NOTICES 10385 cancellation or postponements of hear­ for oral hearing, must be filed with the No. MC-FC-76948, filed January 25, ings in which they are interested. Commission on or before March 24, 1977. 1977. Transferee: CHARLES M. LEAD­ AB-20 (Sub-2), The Texas and Pacific Rail­ Failure seasonably to file a protest will ERS, doing business as CHARLES LEAD­ way Company Abandonment Between Man- be construed as a waiver of opposition ERS TRUCKING, Box 307, Minden, sura and Marksville in Avoyelles Parish, and participation in the proceeding. A Iowa 51553. Transferor: Henry C. Lead­ Louisiana, now being assigned May 4, 1977 protest must be served upon applicants’ ers, Minden, Iowa. Applicant’s represent­ (3 days) at Marksville, Louisiana, in a representative(s), or applicants (if no ative: F. H. Kroeger, 1745 University h e a rin g room to be later designated. such representative is named), and the Avenue, St. Paul, Minnesota 55104. Au­ MC 116763 (Sub-352), Carl Subler Trucking, protestant must certify that such service thority sought for purchase by transferee Inc., now being assigned May 9, 1977 (1 has been made. of the operating rights of transferor, as day) at New Orleans, Louisiana, in a hear­ ing room to be later designated. Unless otherwise specified, the signed set forth in Certificate No. MC 34151 and MC 128007 (Sub-92), Hofer, Inc., now being original and six copies of the protest MC 34151 (Sub-No. 1) issued August 2, assigned May 10, 1977 (2 days) at New shall be filed with the Commission. All 1950 and December 29, 1950 respectively, Orleans, Louisiana, in a hearing room to protests must specify with particularity as follows: Livestock and feed over speci­ be later designated. the factual basis, and the section of the fied regular routes between Bentley, Iowa AB 83 Sub No. 2, Maine Central Railroad Act, or the applicable rule governing the and Omaha, Nebraska and various speci­ Company Abandonment Between Liver­ proposed transfer which protestant be­ fied commodities, between Underwood, more Falls and Farmington in Androscog­ lieves would preclude approval of the ap­ Iowa and points and places within six gin and Fraklin Counties, Maine now as­ signed March 23, 1977 at Farmington, plication. If the protest contains a re­ miles thereof, on the one hand, and, on Maine and will be held in the North Din­ quest for oral hearing, the request shall the other Omaha, Nebr. Transferee pres­ ing Room, Study Center, University of be supported by an explanation as to why ently holds no authority from this Com­ Maine, South Street. the evidence sought to be presented can­ mission. Application has not been filed MC 52460 (Sub-186), Ellex Transportation, not reasonably be submitted through the for temporary authority under Section Inc.; MC 107515 (Sub-1027), Refrigerated use of affidavits. 210a(b). Transport Co., Inc., MC 109365 (Sub-40), Ronald A. Patterson, d /b /a Anthony & Pat­ The operating rights set forth below No. MC-FC-76956, filed February 2, terson Truck Line; MC 113267 (Sub-340), are in synopses form, but are deemed 1977. Transferee: INDUSTRIAL CON­ Central & Southern Truck Lines, Inc.; MC sufficient to place interested persons on STRUCTION COMPANY, INC., 6565 E. 119493 (Sub-144), Mon Kem Company, notice of the proposed transfer. 42nd Street, Tulsa, Oklahoma 74145. Inc.; MC 119988 (Sub-97), Great Western Trucking Co.; Inc.; MC 139495 (Sub-155), No. MC-FC-76849, filed February 7, Transferor: Carl C. Beesley, doing busi­ National Carriers, Inc. and MC 142207 1977. Transferee; READDING VAN AND ness as Industrial Investment & Con­ (Sub-3), Gulf Coast Truck Services, Inc., STORAGE CO„ a Corporation, 1846 NW. struction Co., 6565 E. 42nd Street, Tulsa, now being assigned May 12, 1977 (2 days) Boulevard, Vineland, New Jersey 08360. Oklahoma 74145. Applicant’s representa­ at New Orleans, Louisiana, in a hearing Transferor: Frank A. Dalesandro Moving tive: A. Michael Bernstein, Attorney at room to be later designated. & Hauling, a Corporation, 128 Quince Law, 1441 E. Thomas Road, Phoenix, Ari­ MC 110410 Sub 18, Benton Brothers Film Street, Vineland, New Jersey 08360. Ap­ zona 85014. Authority sought for pur­ Express, Inc., now being assigned May 17, plicant’s Representative:. Robert J. Gal­ chase by transferee of the operating 1977 (4 days), at Atlanta, Ga., in a hearing room to be later designated.* lagher, Attorney at Law, Suite 1200, 1000 rights of transferor as set forth in Per­ MC 115452 (Sub-No. 4), Husband Transport Connecticut Ave. NW., Washington, D.C. mit No. MC 135122 (Sub-No. 1), issued Limited, now assigned March 21, 1977, at 20036. Authority sought for purchase by October 13, 1971, as follows: Equipment, Buffalo, N.Y. is postponed indefinitely. transferee of the operating rights of materials, and supplies used in the con­ MC 140894 (Sub-No.1), H. E. & A. National of transferor, as set forth in Certificate struction, servicing, and operation of a Corp. DBA Robert-Hawaii-Holiday Lines, No. MC 107054, issued May 26, 1976, as telephone system from Phoenix, Ariz, to now assigned March 28, 1977, at Los An­ follows: General commodities with the points in New Mexico and El Paso Coun­ geles, Calif, is postponed indefinitely. usual exceptions over specified regular ty, Tex. and used or damaged equipment MC 125433 Sub 75, F-B Truck Line Co. now routes between Sea Isle City, NJ", and on return. Transferee presently holds no being assigned April 7, 1977 (2 days) at Salt Lake City, Utah in a hearing room to be Philadelphia, Pa.; household goods be­ authority from this Commission. Appli­ later designated. \ tween Philadelphia, Pa., on the one hand, cation has not been filed for temporary MC 135082 Sub Nos. 33 and 34, Bursch Truck­ and, on the other, points in New York, authority under Section 210a (b ). ing, Inc., dba Roadrunner Trucking, Inc. New Jersey, Delaware, Maryland, Vir­ No. MC-FC-76960, filed January 31, now being assigned March 22,1977 (4 days) ginia, and the District of Columbia and 1977. Transferee: EAGLE BUS COM­ at Albuquerque, New Mexico in a hearing between points in Cumberland County, PANY, a corporation, 2811 Guadalupe room to be later designated. N.J., on the one hand, and, on the other, St., San Antonio, Texas 78207. Trans­ No. MC 9859 (Sub-No. 3), Kane Transfer points in New York and Pennsylvania; feror: Bracero Transportation Com­ Company, now assigned March 8, 1977, at Salisbury, Md. is canceled and applica­ and hay rope from Port Norris, N.J. to pany, Inc., P.O. Box 476, Edinburgh, tion dismissed. Eddystone and Downington, Pa. Trans­ Texas 78539. Applicant’s representatives: R obert L. O swald , feree is presently authorized to operate Francis J. Ortman, 7101 Wisconsin Ave., Secretary. as a common carrier under Certificate Suite 605, Bethesda, Md. 20014, and Hol­ No. MC 1647 and subs thereafter. Appli­ lis H. Rankin, Jr., 804 Pecan Ave., McAl­ [FR Doc.77-5328 Filed 2-18-77;8:45 am] cation has not been filed for temporary len, Tex. 78501. Authority sought for authority under Section 210a(b). purchase by transferee of the operating [Notice No. 124] No. MC-FC-76909, filed January 4, rights of transferor set forth in Permits MOTOR CARRIER BOARD TRANSFER 1977. Transferee: CHIEF FREIGHT- Nos. MC 116612 (Sub-No. 1) and MC 116- PROCEEDINGS WAYS, INC., 135 State St., Springfield, J>12 (Sub-No. 8), issued March 13, 1959 Mass. 01103. Transferor: Air Import De­ and July 17, 1974, respectively, as fol­ The following publications include livery, Inc., 19 Milk St., Boston, Mass. lows: Migrant workers, as defined in motor carrier, water carrier, broker, and 02109. Applicants’ representative: David section 203(a) (23) of the Interstate freight forwarder transfer applications M. Marshall, Attomey-at-Law, 135 State Commerce Act, and their baggage in the filed under section 212(b), 206(a), 211, St., Springfield, Mass. 01103. Authority same vehicle, between points in Ala­ 312(b), and 410(g) of the Interstate sought for purchase by transferee of the bama, Arkansas, Colorado, Georgia, Commerce Act. operating rights of transferor, as set Idaho, Illinois, Indiana Iowa, Kansas, - Each application (except as otherwise forth in Certificate of Registration No. Kentucky Louisiana, Michigan, Minne­ specifically noted) contains a statement MC 9855 (Sub-No. 1), issued July 17, sota, Mississippi, Missouri, Montana, by applicants that there will be no sig­ 1969; as follows: General commodities, New Mexico, Ohio, Oklahoma, Texas nificant effect on the quality. of the within the Commonwealth of Massachu­ (except points in El Paso County), Ten­ human environment resulting from ap­ setts. Transferee presently holds no au­ nessee, Wisconsin, and Wyoming; be­ proval of the application. thority from this Commission. Applica­ tween points in New Mexico and Michi­ Protests against approval of the ap­ tion has not been filed for temporary gan, on the one hand, and, on the other, plication, which may include a request authority under Section 210a (b ). points in El Paso County, Tex.; between FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 2?, 1977 10386 NOTICES points in Arizona, California, Connecti­ points in the Towns of Fennimore and be served on the applicant, or its au­ cut, Delaware, Florida, Maine, Maryland, Potosi, Grant County, Wis.; Animal feed thorized representative, if any, and the Massachusetts, Nebraska, Nevada, New and poutry feed, From Dubuque and Protestant must certify that such serv­ Hampshire, New Jersey (except points in Iowa Falls, Iowa, to points in Crawford, ice has been made. The protest must Cumberland, Gloucester, and Salem Grant, Iowa, and Richland Counties, identify the operating authority upon Counties, N.J.), New York, North Caro­ Wis., restricted against service from Du­ which it is predicated, specifying the lina, North Dakota, Oregon, Pennsyl­ buque to points in Paris and Potosi “ MC” docket and “ Sub” number and vania, Rhode Island, South Carolina, Townships, Grant County, Wis. quoting the particular portion of author­ South Dakota, Utah, Vermont, Virginia, Animal and poultry feed, in bulk, and ity upon which it relies. Also, the Pro­ Washington, West Virginia, and the Dis­ in bulk and bags in mixed shipments testant shall specify the service it can trict of Columbia; and between the (except liquid commodities), restricted and will provide and the amount and points described immediately preceding, to traffic moving in vehicles with me­ type of equipment it will make available on the one hand, and, on the other, chanical or pneumatic unloading sys­ for use in connection with the service points in Alabama, Arkansas, Colorado, tems, From Davenpdrt, Dubuque, and contemplated by the- TA application. Georgia, Idaho, Illinois, Indiana, Iowa, Iowa Falls, Iowa, to Viroqua, Wis., Sub- The weight accorded a protest shall be Kansas, Kentucky, Louisiana, Michigan, 8—Dry fertilizer, in bulk, From the plant governed by the completeness and per­ Minnesota, Mississippi, Missouri, Mon­ site of Mobil Chemical Company, a Di­ tinence of the protestant's information. tana, New Mexico, Ohio, Oklahoma, vision of Mobil Oil Corporation, at Du­ Except as otherwise specifically noted, Texas (except points in El Paso County, buque, Iowa, to points in Minnesota on each applicant states that there will be Tex.), Tennessee, Wisconsin, and Wyo­ and south of U.S. Highway 12 and those no significant effect on the quality of ming. Transferee presently holds no au­ in Illinois on and north of U.S. Highway the human environment resulting from thority from this Commission. Applica­ 24; Sub-10—Dry fertilizer, in bags, From approval of its application. tion has not been filed for temporary au­ Dubuque, Iowa, to points in Illinois on A copy of the application is on file, and thority under Section 210a(b). and north of U.S. Highway 24, and points can be examined at the Office of the No. MC-FC-76963 filed February 2, in Minnesota on and south of U.S. High­ Secretary, Interstate Commerce Com­ 1977. Transferee: BLOOMINGTON way 12 (except points within the Min- mission, Washington, D.C., and also in PRODUCE, INC., Box 67 (Wall Street), neapolis-St. Paul, Minn., Commercial the ICC Field Office to which protests Bloomington, Wisconsin 53804. Trans­ Zone as defined by the Commission; Dry are to be transmitted. feror: Alphonse Hinderman and Vin­ Fertilizer, From Dubuque, Iowa to points M otor C arriers of P roperty cent Hiderman, a Partnership, doing in Wisconsin north of Wisconsin High­ business as Hinderman Brothers, Box way 29 (except points in Langlade and No. MC 720 (Sub-No. 25TA), filed 327, Dickeyville, Wisconsin 53808. Ap­ Shawano Counties); Sub-12—Dry ferti­ February 1, 1977. Applicant: BIRD plicant’s representative:"' Michael S. lizer, From the facilities of the Burling­ TRUCKING COMPANY, INC., P.O. Box Varda, 121 South Pinckney Street, Mad­ ton and Northern Railroad located at 227, Waupun, Wis. 53968. Applicant’s ison, Wisconsin 53701. Authority sought or near Potosi, Wis., to Dickeyville, Wis.; representative: Michael J. Wyngaard, for purchase by transferee of the operat­ From Dickeyville, Wis., to points in Iowa P.O. Box 8004, Madison, Wis. 53708. ing rights of transferor, as set forth in and Minnesota and points in that part Authority sought to operate as & com­ Certificate Nos. MC 124417; MC 124417 of Illinois on and north of a line begin­ mon carrier, by motor vehicle, over ir­ (Sub-No. 2 ); MC 124417 (Sub-No. 8), ning at the Ulinois-Indiana State line regular routes, transporting: Medical MC 124417 (Sub-No. 10) and MC 124417 and extending along U.S. Highway 24 to and consumer care products, from the (Sub-No. 12), issued May 2,1963, Novem- junction Illinois Highway 116, thence plantsite and warehouse facilities of be 23, 1962, February 24, 1967, February along Illinois Highway 116 to junction Cutter Laboratories, Inc., at Bensenville, 13, 1968, and February 19, 1976, respec­ U.S. Highway 34, thence along U.S. High­ 111., to points in North Dakota, South tively, as follows: Animal and poultry way 34 to the Ulinois-Iowa State line, Dakota, Nebraska, Kansas, Missouri, feed (except liquid' commodities), in (except El Paso, HI., and points within Minnesota, Michigan, Indiana, Wiscon­ bulk, and in bulk and in bags in mixed its commercial zone as defined by the sin, Ohio and Iowa, for 180 days. Ap­ shipments, From Cedar Rapids, Musca­ Commission), restriction: The author­ plicant has also filed an underlying ETA tine, and Waterloo, Iowa, to points in ity is restricted to the transportation seeking up to 90 days of operating au­ that part of Wisconsin on and south of of traffic originating at the named origin thority. Supporting shipper: Cutter Lab­ U.S. Highway 10 and on and West of U.S. and destined to the named destination oratories, In c.,. 4th and Parker Sts., Highway 51; From Dubuque and Iowa States. Transferee presently holds no Berkeley, Calif. 94710. Send protests to: Falls, Iowa, to points in that part of authority from this Commission. Appli­ Gail Daugherty, Transportation Assist­ Wisconsin on and south of U.S. Highway cation has not been filed for temporary ant, Interstate Commerce Commission, 10 and on and west of U.S. Highway 51 authority under Section 210a (b). U.S. Courthouse and Federal Bldg- (except points in Crawford, Grant, Iowa, R obert L. O swald , Room 619, Milwaukee, Wis. 53202. and Richland Counties, Wis.M Animal Secretary. No. MC 8964 (Sub-No. 34TA), filed and poultry feed (except liquid commod­ February 4, 1977. Applicant: WITTE [PR Doc.77-5327 Piled 2-18-77;8:45 am] ities) , in mixed shipments in bulk and in TRANSPORTATION CO., P.O. Box 3564, bags, From Mason City, Iowa, to points St. Paul, Minn. 55165. Applicant’s repre­ in that part of Wisconsin .on and south [Notice 23] sentative: William S. Rosen, 630 Osborn of U.S. Highway 10 and on and west of Bldg., St. Paul, Minn. 55102. Authority U.S. Highway 51; Fertilizer (except pe­ M OTOR CARRIER TEMPORARY sought to operate as a common carrier, troleum products) From Dubuque, Iowa, A U TH O R ITY APPLICATIONS by motor vehicle, over regular ^routes,: to points in that part of Wisconsin on F ebruary 15, 1977. transporting: General commodities (ex­ and south of Wisconsin Highway 29; The following are notices of filing of cept household goods); (1) from Spring Sub-2—Livestock, From points in the applications for temporary authority un­ Valley, Minn., over U.S. Highway 16 to Towns of Paris, Jamestown, Hazel der »Section 210a(a) of the Interstate its junction with Interstate Highway 9p; Green, Harrison, Potos!, and Smelzer, Commerce Act provided,for under the thence over Interstate Highway 90 to its Grant County, Wis., to Dubuque, Iowa, junction with Interstate Highway 94; and East Dubuque 111.; Coal, building provisions of 49 CFR 1131.3. These rules provide that an original and six (6) thence over Interstate Highways 90 and materials, and livestock, From Dubuque, 94, to Madison, Wis., and return over the Iowa, and East Dubuque, 111., to points copies of protests to an application may be filed with the field official named in same route, serving all intermediate in the above-specified Wisconsin Towns; points; (2) from Spring Valley, Minn- the F ederal R egister publication no Feed and fertilizer, From Dubuque, later than the 15th calendar day after over U.S. Highway 16 to LaCrosse, Wis.; Iowa, to points in Paris and Potósi Town­ the date the notice of the filing of the thence over U.S. Highway 16 to its junc­ ships, Grant County, Wis.; Livestock and application is published in the F ederal tion with Interstate Highway 90; thence poultry feed, From Davenport, Iowa, to R egister. One copy, of the protest must over Interstate Highway 90 to its junc- FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 NOTICES 10387 tion with Interstate Highway 94; thence any other convenient points in the ap­ pendix I to the report in Descriptions in over Interstate Highways 90 and 94 to plicants’ system, for 180\days. Applicant Motor Carrier Certificates, 61 M.C.C. 209 Madison, Wis., and return over the same has also filed an underlying ETA seeking and 766 (except hides, skins, and com­ route, serving all intermediate points; up to 90 days of operating authority. modities in bulk), from Sterling, Colo., (3) from Spring Valley, Minn., over U.S. Supporting shipper: None. Send protests to Baltimore, Md.; Post Elizabeth, N.J.; H ighway 63 to its junction with Inter­ to: Marion L. Cheney, Transportation Springfield and Boston, Mass.; Albany state Highway 90; thence over Interstate Assistant, Interstate Commerce Commis­ and New York, N.Y.; and Philadelphia, H ighway 90 to its junction with Inter­ sion, Bureau of Operations, 414 Federal Pa., for 180 days. Applicant has also filed state Highway 94; thence over Interstate Bldg, and U.S. Courthouse, 110 S. 4th St., an underlying ETA seeking up to 90 days Highways 90 and 94 to Madison, Wis., Minneapolis, Minn. 55401. of operating authority. Supporting ship­ and return over the same route, serving No. MC 100449 (Sub-No. 73TA), filed per: Sterling Colorado Beef Company, a l l intermediate points; (4) from Spring P.O. Box 1728, Sterling, Colo. 80751. Send February 7, 1977. Applicant: MALLIN- protests to: John V. Barry, District Su­ Valley, Minn., over U.S. Highway 63 to GER TRUCK LINE, INC., RFD No. 4, Rochester, Minn.; thence over U.S. High­ Fort Dodge, Iowa 50501. Applicant’s rep­ pervisor, Bureau of Operations, Inter­ way 14 to Winona, Minn.; thence over resentative: James M. Hodge, 1980 Fi­ state Commerce Commission, 600 Federal the Mississippi River to the junction Bldg., 911 Walnut St., Kansas City, Mo. nancial Center, Des Moines,.Iowa 50309. 64106. with Wisconsin Highway 54; thence oyer Authority sought to operate as a common W isconsin Highway 54 to its junction carrier, by motor vehicle, over irregular No. MC 13455 (Sub-No. 90TA) . filed Feb­ with Wisconsin Highway 35; thence oyer routes, transporting: Meat and meat ruary 3, 1977. Applicant: CHARTER EX­ Wisconsin Highway 35 to its junction products, from West Fargo and Fargo, PRESS, INCt- 1559 E. Turner St., P.O. with U.S. Highway 53; thence over U.S. N. Dak., to Omaha, Nebr., for 180 days. Box 3772, Springfield, Mo. 65804. Appli­ Highway 53 to its junction with Wiscon­ Applicant has also filed an underlying cant’s representative: Larry D. Knox, sin Highway 29; thence over Wisconsin ETA seeking up to 90 days of operating 900 Hubbell Bldg., Des Moines, Iowa Highway 29 to Wausau, Wis.; thence authority. Supporting shipper: Flavor- 50309. Authority sought to operate as a over U.S. Highway 51 to Stevens Point, land Industries, Inc., P.O. Box 15346, common carrier, by motor vehicle, over Wis., and return over the same route, Denver, Colo. Send protests to: Herbert irregular routes, transporting: Meat, serving all intermediate points (except W. Allen, District Supervisor, Bureau of meat products, and meat by-products as Cadott, Boyd, Stanley, Thorp, Withee, Operations, Interstate Commerce Com­ defined by the Commission, from Madi­ Owen and Curtis, W is.); mission, 518 Federal Bldg., Des Moines, son, Nebr., to points in Massachusetts, (5) Prom Spring Valley, Minn., over Iowa 50309. New York, New Jersey and Pennsylvania, U.S. Highway 63 to its junction with for 180 days. Applicant has also filed an No. MC 133095 (Sub-No. 128TA) (cor­ underlying ETA seekiiig up to 90 days of Minnesota Highway 60; thence over rection) , filed January 3, 1977, published Minnesota Highway 60 to the Mississippi in the FR issue of January 21, 1977, and operating authority. Supporting shipper: River; thence over the Mississippi River republished as corrected this issue. Ap­ Armour Food Company, 111 W. Claren­ to Wisconsin Highway 25; thence over plicant: TEXAS CONTINENTAL EX­ don, Greyhound Tower, Phoenix, Ariz. Wisconsin Highway 25 to its junction PRESS, INC., P.O. Box 434, Euless, Tex. 85077. Send protests to: John V. Barry, with U.S. Highway 10; thence over U.S. 76039. Applicant’s representative: Kim District Supervisor, Interstate Commerce Highway 10 to its junction with Inter­ G. Meyer, 1600 First Federal Bldg., A t­ Commission, Bureau of Operations, 600 state Highway 94; thence over Interstate lanta, Ga. 30303. Authority sought to op­ Federal Bldg., 911 Walnut St., Kansas Highway 94 to its junction with Inter­ erate as a common carrier, by motor ve­ City, Mo. 64106. state Highway 90; thence over Interstate hicle, over irregular routes, transporting: No. MC 134806 (Sub-No. 46TA), filed Highways 90 and 94 to Madison, Wis., (1L Drugs and intravenous solutions, February 7, 1977. Applicant: B -D -R and return over the same route, serving from the plantsite and warehouse facil­ TRANSPORT, INC., P.O. Box 813, Brat- all intermediate points (except South ities of Invenex Pharmaceuticals, in Erie tleboro, Vt. 05301. Applicant’s represent­ Troy, Zumbro Falls, West Albany, Dum­ County, N.Y., to points in the United ative: Francis J. Ortman, 7101 Wiscon­ fries and Wabasha, M inn.); (6) from States in and west of Florida, Georgia, sin Ave., Suite 605, Washington, D.C. Spring Valley, MfnmT over U.S. Highway Kentucky, Michigan, Ohio and Tennes­ 20014. Authority sought to operate as a 63 to its junction with Minnesota High­ see (except Alaska and Hawaii); (2) contract carrier, by motor vehicle, over way 60; thence over Minnesota Highway Glass containers, from Millville, N.J., and irregular routes, transporting: Tennis 60 to the Mississippi River; thence over Chicago Heights, 111., to the plantsite shoes, from Boston, Mass., to Manches­ the Mississippi River to Wisconsin High­ and warehouse facilities of Invenex ter, Conn., and the plantsite and ware­ way 25; thence over Wisconsin Highway Pharmaceuticals, in Erie County, N.Y.; house facilities of AMF Division in Boul­ 25 to its junction with U.S. Highway 10; and (3) Stopper enclosures, alumnium der County, Colo., under a continuing thence over U.S. Highway 10 to Stevens seeds, aluminum and plastic seals, from contract with AMF Head Division, for Point, Wis.; thence over U.S. Highway St. Petersburg, Fla., to the plantsite and 180 days. Applicant has also filed an un­ 51 to its junction with Interstate High­ warehouse facilities of Invenex Pharma­ derlying ETA seeking up to 90 days of ways 90 and 94 and return over the same ceuticals, in Erie County, N.Y., for 180 operating authority. Supporting shipper: route, serving all intermediate points days. Supporting shipper: Invenex Phar­ AMF Head Division, 4801 N. 63rd St., (except South Troy, Zumbro Palls, West maceuticals, 3175 Staley Road, Grand Boulder, Colo. 80301. Send protests to: Albany, Dumfries and Wabasha, Minn.; Island, N.Y. 14072. Send protests to: David A. Demers, District Supervisor, In­ And serving all off-route points in con­ Robert J. Kirspei, District Supervisor, terstate Commerce Commission, Bureau nection with the above-described regu­ Room 9A27 Federal Bldg., 819 Taylor of Operations, P.O. Box 548, 87 State lar routes, all points in Wisconsin on and St., Fort Worth, Tex. 76102. The purpose St., Montpelier, Vt. 05602. west of U.S. Highway 51 and, unless of this republication is to correct the excepted as intermediate points in the requested authority in this proceeding. No. MC 135082 (Sub-No. 42TA), filed February 7, 1977. Applicant: BURSCH above-described route descriptions, on TRUCKING, INC., doing business as and south of a line created by U.S. High­ No. MC 134755 (Sub-No. 89TA), filed ROADRUNNER TRUCKING, INC., P.O. way 12 and Wisconsin Highway 29 from February 3, 1977. Applicant: CHARTER Box 26748, 415 Rankin Road, Albuquer­ Hudson, Wis., to Wausau, Wis. (except EXPRESS, INC., 1959 E. Turner St., P.O. que, N. Mex. 87125. Applicant’s represent­ Points in the counties of Vernon, Cich- Box 3772, Springfield, Mo. 65804. Appli­ ative: D. F. Jones (same address as ap­ land, Crawford, Grant, Iowa, Lafayette cant’s representative: Larry D. Knox, plicant) . Authority sought to operate as and Rock). Applicant intends to tack all 900 Hubbell Bldg., Des Moines, Iowa a common carrier, by motor vehicle, over of its other existing authority with the 50309. Authority sought to operate as irregular routes, transporting: Gypsum a common carrier, by motor vehicle, over authority sought in this case, and pro­ irregular routes, transporting: Meats, wallboard, from Albuquerque, N. Mex., poses to interline with other carriers at meat products, meat by-products and ar­ to points in Arizona, for 180 days. Appli­ Kansas City, Madison, Minneapolis-St. ticles distributed by meat packinghouses cant has also filed an underlying ETA Paul, Rochester, Eau Claire, Wausau and as described in Sections A and C of Ap­ seeking up to 90 days of operating au- FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 10388 NOTICES thority. Supporting shipper: American SPIDER WRECKER SERVICE, INC., pers: J. B. Consolidators, Inc,, 304 S. Gypsum Company, E. M. McDowell, Jr., P.O. Box 505, Conley, Ga. 30027. Appli­ Mint St.; Montgomery Ward and Com­ Secretary and Treasurer, P.O. Box 6345, cant’s representative: Virgil H. Smith, pany, 3014 Washburn Ave., Charlotte; Albuquerque, N. Mex. 87109. Send pro­ Suite 12, 1587 Phoenix Bldg., Atlanta, N.C. M. Lowenstein and Son, Inc., P.O. tests to: John H. Kirkemo, District Su­ Ga. 30349. Authority sought to operate as Box 10352, Rock Hill, S.C. Springs Mills, pervisor, Interstate Commerce Commis­ a common carrier, by motor vehicle, over Inc., P.O. Box 111, Lancaster, S.C. Send sion, Bureau of Operations, 1106 Federal irregular routes, transporting: Disable or protests to: Terrell Price, District Super­ Office Bldg., 517 Gold Ave., Albuquerque, replacement trucks, tractors and/or visor, 800 Briar Creek Road, Room N. Mex 87101. trailers, between points in Alabama, CC516, Mart Office Bldg., Charlotte, N.C. No. MC 136008 (Sub-No. 81TA), filed Delaware, Florida, Georgia, Illinois, 28205. February 7, 1977. Applicant: JOE Indiana, Kentucky, Louisiana, Maryland, P assenger A p plicatio n s BROWN COMPANY, INC., 20 Third St., Mississippi, Missouri, New Jersey, New N.E., P.O. Box 1669, Ardmore, Okla. York, North Carolina, Ohio, Pennsyl­ N o. MC 141123 (Sub-No. 1TA), filed 73401. Applicant’s representative: G. vania, South Carolina, Tennessee, Vir­ February 3, 1977. Applicant: BERKLEY Timothy Armstrong, 6161 N. May Ave., ginia, West Virginia, Texas, Arkansas G. SEGAR, doing business as SEGAR Oklahoma City, Okla. 73112. Authority and Oklahoma, for. 180 days. Supporting BUS SERVICE, P.O. Box 654, Kilmar­ sought to operate as a common carrier, shippers: There are approximately 8 nock, Va. 22482. Applicant’s representa­ by motor vehicle, over irregular routes, statements of support attached to the tive: Michael A. Inman, Suite 211, Pem­ transporting: Ferromanganese, (in bulk, application, which may be examined at broke Four, Pembroke Office Park, Vir­ in dump vehicles), from the Port of Ca­ the Interstate Commerce Commission in ginia Beach, Va. 23462. Authority sought toosa, Okla., to the facilities of Colorado Washington, D.C., or copies thereof to operate as a common carrier, by motor Fuel and Iron Co.; at Pueblo, Colo., for which may be examined at the field office vehicle, over irregular routes, transport­ 180 days. Applicant has also filed an un­ named below. Send protests to: Sara K. ing: Passengers and their baggage, in the derlying ETA seeking up to 90 days of Davis, Transportation Assistant, Inter­ same vehicle with passengers, in charter operating authority. Supporting ship­ state Commerce Commission, Bureau of operations, from points in Lancaster, per: Leonard J. Buck Co., Inc., agents Operations, 1252 W. Peachtree St., N.W., Northumberland, Richmond and Middle­ for Autlan Metals International Co., 299 Room 546, Atlanta, Ga. 30309. The pur­ sex Counties, Va., to points in New York, Madison Ave., Morristown, N.J. 07960. pose of this republication is to add the New Jersey, Pennsylvania, Delaware, Send protests to : Joe Green, District state of Georgia. Maryland, North Carolina, South Caro­ Supervisor, Room 240 Old Post Office lina, Georgia, Florida and the District of No. MC 142848 (Sub-No. 1TA), filed Columbia, for 180 days. Supporting ship­ Bldg., 215 N.W. Third St., Oklohoma February 7, 1977. Applicant: JAMES R. City, Okla. 73102. pers: There are approximately 14 state­ POSHARD AND SON, INC., P.O. Box ments of support attached to the appli­ No. MC 136553 (Sub-No. 45TA), filed 69, Mt. Vernon, Ind. 47620. Applicant’s cation, which may be examined at the February 7, 1977. Applicant: ART PAPE representative; Norman R. Garvin, 815 Interstate Commerce Commission in TRANSFER, INC., 1080 E. 12th St., Du­ Merchants Bank Bldg., Indianapolis, Ind. Washington, D.C., or copies thereof buque, Iowa 52001. Applicant’s represent­ 46204. Authority sought to operate as a which may be examined at the field office ative: William L. Fairbank, 1980 Finan­ common carrier, by motor vehicle, over named below. Send protests to: Paul D, cial Center, Des Moines, Iowa 50309. Au­ irregular routes, transporting: Coal, be­ Collins, District Supervisor, Bureau of thority sought to operate as a common tween Williamson, Jefferson and Saline Operations, Room 10-502, Federal Bldg., carrier, by motor vehicle, over irregular Counties, 111., and Hopkins and Webster 400 N. 8th St., Richmond, Va. 23240. routes, transporting: Dry fertilizer and Counties, Ky., on the one hand, and, on dry fertilizer materials, in bulk, in dump the other, points in Vanderburgh and No. MC 142738 (Sub-No. 1TA), filed vehicles, from the facilities of Cargo Posey Counties, Ind., for 180 days. Appli­ February 4, 1977. Applicant: SAGELAW Carriers, Inc., at or near Pekin, HI., to cant has also filed an underlying ETA CORPORATION, doing business as DE­ points in Iowa, Missouri, Minnesota and seeking up to 90 days of operating au­ LUXE AMERICA TOURS, 2001 Kirby, Wisconsin, for 180 days days. Supporting thority. Supporting shipper: Mead John­ Houston, Tex. 77019. Applicant’s repre­ shipper: Cargill, Incorporated, P.O. Box son & Company, 2404 Pennsylvania St., sentative: David J. Nagle (same address 9300, Minneapolis, Minn. 55440. Send Evansville, Ind. 47721. Send protests to: as applicant). Authority sought to protests to: Herbert W. Allen, District William S. Ennis, District Supervisor, operate as a common carrier, by motor Supervisor, Bureau of Operations, Inter­ Interstate Commerce Commission, Fed­ vehicle, over irregular routes, transport­ state Commerce Commission, 518 Fed­ eral Bldg, and U.S. Courthouse, 46 E. ing: Passengers and their baggage, in eral Bldg., Des Moines, Iowa 50309. Ohio St., Room 429, Indianapolis* Ind. special and charter operations, begin­ 46204. ning and ending within the Houston, No. MC 140665 (Sub-No. 6TA), filed Tex., zone, to the ski areas of New M exico February 3, 1977. Applicant: PRIME, No. MC 142883TA, filed February 4, and Colorado, and to the race tracks and INC., Route 1, Box 115-B, Urbana, Mo. 1977. Applicant: HARVEY H. MILLER, sports arenas and adjacent municipali­ 65767. Applicant’s representative: Clay­ doing business as CAROLINA EXPRESS ties of Louisiana, for 180 days. Applicant ton Geer, P.O. Box 786, Ravenna, Ohio COMPANY, 304 S. Mint St., Charlotte, has also filed an underlying ETA seeking 44266. Authority sought to operate as a N.C. 28202. Applicant’s representative: up to 90 days of operating authority. common carrier, by motor vehicle, over Melvin L. Watt, 951 S. Independence Supporting shippers: There are approxi­ irregular routes, transporting: Glass­ Blvd., Charlotte, N.C. 28202. Authority mately 10 statements of support attached ware, . from Mount Pleasant, Pa., and sought to operate as a common carrier, to the application, which may be ex­ Toledo, Ohio, to points in Louisiana, by motor vehicle, over irregular routes, amined at the Interstate Com m erce Texas and California, for 180 days. Sup­ transporting: Piggyback shipments, hav­ Commission in Washington, D.C., or porting shipper: L.E. Smith Glass Com­ ing a prior or subsequent movement by copies thereof which may lie examined at pany, Inc., c /o L. E. Smith Glass Co., rail; (1) between Charlotte, N.C., and the field office named below. Send pro­ 1900 Liberty St., Mt. Pleasant, Pa. 15666. the following points in South Carolina; tests to: John F. Mensing, District Super­ Send protests to: John V. Barry, Dis­ Rock Hill, Grace, Ft. Lawn, Lancaster, visor, Interstate Commerce Commission, trict Supervisor, Interstate Commerce Kershaw, Fort Mill, Mullins, Chester, 8610 Federal Bldg., 515 Rusk, Houston, Commission, Bureau of Operations, 600 Greenville, Winona and Columbia; and Tex. 77002. Federal Bldg., 911 Walnut St., Kansas (2) between Charlo.tte, N.C., and the No. MC 142744 (Sub-No. 1TA) (correc­ City, Mo. 64106. following points in North Carolina; tion) filed December 27, 1976, published Laurel Hill. Monroe, Biscoe, Richfield, in the FTt issue of January 18, 1977, and No. MC 142832TA (correction), filed Albemarle, Statesville, North Wilkes- republished as corrected this issue. Appli­ January 19, 1977, published in the FR boro, Winston-Salem, Concord, James­ cant: TRI-COUNTY METROPOLITAN issue of February 2, 1977, and repub­ town, Durham, Welcome, Wagram and TRANSPORTATION DISTRICT OF lished as corrected this issue. Applicant: Tarboro, for 180 days. Supporting ship­ OREGON, Pacific Bldg., 520 S.W. Yam- FEDERAL REGISTER, VOL 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 NOTICES 10389-10409 Kill St., Portland, Oreg. 97204. Applicant’s Hilton, Buffalo, N.Y. 14202. Authority [Notice 123] representative: Robert R. Hillis, 400 Pa­ sought to operate as a common carrier, MOTOR CARRIER TRANSFER cific Bldg., Portland, Oreg. 97204. Au­ by motor vehicle, over irregular routes, PROCEEDINGS thority sought to operate as a common transporting: Passengers and their bag­ carrier, by motor vehicle, over irregular gage, in charter and special operations, F ebruary 22,1977. routes, transporting: Passenger^ and in sightseeing and pleasure tours, begin­ Application filed for temporary au­ their hand baggage, in commuter service ning and ending at ports of entry on the thority under section 210a(b) in connec­ between points in Multnomah, Wash., United States-Canada boundary line and tion with transfer application under sec­ and Clackamas Counties, Oreg., and extending to points in Arizona, District tion 212a(b) in connection with transfer Clark County, Wash., for 180 days. Appli­ of Columbia, Florida, Kentucky, Louisi­ application under section 212a(b) and cant has also filed an underlying ETA ana, Michigan, New York, Pennsylvania, Transfer Rules, 49 CFR Part 1132 : seeking up to 90 days of operating au­ Tennessee, Texas, Utah, Virginia, West No. MC-FC-76977. By application filed thority. Supporting shipper: City of Van­ Virginia and California, for 180 days. Ap­ February 14, 1977, DIRECT VAN LINFS, couver, Vancouver City Hall, 210 E. 13th plicant has also filed an underlying ETA INC., 6121 Lincolnia Road, Alexandria, St., Vancouver, Wash. 98660. Send pro­ seeking up to 90 days of operating au­ VA 22311, seeks temporary authority to tests to: A, E. Odoms, District Supervisor, thority. Supporting shipper: Fettes Tours transfer the operating rights of WAT­ Bureau of Operations, Interstate Com­ and Travel Ltd., 184 Main St., South, SON BROS. VAN LINES, INC., 1700 merce Commission, 114 Pioneer Court­ Mount Forest, Ontario, Canada NOG South Amphlett Boulevard, San Mateo, house, 555 S.W. Yamhill St., Portland, 2LO. Send protests to : George M. Parker, CA 94402, under section 210a (b). The Oreg. 97204. The purpose of this republi­ District Supervisor, Interstate Commerce cation is to correct the applicant’s name. Commission, Bureau of Operations, 910 transfer to DIRECT VAN LINES, INC., of Federal Bldg., I l l W. Huron St., Buffalo, the operating rights of WATSON BROS. No. MC 142834 (Sub-No. lTA)^ filed N;Y. 14202. VAN LINES, INC. is presently pending. February 4, 1977. Applicant: FETTES COACH LINES LIMITED, 184 Main St., By the Commission. By the Commission. South, Mount Forest, Ontario, Canada R obert L. O swald , R obert L. O swald , NOG 2LO. Applicant’s representative: Secretary. Secretary. Robert D. Gunderman, Suite 710 Statler [FR Doc 177-5329 Filed 2-18-77;8:45 am] [FR Doc.77-5326 Filed 2-18-77;8:45 am] FEDERAI REGISTER, V O L 42, N O . 