is hazardous and its use should be prohibited. The faculty of the University of Missouri College of Agricultrue is concerned with this problem. After careful consideration of the matter, a committee of the faculty has prepared a statement summarizing pertinent information cun- cerning it. A copy of this statement is enclosed for your information. Very truly yours, J. H. Lonewet, Director. CHEMICAL RESIDUES IN HUMAN Foops AND ANIMAL FEeEpS—A REeEpPorT OF THE CoMMITTEE ON CHEMICAL RESIDUES, MiIssouRI COLLEGE OF AGRICULTURE The need for protecting the public health from injurious amounts of chemical residues in the food supply is paramount. Agricultural chemicals are widely used in food production. As food demands become greater, the amounts are increasing, and must continue to increase. Since many of these cheinicals, if improperly used, can adversely affect human health, the need for regulations is obvious. For the past 30 years, responsible legislators and individuals in the medical profession, State and Federal agencies, and the chemical industry have been aware of, and concerned with, this problem. Laws have been enacted, and many millions of dollars have been spent on research to insure safe use of agricultural chemicals, The health of its citizens is a prime resource of the United States. Much of the credit for this asset can be attributed to an exceptionally high level of nutrition. Although it is usually taken for granted, the residents of the United States are the best fed people in the world. In no other country is there avail- able—and at reasonable prices—such an abundant supply of wholesome, high- quality food. This situation could not exist, however, were it not for agricultural chemi- cals—fertilizers, insecticides, herbicides, fungicides, growth stimulators, sani- tation compounds, disease control materials, ete. These tools are as indis- pensable to food production as tractors, hybrid seeds, improved crop varieties, and improved livestock. Threats to safe, effective, and necessury uses of these chemicals are very real threats to both the quantity and quality of our national food supply. LEGISLATION NOW IN EFFECT WHICH PERTAINS TO CHEMICAL RESIDUES ON FOOD Three laws have been passed in recent years by the U.S. Congress which spe- cifically regulate the sale and use of agricultural chemicals. The Insecticide, Fungicide, and Rodenticide Act provides that pesticidal chemi- eals can move in interstate commerce only under labels approved by the U.S. Department of Agriculture. For a label to be registered by the USDA, the manufacturer must first prove the compound is effective in controlling destructive pests. The label must state specifically which pests can be controlled with the compound, how much can be used, upon which crops it can be used safely, how it should be applied, and what precautions must be observed, These precautions must include detailed directions which insure no more than the allowable residue remaining on, or in, an agricultural product when it is harvested or marketed. Public Law 518, commouly referred to as the Miller Pesticide Residue Amend- ment to the Food, Drug, and Cosmetic Act, is administered by the Food and Drug Administration, This legislation established procedures whereby the Food COLOR ADDITIVES 567 and Drug Administration sets, and publicly announces, residue tolerances for each chemical on each agricultural product. Many tolerances thus set are zero, Proof of residue safety is made the direct responsibility of the busic manu- facturer. The Delaney clause in the food additives amendment to the Federal Food, Drug, and Cosmetic Act was passed during the closing days of the 1959 congres- sional session. The wording of this amendment, in effect, makes possible the interpretation that virtually all agricultural chemicals are “food additives.” This legislation prohibits the use of a “food additive” in agricultural produc- tion if the “food additive” has been shown to cause cancer in laboratory animals. This is true, regardless of the gross dosages used in laboratory tests. Since the Food and Drug Administration considers livestock feed in the same category as human foods, such prohibitions apply to animal feed production as well as the production of human food. The Delaney amendment eliminates administrative discretionary power by the Food and Drug Administration. It prohibits consideration of whether or not the “food additive” is present in amounts remotely approaching those necessary to be considered injurious. Nearly every State also has legislation modeled after the Federal laws. These State regulations apply to all such chemicals sold in the States, including those which do not cross State lines, and are thus exempted from Federal authority. TESTS NECESSARY FOR A COMPOUND TO MEET THESE LEGISLATIVE REQUIREMENTS An agricultural chemical is not offered for sale until it has been thoroughly tested for safety. These compounds are subjected to more exhaustive testing to determine their toxicological effects than are any other group of compounds— including human pharmaceuticals. As soon as a hew compound shows potential value as an agricultural chemical, comprehensive research is started immediately to obtain the data necessary for satisfying regulations resulting from the above legislation. This research is the responsibility of, and is financed by, the basic manufacturer of the chemical com- pound, Three to five years, and the expenditure of $1 to $3 million are usually required for this research. In addition to detailed studies of performance against both pest and beneficial organisms, exhaustive research must also be done upon the compound itself, and upon its toxicology under all conditions. Although the Food and Drug Adminis- tration has never specifically described or standardized the techniques it will accept for proving a chemical safe, the general pattern of testing is as follows: (A) Erhaustive studies of the compound and its physical propertics (1) The chemical structure must be specifically identified and its physical and chemical properties determined in detail. (2) A specific, practical, and extremely sensitive method of analysis must be developed. Usually this analytical method must be sufficiently sensitive to positively identify, and quantitatively determine, the presence of the compound in amounts of 0.1 part per million. (This is roughly equivalent to identifying and accurately measuring 1 specified inch in 160 miles.) (3) A complete study must be made of the compound's reactivity, and its breakdown components must be determined and identified. Specific analytical methods for each major breakdown component must also be developed. (b) Toxicological research (1) Acute oral tests.—Single lethal doses must be given to individuals of at least three different species of laboratory animals to determine: (a) Lethal doses. (b) Symptoms resulting from such doses. (ec) Clinical course of adverse effects. (d) The presence or absence of gross and/or microscopic lesions, (e) The mode by which death is produced. (2) Subacute oral tests.—Ninety-day feeding tests at several different dose levels must be made on at least 10 males and 10 females of 3 different species of laboratory animals to determine: (a) Dosage-response relationships, (b) Effect upon food consumption. (c) Effects upon growth. (d) Mortality rate. (e) Effect upon blood and urine composition. (f) Effect upon the weights of different body organs. 568 COLOR ADDITIVES (3) Chronic oral tests.—Groups of 25 weanling rats must be fed rations con- taining three different levels of the compound. The lowest concentration must be one which produces no detectable effects on the animals. The highest con- centration must be one at which death will result. The rats must be fed the compound continuously for 2 years, which is considered their normal life span In addition, one other species of animal, such as the dog, must be fed in the same manner for a period of at least 1 year. With certain compounds consid- ered as “problem chemicals”, additional groups of rodents must also be used. These tests are made in order to: (a) Obtain additional data on all catagories of the foregoing tests. (b) Determine if the compound is absorbed and at what rates. (c) Determine if the compound is stored in any body tissue, and at what rates, (d) Determine the rate at which the compound is broken down and/or excreted. (e) Determine the effects upon food digestibility. (f) Determine effects upon reproduction. (g) Determine effects upon lactation. (c) Tests for carcinogenic, or cancer-producing tendencies (1) Detailed observations must be made throughout all toxicological tests for the possibility of cancer which might appear in any portion of the body of any individual animal. (2) Repeated tests must be made whereby the compound is subcutaneously injected into certain strains of mice known to be highly prone to cancer de- velopment. Based upon data from the above research, a dosage level which is safe for rats is determined. If no cancer, which can be attributed to the compound, has appeared in any laboratory animal during the course of the tests, a safe dosage level for humans is then set at approximately one one-hundreds of that con- sidered safe for rats. This figure is subsequently used as the upper limit for residue in human food. It should be noted, however, that with some foods— such as milk—no residue of any chemical at any level will be considered, re- gardless of the data which might have been obtained from toxicological research. Research on basic toxicology is the responsibility of the manufacturer of a chemical. Determination of chemical residues which will remain under use conditions of a particular State is the responsibility of the Land Grant College of that State. Many colleges, including Missouri College of Agriculture, have not yet completely assumed this responsibility because they lack adequate chemical residue testing facilities. Since residue determinations are now as fundamental as data on performance, however, it is anticipated such facilities must be available in the near future. BASIS FOR DIFFICULTIES The greatest difficulty and confusion now encountered with chemical residues is caused by (1) administrative decisions to set zero tolerances for all chemicals in some foods—such as milk—despite results of toxicological research, and (2) the prohibition of use for all chemicals, which, by terms of the Delaney amend- ment, are labeled “carcinogenic”. In both instances, the same basic questions are involved : (1) Do results from exhaustive toxocological tests provide sufficient informa- tion to permit the setting of a tolerance which will allow practical and needed use of a chemical, but still not constitute a hazard to the public health? (2) Is there justification for setting tolerances on the basis of administrative decisions and legislative action instead of upon interpretation and application of scientific research data? The Delaney amendment was responsible for the recent cranberry and caponette episodes. It should be noted this legislation was not introduced at the request of the Food and Drug Administration, and has never had broad scientific sup- port. The reasons for this lack of support are obvious. All foods are a complex of different chemical compounds. M tS posium.”” pp. 66-6 Kneeland, “Medi- cated Feeds and the Law,” 12 F.DC.L.0, 359 (1957). Kleinfeld and Dunn, “Federal Pood, Drug, and Cosmetie Act, Judicial and Adminis- trative Record, 1988-48." po TAD, On the other hand, tolerances could be granted for residues of drugs intended for the prevention or treatment of animal disease on the ground that such use of those drugs was vi ary in the produetion of livesteek. In such eases telerances would only be granted if shown to be safe. Me © “Symposium,” p. 68, ’ Briges and Gay, “Symosium,” pp. 156-158, COLOR ADDITIVES 573 ment of pretesting of additives by their manufacturers. The Food Additives Amendment of 1958 was designed to remedy these conditions.” The House Committee on Interstate and Foreign Commerce, reporting this legislation, stated that— “The purpose of the legislation is twofold: (1) To protect the health of consumers by requiring manufacturers of food additives and food processors to pretest any potentially unsafe substances which are to be added to food; and (2) to advance food technology by permitting the use of food additives at safe levels.” 7* The provisions of the food additives law, in the absence of the Delaney clause, which we will discuss presently, probably would not have adversely affected the animal-health industry. Pursuant to the law, a substance which falls within the definition of a food additive, including a substance added to animal feed, is declared unsafe, unless there is in effect a regulation prescribing the conditions under which such additive may be safely used. In theory, at least, medicated animal feeds meeting the safety requirements of both the new drug law and the food additives law are feasible.” Furthermore, existing feed medications, having been reviewed by the Food and Drug Administration, are considered exempt from reexamination under the food-additives law, pursuant to the prior sanction or the general recognition of safety exemptions contained in the law.™ If a medicated feed is not exempt, it is necessury to obtain a regulation prior to marketing it. But, by virtue of a clause in the food additives law known as the Delaney clause, a regulation cannot issue permitting use of the additive v* * * if it is found to induce cancer when ingested by man or animal, or if it is found, after tests which are appropriate for the evaluation of the safety of food additives, to induce cancer in man or animal * * *." This clause has been interpreted to limit the discretion of the Food and Drug Administration *» The legislative history of the food additives bill amply bears out this conclusion. H. Rept. 2254, soth Cong., 2d sess., Committee on Interstate and Poreign Commerce, House of Representatives, July 28, 1 7S. Rept. 2422, sith Cong., 2d sess., Committce on Labor and Publie Welfare, US, Senate, Aug. 18, 1958. See the summary of the legis- lative history of the bill recently made by Edward Brown Williams for the Pharmaceutical Manufacturers Association, “Hearings” (1960), pp, 518-542. As early as 1956, the Food and Drug Administration supported a poliey to relax the fthit prohibition against unneces- sury or avoidable poisons in food as contained in the 1938 Federal Pood, Drug, and Cosmetic Act. “Heariugs Before a Subcommittee of the Committee on Interstate and Foreign Commerce, House of Representatives, on Bills To Amend the Federal Food, Drug, and Cosmetic Aet (1956)," pp. 1 194 (testimony of George P. Larrick, Commissioner of Food and Druzs), The iinportance of this decision was described a few months later by the Assistant Secretary, Department of Health, Pdueation, and Welfare: “This was a far- reaching step. It means abandonment of the per se rule and would be a modification of the ‘necessity’ rule. It would mean that auy chemical additive—even a kuown poison— could be used in a harmless amount, provided tt would serve some useful purpose in production or be of benetit to the consumer, In my opinion, this is a scientifieally sound position.” Mintener, ‘The Food-Additive Problem,” 11 F.D.C.L.J, 621, 626 (1956). The responsible sclentifie community takes a similar view. See footnote 15. For illustrative discussions of the dual inadequacy of the 1938 act will respect to food additives, see: Snyder, “An Appraisal of the O'Hara Bill To Provide for the Pretesting of New Chemical Additives to Food,” 9 F.D.C.LI, 698 (1954); Foster “Food-Ingredient Legislation,” 10 P.DC.L.I, 82. (1955); Miller, “Chemicals in Food,” 10 F.D.C.L.3, 104 (1955); Markel, “Pood Additives,” 10° F.D.C.LI. 769 (1955); Gosnell, “Food-Additive Legislatlon—A Review of Fundamentals," 12 F.D.C.L.3. 360 (1957). : 71H. Rept, 2284, oth Cong,, 2d sess., Committee on Interstate and Foreign Commerce, House of Representatives, July 28, 195s. =Jt is clear that drugs added to animal feed must contend with both the food additives law (see, 409) and the new drug biw .(see. 505). Insofar as both laws are designed te permit the marketing of safe products, however, presumably safe products can be cleared under both laws. But the overriding problem is whether the Delaney clause (see. 409 (ehiS)CA)) can be reconciled with the basic principles of these laws, Hagan, “The Pood- Additives nendment--Its Mifeet on Veterinary Drugs.’ 15 FLDC.LJ. 117 (1960) : Cheechi, “Food-Additives Procedures and Policies,” 14 FLDLC.L.AS, (1959); Oser, “Current Problems Posed by the Food Additives Amendment,” 14 P.LD.C.L.3. 574 (1959). The food additives law ix not without problems, however, See Oser, ‘wod Additives — New Law Causes Many Problems,” @ & EN, I 15, 1900, p. LOS: Mulford. “Some Vexing Problems of Additives Under the New Law.” 15 FLDCLLI. 10 (1960); Hutehins “The Food Additives Amendment as Seen by the Technologist.” 15 FIDAC.1A3. 