o PORTIONS OF DR. JOSEPH K. PRINCE'S CHAPTER ON "IMMUNOTOXICOLOGY i CHEMICAL CARCINOGENESIS" FROM THE BOOK ENVIRONMENTAL TOXICOLOGY. This chapter establishes the- relationship between a breakdown of THE b o d y 's IMMUNE SYSTEMS AND VARIOUS DISEASES, ESPECIALLY SOFT TISSUE CANCERS, a ST1 SpBef: T* Hazcc-Hagclslcin. W. M. G. Tunbridge. ^ *ï. Reprod. Fenil. Suppl. 26. 12? (1979). 12. K. Ramasharma and M. R. Sairam. Ann. N.Y. Acad. Sri. 383. 307 ( 1982). 13. _____ _ M. R. Ranganalhan. A n a Endocrinol. (Copenhagen) 98. 496 <19811. 14. N. G. Seidah. J. Rochemom. J. Hamclin. M. Lis. M. Chrétien. J. Biot. Chem. 256. 7977 (J981). • 15. M. R. Sairam. in Hormonal Proreins and Pep­ tides: Gonadotropins. C. H. Li. Ed. (Academic Press. New York. 19831. vol. 11. pp. 1-79. 16. A. V. Schally, Science 202. 18 (1978). 17. M. 0 . Da yho ET. Protein Sequence Data Base, Update (National Biomedical Research Founda­ tion. Washington. D.C.. 1983). 18..C. C. Q. Chin. J. M.|Brenner. F. Wold. J. Biol. Chem. 256. 1377 (1981). 19. M. J. Holland. J. P. Holland. G. P. Thill. K. A. Jackson, ibid., p. 1385. 20. The existence of homology in structure as well as function among distinctly related eucaryotes has been reported: see L. T. Hunt and M. 0 . Davhoff. in Peptides: Structure and Biological Function. E. Gross and J. Metnhofer. Eds. (Pierce Chemicals. Rockford. III.. 1979), p, 757: /■* 3. P. Honchar and W. Halperin. Lancet 1981-1.618 M. O. Davhoff. in Alias Sm urare (1981); P. Honchar. M. Fingcrhut. W. Halperin. and Structure (National BiomelficalCResearah^ in preparation. Foundation. Washington, D.C.. 1978). voi. 5. 4. W. Wagner, paper presented at the SOEH Con­ suppl. 3: K. Lederis et al.. Can. J. Biochem. ference. The Scientific and Social Response Cell. Bit)!. 61, 602 (1983): K. C. Robbins. H. N. from Exposure to Dioxin and Related Materials Antontades. S. G. Bevare, N. W. Hunkapiller. (Society for Occupational and Environmental S. A. Aaronson. Nature ILondon) 305 . 605 Health. Arlington. Va.. December 19831. The (1983). Environmental Protection Agency, report was 21. The peptide corresponding to the 31-amino-acid originally intended to be released in November sequence was synthesized by the solid-phase 1983. bui has not yet been released. method. The purity of the synthetic peptide was 5. T. Sterling and A. Arundel. NCAP Nexvs. in established by HPLC and paper electrophoresis, press. and its amino acid composition was identical to 6. O. Axel son and L. Sundell. Work Environ. the proposed sequence [R. B. Memfield, J. Am. Health 11.21 (1974). Chem. Soc. 85. 2149 (1963): D. Yamashiro and 7. L. Hardell, M. Eriksson. P. Lenner. E. LundC. H. Li. ibid. 100. 5174 (1978): C. H. Li. D. gren, Br. J. Cancer AS. 169(1981). Yamashiro, K. Ramasharma. M. R. Sairam. 8. Ton That Tung. Chirurgie 99. 427 (1973). unpublished data). 9. A. Westing. Ed.. Proceedings. International 22. Supported by the Ford Foundation and the Symposium on the Long-Term Consequences o f Medical Research Council of Canada. We thank Chemical Warfare in Vietnam (Stockholm Inter­ C. A. Paulsen. G. Bleau, R. Vaudair. and M. O. national Peace Research Institute. Stockholm. Dayhofffor their contributions, and C. Chagnon Sweden. 1983). Labelle and R. Carrière for technical assistance. 10. E. Silbergeld. paper presented at the SOEH * To whom correspondence should be directed. Conference, The Scientific and Social Response from Exposure to Dioxin and Related Materials 28 November 1983: revised 17 January 1984 (Society for Occupational and Environmental Health. Arlington, Va., December 1983). 6 January 1984 Health Effects of Dioxin The evidence of deleterious health consequences from the environmental use of substances containing 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has appeared in a multitude of studies. Philip H. Abelson’s editorial O) on the dioxin issue is based on a number of misleading inaccuracies about this evidence. First, the results of the accident at Seveso, Italy, are not limited to mild cases of chloracne, despite Abelson's statement that "N o significant change was observed in the incidence of sponta­ neous abortions, congenital malforma­ tions, or postnatal development." The Seveso data (2) show a sharp increase in spontaneous abortions during the first trimester of 1977, followed by a slow decrease to 1976 levels and significant increases in risk of malformations. For example, there was a 100 percent in­ crease in the rate of spina bifida, a 71 percent increase in the rate of neural tube defects, an elevenfold increase in hypospadias, and a 110 percent increase in polydactyly. A number of these mal­ formations are frequently observed in animals exposed to TCDD. The Seveso data are still being analyzed for postnatal effects. Second, the National Institute of Oc­ cupational Safety and Health U) and recently the Environmental Protection Agency [4) followed workers exposed to TCDD in industrial accidents and found, in sharp disagreement with scientists who analyzed that data for industry, a multiple increase in soft tissue carcino­ mas and lymphomas. Third, the question is not whether TCDD has to be ingested before it is toxic (obviously it has to make effective contact) but whether there is an effect from the presence of elevated environ­ mental levels of TCDD. especially as a result of herbicide spraying (J). There is ample evidence that the latter is the case. Multiple studies by Swedish investiga­ tors, notably, Axelson and Sundell (6) and Hardell and Erikson and their col­ leagues (7) show an increase in soft tis­ sue carcinomas in railway and forestry workers exposed to environmental TCDD. Observations from Vietnam (5) have reaffirmed increased liver cancer among populations exposed to Agent Or­ ange during the Vietnam War (5). Spon­ taneous abortions, stillbirths, and mal­ formations are still reported in these areas (9). Fourth, it is misleading to stress the great variability of the median lethal dose (LD.so) when commenting on the value of animal experiments. It would be more accurate to point to the uniformly low effective doses for producing carcin­ ogenic and teratogenic effects (10). T h e o d o r D. S t e r l i n g Faculty o f Interdisciplinary Studies, Department o f Computer Science, Simon Fraser University, Burnaby, British Columbia, Canada V5A iS6 References and Notes 1. P. H. Abelson. Science 220. 1337 (1983). 2. P. Bruzzi rf a!,, "Birth defects in TCDD pollut­ ed areas" (Provisional Report. Seveso Birth Defects Registry, Seveso. Italy. 1981): Reporto Conclusino Sui Defettl Congeniti Ed A Itri Esiii Sfavorevoli Di Gravidanza Relax’d ! Nella Popolaztone Del L'Area Di Seveso Jnterasata Dali' Inquinamento Da TCDD IL 10.7.1976 (Registro Delle Malformazioni. Seveso, 28 June 1983). Pro and con evidence and differing points of view on questions concerning the toxicity of dioxin are cited in a large number of articles and books. Three publications that contain a total of hun­ dreds of references are 1) Further Review o f the Safety’for Use in the U.K. o f the Herbicide 2.4,5-T from the Advisory Committee on Pesticidesj( London, December 1980; 2) Agent Orange Dioxin—The Health Effects o f "Agent Orange" and Poly­ chlorinated Dioxin Contaminants, a technical report prepared by the Council on Scientific Affairs of the Advisory Pan­ el on Toxic Substances of the American Medical Association. Chicago. Illinois, October 1981; and 3) Human and Environmental Risks o f Chlorinated Dioxins and Related Compounds, edited by Richard E. Tuck­ er, Alvin L. Young, and Allan P. Gray (Plenum Press, New York, 1983). As Sterling points out, a number of investigators have taken the position that TCDD has been a causative agent of soft tissue sarcomas. However, to other ex­ perts, the evidence is not compelling. The Agent Orange report includes the following statement (p. 28): “ While 2,4,5,-T and 2,4-D pesticides (phenoxy herbicides in Agent Orange) have been used in agriculture, forest management, and residential landscaping for over 30 years, there is still no conclusive evi­ dence that they and/or TCDD (a contam­ inant of Agent Orange) are mutagenic, carcinogenic, or teratogenic in man. nor that they have caused reproductive diffi­ culties in the human." — P h i l i p H. A b e l s o n 26 January 1984 C03739 1202 cripti^*' u rti n r , I w i Ü i i w Ü w t U G R TTCMonsanto Company 1101 17th Straat. N.W. Washington. 