35— TUESDAY, FEBRUARY 22, 1977 TUESDAY, FEBRUARY 22, 1977 PART II DEPARTMENT OF HEALTH, EDUCATION, AND W ELFARE Food and Drug Administration F O O D P R O D U C IN G A N IM A L S Criteria and Procedures for Evaluating Assays for Carcinogenic Residues 10412 RULES A N D REGULATIONS Title 21— Food and Drugs to be safe. As enacted in 1958, the anti­ t i o n o f s u c h a n im a l a fte r slau gh ter or in (or so-called Delaney) clause o f any food y ie ld e d by or d erived fr o m th e living CHAPTER I— FOOD AND DRUG ADMINIS­ cancer animal * * * TRATION, DEPARTMENT OF HEALTH, section 409 flatty proscribed the approval Modification of the effect of the anti­ EDUCATION, AND WELFARE of any additive that “ is found to induce cancer when ingested by man or animal, cancer clause of section 409 was first SUBCHAPTER A— GENERAL or if it is found, after tests which are ap­ suggested during congressional consid­ SUBCHAPTER E— A N IM A L DRUGS, FEEDS, AND propriate for the evaluation of the safety eration of the Color Additive Amend­ RELATED PRODUCTS of food additives, to induce cancer in ments of 1960. In May 1960, the then- [D o ck e t No. 77N -0026] man or animal * * As applied to addi­ Secretary of Health, Education, and Wel­ CHEMICAL COMPOUNDS IN FOOD- tives added directly to human food, this fare urged Congress to modify the act, PRODUCING ANIMALS language has remained unchanged. Ac­ explaining: cordingly, as a legal matter, section 409 h e re is * * * o n e resp ect t o which the Criteria and Procedures for Evaluating As­ precludes a finding by FDA that a direct a nTtica says for Carcinogenic Residues in Edible food additive that has been shown to lessly nstrin cer p r o v iso h as p r ov ed t o be need­ g e n t as a p p lied to th e use of ad­ Products of Animals cause cancer in laboratory animals (or, d itiv es in a n im a l feed . F or exam ple, in the The Food and Drug Administration of course, in man) can be safely added case o f v ariou s a n im als raised fo r fo o d pro­ (FDA) is establishing procedures and to food, in any amount, for any purpose. d u c tio n , ce rta in d ru gs are u sed in animal fe e d w h ich w ill leave n o resid u e in the ani­ m inim um criteria to ensure the absence Section 706 of the act similarly prohibits m a l a fte r sla u g h ter or in a n y fo o d product of carcinogenic residues in edible prod­ the approval of any carcinogenic color (su c h as m ilk o r eggs) o b ta in e d from the ucts derived from food-producing ani­ additive. liv in g anim al, a n d w h ich are th erefore per­ mals that are administered drugs, food The use of chemical compounds as ad­ fe c t ly sa fe f o r m a n . I f th is is dem onstrated additives, "or color additives. These regu­ ditives to the feed of animals or as ani­ w ith resp ect t o an y p a rticu la r additive in­ lations set forth below provide an opera­ mal drugs has posed more complex prob­ te n d e d f o r a n im a l feed , a n d th e additive will adversely a ffe ct th e a n im a l itself dur­ tional definition of the no-residue re­ lems. The act requires that compounds ninogt its e x p e cte d o r in te n d e d life cycle, we quirement of the so-called “DES proviso” administered to animals as food addi­ ca n see n o reason fo r n o t p er m ittin g such a to the anticancer clauses, sections 409(c) tives, color additives, or animal drugs be u se o f a n a d d itiv e w h ic h c o u ld be highly (3) (A ), 512(d)(1)(H ), and 706(b)(5) shown to be safe for use. Under section u se fu l a n d b en eficia l in th e raisin g of ani­ (B ), of the Federal Food, Drug, and Cos­ 201 (u) of the act (21 U.S.C. 321 (u )), the m als fo r f o o d * * *« metic Act (21 U.S.C. 348(c) (3) (A ), 360b term “ safe” clearly embraces the health W e th e re fo re h a v e in c lu d e d in th e en­ (d )(1 )(H ), and 3 7 6 (b )(5 )(B )). The of man, as well as the health of the ani­ clo se d d r a ft b ill a n a m en d m en t t o perm it use regulations also establish criteria for mals to which such compounds are given. o f a n a d d itiv e in a n im a l fe e d under the acceptance of assay methods and pro­ Thus, in evaluating the safety com­ a b o v e -m e n tio n e d co n d itio n s . cedures for establishing suitable post­ pounds to be administered to animals * * * * * administration withdrawal periods to raised or maintained for production of [U ]n d e r th e a m en d m en t, th e assay prevent the occurrence of carcinogenic food for man, such as cattle, swine, and m eth od s a p p lica b le in determ in in g whether residues in edible products. The regula­ poultry, Congress has from the beginning th ere w ill b e a resid u e sh a h b e those pre­ ed o r a p p rov ed b y u s b y regulations. This tions shall become effective on March recognized that consideration had to be swcrib ill give rea son a b le ce rta in ty in th a t regard, 21,1977. given to the safety of possible residues a lth o u g h , o f cou rse, s u c h regu lation s may Prior to July 19, 1973, FDA had ap­ of the compounds in the products of ani­ fr o m tim e t o tim e b e c h a n g ed as new scien­ plied the proviso to the anticancer mals that become sources of food for tific d ev elop m en ts d em on stra te a need for clauses of the act on a case-by-case basis, man, i.e., meat, milk, and eggs. ch a n ge. I t s h o u ld b e clea rly u nderstood that without published criteria. The Commis­ Prior to 1962, the anticancer clauses th e in d u stry still w o u ld h av e th e responsi­ sioner of Food and Drugs concluded that in section 409 and section 706 did not b ilit y o f d e v e lo p in g a d eq u ate analytical it was appropriate and necessary to distinguish between compounds added m e th o d s f o r d e te ctin g residu es and furnish­ g th e m t o th e G ov ern m en t w ith a petition establish such criteria and procedures directly to human food and compounds in fo r a p p rov a l o f a n add itiv e. H.R. Rep. No. for their application through rule mak­ that might indirectly enter human food 2664, 86th C on g., 2d Sess. (10 6 0 ). ing in order to permit public discussion through administration, as feed addi­ of the scientific, legal, and policy issues tives or drugs, to food-producing ani­ The amendments proposed by the De­ involved. Accordingly, the Commissioner mals. The act was interpreted as forbid­ partment were not included in the color issued these regulations as a proposal, ding FDA to approve the use of a car­ additive legislation. During the follow­ published in the F e d e r a l R e g i s t e r of cinogenic animal drug whether or not ing 2 years, however, concern continued July 19, 1973 (38 FR 19226), and af­ the compounds might leave any residues to be expressed about application of the forded 60 days for public comment. in the edible tissues of the animal. How­ anticancer clause in section 409. As a Forty-six comments on the proposal ever, Congress modified this flat prohi­ result, legislation similar to that earlier were received. These were Submitted by bition in 1962 as part of the Drug recommended by the Department o scientists affiliated with consumer groups, Amendments of 1962, to focus on the Health, Education, and Welfare was in­ universities, scientific societies, State and likelihood that a compound would pro­ troduced in 1962. The House Committee Federal agencies, trade associations, and duce detectable residues. Section 409(c) on Interstate and Foreign Com merce affected manufacturers, and some from (3) (A) now reads: ' . ultimately included modifications of tne nonaffiliated individuals. Many comments anticancer clause in its report on * * * [N ]o a d d itiv e shall be d eem ed t o b e revealed sharp divergence of opinion con­ sa fe i f i t is fo u n d t o in d u ce c a n ce r w h en in ­ Drug Amendments of 1962, with the fol­ cerning FDA’s interpretation of the pro­ gested b y m a n o r anim al, o r i f it is fo u n d , lowing explanation: viso to the anticancer clauses of the act. a fte r tests w h ich are a p p rop ria te fo r th e The committee amended the .anticancer For this reason, the Commissioner has ev a lu a tio n o f th e sa fety o f fo o d a d d itiv es, t o clause of the food additives am endm ent ana set forth, initially, the legal and scientif­ in d u c e ca n cer in m a n or a n im al, e x ce p t th a t the color additive amendment of the ic rationale for these final regulations. th is p ro v iso sh a ll n o t a p p ly w ith resp ect t o eral Food, Drug, and Cosmetic Act by maxing th e u se o f a su b sta n ce as a n in g red ien t o f this clause inapplicable to chemicals s u e Specific comments are described and dis­ fe e d fo r an im als w h ich are raised fo r fo o d veterinary drugs when used in feed fo cussed later in the preamble in connec­ p r o d u c tio n , i f th e S ecretary fin d s (i) th a t, producing animals if the Secretary f in d s ( ) tion with the provisions of the regula­ u n d e r th e co n d itio n s o f u se a n d fe e d in g that under the conditions o fu s e . aI* d tions to which they relate. sp ecified in p rop osed la b elin g a n d reason ably ing specified in the proposed labe ce rta in t o b e fo llo w e d in p ra ctice, su ch a d ­ reasonably certain to be followed in P ’ I. In t r o d u c t i o n d itiv e w ill n o t adversely a ffect th e anim als such additive will not adversely affect tn A. STATUTORY BACKGROUND fo r w h ich su ch fe e d is in ten d ed , a n d (ii) animals for which such feed is ^tended, an th a t n o resid u e o f th e ad d itiv e w ill b e fo u n d (2) that no residue of the additive w Section 409 of the Federal Food, Drug, (b y m e th o d s o f ex a m in a tion p rescrib ed or found (b y methods of examination prescri and Cosmetic Act establishes criteria and a p p rov ed b y th e S ecretary b y regu lation s, ed or approved by the Secretary by regula­ prescribes procedures for the approval w h ich re g u la tion s sh a ll n o t b e s u b je c t t o su b se ctio n s ( f ) an d (g ) ) in an y ed ib le p o r ­ tions) in any edible portion of the anima of food additives that have been shown FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 RULES AN D REGULATIONS 10413 after slaughter or in any food such as milk method of analysis (assay). It is a funda- lowed in practice,” suggesting a congres­ or eggs yielded by or derived from the living mental fact of analytical science that for sional recognition that the occurrence of animal- H.R. Rep. No. 2464, 87th Cong., 2d every assay developed to measure the some residues, i.e., residues resulting Sess. (1962). concentration of a chemical compound from unforeseeable misuse, might not re­ Although controversial, these amend­ in a medium (in this case, a residue in an quire disapproval of a compound even if ments were agreed to by the full House of edible tissue, there is some lowest con­ they were detected. Representatives. The Senate accepted centration or level of such compound A second, and in the Commissioner’s the House-passed modifications of the below which the assay will not yield an view more plausible, interpretation of the anticancer clauses in conference (H.R. interpretable result. If. for example, an DES proviso accepts the words of the Rep. No. 2526, 87th Cong., 2d Sess. assay measures a particular compound amendment and focuses on the language (1962)). in muscle tissue (an edible tissue), and previously quoted: “no residue of such Beginning in 1962, efforts were also the assay has been shown to have a low­ drug will be found (by methods of ex­ made in« Congress to consolidate the est limit of measurement of one part per amination prescribed or approved by the various provisions of the law applicable billion (1 ppb—one part compound in one Secretary by regulations * * Under to animal drugs under the new drug, food billion parts tissue on a weight basis, such this interpretation, an animal drug that additive, and antibiotic sections of the as 1 nanogram of compound per 1 gram is carcinogenic may be approved for use statute, with the objectives of clarifying of tissue), examination of muscle tissue in animals’ if examination of edible tis­ the applicable requirements and expedit­ using this assay will reveal that the com­ sues by an assay approved by FDA re­ ing approvals of new animal drugs. No pound is present only if its concentra­ veals no residues. attempt was made to reopen the issue of tion in muscle tissue is 1 ppb or higher. This in essence is the interpretation the anticancer clause, however, and If the compound is present in the tissue that FDA has followed since the passage neither the committee reports nor the at levels below 1 ppb, use of the assay of the DES proviso: The agency has ap­ floor debates in the resulting legislation will yield no interpretable result. Thus, proved carcinogenic compounds for use mentioned the anticancer clause which the assay cannot distinguish between in animal feed or as animal drugs on precluded approval of a new animal drug muscle tissues containing the compound the basis of assays capable of measuring at levels below 1 ppb and muscle tissues prescribed levels of residues. However, if: from which the compound is absent in * * * such drug induces cancer when in­ the absolute sense of the term. the agency has not previously attempted gested by man or animal or, after tests which Although different assays may have to define and explain the criteria it em­ are appropriate.for the evaluation of the different lowest limits of measurement, ploys in evaluating assays submitted in safety of such drug, induces cancer in man all assays are subject to the same limi­ support of approval of animal drugs, feed or animal, except that the foregoing provi­ additives, and color:additives. That is the sions of this subparagraph shall not apply tation. Thus, when a tissue is examined purpose of this document. with respect to such drug if the Secretary with an assay having a lowest limit of The Commissioner believes that the finds that, under the conditions of use measurement of 1 ppb and no interpret­ specified in proposed labeling and reasonably able response is observed, the analyst can criteria to be applied in evaluating assays certain to be followed in practice (i) such only conclude that the compound under for residues of carcinogenic compounds drug will not adversely affect the animals analysis is not present at levels of 1 ppb in the edible tissue of food animals must for which it is intended, and (ii) no residue and above. It can never be concluded that further the congressional objective of of such drug will be found (by methods of the compound is “not present” in the ab­ minimizing public exposure to carcino­ examination prescribed or approved by the genic compounds, without nullifying the Secretary by regulations, which regulations solute sense. It is thus impossible to de­ decision reflected in the DES proviso, shall not be subject to subsections (c), (d), termine the conditions under which edi­ which the first interpretation of the pro­ and (h)),in any edible portion of such ani­ ble tissues derived from food-producing mals after slaughter or in any food yielded animals that have received a carcinogen viso would do. As. explained more fully by or derived from the living animals * * *. will contain no residue if the phrase “no below, the criteria s e t ,forth in these (21TJ.S.C.360b(d) (1) (H).) residue” is to be interpreted literally. Ac­ regulations for the evaluation of assays for carcinogenic residues are minimum The legislation was enacted without cordingly, this first possible interpreta­ requirements. They are designed to iden­ controversy as the Animal Drug Amend­ tion of the DES proviso would not permit tify assays that are (1) reliable and ments of 1968, and without evident con­ the approval of any animal drug known practical for use by a regulatory agency gressional desire to alter the anticancer to be carcinogenic because the Commis­ and (2) capable of measuring residues at clauses, as modified in 1962 for animal sioner could never find that no trace whatever would remain in the edible levels that have been determined, on the drugs. basis of animal toxicity tests, to present tissues of the animals to which the com­ B. STATUTORY INTERPRETATION pound was administered. no significant increase in human risk of This interpretation would thus render cancer. An assay that does not meet both The enactment in 1962 of the so-called criteria cannot be approved. The Com­ DES proviso to the Delaney anticancer the DES proviso a “ Catch-22.” The missioner recognizes that for some com­ clause has been a source of continuing proviso would permit the approval of car­ cinogenic drugs for animals if the Com­ pounds currently in use no reliable and controversy. There has not been unanim­ missioner could be certain that no resi­ practical assay capable of sufficiently low ity on the proper interpretation of Con­ dues whatever would remain, but since limits of measurement now exists, and gress’ action, and" the legislative history he would only conclude that some trace that approval of their continued use of the proviso, summarized above, does might well remain, no such drug could must be reexamined. not lay to rest all doubts. ever be approved. This seems, at the very The Commissioner further believes Two interpretations of the proviso are, least, an improbable interpretation of an that the policy embodied in the antican­ in theory, possible. The first interpreta­ amendment Congress enacted precisely cer clauses requires application of a third tion, which in the Commissioner’s judg­ because it wanted to relieve animal drugs criterion to the evaluation of assays: ment is the less probable, is that Con­ from the rigid strictures of the antican­ The agency therefore will insist tjiat of gress intended to allow FDA to approve cer clauses. the available assays, the one approved the use of a carcinogenic compound in Furthermore, this interpretation is dif­ for controlling carcinogenic residues food-producing animals only if it could ficult to reconcile with the language of must be the one having the lowest limit be absolutely positive that no traces the DES exception, which specifies that of reliable measurement and capable of whatever—no matter how small—would “no residue” may be “found (by methods satisfying the other two criteria. This remain in edible tissues. of examination prescribed or approved means that, as new practical assays ca­ ,.^bis interpretation presents several by the Secretary * * *) in any edible pable of reliably measuring lower levels difficulties, all stemming from the fact portion of such animals * * This of residues become available, approved mat any introduction of a compound language conspicuously avoids such compounds will be controlled with such (whether or not carcinogenic) is likely words as “occur” or “remain,” and in­ assays and petitioners will be required ;? teave minute residues in edible tissues stead emphasizes detectability. Moreover, to make any modifications in the condi­ tnat are below the level of detection of the same proviso refers to “conditions of tions of use of a compound necessary to any known or likely to be developed use * * * reasonably certain to be fol­ prevent residues from occurring. FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 10414 RULES AN D REGULATIONS The Commissioner recognizes that this tissues containing a residue and tissues (c) If so, what is the chemical nature third criterion may lead to the with­ containing no residue. Without such a of the residues of the compound, in what drawal of approval of some compounds monitoring mechanism, the commis­ tissues are they found, at what levels, because they cannot be used without de­ sioner has no way to determine if a car­ and for what length of tíme? tection by newer assays. (This prospect cinogenic drug or additive administered (d) Is the sponsored compound or any is in part theoretical, however, because to a food-producing animal is or even of the residues it produces in edible tis­ the other minimum criteria defined in can be used in compliance with the act. sue carcinogenic in experimental ani­ this regulation demand a low limit of In these regulations the Commissioner mals? measurement for assays that for many has estabilshed a rigorous premarket (e) If so, what level of residues can compounds is at or below the lower testing process for sponsored compounds be operationally defined as satisfying the limits of present technology.) Any other intended for use in food-producing ani­ no residue requirement of the act? posture, however, would place FDA in the mals. H ie process treats all compounds (f) Can a reliable and practical assay position of approving the use of carcino­ initially as potential carcinogens and be developed to measure the edible tissue genic compounds that could be measured embodies conservative assumptions at residues at a level at least as low as that by new, practical assays capable of re­ each stage of the inquiry to determine which operationally satisfies the no­ liably measuring lower levels of residues. the minimally acceptable lowest limit of residue requirement of the act? It is, of course, also true that the cri­ reliable measurement for a regulatory (g) At what time after cessation of teria outlined in these regulations will assay. Because this minimally accept­ compound exposure do the edible tissues sometimes permit the approval, for use able limit is determined by toxicity data, of exposed food-producing animals sat­ in animal feed or as animal drugs, of the Commissioner may conclude that an isfy the no-residue requirement of the carcinogenic compounds that are likely assay satisfying the requirements of the act, i.e., what is the necessary withdrawal to leave miniscule residues below the -regulations is capable of demonstrating time? lowest level of reliable measurement of the absence of carcinogenic residues in 2. Data collection process. To provide any assay that meets the other criteria food. By thus particularizing the statu­ answers to the preceding questions, a herein set forth. This, however, is the tory requirements, the Commissioner petitioner must gather pertinent scien­ result of congressional enactment of the has established the basis for rejecting tific information, the nature of which is DES proviso. Moreover, this result makes sponsored compounds which are. claimed particularized below. These regulations sense in practical terms, for a regulatory to satisfy the no-residue standard by establish the procedure for gathering and agency cannot effectively control resi­ other mechanisms. evaluating the requisite scientific infor­ dues—of any compound—that are so 1. Fundamental questions. For every mation. The process is stepwise and evo­ small that they escape measurement by drug or additive proposed for use in food- lutionary because the need, as well as every current assay, simply on the* as­ producing animals (hereinafter the spon­ ability, to proceed to the next step of data sumption that such residues must oe oc­ sored compound), the Commissioner is collection depends upon the results ob­ curring. required by the act to determine whether tained at each preceding step. If the eval­ In sum, the interpretation adopted in such sponsored compound can be used uation of the data collected at each step these regulations is reconcilable with in ways which are safe for the animals indicates that questions regarding resi­ both the purpose and language of the to which the compound will be adminis­ dues of carcinogenic concern remain, the DES proviso, and will further the con­ tered (target animals) and whether food process of data collection must continue. gressional objective of minimizing public (meat, milk, and eggs) derived from such If at some point in the process of data exposure to residues of carcinogenic animals (hereinafter edible tissues) will collection it can be decided that the compounds. be safe for human consumption. The sponsored compound presents no human sponsor of such compound (hereinafter risk of carcinogenesis, the sponsored C. OVERVIEW OF THE REGULATION the petitioner) is therefore required to compound shall be evaluated under the The proviso to the anticancer clauses furnish the Commissioner the scientific general food safety provisions of the act. allows the approval of the use of car­ and technological information necessary In such a case, the compound may be as­ cinogens in food-producing animals if, for such a determination; the Commis­ signed a safe tolerance level in human under conditions of use “ reasonably cer­ sioner in turn is required by the act to food if the petitioner provides the data tain to be followed in practice,” no res­ determine on the basis of all available necessary to establish that the compound idue is found by an (assay) prescribed or data whether, in actual practice, the can be used safely. approved by the Secretary. To assure sponsored compound can be used in These regulations deal with carcino­ protection of the public in a manner con­ compliance with the law. genesis, which is a dominant concern in sistent with the anticancer provisions of Although a major obligation of a peti­ appraising the safety of any sponsored the act, the Commissioner must estab­ tioner proposing the use in food-produc­ compound intended for use in food-pro­ lish criteria for approval of assays to ing anim als of a compound that is a ducing animals. Nevertheless, each com­ include, among other things, a required carcinogen is the development of a prac­ pound must also be evaluated for other lowest limit of measurement. tical and reliable assay capable of dis­ potential adverse effects. Thus, for ex­ Accordingly, these regulations estab­ criminating tissues containing residues ample, if the available information lish criteria for accepting assays used to from tissues free of such residues, as de­ raises issues concerning the health of measure carcinogenic residues in edible fined operationally, such as an assay progeny, multigeneration studies of the tissues of food-producing animals which cannot be developed in the absence of sponsored compound and/or its residues have been administered carcinogens. certain scientific and technological infor­ shall be codesigned and conducted as a Such criteria cover assay attributes such mation whose nature is not strictly part of the process of data collection and as dependability, practicability, specific­ analytic. evaluation. ity, accuracy, and precision. Additional­ Specifically, for every sponsored com­ If the Commissioner makes a threshold ly, the regulations establish a specific pound, several questions must be an­ determination, based on (1) preliminary criterion for the lowest limit of reliable swered before assay development can be biochemical, chemical, toxicological and measurement which an assay must meet, undertaken or compound approval con­ physiological data, and (2) proposed pat­ as a minimum, before it can be approved sidered: terns of use, that a sponsored compound by the agency for the control of carcino­ has the potential to contaminate food (a) What is the chemical nature of from food-producing animals with resi­ genic residues. This criterion for the re­ the sponsored compound and how is it quired lowest limit of measurement of an to be used? dues whose consumption would pose a assay derives from toxicological data ob­ human risk of carcinogenesis, the peti­ tain e d f or carcinogenic residues and from (b) On the basis of preliminary toxi­ tioner will be required to undertake the an operational definition of the no-resi­ cological and biochemical information, following six-step procedure for data due objective standard o f the act. Only can it be concluded that the compound collection and evaluation. if an assay meeting the above criteria is has the potential to contaminate human (a) A metabolic study in the target available does the Commissioner have a food (edible tissues) with residues of animals designed to identify edible tissue mechanism to discriminate between carcinogenic concern? residues of carcinogenic concern. FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 RULES A N D REGULATIONS 10415 (b) A metabolic study of the sponsored Comments of two types were received that residues can occur in edible tissues compound in experimental animals de­ on this feature of the proposal. The first when such tissues become available as signed to aid in assessing the carcino­ suggested that extensive studies should food? genicity of residues that can not practi­ be conducted for every sponsored com­ In making a threshold assessment, the cably be tested individually (so-called pound to determine whether it is a car­ Commissioner may or may not have an­ “intractable residue” ) . cinogen. One comment insisted that ex­ swers to these questions and, in some (c) Chronic toxicity testing to assess tensive carcinogenesis testing for every instances, may not need answers to all the carcinogenic potential of residues of sponsored compound is the only accurate of them to make a decision. It will some­ the sponsored compound and to furnish indicator of carcinogenic potential. Sev­ times be obvious that the first step of data suitable for statistical treatment to eral contended that the criteria proposed the six-step process will have to be un­ permit the no-residue requirement of the for use in the threshold determination dertaken. In other cases, it will be equally act to be defined and implemented. were too vague, and objected to the lack clear that no such inquiry need be begun, (d) A detailed metabolic study of the of explanation of how such criteria could and the compound can be evaluated sponsored compound in target animals be applied in practice. under the general food safety provisions designed to identify a residue and tissue Many other comments agreed with the of the act. Finally, in some cases, avail­ that can serve as indicators (“marker Commissioner’s proposal that extensive able information will be so incomplete residue” and “ target tissue” # t o déter­ carcinogenicity testing should not be re­ or ambiguous that a decision will be mine whether the no-residue require­ quired for every sponsored compound, made to move to the first step to assure ment of the act is satisfied. These comments recommended that the protection of public health. As will be (e) Development of a regulatory assay Commissioner review all available data shown later, it is possible that informa­ to measure the marker residue in the tar­ pertaining to a sponsored compound be­ tion developed in later steps may sup­ get tissue at and above the level estab­ fore he concludes that the stepwise test­ port or require revision of the threshold lished in step (d ). ing procedure set forth in the proposal assessment that a compound had the (f) Establishment of the prémarket­ and adopted in this regulation should potential to contaminate tissues with ing withdrawal period required for the be invoked. residues of carcinogenic concern, in safe use of the sponsored compound. When a petitioner initiates the process which case the remaining steps of these Because the partial provisos to the of gaining approval for use of a com­ regulations will not be required and eval­ anticancer clauses of the act, sections pound, information is provided to the uation will proceed under the general 409(c)(3)(A), 512(d)(1)(H ), and 70ÉI agency on matters such as compound food safety sections of the act. (b) (5) (B ), although varying slightly in efficacy and its proposed patterns of use. The following examples illustrate how their language, have a similar intent, the Often a petitioner will also provide pre­ a threshold assessment can be made: Commissioner has concluded that the liminary physiological, metabolic, or C ase I.—A drug is proposed for use in criteria for their implementation should toxicological data derived from its own day-old chickens. Preliminary informa­ also be identical. To avoid needless rep­ studies or from the scientific literature. tion indicates that: etition, however, where appropriate the At this juncture, the Commissioner be­ (à) Neither chemical structure nor Commissioner has used the language of lieves it necessary that a threshold as­ preliminary (short-term) toxicity test­ section 512 of the act in discussing spe­ sessment be made, based on the avail­ ing raise a suspicion that the drug is a cific generic issues because the primary able data, on the need to proceed to the carcinogen. impact of these regulations will be on new first of the six steps of data collection (b) The drug is proposed for therapeu­ animal drugs regulated under that sec­ required by these regulations. Because tic use only in a single administration tion. The criteria set forth in these regu­ entry into the six steps of data collection to day-old birds. lations shall, however, apply to all chemi­ requires that a petitioner undertake a (c) The disease to be treated occurs in­ cals intended for use in food-producing series of very complex and costly ex­ frequently. animals, and the appropriate regulations perimental studies, imposing demands (d) Preliminary metabolic data indi­ will be amended to adopt these criteria on the limited national resources avail­ cate accumulation of residues in kidney by reference. able for determining the safety of chem­ and no detectable residues in muscle. Since issuing the proposal under § 135.- icals entering the environment, the Com­ (e) Residues deplete rapidly and none 38 (21 CFR 135.38), PDA has recodified missioner concludes that it is not reason­ are detected many weeks before the all regulations applicable to animal prod­ able to demand such studies on a spon­ chickens reach marketing weight. ucts in Subchapter E of Title 21 of the sored compound if the preliminary data If presented with the foregoing infor­ Code of Federal Regulations to provide available justified the judgment that mation, the Commissioner would see no space for the orderly development of fu­ public health can be protected without justification for demanding that the pe­ ture regulations and to provide the pub­ so proceeding. titioner proceed to the first step of these lic and other affected parties with regu­ Criteria for this threshold assessment regulatipns which governs compounds lations that are easy to find, read, and cannot be elaborated in detail. The Com­ having the potential to contaminate edi­ understand. For these reasons, the final missioner must examine the available ble tissues with residues of carcinogenic order has subdivided the proposal into 10 preliminary data, which may vary con­ concern. However, if the preliminary individual regulations and established a siderably in quality and content from metabolic study in the example had been new subpart in Part 500, Subpart E— one compound to the next, on a case-by- conducted with an assay having a low­ Criteria and Procedures for Evaluating case basis and determine whether a est limit of reliable measurement of res­ Assays for Carcinogenic Residues in sponsored compound has the potential idues substantially higher than current Edible Products of Animals. to contaminate edible tissues with resi­ technology can attain, the Commissioner dues of carcinogenic concern. However, would conclude that the available data II. T hreshold A ssessm en t certain general characteristics of the were insufficient to justify a favorable In the 1973 notice of proposed rule­ compound shall always be considered in threshold assessment about the sponsored making, the Commissioner proposed that making the threshold assessment: compound, and the petitioner would be carcinogenicity testing not be required (1) Is the compound a known carcin­ required to proceed to the first step of for every sponsored compound. Rather, ogen or is it related, in a chemical or these regulations. It is precisely because he concluded that the necessity for such biological sense, to other known carcin­ of such contingencies that the Commis­ testing will be dictated by an evalua­ ogens? sioner concludes that no more specific tion of the existing evidence from meta­ (2) Is there an indication in prelimi­ criteria for threshold assessment should bolic studies, standard toxicity testing, nary toxicity studies that the sponsored be established by regulation. structural relationships of the sponsored compound may be carcinogenic? C ase H.— A drug having growth pro­ compound and/or its metabolites to (3) Does preliminary information on moting properties is proposed for use in Known carcinogens, modes of physiologi­ the fate of the compound in target ani­ cattle. The preliminary information cal actions and interactions, and the in­ mals indicate that, in combination with indicates that: tended method o f use of the sponsored information on the proposed pattern of (a) The observed physiological activity compound. use, there is a high or low probability of the drug in cattle indicates that it is FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 10416 RULES A N D REGULATIONS in a class of other known carcinogens to have such information on metabolites choice for metabolic studies will be the whose carcinogenic properties appear to in inedible tissues. Further, some com­ use of radiotracers. The regulations, be related to this particular physiological ments stated that radiotracer studies can therefore, recommend that the required activity (i.e., the drug is a suspect car­ be employed to determiné the time by metabolic studies be conducted with cinogen) . which the sponsored compound and its radiolabeled compounds of the highest (b) The drug is used during a large metabolic products are eliminated (“ out specific activity that is available and is fraction of the lifetime of the animal. time” ). However, other comments sug­ consistent with principles that assure (c) The drug is likely to be widely used gested that all metabolites should be scientific quality. These principles con­ in animal husbandry. identified and tested for toxicity. cern the types, the chemical nature, the (d) Preliminary metabolic data show The Commissioner reiterates that the chemical and metabolic stability, and the that residues of the drug accumulate in objective of requiring metabolic studies suitability of radiolabels for metabolic muscle tissue (meat) and deplete very is to assure collection of sufficient scien­studies having specific objectives. They slowly: On the basis of such informa­ tific information on residues to permit a have been developed from past metabolic tion, it is obvious that the Commissioner food safety evaluation which ii\ turn can studies with radiotracers and should be would have to require the petitioner to be used to establish parameters for reg­ followed to assure the scientific quality proceed to the first step of the required ulatory assays. Therefore, he has con­ of the reauired metabolic studies. six-step process. cluded that the following metabolic The tasK of experimental residue de­ i n . M etabolic S t u d y in T arget A n im als studies are necessary to permit a deter­ tection can often be made easier by To I d e n t if y R esidues o f C oncern mination of whether the proposed use of available information on the metabolism a sponsored compound is safe. of related compounds. It is recommended A. NEED TO IDENTIFY RESIDUES IN EDIBLE that metabolically feasible pathways B. CONDUCT OF METABOLIC STUDY TISSUE applicable to the sponsored compound be Before any decision can be made con­ 1. Test animals. The metabolic fate proposed based on relevant literature cerning conditions of safe use of a spon­ of an administered compound in an ani­ references about compounds of similar sored compound, it is necessary to obtain mal may be unique for each livestock structure. This information can usually information on the residues that occur production class. Therefore, the Com­ simplify the choice of radiolabel posi­ in edible tissues when the compound is missioner concludes that a metabolic tions which will assure that all residues administered to the animals for which study in the animals for which a spon­ containing structural moieties of poten­ it is intended (target animals). Without sored compound is intended (target ani­ tial toxicological coneem can be de­ such information, rational decisions mals) is necessary. If the petitioner can tected. However, such projections of about the human safety of edible tissues demonstrate that the data from the likely metabolism can never be a sub­ derived from treated animals are not metabolic study obtained for one pro­ stitute for experimental observation of possible. duction class are applicable to a second, the metabolic fate of the sponsored com­ A compound administered to an ani­ the Commissioner may modify the ex­ pound. mal can be acted upon by the enzymatic tent of investigation required for the Although the use of radiotracers is the systems or physiological fluids of the latter. preferred experimental procedure, some animal and new compounds (metabo­ 2. Required technology. Because the compounds possess inherent physico­ lites and degradation products of the metabolic fate of a compound adminis­ chemical characteristics (e.g., strong sponsored compound) are produced in tered to food-producing animals plays a fluorescence associated with the struc­ the process. Therefore, the sponsored pivotal role in decisions regarding the tural moiety of potential toxicological compound is not the only tissue residue need for an extent of carcinogenesis test­ significance) that will allow the neces­ of concern. And sections 512(b) (7) and ing required to assure public health and sary detection of residues. In such cases, 512(d) (2) of the act explicitly require safety, it is mandatory that such fate the use of radiolabels may not be re­ the Commissioner to consider the safety be adequately determined, i.e., it must quired. of any substance formed in or on food be demonstrated that residues of po­ 4. Dose regimen. The dosing regimen by a sponsored compound before approv­ tential carcinogenic significance have for the metabolic study in the target ani­ ing its use. been detected at levels obtainable by the mals shall be consistent with the maxi­ Numerous comments were received on best analytical technology available. mum proposed use level mad duration of the proposal’s requirement for metabolic Therefore, the Commissioner concludes exposure to the sponsored compound. studies. Several comments stated that that the required metabolic studies shall For compounds administered continu­ there should be no attention paid to be conducted with the best analytical ously over long periods of time, admin­ methods technology can provide. istration for the metabolic study need metabolites. Others contended that continue only until equilibration or satu­ metabolism studies should not be rou­ As will be seen in part VI of this pre­ ration of edible tissues has been demon­ tinely required, on the ground that the amble, it is necessary to select one resi­ pathway of excretion is of no toxicolog­ due that can serve as a practical indica­ strated. The metabolic fate of a compound ad­ ical importance if all of the adminis­ tor to assure that the no-residue require­ ministered to target animals is likely to tered compound has been eliminated ment of the act is met. Such a residue depend on the conditions (level, method, from the tissues of the target animal. can only be selected by reference to a and duration) of use. Because the pur­ Most comments recommended that a metabolic study in which residues are pose of the required metabolic studies is metabolism study should only be required detected and measured at levels dictated to characterize and quantitate residues to determine the major metabolites in by the outcome of actual carcinogenicity under conditions of proposed use, these the edible tissue of target animals, sug­ testing. Because these levels cannot be conditions shall be followed in the meta­ gesting that the public health would not known at the outset of this phase of the bolic studies. However, it is possible that be served if petitioners are required to metabolic study in target animals and under such conditions certain