17 (1960 “FDA Answers to Questions Submitted at Washington Confereuce on November 24-25, 1958, To Discuss Pood- Additives Amendment,” 14 PAC LI. 5 (1950). Federal Pood, Drug, and Cosmetic Act, see, 201(s). There are also problems that have been resolved in the matter of exemptions, for it appears that there are rather sharp differences of opinion as to the scope of beth exemptions, particnlariy as applied te vet- erinary drug: See Hagan, “The Food Additives Amendment —Its Effeet on Veterinary Drugs and Feeds,’ 15 PALC.LJ. 117 (1960), One perplexing problem is the matter of general recognition of safety. For the Administration view, see Goodrich, “The Tegin- ning Point Under the Food-Additives Amendment-—What Substances Do Qualified Experts Generally Recognize as Safe? “14 F.D.C.L.J. 584 (1959). See, also, the references con- tained in footnote 22. 574 COLOR ADDITIVES in respect to compounds having the capacity to cause cancer. Such compounds are thus distinguished from compounds which have the capacity to cause any other disease or which may be toxi¢ at some level. The basic principle of the food additives law, however, in order to accomplish hoth of its purposes, is that a food additive shall be approved for a particular use unless a fair evaluation of the data fails to establish that the additive will be safe under the conditions of its use. The legislative history of the bill sets forth the applicable concept of safety. Safety requires proof of harmlessness under the conditions of use and not proof of absolute harmlessness under any conceivable circumstances. This calls for the exercise of scientific judgment.> The argument for setting apart compounds which have the capacity to cause cancer is that in the present state of our scientific knowledge we cannot be cer- tain that any use of a demonstrated carcinogen is safe. This argument has now been taken up by the Secretary of Health, Education, and Welfare as the reason for endorsing the Delaney clause.” Let us now examine the operation of the Delaney clause upon the animal-health industry. Our object is to de- termine whether or not the Delaney clause is consistent with the basic principle of the food additives law. Diethylstilbestrol is a compound which can be made to cause cancer in a few species of animals under certain conditions. It cannot be made to cause cancer in most animals, however, and no cancer in humans has been found at- tributable to diethylstilbestrol despite its wide medical use in humans for 20 years encompassing hundreds of thousands of patients. Furthermore, many common foods normally contain estrogens similar in physiological effects to diethylstilbestrol, Estrogens are part of the normal background of all of us.” Yet, diethylstilbestrol must be considered a carcinogen, if by carcinogen we mean a product which will produce cancer in any species of animal. Therefore, according to the Food and Drug Administration, no food-additive regulation will be issued permitting the use of diethylstilbestrol in any feed. Its existing use in feeds shall be strictly limited to the scope of its exemption from the food-additives law. The evidence is overwhelming, however, that diethylstilbestrol has been shown to be safe when used in animal feeds as previously sanctioned by the Food and Drug Administration. The Food and Drug Administration has examined data presented for six different uses of diethylstilbestrol, and new drug applications pursuant to the new drug section of the Federal Food, Drug, and Cosmetic Act have become effective for each use. The drug has been used in human medicine since 1941 and in the feed of beef cattle since 1954. The elimination of the drug from the food obtained from livestock fed diethylstilbestrol was demonstrated to “HH, Rept, 2284, 85th Cong., 2d sess.. Committee on Interstate and Foreign Commerce, House of Representatives, July 28, 1958: 8S. Rept. 2422, 85th Cong., 2d sess., Committee on Labor and Public Welfare, U.S, Senate, Aug. 18, 1958, See, also, Food Protection Committee, Food and Nutrition Board, “Principles and Procedures for Evaluating the , of Food Additives,” Publication 750 of National Academy of Sciences-National reh Couneil (1960), p. 1, which states: “Results of critically designed studies of the ‘logic, pharmacologic, and biochemical behavior of a proposed additive in various sof animals can previde a busis for evaluation of its safety at a specified level of e by man, Tt is impossible, however, to establish absolute assurance that the addi- at any level of intake will be completely safe for all humans under all conditions.” concept Was also adopted by the report of the Joint FAO-WHO Expert Committee on Food Additives (1956), reprinted in “Hearings (1958), p. 821, % Matson, “Scientific Judgment in Law and Regulation,” 15 F.D.C.L.J, 70, 75 (1960). Dr. Matson states: “The science of pharmacology performs on the basie assumption that research over a reasonably short period of time combined with insight as to the probable nificance of the results will permit the acceptance of food additives as safe for human os tially no hazard involved. This is the essence of scientific judgment.” ranseripe, * arings” (19000, pp. 19-84. 7 Paper entitled “Safety of MMethylstitbestrol,” transmitted to Committee on Interstate and Foreign Commerce, Feb, 11, 1960, and summarized at pp. 447- 455 of the transcript, “Hearings,” hefore the committee, See, alse, “Panel Discussion; Feeding Diethylstilbestrol to Cattl ymposinm,”” pp, 170-177. Tir, Gassner, head of the endocrine section at Colorado A, & M. experiment station, seid: "Thus it seems that man and animal alike are forced normally to maintain a high threshold of response to estrogen and that the luman is rendered relatively insensitive to the infinitesimally small amounts of hormone that possibly could be ingested with meat produets." Td, at po 173, See QE CPR AAT. “Status of certain veterinury drng components under the food- additives amendment to the F ral Food, Drng, and Cosmetic Act.” published May 30, 54. at 24 PLR 476. The polley statement was a general statement applicable to com- pounds falling under the Delaney chiuse, IMethylstilbestrol was held to fall within the Delaney clause. See Food Chemical News for June 22, 1959, COLOR ADDITIVES 575 the satisfaction of the Food and Drug Administration, in accordance with its policy regarding medicated feeds as previously described. But even if un- detectable residues were to exist in beef, the amount of the drug reaching our food supply would be insignificant in relation to the therapeutic dose of diethylstilbestrol and to the natural estrogenic background.” It is submitted that in the case of diethylstilbestrol the Delaney clause has operated to deprive a safe use of this drug from clearance. This violates the basie principle of the food additives law. Scientific judgment has been en- tirely excluded.” This is a step backward, since even the 1938 act, with its per se rule on poisonous or deleterious substances, did not prohibit the clearance of diethy!stilbestrol under the Federal Food, Drug, and Cosmetie Act. It is not sufficient, however, merely to reestablish the 1938 act for diethylstilbesterol. For the 1988 act would prohibit even insignificant residues of any drug in relation to the normal background. Such residues can be determined to be safe.” Organie arsenicals provide another case in point.” Arsenic in one form or another is ubiquitous in nature. Arsenic compounds have been used in medicine for hundreds of years and for many years they dominated important areas in agricultural pest control. Between 1910 and 1945 organic arsenicals provided the best medical tools against man’s most serious parasitic diseases, such as syphilis. Arsenic occurs naturally in many foods we eat, including eggs and the tissues of poultry. Arsenic occurs naturally in soils and vegetation, and sea water contains traces which are concentrated to high levels in marine algae and crustaceans. Arseniculs have been more widely studied and widely used in medicine and in agriculture than perhaps any other class of compounds, Yet, there is no reliable experimental evidence that any form of arsenic, organic¢ or *# See footnote 27. Dr. AH. Holland, Jr., Veterinary Medieal Director of Food and Drug Administration, Symposium, p- 176: “Our position, | think is very clear. All of the work, all of the literature we have had occasion to study and review over a period of many, many months preponderantly led to the conclusion that diethylstilbestrol as proposed for use in enttle feed was perfectly safe.” “Tt is perhaps significant that certain scientists advocating the prohibition of diethyl- stilbestrol are also among those who do not accept the exercise of scientific Judgment in evaluating food additives. Consider the paper by Knight, Martin, Iglesias, and Smith, “Possible Cancer Hazard Presented by Feeding Diethylstilbestrol to Cattle.” Symposium, pp. 167-169. That their paper was based upon “speculation” and “theoretical considera- tions’ was indleated by the panel discussion that followed (pp. 170-177). Dr. W. Coda Martin, president of the American Academy of Nutrition, testified the following year that the academy approves of the concert of total nutrition, which means food free of chemical additives. He further said: “The human bedy ean utilize only natural foods us hoeurishment and survive. Chemicals are not food elements. Therefore, they can produce only negative or harmful results, even thongh they are by scientific analysis nontoxie”* Hearings (1958), pp. 272, 279. Dr. WLR. Smith. also associated with the American Academy of Nutrition, said: “I submit that the adulteration of food with new chemicals Is not a right, but a privilege that should be permitted only when there is real need.” Id, at p. 173. In a letter to Congressman Delaney, he said: “It is simply not in the public interest to expose consumers to the unforeseeable risks of a host of biologically foreign food additives that may provide eye-appeal or advertising values but offer no nutritive benefit.’ Extension of remarks of Hon, James J. Delaney, vol. 103, Congres- sional Record, app. A1l351-A1S54. Feb. 21, 1957 (letter dated Jan. 28, 1957). These opinions clearly ure not compatible with the scientific community as a whole or with the philosophy of the food additives laws, See footnote 15. See Matson, “Seientifie Judgment in Law and Regulation’ (15 F.DC.LJ. 70, 80 (1960)). Dr, Matson states: “We must provide that scientists of the Food and Drug Administration shall be permitted to use reasonable scientific judgment, not giving regu- latory recognition to those trace amounts of a food additive so distantly related to the amount and duration of use known to coustitute a bazard that no purpose is served by recognizing them.” The validity of thix conelnsion is at least implied in the publication of the Food Protection Committee, Food and Nutrition Board, “Problems in the Evalua- tlon of Carcinogenic Hazard" from “Use of Food Additives.” publication 749 of the National Academy of Sclences—National Research Council (1960), which states at p. 82: “The assignment of a tolerance level, or a safe level of use for man, of a demonstrated carcinogen must at present rest largely on the evaluation of alternate risks and values ly cannet be expressed in quantitative terms, Quantitative knowledge about » @&g., the slope of the dose—response curve, the niaximum experimental he minimum technological amount necessary for the proposed use, can, ‘ into account in assigning such a tolerance level.” Several of the ‘ientists appearing before the Committee on Interstate and Foreign Commerce on Apr. 5-6, 1960, expressed the opinion that tolerances might well be set for “weak” carcinogens. E.g., Dr. Charles J. Kensler, hearinus (1960), p, 743. “Summaries of the data pertaining to arsenicals appear in the following: Frost and Spruth, Symposium, pp. 1236-149; Frost, “Ten-Year Reeord for Organie Arsenicals.’’ in press, for Feed Age, May 1960; Frost. Arsenie and Selenium in Relation to the Food Addi- tive Law of 1958," In press, for Nutrition Reviews, May 1960; Frost. Perdue, and Overby, “Arsenicals in Feeds and Their Residues in Animal ‘Tissues." address presented at Sym- posinm on Chemical Residues in) Agrientture, Michigan State University, Jan. 26-27, 1960; Frost, nsiderations on the Reality of Arsenie Cancer,” unpublished manuscript dated Sept, 30, 1950: Kerr, “A Review of the Literature Pertaining te Arsenic as a Carcinogen,” unpublished manuscript dated June 23, 1059. 576 COLOR ADDITIVES inorganic, can be made to induce cancer in animals. Neither does the medical literature in any way implicate organic forms of arsenic as a carcinogen for man.” There has been a great deal of speculation tending to implicate inorganic forms of arsenic as carcinogens.” The only substantial evidence, as distinguishei from speculation, involving inorganic arsenicals, is that massive long-term potassium arsenite therapy—at a level high enough to constitute arsenic poison- ing—produces a characteristic thickening of the skin of the palms of the hands and the soles of the feet, and abnormal pigmentation of the skin. In about 20 percent of the individuals developing skin thickening, the patches of thickened skin became cancerous. This hardly constitutes reliable evidence of carcinogeni- city of all arsenical compounds. It suggests only that arsenic poisoning by potassium arsenite, a highly toxic compound, may produce a condition which in turn may cause cancer.” Nevertheless, according to the Food and Drug Administration, no food additive regulation can be issued permitting the use of any compound containing arsenic, *3It should be noted that in the recent amp hlet of the Food Protection Committee, Food and Nutrition Board, “Problems in the aluation of Carcinogenic Hazard From Use of Food Additives,” publication 749 of National Academy of Sciences-National Research Council (1960), the only references to arsenic are that inorganie arsenic compounds are listed as agents “associated” with cancer incidence in man, and that arsenic trioxide is a compound which has been reported to be a carcinogen for animals but for which evidence of activity is inadequate. “The first implication of arsenic as a possible carcinogen dates back to 1822 and was based on arsenic in fumes from smelting works. Since that time cases of cancer in man have been attributed to inorganic forms of arsenic to which the individuals have been exposed, These cases involved occupational exposure (for example, vineyard workers, miners, smelters, and factory workers), environmental exposure (for example, excessive arsenic in drinking water in Germany and Argentina), and medicinal exposure (chiefly potassium arsenite therapy). See references at footnote 32, That these observations are largely speculative—with the exception of the medical cases—is illustrated by Eckardt. “Industrial Carcinogens” (1959), who states (p. 11): “Thus in considering the number of employees that might have been involved sinee 1822, 1898, and 1926, respectively, for arsenic creosote, and saltpeter, the number of skin cancer cases attributed to these agents ix so small that there appears to be considerable doubt as to whether they even should be included in the table. However, they have been included for the following reasons : In the case of arsenic, we know that hundreds of thousands of workers must be potentially exposed to it in the smelting industries, so that less than 25 eases reported since 1522 seems remarkably low. Nevertheless arsenic has been left in the table because it is known that medicinal overdosage with arsenie leads to hyperkeratoses of the palms and _ soles. These lesions are believed by practically all authorities to be precursors of cancer.” An illustration of an erroneous implication of arsenic eancer is given by Frost, “Considera- tions on the Reality of ‘Arsenic’ Cancer,” which was the belief that arsenic dust caused lung cancer in Schneeberg, Germany. Eventually, however, radiation injury from fitch: blende was considered a more likely cause of the incidence of lung eancer. Dr. W. C. Hueper, of the National Cancer Institute, perhaps the most outspoken scientist who con- siders “arsenle and its eompounds” (hearings before the House Select Committee To Investigate the Use of Chemicals in Foods and Cosmetics, House of Representatives, pt 3 (1952), p. 1366), as known carcinogenic agents, testified in 1952 that “an apprecta le number” of skin cancers were observed between 1938 and 1942 among vineyard workers in a district in Germany which had had an epidemic of chronie arsenic poisoning from the use of arsenical pesticides (pp. 1366-1367). Dr. Hueper repeated this testimony subsequently (hearings (1958), 372). and ndded: “Now they have among their vineyard Workers not only skin cancer but lung cancer and liver cancers,” However, Dr. Hueper's eonclusion is purely speculative, Consider Eekardt, p. 147: “Thus, the fact that eight Vineyard workers tn Germany developed cancer of the lung, in itself, neither argues for nor against the idea that there is an occupational hazard of lung cancer among vineyard workers. It is necessary to know the number of vineyard workers involved, and deter- mine whether the incidence is significantly elevated on a statistical basis. If one travels down the Rhine River in Germany, one is impressed with the vineyards which occupy the bills for mile upon mile of the trip. There must be thousands upon thousands of people who work in these vineyards, so that eight lung cancers among them may well constitute only the anticipated incidence of this disease. These observations only sngegest that additional studies such as those done by Roth be undertaken in an attempt to develop definitive answers.” In fauet, extensive studies were conducted between 1937 and 1940 by the U.S, Public Health Service of orchurdists around Wenatchee, Wash... where lead arsenate had been used as a tree spray since about 1900. No difference in ineidence of Various disenses, ineluding cancer, Was seen between orchardists and their families regu- larly exposed to unnsunl amounts of lead arsenate and those not so exposed. Frost, “Considerations on the Reality of ‘Arsenic’ Cancer.” * Hearings (1960), pp. 384-335 (testimony of Panl Gerden) ; hearings (1960), p. 810 (testimony of Dr. Morton L, Levine); Frost, “Considerations on the Reality of ‘Arsenic’ Cancer.’ Frost concluded: “Neubauer’s (1947 major review “Arsenieal Caneer” lists only 143 cases of medicinal arsenical epithelioma from the literature. Thus arsenite cancers appear as an extreme rarity, even from 1905 to 1947 when millions of people were treated with arsenicals. Cuaneer is reported to occur in one of five men and one of four women, Eckardt (1959) indieates that cancer of the skin occurs normally in about 30 per 100,000 per year. From the statistical standpoint the reported cases would actually seem far too isolated and few in number to warrant a direct associution between arsenic therapy and cancer.” COLOR ADDITIVES 577 including organic arsenicals, until and unless the compound can be shown not to have any carcinogenic potential.” But scientists indicate that no one can show that any compound cannot cause cancer.” Thus, only those uses of organic arsenical compounds which are exempt from the food additives law may be employed. Yet there is not one scintilla of evidence of cancer induction throughout his- tory by any organic arsenical compound in man. No one has been able reliably to induce cancer with any organic arsenic compound in any species of animal at any level or by any means of administration. The evidence is overwhelming, furthermore, that the organic arsenical com- pounds, which have been extensively tested, and approved by the Food and Drug Administration, under the new drug law, have been shown to be safe under their conditions of use. Because of general recognition of safety of several of the organic arsenicals, in fact, they no longer require regulation under the new drug law as new drugs, and they are considered to be exempt from the food additives law. In each case, however, all organic arsenical compounds were originally marketed pursuant to effective new drug applications under the Federal Food, Drug, and Cosmetic Act. Organic arsenicals have been used in human medicine since the beginning of the 20th century, and in medicated animal feeds since 1951. Residues of the drugs in eggs and tissues, furthermore, when used under recom- mended conditions, are in the same range as normal content of arsenic in such foods. Approval of residues of organic arsenicals under these circumstances is in accordance with established policy of the Food and Drug Administration under the new drug law. Such residues are less than established tolerances in fruits and vegetables sprayed with inorganic arsenicals, and are insignificant in relation to the natural background of arsenic.” It is submitted that in the case of organic arsenicals the Delaney clause has again operated to deprive a safe use of these drugs from clearance in violation of the basic principle of the food additives law. Scientific judgment has been * The basic policy of the Food and Drug Administration applicable to veterinary drugs held to be carcinogens within the meaning of the Delaney clause is set forth in the regu- lations at 21 CFR 3.37 (see footnote 28). Organic arsenical compounds were held to fall within the Delaney elause. See Food Chemical News for June 22, 1959, and for July 13, 1959. The FDA position was expressed in letters which said in part: “It is a known fact that certain inorgante arsenie compounds and certain synthetic materials with hormonelike activity similar to dienestrol diacetate have been found to produce cancer in man, Beeause of this, our selentific advisers cannot say that arsenic compounds used in feed or dienstrol diacetate are safe until it is demonstrated that such compounds do not have this careinozenie potential. They would have to have appropriate data to answer this question. Furthermore, if an arsenic compound, after study, is found not to produce cancer itself, we would need to know whether any residue it leaves in edible products of treated animals is the organie or inorganic form.” “Tt seoms clear that negative results in animal testing are not considered proof of luck of careinogenicity in humans. Food Protection Committee, Food and Nutrition Board, “Problems in the Evaluation of Carcinogenie Hazard From Use of Food Additives,” publication 749 of National Academy of Sciences——National Research Council (1960). Pe 21. See Matson, “* Scientific Judgment in Law and Regulation,” 15 F.D.C.L.J. 70, 77-78 (1960), the Delaney clause uses the phrase “found to induce cancer.” Secretary Flem- ming testified that this phrase applied only to substances which had been “demonstrated” to induce cancer (hearings (1960), p. 63). In testimony given prior to enactment of the food additives law, Dr. Herbert E. Carter stated (hearings (1958), P: 877): “It is commonplace for even a slight alteration in structure to change drastically the biological properties of a substance, Unfortunately each compound must be considered as an indl- vidual and evaluated independently.” Accordingly, it seems improper to prohibit organle arsenienis with a long history of safe use on the basis of inconclusive evidence pertainin, te inorganic arsenic compounds (hearings (1960), pp. 335-341, testimony of Pau serdent). * Tolerances for lead arsenate and calcium arsenate, inorganic arsenic products used on fruits and vegetables, are in effect under see. 408 of the Federal Food, Drug, and Cos- metie Act, applicable to pesticide chemicals in or on raw argricultural commodities (21 CPR 120,101(e)). Dr. William J. Darby, chairman of the Food Protection Committee, testified (hearings (1960), pp. 834-835): “You have heard that many substances which are naturally present in foodstuffs ean, under special conditions, or conditions of very hich intake, be associated with the occurrence of experimental cancer. To mention some of these which were noted yesterday, arseuic, selenium, radioactive materials, even Hpids or fats, some precursors of oxyloc acid and so on. One could extend this list considerably. Por example, one could even question whether the lowly turnip, and its several relatives, contain a substanee which might be considered suspect—that is, a naturally oceurring antithyroid substance, whieh has certain substances In common with aminotrizol. The content of foods very greatly in all of these substances, I do not know, however, of any evidence which links the ingestion of these small amounts present in foods to ecaneer in the human. They are unavoidable, and any workable legislation must allow the decision by someone that this is the case.” (For organie arsenicals, see references cited at foot- note 82, and hearings (1960), p. 336, testimony of Paul Gerden.) 578 COLOR ADDITIVES entirely excluded, not only in the evaluation of safety, but also in the evaluation of whether or not these compounds are even capable of causing cancer.” CURRENT STATUS—COST OF THE DELANEY CLAUSE The cost of the Delaney clause to our growing society could prove enormous. It is purely conjectural whether a single human cancer will have been prevented by this action.” But there is little question about its likely consequences to feed technology, and ultimately to the public health. The chief cost is not the potential loss of any single product to society, although the loss of any valuable product is to be deplored. If diethylstilbestrol and organic arsenicals were to be banned from the market, our farmers would have to produce significantly more animals each year to obtain the same amount of food products that we can now produce with the aid of these drugs." I have said that existing uses of diethylstilbestrol and organic arsenicals are exempt from the food additives law. But the use of diethylstilbestrol for implantation in poultry for the purpose of synthetic caponization was also exempt from the food additives law. That use of diethylstilbestrol has already been suspended because of the pervasive influence of the Delaney clause.” Other uses of that drug and the uses of organic arsenicals must be considered as threatened as long as the flat ban of the Delaney clause can be made to apply to them. The chief cost, however, is the threat to future progress based on research. There is evidence that research projects have already been curtailed and that potential research projects are now being tabled in veterinary medicine.“ These deci- sions of management to shift research effort elsewhere have been taken because the tremendous expense which is involved in the development of new veterinary drugs for use in medicated feeds may not be justified under present conditions, There are several factors which have operated to influence industry in this regard. On the one hand there is the uncertain operation of the Delaney clause. Lack of scientific agreement as to the definition of a carcinogen or as to the tests which will be considered sufficient to establish noncarcinogenicity, coupled with the enormous expense involved in testing new drugs, are a part of the reason.“ On the other hand, there are some interpretations of the food addi- * The operation of the Delaney clause to cover dubious cases of carcinogenicity is a defect of the chiuse that was pointed out by the great majority of the scientists appear- ing Apr. 5-6, 196), before the Committee on Interstate and Foreign Commerce (hearings (1960), pp. 685-889), The tendency to consider compounds as potential carcinogens unless proven nonearcinogenie is an aspeet of repudiation of scientifie judgment. Thns. Dr. Harold L. Stewart proposed not only that the Delaney clause be retained in toto, but also that exhaustive tests be required for each compound to minimize the possibility that it might be earcinogente (hearings (1960), pp, 708-708). But the cost of such testing for one compound was estimated to be as much as $200,000 (hearings (1960), p. 752). Furtermore. such research is considered nonproductive, scientifieally (hearings (1960), pp. S25-S26). There was testimony offered before Congress at the time the food additives bil was being considered that there was no single proven instance of any human cancer related to a food additive. Dr. John H. Folger (hearings (1958), p. 368), and Dr. Emerson Day (hearings (1958), p. 374) so testified. More recently, Dr. Willlam J. Darby. chair- mun of the Food Protection Committee, offered similar testimony (hearings (1960), pp. S34-885). Dr. M. R. Zavon pointed out that if food additives were a significant problem in causation of cancer, one would not expect to tind a decrease in incidence of cancer of the stomach. Yet such has occurred (hearings (1960), p. S25). ‘See, «.g., hearings (1960), p. 462 (testimony of Dr, Thomas Carney). See W. W. Goodrich (“Cranberries, Chiekens, and Charcoal,” in F.D.C.L.5. 87 (1960). Since 1947, there has been a practice to implant pellets of diethylstilbestrol in poultry at the base of the skull for the purpose of synthetic eaponization, New drug applications were made effective clearing this use of the drug on the basis of evidence that only a minute amotnt of residue of the drug would remain in the tlssues of treated birds at the time of slaughter. In 1957 the actual residues were calculated and found to be minute. In December 1959, however, Secretary Flemming saw fit to publicly announce that the principle of the Delaney clause was the basis for re ing immediate suspension of the sale of diethylstilbestrol for use in poultry and immediate suspension of the sale of treated birds, Though the Secretary reported that voluntary compliance with his request had been obtained, that only 1 percent of the chickens on the market were affected, and that consumers cnn buy poultry with full contidence that it is safe and wholesome, nevertheless, the incident was bound te reduce confidence of the public in our food supply. * Hagan, “The Food: Additives Amendment—-Its Effect on Veterinary Drugs and Feeds.’ 15 F.DC.L. 117) (1960); henrings (1960), pp. 465-467 (testimony of Dr. Thomas Carney); CC. & E.N.. Mar, 21, 1960, p, 19, # The panel of scientists which convened on Apr. 5—6, 1960 (hearings (1960), pp. 685- SS9) revealed basic differences of opinion on such vital matters as which substances are carcinogens and what tests might be considered appropriate to establish either earcinogen- jeity or vnoncarcinogenicity, At ene peint Dr, G. Burrenghs Mide admitted it was thee- retically possible to ban salt under the Deliney clause (hearings (1960), p. 7389. Dr. Morton L. Levin thought we should not exclude the possibility that commonly occurring substances might in fact be carcinogenic for humans (hearings (1960), p. 797). Roasted COLOR ADDITIVES 579 tives law already advanced by Food and Drug Administration which seem to be applicable primarily to veterinary drugs and which make costs of development in relation to possible markets virtually prohibitive.” The scope of the exemp- tions from the food additives law which are to be accorded to existing medicated feeds are so narrow that supposedly exempt drugs are no longer exempt from the food additives law when mixed with new drugs in medicated feeds. There- fore, the manufacturer of a new drug is required to obtain a food additive regulation for not only his own drug but also for every existing drug with which his drug will be mixed, all at enormous expense. Yet, the market for the new drug will probably be very small, indeed, because the Delaney clause will pro- hibit issuance of a regulation for a new drug added to any existing medicated feed containing diethylstilbestrol or an arsenical. The cost of the Delaney clause is certainly going to be high. Can our society afford to pay the price? THE FUNDAMENTAL DEFECT—CONFLICTING POLICIES Let us now consider how to restore scientific judgment to the evaluation of food and drugs in a framework which provides maximum public health protection. In my opinion, the problem is not basically the administration of the law. In the past, we have been able to work out problems of administrative interpre- tation with Food and Drug Administration on a scientific basis, and we can probably continue to do so in the future.” But the basic problem, rather, in my opinion, is legislative. It seems reason- ably clear, as previously mentioned, that Congress intended to establish the basic principle that additives whose uses are shown to be safe should be approved for such uses. The policy of the law is stated to advance food technology as well as to protect the consumer. The trouble is that by inserting the Delaney clause into the food additives bill, Congress was, perhaps inadvertently, modi- fying that policy. As a result of the Delaney clause, in the case of compounds which are suspect as carcinogens under special conditions, manufacturers are not legally permitted to show that such a compound is safe under conditions of use.” Inquiry into the actual hazard from the use of the compound is absolutely foreclosed. The law itself makes a prejudgment that safe use of the compound eannot be established. Now Congress has decided that food technology should be advanced. This is a value judgment. It was a decision that followed 8 years of consideration, numerous hearings, a wealth of articles, and much debate. In order to accom- plish this policy, however, it was deemed necessary to abandon the longstanding coffee beans contain minute amounts of a strong carcinogen, according to Dr. James A, Miller (hearings (1960), p. S811). The philosophy of the Delaney clause, pushed to extremes would require us all to wear lead armor, to live a subterrestrial existence, to breathe especially filtered and treated air, to drink especially treated water, to refrain from drinking coffee, ten, or eating any foods processed by roasting or smoking, or from consuming most naturally oceurring foods, according to Dr. William J. Darby (hearings (1960), p, S34). It is likely that food additives would largely be suspect under the Delaney clanse, *See, 201(s) of the Federal Food, Drug, and Cosmetic Act defines the term “food additive.” The general language is broad enough to include a veterinary drug which is also a new drug pursuant to see, 201(p) of the act. But see, 201(s8) contains a clause specifically excluding any substance nsed in accordance with a sanction or approval granted prior to Sept. 6, 1958. under certain statutes, Including the Federal Food, Drug, and Cosmetic Act, from the term “food additive.” In the case of veterinary drngs which may also be food additives this exemption calls for interpretation. An effective new drug application under see, 505 of the act is certainly a prior sanction. But under see, 505 of new drug appHeation is effective only for the manufacturer who obtained it and for the partienlar conditions of nse contained therein. Is the exemption of the drug from the food additives liw also so limited? The Food and Drug Administration has argued that it is. See, 201(s) also excludes from the term “food additive” any substance which Ix generally recognized by qualified experts to be safe under the conditions of its Intended use, FDA contends this exemption, like the prior sanction exemption, is Hmited and does not apply to the drug when it is mixed in feed with a newly developed medication, Theos, the same drug may be both exempt and not exempt from the food additives law at the same time and for the same nse, See Hagan. “The Food-Additives Amerment— Its Effect on Veterinary Drugs and Feeds," 15 F.D.C.L.J. 117 (1960), and other references contained tn footnote 238. * As a envent, however, this Je net to be constrned as an Implied acreement with the interpretations of the food additives law by the Food and Drng Administration. “Dr. Morton TL. Levin, who accepts the Delaney clause, with same latitude, however, in “exceptional eirenumstances” conceded that this means he would “accept false positives” and knowingly “exelnde possibly harmless chemicals from our diet” (hearings (1960), pp. 800-802). This is the necessary effeet of the Delaney clause. It Is a departure ftom the announced purposes of the food additives legislation. 