0 C 20036 Phona. (2021 452-8 680 \J /iu / ✓ y ■- \ > 8tO A jJ W a ~ s^ _ _ Q03740 . M3 South b Abtrdlan, S D. ST ■05-225-B I t ! S)ith Sti Rapid City. S O. ST M5-3U-7 BOO South ( Sloui Falla, S.O. ST «03-334-9 NEWS/INFORMATION 439 Cannon Built Waahlnflton, O.C. 23 1-300-424 5 or 202-235-3 FROM SOUTH DAKOTA CONGRESSMAN TOM DASCHLE DOW AND DIOXIN: A STUDY S t a t e m e n t b y C o n g re ssm a n D a s c h le J u n e 2 , 1983 P a u l O r e f f i c e , p r e s i d e n t o f Dow C h e m i c a l , r e c e n t l y t o l d a n a t i o n a l t e l e v i s i o a u d i e n c e : “T h e re i s a b s o l u t e l y n o e v i d e n c e o f d i o x i n d o i n g a n y dam age t o h um ans e x c e p t f o r s o m e th in g c a l l e d c h l o r a c n e . " T h e s t u d y 1 am r e l e a s i n g , a s t u d y o f w h ic h Dow w as c l e a r l y H r. O r e f f ic e h a s e i t h e r d e l i b e r a t e l y m is le d th e p u b l i c o r i s a w are , i n d ic a te s to ta lly ig n o ra n t o f s t u d i e s p o s s e s s e d by h i s com pany. T h i s s t u d y , c o n d u c t e d b y D r . M i l f o r d W ard o f t h e D e p a r tm e n t o f Im m u n o lo g y , R o y a l H a l l a n s h i r e H o s p i t a l , S h e f f i e l d , E n g l a n d , d o c u m e n ts a l o n g - t e r m im m une s y s t e b re a k d o w n i n hum ans e x p o s e d t o d i o x i n som e t e n . y e a r s , p r i o r t o t h e i r e x a m i n a t i o n . T he s t u d y c o r r o b o r a t e s s e v e r a l s i m i l a r s t u d i e s o n a n i m a l s a n d h u m a n s . O n ly y e s t e r d a y , Dow i n v i t e d j o u r n a l i s t s fro m a c r o s s t h e c o u n t r y t o i t s M id la n d , M ic h ig a n , h e a d q u a r t e r s t o h e a r a b o u t new s t u d i e s a n d r e c e i v e t h e com pany a p p ro v e d l i n e on th e s a f e t y o f d i o x in . I t is my u n d e r s t a n d i n g t h a t t h e s e jo u rn a l! w e r e t o l d t h a t Dow p l a n s t o s p e n d m o re t h a n $ 3 m i l l i o n t o s t u d y d i o x i n d am ag e i n t h e M id la n d a r e a . I c a n n o t h e l p b u t w o n d e r w h e t h e r Dow t o l d th e m o f t h i s s t u d y b y D r . W ard , o r i f - Dow e x p l a i n e d t h e dam age t h i s s t u d y d o e s t o t h e c o m p a n y 's r e p e a t e d c l a i m s a b o u t d io x in . I t i s n o t s u r p r i s i n g Dow h a s m a i n t a i n e d s i l e n c e o b v io u s s i g n i f i c a n c e t o t h e A g e n t O ra n g e i s s u e . o f t h i s s tu d y h as d e s c rib e d i t a b o u t t h i s s tu d y d e s p ite i t s N or i s as " c o n f id e n tia l," it s u r p r is in g th e a u th o r and " n e v e r p u b lis h e d in th e s c i e n t i f i c p r e s s ." T hese th in g s have h a p p e n e d , an d t h e y a r e b u t t h e t i p o f th e ic e b e r g o f e f f o r t s t o s u p p re s s th e f a c t s an d m is le a d th e p u b l i c a b o u t d i o x in . Y et j u s t th is tip o f d ie ic e b e r g , in th e f o rm o f D r. W a r d 's s t u d y , c a s t s t h e g r a v e s t d o u b t o n t h e c l a i m s o f Dow a n d t h e U n i t e d S t a t e s g o v e r n m e n t c o n c e r n i n g A g e n t O ra n g e a n d i t s d e a d ly c o n ta m in a n t, d i o x in . ...m o r e ... A cco m p an y in g C o n g re ssm a n D a s c h le i n t o d a y 's News C o n f e r e n c e i s D r. J o s e p h K. P r i n c t a r e s p e c t e d i m m u n o to x ic o L o g is t who i s a R e s e a r c h A s s o c i a t e w i t h t h e U n i v e r s i t y o f I l l i n o i s M e d ic a l C e n t e r a n d a T o x i c o l o g i s t w i t h t h e E n v ir o n m e n ta l P r o t e c t i o n A g e n c ’ i n C h ic a g o (R e g io n V ) . S ta te m e n t by C ongressm an D a sc h le —. P ag e 2 C o n f i r m a t i o n o f l o n g - t e r m immune s y s te m c o l l a p s e a s a r e s u l t o f d i o x i n e x p o s u i w o u ld r e v o l u t i o n i z e o u r t h i n k i n g a b o u t t h i s e n t i r e issu e . I t w o u ld e x p l a i n t h e w id e - ra n g in g m a la d ie s r e p o r t e d f o r y e a r s b y v e te r a n s e x p o se d t o A g e n t O ra n g e . w o u ld o p e n Dow a n d t h e g o v e rn m e n t t o b o t h m i l i t a r y a n d c i v i l i a n ; It c la im s f o r l e g a l a n d l e g i s l a t i v e re m e d y o n a p o t e n t i a l l y m a s s i v e s c a l e . ' And t h e W ard s t u d y r a i s e s a h o s t o f i m p o r t a n t q u e s tio n s f o r fo llo w -u p — q u e s tio n s l i k e : 1 • Why w as t h e s t u d y k e p t c o n f i d e n t i a l , t h u s p r e v e n t i n g i n d e p e n d e n t e v a lu a tio n by th e s c i e n t i f i c • W hat i s c o m m u n ity ? th e h e a lth s t a tu s o f th e ex p o se d v ic tim s to d a y ? • W ere f o l l o w - u p s t u d i e s m ade? • I f t h e y w e re n o t , why n o t ? • I f t h e y w e r e , w h a t d i d t h e y show a n d why h a v e t h e y ! • And f i n a l l y , : d o c s Dow h a v e f u r t h e r s t u d i e s r e m a in e d s e c r e t ? re la tin g t o d i o x i n w h ic h i t i s w ith h o ld in g ? ^ And t h e r e a r e q u e s t i o n s f o r t h e E n v ir o n m e n ta l ’" P r o t e c t i o n A g e n cy a n d o t h e r g o v e rn m e n t a g e n c i e s a s w e l l : • How d i d E .P .A . o b t a i n t h i s s t u d y a n d why h a s s o l i t t l e • Was t h e W ard s t u d y show n t o been s a id a b o u t th e V e te ra n s A d m in is tr a tio n , to th e D e p a rts o f D e f e n s e , o r t o o t h e r s c o n c e r n e d w i t h t h e A g e n t O ra n g e m a t t e r ? • I f n o t , why n o t ? • And i f t h e V .A . w as show n t h e s t u d y , why h a v e n 't t e s t s | f o r im m une s y s t e b re a k d o w n b e e n i n c l u d e d i n t h e f r e e h e a l t h exam s g i v e n t h o u s a n d s o f V ie tn a m v e • S i m i l a r l y , why h a s n ' t t h e V .A . a w a rd e d a s i n g l e r e s e a r c h p r o p o s a l t o i I s t u d y t h e e f f e c t o f d i o x i n o n t h e im m une s y s te m ? - • L e a v in g t h e A g e n t O ra n g e m a t t e r e n t i r e l y * W ard f i n d i n g s t a k e n in c o n s id e rin g c i v i l i a n j u s e w h ic h c o n t i n u e s t o t h i s day? T h e s e a r e b u t a few o f t h e q u e s t i o n s r a i s e d q u e s t i o n s re m a in u n a n s w e re d f u l l y a s i d e , w as p r o p e r a c c o u n t o f t u se o f d io x in c o n ta m in a te d d e f o l i a b y D r. W a r d 's s t u d y . T h at th e s e 20 y e a r s a f t e r t h e s p r a y i n g o f A g e n t O ra n g e i n V ie a n d f i v e y e a r s a f t e r t h e W ard s t u d y w a s , c o m p l e te d s t a n d s a s a n i n d i c t m e n t o f a l l in v o lv e d i n th is m a tte r. I re le a s e t h is s tu d y , an d c o n t i n u e my i n v e s t i g a t i o n i n t o o t h e r m a t e r i a l s w h ic h may h a v e b e e n s u p p r e s s e d , i n t h e h o p e C o n g r e s s a n d o u r g o v e r n m e n t w i l l a t l o n g l a s t t a k e t h e a c t i o n s r e q u i r e d t o c o m p e n s a te t h o s e a f f e c t e d b y d i o x i n a n d p r o t e c t t h o s e ■ a s y e t u n a f fe c te d . I t i s s u r e l y t h e v e r y l e a s t wo c a n d o . J Pa g e Ail LETTER FROM DR, A.'MILFORD WARD Th i s letter confirms t h a t *his I N D U S T R I A L CO M P A N Y " — study — "w r i t t e n for an WAS C O N F I D E N T I A L AND NEVER P U B ­ L I S H E D IN THE S C I E N T I F I C PRESS, Pa g e s This Pa g e s This in A:2-4 PORTION OF TRANSCRIPT FROM E.P.A. CANCELLATION HEARINGS 0N‘2 A 5 , - T AND SILVEX (NOV. U , 1980) transcript A:5-13 study adult confirms was aware of the Vard study. IMMUNE STUDY BY DR. A. MILFORD WARD reveals males t h at .Dow the exposed presence to of dioxin. l o n g -t e r m immune breakdowns A-l This LETTER'FROM DR, A. MILFORD WARD letter confirms IN D U S T R I A L CO MP AN Y" ” that his study — .. . ' "w r i t t e n for an W A S C O N F I D E N T I A L AND NE VE R PUB­ L I S H E D IN THE S C I E N T I F I C PRESS. CM 357 T*t; Sheffield 107421 76494 Eat. 2837 T r i ta . 54?4S U l,h«f. G. Suprarcyional Protein Rdui once Ui Department of Immunology, Royal Hallamshire Hospital, D utCiO,; Dr. A. Milford W**d AMW/JA Sheffield, S10 2JF 6 A p r i l 1983 e s : ---------------— D ear 9 T h a n k y o u f o r y o u r l e t t e r o f t h e 2 8 t h M a rch r e g a r d i n g my p a p e r on ' I n v e s t i g a t i o n o f t h e Immune c a p a b i l i t y o f W o rk e rs p r e v i o u s l y e x p o s e d t o 2 , 3 , 7 , 8 TCDD". I w o u ld b e m o s t i n t e r e s t e d t o know how t h i s p a p e r cam e i n t o y o u r p o s s e s s i c I t w a s w r i t t e n f o r a n i n d u s t r i a l co m p an y i n 1 9 7 8 a n d w as n e v e r p u b l i s h e d i th e s c i e n t i f i c p r e s s . A s s u c h i t w as a c o n f i d e n t i a l d o c u m e n t a n d w as n o t w r i t t e n i n a fo rm a t f o r w id e r d i s t r i b u t i o n . W h i l s t t h i s w o rk w as d o n e som e y e a r s a g o , my i n t e r e s t i n t h e s u b j e c t i s c u r r e n t a n d I w o u ld b e i n t e r e s t e d t o h e a r y o u r c o m m e n ts a n d e x p e r i e n c e . H ay I a l s o a s k y o u r i n t e r e s t o r i n v o l v e m e n t i n t h e p r o b l e m a r e a . I n o te r e f e r e n c e t o A g e n t O ra n g e i n y o u r l e t t e r h e a d a n d I c a n o n l y a ssu m e t h a t i t i s i n t h i s c o n n e c tio n t h a t y o u r i n t e r e s t l i e s . K ith b e s t re g a rd s Y o u rs s i n c e r e l y A MILFORD WARD st .w 0 - >' A-2 Th i s for V PORTION OF TRANSCRIPT FROM E.P.A. CANCELLATION HEARINGS ON 2 A 5 - T AND SILVEX (NOV. Hi, 1980). transcript Dow. confirms that D r . W a r d 's study was done A-3 17221 P.V MR. !)07.0r: 1 2 > -A rc 3 A Y e s , I nm. 4 0 A re y o u f r e e t o —■ w e l l , l e t ' s 5 f i r s t page. 6 A you at n il fa m ilia r w ith th in s tu d y ? 9 tu rn to th e The f a c t t h a t I ' v e g o t t e n t o d o , i n e f f e c t , o r 7 h a v e t h i s w ork d o n e a g a i n , d o e s n ' t i n an y way i n h i b i t me 8 from s*»caking a b o u t i t , 9 12 no, ¡inti, on t h e f i r s t p a g e , t h e r e i s a n i n d i c a t i o n 10 t h a t t h e immune c a p a b i l i t y o f t h r e e r r o i n s o f a d u l t 11 p a l e s vns ex am in ed , i s t h a t c o r r e c t ? 12 A Y es. «0 v--------------- 13 ■> And one g r o u p w as e x p o s e d t o t o x i c l e v e l s o f more t h a n t e n y e a r s p r e v i o u s l y , sh o w in g c l i n i c a l e v i d e n c e o f t o x i c i t y i n t h e form o f c h l o r a c n e ? * A T h a t ' s C roup 0 T h a t ' s C roup C, an d I m i g h t s a y t h a t t h i s C roup C was n o t i n k e d i n by J;PA. ^T7e r e c e i v e d t h e d o c u m e n t from D o ;/ ii. th is m anner Do you a g r e e t h a t t h a t i s Group C, from y o u r 'inowlciige? 