residues pursue endless structural elucidations because the “best available technology” are produced in amounts that do not and quantitations of all metabolites even may not be adequate to measure the allow extensive chemical characteriza­ though some of them might constitute levels dictated by the outcome of car­ tion. If the structure of any such residue minor fractions of the residue of the cinogenicity testing, it may be necessary must be determined, and residues can be sponsored compound. Comments also to develop improved technology and to produced in sufficient amounts by ad­ contended that it may not be experi­ repeat the metabolic study in target ani­ ministering to target animals larger doses mentally possible to administer to ani­ mals, after carcinogenicity testing has of the sponsored compound, the peti­ mals sufficient quantities of a compound been completed. Another requirement of tioner will be allowed to follow this pro­ to obtain amounts of residues sufficient the second metabolic study will be the cedure. In some instances, chemical syn­ for structural identification. Several development of enough data to construct thesis of residues may be more feasible, Comments asserted the studies should be tissue concentration-time profiles for especially if they are needed for chronic limited to identification of residues in some residues. toxicity testing. the edible tissues of target animals and 3. Analytical techniques. For the fore­ 5. Required data. Since the relative that generally it would be unnecessary seeable future, the general technique of persistence of residues in edible tissues is FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 RULES AN D REGULATIONS 10417 one consideration in selecting specific vide the basis for major public health provides a practical approach to a com­ residues for toxicity testing, the regula­ decisions, the Commissioner considers it plex and important issue. tions require that the total number and essential that they be carried out and This construct has been included in the relative quantities of residues shall be reported in a manner consistent with the the final regulations in response to com­ determined immediately following cessa­ best available criteria. The two profes­ ments that either suggested that all tion of treatment, as well as some later sional societies listed in the regulations metabolites ought to be ignored (which time. The Commissioner has concluded (American Chemical Society and Ameri­ the Commissioner concludes is neither that the identification process shall ordi­ can Society of Biological Chemists) fol­ legally nor scientifically acceptable) or narily continue until the total residue low policies for acceptance of manu­ that all metabolites must be isolated and burden in the edible tissues of the target scripts that embody the best available independently tested (which is not tech­ animals has depleted through at least criteria for collecting, interpreting, and nologically possible). three half-lives. After such time, it is un­ reporting scientific data of the type re­ 2. Selection of residues for chronic likely that new residues previously un­ quired by this regulation. toxicity testing. On the basis of all of detected will appear to alter the residue C. COMPARATIVE METABOLISM STUDY TO AID the studies described above, the Commis­ picture. IN ASSESSING CARCINOGENICITY OF IN ­ sioner will select those residues, in addi­ The need for and extent of chemical TRACTABLE RESIDUES tion to the sponsored compound, that re­ characterization of residues depend on a quire chronic toxicity testing. number of factors. Ordinarily, com­ 1. Sponsored compound always tested: Rationale and procedure. When it is de­ IV. C h r o n i c T o x i c i t y T e s t i n g pounds that constitute a significant frac­ tion of the total residue require sufficient termined that a sponsored compound has The sponsored compound and any physical and chemical characterization the potential to contaminate edible tis­ residues selected for testing shall be sub­ to ascertain whether or not a structural sues with residues whose consumption jected to oral, lifetime, dose-response change has taken place which could in­ may pose a human risk of carcinogenesis, studies in two of the test animal species/ crease the carcinogenic potency of the the sponsored compound itself shall al­ strains selected in accordance with the residue over that expected of the spon­ ways be tested for carcinogenesis. Resi­ criteria described in the foregoing para­ sored compound. In some instances, it dues are selected for testing according to graphs; The purpose of these studies is may be impossible to judge whether the those criteria already discussed in para­ to determine if the compounds under test residue has carcinogenic potential, but graph m .B ., but there are overriding rea­ are carcinogenic and, if so, to establish significant structural alteration alone sons for testing the sponsored compound, the lowest limit of reliable measurement may be enough to signal the need for even if it is not detected as a residue. that must be achieved by any regulatory further characterization. Since such Metabolic transformation or nonenzy- assay for monitoring residues resulting structural changes are not uncommon matic degradation of a sponsored com­ from use of the sponsored compound. during metabolism and since it is the pound can lead to a number of tissue Several comments on this feature of tissue residues to which human beings residues which cannot be obtained (either the proposal dealt with the testing of will be potentially exposed, such charac­ by isolation or synthesis) in sufficient chemical compounds for carcinogenic terization will normally be required. amounts for carcinogenicity testing (such potential, and addressed two major is­ When the agency determines a compo­ residues are herein and in the regula­ sues: (i) The design of chronic studies, nent of the residue requires chronic tion referred to as “ intractable resi­ and (ii) the relevance of animal testing toxicity testing (because of tissue concen­ dues” ) . Testing the sponsored compound in evaluating human safety. tration and persistence and/or expecta­ itself therefore provides one experimen­ The Commissioner appreciates the in­ tion of increased carcinogenic potential), tal means for acquiring data on the car­ herent complexity of these issues. He chemical characterization will ordinarily cinogenic potential of such residues. further recognizes that they are common have to be complete and an effort to ob­ Although the dominant criterion for to many areas of food safety, as well as tain sufficient quantities of the residue (s) selecting test animal species or strains for environmental safety, and must be dealt for toxicity testing will be necessary. chronic toxicity testing will be the degree with in an integrated manner in forth­ (See, however, paragraph i n . C . , below to which a species or strain models man, coming regulations on general food in this preamble.) the application of a secondary criterion safety. However, he believes some discus­ In some instances, a petitioner may be for selection can provide a means for sion of these issues must be included in required to pursue the complete char­ addressing the problem of intractable this preamble as they relate to the con­ acterization of certain relatively minor residues. Specifically, selection of test text of this regulation. metabolites if partial physiochemical animals can also be based on compara­ A. DESIGN OF CARCINOGENICITY STUDIES characterization indicates that a struc­ tive metabolism data (target animal and tural change during metabolism in the test animal) which can be used to de­ Comments on the proposal expressed a target animal has introduced molecular termine the extent to which particular variety of contrasting opinions regarding moieties of carcinogenic potential greater species or strains, by virtue of the way the design features of carcinogenicity than that expected of the sponsored com­ they metabolically convert the sponsored studies with experimental animals. The pound, e.g., nitrosation of an amine of compound, will be exposed during test­ comments specifically addressed: (i) se­ unknown carcinogenic potential to prod­ ing to the same complement of residues lection of appropriate test animals; (ii) uct nitrosamines of known carcinogenic expected in tissues derived from target, conditions, levels, and duration of expo­ potential. animals. sure; and (iii) statistical design as it re­ Because uncharacterized tissue resi­ For example, if a metabolite detected lates to number of animals in bioassay, dues pose a risk to public health, the as a residue in edible tissues of the target distribution of animals to the various regulation requires that the procedures animal is determined to be toxicologi- levels of exposure, and adequacy of con­ for separation, purification, and charac­ cally important, the petitioner will be trols. terization be consistent with the best asked to pursue isolation or synthesis of The Commissioner recognizes that the available scientific and technological ca­ the compound for toxicity testing pur­ impact of these design features on the pabilities. Ordinarily, the agency will re­ poses. If all attempts at this fail, then meaning of animal carcinogenesis data quire attempts at characterization to the comparative metabolism approach is is an important and controversial matter include use of a variety of procedures available if a potential test animal spe­ that is currently the subject of intense based on the various forms of cies is shown to produce the same metab­ scientific investigation. The major effort chromatography, spectroscopy, and olite when it is administered the spon­ at FDA’s National Center for Toxicologi­ spectrometry. sored compound. In this way, there is cal Research is specifically directed to­ 6. Format for data submission. The some degree of assurance that the toxic­ wards development of relevant protocols Commissioner has concluded that the ity test of the sponsored compound also and experimental designs for carcino­ format fo r presenting results o f m eta­ provides some estimate of the toxicity of genicity testing. Until these efforts are bolic studies should be standardized to the intractable metabolite. Because hu­ concluded and the results incorporated nunimize possibility fo r m isinterpretation man food could be contaminated with into regulations, the Commissioner rec­ of data. Because these studies will pro­ the intractable metabolite, such a test ommends that guidance be found in the FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 10418 RULES A N D REGULATIONS report of the Food and Drug Advisory relevance to man of data from tests in V. O perational D e f in it io n o f t h e Committee on Protocols for Safety Eval­ animals must be refocused. The regula­ N o - R esidue R equirem en t uation: Panel on Carcinogenesis, Report tory objective must be to avoid falsely a . alternate operational DEFINITIONS on Cancer Testing in the Safety Evalua­ negative determinations of the carcino­ tion of Food Additives and Pesticides genic potential of compounds under test If its has been determined that a (“Toxicology and Applied Pharmacol­ in experimental animals that are ap­ sponsored compound, when administered ogy,” 20:419-438, 1971). This report re­ propriate models for man. In this setting, to food-producing animals, has the po­ views and analyzes all facets of experi­ the only tenable regulatory posture for tential to contaminate edible tissue with mental design that have been developed the agency is to select bioassay protocols residues whose consumption may pose a and scrutinized by competent scientists which utilize test-animal species/strains risk of human carcinogenesis, the agency prior to 1971. To facilitate incorporation that have the greatest possible suscep­ cannot approve the sponsored compound of later developments in testing stand­ tibility to the test compound and are also unless it can be demonstrated that con­ ards as they have and will evolve, the appropriate models for man. Available ditions of use can be established that regulations suggest that petitioners sub­ toxicologic and metabolic information ensure the no-residue requirement of the mit developed protocols to the Commis­ shall provide a basis for such selection. act can be met. To establish such condi­ sioner for review and updating prior to C. INTERPRETATION OF TEST DATA— IS THE tions of use and to provide a means for initiating studies. ascertaining whether these conditions COMPOUND A CARCINOGEN? B. RELEVANCE OF ANIMAL TESTING IN are met in actual practice, some opera­ The objective of collecting and inter­ tional definition of the term, “no resi­ EVALUATING POTENTIAL FOR HUMAN preting test data is to decide whether or due,” is necessary. Indeed, the act con­ CARCINOGENESIS not the compound under te^t (the spon­ templates that the Commissioner will Several comments cm this aspect of the sored compound and any selected metab­ provide such an operational definition, proposed regulation dealt with the merits olites) is a carcinogen. Within certain for he must have some criteria for pre­ of animal testing as an experimental limits of confidence, statistical treatment scribing or approving methods of exami­ tool. Some comments pointed out that of chemical carcinogenesis data can pro­ nation for measuring residues. even animal testing done under the best vide objective criteria for such determi­ The Commissioner has. considered experimental protocols can never prove nations. To the question “Is the tested three alternate approaches to an opera­ conclusively that a compound is not car­ compound a test-animal carcinogen?” tional definition of the phrase. Under one cinogenic, and that under such circum­ statistics can provide one of two types of approach the term, “ no residue,” might stances, some weak carcinogens are likely answers: be operationally defined as satisfied to escape identification. Other comments (i) With “x ” percent confidence (i.e., when the levels of residues fall below expressed the contrasting view that ade­ in “x ” cases out of 100), “y ” dose of the those that can be measured by available quate protocols can be devised. Still test compound will increase the carcino­ analytical methodology (alternative 1). others questioned the propriety of draw­ genesis risk'of test-animals over controls A second approach would be to estab­ ing conclusions about human carcino­ by no more than “s" and no less than lish some low finite level (e.g., one part genesis from data collected with experi­ “ t” ; or per billion) as a “ practical zero” and to mental animals. (ii) With “x ’l percent confidence, “y ” require assays that can reliably measure The act requires that in assessing the dose of the test compound will increase this “ zero,” insisting on the development safety of animal drugs, the carcinogenic carcinogenesis risk of test animals over of new assays if available assays were potential of residues shall be evaluated. controls by no more than “s.” not adequate (alternative 2). Finally, “no Ordinarily, such evaluation must be Answers of the first type are possible residue” might be operationally defined based on appropriate testing. Given the only when the observed incidence of car­ on the basis of quantitative carcinogen­ gravity of the decisions that depend on cinogenesis in the test animals is sig­ icity testing of residues and the extrap­ the results of such evaluations, the best nificantly greater than that in the con­ olation of test data using one of a num­ relevant scientific information must be trols. When the observed incidence is the ber of available procedures to arrive at developed and assembled. As a source of same for test and control animals, only levels that are safe in the total diet of information, direct carcinogenesis test­ answers of the second type are possible. test animals and that would, if they oc­ ing of chemical compounds in man is and A statistically significant increase in curred, be considered safe in the total must remain beyond the ethical bounds the incidence of carcinogenesis in test diet of man. Under this approach, the placed by society on human experimen­ animals (i.e., an answer of the first type) Commissioner would require assays that tation. In the absence of this source of is sufficient evidence to classify the test can reliably measure that safe level in information, which incidentally would compound as a test-animal carcinogen. edible tissues (alternative 3). For the be most relevant, alternate sources are Because the act does not distinguish be­ reasons discussed in section V.B. of this human epidemiology studies and animal tween human and animal carcinogens, preamble, the Commissioner has con­ experimentation. Human epidemiology for the purpose of these regulations, cluded that alternative 3 should be may provide post facto information classification of a test compound as a adopted. The results of the carcinogenic­ about the carcinogenic effects of chemi­ test-animal carcinogen brings into play ity testing of the sponsored compound cal compounds on man. However, while the requirements of the anticancer and any selected residues shall be treated potentially useful in assessing the sig­ clauses. Revisions of such classification by the statistical procedures described in nificance of new exposures or the risk on the basis of phyllogenetic considera­ this part V and prescribed in § 500.87 (21 posed by related compounds, such ex­ tions can have no bearing on the appli­ CFR 500.87). perience cannot be a central basis for cable legal requirements. B. CHOICE OF AN OPERATIONAL DEFINITION food safety evaluations for several rea­ If the animal test data will permit only sons, including the same ethical objec­ answers of the second type, the decision 1. Alternative one. A number of assays tions that' make direct experimentation whether to classify the test compound as might be developed to measure the con­ in man unacceptable. a test-animal carcinogen is more diffi­ centration of a chemical compound (i.e-. cult. A negative test finding, as pointed rèsidue) in an edible tissue, but for each The Commissioner therefore concludes out in some comments, can mean either there would be some level below which that the agency must continue to rely on that the-test compound is not a test- the compound under analysis could not animal testing for the evaluation of the animal carcinogen at the tested dose, or be measured. (See section I.B. of this safety for humans of chemical com­ that the bioassay protocol lacks a suffi­ preamble). Generally, différait assays for pounds proposed for use in food-produc­ cient number of animals, or animal sus­ the same chemical compound will have ing animals. Moreover, the act does not ceptibility, or both, to discern ah increase different, and sometimes vastly difficult, distinguish between compounds demon­ in the risk of carcinogenesis in the test lowest limits of measurement. The “no strated to be carcinogenic in test animals animals. In such cases, a decision must residue” requirement of the act could be and human carcinogens. Instead, it as­ be made whether to classify a tested translated into an operational definition sumes without proof that an animal car­ compound as a noncarcinogen or to re­ that is based solely on available analyti­ cinogen may be carcinogenic in human quire further experimentation appropri­ cal methodology and specifically on tne beings. In this context, the issue of ate for resolving questions of safety. lowest limit of measurement of an avau- FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 RULES A N D REGULATIONS 10419 able assay. Thus, the degree of public tion because actual chronic toxicity test rates in test animals well below those risk associated with the use of a spon­ data are used to determine the level of rates that can be detected in practical sored compound would become a func­ residues in edible tissue that an assay experimentation. In normal experiments tion solely of the capability of available must be capable of reliably measuring. in which test animals are administered analytical technology. Thus, it permits a rational, uniform pro­ various levels (doses) of a suspected car­ The Commissioner concludes that this cedure for establishing the required low­ cinogen, the observed responses (i.e., the approach is unsound because it ignores est limit of measurement for assays and percent of test animals developing cancer all quantitative aspects of carcinogenic­ avoids the major deficiencies inherent in if the compound is carcinogenic) are ity testing. The carcinogenic potency of alternatives one and two. usually in the range of about 5 percent different chemicals varies widely; fail­ Should new information relating to to 95 percent. To observe responses at in­ ure to consider this fact in developing the carcinogenic potency of residues of cidence rates less than about five percent criteria for the evaluation of sponsored a sponsored compound later appear, this requires large numbers of test animals. compounds would be scientifically un­ approach provides a practical basis for As will be seen, experiments designed to sound. It could produce situations in determining whether a new assay is re­ observe responses in the range of inter­ which residues of extremely potent car­ quired to establish compliance with the est in establishing the no-residue stand­ cinogens were not measured in edible tis­ no-residue requirement. But only under ard, would require very large and often sues at levels as low as the measurable such circumstances will it be necessary impractical populations of test animals. levels of residues of relatively weak car­ for the Commissioner to insist that the Therefore, the procedure of Mantel and cinogens, if the assay available to meas­ petitioner develop a new assay; thus, Bryan,1 and Mantel et al.,2 as modified, ure the former happened to have a low­ this approach contributes to regulatory is used to treat statistically the dose-re­ est limit of measurement that was higher stability and predictability. If an assay sponse data from actual experimentation than that of the assay available to meas­ becomes available with a lowest limit of and to estimate the dose or level of the ure the latter. Accordingly, failure to measurement that is lower than the level compound under test that would result in consider quantitative carcinogenicity required by the analysis of quantitative lifetime test-animal cancer rates no data in establishing the criterion of low­ carcinogenicity data, the Commissioner higher than a certain preselected rate. est limit of measurement that an assay will adopt that method if it also meets Before discussing the many comments must meet would be tantamount to ig­ the other rigorous criteria described in received on this feature of the proposal, noring public health protection in evalu­ part VIII of this preamble and § 500.90 the Commissioner reemphasizes that ating the use of sponsored compounds. (21 CFR 500.90). However, for com­ some operational zero must be defined 2. Alternative two. A second approach pounds that have been approved for use if the no-residue requirement of the act the Commissioner has considered would on the basis of an assay that satisfies the is to be implemented. Regardless of the be to establish “practical zero” for the requirements of the regulation, the de­ arguments for or against the Mantel- residues of all carcinogens. This approach velopment of such a method will not be Bryan procedure, the- Commissioner would have one advantage over alterna­ required. Thus, following this approach, maintains that a procedure that takes tive one; it would provide a well-defined the Commissioner can provide the maxi­ into account the carcinogenic potency in criterion for the lowest limit of measure­ mum public health protection based on test animals of residues (which the Man­ ment that any petitioner’s assay would both quantitative carcinogenesis data tel-Bryan procedures does) is far supe­ have to satisfy. This approach would not, and improved analytical technology. For rior to any approach that fails to do so. however, take into account differences these reasons, the Commissioner con­ The modified Mantel-Bryan procedure in carcinogenic potency among various cludes that alternative three ig the most described in the proposal was labeled ex­ carcinogens and is therefore unaccepta­ rational approach to developing an op­ cessively conservative by some comments ble for the same reason as alternative erational definition of “no residue.” and recklessly liberal by others. Those one. By adopting this approach to imple­ who considered the procedure too con­ Under alternative two the criterion for menting the “no residue” standard, the servative objected to the proposed use of lowest limit of measurement would re­ Commissioner has assumed that: (i) The a series of conservative assumptions flect consideration of what lowest level carcinogenic potency of chemical com­ (shallow-slope, dose-response relations, of measurement is “practical,” given the pounds can be quantified, and (ii) a die­ low acceptable level of risk) and con­ state of the art of analytical chemistry tary level of a carcinogen can be identi­ tended that any one of these assump­ or biochemistry. In addition to failing to fied at which no significant human risk tions alone could provide adequate link the no-residue standard to any con­ of carcinogenesis would derive from con­ protection to the public. Further, sideration of carcinogenic potency, this sumption of food containing residues be­ these comments argued that the practi­ approach fails on the ground of practi­ low this level. cal application of the procedure has not cality. The science and technology of The carcinogenic potency of „ com­ been demonstrated, and suggested that it analytical chemistry, and biochemistry pounds can be determined by testing in would prohibit the use of many valuable are continuously changing, and a lowest experimental animals, although such de­ compounds. Persons who considered the limit of measurement which might be terminations are subject to known limi­ proposed procedure too liberal objected considered reasonable at one time would tations inherent in every measuring de­ to the proposed use of a lower confidence, have to be discarded as unreasonable at vice or system. The second assumption, limit on the observed slope of the dose- some later time. Whenever a new and that potential residue levels representing response curve. Their objection is that lower criterion for the limit of measure­ no significant human risk of carcinogen­ the proposed statistical technique for ex­ ment were established, it would be in­ esis can be assigned, is controversial, but trapolating dose-response data obtained cumbent upon the Commissioner to then it must be fully confronted and resolved from animal tests seriously underesti­ require that use of all compounds ap­ if the public is to be protected from the mates public risk. The technique pro­ proved under the prior criterion be sus­ potential and real dangers that inhere vides a basis for establishing a dose level pended until methods were developed to in the interpretations of the no-residue where there would be no significant hu­ measure the residues at this lower level. standard of the act outlined as alterna­ man risk of cancer, thereby establishing Such a situation, in the Commissioner’s tives one and two. a criterion for a residue detection meth­ Judgment, would be both unreasonable od. Specifically, the comments contended C. ANALYSIS OF ANIMAL CARCINOGENESIS and unmanageable. that if the true statistics of the dose-re­ DATA TO DEFINE OPERATIONALLY THE N O - 3. Alternative three. A third approach sponse relation are logistic or linear, ex- RESIDTJE STANDARD OF THE ACT to defining operationally the no-residue requirement is to establish a required 1. Introduction. The modified extrap­ 1Mantel, N. and W. R. Bryan, “ ‘Safety' lowest limit of measurement for each olation procedure of Mantel and Bryan Testing of Carcinogenic Agents,” “Journal of sponsored compound on the basis of proposed for use in defining the no-resi­ the National Cancer Institute,” 27(2) :455- . ta derived from carcinogenicity test- due standard for a sponsored compound 470 (1961). toK the compound and selected me­ is a statistical technique that allows esti­ Bryan aMantel, N., et al., “Improved Mantel- tabolites. Under this approach carcino­ mation of the level, or dose, or a carcino­ cinogens,” Procedure for ‘Safety’Testing of Car­ “Cancer Research,” 35:865-872 genic potency is given specific considera- gen that would lead to cancer incidence (1975). FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 10420 RULES A N D REGULATIONS trapolation with the slope of a probit The comments failed to demonstrate analyzed in detail the deficiencies of all transformation would seriously underes­ that another procedure is superior to statistical extrapolations and stated that timate public risk. Further, these com­ that of Mantel and Bryan1 and Mantel. approaches are available to define a true ments argued that the probit transfor­ et al.,3 (Mantel-Bryan) and therefore carcinogenic “n6-effect” level. It con­ mation leads to a paradox, in that strong the Commissioner has adopted it with tended that it is more appropriate to carcinogens are treated less conserva­ some modifications. Moreover, the Com­ determine a biologically insignificant tively than weak ones. Regardless of their missioner concludes that some aspects of level using a safety factor based on com­ point of view, however, most of the com­ the Mantel-Bryan procedure offer dis­ petent scientific judgment. ments supported the Commissioner’s ef­ tinct advantages over the other statis­ The Commissioner disagrees with'the fort to elicit public discussion of the im­ tical procedures. It provides a clearly contention that the classical toxicology plementation of the anticancer provi­ defined means for pooling data from concepts of “ thresholds” and “biologi­ sions of the act. multiple experiments and from multiple cally insignificant levels” are generally 2. Choice of the Mantel-Bryan proce­ dose levels within a single experiment, applicable to carcinogenesis.^ There is dure— (a) Alternative statistical models. thus permitting decisions based on the substantial scientific controversy over Most of the comments favored the pro­ fullest use of available data. Further, the whether such concepts apply to irrevers­ posed adoption of the Mantel-Bryan Mantel-Bryan procedure has a clearly ible processes, such as the chemical in­ procedure but without the modifications defined mechanism for handling the duction of malignant neoplasia. “Thresh­ suggested in the proposal. A smaller spontaneous tumor rate. (See paragraph old” and “ biologically significant level” number of comments recommended that V.C.4.(d) of this preamble, below.) To concepts derive from short-term toxicity a linear extrapolation would be a better overcome certain limitations of, the experiments which have no established alternative to the Mantel-Bryan proce­ Mantel-Bryan procedure, the Commis­ meaning in biological processes that re­ dure, and even fewer suggested the lo­ sioner has adopted a number of modifi­ quire long latent periods (up to 20 or gistic or the angle distributions. Still cations, which are described in § 500.87 30 years) before lesion manifestation. other comments suggested that a com­ and discussed in paragraph V.C.4 below Several comments opposing the pro­ parative analysis of animal carcinogen­ in the preamble. posal suggested that the agency should esis data be required emploving all al­ The Commissioner recognizes the maintain flexibility and evaluate the ap- ternative distributions and the smallest significance of the decision to adopt the provability of sponsored compounds estimate of the “safe” level be used to modified Mantel-Bryan procedure to im­ based on assessments of benefit and risk, define the no-residue standard for a plement the no-residue requirement at a in effect offering another approach to compound. Finally, some comments in­ time when that procedure, and similar establishing the operational zero for car­ dicated that, although the logistic and procedures, as well as the relationship, cinogenic residues. The Commissioner angle distributions have been used in between test-animal experience and concludes, however, that an approach biological sciences, there is no indication human risk, are under active and in­ that contemplates consideration of the that either one provides advantages over tense scientific study. He therefore has benefits of use of a sponsored compound the probit (Mantel-Bryan) or the linear concluded that a review of this decision in defining the no-residue standard is in­ distribution, and that, therefore, neither shall be undertaken in 2 years, and any compatible with the anticancer provi­ was appropriate for regulatory purposes. appropriate modifications in the regu­ sions of the act. Some comments favoring the Mantel- lation will then be initiated. 4. Modifications and restrictions on the Bryan procedure argued that it has a 3. Time-to-tumor and other consid­ Mantel-Bryan procedure-^(a) Expres­ theoretical rationale which is probably erations. Several comments contended sion of dose level. Several comments ad­ relevant to the carcinogenic action of that the proposal was deficient because dressed the adjustments the Commis­ chemical agents. A similar argument was it did not address the time-to-tumor sioner proposed to make in the “safe” made by some of the comments favoring aspects of chemical carcinogenesis. Some level of Mantel and Bryan derived from the linear extrapolation. These com­ comments pointed out that Albert and the experimental animal data in order to ments also contended that the linear ex­ Altshuler have developed preliminary establish an appropriate value for man. trapolation has the public health advan­ statistical relationships between low Some comments stated that adjustments tage of being the most conservative of all levels of carcinogen exposure and time for differences in food intake between procedures. experimental animals and man inap­ of tumor manifestation. It is the view of (b) Limitations in available proce­ these authors that characterization of propriate when dealing with carcinogens. dures and choice of procedure. The Com­ carcinogenic potential on the basis of The comments stated that such adjust­ missioner has extensively reviewed the incidence alone is not appropriate, be­ ments would assume erroneously that all known procedures that may be used to cause it ignores the life-shortening toxic materials have the same mode of derive an operational definition of the aspects of carcinogenesis. action on a body weight basis. They fur­ no-residue standard of the act from ani­ ther suggested that the relationship mal carcinogenesis data. This review has The Commissioner generally agrees should be expressed in terms of concen­ persuaded him the same scientific and with these comments. He is faced, how­ tration in the feed of the test animals technological limitations are common to ever, with a dilemma similar to that and in the food of man when the diet in all, Specifically, because the mechanism presented by the choice of statistical dis­ both cases is consumed ad libitum, other of chemical carcinogenesis is not under­ tributions. While statistical analyses than on an amount-per-body-weight stood, none of these procedures has a based on incidence have been subjected basis. Other comments argued that the fully adequate biological rationale. All to the scrutiny of use, the time-to-tumor conversion of animal data to man should require extrapolation of risk-level rela­ relations developed by Albert and be based on surface areas. tions from responses in the observable Altshuler have not. For this reason, the The final regulations specify that car­ range to that area of the dose-response Commissioner concludes that the basis cinogenicity tests shall be conducted with curve where the responses are not ob­ for extrapolation prescribed in the regu­ the test compound’s concentration m the servable. Matters are further compli­ lation shall be only incidence statistics, diet of the experimental animals heia cated by the fact that the risk-level but the agency will initiate a review of constant throughout the study. And the relations adopted by the various proce­ the matter of time-to-tumor statistics “ safe” level derived from the moamea dures are practically indistinguishable in 2 years and consider the desirability Mantel-Bryan extrapolation of test-ani­ in the observable range of risk (5 per­ and practicability of providing for their mal data shall be expressed as a concen­ cent to 95 percent incidence) but diverge consideration. tration in the total diet (weight of com­ substantially in their projections of One comment stated that “ effects pound/weight of total diet) of risks in the unobservable range. Finally, produced at higher dose levels * * * are animals and shall be directly applied ^ the Commissioner concludes, no proce­ useful for delineating the mechanism of the “safe” level forth e total diet of man- dure is intrinsically more conservative action, but for any material and ad­ The Commissioner concludes that tne than any other; the conservatism of any verse effect, some dose level exists for arguments for conversion based on sur­ face areas or on intake per unit ofboay procedure depends entirely upon the man or animal below which adverse ef­ weight have little basis. The comments restrictions and modifications imposed. fects will not appear.” The comment FEDERAI REGSÏE", VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 RULES A N D REGULATIONS 10421 provided no evidence that these concepts tally observed region. In such a case, cally compatible bioassays will be used are applicable to low-dose chronic expo­ the procedure adopted would be ultra­ for analysis. sures. The surface area concept is based conservative. However, it is not possible (e) Level of risk. The proposal sug­ on experience with short-term, high-dose to know the nature of the true slope in gested that an accepted level of risk for studies. Furthermore, measurements of the unobservable region, and the agency test animals, and thus for man, could be surface area are crude. Finally, surface must have a high degree of confidence 1 in 100 million. Many comments argued area and body weight will vary, as will that the maximum projected risk is that this level of risk was unnecessarily food intake per day, throughout the above the actual risk. conservative in light of the many other chronic study, thus requiring constant (d) Spontaneous tumor rates andcumulative, conservative restrictions al­ adjustments of dose. data combination. In the proposal the ready imposed by the regulations. For Until evidence is compiled demonstrat­ Commissioner recognized certain limit­ the reasons set forth below, the Commis­ ing that there is a more appropriate ing features that are common to all ex­ sioner has concluded that this level of means of conversion from experimental trapolation procedures, including that of' risk is unduly limiting without substan­ animal to man with respect to chronic Mantel and Bryan. These limitations tial Compensation in terms of public exposure and carcinogenic manifesta­ concern the rate of tumor incidence in health. tion, the Commissioner will assume that the control groups of animal bioassays As the level of risk is decreased, the the animal is the integrator throughout and the selection or combination of data number of animals that are required in its lifetime of any observed response to from different experiments. Since pub­ each test to bring the lowest limit of the a fixed concentration in the diet: The lication of the proposal, Mantel and co- assay’s measurement derived from a no- Commissioner has thus adopted the workers2 have developed procedures to carcinogenic-response test into the direct conversion approach (the “safe” deal with these issues. The Commissioner range of current analytical technology level in parts per million, parts per bil­ sees merit in these improvements and vastly increases. Thus, the time and re­ lion, etc., of the diet of the experimental has adopted them in the final regula­ sources that are necessary to plan, per­ animals directly applied to the diet of tions. . form, and evaluate the test before sub­ man), which is the most conservative, as In the original procedure published by mission to the agency in proper form in­ well as most practical, of the approaches Mantel and Bryan, the tumor incidence crease enormously. This in turn increases considered. attributable to a given level of a chemi­ the potential for interference from ir­ (b) Degree of data confidence. The Commissioner disagrees with comments cal carcinogen was measured as the dif­ relevant variables or intervening forces. ference between the upper 99 percent Then