56123—60——-38 580 COLOR ADDITIVES per se pronibition against the addition of poisonous or deleterious substances to food. This necessarily meant that Congress was willing to sanction the use of compounds which might be harmful under unusual conditions or in large quantities, but would be beneficial when used under controlled conditions. As a matter of established fact, it is not possible in the present state of scientific knowledge to establish with complete certainty the absolute harmlessness of any substance, under every conceivable condition. However, through the applica- tion of scientific judgment, it was concluded that the health of consumers could be protected.” Scientific judgment, however, is in essence the combination of research over a reasonably short period of time with insight as to the probable significance of the results.” The scientific method requires that a determination of safety must be independently made for each proposed use of a compound. By freezing pres- ent scientific knowledge into law and by prejudging an unknown number of compounds we necessarily depart from the scientific method. Yet there is no reliable evidence that I can find that the Food and Drug Administration cannot make a judgment in each case which is consistent with the public welfare.” Commissioner Larrick had no doubt about the capacity of the Food and Drug Administration when he opposed the concept of the Delaney clause in testimony before the House Committee on Interstate and Foreign Commerce in 1957. He said then: “But we see no more reason to single out cancer production for specific men- tion in the legislation than to single out production of high blood pressure, de- struction of the blood-forming elements of the body, or production of nephritis, diabetes, or a host of other disorders. All of these things are of extreme impor- tance. We, certainly, do not intend to sanction a chemical additive in the food supply unless the evidence rules out any reasonable ground for believing that the proposed use will constitute a hazard to the public health in any respect.” * The panel of eminent scientists who were called upon in 1957 to advise the Committee on Interstate and Foreign Commerce stressed the individuality of each analysis of safety. Summarizing the individual statements of the scien- tists, Dr. W. J. Darby, of Vanderbilt University, said: “It was repeatedly emphasized by the participants that each additive, each chemical additive, is a different substance, and, therefore, it presents certain differences in judging the results of testing and in expressing judgment on the safety for the particular use or uses for which this additive is proposed. “It would seem that in any regulatory procedure there should be an allow- ance for what we might call individuality of additives—individual appraisal of safety.” Nevertheless, the Delaney clause was incorporated into the food additives bill after the bill had been reported by the Committee on Interstate and Foreign Commerce without any cancer clause. The chairman of the committee reported to Congress that the clause was requested by Congressman Delaney. Congress- man Delaney stated that the clause followed the recommendation of the sym- posium of the international union against cancer held in Rome in 1956 and dis- cussions he had with several cancer researchers. There was very little discus- sion of the potential effect of this clause on the legislation, but there is some “Congress rejected the philosophy (except to the degree the Delaney clause restores the per se prohibition of chemicals) of the food faddist who is not willing to accept scientific judgment in the evaluation of food additives. Examples of the food faddist approach are contained in footnote 30. The food faddists were a factor in inducing Con- ress to institute the food additives investigation that got underway in 1950, aceording to the former head of the Food and Drug Administration. Dunbar, ‘Chemical Additives in Food” (6 F.D.C.L.J. 431 (1951)). They were a factor in the pressure which was exerted to enact the Delaney cluuse and they are now active in order to maintain the integrity of the clause against efforts to restore the basie philosophy of the food additives law. Matson, “Scientific Judgment in Law and Regulation” (15 F.D.C.L., 70, 73-76 (1960)). More recently, Representative David S. King, of Utah, read into the record of the Interstate and Foreign Commerce Committee a letter from Dr. Geoffrey Martin, M.D., who wrote: “The Delaney amendment in effeet defends one small area of consumer pro- tection which previously was defended by the per se principle’ (hearings (1960), p. 414). See footnote 20 for the legislative history of the food additives bill, * See footnote 25, “In fact, a number of the sclentists testifying before the Committee on Interstate and Foreign Commerce on Apr. 5-6, 1960, indicated confidence In the ability of the Food and Drug Administration to exercise judgment. (hearings (1960), p. 875 (Dr. Paul Can- non), p. 886 (Dr, William J. Darby), p. 743 (Dr. Charles J, Kensler), pp, 723-724 (Dr. Walter 8S. O'Donnell), p. 825 (Dr. Mitchell Zavon)). *! Hearings (1958), p. 454. *? Hearings (1958), p. 353, COLOR ADDITIVES 581 evidence that the Delaney clause was not thought to alter the basic philosophy of the bill. In fact, the Senate Committee on Labor and Public Welfare reported: “In short, we believe the bill reads and means the same with or without the inclusion of the clause referred to. This is also the view of the Food and Drug Administration.” “ This statement was a monumental miscalculation. The Delaney clause, clearly, departs from the the philosophy of the food ad- ditives law. Its standard of prejudgment reflects the views of some, but not all, cancer researchers—whose experience does not reach into the broader areas of publie welfare—and who are impressed mostly with their lack of knowledge of the factors responsible for cancer incidence. Faced with such lack of knowledge, their remedy is to repudiate scientific Judgment altogether. Yet, it is generally accepted that thresholds do exist for cancer-causing compounds as for other com- pounds, and that in doubtful cases, at least, safe tolerances can be set.” Those scientists who take into account the broader aspects of public health, however, have expressed the opinion that the Delaney clause should be modified or entirely deleted. Thus, summarizing the views of several of the members of a scientific panel that appeared before the Committee on Interstate and Foreign Commerce a few days ago, Dr. William J. Darby, Chairman of the Food Pro- tection Committee, and chairman of the panal, said: “It was indicated yesterday that full protection of the public would be pro- vided without a specific cancer clause.” “ Dr. Darby indicated this was also his personal opinion. The conflict in policy created by the Delaney clause was pinpointed by Dr. M. R. Zavon, Kettering Laboratory of Industrial Health, who told the committee: “* * * the proper question in 1960 is first to determine what is the ultimate object of our food protection laws? “Is it to protect our population against any conceivable hazard or is it to as- sure the greatest measure of good to the greatest possible number with a mini- mum of possible harm to the least number?” “ Answering this question, Dr. Zavon said: “The object is the maximum well being of our population. There is a serious question in my mind whether the Delaney clause will not cause great disruption of the type of research which has gone so far to improve the well-being of our population.” * CONCLUSION—-RESPONSIBILITY OF CONGRESS The responsibility of Congress in this situation seems clear. The establish- ment of policy is the essence of the legislative function.” No administrative agency, subject as it is to many pressures, can consistently administer a law whose policies are in conflict. We may properly expect Congress to determine the policy of the law, and Congress must accept responsibility for the decision which it reaches. Once the facts are obtained, Congress must decide which of the several courses of action serves the total public welfare best. % The legislative history of the Delaney clause is extensively reviewe 5 Williams at hearings (1960, pp. 515-542). ¥ @ by Edward Brown %S, Rept. No. 2422, 85th Cong., 2d sess, Committee on Labor and Public Welfare, U.S. Senate, Aug. 18, 1958, . ®Dr. Zavon said (hearings (1960), p. 825): “Most of the fears conjured up with regard to cancer are to the effect that we don't know, therefore, it might cnuse cancer. ‘There fore, we can't take a chance.” As to the existence of thresholds, see Food Protection Com- mittee, Food and Nutrition Board, “Problems in the Evaluation of Careinogenie Hazard From Use of Food Additives, publication No, 749, National Academy of Sciences-National Research Council, », 31-33. Nearly all the scientists testifying before the Committee on Interstate and Foreign Commerce on Apr. 5-6, 1960, were willing to set tolerances for exceptional or doubtful compounds that might concetvably come under the Delaney clause (hearings (1960), p. 874 (Dr. Charles J. Kensler), p. 875 (Dr. Paul Cannon), p. S79 (Dr. Floyd DeKde), p. S81 Dr. Morton Ly Levin) p. 883 (Dr. James A. Miller) . BSE r. Albert Tannenbaum), p. 8&8 tr. Mitchell Zavon), p. 88 x : Barbr), p. 722 (Dr. Walter S, O'Donnell) ), ‘ »P 5 (Dr. William J; * Hearings (1960), p. 836. Hearings (1960), pp. 821-822. * Hearings (1960), p. 827. ® Mutual Film Corporation v. International Commission of Ohio, 236 U.S. 230 (1915); Paname Refining Co. v. Ryan, 2938 U.S. 888 (1935) ; 0 Cott 1k ve of Wage and Hour Division, 312 U.S. 126 (1941). ) pp Cotton Mills Inc. ¥. Administrator 582 COLOR ADDITIVES It is submitted that the basic policy of the law has already been determined. This is to achieve maximum well being by advancing food technology as well as by protecting the consumer from harm through the application of scientific judgment. As written, the Delaney clause precludes scientific judgment, and frustrates the basic policy of the law. It is imperative that to achieve the maximum well- being of our Nation the Delaney clause must be eliminated or amended so as to permit the use of safe compounds. Congress is now considering the Delaney clause. The forum is the Com- mittee on Interstate and Foreign Commerce. The subject is color additives. But it is the food additives law which is actually on trial. This matter should receive serious attention from the animal health industry. For the decision which Congress will make will be based upon the information with which its members have been supplied. We of the Animal Health Institute are deeply concerned with the public health. Speaking for my company, we would not think of marketing any drug which is likely to cause harm. But we don’t think the public welfare is served in the 20th century by abandoning scientific and technological progress which has given this Nation the highest standard of living in the world. B & D Mnm1s, Grapevine, Tez., March 26, 1960. Hon. Lynpon JOHNSON, U.S. Senate, Washington, D.C. Deak SENATOR JouNsSON: It is my understanding that H.R. 7624 is concerned with the use of additives to impart color to foods, drugs, and cosmetics. I alse believe H.R. 7624 includes a so-called cancer clause known as the Delaney amend- ment. This amendment prevents the exercise of scientific judgment. It im- poses a flat prohibition on the use of any substance which has been proven safe as used, but which can be made to produce cancer when ingested by animals, even if the dose is a million times that for its intended use or if experimental conditions are totally unrelated to actual use. By imposing a flat prohibition on additives which can be made to cause cancer under laboratory conditions unrelated to practical use, this prevents the use of otherwise valuable substances. The “spirit” of the Delaney amendment stifles agricultural research. By so doing, it slows progress in agriculture, and eventually would restrict the supply of quality food and fiber necessary to feed an exploding population. In the last analysis, the Delaney amendment works against the general public interest. If something like the Delaney clause is used, it should be modified to allow scientific judgment by the Food and Drug Administration. Such a modification could read as follows: “A color additive shall be deemed unsafe * * * if the addi- tive is found in amounts under conditions reasonably related to the intended use to induce cancer when ingested by man or animal.” This modification would not take any power away from the FDA. The FDA would apply the same scientific scrutiny to substances coming under the Delaney amendment as they now apply to all other additives. The manufacturer of an additive would still be required to demonstrate the safety of each additive to the satisfaction of the FDA. We also believe that substances cleared under the food additives law should not have to be cleared under the color law. We believe that it is most important to clearly separate the color amendment from the food additives amendment. The basic issues and principles involved in the color additives legislation are not in the best interest of the feed manufacturing industry or of our general economy. Many food additives now in common use significantly reduce the cost of producing a pound of meat, a gallon of milk, or a dozen eggs. Stifing further research by legislation like the Delaney clause will cause a sizable increase in the cost of food to the American public. We hope that the Delaney clause can be modified to allow for scientific judgment in determining which food and color additives are safe when used under conditions reasonably related to their intended use. Sincerely yours, L. E. Deacon. COLOR ADDITIVES 583 Fepruary 16, 1960. Re 8S. 2197 and H.R. 7624. Hon. Oren Harris, Chairman, Interstate and Foreign Commerce Committee, House of Representatives, Washington, D.C. My Dear Mr. CuatrMan: Smith Kline & French Laboratories is a Pennsyl- vania corporation engaged in the manufacture and sale of ethical pharma- ceutical products. These products, which we sell in substantial volume, incor- porate a wide variety of colors used for the purpose of identification, designa- tion of strength, and other purposes related to public health and safety. We, along with 140 other drug companies, are members of the Pharmaceutical Manufacturers Association and support the position so ably presented by Dr. Carney and Messrs. Williams and Worley at the hearing on February 11, 1960. We believe that new legislation permitting the use of color additives in drugs is necessary and that this legislation should be in the form of 8S. 2197 with the important amendments suggested in part I of Mr. Worley's letter dated February 8, 1960. We have prepared a booklet, which has already been submitted to the com- mittee by Mr. Worley, showing how colors in drugs serve a vital health purpose. This booklet contains over 100 letters from physicians, hospital offi- cials, deans of pharmacy schools, boards of pharmacy members, pharmacists, and others with whom we have been in touch. A list by States of these per- sons, together with a summary of their statements, is attached to this letter. The most controversial issue before the committee is the adoption of the arbitrary rule imposed by the present wording of the Delaney amendment. We believe there are serious weaknesses in the argument that once a given color additive has been shown to produce cancer in a single strain of animals, the danger of its use in human beings has been demonstrated. These weak- nesses can be summarized as follows: 1. As in the case of diethylstilbestrol, the substance may have been shown not to produce cancer in most other animals or in human beings themselves, 2. Threshold levels are ruled out even if they can be safely established, 3. A single test is set up which may be entirely at variance with the best scientific judgment. 