22 23 A ‘ n — numoer 2 i s C r o n j .7 an d 3 i s Group A. 24 25 Y ns, t h a t ' s C ro u p C, and t'n e o t h e r s a r e C ro u p ..» And Group d i s t h e g r o u p e x p o s e d t p TCD1), b u t n o t .mowing e v i d e n c e o f d e r m a t o l o g i c a l t o x i c i t / ? " ' NEAL R GROSS COU1T RlPOBTial AND 18*NiC*lli»l I J JO VIR m ONT AVtNUt. HW non j j 4 . * v ) i w a s h i n &t o n . d c . jo o o j ' 17222 A T h a t m eant no c h l o r n c n e . I t m ean t t h a t th ey w e re round a b o u t t h e p l a c e and c o u l d c o n c e i v a b l y h a v e coma i n c o n t a c t w i t h TCDD o r n o t , - n o b o d y knew; t h e y w e re an i n t e r m e d i a t e orotirs. 4 *P ■And t h e t h i r d g r o u p , C roup A, w e r e t h e u n exposed V---------------------- --------------------------- co n tro ls? A T h a t ' s r i g h t , who w e re a p p a r e n t l y s a i d t o be c e r t a i n n o t t o h av e come i n t o c o n t a c t w i t h i t . p Ilow, t h e o n l y n u m b e r in g on t h i s p a g e i s t h e n 1u sh e r' i n t h e r i g h t - h a n d c o r n e r o f t h e s e p a g e s , and I t h i n k i t ' s p a g e ¡MC708 t h a t I w ould l i k e t o draw y o u r a t t e n t i o n to . A I 'v e got th a t. T h e r e ' s a l o t o f u n d e r l i n i n g on ^hat page. A n a m , we r e c e i v e d t n e d o cum ent i n t h i s fo rm , a s n ^ n B fro m Dow, a s a 3 B B a B B n H n D a B n 3 a a a o ^ ¡low, t h e s e c o n d o n r a g r a n h s t a t e s th a t "T est 1 r a j c a s e s w i t h reduce*.: l e v e l s o f Ic u n u n o g lo b in D and Inm uno- j Group C' shows a s i g n i f i c a n t i n c a o m,LIJ„ j_ M r i.w w iu jiija w > » n l n a i n ¡1, and t h i s g ro u p shows an i n c r e a s e d p r o p o r t i o n o f j c a s e s w i t h d e p r e s s e d J'ilA r e a c t i v i t y " . .’low, t h i s s u g g e s t s t h a t t h e r e was cone immuno­ s u p p r e s s i o n o f t h e - ^ r o u > t h a t was e x p o s e d t o TC03 and c : : ! i i b i t e d c h l o r n c n e , d<-»e::n't i t ? NEAL R. G R O S S COURT REPORTIRS ANO TRANSCRIBES 1330 VIR m ONT AVINUI. NW WASHINGTON DC. 3 0 0 0 3 J? -»• A-5 Th i s imUNE STUDY BY DR. A. MILFORD WARD . study reveals the pr e se n c e of long - term immune B R E A K D O W N S IN A D U L T MALES E X P O S E D TO DIOXIN. V t> o M j r c iR c u z - f tT r y v - v - v © tiai INVESTIGATION OF THE IMMUNE CAPABILITY- OF WORXERS PREVIOUSLY EXPOSED TO p a r a - DIOXIN 2 ,’3 , 7 , 8 , TETRACHLORODIBENZO - (TCDD) . D r .A .MILFORD WARD SUPRARZGIONAL S P E C IF IC PROTEIN REFERENCE UNIT a n d DEPARTMENT O f IMMUNOLOGY, * HALLAMSHIRE HOSPITAL, SH EFFIELD . UK. * ........ bu icuo was InitiaC^I'as a result of the * (V i • • reported incidence of secondary immune -defects in the Seves< populatio'n and in view of the available experimental evident Studies in experimental animals, both rodent and primat have shown that thymic atrophy and lymphopenia are consisten v—— ------- *— • — ---- *■--- : ---— — * and sensitive Indicators of TCDD exposure or toxicity (Vos 1978) .* Preliminary studies in man have, however, failet to document a similar abnormality. The studies conducted on | children exposed at Seveso (Para 1977) have shown no diffaren I in serin immunoglobulins, complement, or lymphocyte function * between exposed and nonexposed control children. The present study sets out to examine the in vitro immunt capability of three groups of adult males i) exposed to toxic levels b.f TCDD more than 10 years previously and showing clinical evidence, of toxicity in the fora of chlaracne i i) i exposed to TCDD but not showing evidence of dermatologi toxicity. *1 . , */■ .• £ ill) unexposed controls* /¿yw****. n : . . V Strictly Confidential RESULTS Strictly •'Confidential Is s u n o g lo h u lln s - XgSi T h ara v u no s i g n i f i c a n t d i f f a r t n c t b a t v a e n th a t h r a a g ro u p s o r b etvaen^ th a t s s t groups and th e _ la b o r a t o r y r a f e r a n c a ssn g a a f t e r dua sg a e o r r a e ti o i I--------------------------- 7----- ■ . XgAt ' T h ara was no s i g n i f i c a n t d lf f s z a n e a betw een th e t h r e e g ro u p s o r b etw een th e t e s t groupd and th e la b o r a to r y r e f e r e n c e ra n g e a f t e r due age co rrB C tlo r 51 o f th e p o p u la tio n a r e d e f i c i e n t i n seru s. loA and t h i s p r o p o r tio n was r e f l a c t a d i n e a c h o f th e t e s t g ro u p s . . IgH i T h e r e w as no s i g n i f i c a n t d l f f a r e n c e b e tw e e n t e s t g ro u p s A an d 2 and th e le b o r a to r y re fe r e n c e r a n g e . l a s t g ro u p C s h o v e d a n o r n a l s e d l a n v a l u e f o r IgM** a n d a n o b s e r v e d r a n g e w h ic h w as I n d i a t l n g u l r h a b l e fro m t h e o t h e r g ro u p s b u t t h a r a w as a s i g n i f i c a n t ^----------------------------------- ( p C 0 .0 5 ) i n c r a a s e I n t h e p r e p o r t i on o f c a s e s w h ich g a v e Ig K v a l u e s b e lo w t h e 5 t h c a n t i l e f o r th e la b o ra to ry ra fe ra n c a ra n g e . £XgOt The d i s t r i b u t i o n o f t h i s I c a u n o g l o b u l l n i n t h e n o r n a l p o p u l a t i o n i s t r i n o d a l w i t h 10 % h a v in g ' u n d e te c ta b le s e ru a l e v e l s . T h e r e w as n o s i g n i f i c a n t d i f f e r e n c e i n t h i s s u b s e t o f t h e p o p u l a t i o n f o r t h e t h r e e t e s t g r o u p s 1. 23.6% o f C roup B a n d 21% o f C roup C h a d v a lu e s o f XgD b e le w t h e 5 th C e n t l l e . T h is r e p r e s e n t e d a S i g n i f i c a n t d i f f e r e n c e i r o n t h e l a b o r a t o r y r e fe r e n c * p o p u la t io n {p< 0.005) b u t t h e r e w as no s i g n i f i c a n t d i f f e r e n c e b e tw e e n t e s t g ro u p s 3 an d C. loC^of the normal populatiotvAave very high scrum levels of IgE and these represent the pool of atopic individuals. There was no significant difference between the three groups and between the test groups and the laboratory reference range both with respect to median values and to the proportion of atopic individuals. *. T a li l o I Inumi noe; ] o b i i t - l n r!-— n mediali obsorved* rango No<%) below 5th contilo of roforonoo rango. • KjC A 31 10.0 6.5 - 14.0 g/i B 56 • 9.7 6.5 - 15.8 C 38 - 10.2* 5,6 - 13.1 • Igìr' g/1 A 31 B 56 C 38 ' 1.9 e 2.0 ' 1.5 0 (-)• • 0 (-) 1 (2.6) N.S. i 0.6 - 4.8 1 (3.2) 0.4 - 4.1 T . (1.8) 0.4 - 4.8 1 (2.6) N.S, • IgM A 31 0.8 3/1' B 56 0.8 /r« '. C 38 0.7 1 ’ . ‘ 0.4 - 1.4 . 0.2 - 2.4 2 (3.6) 0.2 - 1.4 7 (18.4) Strictly Confideniial p<0,.05 o i U3 • T.il.la 2 (Conti n* aodian* olisorvod rango* No(t)balow 5til contilo* Ho(t) not dotoctod IgO A 38 31.S 8.5 - 85 1 (3.3) IU/ol 0 S3 U.O 1.0 - 88 13 (23.8) 4 (7.2 34 13.0 . 3.0 - 131 8 (21.0) 4 (10.5) C , ■ • |K *0.005 . . if.B * Ho(l)bolow tha 10th contilo of rofaronoa rango. IflB A 31 40 <9 - 180 XII/»I 0 Sf 44 <5 - >1000 £ (10.9) c 38 37 <5 -, >1000 3 (7.9) . No(l)abovo 90th contila of roferonc rango. 4 (12.9) • • C o o s In which aorua XflD not, dataata^ ara oxaludod. 3 (9.7) t 3 (1.7) 8 (14.3) . 3 (3.3) H.B. • Strictly Confidential I A-10 .Lymphocytes, lymbf^tcyte -subpoculations and (y";itogen transfornatl There was no significant difference between the three groun or between the test groups and the.laboratory reference range fo total lymphocyte count, T-calls, or B-cells- There was, however, an increased proportion of cases in test i group C (p<0.10) in whoa the lymphocyte transformation in rescon to phytohaemagglutin was reduced. . ^ Strictly C o n i L d e n c i a l o Tablu li liyinphucyLoa and An vitro _nltorron transformation n 10 th 'Contilo median A 29 . 1.6- 2.3 4.3 B 56 1.6 2.2 .. 3.6 C 38 1.6 2.5 4.0 A 29 1.0 1.3 2.7 B 56 0.7 C 38 1.0 1.5 . 2.5 B - c e lls A 29 0.2 0.4 0.9 109/1 B ■56 0.2 0.3 0.6 C 38 ■ 0.2 0.4 0.9 A 2/29 6.6« B 2/56 3.5« C 5/38 13.0« X 109/1 A-ll T o t a l L y m p h o cy tes 90th contilo’ • N .£ • O T - c e lls * X 109/1 * X P tW t r a n s f o r m a t i o n depressed • 1.4 . , 2 ml N .i • • N .£ '•Sv * •p<0.1C • Strictly Confidential. A-12 n r.n ( CONCLUSIONS e H T«j\rn mii(h iitrim n n over ih r laM leverai ycari. Bioawayi ni a chiom e duratimi 1 1 tiri) a l ihort-lerm grnrtic a "a v i havr been devrleru-d **nh in ry c U w ird thè rarly rrcugmiifin ut thè occhi t e m e ni a Iciion in tom e larari nrgan. rhviu.lngii al ami limt lim ili ai chance* are unti-tui tir anali*!* and uiivnllatH i- in au rllmi In ilrn'lnp a Mreeit llu t tu li ugual thr |r»*iin li:\ ni ilir « tur retite ni rhriniit linea***. Aflhough thr lin-r ami lubiey h jie hi* n nm*i ino ii'iu-K iliiT'tipalrd. tilhrr i l ' i n n i h jn - h*vn in n i in tlu* rilori tu n ta h liih an rarly m m n t iv 'im i. T he nij|nrui- ni thè ttv d iii Carrif Huni t u ie noi lali-n min .1 culmi 1In- |Hn»diility thal thè im m une *\*rem n uv In- ihe nltul vi-hu lo Inr lu th hiojViali, l'or whalever rraw m . un i-Migainri li a u ­ lì ndervit ini n ed thè inigiortaiirr ol Ihr im m une u u e n t ai T - T V U lM fri ■ V II» M U 'ih 1 4 tubili I Ni llv M |^ l H U .h .11 V ig ili I Kt M mot U ém di I——**ra*-. « ta l Piar irli 7»'L|*4>J ■‘ U ta | f r ’Ai»» | | IJ4 l l h i i l 11)**-l*|»**l il il r th i- u e • | »Ik »wB+iira*Mf*4 I ir frtk d *k t r tl* h t f W h « a n ■|l* 4 i 4 |-H t< n > k > d fe 'i a i t a i CH A RLES C T H O M A S • PU B L ISH E R • lltinmo • U.S.A. ¡1 r 1 »• |4‘!v 71 £ m w M tn J ltnKnt|T /ai ai aacacia i-J*e r «ad CkrmHol (la iw i^ n r u rrlalrtl tn iliwj*r Mairi. T liii aulliur fe d i that a mu Irui ut in hir mal ìi 111 lu i beni drvvlupnJ bv numi moli tir a 1 invti■igaturi lu indirà le that ihr ¡ninnine iy*iem organi ami tìiiite llhymui, *piren. bone mantra*. lymphocyte*. nuuiocvlei) mav provide a ferule m il tur lu d i in m iica tio n i that alleni|*t 111 pmviiL-eailv ilei ertimi olCJ]van1v tv ilim n it d i y i f by rtivim nm nilal ■hcmtral*. * Imtininedvfiitrncvnr mndulalienul ihr immune r o n u n v hai been I n m n tir mane vrarv. Irradiai ioti, malnutrition, ihym «lum e and m ia in aniiranci-r lim e* currently in u*e are proven lo rame a li m ile in thè, immune *v*rrm. Although the immune »inerti »com pie* and nul rumpletelv tliuk-n Irani, .lulliiinil information i* available in until ale that ran n i» clementi in ihr immune iy»inn ap|*-ar qmle «•nvilivr lo chetnital*. il il veli eMjblithed thal art ¡ve celi) are ihr r w .