the amount of agency resources that characterized the proposal’s require­ confidence limit of the observed response that must be committed to evaluate the ment for 99 percent confidence intervals of test animals and the lower 99 percent data also increases almost geometrically. as another in a series of unnecessarily confidence limit of the observed response Finally, all these additional factors pro­ conservative assumptions. Confidence in­ of control animals. The effect of this pro­ vide only a minor incremental increase tervals characterize the quality of experi­ cedure on the derived “safe” level is in the degree of confidence in any deci­ mental measurement. The Commissioner concludes that a high degree of confi­ minor when the tumor rate in control sion that must be made on the results of dence should be demanded for decisions animals is low; however, when the con­ these chronic toxicity tests. Conse­ respecting carcinogens. He therefore has trol animals exhibit a high rate of spon- quently, the final regulations establish adopted the 99 percent level of confi­ toneous tumors, the effect of the pro­ the maximum risk to be used in the Man- dence, and the final regulations require cedure is far more pronounced. The im­ tel-Bryan calculation as 1 in 1 million. that all calculations based on experimen­ proved procedure published by Mantel et The following clarifications of the mean­ tal observations shall be made from or al.2treats the rate of spontaneous tumors ing of" the 1 in 1 million risk level dem­ with the 99 percent confidence limits. as an additional statistical parameter, onstrate why the Commissioner believes (c) Slope used for extrapolation. The which it is, and thus resolves this that such a risk level can properly be problem. considered of insignificant public health proposal would have required that extra­ polation be made with the lower 90th In many instances, the male and fe­ concern. male animals of the same strain may ex­ (i) The risk level of 1 in 1 million is a ' percentile of the observed dose-response curves. Numerous comments stated that hibit significantly different responses to risk level for the entire lifetime of an the extrapolation should be performed a compound. It is also apparent that the individual. responses of different strains and species (ii) This lifetime risk is the maximum, with a slope of one, as proposed by Mantel and Bryan. may be similar. It is always desirable to and therefore unlikely, human risk level.' make maximum use of available infor­ Because of the series of conservative as­ The Commissioner agrees with com­ mation by appropriate combination of sumptions built into the modified Man- ments that suggested that use for extra­ different data sets however, but prudence tel-Bryan procedure and into the deriva­ polation of the observed slope of the ex­ must govern the process of selecting and tion of the final “safe” level (see para­ perimental dose-response curve could combining data. Combining different graph V.D., below in this preamble), the underestimate public risk, and has modi­ data sets increases the number of ani­ most likely human risk level will be sev­ fied the regulation to call for a maximum slope of one. This requirement affords a mals used in the analysis and therefore eral orders of magnitude less than this high degree of confidence that, regard­ increases the confidence in the results. maximum. i Yet, in many instances, different data (iii) The 1 in 1 million lifetime risk less of the actual configuration of the dose-response curve in the unobservable sets contain different types of informa­ level assumes that an individual will con­ region, the maximum projected risk will tion. Mantel et al.2 discuss the informa­ sume maximum residue levels every day be higher than the actual risk. tional aspects of data combination with over a lifetime. respect to pooling data from different (iv) The use of this procedure for esti­ If the experimental dose-response experiments and from different doses. mating acceptable level is based on the curve exhibits a slope that is less than The Commissioner agrees in principle assumption that the only risk to the one, it is possible that this slope charac­ with most of their conclusions; neverthe­ human population is that from residues teristic may also prevail in the unobserv­ less, he anticipates that situations will of the sponsored compound, not from able region. To maintain the conserv­ arise where the evidence in support of such intervening causes as disease or atism of the procedure, in such situa­ combining or not combining data will be accidents (e.g., the average risk of fatal­ tions, the regulations require that the equivocal. Therefore, he concludes that ity by motor vehicle accident per year extrapolation be performed with the the statistical and biological evaluation is approximately 1 in 4,000). Because the shallower slope. The Commissioner rec­ of data will determine which data sets, population is constantly at risk from a ognizes that there may be weak carcino­ if any, will be appropriate for pooling. wide range of factors, however, any in­ gens whose actual dose-response curve Where there are significant statistical crement of increased risk associated with slope may be relatively steep at the lower and/or biological differences in the ob­ exposure to residues of multiple com­ levels of response, with a plateauing (i.e., served responses, only subsets of data pounds is at most in the vanishingly very shallow slope) in the experimen­ representing statistically and biologi­ small range. FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 10422 RULES AN D REGULATIONS D. DERIVATION OF THE LEVEL OF TOTAL upper allowable limit in man’s diet and The final regulations use the symbol RESIDUES OF CARCINOGENIC CONCERN in any component food in the, human Sm to represent the level of total residues W H IC H CAN BE TAKEN AS SATISFYING THE diet. These comments argued that this of carcinogenic concern that can be op­ NO-RESIDUE REQUIREMENT OF THE ACT limit should not be raised by considera­ erationally defined as satisfying the no­ As explained in the previous section, a tion of-intermittency of consumption of residue requirement of the act for spe­ potential residue level corresponding to a particular foods or of the proportion of cific tissues. If, for example, a particular risk of 1 in 1 million in test animals (i.e., the total diet represented by an individ­ animal drug used in cattle were found the “safe” level derived from the modi­ ual food. They suggested that individ­ to have an So of 10 parts per trillion, the fied Mantel-Bryan procedure) can be uals who consume above average assay required for approval of the drug considered the level that represents no amounts of food would be exposed to would have to be capable of reliably measuring residues of 30 parts per tril­ significant carcinogenic burden in the above average, and thus possibly harm­ lion and above in muscle tissue. total diet of man. This level is assigned in ful, levels of residues. Further, these the final regulations the symbol Sn and, comments contended that the act does F. OTHER POSSIBLE ADJUSTMENTS expressed -as a fraction in the total diet not provide a distinction between peo­ Several comments urged that the reg­ (i.e., parts per billion, parts per trillion) ple who consume average diets and peo­ ulation should not provide for adjust­ of the test animals, shall be directly ple who consume above-average quan­ ments for the degradation of residues in taken as the potential undetected residue tities of exotic foods;- both groups are food under normal conditions of storage level that is safe in the total diet of man. entitled to equal protection. They argued and cooking. Others suggested that such that adjustments for exposure frequency In some cases, residues in addition to based on food consumption patterns as­ data should not be required but should the sponsored compound itself will have sume that continuous long-term expo­ be taken into account when available. been selected for carcinogenicity testing. sure to a carcinogen precedes the devel­ Still other comments expressed the fear In these instances, “ safe” levels will be opment of cancer. that such data would be used to dilute derived for each of the compounds that Many other comments urged that ad­ the conservative intent of the regulation; have undergone testing. The compound justments should be made based on the they argued that the term “normal con­ exhibiting the lowest value for the “safe” proportion of the specific food in the dition of storage and cooking” would level is the most potent carcinogen of total diet and the frequency of exposure. be difficult to define, and it might reduce those tested and constitutes the greatest These comments generally favored the protection in situations where actual potential carcinogenic threat among the use of food consumption data, so that storage and food preparation practices residues. The Commissioner will, accord­ the degree of conservatism was more did not approximate experimental con­ ingly, choose the smallest value of the uniformly applied taking into account ditions. Finally, some comments sug­ various “safe” levels, assign to it the the relationship of the particular food gested, generally, that such studies symbol So, and assume that it represents to the total diet. should be required only when there is the potential carcinogenic burden that The Commissioner disagrees with the reason to believe that such information may result from the administration of a contention that no adjustments should would assist in protecting public health. sponsored compound to food-producing be made for factors of exposure. Sec­ The Commissioner agrees that the pa­ animals. Additionally, because other tion 512(d)(2)(A ) of the act requires rameters appropriate to such studies tested residues may have exhibited car­ have not been defined, and he has de­ cinogenic properties (albeit less potent) the Commissioner to consider the prob­ leted from the final regulations refer­ and still other, untested residues may able consumption of a drug and of any ences to postslaughter residue degrada­ represent carcinogenic risks, the So will substance formed in or on food because tion studies. When there is reason to be­ be taken as the sum of the levels of all of of its use. Analysis of carcinogenesis data lieve that storage conditions or food the residues. Potential residues in the provides S0. The no-residue standards of preparation methods" might lead to the total human diet cannot exceed So if that the act has been defined as satisfied when formation Of potentially toxic residue diet is to bear no significant carcinogenic the sum of the levels of all potential un­ products, however, the Commissioner risk to man. The only residues that can detected residues of the sponsored com­ will require appropriate special investi­ be excluded from the sum of residue pound (excluding only those that have gations. Petitioners are encouraged to levels are those that have been unambig­ been found to be noncarcinogenic) would explore the postslaughter stability of uously shown to be noncarcinogenic. not exceed S„ in the total diet of man. Because products derived from food-pro­ residues. Experience has shown that res­ Although it will already be apparent to ducing animals do not constitute the idue stability can be a complicating fac­ the attentive reader and to the trained total human diet, it is therefore appro­ tor in studies for the validation of assays scientist, it bears reiteration at this point priate that So be corrected for probable for dosed tissues. The Commissioner en­ that So (or any figure derived on the human consumption of specific tisues. courages research in this area but until basis of adjustments described below) The Commissioner agrees, however, that appropriate information can be reliably does not represent a level of residues any adjustments must be conservative incorporated in the food safety decisions, “ approved” for introduction into the to assure that all segments of the popu­ such data will not be Used to liberalize human diet. The purpose of these regula­ lation are protected. the requirements of the regulations. | tions is to establish criteria for the evalu­ The Commissioner 'has consulted G. CONSIDERATION OF OTHER RELEVANT ation of assays for the measurement of available data on food consumption pat­ SAFETY FACTORS carcinogenic animal drugs. These criteria terns in the United States, and concludes must include some lowest level of reliable that muscle tissue and eggs can be con­ Originally, the Commissioner proposed measurement that an assay is required sidered, conservatively, to each con­ that the Mantel-Bryan calculation be to meet. In defining a level of potential stitute one-third of the total daily hu­ modified to account conservatively for residues that can be considered “safe,” man diet. Since milk can constitute the drug use patterns, e.g., the administra­ therefore, the Commissioner is establish­ total daily diet of any individuals (e.g., tion of a drug in the treatment of dis­ ing a criterion of assay measurement infants), no adjustment will be made eased animals. Comments demonstrated that, if it can be met for a compound, will for this commodity. Adjustments for fre­ that disease incidence does not occur assure that any undetected residues re­ randomly within a geographic area or sulting from the compound’s use will not quency of exposure for tissues other than within specific animal groups. Although increase the risk of human cancer. muscle, milk, or eggs (i.e., kidney, liver, a disease may have an overall incidence etc.) will be considered only if the pro­ of only 10 percent, the affected group E. CORRECTIONS FOR FOOD INTAKE portionate levels of potential undetected may be located in a single area. There­ Several comments argued for and oth­ residues in such other tissues, compared fore, the Commissioner is unable to con­ ers opposed further adjustments based on to muscle, are such that intake of muscle clude that evidence exists, or other safety tissue on days when other tissues are factors are available, to permit him t patterns of food consumption. Some not being consumed provides an insig­ comments contended that the “safe” nificant contribution to the total expo­ calculate the effect of such drug usage, level of Mantel and Bryan in the animal sure to residues (i.e., S0 is never exceeded and he has deleted this provision from diet should be directly applied as the in the total diet of human beings). the regulation. FEDERAL REGISTER, VOL, 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 RULES AN D REGULATIONS 10423 VI. M e t a b o l ic S t u d y t o S e l e c t M a r k e r tissue under examination. Residues that b . a p p l ic a t io n : d ata d e v e l o p m e n t and R e s id u e and T arget T is s u e CALCULATION OF Rm are potential markers will be present at a. th e concept 1. Marker residue. Application of the a known concentration (Rm) at this same Before he can approve the use of a concepts of márker residue and target time ( T l of Plate I ) , and in a definite sponsored compound, the Commissioner residue requires an experimental deter­ (although perhaps rapidly changing) jnust assure that a practical and reliable mination of the quantitative relation­ quantitative relationship to the total res­ assay is available that can measure car­ ships of residues that might serve as idue (Plate I I ) . markers (including any which have def­ With the quantitative relationships cinogenic residues at the level which dis­ criminates safe from unsafe food, i.e., the initely been shown to be noncarcino- established, it will be possible to select assay must be capable of determining genic, since theoretically one of these one of the residues as a marker. Ordi­ when Sm is exceeded in each edice tissue. might be selected as marker residue) narily, the residue selected will have the One approach to this problem would be to the total residue in each of the various following characteristics: (i) It will rep­ to require assays that can. be used to edible tissues which might serve as tar­ resent at least 10 percent, and usually a measure every residue in each of the get tissues. Further, because these rela­ great deal more, of the total residue bur­ various edible tissues. Because the num­ tionships change with time, the levels of den -at the time when the total residue ber of residues in edible tissues and the potential marker residues in the potential was depleted to Sm; (ii) it will be stable, number of tissues can sometimes be target tissues must be measured over easily isolated and characterized, and large, it is unlikely that such an ap­ time, and tissue concentration-time pro­ susceptible to manipulation for assay de­ proach could be put to practical use. The files must be constructed. These deple­ velopment and implementation; (iii) it Commissioner has determined that an­ tion profiles will be derived irom mea­ will be undergoing relatively rapid other approach is possible that is far surements made in target animal tissues change- in concentration at the time the more practicable and sacrifices no prin­ after cessation of exposure to the spon­ total residue burden is at or near Sm ciple of safety. This alternative approach sored compound. Finally, because the re­ (i.e., a change in its concentration will centers on the concepts of a marker resi­ sults of carcinogenicity testing have been be a sensitive indicator of the time when due and a target tissue. used to set limits for total potential un­ the total residue burden has depleted detected residues in each of the individ­ below Sm. While other considerations A marker residue is a residue whose ual edible tissues, the depletion profiles may enter into the selection of a marker level in a particular tissue is in a known must include measurements of the total residue, these three will ordinarily be relationship to the level of the total resi­ residue in each potential target tissue to most important. due of carcinogenic concern in all edible levels at least as low as the Sm appropri­ There may be instances in which no tissues and which, therefore, can be ate to the tissue. Additionally, deletion single residue can adequately fulfill the taken as measure of the total residue of profiles for one or more potential marker requirements which a marker residue interest in the target animal. Once a residues must be constructed and include must meet. In such instances, it may be marker residue is selected and its quanti­ measurements of levels of residues cor­ necessary to select some combination of tative relationship to the total residue is responding to the times when the total residues which, taken together, can rep­ determined, it is possible to calculate a residue has reached Sm (Plates I and II resent the total residue burden. It should level,.for purposes of these regulations, set forth in § 500.89 (31 CFR 500.89).) be noted that a marker residue can be a Rm, which is that level of the marker residue that must not be exceeded in a Part III of this preamble describes the compound which is not a carcinogen, but selected tissue (the target tissue) if the requirements for the study of the meta­ is an unambiguous indicator, in the man­ total residue of carcinogenic concern in bolic fate of a sponsored compound in ner already described, of the presence or the edible tissues of the target animal is target animals. Although the purpose of absence of carcinogenic residues. this earlier metabolic study is to provide 2. Target tissue. Selection of a target not to exceed So. The marker residue can be the sponsored compound or a-ny of its information for selecting - residues for tissue requires a comparison of the deple­ carcinogenicity testing, the same prin­ tion profiles for each of the edible tissues metabolites, or a combination of residues for which a common assay can be ciples and requirements are applicable (Plate I set forth in § 500.89). A target developed. here and must be followed in acquiring tissue will be selected based on assurance the information necessary to construct that the absence of the marker residue at The target tissue is that tissue in depletion profiles. However, to meet the or above Rm assures that carcinogenic which the absence of the marker residue depletion profile requirements pre­ residues are absent from the slowest de­ at R m or above can be taken as confirma­ scribed by the regulations, a second pleting tissue, and thus that the entire tion that the safe residue level, Sm, is metabolic study of the sponsored com­ animal is free of carcinogenic residues: not exceeded in any of the edible tissues. pound in the target animals may be When a compound is to be used in When a marker residue and a target tis­ necessary. This second and possibly milk- and egg-producing animals, milk sue are selected, a practicable assay must more refined study may require the and eggs will be target tissues in addition be developed that can reliably measure use of a larger number of animals, to one tissue selected as the target tis­ the marker residue in the target tissue at for it will be necessary to determine the sue to represent the depletion of residues levels at least as low as R m, and condi­ total number and the quantities of res­ in all of the edible carcass, in such cases, tions of use of the sponsored compound idues, not only at two points in time, but it may be necessary to select a marker must be established that assure that, in at several appropriately spaced time in­ residue for milk or eggs that is different practice, the potential marker residue tervals starting immediately after cessa­ from the marker residue selected for the level in the target tissue does not exceed tion of exposure and continuing until the target tissue representing the edible ■Rm. residues in each of the potential target carcass. When it is determined, using as assay tissues has reached a level corresponding 3. Calculation of R m. The level of the demonstrated to be capable of reliably to a total residue level of the appropriate marker residue which is present in the measuring the marker residue in the tar­ Sm (e.g., for meat, milk, or eggs) . If the target tissue at the time ( T l ) when the get tissue at levels at least as low as initial metabolic study were done with sum of the levels of the residues in the Rm, that there is no such residue at levels the degree of precisión required to select slowest depleting tissue (excluding any or above Rm, it can be concluded that a marker residue and a target tissue, of residues that have definitely been shown the no-residue standard of the act has course, it need not be repeated. « to be noncarcinogenic) is equal to Sm for been satisfied for all edible tissues in the Selection of a marker residue will be that tissue, is the Rm for that marker res­ animal under examination. Conversely, based on examination of depletion pro­ idue. The depletion profiles will be used to if the market residue is found in target files. Generally, there will be some time select Rm (Plate II set forth in § 500.89). hssue at levels equal to or greater than at which the sum of the levels of the in­ For example, assume (i) that liver is Rm, all edible tissues must be considered dividual residues of carcinogenic concern the target tissue of animal drug, P, in­ unsafe for human consumption. will fall below the Sm appropriate to the tended for use in cattle; (ii) that the FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 10424 ROLES AND REGULATIONS only residues of P are the parent com­ that normal background levels are not between administered compounds that pound, P, and a metabolite P,; (iii) that exceeded in the animal when the animal can cause changes in normal back­ Tl is 3; (iv) that Sm for the sponsored is slaughtered. The regulations also re­ ground levels of potentially carcinogenic compound is 29 parts per trillion; and (v) quire the development of practical assays endogenous compounds, which can un­ that the following is a chart of the deple­ for measuring endogenous compound ambiguously be defined, and those ad­ tion profile of the drug. levels. ministered compounds that do not affect Several comments on this segment of such levels. [In parts per trillion] the proposal expressed concern over the Essential nutrients are not included in meaning of the term “ endogenous com­ the definition of the classes of com­ T im e T o ta l residue P P> pounds” and questioned how such com­ pounds that will be regulated by these burden pounds are to be distinguished from “ ex­ regulations. In a strict sense, essential ogenous compounds.” Others questioned nutrients are not endogenous. Although 0 100.0 75 .0 25 .0 whether the former term includes chemi­ present in the tissues of animals and 1 65.4 44 .6 • 21.8 cal derivatives (estradiol benzoate) of required for growth and health, they are 2 4 2 .0 26.3 17.3 3 29.0 15.0 14.0 bona fide endogenous compounds (estra­ not produced by the animals and must 4 21 .0 9 .0 12.0 diol) or essential nutrients (some amino be supplied from external sources. These 5 16.0 5 .0 10 .0 acids, minerals, vitamins). Comments features place essential nutrients in a also expressed doubt about the distinc­ distinct class of “required exogenous In this case, before the drug can be ap­ tion between endogenous and exogenous compounds,” which must continue to be proved for use, the petitioner must de­ compounds in cases where the adminis­ regulated in a unique manner. Deter­ velop an assay that will satisfy the eval­ tered compound can be metabolized to mination of the allowable use of essen­ uation criteria in liver for either P at residues of both classes. Some comments tial nutrients must reflect the nutri­ least as low as 15 parts per trillion or Px also argued that all externally adminis­ tional requirements of the target ani­ at least as low as 14 parts per trillion. tered compounds should be considered mals. When used according to label di­ Because P is depleting faster than Px, exogenous, as the true meaning of the rections, essential nutrient supplements when the total residue burden is 29 parte term implies. should restore but must not exceed the per trillion, P may be the preferred com­ Other comments suggested that en­ essential nutrient levels found in natural pound to select as the marker residue dogenous substances of interest be sub­ foods adequately sustaining normal since it does provide a more accurate as­ jected to toxicological testing and toler­ growtlT of healthy animals. Further­ sessment of when the total residue bur­ ances be set if such substances are found more, the levels of animal essential nu­ den reaches 29 parts per trillion (Sm). to be* not carcinogenic. Some expressed trients found in human food derived Another example is provided in Plate n doubt that available technology could from supplemented animals must not ex­ in § 500.89. meet the requirements of the proposed ceed the levels in food derived from nor­ regulation. They contended that the mal healthy animals fed a nutritionally VIII. S ponsored C ompounds A ffecting terms “ normal conditions of use” and adequate natural diet. P ools of C arcinogenic or P otentially “normal background levels of endogenous C arcinogenic S ubstances E ndogenous compounds” would be either extremely C. GENERAL procedures to T arget A nimals If available information shows a difficult or impossible to define. The Com­ a. applicability of n o - residue missioner recognizes the difficulty of the sponsored compound might affect pools requirement task, but concludes that administered of potentially carcinogenic endogenous compounds that increase the naturally substances in target animals, and cause The act requires that in making food occurring level of potentially carcino­ an increase in the level of such sub­ safety decisions, the Commissioner take genic endogenous compounds present stances above the level considered to be into account all substances formed in or special problems of control which the safe by the criteria of these regulations, on food by the administration of spon­ regulation must address and resolve. the petitioner shall be required to dem­ sored compounds to food-producing ani­ onstrate whether or not these suspicions mals. It is well recognized that: (i) Sev­ B. DEFINITIONS are true. The need for, and the depth eral substances endogenous to food-pro­ An endogenous compound is any com­ and breadth of, studies required to dem­ ducing animals are suspect or proven pound that is metabolically produced by onstrate this effect must be specified on carcinogens; (ii) in any given animal and is present in untreated target ani­ a case-by-case basis. species or breed, the size of pools of such mals. Any sponsored compound that is The procedure required is fourfold: endogenous substances vary widely with found to increase the normal background (i) Establishment of normal background such attributes as sex, age, lactation, levels of a potentially carcinogenic en­ levels (or “ norm” ) of the endogenous state of estrus, pregnancy, geographic dogenous compound shall be subject to compound of carcinogenic concern in the location, and animal husbandry prac­ these regulations regardless of how the target animals; (ii) determination of tices; and (iii) man has had sustained increase is brought about. the effects of the sponsored compound exposure to such endogenous substances For instance, estradiol benzoate, which on the norm; (iii) establishment of safe for centuries. Whether normal levels of is by the above definition clearly not an conditions of use of the sponsored com­ human exposure to these substances are endogenous compound, is metabolically pound by demonstrating how the com­ responsible for human carcinogenesis is converted to the endogenous compound, pound can be used in a way that assures unknown, but the Commissioner main­ estradiol, and may thus cause an in­ that the norm is restored in the target tains that the use of drugs that can crease in normal background levels of animals before slaughter; and (iv) de­ cause an increase in human exposure to that substance. Estradiol may itself be velopment and validation of a practical such compounds has the potential of in­ ' administered, possibly again causing assay to measure the endogenous com­ creasing the risk of human carcinogehe- target animal pools of estradiol to in­ pound at levels determined to be normal. sis.~'The use of such drugs must there­ crease above background. Finally, a The regulations specify how each of fore be controlled. sponsored compound may indirectly these steps is to be accomplished. In dealing with potentially carcino­ cause an increase in tissue levels of es­ D. SPECIFIC STEPS REQUIRED genic endogenous compounds, the pro­ tradiol by affecting any number of hor­ posal declared that the intent of the no­ monal regulatory systems in the target The petitioner shall first be required residue requirement of the act is the animals. While in each of the above cases to determine experimentally the normal maintenance of the normal human die­ the cause of the increases in normal background levels, or norms of the po­ tary content. Thus, the regulations re­ background levels of estradiol was dif­ tentially carcinogenic endogenous com­ quire the determination of the effects of ferent, the result was the same. And it pounds of concern in untreated target sponsored compounds on the normal is the result that must be monitored and animals. A norm must be specific for the background levels of potentially carcino­ controlled. It is thus of little use to dis­ target animals and for the intended con­ genic endogenous compounds. If a com­ tinguish between “ endogenous” and ditions of animal husbandry, and must pound is found to increase such levels, “ exogenous” sponsored compounds. include the effects of age, sex, breed, ana conditions of use must be established so Rather, it is useful only to distinguish geographic location. The sponsor shall FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 RULES A N D REGULATIONS 10425 provide the norm in the form of a curve as to other compounds covered by these VIII. R egulatory A s s a y : E valuation of cumulative frequency distribution of regulations. C riteria and A pproval P rocess untreated target animals over the ob­ Accordingly, the Commissioner has re­ a . introduction served levels of the endogenous com­ vised the regulations, which as proposed, pound. The curve shall also include 99 would have established the lowest limit The Commissioner can approve a percent confidence bounds (Plate III ap­ of reliable measurement at the 99th sponsored compound for use in food- pearing in § 500.89). percentile of the norm. As the comments producing animals only if the intended The median and shape of the frequency noted, an assay that can measure only use of the compound does not result in distribution must be known so*that shifts the upper 99th percentile would not be the accumulation of potentially carcino­ in the norm can be measured. For this able to detect many shifts in the norm, genic residues in edible tissues and if an reason, the assay used to determine a which is its primary function. The final assay is available that can reliably meas­ norm must yield values for the endoge­ regulation^ require an assay capable of ure such residues at and above the Rm. nous compound different fremi zero for at a lowest limit of reliable measurement The assay must also be suitable for moni­ least two-thirds of the untreated target of the 33d percentile of the norm, which toring food from animals administered animals. This latter requirement will per­ will readily detect any shifts in the me­ the compound to prevent food from mit calculation of the median and fre­ dian or mean of the norm. Actual moni­ reaching the marketplace if it is adulter­ quency distribution with a high degree toring, which is performed by the Ani­ ated with potentially carcinogenic resi­ of reliability, while recognizing the prac­ mal Plant and Health Inspection Ser­ dues resulting from misuse of the com­ tical limits of technology. Morever, be­ vice of the United States Department of pound. cause the area of interest is that around Agriculture, may occur at or above the Several comments argued that the pro­ the median, the requirement does not 50th percentile of the norm but such posal would discourage the search for compel the petitioner to gather unneces­ monitoring will detect violative residues better assays, and that this was not in sary data since the values at the lower and detect significant shifts in the norm. keeping with the intent of the cancer end of the distribution are irrelevant. provisions of the act. Further, some com­ The sponsor shall then determine the F. ALTERNATIVE PROCEDURE ments contended that FDA should only effects of the sponsored compound on Comments contended that an alterna­ be concerned with the approval of assays the norm, and shall provide data on the tive to the foregoing procedure should be that avoid false negative results and that postexposure decay of any observed in­ available for regulating endogenous sub­ any detected residue should be investi­ creases in the norm. The norm shall be stances. It was suggested that a tolerance gated to determine its identity. Other considered restored when the distribu­ for an endogenous compound can be comments proposed that when more tion of values for the endogenous sub­ established, even at levels above the “sensitive” assay methods (i.e., assays stance of concern observed h i a group of norm, provided appropriate toxicity test­ with still lower limits of reliable measure­ treated animals is with 99 percent con­ ing on the compound is carried out and a ment) are developed, the assays should fidence the same as the norm. safe level can be established in accord­ only be used as screening tests and that The norm, as defined,, takes into ac­ ance with parts IV through VII of the the required “sensitivity” (or safe level) count those variables that affect back­ preamble and §§ 500.84 through 500.90 derived from the statistical analysis of ground levels. The final regulations thus (21 CFR 500.84 through 500.90). Sepa­ animal carcinogenesis data should be re­ attempt to respond to those ' comments rate mechanisms with distinctly different tained for regulatory action. These com­ suggesting that “normal background rationales have been developed to meas­ ments arguedwarrants that unless new biological levels” would be difficult to define. ure compliance with the no-residue information a change in assay “ sensitivity,” new regulatory assays E. ENDOGENOUS MARKER RESIDUE; CALCULA­ standard of the act for endogenous and should not be adopted. Comments stated TION OF Rm exogenous compounds. that the efforts to increase “sensitivity” If the norm of an endogenous sub­ As noted earlier, for exogenous com­ had to be balanced by the need to assure stance of carcinogenic concern can be pounds the regulations require develop­ the practicability of an assay for reg­ increased by the administration of a ment of an assay with a minimally ac­ ulatory use, the desirability of avoiding sponsored compound, the endogenous ceptable lowest limit of reliable meas­ false negatives, and the importance of substance can become an endogenous urement at or below the level needed to reproducibility of results. These com­ marker residue, i.e., its presence above assure that any undetected residues pòse ments implied that, given these counter­ certain levels can be considered an in­ essentially no increased risk of cancer vailing concerns, more “sensitive” assay dicator of potentially carcinogenic resi­ in the population. Moreover, should a methods should not be adopted because dues in food. Approval of the use of such new" assay with a lower limit of reliable the proposed statistical treatment of car­ a sponsored compound shall be contin­ measurement be developed at a later time cinogenesis data is sufficiently conserva­ gent upon the petitioner’s furnishing that will satisfy the essay evaluation tive to protect the public health. data demonstrating that the norms are criteria, that assay will be adopted by Still other comments suggested that restored in the target animals before the Commissioner. On the other hand, more practical methods should be ap­ slaughter, and upon the availability of a the method for measuring compliance proved for purposes of screening which Practical assay that can reliably meas­ with the no-residue standard for an en­ would accept a low level of false positives ure the endogenous marker residue in dogenous substance is based on calcula­ with a high degree of assurance that false target animals. Such a regulatory assay tion of the norm, a calculation that is negatives would not occur. Confirmatory must be capable of measuring the marker independent of and probably unrelated methods, which would undoubtedly re­ residue at the level, Rm, corresponding to the lowest limit of an appropriate as­ quire more time for cleanup of samples to the 33d percentile of the norm (Plate say’s reliable measurement. The Com­ and greater instrument specialization, HI set forth in § 500.89). missioner concludes that monitoring of should then be used to provide evidence changes in the norm is the best avail­ that can withstand legal scrutiny. Some The Rm for an endogenous marker resi­ able method for regulating the use of comments stated that certain reagents due derives from an entirely different compounds that may increase pools of and instruments required for an assay conceptual approach to safety than that potentially carcinogenic endogenous may not be readily available because of used for the derivation of an Rm for an substances, and rejects the suggestion their unique applicability. They suggested OjTOgeiioufc marker residue. To monitor that a tolerance for such compounds be that the regulation be changed to allow m * uin norm> the Commissioner established. The Commissioner would be sponsors to supply such items when must be able to measure the median and receptive to suggestions for alternative necessary. One comment pointed out that Jr determine the shape of the distribu- mechanisms of control, but until an ac­ the word “control” in the phrase “ well- S®?