4. Congress would be inconsistent in permitting the Food and Drug Ad- ministration to make the determination of safety in all danger areas other than cancer. In effect, it would rely on the FDA in most medical areas but would deny the administration’s competency in the field of cancer. If the committee favors a clause highlighting the danger of cancer, we suggest a provision which would permit the decision as to the safety of a color additive to the based on the best scientific evidence available. The PMA has submitted a modification of the present Delaney clause which would accomplish this. We heartily support this modification which appears in part II of Mr. Worley’s letter. Very truly yours, Smirn, Kring & FrReNci LABORATORIES, By Appison 8. Exwis, Vice President. LIST OF PEOPLE WRITING TO SKF RE COLOR ADDITIVES Arkansas Calvin J. Dillaha, M.D., 586 Waldon Building, Little Rock, Ark. Stanley G. Mitteistaedt, dean, University of Arkansas Medical Center, Little Rock, Ark. BE. K. Clardy, M.D., Leo N. Levi Memorial Hospital, Hot Springs National Park, Ark. William G. Smith, secretary-manager, Arkansas Pharmaceutical Association, Little Rock, Ark. Mrs. Helen B. Mahaffey, R.N., Leo N. Levi Memorial Hospital, Hot Springs National Park, Ark. California T. C. Daniels, dean, University of California, San Francisco Medical Center, San Francisco, Calif. Alvah G. Hall, dean, University of Southern California, University Park, Los Angeles, Calif. 584 COLOR ADDITIVES Freeman H. Adams, M.D., Stockton State Hospital, Stockton, Calif. Walter Rapaport, M.D., Agnews State Hospital, Agnew, Calif. William C. Keating, Jr., M.D., Sonoma State Hospital, Eldridge, Calif. Theo K. Miller, M.D., Napa State Hospital, Imola, Calif. Louis J. Fischel, Ph. C., F.A.C.A., Medical Center Prescription Pharmacy, Medi- cal Center Building, Oakland, Calif. Cecil A. Stewart, executive secretary, California Pharmaceutical Association, Los Angeles, Calif. District of Columbia W. A. Neil Wilson, pharmacist, Washington Sanitarium and Hospital, Ta- koma Park, Washington, D.C. M. Eileen Brooks, executive secretary, District of Columbia Pharmaceutical Association, Washington, D.C. Florida P. A. Foote, dean, University of Florida, Gainesville, Fla. J.T. Benbow, M.D., Northeast Florida State Hospital, Macclenny, Fla. Mr. F. A. Canova, Canova Drug Co., Gainesville, Fla. Georgia H. L, Chichester, president, Chichesters Pharmacies, Macon, Ga. Illinois George L. Scharringhausen, Jr., R. Ph., Scharringhausen Pharmacy, Park Ridge, Il. Edward F. Keating, president, American College of Apothecaries, Chicago, IL Kansas Mrs. Clara Miller, secretary-manager, the Kansas Pharmaceutical Association, Topeka, Kans. Robert L. Jenkinson, secretary, Board of Pharmacy, Belleville, Kans. Maryland Bennett A. Robin, M.D., 8723 Piney Branch Road, Silver Spring, Md. Joseph Cohen, executive secretary, Maryland Pharmaceutical Association, Kelly Memorial Building, Baltimore, Md. Massachusetts John BE. F. Cusick, secretary, Department of Civil Service and Registration, Board of Registration in Pharmacy, Boston, Mass. Michigan O. R. Yoder, M.D., Ypsilanti State Hospital, Ypsilanti, Mich. Philip N. Brown, M.D., Northville State Hospital, Northville, Mich. Charles R. Shaw, M.D., Hawthorn Center, Northville, Mich. Robert J. Gillespie, Gillespie’s Drug Store, St. Joseph, Mich. William B. Hennessy, Hennessy’s, Detroit 5, Mich. Albert R. Pisa, Al Pisa Pharmacy, Detroit, Mich. Minnesota George P. Hager, dean, University of Minnesota, Minneapolis, Minn. Henry M. Moen, executive secretary, Minnesota State Pharmaceutical Asso- ciation, St. Paul, Minn, Arthur L. Eide, secretary, Minnesota State Board of Pharmacy, Minneapolis, Minn. Mississippi E. L. Hammond, dean, the University of Mississippi, University, Miss. Mrs. W. W. Johnson, secretary, Mississippi State Pharmaceutical Association, University, Miss. Missouri Emmett F, Hoctor, M.D., State Hospital No. 4, Farmington, Mo. Homer A. George, F.A.C.A., Broadway Prescription Shops, 706 Broadway, Cape Girardeau, Mo. Nebraska Salvatore J. Greco, dean, the Creighton University, Omaha, Nebr. Joseph B. Burt, dean, the University of Nebraska, Lincoln, Nebr. COLOR ADDITIVES 585 Juul C. Nielsen, M.D., Hastings State Hospital, Ingleside, Nebr. Cora Mae Briggs, executive secretary, Nebraska Pharmaceutical Association, 414 Federal Securities Building, Lincoln, Nebr. R. K. Kirkman, director, Bureau of Examining Boards, 1009 State Capitol Building, Lincoln, Nebr. New Jersey Harold 8. Orchow, M.D., 721 Cinnaminson Avenue, Palmyra, N.J. Harry H. Brunt, Jr., M.D., Hammonton, N.J. Norman K, Boudwin, M.D., 64 Church Street, Beverly, N.J. Carl R. Blanche, M.D., 1457 Nottingham Way, Trenton, N.J. John Carl Voss, M.D., Riverton, N.J. John B, Gearren, M.D., 100 Farnsworth Avenue, Bordentown, N.J. Charles W. Burroughs, M.D., 688 Stuyvesant Avenue, Trenton, N.J. Miles FE. Drake, M.D., Vineland State School, Vineland, N.J. Hans W. Freymuth, M.D., New Jersey State Hospital, Trenton, N.J. Martin H. Weinberg, M.D., New Jersey State Hospital at Ancora, Hammonton, Gertrude Heinsohn, R.P., Vineland State School, Vineland, N.J. James FE. Delahanty, Delahanty’s Pharmacy, East State and Chambers Streets, Trenton, N.J. New York Joseph E, Sokal, M.D., Roswell Park Memorial Institute, Buffalo, N.Y. Jugene L, Lozner, M.D., State University of New York, Syracuse, N.Y. H. Houston Merritt, M.D., professor of neurology, College of Physicians and Surgeons, Columbia University, New York, N.Y. Vineent J. Fontana, M.D., 150 East 56th Street, New York, N.Y. Francis J. O’Brien, dean, Union University, Albany College of Pharmacy, Albany, N.Y. Kenneth R. Crispell, M.D., New York Medical College, Flower and Fifth Avenue Hospitals, Fifth Avenue at 106th Street, New York, N. Y. Elsie B. Kris, M.D., State of New York, Department of Mental Hygiene, New York, N.Y. Frederick D. Lascoff, president, J. Leon Lascoff & Son, 1209 Lexington Avenue, Corner 82d Street, New York, N.Y. Calvin Berger, Calvin Berger & Son, 1443 Sixth Avenue, New York, N.Y. William F. de Neergaard, Neergaard, 454 Fifth Avenue, Brooklyn, N.Y. Kenneth 8S. Griswold, secretary, New York State Board of Pharmacy, the University of the State of New York, Albany, N.Y. Ohio Lioyd M. Parks, dean, Ohio State University, 1958 Neil Avenue, Columbus, Ohio, H. H. Peppel, M.D., Hawthornden State Hospital, Macedonia, Ohio. Rupert H. May. M.D., Cleveland Psychiatric Institute and Hospital, 1708 Aiken Avenue, Cleveland, Ohio. William L. Grover, M.D., Cleveland State Hospital, Cleveland, Ohio. Lee BE. Eiler, president, Fidelity Prescriptions, Ine., 42 Wyoming Street, Day- ton, Ohio, Frank FEF. Kunkel, Kunkel Apothecary, Cincinnati, Ohio. James 1). Cope, executive secretary, Ohio State Pharmaceutical Association, 40 South Third Street, Columbus, Ohio. Oklahoma Robert E. Ashley, M.D., Central State Griffin Memorial Hospital, Norman, Okla. Elbert R. Weaver, executive secretary, Oklahoma Pharmaceutical Association, Box 510, Stillwater, Okla. Pennsylvania Wilmer S. Trinkle, M.D., Office of the Coroner, Sellersville, Pa. Robert M. Kline, M.D.. 9 East Walnut Street, Lebanon, Pa. William Gordon Pauley, M.D., William J. Cauffman, M.D., 3 Palm Lane, Levittown, Pa. Frank R. Boyer, M.D., 530 North 20th Street, Allentown, Pa. Robert F. Early, M.D., Walnut at Second Street, Lebanon, Pa. 586 COLOR ADDITIVES Samuel W. Gladding, M.D., 1342 Walnut Street, Allentown, Pa. H. P. Thomas, Jr., M.D., 100 South Main Street, Telford, Pa. Louis A. Pegel, M.D., Bethlehem Pike and Bysher Avenue, Flourtown, Pa. Robert M. Yost, M.D., 223 Summit Avenue, Fort Washington, Pa. Joseph B. Sprowls, dean, Temple University, Philadelphia, Pa. Robert E. Abrams, professor of pharmacy administration, Philadelphia Col- lege of Pharmacy and Science, 43d Street, Kingsessing and Woodland Avenues, Philadelphia, Pa. Howard T. Fiedler, M.D., Allentown State Hospital, Allentown, Pa. William J. Schilling, M.D., Torrance State Hospital, Torrance, Pa. I. M. Ostrum, Ph. G., Ostrum’s Pharmacy, 100 East Tulpehocken Street, Phil- adelphia, Pa. Daniel L. Wertz, Wertz Pharmacy, Corner Main and Clinton Streets, Johns- town, Pa. Ann L. O’Hagan, R.N., Industrial Clinic, Pier 27 North, Delaware and Spring Garden Streets, Philadelphia, Pa. South Carolina William A, Prout, dean, Medical College of South Carolina, 16 Lucas Street, Charleston, S.C. Edward M. Burn, M.D., South Carolina State Hospital, Columbia, S.C. Wilkins Harden, vice president, American College of Apothecaries, Hampton at Bull, Columbia, 8.C. George S. Inman, secretary, Pharmaceutical Association of the State of South Carolina, 3303 Augusta Road, Greenville, S.C. Thomas D. Wyatt, secretary, the Board of Pharmaceutical Examiners, Post Office Box 1563, Spartanburg, S.C. Texas N. M. Ferguson, dean, University of Houston, Cullen Boulevard, Houston, Tex. Henry M. Burlage, dean, University of Texas, Austin, Tex. Felix S. Bambace, M.D., San Antonio State Adult Mental Health Clinic, 5800 South Presa Street, San Antonio, Tex. Walter L. Peterson, M.D., San Antonio State Tuberculosis Hospital, Post Office Box 7206, Hackberry Station, San Antonio, Tex. E. W. Bennett, M.D., San Antonio State Hospital, Post Office Box 1840, San Antonio, Tex. Cc. J. Ruilmann, M.D., Board for Texas State Hospitals and Special Schools, Box 8., Capitol Station, Austin, Tex. West Virginia J. Lester Hayman, dean, West Virginia University, Morgantown, W. Va. William J. Dixon, secretary-manager, West Virginia State Pharmaceutical Association, Post Office Box 119, Oak Hill, W. Va. Wisconsin Louis W. Busse, associate dean, the University of Wisconsin, Madison, Wis. SUMMARY OF LETTERS COMPRISING BOOKLET ENTITLED “MATERIALS SURMITTED BY SMITH KLINE & FRENCH LABORATORIES RE 8, 2197 AND H.R. 7624, FEBRUARY 11, 1960” FILED BY MR. WORLEY ON BEHALF OF THE PHARMACEUTICAL MANUFACTURERS ASSOCIATION 1. Where a patient is taking more than one drug, color helps him distinguish them. This is particularly true in the case of elderly and illiterate people. 2. Coloring of drugs may be a lifesaving device in case of overdosage and accidental poisoning because it permits rapid and accurate identification of the drug without the necessity of long chemical analysis. 3. Coloring of drugs helps to eliminate serious errors by nurses and others who administer drugs to patients in hospitals, particularly in State hospitals where use is made of subprofessional personnel whose knowledge of drugs is limited. Normally, the medication is sent to them for distribution apart from the labeled container so that there is always a possibility of accidental inter- mingling. 4, Coloring makes a drug more acceptable and pleasant for patients, especially children. This increases the likelihood that a given patient will continue with needed medication. COLOR ADDITIVES 587 5. Patients occasionally develop allergies to one of the medications they are taking. If the medication is colored or carries other color markings, it is easier to identify the medication causing the allergic reaction. 6. A patient may already be taking medication the first time a doctor sees him. Color helps the doctor identify such medication and prescribe the course of treatment. 7. Doctors often check on the medication the patient is taking to make sure it is what has been prescribed. The use of colors and markings makes this possible. In talking to a patient on the telephone, color helps the patient de- scribe his medication. 8. Many drugs have a repellent natural color. Other drugs change color over a period of time without loss of therapeutic effectiveness. This may cause un- favorable patient reaction. A stable color would prevent this. 9. Coloring to indicate dosage strengths serves as a safety check for the pharmacist in filling prescriptions. Dots and other markings used for this purpose require inks which are also color additives. 10. A number of pharmacists write on the back of the doctor's prescription the color of the medication used as a check on the accuracy of refills. 11. Pharmacists frequently transfer drugs from the bottles in which they purchase drugs to stock bottles. Color serves as a safety check in making sure the right medication is placed in the proper bottle. 12. Colors serve as an additional safety check in preventing accidental mis- haps in manufacturing and packaging. Sura Krink & Frexncu Lanorarories, RESEARCH AND DEVELOPMENT DIVISION, Philadelphia, Pa., April 20, 1960. Hon. Oren Harris, Chairman, Committee on Interstate and Forcign Commerce, The Capitol, Washington, D.C, Dear Mr. Harris: H.R. bill 7624 dealing with color additives legislation, because of its “anticancer clause,” the Delaney amendment, may throw an insur- mountable obstacle in the path of valuable chemical and pharmaceutical additive research. This bill, in its present form, would completely ban the use of all substances, including food additives which are capable of imparting color, which have produced cancer in animals under abnormal feeding or laboratory condi- tions although they may be safe when used as instructed, The effect of this may be that many potenially valuable substances will never be made available to the consumer. For example, under the existing Delaney amendment to the Food Additive Act of 1958S (after which the cancer clause in H.R. 7624 is patterned), the FDA has not allowed any new drug applications on diethylstilbestrol to become effective. Diethylstilbestrol is a hormone fed to cattle in feed supplement form at the recommended rate of 10 milligrams per animal daily. Only selected strains of susceptible animals could be used, e.g., Syrian hamsters, guinea pigs, and even in these many of the tumors have no counterpart in buman beings. It is estimated that at present there are about 300,000 women in the United States taking diethylstilbestrol for a number of different conditions in which it is a valuable means of therapy. The normal dose of diethylstilbestrol in women is 0.5 to 5 milligrams daily, with the dosage period ranging up to years, Any undetectable amounts of diethylstilbestrol ingested through the consumption of meat from animals fed a diethylstilbestrol- containing feed supplement would be totally insignificant when related to these normal therapeutic dosage levels, It is, of course, mandatory that there be governmental control over poten- tially harminful chemical substances which are sold to the public. However, if a manufacturer is able to prove to the satisfaction of the Food and Drug Admin- istration, the Government clearinghouse, that a particular chemical is indeed safe (according to qualified specifications) when administered and used properly, then he should be permitted to sell this product. By imposing a flat prohibition on additives which can be made to cause cancer under laboratory conditions unrelated to practical use, the Delaney amendment prevents the use of other- wise valuable substances. 