| n-nulive lo thvmiral'. A p u d deal uf informalum hai heen di'ieb|K i! un ihe u*e of am tranter agenti ami their rana* bili»* lo induce vecnnjjry and Irrtìarv u n u n in p a n n i» undergoing antiranrer trealntriil. Sume ut ihe riunite' attneiated villi 'iirh irt-jinu-nt al die cvilular trivi are alni irmi ia in*' and m nlru ami ni em ine raivev tlu- ipievUnn ut grain. the en iim iim eiital clientiial* that | irm i it a t ari iiirrci-ni rLik lo human*, ari* an ideai taf gel tur m* I-Migjliim.* In order tor*laldi*h unne ini*a*uteul rivi, pii-dii live Invniih 1 ; hat had lo live the varimi* available Inni* 1 e] ili Irm i'.u-gì. *ljti*ln . m rsp o la fin n i o l jdia r m ai illogica i iin*c rr*]Hiii*e Mutili**, lile nm tiple ip ecie end target oigan hhiawayt, mirrnhi d ,'h iu th rin :i. U u diri, a n d d iem u a l iln tc lu ir re la limi* hip*. ‘*'* 1 lu-*e toni*, -e* nnlH iuily, have ie ri rii u i very a ril. I Jnai-M-r. ilio lavi llu t lumia dala ii lacking in a majority uf die ca*e* ha* Invìi a m u nì- > con vi eri ia lion. Recent devehipm enll in the area uf immutntloicv have prm itfe a nucleui of data and of concepii that nuv help n**tdve m ine 1 th n e [inibirmi a v u vialn lu ilh c.\lra|H ila unti* tu iimi un». AM..... . im m u n e nu-chanU m i and th e n v in ii ha* noi heen ilelu trii aii**i lulely, reiearch iL ia ha* h*vu ih-irtu |ieil thal »Inn.* that im m illi ivitrm celli (*mall liinjihi>rytr*.'1 and U ceti*. ................. ji. produci* tuch a» IvmphnViiu-» (ila*- a w rv iiii| mh taut r■->i- in -fi body'* immuni rear;mu io powthte pjihidng* linai in iiiu 'iu inlrciiou, grall rvjvctiun. ami tumum prixluum n. T h e fact thal (lieve cell* are readily accevvdile ami are huma liu o e prcvc’ill in eilenvivi* aninuiit* in |H‘t iplu i al IiIihhI jiii I t:.n polen lial fnr rapid pini ¡tei a linn m a lli them an ¡ilea I vehicle !-. the ilud e of jMlenlial loiìcilv. i h c l h r r ¡In* a r t » il y can Ih* j I m i r i d o n e i: ■ira**...... In A J. ^ 4 irj■ ^ MI «Hi 1 |4 a |^ | U lti t« * l i j li: 7 environ meni al (ln-iiiiialu TU» anlliur le d i llial tlurr are Mine rei atinn dii] » d u i make thè tie.ii ilreaile io ìmmnnokuicnlugiral n v a a h pwnblv ibe mira cam m e im i (HilenI¡all V ibi- nut'l un| aif1.itil. Ini mdu ci ion During (he lau lite v e in , maul* ni il* h a ie heard liti Mjlrrirtit thal “a laige munla-r ut tatù ri» uuv Itale tlu-ir rimine*- in die ctvvim 11011-111.“ "Ibi* naieineni hrl|H<| tu pni|H-l an alieailv eiu*r* p l i t lUlìuiijl i l ’ iti- tn « n i u n ic i u i u * atnl u n i* Mdoxigli there are many itill<-rriti ojumtnii a* lo thè ai Inai numla-r* ni earner ra*e* rimn diun-d hv die < -I iihi* riiviinnnieinal Lh Iui*. it ha* la-rii gi-ueiallv agri-vii U|»in. anioni; limiiiedu ally ni lenirai n-M-inb *t lei imi*, llu t rfiviiiinineiiljl ta li u,ugeiit-»i* » a real etti iti.1 In alt vlliirl tn n v l a Ulte 1-1 in La gin a pi 1 vviilitni pm- I mimine Ceti A niliiel Olir alea llut lu i mu I n v i nell io*e*ligaleil hm i l » ile* al lei e u ­ ri thè human -mmiinr »i-:i*m. Vn»'" a* *u-ll a» Sill*n*Mli ar Loii'*-.‘: hall fn um 1eiiiteiiieili.il *n|p(*»il' tlu -u n u-|>l 'b it *1 nmm entai iliem iia lira n ptiahne miHlifii alino* 10 ilo* ai Iti 1lie* ■ do* iti'.tome v i vie ni irli*. A m I i I m h Iv i i » » I Ì j I i * I re*.la m i •* 1 eli nt> ■! a ln i lev i'ijiu e. a* n ell a» umva*i*l leve!» ni o u n la liti due 1 lira ri ivi resinanti* tn lurtetial inleiliun» Inni* U-eo I i|n r l n i . llwn ir vii-“ *. /nniMiikti(ol'*(l tméChinimi CarriflOfMeiil Immune Deficiency and Malignancy O ik- ul the mod significant advance* in o n c e r inltirmaiion i* llic [incline that immnnodcfieirnl Main* arc asviciaied with an inere***xl incidence of malignancy. Henry" ha* shown ihai patients whn have naturally occurring slates o( immunodeficiency such as W islnll-Aldrich disease. Ataxia telangiectasia. or acammaglubulinemia have an unusually high incidence uf malignant disease. Numerous experimental hinassay* are cited in his review, show­ ing that immune suppression facilitates transplants of malignant cells, increases a normally Inw incidence ul viral or chemically induced careen and accelerates g r o t l i of mctastascs. Immunosuppressive therapy has been used for some twenty odd years and has had a significant impact in producing secondary and tertiary cancels in patients who were under such treatment. Penn** has been maintaining a tumour reentry of patients who were on immunosuppressive therapy and classified them into five groups with the following result*. f a tim ti n lA TranKptantfd CancVri Sixtv-om* patient* who had received organ transplants from non who wrre neoplastic or w ithin several month* solw i|u en l to tkitution drsvlu|m l es iiletuv of malignancy showed lliat tswrniy-cinc patients or 31 percent had evidence ul transmitted cancers. Cessa­ tion or immunosuppressive therapy and removal o l the graft re­ sulted in thecompletr disapgiranintr of the disseminated neoplasms. T n m plan t Patienli with Dr-noro il/n/ignnneief derna- of 5.7 [terem l. T he Denver Transplant Tumor Registry data on 401 Jr »mucancers that have occurred in 374 patients t have rrceivetl khtucyv T he average age of the paiieui* were (hi nine yeart old (range eight to sevrntv years) and the neopla1 occurred from one month to one hundred fifty four m onths |. 151) after the transplant (average 32 months). Alter the Ira plants, the following immunosuppressive procedures were us Prednisone. Anoihioprine. ami-lymphucyie globulin (A l.(i|. A nomyrin. eyilophnsphomidn. Radiation, spletsecioinv, tlism nui and thoracic duct fistula procedures sverc also in use In ct.njti lion with A LG treatment. O-mercaplopurinu. methotrexate. , aiascrtne were a Iso used. T h e patients receiving irradiation, splcncctoms-. ihvmecto: or thoracic duct drainage iriaim cni accounted for 2)7 dr n cancers, while the patients on pharmacologic Ihetapv accoun for the remaining 164 cancers. T h e development m malignat could nut be related to the use of any one agent, but ap|H-arcd ta an effect of the general immunosuppression. A sjgmfiram fintli wai that the incidence rate of solid lymphoma* among the ore transplant patients was disprnportionally higher than tin' gene population. One variety. Reticulum Cell Sarcoma, was calcula to be 350 times more common. T he lymphoma patients wi slightly younger than the other cancer patients (36,3 sersui yean old), and the tumours appeared earlier than the other cam patients (iwcniy-rhrcc sem i» thirty-five months |, ' ( he solid ly phomas occurred in ninety-five patients wsih the following bre; down: Reticulum rcll sarcomas . . ............................................ (One patient also had a Kapo*i‘i sarcoma.| Kaposi'* sa rco m a ....................... ................................................. Lymphoma........................................................................................ (Including 1 plasma cell lymphoma). Lymphosarcoma............................................................................... Lymphorclicular m alignancy....................................................... lludgLins D is e a s e .......................................................................... Histiocytic Reticulosis (.').............................................................. In a long-term follow up of the University of Cutorado serirs of renal hu meg rafts. 32 ol 46-1 patients developed cancer, an inci- M» amtiChrmnal C-r< IS--V- tii-iniMmrmlmt 7>n„ iJ.fr Ktm Tramp)font filir n li Trrrttrrl trilh ImmHnmupprtitiixt M nliinflammaturi thriapxf Data has hevn colliels-d that indicates that of seventy patients who Itavi- In n i lim bi jniiiiinjiiniialnry therapy. sesTiity-two canrent dove lo) hvI during trvaiioenl with various agents. .Vo fu n Drrsv An Cairi Thrrapi •Vis Cue* CaartrTxpx Psoriasis 24 Mrt hoi m a te Ami mips rr in Other 23 3 H Lvsnphoma IjukrmLl Skin Mise. 1 1 5 16 ttrsial U iv a v 13 AralliHijiriinCycluphosphaimdr Other 7 7 in Skin Lymphoma Mise. 3 1 6 tthmiualuid Art hr it is 10 Cyclnphosphamidc Othrr s 8 Lymphoma Leukemia Lymphoma Mbc. 5 3 2 4 System r Lupus Erylltematosui 7 Cyclophosphamide Amiheoprine Other 3 6 6 Kaposi'* Sa reuma 1 Other In Itami lory Disease* 16 tr - \ Agent* C w i |i* above, alune ur X* combi unp s . a- . chlornapllarim *. (Iiluraiiiltui il. l liio le |u . m i-llm H isa le , a n d |i nisiHie. alune »1 in m m hi nation . I*11 new m a lig n a iu m- i iL s r ln Various letileim asa» iihiii IivI tor rtglisv-iwo ol iln-tn-u lualigitair thirty-five lyniplium as. tw em v blailiti-r ta it innm as. tw o taw r a m r r o f the se rv i* , am i •■in- H od gk in s i Iivmju- .......... m l . remaimler uf the iaw-* were sa n o u s anil missel Iain-mis tom malignancy and totalled filtv-fivr. Acute leukemia octiirieil in llurty-nine cjm-s where lite pali originally had multipli- myeloma. Iwt-iily-ts-sru solid lvmphn sievelojicd in cases w h ite the p a lim i* original neoplasm chronic granulocytic le n ir mi a. T lir-v uinisnal cl irretii i-v **i tend to dispel any iils-a* that these cancels wen- transition turn the existing malignant v. T hus, nne can rautioiislv extrapolate sfata and itlrniifv a signifirani association lie|wtx-ii the dwtmeut of malignancy ol lynsphnid i-lrmenis anil tin* use o l cht cals that have the capability of suppressing s-lemrtiis in immuiic/host riefrnse system. (C lilnm aplia/inr it the ou r at capable of directly causing cancer in man since it metabnlirr befana jih thy famine. It ha* causes I bladder cancer in aniline worker».) Leukemia» and Chemical Immune Modulation Cancers 16 | Lymphoma s.. Leukrntiai, Hodgkins. and cancer pf tlin. blackIrr. culón, brunchu*.) ■- - * t . .. 