- An assay capable of measuring the equipped analytical control laboratory”- J r Percentile of the norm, and levels ceptable alternative is identified, all connotes a highly specialized laboratory cove this, provides the required analyti- such compounds will be required to com­ which is unlikely to have the necessary i capability. The same assay evaluation ply with the requirements imposed by instrumentation for residue analysis, and iteria apply to endogenous compounds §§ 500.89 (cy through (e) and 500.90. hence urged that it be deleted. FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 10426 RULES AN D REGULATIONS Because the assays required by these A petitioner should also be satisfied D. FDA REVIEW regulations are to be used for regulatory that the assay meets all of the evalua­ The Commissioner will conduct a paper monitoring of residues of potential carci­ tion criteria and also that it is consistent review of a petitioner’s submission to de­ nogenic concern in human food, the with general principles of good analyti­ termine whether an assay complies with Commissioner concludes that rigorous cal practice before submittal for FDA the acceptability criteria. These regula­ criteria must be established for approval review. Past experience shows that a tions generally alert potential petitioners of these assays. Furthermore, a proposed petitioner’s failure to follow good ana­ to the applicable statutory standards and assay must be subjected to an objective lytical practices during initial assay criteria, which should permit a petitioner evaluation to determine if it meets the studies often results in interlaboratory to assess preliminarily the acceptability criteria. Only then can the Commissioner failure even though the initial results of an assay before filing a petition, and assure that an assay will provide a reli­ may appear satisfactory during a paper thereby reduce the agency’s workload. able and practical monitoring device to review of the assay by FDA. A petitioner If on preliminary review an assay ap­ prevent violative residues in food. Many should assure that no results enter the pears to comply with the evaluation comments in essence contended that construction of an analytical curve when criteria, it will then be subjected to the more explicit criteria and evaluation it is known that the results were obtained interlaboratory assay validation study to procedures should be specified, and the using other than acceptable principles determine whether it is indeed a practi­ Commissioner concurs with these com­ of analytical practice. cable and reliable regulatory tool. Should ments. In addition to the spiked tissue tests, the initial review establish that the a petitioner must also submit data show­ assay fails to meet these criteria, the Any assay is characterized by a set ing the applicability of the proposed of attributes which determine its qual­ assay to target tissues taken from target petition will be denied. A conclusion that ity:. dependability, practicability, speci­ animals treated with the sponsored com­ an interlaboratory assay validation study ficity, accuracy, and precision. These pound (“ dosed” tissues). To validate the should be initiated, however, in no way regulations specify objective criteriar for assay, dosed tissue samples are required guarantees that a proposed assay will these attributes. À proposed assay must that contain the marker residue at a level be eventually approved. be shown to meet these criteria during approximating Rm. A standard curve E. ASSAY ATTRIBUTES AND ACCEPTABILITY study in a single laboratory and also in must also be submitted, constructed by CRITERIA interlaboratory study in government reg­ taking the marker residue of known ulatory laboratories. The latter require­ purity at different concentrations, deter­ An assay must meet the following at­ ment is essential, because the assays are mining the response, and plotting the tributes and criteria: to be used in several regulatory labora­ relationship. 1. Dependability. Dependability is the tories (FDA, USDA, and State labora­ attribute denoting the likelihood that the tories) , and the Commissioner must de­ c. SUBMISSION OF DATA proposed assay will yield no result be­ termine in advance that an assay will Agency resources for reviewing and cause of uncontrollable features inherent perform in more than one such labora­ validating assays are limited. The Com- in its design. Almost all assays will, on tory. The regulations specify that the * missioner therefore has established a occasion, fail to yield any result. Often interlaboratory validation study shall be precise format for submitting the data this occurs because of mishandling by carried out in those laboratories (USDA to support acceptance of an assay. It is a the analyst, but sometimes failure may and FDA) that will be using the method well-recognized principle, applied both be the result of some aspect of the assay in surveillance and enforcement pro­ by the courts and administrative agen­ itself that may have been inadequately grams. cies, that a standard format can be re­ studied and defined or that cannot be The steps in obtaining approval of an quired for pleadings, requests for licenses, controlled. For example, assays depend asay are: (i) Assay development and and other applications. This format may upon the availability of a standard study by thé petitioner to determine if also designate special types of informa­ against which measurements are com­ the assay satisfies the acceptability cri­ tion that must be contained in the sub­ pared. If the integrity of the standard teria; (ii) FDA review of the petitioner’s mission. Therefore, the agency will re­ depends on certain environmental fac­ study to determine suitability of the fuse to accept a petition or review an tors (e.g., purity of the solvent in which assay for evaluation in interlaboratory assay when the request for approval fails it is maintained, temperature, light in­ study; and (iii) interlaboratory valida­ to conform to the format outlined below. tensity, etc.) and these factors are tion study, again approval contingent 1. Assay description and petitioner’s understood, it may be possible to prevent upon satisfaction of acceptability cri­ evaluation. The petitioner must provide assay failure. If this dependence is not teria. a complete description of the assay to known, however, the assay may fail and, allow FDA to determine whether it is po­ depending on the sensitivity of standard B. SOURCES OF DATA TO SUPPORT tentially acceptable. Because this thresh­ integrity to the environmental factor of THE ASSAY old determination of acceptability will importance, may fail often. In this Data from studies of an assay using trigger an extensive interlaboratory val­ example, failure can mean a highly three types of samples are necessary to idation procedure, the Commissioner inaccurate result, assuming some frac­ support approval. The petitioner must concludes that the discussion must be tion of the standard’s integrity is re­ prepare samples of target tissue to which sufficiently rigorous to minimize waste of tained, or it can mean no result at all, known amounts of marker residue are agency resources. Therefore, the submis­ assuming complete loss of integrity. added (“spiked” tissues), and compare sion must discuss in detail: The Commissioner concludes that responses obtained from assays using (a) What equipment and reagents are assays used to monitor carcinogenic resi­ these tissues with responses obtained necessary; dues in food must be free of such uncon­ from assays of target tissues known to (b) How the assay is performed; and trollable features, and failure of a pro­ be free of marker residues (control tis­ (c) How the assay complies with the posed assay to yield results during the sues). In constructing an analytical dependability, practicability, specificity, petitioner’s assay development studies oi curve from these data and determining accuracy, and lowest limit of reliable interlaboratory validation study can be its 99 percent confidence limits (plot of measurement criteria prescribed in a cause for refusing to accept the assay observed response versus concentration § 500.90(d) (21 CFR 500.90(d)) and dis­ and for denying the underlying petition. of marker residue), as many samples as cussed under paragraph VHI. E. below in Accordingly, the regulations require a possible should be run, preferably by this preamble. petitioner to record and furnish all tne different analysts, for interlaboratory 2. Data. The data and worksheets, in­ information on, and provide an explana­ validation of the assay will eventually cluding spectrograms, chromatograms, tion of, runs of the developed assay that be required. The variability among dif­ etc., from the spiked tissue, dosed tissue, are begun, but never finished. ferent analysts can be determined at the and control tissue analyses are also nec­ 2. Practicability. The regulation under developmental stage and adjustments essary for the preliminary review of the § 500.90(d) (2) defines the practicability made before the assay is submitted for assay to determine whether it actually attribute as follows: FDA review. complies with the evaluation criteria. FEDERAL REG'i'TE“ , VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 RULES A N D REGULATIONS 10427 The assay shall be considered practicable of response or stimulus or to the nature tinction must be reproducible and capa­ only if it is suitable for routine use in a of the relationship between response and ble of supporting legal action when vio­ government regulatory laboratory. The time required to complete the assay must be con­ stimulus. Both of the latter criteria, lative residues of the sponsored com­ sistent with regulatory objectives (monitor­ which might also be considered aspects pound occur. ing, compliance, etc.). All supplies, equip­ of specificity, are central to good analyti­ To provide the necessary degree of dis­ ment, reagents, standards, and other mate­ cal practice. The regulations consider crimination, the regulations require that rials necessary to conduct the assay must be both the qualitative and quantitative the assay be capable of producing a re­ commercially available except that refer­ aspects and groups them together under sponse when the marker residue is pres­ ence standards may be supplied by the peti­ the general attribute of specificity. The ent in target tissue at or above Rm that tioner if they are not commercially available. Commissioner’s objective is to assure is, with 99 percent confidence, different The Commissioner will withdraw approval of any assay method and initiate regulatory that, whatever the observed response, it from the response in nontreated (con­ action against the sponsored compound, if is uniquely related to the marker residue trol) target tissue (i.e., the difference the petitioner breaches such a condition of both qualitatively and quantitatively. between the responses of control target -the compound’s approval. The establishment of an analytical curve tissue and target tissue containing the (not simply a standard curve, but one de­ An assay must possess no characteristics rived from actual measurements ob­ marker residue in target tissues at or that may counteract the purpose for tained on tissue samples containing above R m is, with 99 percent confidence, which it is developed. Accordingly, the known amounts of marker residue at dif­ greater than zero). The actual lowest Commissioner has established criteria ferent levels and from control samples) limit of reliable measurement, Lm, will be for practicability in terms that relate provides the means to determine whether determined by reference to the analyt­ specifically to the nature of the labora­ the responses produced by an assay are ical curve of the proposed assay; If the tories in which the assay will be used single-valued, as they must be if an assay determined lowest limit of reliable meas­ (i.e., regulatory laboratories where time is to be considered fully specific. Only as­ urement, Lm, of the proposed assay is at and availability of equipment and rea­ says that yield continuously increasing or below the R mas determined in accord­ gents are critical factors in their ability or decreasing analytical curves will sat­ ance with paragraph VI.B.3. or para­ to perform satisfactorily the mandated isfy the criterion of single-valuedness. graph VILE, of this preamble, this cri­ functions). Finally, the regulations require that terion shall be considered satisfied. This The inability to use an assay at a reg­ the assay contain a sufficient number of procedure tests the critical factor of as­ ulatory laboratory because a needed rea­ independent measurements utilizing in­ say precision. Thus, an assay that satis­ gent is not readily available or because dependent physicochemical principles to fies this criterion will provide a reliable excessive time is required to complete the assure specificity (i.e., the identity of the regulatory tool to enable the Commis­ assay presents potential risks to public marker residue must be confirmed). sioner to discriminate safe from unsafe health and cannot be sanctioned. Ob­ There may be many ways in which spec­ food. viously, some assays will require some ificity can be demonstrated experimen­ An assay that satisfies this criterion unique items, particularly reference tally. A petitioner may use highly sophis­ will often have a high signal-noise ratio, standards. The Commissioner agrees ticated research tools to demonstrate that although this ratio may be a function of with comments suggesting that as long a proposed assay is specific in the senses the fluctuations in the equipment used as a sponsor makes reference standards discussed above; However, a regulatory to conduct the assay. The mechanism available to all persons having an in­ analyst, using an approved assay, must established by the regulations is geared terest, the requirements of the regula­ have at his disposal , some technique to the assay’s variability; if the assay tion will be met. A commitment to sup­ (again capable of meeting other criteria) yields readily reproducible results, the ply reference standards when they are which can provide assurance that an ob­ importance of determining the signal- not commercially available may be made served response is due to the marker res­ noise ratio is diminished. Every regula­ a condition of the sponsored compound's idue. At present, mass spectroscopy is tion has a zone of ambiguity, however, approval, and failure to supply the gov­ probably an ideal choice for acquiring and the Commissioner believes that it is ernment or other laboratories as required the requisite specificity, although there not now appropriate to define more pre­ is a basis for withdrawing a compound’s are other possibilities. Some determina­ cisely this requirement for an assay’s approval. The Commissioner concludes tions (e.g., those requiring enzymes) may approvability. In such instances, the pro­ that an assay is not practical if it is de­ have an inherent high specificity, but fessional judgment of the reviewing pendent on the use of any other unique others have low specificity (e.g., gas, scientist will come in to play within pre­ equipment or materials that are not com­ thin-layer, and liquid chromatography) scribed limits. Sophisticated methods of mercially available. and require other, independent, types of statistically analyzing the results of as­ 3. Specificity. The regulations specifymeasurements to achieve the requisite says offer the promise of more refined that for an assay to be accepted, an ob­ confirmation of identity. By adopting standards for this feriterion that will take served response must without question be this definition of specificity, the Com­ into account assay variation and yet due to the compound being measured and missioner concludes that all concerns ex­ yield the high degree of confidence in that compound only. It is a fundamental pressed in the comments over “false posi­ assay results, e.g., regression analysis of part of the development of an assay to tives” or “false negatives” are moot. the spiked tissue, dosed tissue, and tissue determine whether or not it possesses 4. Accuracy. Assays yield measure­ blank results. The agency, in conjunction this important attribute. Among ana­ ments of concentration that are in some with the Animal and Plant Health In­ lytical chemists and biochemists, an proportion to the true concentration of spection Service of the U.S. Department ‘assay” that does not demonstrate this the compound being measured. The ac­ of Agriculture (APHIS), will be develop­ attribute is of little value, and indeed, in curacy of an assay is expressed as a per­ ing in guidelines for further refining this aregulatory setting, such an assay could cent of the compound’s true concentra­ criterion and may subsequently propose be dangerously misleading. For this rea­ tion. The, regulations prescribe a specific amendment of the regulations to pre­ son, the Commissioner has established accuracy criterion: The averages of the scribe precise standards for evaluating rigorous specifications for this attribute. observed responses must fall within 60 assay accuracy. In general terms, specificity describes to 110 percent of the true value. The cri­ The Commissioner recognizes that the the uniqueness of the relationship be­ terion is consonant with current, good term “ method sensitivity” is widely used tween the observed effect (or response) analytical practice and is based on to describe the lowest level of a com­ ^he applied stimulus (in this case the agency experience with methods that pound under analysis which can be de­ chemical under analysis). In analytical are routinely used for trace analysis. tected as measured with an analytical chemistry and biochemistry, the term 5. Lowest limit of reliable measure­ assay. Indeed, the original proposal used specificity is commonly used in reference ment (Lm) . To be accepted for regulatory this term to describe what in the final to the uniqueness of a response resulting purposes, an assay must be able to dis­ order has been termed “ the lowest limit hom the application of a stimulus having tinguish, with a very high degree of cer­ of reliable measurement.” However, specific characteristics; that is, the term tainty, target tissues that contain levels there is some confusion surrounding the has a qualitative dimension only in that of the marker residue at or above Rm term “sensitivity,” which derives in part 11 does not relate to either the quantity from target tissues that do not. This dis­ from the fact that the term has been FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 10428 RULES AN D REGULATIONS used in two senses: (1) As the lowest FDA facilities and one USDA facility) B. DATA TO SUPPORT WITHDRAWAL PERIODS level of a compound which can be de­ independently validate an assay before tected by an assay; and (2) as the low­ he can determine that use of a sponsored The depletion studies required by the est level of a compound which can be compound can be approved. The delicate regulations to establish withdrawal measured reliably by an assay. In fact, nature of the assays, their importance in periods must take into account the bio­ the correct meaning of the term assuring that no residues of carcinogenic logical variability among animals and “method sensitivity” is unrelated to a concern will occur in food o f animal other variables that may influence deple­ particular level of compound concentra­ origin, and the practical limitations on tion times. tion, but rather relates to the ratio of the Government’s capacity to monitor Residue depletion studies must be con­ change in instrument response to the food production and distribution make ducted under conditions of the sponsored change in compound concentration. The this requirement mandatory. These three compound’s maximum proposed use. If a term “sensitivity” has therefore been laboratories must study an assay suffi­ petitioner can demonstrate target tissue dropped from the final regulations. The ciently to assure that the conclusions equilibration with the marker residue, Commissioner has adopted the term about its acceptability drawn by the pe­ however, a shorter period of administra­ “lowest level of reliable measurement” titioner in his submission are correct tion of the maximum dose can be per­ because that term more precisely de­ and that all criteria are met. mitted. The conditions of the study must scribes the attribute. also simulate actual use practice. That a In response to comments urging that G. CONCLUSION compound is intended for a therapeutic any “detected residue” should be subject If an assay complies with the cri­ use is irrelevant, because the function of to regulatory control, the Commissioner teria described above and prescribed by this study is to determine the safe with­ points out that it is an inherent char­ the final regulations, and compliance can drawal period, regardless of the com­ acteristic of almost all analytical meth­ be verified under actual conditions of pound’s intended mode of use. The pro­ ods that compounds can sometimes be regulatory use, the Commissioner will posed regulatory assay must be used to detected at levels below' the levels at approve the assay. A full description of measure the marker residue in the target the approved assay will be published in tissue, including milk and eggs where which they can be reliably measured. appropriate, because it is this assay that More precisely, detection of a compound the F e d e r a l R e g i s t e r upon approval of the petition, in accordance with the pro­ will be used for regulatory monitoring. simply means that there is some instru­ ment response above background levels visos to the anticancer clauses and sec­ All raw data and evaluations must be which could be the compound of interest, tion 512(i) of the act. submitted with the petition along with a but this response cannot be considered graphical presentation of the tissue de­ IX . W ithdrawal P eriods pletion curve (concentration of marker as a reliable measurement of the com­ pound. Since protection of public health A. INTRODUCTION residue in target tissue versus time). is the issue, the Commissioner must be The regulations define the withdrawal The analysis of the data must include in a position to document conclusions period for a sponsored compound as the the estimated depletion curve, which in based on analytical data, often in a time required, after cessation of target most instances can be adequately ap­ court of law. A major aim of these reg­ proximated by a first order decay proc­ animal exposure to the sponsored com­ ess. The upper 99 percent confidence ulations is to assure that assays used to pound, for the marker residue to deplete obtain such data can reliably measure bound will be determined for the sam­ to L m in the target tissue. The withdraw­ ples from individual target anim als and residues. Hence, the Commissioner con­ al period must also be compatible with cludes that the discriminant for samples the time of intersection of this upper 99 actual conditions of livestock manage­ percent confidence bound with the Lm containing potentially violative exog­ ment and reasonably certain to be fol­ enous marker residues shall be the lowest value will be determined. The withdraw­ lowed in practice. Because of the way in al period is the interval of time between limit of reliable measurement, Lm, of the which the regulations define marker approved assay. Moreover, by imposing the last administration of the compound residue, target tissue, and Lm, the use of and the time of intersection of the upper these criteria at the preapproval stage, a sponsored compound in accordance the Commissioner will provide an added 99 percent confidence bound on the ob­ with the prescribed withdrawal period servations and the Lm of the approved measure of public health protection by will assure that no carcinogenic residues barring potentially unsafe compounds regulatory assay, plus an additional in­ of such compound will be present in terval determined by rounding out this from tiie market place. human food derived from treated time interval to provide a practical with­ P. INTERLABORATORY VALIDATION OF ASSAY animals. At any point after cessation of drawal period compatible with animal exposure but prior to the determined managemeht practices. Although PDA will review the assays withdrawal period, treated animal tissues for each sponsored compound, the actual must be considered as containing For example, if the time of intersec­ regulatory field screening of foods of residues of carcinogenic concern. Thus, tion of the upper 99 percent confidence animal origin will be primarily per­ the withdrawal period specifies the bound on the individual tissue determi­ formed by APHIS, pursuant to the Meat length of time after the last treatment nations and the Lm for the marker resi­ and Poultry Products Inspection Acts, with a sponsored compound in which due is 39 hours, the withdrawal period and by the States pursuant to the Public animals shall not be slaughtered for food (preslaughter interval) would be estab­ Health Service Act. The Food and Drug and during which milk shall be lished as 2 days. In the case of milk sam­ Administration performs a complemen­ discarded. ples, if the time of intersection were tary regualtory function: followup ana­ 63 hours, a withdrawal time of 72 hours lytical and field investigations of viola­ Several comments addressed the pro­ (discard of 6 milkings) would be estab­ tive residues to assemble evidence for cedures for establishing posttreatment lished. withdrawal periods. Some contended The use of a compound could not be use in regulatory actions. that the requirement for tissue equili­ The initial paper review by FDA of approved if the necessary withdrawal material in a petittion permits the bration with residues in the experimental period exceeds a period that is compati­ agency to make a threshold determina­ procedure for establishing withdrawal ble with animal management practices- tion of the acceptability of an assay. times was inappropriate for therapeutic For example, the use of a compound m Adequate protection of the public health, drugs. Other comments suggested that lactating animals will not be approved however, requires assurance that these the withdrawal periods be established to if the required withdrawal time for nauk assure the absence of residues from exceeds 96 hours (4 days) because the assays will function in the Government’s edible tissues only, since they are the regulatory laboratories. Therefore, these economics of milk production make ob­ ones destined for human consumption. servance of such discard times unlkeiy, regulations also prescribe the procedure Finally, some comments expressed con­ that will be used to assure that an assay or at least not reasonably certain, to oe cern about the practicality of applying followed in practice. is appropriate for use as a regulatory tool by Government laboratories. confidence-interval techniques to estab­ When the marker residue is an endog­ The Commissioner will require that lishing withdrawal periods, especially enous compound, the withdrawal P®” three Government laboratories (two when dealing with large animals. riod is the time after cessation of Bd* FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 197/ RULES AN D REGULATIONS * 10429 ministration of the sponsored compound petitions, and appropriate color additive the final regulations resolve some issues required for the norm to be restored, with petitions, including appropriate supple­ not specifically dealt with in the proposal 99 percent assurance, extended if nec— mental applications, submitted subse­ but raised by the comments. For these essary to be compatible with conditions quent to the effective date of the regula­ reasons, the Commissioner is providing of livestock management. The validated tions. In addition, the requirements of an additional 60 days for any interested regulatory assay must be used to collect the regulations shall apply to all pending person to submit further comments on this information. petitions and applications unless the these specific issues. The Commissioner Commissioner determines that compli­ will evaluate any additional comments C. RATIONALE FOR USING THE CONFIDENCE ance with the anticancer provisions of and will later publish any revisions to BOUND APPROACH the act can be adequately assured by the final regulations, if appropriate. To establish that carcinogenic resi­ requiring completion of one or more of The Commissioner urges that any com - dues are absent from edible tissues of the required studies subsequent to ap­ ments submitted within this additional food-producing animals treated with the proval. The criteria set forth in the reg­ period address only new issues, and not sponsored compound, the Commission­ ulations are based on generally recog­ reopen matters raised by the initial pro­ er must have information about the rate nized scientific principles for testing and posal and discussed in this preamble. The of residue depletion and the inherent evaluating chemical componds for po­ Commissioner is particularly interested metabolic variabilities among individ­ tential carcinogenesis requirements that in receiving comments on four specific ual target animals. Confidence bounds Congress contemplated PDA would ad­ areas of the regulations. First, he invites on experimental data are the only means here to when it enacted the Food Addi­ further discussion of the acceptable level to allow prediction, with a given degree tives Amendment of 1958 and the Animal of risk for use in the modified Mantel- of confidence, of what will occur in the Drug Amendments of 1968 (21 U.S.C. Bryan calculation. At the present time, total target animal population. The 348 (b) and (c) and 360b (b) and (d) ). .FDA is involved in administrative ad­ Commissioner has prescribed 99 percent The Food and Drug Administration judications concerning potentially car­ confidence bounds throughout these has already applied these standards to cinogenic animal drugs. These proceed­ regulations as the degree of confidence compounds currently being evaluated for ings may assemble additional evidence necessary to assure protection of public approval or subject to proposals to with­ on the acceptable level of risk. Because health. draw approval (e.g. diethylstilbestrol this issue is important to application of X. W aiver of R equirements published in the F ederal R egister of the regulations, the Commissioner be­ November 2, 1976 (41 FR 52105) and the lieves additional comment will contribute The regulations permit the Commis­ nitrofurans published in the F ederal to public understanding. This action will sioner, in response to a petitioner’s re­ R egister of May 13, 1976 (41 FR 19906) in no way jeopardize the public health, quest or on his own initiative, to waive, and August 17, 1976 (41 FR 34884)). for the administrative record adequately in whole or in part, any of the foregoing Accordingly, all previously approved ap­ supports the current level of risk; the requirements for the scientific evalua­ plications for compounds subject to thè Commissioner is interested in comments tion of sponsored compounds that have anticancer clauses will be reviewed as on whether the level of risk should be the potential to contaminate human food part of the general review of the safety further reduced. with residues whose consumption could of marketed animal drugs. When the Second, the Commissioner will enter­ engender a human risk of carcinogenesis. agency finds deficiencies in the data sup­ tain comments on the concept of com­ When an agency particularizes a statu­ porting a prior approval, it will issue parative metabolism. This unique ap­ tory standard of conduct by regulation, either a F ederal R egister notice or a proach was developed in response to the due process requires that it permit af­ letter pursuant to section 512(1) (1) of diverse comments on the issue of which fected parties to demonstrate how their the act establishing the time within metabolites of a sponsored compound, if alternative mechanism satisfies the stat­ which the provisions of these regulations any, should be tested. An analogous pro­ utory standard, and why the regulation must be satisfied. For notices previously cedure of the Environmental Protection should then be waived in the public in­ published or letters previously issued, the Agency has received judicial approval. terest. “Weinberger v. Hynson, Westcott, criteria of these regulations will be used “Environmental Defense Fund, Inc., et and Dunning, Inc.,” 412 U.S. 609, 620 to determine whether the data support­ al., v. Environmental Protection Agency,” (1973) .'¡Moreover, it has been long set­ ing applications are acceptable. The No. 75-2259, (D.C. Cir., November 10, tled that an agency may adopt a rule Commissioner will, however, immediately 1976), slip op. at 14. The Commissioner shown to be appropriate for the general­ proceed to withdraw approval of applica­ welcomes suggestions for alternatives to ity of instances and leave the correction tions on the basis of information Indi­ this approach. of injustices to applications by those cating that a health hazard exists or Third, as previously noted, the Com­ concerned. “National Nutritional Poods that no studies necessary to bring a spon­ missioner invited suggestions for alter­ Ass’n v. Pood and Drug Administration,” sored compound into compliance with native mechanisms for dealing with 504 F.2d 761, 784 (2d Cir. 1974). For the regulation have been conducted. endogenous compounds. Several com­ these reasons, the Commissioner has ex­ ments on the proposal urged that an pressly included the waiver provision. A dditional T ime for C omment alternative procedure for evaluation of The Commissioner advises, however, that These final regulations largely reflect such compounds should be available, but a waiver will be granted only in excep­ not only the proposal published in July failed to suggest any feasible approaches. tional circumstances, and, as the regula­ 1973, but the current FDA practice in re­ Finally, the Commissioner welcomes tion provides, the basis for any waiver viewing sponsored compounds. Comments suggestions of refined mechanisms for must be extensively documented. on the proposal and petitions filed during statistically differentiating target tissue XI. I mplementation the intervening 3 years have raised most containing the market residue from of the issues discussed in this preamble blank target tissue. The proposal would have applied the and resolved in the final regulations. In The Commissioner concludes that all requirements of the regulations to all the main, therefore, the regulations em­ of the provisions of the final regulations new approvals (basic or supplemental) body no new decisions. The DES proviso should be implemented pending recon­ nled or approved after the effective date to the anticancer clauses is self-execut­ sideration of any specific provisions of the regulations. Prior approvals were ing, and FDA has therefore been obli­ based upon additional comments. This to be dealt with on a class-by-class basis, gated to deal with the issues posed by will work no hardship since all provisions beginning with known carcinogens, sus­ carcinogenic compounds proposed for use of the regulations are supported by the pect carcinogens, and continuing through in food-producing animals in the absense record, and, except for the level of risk, compounds previously approved on of regulations. Accordingly, the Commis­ the only changes the Commissioner con­ the basis of zero tolerance. These were to sioner concludes that these regulations templates concern alternative methods be reviewed as part of the agency’s gen­ of satisfying the statutory requirements. eral safety review for previously ap­ shall become effective March 23, 1977. The Commissioner has carefully con­ proved new animal drugs. Nevertheless, the Commissioner recog­ sidered the environmental effects of the 'Die final regulations apply to all new nizes that it has been over 3 years since regulations and, because this action will animal drug applications, feed additive these regulations were proposed and that not significantly affect the quality of th© FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 10430 RULES AN D REGULATIONS human environment, has concluded that 82 Stat. 343-351 (21 U.S.C. 342, 343, 348, 360b, lowing procedure for data collection and an environmental impact statement is 371(a), 376). evaluation shall become applicable: not required. A copy of the environmen­ Subpart E— Criteria and Procedures for (1) A metabolic study in the animals tal impact assessment is on file with the Evaluating Assays for Carcinogenic Res­ in which the sponsored compound is in­ Hearing Clerk, Food and Drug Adminis­ idues in Edible Products of Animals tended for use (target animals) designed tration, Rm. 4-65, 5600 Fishers Lane, § 500.80 Chemical com pounds used in to identify metabolites of concern; Rockville, MD 20852. food-produ cin g anim als; procedures (ii) A metabolic study of the spon­ This final order was proposed prior to and criteria fo r determining the ac­ sored compound in experimental animals Executive Order 11821, requiring agen­ ceptability o f assay methods fo r car­ designed to aid in assessing the carcino­ cies- in the executive branch to review cinogenic residues in edible products genicity of residues that cannot practi­ regulatory and legislative proposals they o f such animals. cably be tested individually (intractable initiate for inflation impact, and so does residues) ; (a) Purpose and applicability of this (iii) Chronic testing in test animals to not require inflation impact review. subpart. (1) The act requires that com­ Therefore, under the Federal Food, pounds intended for use in food-produc­ assess the carcinogenic potential of resi­ Drug, and Cosmetic Act (sections 402, ing animals shall be safe and that food dues of the sponsored compound and to 403, 409, 512, 701(a), 706, 52 Stat. 1046- produced from animals exposed to such furnish data suitable for statistical treat­ 1048 as amended, 1055, 72 Stat. 1785- compounds be safe for human consump­ ment by the procedure of M antel and 1788 as amended, 74 Stat. 399-403, 82 tion, and prohibits the use of any com­ Bryan, (Mantel, N., and W. R . Bryan, Stat. 343-351 (21 U.S.C. 342, 343, 348, pound found to induce cancer when in­ “ ‘Safety’ Testing of Carcinogenic 360b, 371(a), 376)) and under authority gested by man or animal in food-produc­ Agents,” “ Journal of the National Cancer delegated to the Commissioner (21 CFR ( ing animals unless it can be determined Institute,” 27(2) : 455-470 (1971)) as 5.1) (recodification published in the F ed- ' by methods of examination prescribed modified by Mantel et al. (Mantel, N., et eral R egister of June 15, 1976 (41 FR al., “ Improved Mantel-Bryan Procedure or approved by the Commissioner that for ‘Safety’ Testing of Carcinogens,” 24262))., Chapter I of Title 21 of the Code no residue of such compound will be of Federal Regulations is amended as found in the food produced from such “Cancer Research,” 35:865-872 (1975))3 follows: and by this subpart, to permit the no­ animals under conditions of use reason­ residue requirement of the act to be op­ PART 8— COLOR ADDITIVES ably certain to be followed in practice. erationally defined for purposes of estab­ Petitions for the approval of the use of lishing a lowest limit of reliable measure­ 1. In Part 8, by amending § 8.36 by a compound in food-producing animals adding new paragraph (c) to read as shall include adequate data for estab­ ment for an assay to measure residues of follows: lishing the absence of residues of carcino­ the sponsored compound; (iv) A detailed metabolic study of the § 8.36 Application o f the cancer clause genic compounds in the food produced sponsored compound in target animals o f section 706 o f the act. from such animals. designed to identify a specific residue (2) The provisions of this subpart * * * * • * establish the following: (i) The lowest and tissue to serve as indicators (marker (c) Color additives for use as an in­limit of reliable measurement for the reg­ residue and target tissue) to determine gredient of feed for animals that are ulatory assay required for carcinogenic whether the no-residue requirement of raised for food production. Color addi­ residues by sections 409(c) (3 )(A ), 512 the act is satisfied; tives that are an ingredient of the feed (d )(1 )(H ), and 706(b)(5)(B) and sec­ (v) Development of a regulatory assay for animals that are raised for food pro­ tions 409(b)(2)(D ), 512(b)(7) and 706 to measure the marker residue in the duction must satisfy the requirements (b) (5) (A) (iv) of the act; target tissue at and above the level op­ imposed by subpart E of Part 500 of this (ii) The procedures and criteria for erationally defined as satisfying the no­ chapter. evaluation and approving such assays; residue requirement of the act; and and (vi) Establishment of the prémarket­ (iii) The procedures and criteria for ing withdrawal period required for the PART 500— GENERAL establishing the premarketing with­ safe use of the sponsored compound. 