588 COLOR ADDITIVES Therefore, it is proposed that a phrase be added to the Delaney amendment making it more workable from the point of view of the general public. The additional wording would protect the public from the cancer-producing agents but would allow the FDA to exercise scientific judgment in the appraisal of new additives for food, drugs, and cosmetics, The proposed addition is printed in italic: “A color additive shall be deemed unsafe * * * if the additive is found to induce cancer when ingested by man or animal, in an amount and under other conditions reasonably related to its intended use, or if it is found, after tests which are appropriate for the safety of the additive for its intended use, to induce cancer in man or animal.” Sincerely yours, R. F. Der, Manager, Animal Health Products Department. Wasuineoron, D.C., May 18, 1960. Hon. Oren Hargis, Chairman, Committee on Interstate and Foreign Commerce, House Office Building, Washington, D.C. Dear Mr. CHAIRMAN: Enclosed for your information is a copy of a statement submitted on behalf of the Pharmaceutical Manufacturers Association as a sup- plement to my testimony before the Interstate and Foreign Commerce Committee on February 11, 1960, concerning the anticancer provision of H.R. 7624, the color additives bill. The statement comments upon certain questions which have arisen as a result of the discussion of the expert scientific panel before the committee on April 5 and 6, 1960, Secretary Flemming’s testimony of May 9, and the report of the President's Science Advisory Committee (the Kistiakowsky report) released by the White House on May 14. The statement points out the basic inconsistency between the position of the Department of Health, Education, and Welfare, which opposes any modification of the anticancer clause, and the views expressed in the Kistiakowsky report and by the most of the panel of experts who appeared before the Interstate and Foreign Commerce Committee. The Kistiakowsky report and the majority of the committee’s panel favor such modification of the anticancer clause as would permit appropriate exercise by the Food and Drug Administration of scientific judgment as to the safety of food additives which are found to induce cancer in some animals under given test conditions. I would be grateful for your consideration of the analysis of this matter in my supplementary statement. We would appreciate inclusion of the supple- mentary statement and the accompanying enclosure in the record of the hearings on H.R. 7624. Sincerely, Epwarp Brown WILLIAMS. SUPPLEMENTARY STATEMENT OF EDWARD BROWN WILLIAMS ON BEHALF OF PHAR- MACEUTICAL MANUFACTURERS ASSOCIATION, CONCERNING THE ANTICANCER CLAUSE or H.R. 7624 Since the position of the interested industries was presented to the Interstate and Foreign Commerce Committee on the so-called anticancer clause of the pro- posed color additives bill (H.R. 7624) there have been presented to your commit- tee the views of a distinguished panel of experts assembled by the committee (hearings of April 5 and 6, 1960) and additional testimony of the Honorable Arthur S. Flemming, Secretary of Health, Education, and Welfare (May 9, 1960). More recently, on May 14, 1960, the White House released the report of a study of the problem posed by the proposed anticancer provision of H.R. 7624 and the Delaney clause of the food-additives amendment to the Federal Food, Drug and Cosmetic Act. The study was made by the Departments of Agriculture and Health, Education, and Welfare and the President's Science Advisory Committee. The White House release recites that the report of the study group was approved by the President's Special Assistant for Science and Technology, Dr. George B. Kistinkowsky, and also concurred in by the Departments of Agriculture and COLOR ADDITIVES 589 Health, Education, and Welfare. The group which submitted the report is here- inafter referred to as the Kistiakowsky panel. We take this opportunity to submit, on behalf of the Pharmaceutical Manu- facturers Association, certain comments on the testimony and report in ques- tion, as a supplement to the testimony presented on behalf of the association on February 11, 1960. it is evident from a study of the report of the Kistiakowsky panel and of the opinions expressed by most of the members of the panel which appeared before your conunittee that these groups do not share the views of the Department of Health, Education, and Welfare, that the anticancer clause as it now appears in the food-additives amendment and in H.R. 7624, is scientifically sound. The significance and application to the problem before the committee of the findings of the Kistiakowsky panel, the most recent expression upon the matter, are first considered. I. THE REPORT AND RECOMMENDATIONS OF THE KISTIAKOWSKY PANEL Among the recommendations of the panel are the following: (1) That the Secretary of Health, Education, and Welfare appoint an Advisory Board “to assist him in the evaluation of scientific evidence on the basis of which decisions have to be made prohibiting or permitting the use of certain possibly carcinogenic compounds,” including evidence relating both to applica- tions for approval of new food additives and to cases where the withdrawal of a prior approval or sanction is under consideration. The Board would consider, among other matters: (a) Whether or not the tests for carcinogenicity are appropriate and reasonable, (b) Whether the substance is nor is not in reality carcinogenic as deter- mined histopathologically or by other criteria. (2) “If existing legislation does not permit the Secretary of Health, Educa- tion, and Welfare to exercise discretion consistent with the recommendations of this report, it is recommended that appropriate modifications in the law be sought.” The key words in the second recommendation, just quoted, are “discretion consistent with the recommendations of this report.” Unfortunately, in order to determine whether this recommendation means that a modification of the Delaney clause is being advocated, it is necessary to review the statements and conclusions upon which the recommendation is based. But it seems clear, initially, that a rigid legislative test such as that of the anticancer clause with its severe limitation of the exercise of scientific judgment, itself precludes the use of “appropriate and reasonable” tests of carcinogenicity, within the meaning of 1(@) above. The report states, with respect to the Delaney clause: “The panel subscribes to the intent of the Congress in approving this section of the food-additives amendment to protect the public from increasing cancer risks through the diet. However, there are certain difficulties in its practical application—difficulties which give rise to many uncertainties both on the part of the public and those whose responsibility it is to administer the law” (p. 3). The industry also, as it has demonstrated, endorses this intent of protecting the public. The problem is solely one of method. It is said, in part 2 of the report, referring to the use of cancer-inducing substances, as affected by the section of the food additives amendment con- taining the Delaney clause (sec. 409(3)(c)(A) of the Food, Drug, and Cos- metic Act, that-—— “A literal interpretation of the section must lead to the prohibition of such a substance even though present in trace amounts.” * . * * * * * . “For a number of carcinogens that have been studied, however, there is evi- dence for the existence of a level of ingestion at which no carcinogenesis occurs during the life of the animals when tested in limited numbers” (p. 6). Dose-response curves for certain potent carcinogens in animals have been worked out, the report states, “from which can be reliably predicted the proba- bility of an individual, in a given sized population, developing a tumor from agiven dose of carcinogen.” And— 1 This is of course, the interpretation made by the Secretary. 590 COLOR ADDITIVES “Such curves lend to the conclusion that dietary levels of carcinogenic agents exist at which the probability of cancer induction in animals is near zero” (p. 6). "The report then cites evidence which indicates that a dose-response relation for certain carcinogens exists in man—that is, that the safety of the carcinogen for use in human food is related to the amount ingested. Foodstuffs contain- ing traces of chemicals which in larger amounts are generally accepted as car- cinogenie but which are not suspect in trace quantities, are mentioned; other situations and evidence are referred to which indicate that the incidence of eancer in man is related to the duration and amount of exposure to carcino gens (pp. 6and 7). It is concluded that— “From the experience obtained in animal experiments and study of humans who have been exposed to carcinogens in the course of their work such as cited above, the panel believes that the probability of cancer induction from a par- ticular carcinogen in minute doses may be eventually assessed by weighing scientific evidence as it becomes available” (pp. 6 and 9). Specifically, in part 3 of the report it is pointed out that— (1) Selenium, which is carcinogenic in animals when consumed for long periods in considerable amounts, is reported to be an essential nutrient element in the diet of lambs. (2) Inorganic arsenic (some compounds of which have been indicated of carcinogenic) is released when organic arsenicals are added to animal (3) Minute traces of polyethylene stearate in the human diet “are not likely to produce bladder cancer, and can be treated as any other toxic material,” despite the fact that, when fed to rats at a level of 25 percent of the diet (but not at lower levels) this substance produced urinary bladder stones “which induced bladder tumors, some malignant.” This list of examples, the report states, may be expected to lengthen “and each case requires scientific judgment to determine the issues involved” (p. 7). It will be seen from example number (3) that the committee has already "weighed the scientific evidence” relating to polyethylene stearate, or it could not have concluded that it “can be treated as any other toxic material.” It is thus apparent that the Kistiakowsky panel believes that scientific judg- ment in assessing the safety of carcinogens or suspected carcinogens should be brought to bear, not only in determining whether such substances cause cancer in animals, but also in deciding whether the use of such a substance in the amounts proposed would be carcinogenic (1) in animals, and (2) in man. Secre- tary Flemming has testified before your committee that the only permissible exer- cise of judgment is in the area of determining whether a given substance has caused cancer in the diet of test animals, thus foreclosing consiueration of the fundamental question of whether under different conditions and in different (smaller) dosages it would have the same effect in animals or, more impor- tantly, in man. The report advocates application of the “rule of reason” to determinations of the safety of food additives, including carcinogens and suspected carcinogens. It is difficult to understand how foreclosure of any consideration of the safety of certain substances naturally occurring in foods (the panel named inorganic arsenic compounds, radium, and selenium) on the ground that they cause cancer in some animals under specified test conditions, could be regarded as consistent with the panel’s standard that the rule of reason should govern determinations of the safety of such substances when added to foods, It must be concluded that the approach of Secretary Flemming is not consistent with that of the Kistia- kowsky panel and that its recommendation No. 2 (above quoted) means that the Delaney clause should be modified to permit recourse to such a rule. Moreover, the specific declaration in the report, which we have noted, that a substance which causes bladder stones resulting in cancer can, when used in minute amounts. “be treated as any other toxie material,” is inconsistent with the view of the Secretary, which would preclude any consideration of the safety of such a substance. It is evident, therefore, that the legislative test of whether a substance causes eancer in animals under test conditions must be modified if effect is to be given to the recommendations of the Kistinkowsky panel. Since, as the report states, “dietary levels of carcinogenic agents exist at which the probability of eancer induction in animals is near zero” (p. 6) it is not reasonable (within the mean- ® COLOR ADDITIVES ing of the report) to exclude from examination and the application of scien judgment (as Secretary Flemming would do), the question of whether, in man, a given level of use of a carcinogenic agent might be safe. Thus, there seems to be no doubt of the intent of the report of the panel, despite the imprecise language in which its final recommendations are expressed. Il. THE RECOMMENDATIONS OF MEMBERS OF THE PANEL ASSEMBLED BY THE INTERSTATE AND FOREIGN COMMERCE COMMITTEE The statements of the panel of scientific experts at a hearing held by your com- mittee on April 5 and 6, 1960, were more specific than was the report of the Kistiakowsky panel. In the hope of aiding the committee in its consideration of the problem of the anticancer clause as it appears in H.R. 7624, we have pre- pared the enclosed summary (enclosure A) of the views of the 13 experts who addressed themselves to the question whether that clause should be modified. This summary, which is keyed to the pertinent record references, shows that only 3 of the 13 experts in question (Drs. Mider, Stewart, and Blum), supported Sec- retary Flemming in his position against modification, One (Dr. Shubik), ad- vocated modification but seemingly agreed with the Secretary that a substance should be deemed unsafe if it causes cancer in animals, regardless of considera- tions dosages and other conditions of use. The other nine experts favored modification of the Delaney clause to the extent necessary to permit the exercise of scientific judgment in determining the safety of all substances proposed for use in food since, in extraordinary cases, there might be justification for the es- tablishment of tolerances for substances which are found, under certain con- ditions, to induce cancer in animals. These experts, like the Kistiakowsky panel, would not limit the exercise of judgment to the question whether a given substance induces cancer in test animals, Ill. COMPARISON OF VIEWS OF THE KISTTAKOWSKY PANEL, THE COMMITTEE PANEL, SECRETARY FLEMMING, AND THE INDUSTRY (1) Both the Kistiakowsky panel and the great majority of the panel of ex- perts assembled by your committee have, therefore, refused to limit the principle of “exercise of scientific judgment” as Secretary Flemming advocates. The saine position has been taken in testimony presented to your committee by the in- terested industries. It was, therefore, with some surprise that we found Sec- retary Flemming declaring, in his testimony of May 9, that— “The rallying point against the anticancer provision is the catch phrase that it tukes away the scientist’s right to exercise judgment. The issue thus made is a false one, because the clause allows the exercise of all the judgment that can safely be exercised on the basis of our present knowledge.” In substance then, the committee is faced with a conflict of views between See- retary Flemming on the one hand and the Kistiakowsky panel and most of the panel assembled by your committee, on the other, It was emphasized by some members of your committee's panel that a rigid test which allows for no scientific judgment once it is found that a substance induces cancer in animals under certain conditions, should not be incorporated into legislation. Such a test, it was pointed out, tends to discourage research generally. Specifically, it retards research efforts to shed further light upon the very question posed by the controversy under discussion: Whether and to what extent, in the case of a given substance, dosage and other conditions of use will determine the capacity of the substance to induce cancer. We respectfully submit that, for this reason alone, it is unwise legislative policy to establish a test of safety of such rigidity as that resulting from the administrative interpre- tation of the Delaney clause and its counterpart in H.R. 7624, (2) The question arose when Secretary Flemming testified on May 9, whether the burden was on the industry to prove that a food additive will not induce can- cer. We want to avoid any misunderstanding which may have arisen on this point. There are two aspects of the question. First, the basic burden of testing to show safety is upon the industry. This is entirely clear from the language of the food additives amendment and H.R. 7624, If suspicion of carcinogenicity is involved with respect to a particular substance, it is equally clear that an additional burden of disproving specifically that the substance is carcinogenic likewise falls upon the industry, without regard to whether the substance has been shown to induce cancer in animals under given test conditions. In the event, however, that the substance is found to induce 592 COLOR ADDITIVES eancer in animals under such conditions, it is evident that no question of proof arises at all since the substance is absolutely banned from use in food by reason of the operation of the Delaney clause as administratively applied. This is the legal situation which exists today. Secondly, substances which have heretofore been found by the Food and Drug Administration to be safe under the new drug provisions of the statute (sec. 505), such as Diethylstilbestrol and certain arsenicals, may be used under the prior approval or prior sanction provisions of the food additives amendment, by the persons who obtained such prior approvals. But such substances, although already found to be safe, cannot be used by other persons who did not obtain approval of their use before January 1, 1958, because of the application of the Delaney clause by the Department of Health, Education, and Welfare. Under these circumstances it is immaterial whether the burden of the industry ‘gs stated in terms of proof of a negative or is characterized in some other manner. The burden is there and, insofar as we can see, cannot be met under any reason- ably circumstances because of the present policies of the Secretary under the anticancer provision. IV. INDUSTRY PROPOSAL It was proposed, in testimony on behalf of the Pharmaceutical Manufacturers Association, with the endorsement of other industry witnesses, that the anti- cancer clause of