31 W ra^utit D u n ln f fitir n li lt7fho*i Tramutanti lit ttioil:jo>i>ljnl pjltetils with it,n]'lj'itit r n i'i'm ; minium»sitppressive cancer therapy, l’elio" ami Ki im-v*1 slu-wcd that sec­ ond ami r i m third tiiiiunin have arisen during in-ainu-in with theiiuuhoTjpr-niies. (If |M*t |i..n>'iil' with urniiuirs treated with eillu-r Melpl talan. CSVInphu-ph amule. Unsu IIan. O-meirapiopui me. Of the four major lyin'* o l cytnlogiral leukemia, im e lo it l, lymphatic Constitute the- greatest ¡vrcvtitagi-. Mveiutd cj*v* p o u t at about mt ps'iCrnt Ilf all It-nLemi.is jl agi- thirls to lori*-, it decline* thcresllrt. Msv Isinphatic type has the highest p n lence in children ]v a lin e at abmit V) prreent ami then ili-eli till age thirty to forty It then rises tota) percent (v a c Leo-ten a eighlv to ninetS". On the wav up in ns peak, tin- lsm phatic I’ passe* mtrlinil type li iiketiiia al a lm i' \ i n u \r .n s ,.1 age.,: Ancpids-miulngtial smilt of solvi-ut exposure jiii I Ji-nkt-uoa1 condor ted among robber workers hv McMirharl et a!.*" iinlieal that l o associaiinn between le.ilem ia ami ioli« d u i n ivol'etl si* solsvnis existed Prim to tin- mite. h>-..Jei ,„(,t | liV u h lil r Pa* well as Viglialo a ml Sana** liad |iie)iati-st pj|«-is iiuloatoig II thought that the d o reni i-sdib-ni e soppot i.-tl tn-o/i-ue. pin-ii butanoic, and clilto aniplieincol as thing In it cm, >-;,ii-. lume* they hail, fumili lo lle s-pnb .nm lngiuj eu ik n ie i>> sup)wot I B-3 h n ' i u n n i k i TnMXnltifr /minaatitaitenbft aa j Ckimitaf Gtrnsi'ersrui jxnlnre. Ml Michael cl a!.* had analysed nunc W ill ru-workers (male rubber wnikcrs) '»'bo were m ii Vine during the yean l^trl to 1972. bul had an employment dural bin nl iwx-nlv-fivr yean. T hey were followed for nine y ea n with a I percent lim . M airhitl run* trnl* were also analysed, with standard mortality raitm and pro­ portional mortality ratios ealculalriL Of the varimtv relationships dial wvrvanalyirsL tlicaw ii talinn of ilcaili from lympliaiir leukemia * with a history of having wot Lid in solvent cx|iro.urc environ men I Mood mil. It is id interest thai llte lvm p lu iir leukrniia stands mil as associated with solvent r.\|*isorr jobs, l itis leukemia Inuls in lie the myeluhtasic nr the stent cell tvpc. Mr.Michael had indicated that the Icukcmogcnir effects may have been (lie result nf concom­ itant es]>osiire in other solvents that were used in the rubltcr industry. Iluwi-ver. Infante el al.w studied a ]V)|>iilaiimi nf workers who were occupationally exposed to only benzene during 1940 to 1949 and who were followed until 1973. Comparisons wilh two control pom ps show a viguifitanl excess nf observed leukemia ip Irss than 11.11)2). A live fold excess risk nf all leukemias anil a ten fold esress r isk 'd death from myeloid and monocytic leukemias combined wen* demonstrated in the comparison between pu|iutations. T he environments of those workers were analyzed, and records have lhnwti that the benzene levels were generally lower than the recoin mended limits at the tim e they were measured. T i l e observations arr in a p eem en l wtih Vigliani and.Saita.** whereby a «[*x ¡tie |v)ie nl leuLeinia is aswuiaUxl wiih the es]»tsorr in Iwti/riicr. T hr myelogenous or monoesfir leukemia has been shown lo correlate very well with llir ex | mo ire and ton lim it the M isp ifio n that Iten/eue is a powerful bone marrow ix iiso o . '1 OoltfM ein' 1 has written an excellent review o f the lo tic hen»ijwwilie elfrtts nf iN'im-m- e.s|Hisure. I hese eHerts, although somewhat complicated by ronconiitanl exposure in some cases, are latriy well demonstrated. T h e mechanism by which this toxicity occurs is not known: however, the alteration of item tell function is apparent.'1'^ '1 Occupationally exposed persons js well as laboratory animal stud, i « h a w shown chromosomal ahuotmaliiic*. and correlates well with the known clinical picture of benzene lux i c i l y . G o l d s t e i n has rojionrd that in mice (hionicallv cx|>o«txJ to ltd jtpm t benzene. Iciikojiema. due primarily lo lvni|ihoryio|H Uta. was tlearl dcmoniirated. T hese manilesiatinns of pancytopenia tm v reprt sent ■ deslruction nl the stem crllv. failure nl the cells to mamri or prevention of diHereofialmn at some critical stage. fJiher agrtii known to produce pancyiopenia art in this fashion ihruugli nun tlicjtion o f nuclear material. They inrhtde ionizing raitialin chlominyretin, vinhlasiine, m iioitm in, puromyt in. iohh'i( m ean cy tor ha las in B. Many nl these 1ailer rttm|uniiuLs have been, usee I i clinical treatmrot of malignancy. Form el al,u tarried uni eynigi-nie slodies anil have ronlirmv chromosomal aberrations occurring in |H'riphi ral hhwxl lymplu Cytes. due in benzene exposure. If on e exam ines the oniogrny of lyntphocvies. ii is rradii apparent lhal bone marrow stem tells develop inm two d ilh ie i lines of cel Is., The one line produces hemopoieiiv pret ttrsors. an the second line produces the lymphoid cells. Logically. inter hr cnee at the stem cell lcs*rl is bound to affect both the him« elernenis* as well as the onrtitine sysiem elruu nis. laihuraiur in vestip tiu n s have observed pancvinjtenias inch as monocytic and m yelogenous leuLcmias due in Ix-nzcnc exposure also stun stem cells that hast; produced abnormal mature erythrocytes, whirl further suji|xim stem cell nuclear fmit lion interfereitte. \VoImanM has indicated lhai ample evhlenre is present to sfo>« that chrumositnul jlwrralhms call W ouhicrd through oxjmvnn to bfhizeue. Gaps and jumtion h teals Itase Ihvii hIw i i m I ii cultured hiiniau cells (It-Hkiuytrs ami 1 li-I.j ii-ll'l at l.l or 2.2 - 1<1 * M. Iwn/itic. tlichertkises rao-ixl tnhihitnl UNA synthesis 1‘ixiph eral lymphocytes sitimdalixl hv phviohriHjgtuiiuin (I'l (At r\(n**«x to U n tr u e for levi-my-two hours rescaled Imtli im nierual aui sm tiliiral alterations. A nenploiifv and throm nsom c hirakagi occurred seven and eight lim n mure (rtxpieully in treated tells. M ■si fnm m ocJiniiicili and C o n fe r Advanres in pharmacological ihi-rjpv has prixhtiixl problem1 as well as remissions to the liejln irin nl ill'ease stales. L‘j Iii-i] l who hase been Ireal ix I with auiilivpvnviisixc. au lu ri vllnutr a-genl as w ell as amubercolar or anitsouvnlsise agents have shown to In t j t v n w r a f /Iom. J-.fr S|t*aeplihle lo a s y u d io m e re la le d lo lite ¡n in o n tc ili si*a se «atleti sv ste n lil lu p u s et « Ib ern atiisiis IM .h ) .r- ’ 1 111 Sl.K , ih e p .itie n l ite v e lo p s anlìlH H ties s lim n la le il hy th è p a li e n l ’s u w n l e l l u l a r m a te ria l. IX|«11.1Uy th è im i le a i r lr iu e iiis . li alti-1 Is sai m in lissues, a n d I la ' a (alai to rn i. O n e n i th è n ijjn i liiu liiig s in d iag n o si« h a s b u i il ir* |iiis a x n i' <>l a ll 1,h i eli 11* ilvm«ir| .|n UHM||-JT Iti u IX i t e — l'M N ) ih a l iiio la m s phag«« ylisix l n n i le a r m a le n a l. I b is i r l i is form e«] a s a rnTiwxp t r i n e o l r e a rliim l e l s i v i i all a iililx n ly p re s e u l t h a l j a n lu m i l e l l u la r I iiiile o p ru le iu s . l’ri-sin il a lile ilo* mix lia iro n i in so lv e s (h e ly m p lim y lir m u l i ) (hai r e a tts w iili th è a n tiliu h -. I.ym pluH yli-s lux u rn e saturale«! u n Ih e ir ai u v e « ilrs, am i l ’M S re lfs «u ln e lo c o g lili th è " s o ile i! lym phiw yii-s. Ilig i-stin g jw ay fjih a co e y to sìs) ih«* le m a im h -r u t th è ly m p im s v ir. lite l'M N p a c k ­ age-. th è n u ilix tp r o ie m m a te ria l as a re s id u a i hoaly calte li Lh. A h lin n g h ib is itiw asi- is u s u a llv v ir jlly iiuhicixL lb i-ra |w iiitr agi-ms sut h a s ili piteli« Ihyt tanni) il. iwimazid. In i b a ia i inv. am i p m t jiiiam nU h a v r in d u iix l th è sv io In im e th a l g r n r r a ll y disap]n-arx u{tnn w ilhd raw al n f t h r clrug. T h e s e m ec h a tiism s th a t in d u c e r h e M .K xvnd ro n o - ars* n o i s e t s r l l u ik ìi is IlkxI; huwevsT, C hem ical m lh ie n c e c o th è im m o n e xsxim i h as p ro d u re d atiiibotfìrs ih at m clu ile am iU N A . a n lin u c ltx ip ro lc in . a n tih is to u e s . a n li i iu r lr u la r KN A. a n d a n lih o d ie s to fib ro u s o r p a rtic u la le n u c iv o p ru le in s . I h e im js irl a n r r l>[ ih.-se d a ta rv lh x t ih a l e s tig e iu m s c h r n n ia f s . w iu ih m in lilv o r in llu e iic e b io lo g iia t sy slen is, b a v e i m i i 't u l v l li x l' Ih al a re noi alwavx rvatlìly ap]> areni. llo w th is in i|so ru M i ih d en se m i-cn am sm h a s b e e n m o d u la te li b v iu le i p lav w ilh C hem icals is iiu k n o w n . bill i n v re a i r a p a c iiv lo e lu v i n u r le a r m a lrc ia l creai ex g r c j t e r possi* b ililìe » n l b jn h ig h al ils s tu ii/iiin i, Zarrabi cl al.'r slmluxl lour gronps ol h um jn . under trealmenf ior nim r two andone-half years. wilh chlurpcumaiineaml vanrvns « b e r a n i¡in y c hulic drugs. T h r malli Iihsrrsaiion Was lite |>IVVJ. lente nf in un limilo);!« ami ihrimi!»i]>lastir riu'.'iibiiie ih'oiderx. Ili palienls un long terni ■iiloi pi oiuj.mie. ihe aiilhoix Imitili ih al paiirnls luti iiirrrjsed levelsnl st*rum IgM. 4')") i Vi (in i lilurpinmattile leva Ini parteutsi. wlivrea* con Imi« luti !*•; « I I, jm l nor­ ma! is «oii'iiUiixl lo u n g e !