2. In Part 500, by adding a new Sub­ drawal period for use of compounds likely (2) If, at any point in the sequential part E, consisting of §§ 500.80 through to produce such residues. process of data collection set forth in 500.98, to read as follows: (3) This subpart shall apply specifi­ paragraph (b) (1) of this section, the Subpart E— Criteria and Procedures for Evaluat­ cally to compounds intended for use in evaluation of the data satisfies the Com­ ing Assays for Carcinogenic Residues in Edible food-producing animals and their feed missioner that no human risk o f carcin­ Products of Animals ogenesis attaches to the proposed use of that have the potential to contaminate Secs. the sponsored compound, the compound 500.80 Chemical compounds used in food- human food with residues whose con­ shall be considered for a p p r o v a l under producing animals; procedures and sumption could engender a human risk of the general safety provisions of the act. criteria for determining the ac­ carcinogenesis. The determination of this ceptability of assay methods for potential shall be based on considerations § 5 0 0 .8 4 M etabolic study in t a r g e t a n i­ carcinogenic residues in edible of chemical, biochemical, physiological, mals to identify residues for c h r o n i c products of such animals. and toxicological data derived from the testing. 500.84 Metabolic study in target animals to scientific literature and from other identify residues for chronic test­ sources available to the sponsor or to the (a) A metabolic study, described m ing. paragraph (b) of this section, shall be Commissioner and on the proposed pat­ conducted in target animals to provide 500.85 Criteria for test animal selection; terns of compound use. The subpart Comparative metabolic studies to data on the physicochemical character­ aid in assessing the carcinogenicity establishes a sequential process for the istics of residues, their relative propor­ of residues that cannot practicably collection of other chemical, biochemical, tions, their distribution among the var­ be tested individually (intractable physiological, and toxicological data per­ ious edible tissues (which include milk or residues). tinent to the safety of the proposed use eggs when applicable), and their reten­ 500.87 Chronic testing. of the sponsored compound. This subpart 500.89 Metabolic study to identify the shall not apply to essential nutrients. tion and depletion by the animals. marker residue and target tissue. (b) The target animal metabolic 500.90 Evaluation and approval of a regu­ (b) General approach. (1) When the study shall satisfy the following mini­ latory assay. Commissioner determine that a spon­ mum requirements: 500.92 Withdrawal periods. sored compound has the potential to (1) The metabolic study shall be con- 500.94 Publication of the approved regula­ contaminate food from food-producing i n t o r v e t . n .T lI m a ls W i t h t h e SPOn- tory assay. animals with residues (the sponsored 500.96 Waiver of requirements. compound, metabolites, conversion prod­ 3Copies may be obtained from: A s s o d a , 500.98 Implementation. ucts, or any other substances formed in Director for Scientific E v a l u a t i o n ( A uthority : Secs. 402, 403, 409, 512, 701(a), or on food because of the compound’s 100), Bureau of Veterinary Medicine, F«*1 706, 52 Stat. 1046-1048 as amended, 1055, 72 use) whose consumption may engender and Drug Administration, 5600 Fishers La . Stat. 1785-1788 as amended, 74 Stat. 399-403, a human risk of carcinogenesis, the fol­ Rockville, MD 20857. FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 RULES A N D REGULATIONS 10431 sored compound bearing appropriate § 5 0 0 .8 5 Criteria for test animal selec­ dures described by Mantel and Bryan radiolabels, unless other experimental tion; comparative metabolic studies (Mantel, N., and W. R. Bryan, “ ‘Safety’ methods permit equivalent measurement to aid in assessing the carcinogenic­ Testing of Carcinogenic Agents,” “ Jour­ of residues. Such labels must assure that ity o f residues that* cannot practi­ nal of the National Cancer Institute,” residues containing structural moieties of cably be tested individually (intracta­ 27(2) :455-470 (1961) ) and Mantel et al. potential carcinogenic concern can be ble residues). (Mantel, N., et al., “Improved Mantel- detected and measured in edible tissues (a) The primary criterion for the se­ Bryan Procedure for ‘Safety’ Testing of at levels as low as the best available tech­ lection of species or strains of test ani­ Carcinogens,” “ Cancer Research,” nology will permit. Hypotheses about the mals for chronic testing of the sponsored 35:865-872 (1975)) 8; subject to the sponsored compound’s projected meta­ compound and any metabolites selected modifications and restrictions set forth bolic pathways may be used as a guide in accordance with § 500.84 shall be the in paragraph (c) (1) through (9) of this to experimentation, but shall not be a suitability of -the species or strain as a section. The purpose of this analysis shall substitute for actual experimentation. model for man. be to define the no-residue requirement (2) The dosing regimen shall be con- (b) If one or more intractable residues of the act as it applies to the total residue sistént with the maximum proposed use are also selected for chronic testing based of carcinogenic concern of the spon­ level and proposed duration of exposure upon the metabolic study in the target sored compound and thereby to deter­ to the sponsored compound. For a com­ animal, a secondary criterion for the mine the lowest level of reliable meas­ pound that is proposed for continuous or selection of species or strains of animals urement that shall be required for a reg­ repeated use in targèt animals, adminis­ for the testing of the sponsored com­ ulatory assay to be approved for the tration for the metabolic study need con­ pound shall be employed. Metabolic stud­ measurement of such residues. tinue only until residue equilibration or ies of the sponsored compound in the test (1) The administered dose of each test tissue saturation has been demonstrated. animal species or strains deemed suit­ compound shall be expressed as a frac­ (3) The metabolic study shall be de­ able for chronic testing by the primary tion of the total diet fed the test animal signed to yield the following information : criterion shall be conducted to deter­ species/strains, e.g., parts per million, (i) The concentrations and total num­ mine if the intractable residues present parts per billion, etc. ber of residues detected in edible tissues in the tissues of target animals are also (2) The “safe” level of Mantel and of target animals immediately following produced in the test animals. Chronic Bryan, calculated for each test compound cessation of exposure; testing of the sponsored compound in a in accordance with this section, shall be (ii) Except when the Commissioner species or strain of test animals in which expressed as a fraction of the total diet specifies otherwise, the concentrations the residues produced are similar to the fed the test animal species/strains. It and total number of residues detected in complement of residues in the tissues of shall be calculated with 99 percent confi­ edible tissues of target animals when the the target animals shall be considered an dence for a maximum lifetime risk that is total residue burden has depleted for at appropriate method of assessing the essentially zero but never expected to ex­ least three half-lives; and carcinogenic potency of the intractable ceed 1 in 1 million. residues, (3) A slope of one probit per unit log (iii) The physicochemical properties of dose shall he used for extrapolation to the detected residues to identify com­ § 5 0 0 .8 7 Chronic testing. pounds of potential carcinogenic concern. the “safe” level unless the experimental (a) Chronic toxicity tests shall be con­ data indicate that a shallower slope is re­ (4) The results of the metabolic studyducted to assess the carcinogenic poten­ quired to maintain the conservatism of shall be submitted in the form of a de­ tial of the residues of the sponsored com­ the procedure. tailed report conforming to the standards pound. (4) Data obtained from more than one required of scientific manuscripts sub­ (1) The sponsored compound and any dose level fed to groups of experimental mitted for publication in the journals of residues selected for chronic toxicity animals of the same strain shall be com­ professional scientific societies such as testing shall be subjected to oral, life­ bined as described by Mantel et al. (Man­ the American Chemical Society and the time, dose-response studies in the test tel, N., et al., “Improved Mantel-Bryan American Society of Biological Chemists. animal species or strains selected in ac­ Procedure for ‘Safety’ Testing of Carcin­ In addition, all raw data shall accom­ cordance with § 500.85. Each of these ogen,” “Cancer Research”, 35:865-872 pany and be referenced in the report. studies must be designed to determine (1975)),8 and subject to the restrictions ' (c) If the Commissioner determines whether the test compound is carcino­ specified by these authors. that a sponsored compound has potential genic. Protocols for these studies should (5) Pooling data from various chronic to contaminate food with residues whose be submitted to the Commissioner for tests using different animal sexes, species, consumption engenders human risk of review prior to commencing testing. or strains shall be permitted if it can be carcinogenesis, the petitioner shall be re­ (2) The Commissioner will determine demonstrated that the protocols are of quired to determine the carcinogenic po­ whether any of the compounds tested is compatible design. If statistically signif­ tency of the sponsored compound and carcinogenic on the basis of the results icant biological differences in tumori- any of its residues that might be of pub­ of these chronic toxicity studies and genie responses are observed between lic health concern because of chemical other available information. If this evi­ sexes or among species or strains of ex­ structure or persistence and concentra­ dence is equivocal, the compound shall perimental animals, only subsets of data tion in edible tissues. Ordinarily, chronic be classed as a carcinogen until further representing statistically and biologically testing of the sponsored compound and testing resolves any remaining questions compatible bioassays may be combined selected residues in experimental animals regarding carcinogenicity. for analvsis. shall be the preferred means of assessing (b) When the Commissioner deter­ (6) All tumors (benign and/or malig­ carcinogenic potency. (Section 500.85 de­ mines that a sponsored compound has nant) shall be considered in the analysis. scribes an alternative means of assessing the potential to increase the normal (7) The number of animals at risk may the carcinogenic potency of residues levels (pools) of carcinogenic and poten­ be adjusted for competing risks unrelated whose isolation or synthesis in sufficient tially carcinogenic substances endoge­ to the compound-induced carcinogenesis quantities for chronic testing proves to be nous to the target animals, the petitioner only when the data clearly support such beyond the practical limits of current shall meet the requirements of § 500.89 an adjustment. chemical technology (intractable resi­ ( c ) , (d) and (e ). (8) When only the sponsored com­ dues) by establishing additional criteria (c) For .each tested compound classed pound is subjected to chronic testing, the for selecting test animal species/strains as a carcinogen, the appropriate data calculated “safe” level shall be desig­ U?®J* t° conduct chronic toxicity testing from the chronic dose-response studies nated at So. When more than one com­ the sponsored compound.) shall be analyzed according to proce- pound is subjected to chronic testing, the FEDERAI REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 10432 RULES AND REGULATIONS lowest of all calculated “safe” levels shall (2) Calculation of Sm for tissues con­ be designated So. So shall be expressed as sumed less frequently than muscle may the fraction of the diet fed the test .ani­ take into consideration the frequency of mals (e.g., parts per million, parts per consumption of such tissues if it can be billion, etc.). clearly shown that So will not be ex­ (9) The no-residue requirement of the ceeded in the total human diet. the act shall be considered satisfied when § 5 0 0 .8 9 Metabolic study to identify the conditions and use of the compound, in­ marker residue and target tissue. cluding any required withdrawal period, (a) The petitioner shall conduct a can be prescribed to assure that the sum study of the metabolic fate of the spon­ of the levels of all potential residues of sored compound in target animals ade­ carcinogenic concern will not exceed So quate to provide the data necessary for in the total diet of man and a regulatory the selection of a marker residue in assay is available that is capable of reli­ ably measuring such residues at and target tissue. above that level. All residues of the spon­ (1) The target tissue is that tissue in sored compound shall be classed as car­ which measurement of the total residue cinogenic except those that have been burden of carcinogenic concern is a reli­ unequivocally shown to be noncarcino- able measure of the total residue burden genic. of carcinogenic concern in all edible (d) The So value represents the sum of tissues. all residues of carcinogenic concern that * (2) The marker residue for the spon­ must not be exceeded in the total diet of sored compound shall be that residue man. For individual edible tissues, the (the sponsored compound, any metabo­ value that must not be exceeded shall be lite, or more than one of these) whose designated Sm and calculated according level in the target tissue is a reliable to the following formula: measure of the total burden of all resi­ dues of carcinogenic concern in all edible tissues. (b) The metabolic study to establish N o t e .—T is the fraction of the total daily the marker residue and target tissue diet of man represented by an individual shall comply with the requirements set edible tissue. forth in § 500.84(b) (2) and (4), with the (1) The principal Sm calculations are following additional specifications: as follows: (1) For each edible tissue, the deple­ tion profile of the total residue of carci­ E d ib le tissue T Sm nogenic concern shall be constructed and shall include measurements of levels at M u s c l e ...--------------------------- 1/3 3So least as low as the Sm appropriate to the M ilk _______________________ 1 So tissue under study, set forth in Plate I E ggs----------------------------------- 1/3 3So as follows: FEDERAL REGISTER, VO L. 4 2 , MO. 35— TUESDAY, FEBRUARY 22, 1977 RULES AN D REGULATIONS 10433 P L A T E l. R E S ID U E D E P L E T IO N C U R V E S T O B E U S E D IN T H E D E T E R M I N A T I O N O F M A R K E R R E S ID U E A N D T A R G E T T IS S U E . TOTAL RESIDUE LEVELS IN VARIOUS EDIBLE TISSUE EXPRESSED IN SM UNITS (APP R O PR IA TE U N ITS, U . , HOURS, D A Y S , ETC) (2) Depletion profiles for one or more potential marker residues shall be constructed as set forth in Plate II in this paragraph, and shall include measurements of levels corresponding to the time when the total residue level has reached Sm in tne edible tissue requiring the longest time to deplete to Sm (.Tl of Plate I in paragraph (b) (1) of this section). FEDERAL REGISTER, VOL. 42, N O . 35— TUESDAY, FEBRUARY 22, 1977 10434 RULES AND REGULATIONS P L A TE I t S E L E C TIO N O F M ARKER RESIDUE A N D ITS L E V E L RM TH A T M U ST SE M EASURED B Y T H E R E G U L A T O R Y ASSA Y. (3) If these specifications have been as confirmation that the total residue the potentially carcinogenic endogenous met by the metabolic study required by burden of carcinogenic concern does not substances of concern in untreated tar- § 500.84(b), a second metabolic study 'exceed Sm in each of the various edible get animals. need not be performed to satisfy this tissues and therefore that the total bur­ (i) The norm shall be specific for tne section. den of carcinogenic concern in the hu­ target animals and the intended condi­ (4) Prom these data, the Commissioner man diet does not exceed So, tions of animal husbandry, and shall d will select a marker residue and target (c) When the Commissioner deter­ determined from studies designed to taae tissue, and he will also designate the mines on the basis of available scientific into account differences due to factor such as breed, age, sex, state of estrus, required level of marker residue, Rm (set information that a sponsored compound forth in Plate II in paragraph (b) (2) of has the potential to increase the normal and geographic location. , , r, (ii) Each norm shall be submitted in this section), that regulatory assays must levels (pools) of potentially carcinogenic substances endogenous to target animals, the form of a graph of the cumulative be capable of measuring in the target tis­ the petitioner shall provide the following frequency distribution versus the ob­ sue. The selection of Rm shall be such additional data: served naturally occurring levels, delud­ that the absence of the marker residue (1) An experimental determination ofing the 99 percent confidence bounds, set in target tissue above Rm can be taken the background levels (norm) of each of forth in Plate III as follows: FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 RULES AUD REGULATIONS 10135 LEVEL OF ENDOGENOUS SUBSTANCE IN TARGET ANIMALS (APPROPRIATE UMTS, i.e„ MG OR MG PER ML) (iii) An assay shall be acceptable for of the sponsored compound, the marker (2) Samples containing various levels the determination of a norm only if it residue for all endogenous compounds of of the marker residue obtained from yields values for the endogenous com­ concern shall be that endogenous com­ target tissue at appropriate time inter­ pound of interest greater than zero in at pound whose norm requires the longest vals after the sponsored compound is least two-thirds of the untreated target time for restoration. administered in accordance with the animals. (e) For an endogenous compound se­ proposed labeling, i.e., “ dosed” tissue (2) Studies to measure the effect of lected to be a marker residue, the re­ samples: the sponsored compound on the norm quired level of measurement, R m, for the (3) Samples obtained from untreated and the postexposure decay of any in­ •regulatory assay shall be the level of that target animals, i.e., “ control” tissue crease in the norm caused by adminis­ endogenous compound corresponding to samples. tration of the sponsored compound. the 33d percentile of the norm, set forth (c) The petition for approval of the (3) All data from these studies sub­ in Plate III in paragraph (c) (1) (ii), of proposed regulatory assay shall contain mitted in accordance with the require­ this section. the following: (1) A complete description of the ments established in paragraph § 500.- § 500.90 Evaluation and approval o f a 84(b)(4). regulatory assay. assay. (2) A list of all necessary equipment (d) For a potentially carcinogenic (a) Before a petition can be consid­ and reagents. endogenous compound whose norm is in­ ered for approval, the petitioner shall (3) A standard curve prepared from creased by tiie administration of a submit for evaluation and validation a samples of the marker residue of known sponsored compound, the no-residue re­ regulatory assay developed to monitor purity. quirement of the act shall be considered compliance with no-residue requirement (4) An analytical curve of the observed satisfied when the norm is restored. of the act. The regulatory assay shall re­ assay response versus the tissue concen­ (1) The norm shall be considered re­ liably measure the marker residue in the trations of the marker residue in spiked stored when the distribution of values target tissue at levels at least equal to target tissue. The curve shall include the for the endogenous substance of concern and above Rm, as defined in § 500.89 (b) 99 percent confidence bounds of a single observed in a group of treated animals is and (e ). The criteria and procedures in assay response. with 99 percent confidence the same as paragraphs (b) through (g) of this sec­ (5) All raw data and worksheets from the norm. tion shall apply to the evaluation and the analyses of spikedi dosed, and control (2) The marker residue for a spon­ approval of assays. tissue samples, and from the analysis sored compound that affects a poten­ (b) The regulatory assay shall be used in preparing the standard curve, tially carcinogenic endogenous sub­ evaluated and validated using data col­ including spectrograms, chromatograms, stance shall be the affected endogenous lected from three types of samples: etc. substance. (1) Samples containing various (6) A discussion of the data generated (3) When the norm of more than one known concentrations of marker residue in the assay development process per- potentially carcinogenic endogenous added to the target tissue, i.e., “ spiked” tihent to the evaluation criteria set forth compound is increased by administration tissue samples. in paragraph (d) of this section explain- FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 10436 RULES AN D REGULATIONS ing how the data show that the proposed interlaboratory validation study de­ only if the available evidence demon­ assay conforms to those criteria. scribed in paragraph The most significant change in wording the State did not feel that the short line of such negotiations are dubious. There is came in the last sentence— “Firms will not alternative was a very feasible one. It also some uncertainty regarding Conrail’s role in locate along a subsidized line without in­ did not believe that rate increases or such negotiations since the lines to be sub­ centives* * *” (emphasis added). See: In­ sidizedwill not be purchased. diana State Rail Plan, Preliminary Phase 2, arbitrarles were workable in the long The fact that the Federal subsidy program Volume I, op. cit., pp. 11—12; and Indiana run since additional costs would inhibit lasts only two years is further reason for State Rail Plan, Final Phase 2, op. cit., p. 6. future traffic development and, therefore, skepticism. Although there are indications 21See Indiana State Rail Plan, Phase I, op. would be self-defeating. that this might be extended, itisnot certain. cit., p. 11; Indiana State Rail Plan, Prelimi­ On the other hand, Indiana believed The State does not at this point in time nary Phase 2, Volume I, op. cit., p. 12; and that industrial development or relocation intend to take over the full burden of the Indiana State Rail Plan, Final Phase 2, op. programs were a viable alternative. The subsidy program (emphasis added). cit., p. 7. USRA has set its criteria for inclusion in - Ibid. State also postulated that significant Conrail rather high which means that far =3 Ibid. savings were possible through service more segments are available for subsidy than -»Indiana State Rail Plan, Phase I, op. level changes. Additional actions that the the State expected. If in practice these lines cit., pp. 12-13; Indiana State Rail Plan, Pre­ State could employ to possibly further are demonstrably profitable, USRA will have liminary Phase 2, Volume I, op. cit., pp. 13- reduce costs included: the lowering or inhibited development of future traffic on 14; and Indiana State Rail Plan, Final Phase elimination of right-of-way taxes and Phase 2, op. cit., p. 7. changes in the State’s full crew law. The 18U.S.R.A. Segments in Indiana: State 25The reliance on economic self-sufficiency Analysis and Recommendations— Volume I, was tempered somewhat by the State’ s posi­ able lines within the State. This position was op.cit.,p. 60. tion on cross-subsidy. In its Indiana State alluded to in the subsequent reports but was 17The Center for Urban and Regional Rail Plan, Phase I of May 15, 1975, the State not mentioned at all in the Indiana State Analysis, U.S.R.A. Segments in Indiana: devoted Appendix B to a “Policy Statement Rail Plan, Final Phase 2. State Analysis and Recommendations— on Cross-Subsidy Issue”. Indiana defined a 24See Indiana State Rail Plan, Phase I, op. Volume III, (Bloomington, The Center for cross-subsidy as an “accounting method by cit., pp. 14-15; Indiana State Rail Plan, Pre­ Urban and Regional Analysis, January 31, which the profits generated by one sector of liminary Phase 2, Volume I, op. cit., p. 15; 1975),p.iii. an enterprise are utilized to cover the losses and Indiana State Rail Plan, Final Phase 2, 18The Center for Urban and Regional of another sector”.It went on to say that “it op. cit.,p. 8. Analysis, Indiana State Rail Plan, Phase I is desirable that the light-density branch 27Ibid. (Bloomington, The Center for Urban and lines located within itsboundaries be subject 98See Indiana State Rail Plan, Phase I, op. Regional Analysis, May 15, 1975), p. 7. Indi­ to cross-subsidies”. Specifically, the State cit., p. 16; Indiana State Rail Plan, Prelimi­ ana state Rail Plan, Preliminary Phase 2, maintained that profits from revenue gener­ nary Phase 2, Volume I, op. cit., pp. 16-17; Volume I, op. cit., p. 9. Indiana State Rail ating branch lines within Indiana should be and Indiana State Rail Plan, Final Phase 2, Plan, Final Phase 2, op. cit., p. 4. allowed to subsidize operations on unproflt- op. cit.,p. 8. FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22. 1977 10444 NOTICES latter option was discounted somewhat achieved simply by obtaining the sum segments and their priority-rank is by the State because it contended that of the ratings for each of the seven fac­ found in Table 2. By a letter dated Feb­ the full crew laws had not been enforced tors, the smallest sum receiving the high­ ruary 16, 1976, the State of Indiana re­ in Indiana since 1972. est priority. In instances in which more quested that RSPO evaluate 14 of these The State’s View on Acquisition, Opera­ than one line achieved a similar rating, 28 line segments. The State later revised tion and Rehabilitation the segment with the smallest sum on a its request in a letter, dated May 11, per mile basis was given priority over the 1976, which is attached to this report as In both its October 10, 1975 and Janu­ others. The final list of USRA rail line Appendix A. ary 26, 1976 reports, the State took the following position on rail acquisition and T a b l e 1.— Ranks on evaluation criteria operation: At this time [prior to the Final System USRA Cars E nergy E n viron ­ A lternate Jobs W ages S ubsidy Sum of Segm ent N o . m en t m od e ranks Plan] the State does not intend to acquire or operate any rail properties. Indiana be­ lieves that the solvent railroads should ac­ 39 9-99___________ . . . 8 20 6 5 5 .0 6 16 66.0 quire and operate segments and generally 4 0 1 -9 9 _______________ 13 8 8 6 12.0 12 14 73.0 4 1 4 -2 ..................... .. 22 15 25 25 19.5 21 26 153.5 supports proposed solvent acquisition of the 417a-99______________ ri 5 ■ 18 15 3 .0 3 5 60.0 segments analyzed here. 4 1 8 -1 ________________ 9 22 11 10 1 .0 2 19 74.0 4 1 9 -4 ________________ 16 14 12 9 14 .0 14 17 06.0 * * * * * 4 2 0 - 2 . . . ; . . . . ______ 17 9 26 24 10.0 11 12 109.0 Under no circumstances conceivable at 4 2 3 -2 ______________ V 18 11 13 13 13.0 13 8 89.0 present will the State become involved in 4 2 9 -2 ________________ f! 25 7 7 4 .0 4 2 HÜ . 55.0 5 2 1 -2 . . . . . ______ . . . 23 13 19 17 23 .0 23 18 operating ^railroad. It may, however, lease 5 2 3 -1 ________________ 7 16 17 14 24 .0 24 3 136.0 105.0 acquired properties,to solvent railroads. 524r-2________ ______ _ 15 12 10 8 2 7 .0 27 11 110.0 554r-8________________ 12 26 9 11 9 .0 9 27 103.0 With respect to rehabilitation the State 556-99_______________ 24 17 22 22 2 1 .0 20 20 146.0 declared that: 5 5 7 - 9 9 ._____ ________ 25 5 21 3 21 20 1 19.5 19 7 23 148.5 571/571a-99__________ 3 7 .0 21 47.0 The Plan which follows ties rehabilitation 5 7 4 -2 _______________ _ 26 7 23 21 18 .0 18 10 123.0 to the profitability of the segment. For those 578/579a-99__________ 3 1 5 4 8 .0 8 4 33.0 582-99_______________ 21 10 14 12 2 5 .0 25 9 116.0 lines which are currently profitable immedi­ 5 8 4 -0 . ........................... 28 4 28 26 15.5 16 7 124.5 ate rehabilitation is recommended. For other 5 8 5-99_______________ 10 24 16 19 2 8 .0 28 22 147.0 lines the rehabilitation is tied to the po­ 589/590-99.__________ 4 2 4 2 2 .0 1 13 28.0 tential solvency of the segment. Generally, in 5 9 1 -3 ____ _ . _________ 20 19 20 18 2 2 .0 22 15 136.0 5 9 6 - 9 9 ..................... .. 19 6 27 27 15 .5 15 6 115.5 the latter case the operating plan calls for 602-99_______________ 27 18 24 23 17 .0 17 24 150.0 10 percent of the rehabilitation during the 6 3 0 - 9 9 .______________ 2 27 1 3 11 .0 10 28 82.0 first year. At the end of that time an addi­ 6 3 3 -8 .......... ................... 14 23 15 16 2 6 .0 26 25 145.0 tional 40 percent of the rehabilitation will i 261/1262-17________ 1 28 2 28 6 .0 5 1 71.0 be undertaken if the line is increasing its traffic sufficiently. If by the end of the Source: “ Indiana State R a il P lan, Final Phase 2,” op . cit;,p . 35. subsidy period the line is profitable, it will be completely rehabilitated prior to transfer T able II.— Subsidy priority ranks Indiana lines. Full evaluations of the to a solvent railroad. individual lines will be published sepa­ A firm commitment by shippers on the line Priority USRA rately at a later date. Included in the to continue subsidizing the service, or their ■rank segm ent L in e description 1 present discussion are summaries of the active participation in the subsidy program, N o. evaluations of each of the lines and of could also result in complete rehabilitation. the actions^ which may be necessary to It is assumed that the FRA will permit 1 589/590-99 N orth V ernon to M adison; make the lines economical. The Office operations on the line at less than Class I 2 578/579a-99 E m p oria to Carthage. levels until the line is rehabilitated. 3 571/571a-99 V alle y Jet., Ohio, to B rook - has found that there are many actions One final point on rehabilitation is that 4 4 2 9 -2 ville. P ortland to Monroe. which could be applied to all of the this work should be let for bid to firms in­ 5 417a-99 A u b u r n to A u b u rn Jet. lines; therefore, this discussion will first volved in rail rehabilitation.29 6 399-99 G oshen to Shipshew anna; analyze those actions capable of general 7 1261-1/1262-17 N orth Judson to Decatur. application. It will then briefly discuss Lines to be Subsidized 8 401-99 M ontgom ery, M ic h ., to A n ­ gola. the lines on an individual basis, identi­ In selecting those essential rail lines 9 418-1 W olcottville State line. to Michigan fying the lines, some of their specific to be considered for Federal/State as­ 10 630-99 K enn eth to Effner. problems, and the actions best-suited to sistance monies the State Planning Staff 11 4 2 3 -2 41 9-4 Logansport to Lucerne. Mexico to R oann (served dealing with those problems. 12 considered the following seven factors: from D e n v e r). Actions which may be Necessary for all 13 554-8 H u n ter to M axw ell and (1) Traffiic on the segment. W ilk in son to L y n n (served Lines Studied. (2 ) Energy consumption impact. from N e w Castle). For purposes of this report, the courses (3) Environmental impact. 14 523-1 E lw ood to Frankton. (4) Alternative mode operating cost im­ 15 4 2 0 -2 South W h itley to Lib erty of action which may be pursued in at­ pact. 16 524-2 M ills. E lw ood to H em lock. tempting to make the operation of the (5) Jobs lost to the community. 17 596-99 D u ff Jet. to W ashington. 14 lines economical have been divided (6) Wages lost to the community. 18 582-99 C olu m b u s to F la t R ock . into five categories: subsidization by the 19 574-2 Zionsville to W hitestow n. (7) Amount of subsidy required.30 20 584-0 Shelbyville to Fenns. public sector; increased railroad revenue Using these seven evaluation criteria 21 591-3 C ory to Mancourt (served and/or traffic; decreased railroad costs; as a base, the state assigned priorities to 22 5 2 1 -2 from C la y C ity ). N e w C astle to H agerstow n; acquisition by other railroads and/or 28 USRA rail line segments identified as 23 633-8 G erm an tow n to K n igh ts- government entities; and economic de­ eligible to receive a Federal/State sub­ tow n (served from C a m ­ bridge C ity ). velopment programs. Each of the alter­ sidy. Table 1 gives the ranking based 24 556-99 R ich m on d to L y n n . natives has certain advantages and dis­ upon the seven evaluation criteria, for 25 585-99 S helbyville to R u sh ville. advantages, and it must be recognized 26 557-99 L y n n to Ridgeville. the 28 line segments. The sum of the 27 602-99 Craw fordsville t o W aveland. that there is no single “magic” formula seven rankings is also included in Table 28 414-2 H artsdale to Liverpool. for success. Obviously, these strategies are not mutually exclusive, and the par­ 1. The final priority rankings were ticular combination which will prove 1 Unless otherwise noted, rail service is from the first station.' most successful can best be determined 20 Indiana State Rail Plan, Preliminary See only after an extensive examination of Phase 2, Volume I, op. cit„, pp. 18-19; and p . Source: Indiana State rail p lan, final phase, 2, op. cit., Indiana State Rail Plan, Final Phase 2, op. 36. the many factors affecting traffic and cit., pp. 9-11. R esults of the RSPO E valuations market potentials. The ultimate choice 30See Indiana State Rail Plan, Preliminary among strategies may vary with the line Phase 2, Volume I, op. cit., p. 83; and Indi­ The remainder of this summary con­ segment and may be determined by po­ ana State Rail Plan, Final Phase 2, op. cit., sists of a discussion of the results of litical imperatives as well as the de­ p. 33. RSPO’s in-depth evaluations of the 14 mands of economic efficiency. FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 NOTICES 10145 Subsidization by the public sector. could be variable, e.g., the amount of the stantially greater than the State’s rev­ subsidy could vary with the volume of enues derived from taxes on shipments Direct subsidization by the public sec­ traffic, or the profit, or any specified generated on the branch lines and from tor is often advanced as the single best condition. One major problem is that county property taxes on line segments alternative to abandonment of light- with existing branch line data problems, proposed for discontinuance. Tax for­ density lines. Proponents of this view­ it would be very difficult to determine giveness on the basis of rail usage is point cite the provisions of the RRR Act the exact amount of subsidy needed. A another possibility which might be con­ which imply that, if it is in the public reliable technique for estimating future sidered. Tax relief programs used in con­ interest to continue rail services that demands for market conditions for each junction with other techniques would are not financially viable in the private firm on the line is mandatory. further reduce the apparent cost of sup­ sector, the public must be willing to as­ An indirect form of subsidy which porting rail operations, e.g., tax relief sume at least partial financial responsi­ could be employed is a user tax based on could reduce the reported breakeven op­ bility for the losses incurred. other modes serving the area, with the erating cost and thereby reduce any sub­ Section 402(a)(1) of the Act provides resultant revenues either helping the sidy payments. A rate increase, in con­ financial assistance “ * * * in the provi­ branch line or being used for other eco­ junction with tax relief could also be em­ sion of rail service continuation pay­ nomic stimulus in the area. The main ployed. Another combination would be to ments, the acquisition or modernization problem with this form of subsidy is increase traffic volume in conjunction of rail properties, including the preserva­ that the basic costs of transportation to with tax relief so that the breakeven tion of rights-of-way for future rail serv­ area firms might effectively eliminate point could be reached. However, it must ice, the construction or improvement of them from more distant markets and, be pointed out that the difference be­ facilities necessary to accommodate the in effect, cause a downturn in their over­ tween tax relief and explicit subsidy is transportation of freight previously all business. more illusory than real. If county prop­ moved by rail service, and the cost of op­ Another form of subsidy to be consid­ erty taxes are forgiven, either the bur­ erating and maintaining rail service ered is a payment by the State to rail den must be borne by other businesses facilities such as yards, shops, docks or users for increased rail use, which would and. residents in the county, or county other facilities useful in facilitating and be the same as a rate reduction to ship­ services will have to be reduced. Essen­ maintaining main line or local rail serv­ pers and consignees. The amount of the tially, this is also true on the State level. ice.” 81 The Act provides a detailed pro­ subsidy could be determined by how re­ The local or State government could cedure for the determination of rail serv­ sponsive the demand for rail services was assist branch line operations with a vari­ ice continuation payments; however, to the reduction in rates. If the subsidy ety of other capital subsidy programs from the language of section 402 and were paid for terminating as well as orig­ used separately or together with operat­ from the funding provisions of the Act, inating traffic, it would provide a di­ ing subsidies or tax relief. SUch programs as amended by the RRRR Act, it is clear rect incentive to induce consignees as could involve grants for line rehabilita­ that a service continuation subsidy is to well as shippers to use rail. A word of tion and repair; the purchase of equip­ be viewed as a short-term transitional caution, however, is warranted. An in­ ment; interest rate subsidies; or loan measure and not as a permanent solution centive to compensate for any imbal­ guarantees. The latter two types of sup­ to the problem of a light-density line. ances found between inbound and out­ port are longer range in nature and There are numerous alternatives to rail bound traffic would have to be devised to might be expected to have little immedi­ service >continuation payments which insure the success of a subsidy program. ate effects on branch line continuance; could be employed by the State of Indi­ It should be stressed that a complete however, if offered in cooperation with ana. However, before discussing these al­ understanding of traffic flows, rates, and other types of State aid, they might prove ternatives, it is necessary to discuss the comparative system costs is necessary attractive. question of rehabilitation of the lines. prior to the implementation of any of the Increased railroad revenue and/or The Office has concluded from its study subsidy alternatives discussed in this Re­ traffic. The State should explore all pos­ that, in almost all cases studied, unless port. Shipper responses provide little sibilities which might result in increas­ the individual lines are rehabilitated to basis for judging the likely success (or ing the revenues generated by the lines. at least FRA Class I standards, imple­ cost) of different subsidy alternatives. The adoption of one or more of the fol­ mentation of any other courses of action Information must be obtained through a lowing actions on each line could help to will not prove sufficient to make the detailed review of the transportation re­ accomplish this objective; • lines economical. In some cases, lines quirements and market potential for (1) A restructuring of freight rates on which could ordinarily be served easily each of the firms on the line to be sub­ traffic on the branches is necessary.32 in one day require two days because the sidized. Based upon the ability of users and con­ trains must literally creep across the Many shippers or consignees will not sumers to stand the burden, freight rates tracks. It is doubtful that any combina­ use rail service unless the service is im­ need to be increased. An examination of tion of incentives will serve to increase proved over its current levels of opera­ the users surveyed by the RSPO Teams traffic over such lines as long as their tion, which means an increase in costs, found that on many of the lines the in­ condition, and consequently, their serv- both in operations and maintenance. The creased costs to the users which would ice, continues to deteriorate. Conversely, State could grant a subsidy either to a result from a rate increase on most traf­ the rehabilitation of these lines will con­ carrier or to the firms using the rail serv­ fic was small, i.e., transportation costs tribute to an immediate reduction in op­ ice, with the necessary revenues pro­ do not comprise a large share of the total erating costs, and the improved service vided by the users as a supplemental costs of products shipped. over the line should, hopefully, produce charge which would cover both operating an increase in shipments. Furthermore, and capital losses of the branch line. once a line is rehabilitated it will be more This form of exchange would avoid any with 32 Railroad rates aire set in a complex way many factors given consideration