H.R. 7624 be amended to read as follows: SECTION 706 (b) (5) (B) “A color additive (1) shall be deemed unsafe, and shall not be listed, for any use which will or may result in ingestion of all or part of such additive, if the additive is found to induce cancer when ingested by man or animal, in an amount and under other conditions reasonably related to its intended use, or if it is found, after tests which are appropriate for the safety of the additive for és intended use, to induce cancer in man or animal * * *” We renew this suggestion for the consideration of the committee. It is sub stantially consistent with the prevailing points of view heretofore discussed. It is more restrictive than the position heretofore taken by the Department of Health, Education, and Welfare as stated by former Assistant Secretary Richard- son in a letter to the chairman of the committee, dated August 8, 1958, which read, in part, as follows: “To single out one class of diseases for special mention would be anomalous and could be misinterpreted. Hence, in drafting the Department’s bill we chose general language that would restrain any use of an additive that would have any adverse effect on the public health * * *” We stand ready to render such assistance to your committee on the problem discussed in this statement as appears to you to be appropriate. Views oF Experts ASSEMBLED BY THE COMMITTEE ON INTERSTATE AND FOREIGN CoMMERCE APRIL 5 ANp 6, 1960 Dr. Darsy (chairman of panel). Would modify Delaney clause to permit exercise of scientific judgment and, in exceptional situations, the establish- ment of tolerances for substances which induce cancer in animals under vertain conditions (R. 885-838, 885), with provision for referral of controversial problems to expert panel (R. 836). Dr. Miper, Would not modify Delaney clause or permit establishment of toter- ances at the present time (R. 873). Dr. Stewarr. Agrees with Dr. Mider (R. 873). Dr. Brum. Considers Delaney clause necessary (R. 877). Dr. Kinster. Would modify Delaney clause to permit establishment of toler- ances in exceptional situations, in exercise of scientitic judgment. Should not have to wait for new legislation where situations arise justifying tolerances (R. 873-874). Dr. Cannon. Would modify Delaney clause to permit exercise of scientific judgment as to safety of use under given conditions. See no hazard in en- trusting decisions in this area to Food and Drug Administration (R. 875-876). Dr. De Epos. Would modify Delaney clause to permit establishment of toler- ances in exceptional situations (R. S880). Dr. Levin. Would favor provision permitting final decision by scientifie panel, in exceptional instances, on question of whether there should be a tolerance. COLOR ADDITIVES 593 Dr. MILLER. Would modify law to provide that, in unusual situations where the question of hazard is in dispute, the Secretary should seek the opinion of a board of experts, and should then make the final decision as to whether a tolerance should be established (R. 883). Dr. TANNENBAUM. The Delaney clause should be retained but should include a provision for review of controversial problems by a scientific panel “and only for special borderline problems should the Food and Drug Administration give consideration to tolerances” (R. 883). Dr. Zavon. Would modify Delaney clause by eliminating provision relating to safety of substances found to induce cancer in man or animal. Agrees with Dr. De Eds (R. 584). Dr. O'DONNELL, Unwise to single out cancer for special consideration in legis- lation. Decision whether to set tolerance should be one of scientific judgment, not of legislation (R. 722). Dr. Suusik (by letter to Dr. Darby). “It is not possible to determine the tolerance dose of an established carcinogen on an experimental basis. In spite of this the Delaney clause cannot be defended since the phraseology used is too broad and may well encompass agents that might not be considered to be truly carcinogenic by any panel of experts in the field.” It would be suflicient if all additives were required to be subjected to test procedures adequate to detect earcinogenic action, with the results to be evaluated by committee of experts CR. 831). Cras. Prizer & Co., INnc., MANUFACTURING CHEMISTS, Brooklyn, N.Y., March 16, 1960. Re S. 2197 and H.R. 7024. Hon. Oren Harris, Chairman, Interstate and Foreign Commerce Committee, House of Representa- tives, Washington, D.C. Deak Mr. CUAIRMAN; The representatives of the pharmaceutical industry who testified before your committee on February 10 and 11 spoke at some length about the inequitable situation which has developed with regard to the use of diethylstilbestrol (DES) and certain arsenical compounds in animal feeds. The principal inequity which these witnesses brought out is the fact that those feed manufacturers who received, prior to p:ssage of the food additives amendment, effective new drug applications for feeds coucaining either DES or those ar- senicals which are still new drugs, can continue to market such feeds, but that the Department of Health, Education, and Welfare refuses to make effective any additional new drug applications for feeds containing these drugs. Consequently, we have the anomalous situation of some feed manufacturers being permitted to manufacture feeds containing DES and those arsenicals, while other feed manufacturers are barred from doing the same thing. This situation results from the interplay between the “prior sanction” exemp- tion from the definition of the term “food additive,” and the per se prohibition of the Delaney amendment in the food additives amendment, as those provisions are interpreted by the Department. While it is manifest that the effects of the above interpretation on the use of DES and arsenicals in animal feeds are inequitable, we submit that its effect on virtually all newly developed drugs for feed use is even more inequitable and merits most careful consideration by your committee. A brief explanation of the effect of the above interpretation on newly developed drugs is necessary at this point: Today, between 70 and 80 percent of all manufactured broiler feeds contain arsenicals either to promote growth or to prevent the disease coccidiosis. A high percentage of swine feeds also contain arsenicals. Similarly, about 8O percent of manufactured cattlefeeds today contain DES to stimulate growth and im- prove feed efficiency. Under the Department's interpretation, these high per- centages of such feeds can continue to be marketed, provided there are no changes in composition, manufacturing procedures, labeling, etc., which would be significant from the standpoint of satety. Because DES and the arsenicals are quite effective, and relatively inexpensive, it is not likely that their use by feed manufacturers will decline for a consider- able period of time to come. Consequently, when a new drug is developed by Pfizer or by another company for use in feeds produced by these manufacturers, if its sale is to be successful, it must be added to the 70-80 percent of the ex- 594 COLOR ADDITIVES empted feeds which already contain DES or arsenicals. The combination of a newly developed drug with either DES or arsenicals in feed is, however, a new drug, and cannot be marketed until the Department makes effective a new drug application for such combination. Because of its aforementioned interpretation, however, the Department is refusing to make effective any new drug applications for such combinations. The practical effect of this interpretation is to bar automatically the use of any newly developed drug in 70-80 percent of the manufactured animal feeds marketed today. : When the cost of research and development of such new drugs, and of obtain- ing the data necessary for clearance by the Department is considered in the light of the small percentage of feeds in which it is presently possible to obtain clear- ance by the Department for use of such drugs, it is quite apparent that drug man- ufacturers must drastically curtail research and development work on such drugs. A few concrete illustrations will serve to make the above comments more evident : (i) Pfizer has spent at a conservative estimate $400,000 to develop a new anti- biotic for use alone and in combination with other drugs in poultry feeds as a growth stimulant. There is not included in this estimate the very substantial expenditure which we have made to develop data to demonstrate advantages over competitive products, and other data required for sales reasons. Oleandomycin Premix was the result of that research. Although FDA cleared Oleandomycin Premix for use, as the sole drug ingredient, in feed under the new drug pro- cedure on May 5, 1959, and cleared Oleandomycin Premix in swine feeds also con- taining Terramycin on July 7, 1959, and although oleandomycin is an exceedingly good growth stimulant, we have not even commenced sale of this product to date. Our delay in commencing sale has been primarily due to the commercial need to incorporate oleandomycin in the 70-80 percent of feeds which also con- tain arsenicals, and FDA’s unwillingness, because of its above-mentioned inter- pretation, to grant such clearance. This is particularly disturbing when you con- sider that the use of these arsenicals, in combination with a number of older antibiotics, was cleared by FDA prior to the amendment, and those combinations are widely used today. (ii) Ptizer has spent at a conservative estimate $200,000 to develop Tran-Q Premix for use, primarily with DES, in eattle feeds as a growth stimulant. There is not included in this estimate the very substantial expenditure which we have made to develop data to demonstrate advantages over competitive products, and other data required for sales reasons. Although we obtained new drug clearance for Tran-Q Premix, as the sole drug ingredient, in feed on August 13, 1958, and cleared Tran-Q in feeds also containing terramycin on April 15, 1959, and although Tran-Q significantly increases the growth stimulating effect of feeds containing DES, our sales of Tran-Q Premix to date are materially less than its research costs. Our low sales result because FDA, under its aforementioned interpretations, will not clear the use of Tran-Q in the 70 percent of cattle feeds which contain DES. Again, this is all the more disturbing in view of the fact that DES for use alone, and in combination with various other drugs, was cleared by FDA prior to the amendment, and those combinations are in wide use today, (iii) Ptizer has spent $300,000 to $400,000 so far in the development of GS-— 1777 a most promising new coccidiostat. We would need to spend between $230,000 and $300,000 to obtain the data necessary for FDA clearance for this product. Because we realize that we will be unable to obtain FDA clearance for its use in feeds containing arsenicals under FDA’s present interpretation, we are contemplating discontinuation of further development work on this product, We have used Pfizer new drugs in the above examples, but other pharma- ceutical manufacturers are undoubtedly also in a position to furnish similar examples involving their newly developed drugs. It is important to note that the above interpretation virtually assures those manufacturers who obtained clearance by the Department for marketing various drugs in feeds which also contain DES or arsenicals, prior to the food-addi- tives amendment, that they will be free from competition from new developed drugs. Pfizer has been a leader in research for drugs to improve growth, feed effi- ciency, and fight disease of animals. COLOR ADDITIVES 595 During the past several years, we have been spending approximately $1.4 million per year for research and development at our agricultural research farm for products to improve animal health and nutrition. This farm is lo- cated on our plant site, comprising 1.865 acres at Terre Haute, Ind. In addi- tion, we have been spending about $154,000 for research by our parasitology research department at Maywood, N.J., converned with discovery of drugs effective against coccidiosis and other animal diseases. The obstacles to success- ful marketing of new drugs for feed use, which have resulted from the inter- pretation which we have been discussing have been so drastic, that Ptizer has severely curtailed research in this field. The drugs which have already been developed by Pfizer and others in our industry have contributed greatly to the present abundance, at reasonable prices, of meat, milk, and eggs in this country. The modern feed lot and broiler raising operations which have reduced so substantially the cost of raising livestock and poultry, would not be practicable without these drugs. New and improved drugs will be necessary for further advancements. Unless appropriate legislative and/or interpretative revisions are forthcoming without delay it is our belief that the need for such drugs will not be met. We do not want to create the impression that we believe the Department is being arbitrary or unfair in its dealings with us or other members of our in- dustry. We have the utmost admiration for the personnel of the Department, and we regard them as highly competent and fair. It has been our intention in this letter merely to point out the inequities which have arisen out of the Delaney amendment, as interpreted by the Department. In view of the above, as well as for the reasons outlined by Dr. Carney, Mr. Williams, and Mr. Worley during their testimony on February 11, Pfizer sub- mits that the cancer clause in proposed section 706(b)(5)(B) on page 10 of H.R. 7624 should not be enacted. If your committee believes that a cancer clause should be included in color-additives legislation, then we submit that such a clause should read as follows : “(B) a color additive (i) shall be deemed unsafe, and shall not be listed for any use which will or may result in ingestion of all or part of such additive, if the additive is found to induce cancer when ingested by tan or animal in an amount and under other conditions reasonably related to its intended use, or if it is found, after tests which are appropriate for the evaluation of the safety of the additives for its intended use, to induce cancer in man or animal, and (ii) shall be deemed unsafe, and shall not be listed, for any use which will not result in ingestion of any part of such additive if. after tests which are appropriate for the evaluation of the safety of additives for such use, or after other relevant exposure of man or animal to such additives, it is found to induce cancer in man or animal.” We also submit that he so-called Delaney amendment (sec. 409(c) (3) (A)) in the Food Additives Amendment should be similarly amended, Whether or not this suggested revision of the Delaney amendment if enacted, would overcome the inequitable situation described throughout this letter will depend, of course, upon how it is interpreted and administered by the Depart- ment. It is our hope that if the suggested revision is enacted the report of your committee will contain appropriate statements to guide the Department toward interpretation and administration which will overcome this situation, Respectfully submitted. ALLAN J, GREENF, Administrative Vice President. Witmer & Broun, Washington, D. C., February 26, 1960. Re color-additives amendment to the Federal Food, Drug, and Cosmetic Act, H.R. 7624 and 8. 2197 Hon. Oren Harris, Chairman, Committee on Interstate and Forcign Commerce, House of Representatives, Washington, D.C. Dear Mr. CHatrMan: On behalf of the Certified Color Industry Committee, spokesman for the industry most directly concerned by the proposed color-addi- tives legislation, I respectfully request that this letter, commenting on matters occurring after Mr. Schramm’s appearance before your committee on January 56123—60——39 COLOR ADDITIVES 27, 1960, be included in the record of the hearings. Sufficient copies of this let- ter are enclosed for all members of your committee and for its professional staff. 1, THE COLOR ADDITIVES WHICH WILL BE REGULATED DO NOT PRODUCE CANCER A few statements were made in the hearing on February 11 which may be con- strued as inferring or asserting that some color additives may produce cancer. Those statements are set forth in the appendix to this letter. The facts are to the contrary. There is no evidence that any of the colors in use, or even those which have been recently delisted, will produce cancer. As Secretary Flemming stated in his testimony on January 26, 1960, with re- spect to the colors used in lipsticks, which are now involved in delisting pro- ceedings (Tr. 119, 121): “None of the colors have produced cancer in the test animals, however.” * * * * * * * “Again, may I underline the fact that there is no question of cancer involved in any of these colors. I mean, none of them have been shown to induce cancer in animals when ingested by an animal, so that issue is not present.” The Food and Drug Administration has been retesting almost all of the food colors and many of the other drug and cosmetic colors, some for as much as 7 years, and they have advised industry that none of their tests to date have disclosed carcinogenic manifestations. The statement of Dr. Aaron (Tr. 585) that a number of the food colors are listed “in a compilation of carcinogenic substances” reported by “Dr. Shubie and Dr. Howell * * * published by the Public Health Service,” is erroneous and mis- leading. The publication so referred to is Public Health Service Publication No. 149, second edition, 1951, by Jonathan L. Hartwell of the National Cancer Institute, and supplement No. 1 thereto, 1957, by Philippe Shubik of the Chicago Medical School and Jonathan L. Hartwell. This publication is not a compilation of carcinogenic substances. Instead, as stated in the introduction to supplement No. 1, it is simply a survey of the literature on the testing of compounds for carcinogenic activity and “it is not the purpose of this survey to pronounce upon carcinogenicity of tested material.” The fact remains, that, as Dr. Carney testified on February 11, 1960, when he appeared for the Pharmaceutical Manufacturers Association (Tr. 475) : “The coal-tar colors do not produce cancer.” 