• ohi lo 2*xl palienls w In, « e ie gì veli rombi ned Iherapv, chl>ii)oumazine plnv amnlier «bug. for thè sa n ie leu gl h nf lim e show ixl levelsnl »«-rum IgM jt fi.l * 7Y Olhcr t / H i M i u a e r m J [ i r n s a f Can H i.e n s i . , . ■■ -----*...........i - ' . ....................... |iri|ilu 'iia z iiie , luhi|i«ri*l«il. lillu u m . a n d a m ili s p i l l i n o 1 b is gin. a lo n e itili lini p io v itli-a iis - i g i n l i u i i l dilli to n i e s w ln-n i i . n i j u w tiis w e r r in aile Im I w h ii ibi- " ii i n |is viiuliixl. Als*. n o li il wav iocTiaw in len g lti ni j u i l i a l ih io m l» ip l asini lim e. Io In o h installi i sig iti Ih a n i i*o le l j li o ii I r l s i m un u-asixl h -s rls •>! I g \ l n i s i n atoaig s u iti ||iiii»i1i>Éplaslui lim o s o li- nniixl in i i ljii- o i lo ib.i.eii •reale«! with T .h lu rp rn m a z in e and iw eriiv im i n i fortv.iho p a iie n under vitiglc o r combinivi In -a iin c n i ile v rlo p e tl s p le n u n ie g aly . Recemfy. Docliir 1. Fidlrr'* al lite iJelrich M arsljiul (la m i Research Center, w orking wiih macronhages lunn m unse jwr toneum . fouiitl thal Ior vome i«hl rejuiu lite man npli.igev lu g j loving iheir tutunririila] ailivilv ilnrmg m i-itr- «tudicx Ordinar Iv, sudi macruphages in ihe iwrituneinn are noi i vu-rusti fu liitinm Crlls ut urm. hm.eser. a lem phokiiie rrhusotl In an ai livalo lyinphocyir. relerred to av m aim phagr aclii?iìng laitor iM A t ha» ihe abilily In slinm lale ihe mairnptiage lo In ) urne m inim i ulti Surh pcnlnueat exudale macriiphages u n ih n K* stimi! lai ed Io hi xin ne rvlntnsir hv hjrrei i.:l pim lm ls llip .jsd« «ai ■lu i iilr —1.1*M. i-nilomsins. pvrau r«*|wih nn-i s. ikniliie sii'ji'«l« d KNA or ilurinj; chnniic infixiioii wilh «Jdigale lu i lei la. I tu- u* t if i siudies «vere sinp|*xlaniL in renaio « n ■ineil i* lu n e U le wilh a tnnint shangr in ih e ilcinkmg water nwxl Ior (hi muove cotonii-x. (V aler I n i lo th è n i n o Ii j i I a i h lm o io tevel of a ls n il iwolv«- h Sixtlx tl |s jl l s ]M r in d ilo » (p illili. ) bis lu g li l e n i ■« in le s s a rv In r r t h ic e i h e vaio n i l a i l v «k a ih s u n tio in o io ilo- ■» I i .i i ios ,J>n. t. ric s ik w iiw a i inlix In n i so ., i* dia- im i •* hall l*x*o le d ia tls n vaihaiaxl 92 fm in u u a liJ Toik*J"X? /n n iin a n a i^ r tati Chrmtiat ('itntnfrirui Itila* In i l l u i li i'i u ll y liii;li ¡ m i il r n ii ' of - u il i r a i l s rlra tll seti* i ll ii n ii i, Mie ( li ln r i n r Irvi-1 « a i ra ise d In 2*i '<1 .HI p p m , a n il Iho * M aim p lu gis that b a ie U n i attivali*! )•! lim pbóknies bave m ilit im i bai lei i» piai aitisilv, and nu-talailii a!l\ a ie *1u>iui lo bave a tour to figh i lune' mcrease in tlu* iipiake ni »linose and ils nxitb Itoti a' innijurrd lo -ipji‘ily will alhns almi tati! ■>11' in i outinio* g iim nig and trl*a.i)i/nig' Conni rrenlly.il idi risi pjllm logv alai <»( nr-’ ( lilm in» b tris aitisi crylhriwylrs' jlu o is f nirlaUJism, and laigr aoioiints ol hrtiìugìn-, bin degratLiimi produci'um l/iir lam e inniilieisiil ih iw ip il K ilt>. Ctn supjHess mai mpliagr liinioinlii j ) ai lìs ilv, Rrgardlfs* »f thè misbanistu hy w liìdi Ilo* ihlut inaliti «an i or chlurinc mnifamiids may eseiI llieii iiifloriite. Mie ntijmilanl lai l rrmains Miai niairiiphagt-ariivhv is rom ponaiscil. V o te il u i t i e s a major ride in Im*! deli-use agai no um plusiif iliseasi*. Mie fawsibililv esisti ihat a Itosi who is c.*|aised io sotti ium|aiiiutls may ili bici bccome im nioootouiprom iosl. Sdita. uragrenan, ami irvpan b lu e are subsia n ics Miai al su frase ilo* a llib ir In snppiess mai rie phagc* in lab Mutlies basa* lacco rcporlctl lo disreast* Imsl resisiance a^ainsl iransplaiiiaidr himnur*. * Ihm tllìkcrcl al.** n sr o ily rejmrteil lht*ir stmlies o( Mie i-lhs Is ol pr.sticiiles dii Mie imnume irsjmnw* lla in siers(|.t Iti, | AKj lise lo cìghl wevks olii ami «ciglim i; alami It») grane. wctc » itis i a tinse ol |a*s)i( nk* eipi.il lo m ir-luff M:e l.l)'"' tlissolveil m t od ol im o oil. A lia liior IL"», tlioosi ti. l'araibioii. p»itUi liloinnun luoortte. pìfa-rnns I bniosiile, im seil ps it-ilo iiis. ami ir so m lu io h ir r adulili ¡siri tsl inii»gatti n aiti [ In* .nom ais tven- esam ini i1 !••■ ali etiti Jabot ol **li |llti*ss and sws-lhng~ tìullaiiiiualoi s‘ trs|»iiisr| and riu n g e in Im i|w iadire of il»- fool futh. as o rli js Iii.inh.giial exam. atler an juiigeitir iballengi*. Sei ulti alili In» tv litri, lo ioti ili; affinile, and hetriogriirily w eie lU-orm ond liy .........*m eoi jmlat iralinu nii'a'nreiiii nis. T tie auìnials w u e tirsi »iss-n an m ps litui ol lluotest eo i la belisi ovai bum in. alloweil olile waler atf ith liti 1» rlll v 'Ioni Imins. ami Ih et) gì veli a lailus 111 baiti wilh ih e pestò ¡ile l»v inliaga-li ii Im imi; tube twenty-lour Inmrs alli-r Mie iniinim i/aliou. Ilo* musi experimental studies v er e carried ml as im u l. At the 'lari tit the experiment ami just bcluro treatment. ih t mean number of I’KMs per m oine was 2l * *1 ■ hr*. IJur week taler Ilu* level nr I'KMi in Ihe m ite rrteivntg lieperthlnrinaird t u tc f hat] d c tn iH il in 1:1 ± 1 « Ilf* jier mouse. (jiiiin ilt vrre yielding 25 * .1 * III" per mi him.*. On co n o tti li ve weeks. I'KM Jrieltl int erased |m m Mirini Mini mite, but tinte mi liv*»r[ied arnie hemolytic anemia when treated wiih water lhal, although (iliert-il by reverse osmosis, has 2 to I jiptn fillorini*, Chini ine nun poi »Is brought a)«nit a ib’iiaiiiiatton ol the heinnghdiin Its it im i usitlaiiwt amt also lis* inhibit ion of th f itili* i i is id.it IiLe pal lot »s 11 It*sow* mom jihnspliale sliiiiitj ol n il blond rei Is |Kl>(ls|. T he iLmiago to Kilt!* wiis fmnol 11.* ninnila lite over sesera) |w*i o » h oi ilutssis. Although the mechanism lor this tlepiessioii ol mat rnphagr lum oririibl ailivitv is tmkiiowt). Hiller suggesis ses-rral fins'ihili* tk-v H ie vat Holes ol the macrophage system art* jo u lulile involved it) the rvlolnx'n mi s ) i.i ills ni. 'Iliis lias hern simun he llih lis and Wei oberi;'' whereliy inhibition o l die lisn sim al n o vines of ihe marmphages ntturs by addìi ion of irypun blue, and siali il ira lion o f (hr IvMeannat nieiutoaues nenie» with the addition of hyttrocortiannr, and the cytotoxic a n iv iiy is iup|>ressnL *r| f ittn a a r s a l 7riisi4.^r striking feature rejan tisi by the Jiuhois allrr iom itoiaoalysis m ili­ tatisi mai Lisi Immolai ami • - Itulor ini nini iieii|i]in-ss|oti Insiligli* ■kiss ol DillirM’l) ami l’aralhion, ami a niaiktsl snuiiilaiioii ol Mie cvllular n*s|amse hv resine Mirili, The oilier |n*siicitlt*s sliimetl little or no effert tuuler ih o -e lom hlions. In aiiollier simlv*1 lisio» ilo* ]icsio iik-s Atoeirvite. (iarluivl. (Dilla li me li ir in, DlJ I*. Malalliiini. M nex. ami Jiatalhiim. a single dose resst*| l u i r weight as well as tl*j*M*sml ihvtnir '-eights. I lle s e siepiessftl vjiurs were evnleul al tiay 12.' |w>slifosiog. I In* weight ol Ihe *jsleviis were also loiind in be alti* ted. FJItsIs of TO M ) extaisiire on ihe Ilumine pa net ns nl Ivinjitiiwvles sren* also símil t*l ni Ihew same rat strains, h] dente cells taken hunt /M n tn a tw .^ t* r ta ( ( ( a i , ih.»* a - » tn ** l l i f I C D l i r t | > n n l ra is w e le i i i p s l n l in n i iio iii -.sjmis-*) i j t s . aio Mie lliy in n s w js li.u m l lo 'ig o i l ii a iitls nnie-tsi* ilo- n p i a f e o l sm ! t ells. l livloil tells laLnl liom ri...... . il la i' s i i e inp* l.*t| un. 1 0 ) 1 ) rx|HiM-tl tals. a m i il was lo n io i Miai ¡lie te iva- iN xieasei i . 7i ^ it h o m in g ald i il y lo ilo* l l m i i i i s '1 h e s tili» » s |tio|H tsi»l Miai a i luog* i n r e llu la r m eta l» ,listo - a i t i r r i i l a ll e iì n g Mie t i ll n te to b ts n e . or llta l in se rì ioti o l lite 1 O i l ) in i» Ilo- m em brant* i j n s . i l sol lati a l t m t i o n s . aliti ib is ih a n g e in lite t e l i m ia tilie il ils m u tu a i In n o lo g p a Ite rn s . Vai im is tiisi-.iig a n .rs f u s e sh o w ii sui li a h e ta tto iis it im m u n e funi tim i «lue lo 'IO D O l'.s fa rs iiie ."'.'1.*' 'I h i g j a ii*' tias show ii Miai s u l» l iu i t a l i to s i' u t I f '. l l l ) fiati ilo a b ilily lu allect In n i ie s [a m s e . wlit'll su li'e tp ie U t e \ |» i s n r e lo .taf monelLi in fitlim i resu llt* l in re ilu n * ! lim e lo m oM ahlv. f in i s far, e s fa e in r e tu 1 0 ) 1 ) lias b r ì i slm w n lo taiiM* s u i i h o j h * in thè s u s c e p lib ìlily 111 b a r le r ia l iu fe c lio tis is n p ju e s s im i o l im m u n e n rsp o n w ) as w ell as sii p |i ressi m i of in in •geli resjam V iseiii-ss. silfo [tre ssin n nf lite s k in g rafi r e j i s l i o u . a n d ileprt-ssim i III ilie delavial h y p c T sc m u iv ìiy res|am * s‘. tS u jijiressio it td llie V-tell ileja-m lt-iu im m u n e f iu in iin is jjijw a r s lo im ciit as a n ¡M ilated resfa m se .j ‘v . Summary T h e influence o f em'ironnicnlal elim inai« ujmm the public health is of cnmiik-rahlc im|mrlauce. Determining hirw 'in h i In-itt­ ica Is may cause aihrrst* elfin» ii|Miii human« is a cun Iinn me problem dial (tc-rpleM-s ail phase« ul scientific inquiry. lli-in n c chronic toxicity ami il>n« rc*»|>mi'r» art* donned Itoni animal bi nassavs and microbial UNA Minile« lor human use. ami emisi ilulr ■ major source of cunt roveri«* a m one predictive lexicologists. A major su-p forward in resilvini; «neh pm hlenn rtmlil he allained with th e u h * of liuiiian lym phoid cell«, « h id i are r e a d ily available Irom the peripheral circulating blood. T he lymphoid cells of the immune sy«u*m aie an integral pail nl the drfen«e mechanism known as immune surveillance and are very impor* tanl in the recognition and removal of ahlierani nr malignant cells. It is this