that attractive to potential rail patrons and, subsidy and place the burden of main­ frequently result in charges for particular in some instances, to railroads, which taining the service on the beneficiaries. shipments having little relationship to the at present are not interested in either In effect, the objections of an indirect cost of trasporting the commodities moved. acquiring or operating it. charge from other modes would be elim­ In addition, once negotiated, the rate levels, Among the alternatives to rail service inated; however, the result might well as well as the specific rate, are difficult to continuation payments would be a direct be the same, an eventual loss of business proach change. It is imperative that a systems ap­ be utilized in examination of the payment of an operating subsidy to cover and rail traffic to other modes because of reasonableness of the level of rates for the some specific portion of the branch line the higher effective costs of using rail specific branch lines. In many cases, the costs, e.g.,. maintenance or operating service. cross-subsidization of rates by previous rail costs. Another form would be a general Another alternative to direct payment carrier managements may have been utilized subsidy based on factors such as antic­ o f a specific subsidy would be some form to accomplish a completely different set of ipated traffic volume. Such a subsidy of tax forgiveness by the State and/or goals, with a dfferent operating configura­ local communities and counties. Most tion, than those of the present rail opera­ ** 45 U.S.C. 762. branch line deficits appear to be sub­ tions. FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 10446 NOTICES (2) The effects of reducing rates to arrange for those levels of service over local shippers, employees, or other rail should also be explored. In some in­ a line which would encourage rail usage. carriers. Under such an arrangement, stances, such a reduction might result Acquisitions by other railroads and/or the owners might lease the line to Con- in more revenues through increased traf­ government entities rail or some other carrier and contract fic than would an increase in rates, for desired service levels. The local which could have the effect of reducing Besides subsidizing light-density lines, group might also decide to operate the traffic. whether directly or indirectly, the State branch line as a shortline railroad; how­ (3) A surcharge could be placed on all should consider purchasing some of the ever, it must be recognized that the as­ shipments, either on a per-unit basis or lines in order to continue needed rail sumption behind all such proposals is on the basis of an absolute charge per service. The concept of State-owned rail­ that the new owners can operate the line rail patron. roads is neither a new nor novel ap­ at lower cost or generate more traffic (4) Rail patrons and the railroad proach. The States of Georgia, North revenues than the prior rail manage­ could engage in cooperative activities de­ Carolina and Vermont have owned and ment. In these types of proposals, lower signed to increase business. For example, leased rail lines for many years.33 Many costs are expected to result from “im­ some of the lines serve areas where individuals expect more States to adopt proved” labor conditions and the use of the mobile home industry is predomi­ this course in the future; however, the different techniques for maintenance nant. The finished product of this indus­ long-term financial commitments in­ and operation. Some shortlines have op­ try does not move out by rail at the volved in this aproach may not be uni­ erated with less restrictive labor rules, present time; shippers and the railroad versally appealing. but unless better service levels results, could work together to try to develop In considering whether to purchase a it cannot be assumed that local busi­ a rail car to move this product. line, a State must consider the purchase nesses, even with a financial interest in (5) Users of a line could agree to guar­ price and the rent to be paid to the State the railroad, will assure greater freight antee to ship a specific amount of goods for use of the line. The salvage value of revenues and profits. Short line reve­ a year. Agreements for such “ loyalty” the line, assuming abandonment, should nues, to a large extent, depend upon the shipments could include a scale to adjust be the upper limit of its purchase price; rate divisions or freight absorption for future cost changes. rent should be based on the traffic vol­ worked out with the main line carriers, (6) The State should explore the pos­ ume generated. Any difference between and the feasibility of such ownership sibility of taking an active role in rate the rental costs and the cost of main­ proposals must be examined with care. negotiations, either through trying to taining the line and the return the State There is an advantage in placing the help a branch line obtain a larger share could have earned on the funds (through responsibility and control in the charge of existing revenues or through encour­ other projects), in effect would repre­ of those who benefit most directly from aging shipper routings that would result sent the subsidy fofr the operation of the preservation of the service. However, in the operating carrier receiving a the branch line. it must be realized that in many cases longer haul. these are small businesses and their After purchasing a line the State could managements simply may not be capa­ (7) Local industries should be encour­ lease the line to a rail carrier for a spec­ aged to use the branch line, even if it ified level of service. This procedure ble of running their business and a rail­ means shifting tonnage from a preferred would assure service in instances where road at the same time. It is suggested mode. that the State might have to play a sig­ the railroad was uncertain about the nificant role in freight rate negotiations (8) The State should pursue an indus­ duration of operating assistance from trial development program designed to a State or had failed to adequately fore­ and be ready with subsidy if the opera­ bring about a greater diversification of cast future traffic levels. The State may tion failed. Such failure would obviously traffic on the lines. reflect on the financial viability of the wish to take an equity position in the owners of the branch line and could re­ (9) The use of team tracks should case of several branch lines to improve sult in the failure of the firms involved also be encouraged. its bargaining position in negotiations and economic catastrophe for the en­ Reductions in railroad costs. The State with rail earlier management with re­ tire region. should also explore all possibilities for spect to service levels on other branch It should be noted that a State may reducing costs of operations on the lines. lines. It is important to recognize that use Federal funds under the RRR Act, The following actions should be con­ unless a State purchase/lease-back or as amended, to purchase the lines or to sidered : purchase/contract for services allows a provide for their operation and rehabil­ (1) The State should meet with the savings on the maintenance or rehabili­ itation to FRA Class I standards through operating railroads, organized labor, and tation costs of a line, there is little to accelerated maintenance. The State other interested parties to examine recommend it. In other words, a truly cannot do both. In other words, once a whether special labor agreements may be uneconomic line will not change its per­ State uses the funds to purchase a line, negotiated which might result in lower formance as a result of a change in it can no longer receive Federal funds operating costs and greater productivity ownership. for the operation or the rehabilitation of in the service of the branch lines. Among If a State purchased a line and con­ that line. Therefore, it would be to the the things to be considered would be: tracted for services, it would be in the State’s advantage, whenever it decides crew size reductions; local operating/ transportation business and have a di­ that it wants to acquire a line, to post­ work rule modifications, and crew as­ rect role in the determination o f freight pone acquisition until the line has been signments on main-line and yard termi­ rates over its portion of the lines. Such rehabilitated. nal operations. The parties should also an arrangement could be handled in two It should also be noted that in some explore ways in which costs could be ways: the State could contract with Con- cases, it may prove cheaper in the long reduced by such actions as sharing rail or another carrier for a specified run for a State to rehabilitate the line clerical responsibilities. level of service on the branch line and and actually give that line to a profitable ( (2) The State could asume responsi­ in turn, sell that service to users; or the railroad, than for the State to continue bility for vegetation control programs States could publish a set of tariffs and to participate in paying for subsidized near highway crossings; maintenance of negotiate the division of revenue as well operations over that line. grade crossings; installation of highway as the price that Conrail or another car­ One other alternative that should be crossing protection; and other high rier could charge for providing service considered by the State is the preserva­ maintenance, cost items. Individual com­ over the branch line. tion of rights-of-way. If a decision is munities, with or without State assist­ Another alternative to maintain rail made with regard to a particular line ance could assume shared responsibility service would be ownership by groups of that no combination of actions can rea­ for such programs. The State could also sonably be expected to make operation arrange for a reduction of highway grade 33William R. Black and James F. Runke, of the line economical, the State must crossings. The State and Rural Rail Preservation; Al­ ternative Strategies, (Lexington: The Coun­ consider whether the line should be pre­ (3) The State, the operating railroadscil of State Governments, October, 1975) pp. served for the future. A State may have and interested parties should also seek 61-62. a quite distinct interest in the preser- FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 NOTICES 10447 vation of a right-of-way and the preser­ point. The day has long since passed when Line-by-Line Analysis vation of operations over It. Even if a cheap rail transportation costs invited major industrial facilities to locate inland. VSRA Line No. 399: Shipshewana right-of-way has little present potential, Branch. The Shipshewana Branch, for­ its dismantling could have a serious fu­ Nowadays the pressure to cut the cost oi handling baslo bulk materials dictates the merly part of the New York Central ture impact on the area in which it is choice of coastal sites for major industrial Railroad, extends easterly from Goshen, located. Furthermore, as energy costs in­ facilities.8* Indiana (milepost 0.2) to Shipshewana, crease in the future, motor carriers may Indiana (milepost 16.7), a distance of lose their competitive advantage in serv­ It should be noted that some of the 16.5 miles. (Goshen traffic is not in­ ing industries located on some of the methods listed earlier that could be em­ cluded in this line analysis since it is light-density lines, and many of the ployed to keep an excluded line in serv­ being served by Conrail.) The line is costs and service disadvantages of these ice, such as a rail patron surcharge, may located in both Elkhart and La Grange lines may decline. discourage new industries from locating Counties. The Branch connects at Economic development programs to on that line. All other factors being Goshen with both Conrail’s Chicago to attract, rail-dependent industries. Every equal, a decision by a prospective rail Buffalo line and its Warsaw to Marion possible effort should be expended to at­ user to locate on a rail line excluded line. On April 16, 1976, the Penn Cen­ tract rail-dependent industries to light- from Conrail generally involves a much tral stopped all operations over the density lines. Essential to the achieve­ higher risk than a similar decision to Branch because of unsafe track condi­ ment of such a goal is the rehabilitation locate on a profitable railroad. tions. An embargo notice (No. 14-75) of the lines, since new industries will not was issued on all traffic, effective April 21, even consider locating on a line which 1975, to or from* all stations on the line is not up to at least FRA Class I Stand­ 84 Eliot Janeway,“ U.S. Steel Bets Against Inflation,” The Washington Star, July 7,1976, except Goshen. Rail service had not ards. Even when a line is in good con­ p. A-19. been resumed as of December, 1976. dition, the competition to attract indus­ tries is extreme.®4 As David Richmond, FIGURE 1 the Economic Development Director of the Columbus Area Chamber of Com­ merce (Indiana) pointed out, “ While some 3,500 new industrial plants are built each year, 16,000 development groups are at work trying to lure them.85 It should also be recognized that while available rail transportation is an im­ portant criterion in site selection, it is only one of many and in a number of cases is actually the least important. In discussing the U.S. Steel Corporation’s decision to locate a major steel mill in Conneaut, Ohio, Eliot Janeway made the following observation: * * * The consideration that stamps Con­ neaut, Ohio as a growth center of the future is neither accidental nor whimsical. Conneaut will be a major steel mill center because it already is a minor water shipping The recent establishment of a Volks­ wagen “Rabbit” assembly plant at New Stan­ ton, Pennsylvania, is a classic example o f the lengths to which development groups will go to secure industries. The reported initial package of incentives offered Volkswagen in­ cluded the following: The company would be exempted from franchise and realty transfer taxes. The Pennsylvania Industrial Development Authority would grant a $40 million loan to The Shipshewana Branch'" serves an trons, and, information received from the buy an unused Chrysler Corporation plant area of northeastern Indiana which is Penn Central during the restructuring for the auto firm to lease. primarily agricultural and rural in na­ in 1974 provided the RSPO Project Team, The State would spend $30 million of high­ ture. It is characterized by a number of with a list of 37 firms that were alleged way and rail links to the plant. The State would waive 95 percent of local small towns which serve as trading cen­ to have used the Shipshewana Branch. taxes the first two years and 50 percent the ters for the surrounding farms. In the Of these 37 firm», four were no longer following two years. two counties which the line serves, only in existence at the time the RSPO Proj­ The State would arrange for employee the towns .of Elkhart and Goshen are ect Team was interviewing, and local tr°ining. of sufficient size and market area to sup­ officials and rail patrons had no knowl­ The State would provide a $135 million port a relatively extensive non-agricul- edge of the existence of four other firms. tooling loan (Volkswagen decided later to tural sector. While industrial develop­ The 29 remaining firms were judged ca­ do its own financing on this proposal when negotiations with Pennsylvania became ment in the general area served by the pable of generating carload business. snagged). line has been impressive over the past The other businesses in these towns are Source: “Rabbits In The Cabbage Patch,” decade, that growth has been primarily almost exclusively small commercial and The Wall Street Journal, Vol. C L X X X V m , in an industry, the manufacturing of retail establishments that rely entirely No. 6, August 17, 1976, p. 18; “ GOP Study mobile and modular homes and recrea­ on motor carriers to handle their pre­ Queries VW Plant Figures,” The Washington tional vehicles, which appears to be dominantly small shipments. Star, No. 275, October 1, 1976, p. C-6; Terry P. somewhat limited in its ability to use Of the 29 principal businesses, seven Brown, “VW Delays Start-Up Date At Its rail service. Lumber used by this indus­ are directly associated with the manu­ Facility in New Stanton: Parts Problems De­ velop,” The Wall Street Journal, Vol. try may be shipped in by rail, but the facture of mobile and modular homes C L X X X V m , No. 68, October 6, 1976, p. 2. finished products are shipped out by and recreational vehicles; six provide ac­ 86David Richmond, “Americans Battle For truck. cessories or services to this industry; six Industry,” The Republic, June 18, 1976, p. The State of Indiana, the Goshen have an agricultural orientation; three A-l. Chamber of Commerce, local rail pa- are retail lumber and building supply FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 10448 NOTICES dealers; and seven are engaged in a wide fic is not included in this line analysis through Pleasant Lake (milepost 35.7) range of other activities. Ten of these since it is being served by the Hillsdale to Waterloo, Indiana (milepost 25.6). it firms stated that they had never used the County Railway Company, Inc.) That should be noted that during the 1976 Shipshewana Branch and had no in­ portion of the line which is located in tourist season, the Little Miami Railroad tention of using it in the future. Four Indiana serves portions of Steuben operates steam engine passenger train firms indicated that they had used the County. At one time the Waterloo Branch service on Saturdays, Sundays, and holi­ Branch in the past (between 1961 and extended directly south from Angola days between Angola and Pleasant Lake. 1970) but had no intention of using it in the future. One firm stated that it had FIGURE 2 never used the Branch but did use the former Penn Central line at Goshen. Four firms stated that they were active users'of the Branch during the period from 1967 to 1973, but for a variety of reasons they have curtailed their use of the service. The remaining ten rail pa­ trons were active users of the line during .1974 and until its close in 1975. Carload traffic statistics for the Branch for the years 1952 through 1975, indicated: (1) There was a 55 percent decline in traffic volume between 1970 and 1974; (2) only 3.5 percent of the total-volume generated by the line was originating traffic; (3) in 1973, lumber and wood products accounted for 70.7 percent of the total carloads generated; (4) traffic on the line was predominantly “short-haul” business for the Penn Cen­ tral; (5) of the total revenue generated by the line, only 19.5 percent was Penn Central’s share; and (6) average reve­ nues received on this line were lower than system averages. Ten firms presented RSPO with in­ formation concerning their alternate shipping arrangements. Six of the firms have shifted traffic to other railheads in the general area, using motor carriage The Waterloo Branch provides service patrons had no knowledge of the exist­ for the last segment of the journey. Four through the extreme northeastern por­ ence of five other firms. Seven firms were firms have totally abandoned rail service. tion of the State of Indiana. Steuben immediately rejected for interviewing County is contiguous with Branch and purposes because of their size, type of C onclusions Hillsdale Counties in Michigan, and Wil­ product sold or service rendered. The The option of operating this line as a liams County in Ohio. This area is pri­ remaining 45 firms were judged capable short line railroad owned by an inde­ marily agricultural and rural in nature, of generating carload business. The pendent and/or rail patron operator producing significant amounts of live­ other businesses in these towns are al­ should be considered. The new operator, stock, dairy products, soybeans, small most exclusively small commercial and with State assistance, could attempt to grains, and the usual wide variety of retail establishments that rely entirely renegotiate rates with Conrail, based truck crops which are typical of the en­ on cars being terminated at Goshen, and tire State. Geographically, the area is on motor carriers to handle their pre­ could assess patrons on the line a flat characterized by flat to gently rolling dominantly small shipments. charge for handling their traffic between fertile farm land, with numerous lakes Of the 45 firms interviewed, 23 firms Goshen and their siding or the nearest and rivers which attract a substantial stated that they had never used the rail­ team track. Off-track mobile track equip­ number of tourists. No large towns are road and have no intention of using it ment of the type employed by the Hills­ in the future. Six firms indicated that dale County Railway Company, Inc., on situated within Steuben County or with­ they had used the railroad in the past USRA Line No. 401, to handle a limited in the service area of the Branch. Most (between 1964 and 1975) but had no in­ number of cars might be effectively em­ of the towns within the County are ba­ tention of using it in the future..Eight ployed on these excluded rail lines. More­ sically trading centers, servicing the sur­ firms claimed they were active users of over, the employment of this equipment rounding agricultural area. Angola is the the railroad until 1975 but for a variety to serve several Indiana light-density County seat and is typical of the towns of reasons has curtailed their use of the lines is a possibility. in the region. Industrial employment in service. The remaining eight rail patrons Rail patrons should explore with Con- the town is dominated by light manufac­ are active users of the line. Of the eight rail the feasibility of developing a new turing and professional and related firms interviewed, three flatly stated that type of rail car designed to move recrea­ services follow close behind. they were not contemplating any future tional vehicles or mobile homes. The State of Indiana, the Angola and expansion and one stated that, while no USRA Line No. 401: Waterloo Branch. Fremont Chambers of Commerce, the future plant expansion was contemplat­ The Waterloo Branch, formerly part of Hillsdale County Railway Company, lo­ ed, sales were expected to rise. Four firms the New York Central Railroad, extends cal rail patrons, and information re­ expected to increase their storage facili­ northeast from Angola, Indiana (mile­ ceived from the Penn Central during the ties. post 39.7) through Fremont (milepost Carload traffic statistics applicable to 47.4), Ray, Indiana (milepost 51.5), and railroad restructuring in 1974, provided the Angola-Montgomery line indicate : Montgomery, Michigan (milepost 54.8) the RSPO Project Team with a list of 60 (1) The line has a limited number of rail to Hillsdale, Michigan. The State of Indi­ firms that were alleged to have used the patrons and commodities; (2) traffic vol­ ana requested the RSPO to analyze only Angola-Montgomery Line. Of these 60 ume is declining; (3) the line generates that portion of the Waterloo Branch that firms, three were no longer in existence primarily terminating traffic; (4) the extends from Angola to Montgomery, a at the time the RSPO Project Team was Penn Central received only approxi­ distance of 15.1 miles. (Montgomery traf­ interviewing, and local officials and rail mately 32 percent of the total revenue FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 NOTICES 10449 generated; and (5) average line revenues The continued operation of this line were lower than system averages. by the Hillsdale County Railway Com­ For the period April through Septem­ pany, Inc., a short line railroad, should ber, 1976, actual train operations over result in the most economical operation. the line segment incurred a, deficit of USRA Line No. 417a: Auburn June- $28,358. For nine months of operation tion Branch. The Auburn Junction (April through December), the line gen­ Branch, formerly part of the New York erated 139 carloads of freight; on an an­ Central Railroad, extends northeasterly nualized basis this indicates that traffic from Auburn Junction, Indiana (mile­ levels have fallen by more than 30 per­ post 81.4) to Auburn, Indiana (milepost cent since 1973. 82.8), a distance of 1.4 miles. H ie line is C onclusions located in Dekalb County and connects The viability of the line could be im­ at Auburn Junction-with the Chessie proved by upgrading and promoting the System’s main line between Chicago and use of team tracks along the line. Pittsburgh. F IG U R E 3 The Auburn Junction to Auburn line Carload traffic statistics applicable to provides service through an area of In­ the line indicate: (1) The line is de­ diana which is predominantly agricul­ pendent on the shipment of one rail pa­ tural in nature. The area produces live­ tron, and he ships a limited number of stock, dairy products, soybeans, and a commodities; (2) traffic volume is de­ number of small grains, such as wheat. clining; (3) the line generates only termi­ Cash truck crops also are produced by nating traffic; and (4) Penn Central re­ farms in the area. Most of the towns in ceived only 32.9 percent of the total rev­ the County are small, serving as market enues generated by these shipments. centers for the surrounding agricultural For the months of May, June, and July, area. Auburn, however, and several of 1976, actual train operations over the the smaller towns in the southern por­ line segment incurred a deficit of $4,592. tion of the County, possess a greater pro­ However, for the three months of April portion of manufacturing activity than to June, the line generated 81 carloads is true of towns in counties to the north of freight; on an annualized basis, this and west. The proximity of Dekalb indicates that traffic levels have increased County to the Fort Wayne SMSA is un­ nearly 9 percent over 1973 levels. doubtedly the major reason for this C onclusions higher level of manufacturing activity. The State of Indiana, the Auburn The viability of the line could be im­ Chamber of Commerce, local rail patrons, proved by upgrading and promoting the and information received from the Penn team tracks at Auburn. Central during the railroad restructur­ The purchase of the line by the State ing in 1974, provided the RSPO Project for an ultimate transfer to the Chessie Team with a list of 23 firms that were System should be considered. alleged to have used the Aliburn Junc­ A short line operator, with State tion to Auburn line. Of these 23 firms, assistance, could attempt to renegotiate only three were active rail users in 1976. rates with the Chessie, based on the The RSPO Project Team found no evi­ cars being terminated at Auburn Junc­ dence of industrial planning or develop­ tion, and could assess rail patrons a flat ment along the line. charge for the handling of the cars be- FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FLBRUARY 72, 1977 10450 NOTICES tween Auburn Junction and their siding the GR&I Branch that extends from or the nearest team track. Kendallville (milepost 121.0) to the USRA Line No. 41ft; Grand Rapids and Indiana-Michigan State line (milepost Indiana Branch. The GR&I Branch, for­ 146.4), a distance of 25.4 miles. (Ken­ merly part of the Pennsylvania Railroad, dallville traffic is not included in this line extends northwesterly from Kendallville, analysis since it is being served by Con- Indiana (milepost 121.0) through Wol- rail.) This portion of the line is located cottville (milepost 129.3), La Grange in both La Grange and Noble Counties (milepost 138.0), and Howe, Indiana (milepost 143.7) to Sturgis, Michigan and connects at Kendallville with Con- (milepost 149.4), a distance of 28.4 miles. rail’s Chicago-Toledo line; at Wolcott- The State of Indiana requested the vilie with the N&W Railway; and at RSPO to analyze only that portion of Sturgis with Conrail. FIGURE 4 The GR&I Branch provides service of industrial planning or development through a rural area of extreme north­ along the line. eastern Indiana which is dominated by For the months of May, June and July, agriculture. The area produces livestock, 1976, actual train operations over the dairy products, soybeans, various small line segment incurred a deficit of $7,532. grains, and the typical variety of truck For six months of operation (April-Sep- crops common to farms in this part of tember) the line generated 77 carloads the country. The region also has a sig­ of freight; on an annualized basis this nificant forestry industry. In addition indicates that traffic levels have fallen to-agriculture and forestry, the area is to 35.3 percent of 1973 levels. influenced by the manufacturing of mo­ bile an dmodular homes and recreation­ C onclusions al vehicles. Towns in this area are small The benefits of terminating rail serv­ and typically serve as market centers ice between Kendallville and La Grange for the surrounding agricultural area. should be considered. The only towns of significant size in the Upgrading and promoting the use of service area of the branch are La Grange, the N&W team track at Wolcottville the county seat of La Grange County, should be considered. and Kendallville. The possibility of having rail patrons Of the list of rail patrons supplied to between the Indiana-Michigan State the RSPO Project Team, only nine firms, line and La Grange served by Conrail’s six of which are located in La Grange, Quincy-White Pigeon line which runs were active rail users in 1976. The line’s south from Sturgis, Michigan, should be traffic is dominated by Duo-Therm, a considered. division of Motor Wheel Corporation, USRA Line 419: Columbia City Sec­ which manufactures heating equipment ondary Track. The Columbia City Sec­ for the mobile and modular homes and ondary Track, formerly part of the Penn­ recreational vehicles industry. Duo- sylvania Railroad, extends northeaster­ Therm, which employs an average of ly from Mexico, Indiana (milepost 14.2) approximately 500 people in La Grange, through Denver (milepost 18.2), Roann accounted for 61.4 percent of the total (milepost 29.5), Ijamsville, and North carloads and 32.7 percent of the total Manchester (milepost 36.9) to Columbia tonnage generated in 1973 by the Branch. City, Indiana (milepost 55.3), a distance There are no longer any active rail pa­ of 41.1 miles. The State of Indiana re­ trons of this line in Wolcottville. The quested the RSPO to analyze only that RSPO Project Team found no evidence portion of the Columbia City Secondary FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 NOTICES 10451 Track that extends from Mexico (mile­ cated in both Miami and Wabash Coun­ months of operation (April-Sepiember), post 14.2) to North Manchester (milepost ties. This line branches off Conrail’s the line generated 65 carloads of freight; 36.9) a distance of 22.7 miles. (North Goshen to Anderson line at North Man­ on an annualized basis this indicates that Manchester traffic is not included in this chester, and crosses at grade with both traffic levels have fallen to 83.3 percent line analysis since it is being served by the EL line at Newton and the N&W at of 1973 levels. Conrail.) This portion of the line is lo- Denver, Indiana. While North Manchester appears to have the potential for modest growth, the FIGURE 5 area from Mexico up to North Man­ chester is essentially tied to a single in­ dustry and does not appear to have the potential for significant growth or the introduction of rail oriented industries (other than agri-businesses). The RSPO Project Team found no evidence of in­ dustrial planning or development along the line. C onclusions Terminating rail service between Ro- ann and North Manchester should be considered. The possibility of having rail patrons in the cities of Mexico and Roann served by the N&W should be considered. Consideration should be given to the possibility of terminating service along the entire line after establishing, upgrad­ ing, and promoting the use of the N&W team track at Denver. The purchase of the line for ultimate transfer to the N&W or a short line oper­ ator should be considered. A short line operator, with State assis­ tance, could atempt to renegotiate rates with the N&W based on the cars being terminated at Denver and could assess The Columbia City Secondary Track mercial and retail establishments that rail patrons a flat charge for the han­ services an area which is predominantly rely on motor carriers to handle their dling of the cars between Denver and agricultural and rural in nature. It predominantly small shipments. Mexico and Roann and their siding or specializes in the production of live­ Of the six firms interviewed, one firm the nearest team track. stock, dairy products, soybeans, and var­ indicated that it had used the railroad USRA Line No. 423: Culver Secondary ious small cash grains. The towns along in 1964 but had no intention of using it Track. The Culver Secondary Track, the line and in the immediate area are in the future. The remaining five firms formerly part of the Pennsylvania Rail­ typical small rural towns, whose prin­ are active users of the line. Of the five road, extends directly north from cipal reason for being is to service the firms interviewed, four stated that they Logansport, Indiana (milepost 115.9), surrounding agricultural community. do not contemplate f uture expansion and through Lucerne (milepost 124.5) to Cul­ None of the towns involved has devel­ the remaining firm stated that it was ver, Indiana (milepost 148.6), a distance oped large nonagricultural economic sec­ just completing its new 50,000 bushel of 32.7 miles. The State of Indiana tors. Of the six principal establishments grain storage facility. requested the RSPO to analyze only along the line, five have an agricultural Carload traffic statistics applicable to that portion o f the Culver Secondary orientation and one is a brass foundry. the Mexico to North Manchester line in­ Track that extends from Logansport to The State of Indiana, the North Man­ dicate: (1) That with but few exceptions, Lucerne, a distance of 8.6 miles. (Logans­ chester Chamber of Commerce, local rail the basic commodities transported to or port traffic is not included in this line patrons, and information received from from points on the line have historically analysis since it is being served by Con- the Penn Central during the railroad re­ consisted of agriculture-related prod­ rail.) This portion of the line is located structuring in 1974 provided the RSPO ucts; (2) the line serves a limited num­ in Cass County. At one time the Culver Project Team with a list of 11 firms that ber of rail patrons; (3) traffic volume is Secondary Track extended northward were alleged to have used the Mexico declining; (4) the line originates pri­ from Logansport through Plymouth and to North Manchester portion of the line. marily seasonal traffic; (5) originating all the way to South Bend, Indiana. That Of these 11 firms, three were no longer traffic on the line was mainly destined portion of the line under study connects in existence at the time the RSPO Proj­ for export via the east coast; (6) of the at Logansport with Conrail’s Chicago-to- ect Team was interviewing and two total revenue generated by the line, over Columbus line, the N&W and Conrail’s others were found to be located on an­ 67 percent was Penn Central’s share; and other Penn Central line in North Man­ <7) average line revenues were higher I&F Branch. Kewanna is served by the chester. The remaining six firms were than system averages. Chessie System’s Chicago-Cincinnati line judged capable of generating carload For the months of May, June and July, and DeLong is served by the Chicago- business. The other businesses in these 1976, actual train operation over the line Marion, Ohio line which is being oper­ towns are almost exclusively small com- incurred a deficit of $11,073. For six ated by Conrail. FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 10452 NOTICES FIGURE 6 The Culver Secondary Track provides 1973 to 1975; (2) traffic density, cars per service through an area which is pri­ mile, along the entire line was: 11.3 in marily agricultural and rural in char­ 1969; 5.4 in 1970; 5.2 in 1971; and 3.4 acter. Case County is not located near in 1972; <3) with but few exceptions, the any of the highly populated SMSA’s in basic commodities transported to or from Indiana and is not distinguished by any points on the entire line have historically significant industrial development. With consisted of agriculture related products; the exception of Logansport, which (4) only terminating traffic was gener­ serves as a distribution center and the ated by the line; and (5) while per ton county seat, the towns along the line are revenue averages were lower than sys­ small in size and provide services for the tem averages, car revenue averages were surrounding farms. higher. The State of Indiana, the Logansport For the months of May, June and Chamber of Commerce, local rail patrons, July of 1976, actual train operations over and information received from the Penn the Logansport-Luceme line segment in­ Central during the railroad restructur­ curred a deficit of $1,257. For six months ing in 1974 provided the RSPO Project of operation (April-September) the line Team with a list of 4 firms that were al­ generated 22 carloads of freight; on an leged to have used the Logansport- annualized basis this Indicated that traf­ Luceme portion of the line. Of these 4 fic levels have fallen to 45.8 percent of firms, one was located in Logansport and 1973 levels. smother, Scheetz Sales and Service, was While Logansport appears to have the preparing to go out of business. Lucerne potential for modest growth, the Lu­ Elevator and Sohigro are the only two cerne area is essentially a very small one- rail users of this line. industry town and does not appear to Carload traffic statistics applicable to have the potential for significant growth the Culver Secondary Track for the or the introduction of rail-oriented in­ years 1964-1975 indicated: (1) That dustries (other than agri-business). The while traffic over the entire line was de­ RSPO Project Team found no evidence creased steadily since 1969, it did sta­ of industrial planning or development bilize in Lucerne during the period from in the immediate area. FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 NOTICES 10453 C onclusions portion of the Ridgeville Secondary Team was interviewing, 4 firms were ac­ Track that extends fr o m ' Portland tually located on the N&W line in Port­ The extension of Conrail’s Logans - through Bryant (milepost 50.3), Ge­ land, and 3 firms were counted twice. port Yard Limits to include Lucerne neva (milepost 54.2), Berne (milepost Local officials and rail patrons had no should be negotiated. 