2. ACCEPTABLE PROPOSED AMENDMENTS We have noted that on February 10 and 11, various amendments were proposed by one or more of the following organizations : National Canners Association, Abbott Laboratories. The Society of the Plastics Industry. The Manufacturing Chemists Association. The Pharmaceutical Manufacturers Association. The Proprietary Association. which would generally: (a) Narrow the definition of “color additive” to exclude materials which need not be regulated as color additives for various reasons; (b) Remove economie factors and functional value concepts from, and limit the Secretary to safety considerations in, the determination of whether to list color additives for use; and (¢) Write the usual procedural safeguards for hearings and judicial re- view into the provisional listing and transitional provisions of the bills, Our committee has no objection to those amendments. Indeed, we think they will generally strengthen the proposed legislation—by eliminating extraneous matter and avoiding needless duplication, thus making it easier to administer, and by adding traditional due process rights—without impinging in any way on the central purpose of safety for use and the protection of the public health. Accordingly, we hope those amendments receive favorable consideration from your committee. 3. THE CANCER OR DELANEY CLAUSE (SEC. 706(b) (5) (BR) OF H.R. 7624) We note that several responsible organizations: Abbott Laboratories, the Manufacturing Chemists Association, the Pharmaceutical Manufacturers As- COLOR ADDITIVES 597 sociation, National Feed Ingredients Association, and the Proprietary Associa- tion, took the same general position as we did concerning this clause—that it is unnecessary, that it is scientifically unsound, and that at the very least its rigidity should be relaxed to allow a certain area of flexibility and judgment on the part of the Secretary, with the burden firmly remaining on industry to produce data which demonstrates that the proposed use of a color additive will be safe under the conditions of that use, Those presentations of those organiza- tions effectively demonstrate how the per se ban of the Delaney clause in the food additives amendment as it is now construed by the Department of Health, Education, and Welfare can lay a stifling hand on scientific research and the economic growth which depends upon that research, particularly in the field of agriculture. We are encouraged by the interest which you, Mr. Chairman, and other members of the committee have expressed concerning this problem and its possible resolution. While we would prefer to see the cancer clause wholly eliminated, or made wholly discretionary, as proposed in Mr. Schramumn's testi- mony of January 27, 1960, we can understand why it may nt be possible to go that far. Accordingly, we suggest that as a minimum your committee should adopt the proposal advanced by the Pharmaceutical Manufacturers Association, which appears at page 541 of the transcript for February 11. That proposal makes the least possible change in the language of the Delaney clause, while at the same time allowing for some exercise of judgment on the part of the Secretary. It still leaves the Secretary with ample power to protect the public health, and we believe that it is an eminently modest suggestion which should cause no concern to the public. Finally, we would like to stress again the urgent need for this legislation. We are even now engaged in litigation and delisting proceedings with the Food and Drug Administration because of the outmoded “per se harmless” concept of the present legislation for regulation of colors, Prompt enactment of the proposed legislation will eliminate this burden from both industry and government and will permit the continued use of needed colors in foods, drugs, and cosmetics under conditions which are safe. Thank you very much for your interest and consideration. Very truly yours, JouHN H. PICKERING, Attorney for the Certified Color Industry Committee. APPENDIX Representative King, transcript 412 “And so, they argue, since the odds already seem to favor the probability that colors and other additives which in enormous quantities have carcinogenic effects upon test animals are harmless in the amounts in which they are normally consumed, so why ban them—why not authorize their continued use until science ean conclusively show that they are harmful.” Representative King, transcript 413 “The colors which go into our foods and cosmetics are in no way essential to the public interest or the national security. If those which are carcinogenic in any degree are kept out of the market, the consumers will easily get along without them.” Transcript 566 “Mr. WILLIAMS. They tell me, Mr. Chairman, that there are a great many more chemical substances than you would think even from what you have heard, which will, when ingested or injected in animals cause cancer under certain conditions and in certain strains of animals, and we do not know how many of these coal- tur colors may do that.” Dr. Aaron, transcript 585 “* * * that colors used in foods, drugs, and cosmetics have carcinogenic proper- ties is more difficult to establish, since tests have to be carried on during many years in several species of laboratory animals. But a number of such food colors are listed in the report by Dr. Shubic and Dr. Howell, I believe, of the U.S. Public Health Service in a compilation of carcinogenic substances published by the Public Health Service.” 598 COLOR ADDITIVES Transcript 595 “Mr. DINGELL. Would you say our knowledge is sufficient to determine whether or not these substances, when ingested, will cause cancer over a long period? “Dr. Aanon. For some of the colors there is sufficient knowledge. For others, more work is required to be done.” New York, N.Y., May 13, 1960. Color additives legislation—S. 2197 and IL.R. 7624 Hon. OREN HarzIs, Chairman, House Committee on Interstate and Forcign Commerce, New House Office Building, Washington, D.C. Dear Mk. CHarkMan: The certified color industry deeply appreciates your statement, made at the close of the hearings on Monday of this week, May ¥. that you intend to begin executive sessions next week to consider the proposed color additives legislation. As we have stressed to your committee, this legis lation, which was proposed by the Department of Health, Education, and Wel- fare, after consultation with industry, is urgently needed in the public interest to insure an adequate supply of colors for use in foods, drugs, aud Cosmetics under conditions which will be safe. Since the legislation passed the Senate in the last session, it is our fond hope that action can be completed before the present Congress adjourns. We respectfully urge that you do all that is in your power to accomplish that, so that the matter will not have to be started again in the new Congress to follow, with consequent loss of the considerable amount of time which has been devoted to the matter by you and your com- mittee, by the Senate, by the Department of Health, Education, and Welfare, and by industry. As we see it, the only substantial problem remaining to be resolved is the treatment of the so-called Delaney clause. While this is a serious matter, we believe it has assumed proportions which are out of ull relationship to the use of colors in foods, drugs, and cosmetics. From the practical standpoint, the in- clusion or deletion of the clause should have no present effect because, so far as we know, none of the colors now in use are suspected carcinogens. Also, the discussion of the clause in the present hearings has tended to center on issues unrelated to the use of colors—issues which instead properly come under the food additives and pesticide chemicals amendments to the Federal Food, Drug, and Cosmetic Act and involve the use of noncolor chemicals in animal feeds. and the problems arising from the recent cranberry and poultry episodes, none of which involve the use of color additives, Nevertheless, because of those prob- lems. and because of inability to forecast the future, we have felt impelled te point ont what we regard as the undesirable rigidity of the Delaney clause and to suggest its deletion or modification, despite the fact that it does not raise any practical problem for the color industry at the present time. We accordingly hope that your committee will see fit. for the reasons advanced by us and by witnesses for other interested industries, to delete or modify the Delaney clause. However, if that should net be possible, we would be prepared to accept the Delaney clause for the present if that is the only way in which the pending color legislation ean be enacted in this session. The thing which we desire to avoid if at all possible is to have such legislation founder on an issue which is not a present problem in the use of colors, or to have this legislation held up for resolution of problems which relate to the use of other forms of additives under other provisions of the Federal food, drug, and cosmetic law. It is requested that this letter be made part of the record of the hearings Respectfully submitted. Arrnur T. Scuram™M, Chairman, Certified Color Industry Committee. NATIONAL CANNERS ASSOCIATION, Washington, D.C., May 11, 1960. Hon. OREN Harris, Chairman, Committee on Interstate and Foreign Commerce, House of Repre- sentatives, Washington, D.C. Deak Mr. CuarrMan: Under the date of April 21, 1960, Secretary Flemming of the Department of Health, Education, and Welfare submitted to you, as COLOR ADDITIVES 599 chairman of the House Committee on Interstate and Foreign Commerce, his views on the various amendments proposed by industry witnesses to the proposed color additive bills (H.R. 7624 and 8. 2197). Although his letter and detailed comments make no explicit reference to the statement submitted on behalf of the National Canners Association, many of the Secretary’s comments and objections to proposed amendments are directed to the substance of certain of the proposals offered by this association and others in the food industry. In view of these comments and objections, we deem it desirable and neces- sary to reply to some of the points made by the Secretary in his “enclosure I” and would greatly appreciate your including this letter as a part of the record of your committee’s hearings. We submit these comments on behalf of an important branch of the food in- dustry that has for more than a half century sponsored and supported effective food and drug legislation. Its position with respect to H.R. 7624 and S. 2197 is predicated upon its erystallized views that effective legislation must be specific and directed at the particular problem, in this instance coal-tar coloring; that prior licensing con- trols have been determined by Congress to be necessary only in the area of public health and safety, and should not be incorporated into the entire regulatory structure, and particularly not on such questions as the functional utility of an ingredient or administrative a priori apprehensions about misbranding. The latter two areas are fully covered already by the Federal Food, Drug and Cos- metic Act and left by Congress to judicial determination. These reasons underlie our basic approach to this proposed legislation— namely, that it be specifically limited to coal-tar colors and other identified toxie colors about which problems exist, and that no comprehensive licensing system be created for all food ingredients that might impart color, including, as does this bill, food ingredients whose safety is already covered by the food additives amendment, and from which licensing system exemptions might be carved out only in the Secretary’s discretion and only after burdensome admin- istrative procedure. I. SCOPE OF THE BILL Although Secretary Flemming undertakes to criticize and reject all industry proposals to limit the scope of the proposed bill, at no point does he attempt to meet the fundamental food industry objection that the broad definiion of color additive in the bill would extend the scope of the comprehensive licensing system far beyond its announced objectives, As the bill now stands, it applies to a “dye, pigment, or other substance made by a process of synthesis or similar artifice, or extracted, isolated, or otherwise derived, with or without intermediate or final change of identity, from a veqge- table, animal, mineral or other source, and when added or applied to a food, drug, or cosmetic, or to the human body or any part thereof, is capable (alone or through reaction with other substances) of imparting color thereto * * *.") The italic words make it clear that any substance derived from an animal or vege- table source without a change of identity, when added to a food and capable of imparting color to it is covered by the bill. It is difficult to imagine any food ingredient of a combination product that would not come within this extremely broad definition. For example, peas added to carrots, tomatoes added to catsup, raspberries added to apple sauce, pineapple juice added to grapefruit juice, pepper added to any food, eggs added to bread, and cheese added to sauce, would be included within this broad definition, for in each case the food is clearly capable of im- parting some of its own color to the mixture, and has itself been added to the food ingredients in the product. The Secretary does not acknowledge that his proposed definition of color additive is so broad that it would include virtually every food now made. This is not, we submit, what Congress or any members of the food industry has in mind with regard to the color bill. Throughont his statement Secretary Fiemming continually refers to dye materials or colors as if the bill concerned only substances added to foods solely to impart color thereto. If this is in fact the case. there should be no opposition whatsoever to limiting the definition of color additive. The Secretary refers in his statement to the provision in the bill that would enable him “by regulation” to determine that a substance is not used solely for coloring purposes. This provisions is offered in mitigation of the broad 600 COLOR ADDITIVES definition of color additive. As pointed out above, the definition of color addi- tive includes virtually all foods. In order to exempt these foods for each use from the licensing and pretesting requirements of the bill, the rulemaking procedures would have to be initiated and completed before the exemption could apply. We can see no reason whatsoever for such procedures, nor does the Secretary put forth any convincing justification for them. Instead, he suggests that the proposed limitations would involve the FDA in difficult determinations of the purpose for which a substance is used, would lead to uncertainty and confusion among users of color, would be a backward step with regard to coal-tar colors, and would create scientifically unsound distinctions among coloring substances. We submit that each of the objections offered by the Secretary to limitations on the scope of the bill derives principally from the definition of color addi- tive proposed by him, rather than from the proposed industry amendments. A determination of purpose for use would be required under the present bill in every proceeding designed to exempt foods and food ingredients from licensing as color additives. The Secretary would be obliged to find that a food ingredi- ent capable of imparting color to a food (and again we must emphasize that this all-inclusive definition would include virtually all foods) was used solely for purposes other than coloring. Any potential uncertainty and confusion created among users of color must be initially traced to the Secretary’s broad definition of color additive. Under present law there is no marked degree of uncertainty—food colors other than coal-tar colors are covered by the food additives amendment, and coal-tar colors are covered by their own special listing provisions. The proposed bills would introduce the uncertainty, by changing the status of non-