relationship dial may Ih*disunited by envnonm riilal chemicals and allows carcinogen c»i« tu proceed iti «usrrptibh* individual«. T lir ii«c* of imiiiimosiippiessivr clierapv Ita« shimvi there 1« an increased Ircipirtii y ol «arimi« tvjie« ol malignant disease a«» ■ tateil with continued u«e ol «utli agent«. S m u n b iy as «*ell a« li-ilurv earners have b m l ptmliued liv llierapeolis «uppression lit the immuitr ««*«1001. (ioni u n eiillv. iuit-'ligJInr» h a lea lw i sliuwn that oceurrvnre ul malignant disease i« aiwi Inumi in individual« o lili genti ir initmmnilrfii ¡entries al a higher fit-tpinirv than in immune normal hint«. So it lias lin o me appai cut that inatiguant rr«|>nn«e in a given host may in Ian be vety «<*non«ly ikqieniti-ni ii(»>ii an immune system that lias Invìi «01 nel low t ompiunuwvL ini H /a r im iir ilif J in iu lu t fa rt/m ami in o «tiulies iisiug (tesiliiili-s. inelatlo-oig.iuìis ami vai il 11»' phaimat nlngiial agi-nl'. Itavi* show 11 ilial teriain allividì*« ol 1volpinoli celi' arr modulateli liv thè pri'wiue o l mane n i il k m - rtinl|sutmK. l.yiiipliooyto» haiv* heen either «nppiv«vvl «r «limolateti, ami ri il ter lomlitiim niay In* alliviiug iminniu* n*s)H>n««*. Hit* lit o t i monne vie«, wliich play a viial tuie in thè |1h i-II/I h oli iun-i ar­ ióso«. are showii 111 he vrrv «r«v*n*l v disturbivi In* esressìsv* a monili» of chlnriue nf hcmogtnbin ib-gradalimi proaluti«. So. direct or in d im i filivi« can modulale thè iiunmuc rrsjimiw. «howilig ihr srnsiliviiy of tlie lympiloni (stipulatimi lo em immne-iil al infili' cure. T h e celi» tlienueUv« nuy bivom e ilekviive tlinuigh riirtvl action, or thè ii»«u<* in whtrh divy mature ami itìilereinìaic n i» be nmdifii-iU poalm ing au im|Mii..L>lirirnt Imlivufuals is sigmliraul and >amml be igiuuml 1 he com plrsiis ol 1I11- im m im e «««lem. details of niv\lijni«ms. in lari, whelhrr tells or pnwtucl« may be influencing tin» svsirm is in most cases not known, Ilru.esrr. it ran be stativi that many of the substance» rarnlim inl herr lodai* a ie il) ti»* ell« lum inelli Jill! tlu-y ilo li.ne niiiiinuou»xlnljlii eth-cls. I low ik a s tln» m ie ni iimtimuitnodiilat »>u alltv I ioti 1 pi Ialino ol p ievious •loilu's ilu i iliw i-uusl Miai j mouse ■.il. gum* pig. nr sono* Other lai» animj] ha« or ha« nì.i i>-»(»mii*i-d 011 malignancy lo a 1 ariinogenii ■Im-iuii al* Ila s e those mi« li daini rlk v li h irn lab-n luto ai • unni in rom lulling d u i «olile 1 tinnii iv or i» not a 1 ariiiingeor t.learlv «uili tpii-'lu.ns ntpla«ltt re«|j>ui«e tu la u ir Im muntitiisirohigy i» ih.- iu -w Vid mi lite lilia k ami i \ able lo js some «-eri* riillirult quesiiun». Questions tor which « i-lu v r noi al ihe answers.. In lite arca of predittive to.iìtology. however. I would «ugge* the following, Btvacisf immutwiutvititlngy mav bring alam i ai additional dimension in rv tra poi al inn, I would «uggesi lliai fnlm «llidir» bi- tlirecifil toward vvam inuig illeso intitiiine svst. ni rio mene, and ho» they ri-»|miid ni iiuttagenir nr rarrmngenu agents Not only in the lah animal «petu-s. bui bv using the p enplu-u blond rlrnieiits (rum humans, K'tjhh'hing a lis'n ecu liu ii- primdure with Innnan 1« mplnv vtes aml/or nurrophages. o iv u Iboiigl: u nirq. wmiM allow fnmtum and stillate ideili Miratimi stu d ie s a. well as hinclieniical mii-siigalinns lo (iitMivle and perhaps (iris mote greater riuìfiils-nti* when (tossili!«* idetthls mg luxit ri-'(SMtM ’ tlthim uns. Other bmitait cell« base been 1 uhurivl. «uth a« lilirobljsi. and the 1lel.a ceti», 'uri-lv ilo* «ami* tould Iv ilone I01 tin* iiitittimr syslrm rolls. | | wiudd go far in ìn i|u ittn g (he program ol pullin' health fur which « e are all res|» m ib le Reference» | k lix b ill, ] | K ‘ r * r t tr w « < e n r « l « i n t l i m i t b i i l r « p H M i i |f n t |t i i m i n *VfT MIIX I1*:» L ¡Ulilh. |. Ks! (dhiTurtimf «1V4 CMmti Idtr h Iiwri'4xm| ( ■ /. 1Ï ¿ i ï '.S V I ; =ì k- »? ■ , ir ï C3 P KI f i l i ? ! S U tf ? - r ìÍ n £ *i - ï 2 ilHK < tr - ?! 3 54 P • i- u ? sH 1 *5' =¡J1. i 3 1 3 î 3 3 î .ï ï 1-Í t ? .« y i f i*j ? m i S?: ^ 5 ?9 U“ ? y ï i i w £• ■->I ; T 3 î I ? t i i î ; -, : i i l i i t î ?î A 2. 3 $â £ i = L' T ïî B. i ?« iï «A H 5 S a i l .- ’; “ m ? ¿ TL » r î' '1- A ï l s l ? i fc- ; \ i II. f? 3* . 3 ? l\ y = î’ f Hî !? 3 t ? H i ri ç f r î ¿P Sill I ïfllîiflïï J;p %l g$ s3Is-; ? ï : =. ? V 3. i l ^ t liI i : è ì 3 —1 3? 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Sn ft- - *3! 3 ?I a t : Zî5_ ïl ^ ïï -i ? 4 3 í .H n^ * r r r i l :ï ;9 ,3 ï- î I *ï i i îä Ï 3 ?; I ! ' !h pÌÌ:.t -îl T5 Î l fi V ? = s f ? I XI > Í1 » îï , n ïï- ii H i f* i í iï- V * 5 1f r^ j= l, F ^ *1 L > F 3''!1 3 h' i* ¿>.^.1* 1.^ ¡*ai*tntty*f s E Í Ml .«ou*ww/ y ..•aS.miu*j ÈÍ *3 ï r. ; *J fi s S ¡p _ iï 3. 5¡ ¡ ï j p r 3- rFÏÏ rir 3t u î * %ï v Î3J Q The attached BACKGROUND 1NFQRHAT1QN reprints- from Co n g r e s s i o n a l Re c o r d are periodicals intended to and the provide B A C K G R O U N D INFORMATION RE GA RD IN G A G E N T ORANGE, d i o x i n ,, D o w , a n d related The this last page Agent Orange Da s c h l e in bill topics. group introduced (H.R. 1961), TIME OF INTRODUCTION. and his is by a copy of the Co n g r e s s m a n remarks at the W ASHINGTON, T U E S D A Y . A PR IL 19, 1983 DOW CHEMICAL CO., AND DIOXIN public because the situation might- "ex plode" and generate a new wave of govern ment regulation for the nhpm imi industry Another scientist noted that Dow official HON. THOMAS A. DASCHLE had disclosed at the meeting a study whlci OP SOUTH DAKOTA showed that dioxin caused "severe” livej IN THE HOUSE OF REPRESENTATIVES damage in rabbits. . Dioxin, which has also been linked ■tc Tuesday ; April 19, 1983 birth defects and skin disorders in labora O M r. DASCHLE. Mr. Speaker, in tory flnimah, is believed to be the deadliesi to d ay ’s. • New. York Times, April 19, chemical made by man. -hut its effects or 1983, a fro n t page article appeared re­ humans have been difficult to prove conclu vealing w hat many of us‘ have been slvely. Since the Midland session, various saying for some time; th at th e Dow studies have yielded conflicting evidence or whether dioxin Increases the risk of cancel Chemical Co. was aware of the health In humans. • hazards and toxicity of dioxin, thè Although It has been known for man; contam inant found in agent orange years that Dow held the IS65 meeting with and oth er herbicides, before extensive its competitors, excerpts from corporal* use of agent orange and these other 'memorandums about the session are-onlj herbicides occurred both in Southeast now beginning to emerge as a result of i Asia and in the United States. Dow of lawsuit filed in 1979 against Dow and sever ai other chemical companies. The memoran course, made no effort to notify the duns raise the possibility that Dow scien TJSDA, DOD, or any other m ajor gov­ lists have been saying one thing in privatt ernm ental purchaser of dioxin con­ about dioxin while the company's manage tam inated herbicides of th eir con­ ment has said something else in public. • cerns. “There is absolutely no evidence of dloxii Dow’s track record on dioxin has doing any damage to humans except foj •been far from exemplary and the in­ something called chloracne," Paul F. Orel form ation revealed in the Times arti­ fice, the president of Dow, said last montt NBC’s "Today” show.'"it’s a rash.” Do^ cle today furth er damages the claims on has performed medical tests on individual: of Dow, the Veterans’ Administration suffering from chloracne for "over 2C and others th a t dioxin is relatively years." he added, “and. there is no evidenc* safe and th a t veterans in Vietnam are of -any damage oLher than this rash which unlikely to be suffering unusual went away soon after." Dow’s critics“ challenge the accuracy o: h e a lth effects as a result of their ex­ posure to dioxin contaminated chemi­ Mr. Oreffice’s flat assertion that there is nr cals. I submit this article for the evidence that dioxin causes human damage other Lhan chloracne and also charge t-hnj R ecord and hope th a t aD Members Dow has failed to publish all the Informa and staff will take the time to read it. Lion it has collected in its own dioxin' re­ search. Furthermore, they say,* Dow has sys T h e article follows: [From the New York Times, Apr. 19, 1983] tematicaily resisted Federal and state ei forts to learn about and regulate rflnrin. 1965 Memos S how Dow’s A anO T on Accordlngto a pretrial motion filed bj ■D ioxxh Yannacone dz Associates, the iegal organiza (By David Burnham) lion created to represent the Vietnam Veter Washington. April 18—Almost 20 years ans in the Agent Orange case, the 1961 ago. scientists from four rival chemical com­ meeting on dioxin was attended by eight tx. panies attended a dosed meeting at the Dow's senior scientists and six officials c; Dow Chemical Company's headquarters. Hooker Chemical; the Diamond Alk l Com The subject was the health hazards of pany. which later became part of D Lament dloxon. a toxic contaminant found in .a Shamrock, and the Hercules Powder Com widely used herbldde that-the companies ■pany. A representative of the Ltonsanu Chemical Company was invited but did noi manufactured. Shortly after the meeting tn Midland. attend Donald R. Frayer, a spokesman for Dow Mich., on March 24. 1965. one of those at­ tending wrote in a memorandum that Dow confirmed in an interview April 5 that thf did not want its findings about dioxin made giant chemical company had called the (Over! meeting to discuss tne fteeim nnxaxaa oi Daniel Bishop, a Monsanto spokesin; dioxin. *'V7e feel the meeUn.T was pretty said In an interview that his com pa dam straightforward and proper.