56.8), and Monroe (milepost 64.8) to knowledge of the existence of 4 other Purchase of the line for ultimate Decatur, a distance of 27.2 miles. (Deca­ firms. The remaining 50 firms were transfer to Conrail should be consid­ tur traffic is not included in this line ana­ judged capable of generating carload ered. ': 'r: > ,;r v ;.T lysis since it is being served by Conrail.) business. The other businesses in these Upgrading and promoting the line’s This portion of the line is located in both towns are almost exclusively small com-, use as a team track should be con­ mercial and retail establishments that sidered. * Adams and Jay Counties. The Ridgeville rely entirely on motor carriers to handle VSRA Line No. 429: Ridgeville Second­ Secondary Track continues south from their predominantly small shipments. ary Track. The Ridgeville Secondary Ridgeville to Richmond and north from Of the 50 firms interviewed, 10 firms Track, formerly part of the Pennsylvania Decatur to Ft. Wayne. That portion of stated that they had never used the rail­ Railroad, extends directly north from tljp line under study connects at Decatur road and have no intention of using it Ridgeville, Indiana (milepost 33.0) with both the N&W and the former EL’s in the future. One firm indicated that it through Portland (milepost 43.2) to De­ had never used the railroad, but “antici­ catur, Indiana (milepost 70.4), a dis­ Chicago-Marion, Ohio line: there is also pated” its usage. Twelve firms indicated tance of 37.4 miles. The State of Indiana a non-active connection at Portland that they had used the railroad in the requested the RSPO to analyze only that with the N&W. past (between 1940 and 1973) but had no intention of using it in the future. ElE 7 Two firms claimed they were active users of the railroad until 1972 but for a vari­ ety of reasons had curtailed their use of the service. The remaining 25 rail pa­ trons are active users of the line. Of the 25 firms interviewed, 14 stated that they did not contemplate future production expansion and 5 stated that, while no plant expansion was contemplated, sales were expected to rise significantly. Carload traffic statistics applicable to the Portland-Decatur line indicate: (1) The line has a limited number of rail patrons and commodities generated; (2) traffic volume is declining; and (3) the line generates primarily terminating traffic. For the months of May, June and July of 1976, actual team operations over the line segment incurred a deficit of $11,121. For six months of operation (April- September), the line generated 213 car­ loads of freight; on an annualized basis this indicates that traffic levels have fallen to 57.4 percent of 1973 levels. C onclusions Rail patrons should explore with the operating railroad the feasibility of devel­ oping a new type of rail car designed to move mobile homes outbound from Mon­ roe and Portland over the railroad. The feasibility of extending Conrail’s Decatur Yard limits to include Berne and Monroe should be explored. Consideration should be given to serv­ ing rail patrons in the City of Portland by the N&W. The creation of a short line railroad by an independent and/or rail patron op­ *under sutoskfy tout of service erator to serve the branch should be con­ sidered. The operator, with State assist­ The Ridgeville Secondary Track serves 25 assemble and/or manufacture a di­ ance, could attempt to renegotiate rates an area which Is predominantly agricul­ versified number of products, 14 have an based on the cars being terminated at tural and rural in nature. Most of the agricultural orientation, 7 are retail lum­ Decatur or Portland and could then towns in the general area, and specifi­ ber and building supply dealers, and 8 assess rail patrons a flat charge for the cally in and around the branch line, are engage in a wide range of activities. handling of the cars between Decatur small in size, and serve primarily as The State of Indiana, the Chambers and Portland and their siding or the market centers for the surrounding agri­ of Commerce of Portland, Berne and nearest team track. cultural communities. Adams County, Decatur, local rail patrons, and informa­ The benefits of terminating rail serv­ however, is located in the extreme south­ tion received from the Penn Central dur­ ice between Portland and Berne should eastern comer of the Port Wayne SMSA, ing the railroad restructuring in 1974, be considered. and, therefore, has some industrial de­ provided the RSPO Project Team with a VSR A Line No. 523: Richmond velopment in its northern half. list of 68 firms (excluding those firms Branch. The Richmond Branch, formerly An analysis of the establishments located in Decatur and Hoagland which part of the Pennsylvania Railroad, ex­ along the line shows a heavy prepon­ are served by Conrail) that were alleged derance of firms that produce or sell to have used the Portland-Decatur line. tends from Anderson, Indiana (mile­ items that are not particularly rail- Of these 68 firms, 7 were no longer in post 123.3), northwest through Florida oriented. Of the 54 principal industries, existence at the time the RSPO Project (milepost 128.0), and Frankton (milepost FEDERAL REGISTER, VOL. 42, NO. 35;— TUESDAY, FEBRUARY 22, 1977 10454 NOTICES 132.8) to Van (Logansport), Indiana ysis since it is being served by Conrail.) Inbound shipments have been decreas­ (milepost 183.4), a distance of 60.1 miles. This portion of the line is located in ing slightly in the past five years, but The State of Indiana requested the RSPO Madison County. The line segment is part outbound shipments, due to the growth to analyze only that portion of the Rich­ of the Logansport-Richmond-Cincinnati of one of the shippers, Rydman and Fox, mond Branch that extends from Ander­ Branch. At Anderson, Oonrail’s Cleve- have been increasing. The great majority son (milepost 127.0) to Frankton (mile­ land-Indianapolis line, its Michigan of traffic on the line is accounted for by post 132.6), a distance of 5.6 miles. (An­ Branch, and its line to Emporia and the Rydman and Fox grain elevator, derson traffic is not included in this anal- Knightstown cross. which has increased its share and total amount of traffic as other firms de­ FIGURE 3 creased or kept theirs the same. This growth has occurred since 1974, when Rydman and Fox finished an 1800 foot siding to their plant and began shipping out grains. Before that year, shipments over the line were predominantly in­ bound; now the majority of shipments are outbound. The Rydman and Fox ele­ vator has more than doubled the car­ loads it shipped between 1974 and 1975. The firm has said that in two or three years this volume could double again, due to plans for additional storage which would allow the movement of grain in 100 car unit-trains. For the months of May, June and July, actual train operations over the Ander­ son to Frankton line segment incurred a deficit of $637. For six months of opera­ tion (April-September) the line gener­ ated 72 carloads of freight; on an annu­ alized basis tills would indicate that traf­ fic levels have increased to 248.3 percent of the 1973 levels. C onclusions The feasibility of extending Conrail’s Anderson Yard Limits to include the facilities of Rydman and Fox at mile­ post 130.2 should be explored. Simul­ This is a non-signaled, single track The track beyond milepost 130 to the taneously, the viability of the line could line served by a 4 or 5 man extra local end of track sign, milepost 132.6 has a be improved by upgrading and promot­ freight crew using a general purpose die­ number of deteriorated ties and loose ing the use of the line as a team track. sel unit (1750 H P). The train, consisting and broken rail joint bars and does not The improvement could be made around of 3 to 12 cars is assembled by a yard meet Class I track standards. milepost 130.2, with the cooperation of crew at Anderson and the extra local This 5.6 mile line was inspected by In­ Rydman and Fox. freight crew departs with the train and diana state track Inspectors who estimate The rehabilitation of certain sections travels a maximum of 0.6 miles from it would cost $97,608 to restore it to (milepost 127.0 to milepost 130.2).of the Anderson Yard to the most distant point, Class I standards. This cost would cover line would lower the operating costs, milepost 132.6, in serving rail patrons retieing through and repairing three thereby contributing significantly to the at Frankton. This crew will usually com­ road crossings. This line has 12 public future viability of the line, and at the plete work on the subsidized portion of road crossings at grade, one passing sid­ same time, improving its attractiveness the line in one hour. ing and several spur tracks in or near to both potential rail users and other This line from Anderson to milepost Frankton. railroads. 127 is in Conrail, and the patrons are The Branch serves an area which is The advantageous of purchasing the served by Conrail. ( . predominantly agricultural ahd rural in line »for ultimate transfer to Conrail This line is a portion of the former nature, characterized by general farm­ should be considered. Richmond Branch of the Cincinnati Di­ ing, livestock production, hog raising, USRA Line No. 554: Springfield vision and train and engine employees and the growing of winter wheat. Frank­ Branch. The Springfield Branch, former­ having seniority are used in manning ton is located within the Anderson SMSA ly part of the New York Central Railroad, trains operating on this line. Employees and is influenced by more non-agricul- extends directly west from Glen Karn, for the local freight crew are based at tural economic activity than would be Ohio (milepost 60.4), through Lynn, In­ Richmond, Indiana and, when called, are true of most rural locations. Frankton diana (milepost 68.6), Carlos City (mile­ deadheaded to Anderson. After perform­ has a population of 1,796 and has over post 74.5), Modoc (milepost 80.0), Lo- ing service on the line the crew is dead­ 340 farmers in its immediate vicinity. santville (milepost 83.5), Mooreland headed back to Richmond. Members of (milepost 87.6), Epileptic Village (mile­ The State of Indiana, the Anderson post 93.6), New Castle (milepost 95.3), the crew are paid two hours deadhead Chamber of Commerce, local rail pa­ from Richmond and two hours dead­ Kennard (milepost 104.1), Shirley (mile­ trons, and information received from the post 107.3), Wilkinson (milepost 109.0), head back to Richmond, plus mileage al­ Penn Central during the restructuring in lowance account, furnishing their own Maxwell (milepost 118.0), Mohawk (mile­ 1974, provided ttie RSPO Project Team post 121.5), and Mount Comfort (mile­ transportation. with a list of 6 firms that were alleged to post 125.6), to Hunter, Indiana (milepost This is a single track line consisting have used the Anderson to Frankton por­ 131.2), a distance of 70.8 miles. The line of 130 and 100 pound rail laid in lengths tion of the line. Of these 6 firms, one had continues west from Hunter to Indianap­ of 30 and 33 feet. The track between gone out of business and another “firm” olis and east from Glen Karn to Spring- milepost 127 and a point near milepost was actually two farmers who had last field. The State of Indiana requested thè 130 exceeds FRA Class I track standards. used the railroad in 1972. Of the remain­ RSPO to analyze two portions of the Conrail does not have any slow orders in ing four rail users, one had never used Branch : from Hunter to Maxwell, a dis­ effect on this line and timetable 6 au- the railroad in Frankton. The other three tance of 13.2 miles and from Wilkinson thorizes 30 m.p.h. on the line. rail patrons are active users of the line. to Lynn, a distance of 40.4 miles. The FEDERAL REGISTER, VOL. 42, NO. 35— -TUESDAY, FEBRUARY 22, 1977 NOTICES 104 nine-mile portion between Maxwell and Indiana serves portions of Marion, Han­ Wilkinson is not included in Conrail nor cock, Henry and Randolph Counties. is it being operated under the subsidy USRA Line No. 554 has connections with program. The 1.6 mile portion of the line the following lines ; the former Penn Cen­ at New Castle (milepost 96.9 to milepost tral’s Anderson to Grensburg Secondary 95.3) is included in Conrail; and, there­ Track at Shirley; Conrail’s Richmond fore, the traffic generated by it has not Branch, and the N&W at New Castle; the been included in this line analysis. That Chessie System at Losantville, and Con- portion of the line which is located in rail’s Newman Secondary Track at Lynn. FIGURE 9 The Springfield Branch provides serv­ ties; the remaining firms did not expect ice to an area that has a mixed rural and any expansion of facilities or sales. Rail diversified industrial environment. The shipments of grains are expected to in­ land use along the rail line from Hunter crease. to Lynn is devoted primarily to farming This line is heavily dependent upon the and agricultural activities. Com, hogs, agri-business, and 17 of its patrons are and winter wheat constitute the major directly associated with agriculture and cash crops in the area. Industrial activ­ account for 89.2 percent of all carload ities are concentrated in the area from traffic on the line. Indianapolis eastward to Hunter and in The RSPA Project Team found no evi­ New Castle. Most of the towns in the dence of industrial planning or develop­ general area are basically trading centers ment along the portions of the Branch servicing the surrounding areas. New under study. Castle, however, is the county seat of For the months of May, June and Henry County, where employment is July, 1976, actual train operations over dominated by light industries and sup­ the segment between Hunter and Max­ porting services. well incurred a deficit of $408. For six The State of Indiana, the New Castle months of operation (April-September), Chamber of Commerce, local rail patrons the segment generated 145 carloads of and information received from the Penn freight; on an annualized basis this in­ Central during the railroad restructuring dicates that traffic levels have fallen to in 1974, provided the RSPO Project Team 278.8 percent of 1973 levels. with a list of 58 firms that were alleged C onclusions to have used the portions of the Spring- field Branch under study. Twenty-four The following operational changes of these firms were judged capable of should be considered: generating carload business. The remain­ (1) Serve the line with crews from ing businesses in these towns are almost Hawthorne Yard on the east side of exclusively small commercial and retail Indianapolis instead of crews out of the establishments that rely entirely on Avon Yard on the west side. motor carriers to handle their predomi­ (2) Upgrade the entire line to FRA nantly small shipments. Class n track standards (25 mph) be­ Of the 24 firms interviewed, six firms tween Hunter and Lynn. indicated they had used the railroad in (3) Serve the entire line between Hun­ the past but had no intention of using it ter and Lynn with a train crew assigned in the future. The remaining 18 rail pa­ to go on and off duty at Hawthorne Yard. trons are active rail users. Of the active (4) Abandon USRA Line No. 578/579a rail users interviewed, three stated that, between Emporia (milepost 173.5) and while no plant expansion was contem­ Shirley (milepost 181.0). plated, their sales were expected to in­ (5) In lieu of (2) and (3) serve USRA crease significantly. Three firms pro­ Line No. 554 from Hunter (milepost jected increases in their storage facili­ 131.2) to Shirley (milepost 107.3) and FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 10456 NOTICES USRA Line No. 578/579a from Shirley USRA Line No. 571/571a: Whitewater Of the 23 firms interviewed, five firms (milepost 181.6) to Carthage (milepost Running Track. The Whitewater Run­ indicatéd that they had used the rail­ 193.5) with a crew serving out of Haw- ning Track, formerly part of the New road in the past but had no intentioh . thorne. York Central Railroad, extends north­ of using it in the future. One individual (6) Abandon USRA Line No. 554 east west from Valley Junction, Ohio (mile­ stated that he had just purchased the of Shirley (milepost 107.3) to (milepost post 17.7), through Harrison, Ohio (mile­ firm but had no intention of using the 96.9) just east of New Castle. post 25.4), New Trenton, Indiana, (mile railroad, and one active rail patron was (7) Continue to serve USRA Line No. post 32.0), and Cedar Grove (milepost in the process of selling out his busi­ 554 between New Castle (milepost 95.3) 36.7) to Brookville, Indiana (milepost ness. The remaining 16 rail patrons are and Lynn (milepost 68.6) as is presently 43.5), a distance of 25.8 miles. The State active users of the line. Of these firms being done with the Anderson-New of Indiana requested the RSPO to six stated that they do not contemplate Castle Conrail crews. analyze the entire line. Valley Junction, any expansion; four stated that while no . Team tracks along the line offer poten­ Ohio, traffic is not included in this line plant expansion was contemplated, sales tial revenues and consequently should be analysis since it is being served by Con- were expected to rise; and two claimed upgraded and their use promoted. Rail. That portion of the line which is they have only a limited possibility of expansion'. Four firms indicated that FIGURE 10 there was a possibility for future ex­ pansion in their facilities. Crest Com­ ponents stated that a plant expansion was possible within two years, and Cin­ cinnati, Inc., expects to expand within six or seven years. The Farm Bureau Cooperative in Brookville is in the process of building a grain storage facility with a capacity of 50,000 bushels. The Sea- songood Folding Box Company stated its usage of rail “probably will doub’e or triple in the next two to three yea^s due'to change in raw materials” . Whii* there áre a variety of industries on tlm line, it is, nevertheless, heavily dependent on traffic associated with the housing industry, an industry which is just begin­ ning to recover from its decline of th* past few years. ■Carload traffic statistics applicable to the Valley Junction to Brookville line in­ dicated that: (1) The line has a limited number of rail patrons and commodities: (2) a declining traffic volume; (3) the line generates primarily terminating traffic; (4) the Penn Central received only 37.2 percent of the total revenues generated; and (5) the average line revenues are lower than system averages. For the months of May, June and July, 1976, actual train operations over the Valley Junction to Brookville line seg­ ment resulted in an operating surplus of $10,220. However, for six months of op­ eration (April-September) the line gen­ erated 478 carloads of freight; on an an­ nualized basis this indicated that traffic levels have fallen to 84.4 percent of the 1973 levels. C onclusions Team tracks along the line offer po­ tential revenues and consequently they located in Indiana serves portions of both employed in professional and related should be upgraded and their use pro­ Dearborn and Franklin Counties and services. Other employment sectors moted. connects at Valley Junction with Con- showed relatively low numbers of em­ The option of the line being served by Rail’s Cincinnati-to-Kankakee line. The ployees. The picture is clearly that of a a short line railroad owned by an inde­ northern connection from Brookville small, rural, county seat, with a mini­ pendent and/or rail patron operator (milepost 43.9) to Connersville (mile­ mum amount of light manufacturing. should be explored. The new operator, post 67.3) is out of service. The State of Indiana, the Brookville with State assistance could attempt to The line is a non-signalled, single track Chamber of Commerce, the Brookville renegotiate rates, based on the cars be­ line with industry and team tracks near Rail Research Committee, local rail pa­ ing terminated at Valley Junction and milepost 19 and milepost 21. There is also trons, and information received from the could assess a flat charge for the han­ a runaround passing siding at Brookville. Penn Central during the railroad restruc­ dling of the cars between Valley Junction The Whitewater Running Track pro­ turing in 1974, provided the RSPO Proj­ and Brookville and their siding or the vides service through an area which is ect Team with a list of 26 firms that were nearest team track. primarily agricultural and rural in char­ alleged to have used the Valley Junction Rehabilitation of this line could acter. Brookville, the northern terminus to Brookville portion of the Whitewater greatly reduce the time that it takes of the line, is the only city of any size Running Track. Of these 26 firms, one to service it and thus reduce the costs in the area served. The 1970 Census in­ was counted twice and local officials and of its operation. dicated a total employment in Brookville rail patrons had no knowledge of the The State should determine whether of 1,073 persons. 409 of these held manu­ existence of two others. The other 23 the U.S. Department of Agriculture, facturing jobs; 246 were employed in firms were judged capable of generating which has expressed interest in this line, wholesale and retail trade; and 138 were carload business. will share in the cost of its operation. •FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 NOTICES 10457 USRA Line No. 578/579a: Anderson- extended southward from Anderson were alleged to have used the Empox-ia Greensburg Secondary Track. The An- through Carthage and Rushville to to Carthage line. Of these 17 firms, one derson-Greensburg Secondary Track, Greensburg, Indiana. The State of In­ was no longer in existence at the time formerly part of the New York Central diana requested the RSPO to analyze the RSPO Project Team was interview­ Railroad, extends southward from An­ only that portion of the track that ex­ ing and one firm was counted twice. derson, Indiana (milepost 166.7) through tends from Emporia to Carthage, a dis­ Local officials and rail patrons had no Emporia (milepost 173.5), Markleville tance of 20 miles. (Anderson traffic is not knowledge of the existence of 4 other (milepost 174.8), Shirley (milepost 181.0) included in this line analysis since it is films. One firm explained that, although and Knightstown (milepost 187.5) to being served by Conrail.) This portion of it once had used the line during the past Carthage, Indiana (milepost 193.5), a the line is located in Madison, Hancock, 5 years it had been receiving its freight distance of 26.8 miles. At one time the Henry and Ruch counties and connects at Greenfield. One film was presently Anderson-Greensburg Secondary Track with the former Penn Central’s Spring- being served by ConRail from Anderson. The remaining 9 firms were judged ca­ F I GURE 11 pable of generating carload business. The other businesses in these towns are almost exclusively small commercial and retail establishments that rely entirely on motor carriers to handle their pre­ dominantly small-shipments. Of the nine firms interviewed, three firms indicated that they had used the railroad in the past (between 1964 and 1974) but had no intention of using it in the future. The remaining six rail pa­ trons are active users of the line. Three firms stated that they are not presently contemplating any future expansion, and two stated that, while no expansion is contemplated, sales are expected to rise. One firm expects to increase its storage facilities. Two of the six firms indicated that the loss of service over the line would have little effect on them. The RSPO Project Team found no evidence of industrial planning or development along the line. Carload traffic statistics applicable to the line indicate: the line depends heav­ ily on one patron who ships only a lim­ ited number of commodities; and traffic over the line is declining in volume. For the months of May, June and July of 1976, actual train operations over the line segment, including the Wilkin­ son to New Castle segment of USRA Line No, 559, incured a deficit of $2,877. For six months of operation (April-Septem- ber), the line generated 339 carloads of freight; on an annualized basis, this in­ dicates that traffic levels have fallen to 48.2 percent of the 1973 levels.. C onclusions Termination of rail service between *under subsidy Emporia and Shirley at milepost 173.5 should be considered. field Branch (USRA Line No. 554) at tural employment, and light manufac­ The line’s use as a team track offers Shirley and passes under Conrails’ Co­ turing and some heavy manufacturing in potential revenues and, consequently, lumbus to Indianapolis line (USRA Line the two SMSA’s provide significant should be upgraded and promoted. The No. 633). amounts of industrial employment. In improvement could be made around mile­ The Anderson-Greensburg Secondary and around Anderson, manufacturing is post 173.5, with the cooperation of the Track provides service through an area characterized by the production of auto­ Emporia Elevator Company. which is primarily agricultural and rural mobile parts, electrical and metal prod­ The possibility of having rail patrons in character but which also exhibits a ucts, and furniture. Indianapolis pro­ in the cities of Shirley, Knightstown and variety of other economic characteris­ duces significant quantities of transpor­ Carthage served in one o f the following tics. The northern terminus, Emporia, is tation equipment, machinery, electrical ways should be considered: (1) from an located within the Anderson SMSA, products, chemicals, food products, mo­ intact, rehabilitated USRA Line No. 554; which in turn is contiguous to the north­ tor vehicles, and pharmaceuticals. (2) from Hunter via Shirley (USRA Line eastern portions of the Indianapolis . An analysis of the establishments No. 554) to Carthage; and (3) from An­ SMSA. The line extends along the east­ along the line segment under study re­ derson via New Castle and Shirley (USRA ern border of the Indianapolis SMSA veals a concentration in a limited num­ Line No. 554) to Carthage. into Rush County. Most of the towns in ber of activities—agriculture, lumber The operation of the line as a short the service area of the line are small and and building supplies and light manu­ line railroad, owned by an independent have grown up primarily to service the facturing. and/or rail patron operator, should be agricultural areas around them. In gen­ The State of Indiana, the Anderson considered. The new operator, with State assistance, could attempt to renegotiate eral, this portion of the state produces and Knightstown Chambers of Com­ rates, based on the cans being terminated significant amounts of field and truck merce, and information received from at Emporia, and could assess rail patrons crops, com, hogs, winter wheat, and some the Penn Central dining the railroad re­ a fiat charge for the handling of the cars other livestock. Natural gas fields found structuring in 1974 provided the RSPO between Emporia and Cartilage and their In the area provide some non-agricul- Project Team with a list of 17 firms that siding or the nearest team track. FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY; FEBRUARY 22, 1977 10458 NOTICES USRA Line No. 582: Shelbyville Sec­ miles. Columbus traffic is not included they had never used the railroad and ondary Track. The Shelbyville Secondary in this line analysis since it is being had no intention of using it in the future. Track, formerly part of the Pennsylvania served by Conrail. This portion of the Armuth Farm Service and Swift Agricul­ Railroad, extends northeasterly from Co­ line is located in both Bartholomew and tural Chemical Corporation are the only lumbus, Indiana (milepost 3.8), through Shelby Counties. The portion of the line active rail users. Shelbyville (milepost 23.0) to Rush ville, under study connects at Columbus with Carload traffic statistics applicable to Indiana (milepost 44.-3), a distance of both Conrail’s Louisville Branch and its the Columbus to Flat Rock line indicate: 40.5 miles. The State of Indiana request­ Columbus to Madison Secondary Track. (1) Traffic has declined since 1970; ed the RSPO to analyze only that portion The line is currently in service only be­ (2) traffic density, cars per mile, was of the Shelbyville Secondary Track that tween Columbus and Clifford. There is never more than 8.5 for the years 1963 to extends from Columbus (milepost 3.8) an end-of-track sign at milepost 7.2, lo­ 1972; (3) shipments consist of only ter­ through Clifford (milepost 6.4) to Plat cated approximately 300 feet beyond Ar- minating carloads of chemicals and fer­ Rock (milepost 12.6), a distance of 8.8 muth Farm Service. tilizers; (4) Penn Central’s share of rev­ enues generated by the line was only FIGURE 12 24.7 percent; and (5) average revenues received on this line were lower than sys­ tem averages.. For the months of May, June and July of 1976, actual train operations over the line segment incurred a deficit of $289. For six months of operation (April to September), the line generated nine car­ loads of freight; on an annualized basis this indicates that traffic levels have fallen to 31.6 percent of 1973 levels. While Columbus is expected to con­ tinue its economic growth, the Clifford and Flat Rock areas are essentially very small, one-industry towns and do not ap­ pear to have the potential for significant growth or the introduction of rail ori­ ented industries (other than agri-busi­ nesses) . The RSPO Project Team found no evidence of industrial planning or de­ velopment along the line. C onclusions The purchase of the line for ultimate transfer to Conrail should be considered. The line’s viability could be improved by upgrading and promoting the use of team tracks along it. USRA Line No. 589/590: Columbus to Madison Secondary Track. The Colum­ bus to Madison Secondary Track form­ erly part of the Pennsylvania Railroad, extends in a southeasterly direction from Columbus, Indiana (milepost 0.0) through North Vernon (milepost 19.1) to Madison, Indiana (milepost 44.9) a dis­ tance of 44.9 miles. The State of Indiana requested the RSPO to analyze only that portion of the line from North Vernon (milepost 19.1) through Dupont (mile­ post 32.0) Jeff (milepost 36.9), and North Madison (milepost 43.0), to Madi­ The Shelbyville Secondary Track towns throughout Indiana, providing son (milepost 45.2), a distance of 26.1 serves portions o f Bartholomew County services for the farm communities which miles. Columbus traffic is not included in which lies just south of the Indianapolis surround them. Only Columbus, of the this fine analysis since it is being served SMSA and is contiguous to it, and Shel­ two termini, has extensive manufactur­ by Conrail. That portion of the line from by County which is within the SMSA, ing and nonagricultural development. Columbus (milepost 2.5) to North Vernon constituting its southeastern corner. Al­ The State of Indiana, the Columbus (milepost 19.1) is presently out of serv­ though both counties may be considered Chamber of Commerce, local rail patrons, ice. The fine is located in both Jennings primarily agricultural and rural in ori­ and information received from the Penn and Jefferson Counties, and it connects entation, having slightly rolling fertile Central during the railroad restructur­ at North Vernon with a Chessie System land available for cultivation, both have ing in 1974, provided the RSPO Project east-west main line and a Chessie Sys­ relatively significant nonagricultural Team with a list of eight firms that were tem branch line to Louisville, Kentucky; sectors. The branch itself extends over alleged to have used the Columbus to Madison is the end point of the line only a short portion of the two Counties, Plat Rock line. Of these eight firms, one traversing the northern half of Barthol­ under study. The loss of a bridge at was no longer in existence at the time the omew County, and barely entering RSPO Project Team was interviewing, Scipio necessitates the line being served neighboring Shelby County. It is situated and two firms indicated that they had from Columbus over USRA Line No. 619 mainly in an agricultural area, with a not used the railroad since 1970 and had . (Conrail) to Seymour, then over the number of small towns surrounding the no intention of using it in the future. Chessie System tracks to North Vernon line. These towns are typical of small Three firms at Flat Rock indicated that and thence to Madison. FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 NOTICES 10459 FIGURE 13 rail patrons and commodities generated; and (3) a predominance of terminating traffic. For the months of May, June and July 1976, actual train operations over the line segment incurred a defiiit of $118,109. For six months of operation (April-Sep- tember), the line generated 296 carloads of freight; on an annualized basis this indicates that traffic levels have fallen to 50.3 percent of 1973 levels. C onclusions Consideration should be given to ter­ minating rail service at Madisoh, which would allow for the removal of the spe­ cially designed locomotive permanently stationed at Madison, thus significantly reducing the costs of operating the line. Terminating the service to North 'Vernon also should be considered. The possibility of having rail patrons between Vernon and North Madison served by the Chessie should be explored. The team tracks at North Madison of-- fer potential revenues and, consequently, should be upgraded and their use should be promoted. Rail patrons should explore with the operating railroad the feasibility of de­ veloping a new type of rail car designed to move bulky mobile batch plants out­ bound over the line. The option of operation the line as a short line railroad owned by an independ­ ent and/or rail patron operator should be considered. The operator, with State assistance, could attempt to renegotiate rates based on the cars being terminated at either Vernon or North Madison and could assess rail patrons a flat charge for the handling of the cars between Ver­ non and North Madison and their siding Indiana State Track Inspectors have Of these 53 firms, two were no longer in or the nearest team track. made a close inspection of this line and existence at the time the RSPO Project USRA Line No. 1261 /1262: Jersey City estimate it would cost $619,212 to restore Team was interviewing, and one firm to Chicago Line. The former Erie Lacka­ it to FRA Class I track standards. was counted twice. Local officials and rail wanna Jersey City to Chicago main line This branch provides service to a two- patrons had no knowledge of the exist­ extends westward from Jersey City across county area which is predominantly agri­ ence of three other firms. The other 47 New Jersey, Pennsylvania, and Ohio and cultural and rural in nature. It lies di­ firms were judged capable of generating terminates at Hammond, Indiana (mile­ rectly between the Louisville SMSA and carload business. The remaining busi­ post 249.6). The State of Indiana re­ the Cincinnati SMSA. The region pro­ nesses in Vernon, Dupont, North Madi­ quested the RSPO to analyze only that duces primarily tobacco, livestock, and son and Madison are almost exclusively portion of the Jersey City to Chicago truck crops. North Vernon, Madison, and small commercial and retail establish­ line that extends from Decatur, Indiana Hanover, are the only towns of any sig­ ments that rely entirely on motor car­ (milepost 96.9) to North Jersey, Indiana nificant size in the service, area of the riers to handle their predominantly small (milepost 199.4) a distance of 102.5 miles. branch. Most of the other towns in the shipments. There are a number of addi­ Decatur traffic is not included in this two Counties serve as trading centers for tional industries within the North Ver­ line analysis since it is being served by the agricultural areas which surround non area that are being served by the Conrail. This portion of the line is lo­ them. Chessie System. cated in the following counties: Adams, Of the 48 principal industries located Of the 47 firms interviewed, six firms Wells, Huntington, Wabash, Fulton, Pu­ along the North Vernon to Madison stated that they had never used the rail­ laski, and Starke. It connects with the line, 22 are directly associated with the road and had no intention of using it in following railroads: at Decatur with assembling, fabricating, processing, or the future. Thirteen firms indicated that Conrail and the N&W; at Huntington manufacturing of a diversified number of they had used the railroad in the past with the N&W’s Fort Wayne-Decatur, products, six have an agricultural orien­ (between 1952 and 1975) but had no in­ Illinois line; at. Bolivar with Conrail; at tation, six are retail lumber and build­ tention of using it in the future. The re­ Newton with the former Penn Central’s ing supply dealers, three are public utili­ maining 28 rail patrons are active users Columbia City Secondary Track; at ties, and 11 engage in a wide range of of the line. Twelve firms have stated that Rochester with N&W’s Michigan City to other activities. the termination of rail service would have Indianapolis line; at Delong with the The State of Indiana, the Chambers of little effect on their operation. Many former Penn Central’s Culver Secondary Commerce o i North Vernon and Madi­ firms are already making extensive use Track; and at North Judson with the son, local rail patrons, and information of alternative transportation modes. Chessie System’s Cincinnati to Ham­ received from the Penn Central during Carload traffic statistics applicable to mond line and Conrail. The N&W De­ the railroad restructuring in 1974 pro­ the North Vernon to Madison line indi­ catur, Illinois to Fort Wayne line crosses vided the RSPO Project Team with a cate: <1) A declining traffic volume ex­ at Huntington, the Fort Wayne to Mun- list of 53 firms that were alleged to have acerbated by the recent loss of four major cie line at Kingsland, and the Delphos- used the North Vernon to Madison line. rail patrons; (2) a limited number of Frankfort line at Decatur, Ind. FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977 10460 NOTICES FIGURE 14 The Decatur-North Judson line serves For the months of May, June and July A p p e n d ix A—S t a t e R e q u e s t L e t t e r a portion of Indiana which is primarily 1976, actual train operations over the line S t a t e o p I n d ia n a , agricultural in nature. From North Jud­ segment incurred a deficit of $38,524. For P u b l i c S e r v ic e C o m m i s s i o n , son the line moves east through a highly six months of operation (April-Septem- R a il P l a n n i n g D i v i s io n , agricultural section of Starke County, ber, 1976), the line generated 1,098 car­ B l o o m i n g t o n , I n d ., M a t i i , 1976. south of the South Bend SMSA, and then loads of freight; on an annualized basis, M r . A l a n F it z w a t e r , proceeds through several primarily agri­ this indicates that traffic levels have Director RSPO, cultural counties and terminates in the fallen to 30.3 percent of 1973 levels. Since 1900 L Street, N.W., southern half of the Fort Wayne SMSA, June of 1976, there have been no requests Washington, D.C. where agriculture is still the dominant for service west of Monterey (milepost D e a r M r . F i t z w a t e r : Please accept this economic activity. Even though there are 183.7). letter as a revision of my letter to you dated February 16,1976. several towns (Decatur, Huntington and C o n c l u s io n s As set forth in Section 205(e) (2) of the Rochester) of some commercial promi­ In view of the interest expressed by RRRA (as amended by Section 309 of the nence located in the immediate service the U.S. Department to Agriculture, the RRRRA) the State o f Indiana formally re­ quests the RaU Services Planning Office to area of the line, most of the towns and State should determine whether the De­ prepare and publish an evaluation of the cities along the branch line are small partment will share in the cost of con­ economic viability o f the light density lines in size, and serve primarily as market tinuing operations over the line. in Indiana not designated for inclusion in the Final System Plan listed below. centers for the surrounding farm com­ Team tracks along the line offer poten­ munities. This line serves a portion of tial revenues and, consequently, should Lines in Indiana eligible for subsidy u n d e r the state where general farming and for­ be upgraded and their use promoted. the State rail plan estry is practiced and there is extensive Termination of rail service from Mon­ L in e Description Designated production of potatoes. The line also terey to North Judson (16.4 miles) ; from N o. operator serves a more highly developed section Huntington to Akron (32.0 miles) ; and of the state which is dominated by the from Uniondale to Preble (11.8 miles) 399 . 401 Goshen to Shipshew anna_____ C R C ; A n g o la to M ontgom ery, M ic h ._ Hillsdale Coun­ production of livestock, dairy products, should be considered. t y B R . Co. 417a A u b u r n Junction to A u b u r n ... Chessie. soybeans, and a number of small cash The feasibility of extending Conrail’s 418 K e nd allville to State lin e______C R C . grains. The RSPO Project Team found Decatur Yard limits to include Preble 419 423 N o rth Manchester to M e x ic o ... C R C . Logansport to Lucerne________ C R C . no evidence of industrial planning or de­ and reestablishing a connection at Boli­ 429 D ecatur to P o r t l a n d ..________ C R C . 523 Anderson to F r a n k t o n .. . . . ___C R C . velopment along the line. var, in order to serve Servia rail patrons 554 H u n ter to M a x w e ll.____________ C R C . Wilkenson to L y n n ________ ____ C R C . Carload traffic statistics applicable to should be explored. 571/ V a lle y Junction, Ohio to C R C . the Decatur-North Judson line indicate: The possibility of having rail patrons 571a Brookville. 578/ E m p oria to C arthage----- ---------- C R C . (1) A limited number of rail patrons use served from Rochester east to Akron and 579a 582 C olu m b us to F latrock _____ . . . C R C . the line; (2) traffic volume is declining; west to Monterey; and from Huntington 589/ N o rth V ern on to M a d iso n .------ C R C . (3) more than three-quarters of the traf­ east to Uniondale should be explored. 90 - 1261/ Decatur to N orth J udson-------- C R C . fic on the line can be attributed to four Discounting the use of the second main 1262 locations—Huntington, Monterey, Akron EL track, as well as existing track signal-, Thank you and I look forward to being of and Rochester; (4) the Huntington area ing equipment should be considered. service to you if the need arises. clearly is the most important traffic and The possibility of having a completely Sincerely, revenue source for the line, accounting rehabilitated Deeatur-North Judson line, B r u c e W m . P ig o z z i, for more than half of each; and (5) owned and operated entirely by those Acting Director, State Rail Planning, nearly all of Huntington’s traffic moves employees presently located at Hunting- Public Service Commission. via COFC/TOPC rail service. ton should be considered. [FR Doc .77-5325 Filed 2-18-77; 8:45 am] \ FEDERAL REGISTER, VOL. 42, NO. 35— TUESDAY, FEBRUARY 22, 1977