** he said. "didn't do any testing, period, not then a "I think on the balance that the record ■ not now." He said that a fair reading of I shoe's we discovered a problem, sought out FrawleYs full statement would make It cle our competitors and tried to give them in­ that he had not received the toxicity lnf< formation and & mwtm to control the prob­ mation from Monsanto, but was not able lem." V •. i Identify the Information's source becau the material In the Agent Orange case h, INVITATION TO MEETING been sealed by the Judge. The documen The pretrial motion filed by Yannacong & were sealed at the chemical companies' z Associates quoted a number of documents. quest. V. K. Rowe, then director of Dow's Bio­ GROUP 07 75 COMPOUNDS. chemical Research Laboratory, said in his Dioxin Is the name given to any of Invitation to tne^ meeting-that Dow had been researching “toxicological problems family of 75 compounds, called dibenz caused by the presence of certain highly para-dioxins, composed of benzene mo: toxic Impurities In certain samples“ of the cuiss and oxygen atoms. The compounds bj herbicide 2,4,5-T and wished to share lts an unwanted byproduct of several chemic findings. The Dow laboratory was and is rec­ processes, including the manufacture ( ognized as one of the world's finest private­ 2.C5-T' under certain circumstances; 2,4,51s one of the two major components ( ly owned toxicology labs. Two days after the meeting. C. L. Dunn, a. Agent Orange. ■Proving the specific effects of toxic chem chemist who was manager for regulatory af­ fairs for Hercules, summarized in-writing* cals on humans la; extremely difiicul human experiments are generally promo:; what he had been told. “Dow says that their examination of their ed by medical ethics. Animal tests, whic own and competitors’ 2,4,5-T products con­ are universally accepted by scientists as pre tain what they call ‘surprisingly high* viaing essential guidance on appropriate e> amnpnts of the toxic Impurities,” he wrote. posure levels for humans, are not a perfec “In addition to the skin effect,” he wrote, guide because various species react diffei describing the results of tests on rabbits, ently. “liver damage is severe, and a no-effect level * In laboratory rats, concentrations as sma! based on liver response has not yet been es­ as five parts per 1,000 million have cause tablished. Even vigorous washing of the skin statistically significant increases of cance 15 minutes after application will not pre­ In rats.. vent damage and may possibly enhance the ' Two studies, conducted on a group of. for absorption of the material. There is some estry workers In northern Sweden and on : group of agriculture workers In souther; evidence it is systemic." Sweden, point to a possible association be THAR OH SITUATION . exposure to herbicides contaminate) Dr. John Prawley, the chief toxicologist tweendioxin and an' increased risk of soft for Hercules, who had also attended the with tissue cancers. Other studies, however, m March meeting, got a follow-up telephone eluding one in New show no highe r-aTi four months later from Earl Famum, a risk of cancers for Zealand, a group of for Dow executive. -Dr. Frawley immediately esters and fisherman exposed tofarmers, dioxin tha; wrote a confidential memorandum to the in men in other occupations. file. W ARNING ON D IO X IN STUD IES Mr. Famum, he wrote, said he was calling on behalf of a Dow vice president, Donald Dr. Samuel S. Epstein, a*physician who i Baldwin, and “stated that Dow was ex­ professor of occupational and enviromnen tremely frightened that this situation might tal medicine at the University of Illinoi explode." Medical Center in Chicago, cites the Swea “They are aware that their competitors ish studies and other research on such ques are marketing 2,4.5-T which contains tlons as reproductive abnormalities to chal 'alarming amounts' of acnegcn," Dr. Fraw­ lenge the statement of Dow's president tha ley continued, referring to dioxin, "and if there is no evidence that dioxin causes an; the Government learns about this the whole more damage than a skin rash; "For Mr industry will suffer. They are particularly Oreffice to make that statement is absurd,' fearful of a Congressional investigation and he said in a recent Interview. excessive restrictive legislation on the man­ . On March 23. Dr. Perry J. Gehrig, Dow*; ufacture of pesticides which might result." vice president for agricultural research an; A second memorandum «Tilton - by Dr. development and director of health and en Frawley, and quoted In part by lawyers for vironraental science, cautioned the Housi the veterans, said he had just received new Subcommittee on Natural Resources, Agri .information about health effects of dioxin culture 'Research ana Environment again;: fr o m Monsanto, which did not sent a repre­ "overinterpreting" the Swedish studies. Tin sentative to the meeting. "From the data reports, he argued, "are too incomplete provided, a sample which contained 5 parts both Individually and Ln aggregate, to cur per million Would be acutely. toxic," he rently formulate a clear picture of the possi wrote. "Whether this refers to death or ble associations between 'iCDD and suit liver damage Is not dear." tissue sarcomas." TCDD Is a form of dioxin More : »9 N. « In 1982, Dow scientists published a report SUITS AGAINST COtn*ANIE3 of a company survey on the occurrence of Billions of dollars !are zit stake in thi spontaneous abortions, stillbirths. Infant answer to the question of what the chemica deaths and several categories of birth de­ companies knew and when they knewlL Ii fects among the wives of Dow workers who addition to the tens of thousands of veter had been directly exposed to dioxin. The oris who have sued the chemical com panic; study concluded there were few differences because of their exposure to Agent Orangf in the.number and kind of birth abnormali­ in Vietnam, thousands of other American: ties found In these women compared with living near toxic dumps, such ax the one ir the wives of Dow workers not exposed to the Love Canai area, of Niagara Palis, N.Y. dioxin, and the report has been used fre­ are seeking damages on the grounds Lha quently to support the theory that dioxin is dioxin and chemical poisons left there havi not as 'dangerous as generally believed. shortened their lives and caused cancer But Dr. Marvin S. Legator, professor and birth defects and genetic damage. director of environmental toxicology at the In -Tannery 1079, a group of veteran: University of Texas in Galveston, questions brought a Federal suit in r^ il Cwtt3 li i £ i 1 (m I J ■gsts us day In court When the first phase of the long-await­ ed Agent Orange trial begins in U. S. Federal District Court (Uniondale, . N.Y.) next month, iL «nil focus on the "government contractor" defease. . Chemical makers who supplied the Dept, of Defense with Agent Orancre and other herbicides that contain 2.4.5,Tricholorophenoxyacetic acid 12,4,5-T) will argue that at the start of the Vieb nam war, data concerning the potential human health effects of 2,3.7.S-ti’trachkridibenzo-p-dioxin j2,9,7,B-TCDD), a contaminant of 2,’4,5-T commonly known as dioxin, were equally accessible to both government and industry. And they will argue that what data existed were scanty a t best. But a closer look at some trial documents—sealed in the courtroom but publicly available elsewhere—indicates that a great deal more was known about potential health troubles associat­ ed with dioxin than most companies have allowed. In fact, data were emerg­ ing in Germany as far back as the late 1950s that suggested that dioxin was a potentially hazardous substance. Outbreak The early warnings about dioxin came from Karl Schulz, a young German physician who, in 1955, was treating a Boehringer Ingelneim factory worker for chloracne. The worker, says Schulz, told of similar cases among oth­ er 2,4,5,-T workers in Boehringer's Hamburg plant Boehringer stopoed producing 2,4,5-T and asked Schulz, then a member of Hamburg Universi­ ty's dermatological program, and Josef «4 Kimmig, the program's director, to help seek the cause of the outbreak. By 1957, the collaborative effort was bringing results. Schulz's research iden­ tified dioxin as a by-product in the pro­ duction of both 2.4.5-T and its precur­ sor, tricnlorophenol (TCP). Skin testa on his own body and on animaia indicated a direct link between dioxin and chlor­ acne. Monitoring of employees who had contracted chloracne showed a possible link between dioxin and liver disease. At the same time George Sorge, a Boehringer chemist, was seeking ways to cut dioxin levels in fin­ ished products. "He be­ lieved that temperature waa the key to dioxin control," Schulz says. Sorge subsequently de­ veloped a low-tempera­ ture TCP production process whose endproduct showed neira* live results in Schulz's animal tests. Uver damage. Schulz's findings were published in four German medical publications in 1957. They became widely available in the U.S. when one of the Schulz articles ap­ peared in the Dec. 10, 1958 issue of Chemical Abstracts. The article clearly points to the presence of liver damage found in several Boehringer workers. The chemical makers want to prove that the government knew cf Schulz's work. About a year ago, two Dow law­ yers met with Schulz and asked him whether he had been contacted by Air Force personnel or by Friedrich W. Hoffman, who in 1953 was chief of the research branch of the U.S. Army Chemical Warfare Laboratories and was charged with scouting Europe for potential chemical warfare agents. Schulz says he told them that he “had never been contacted by either Hoff­ man or anyone from the Air Force.” But Dow asserts that a report by Hoff­ man noting Schulz's article was circulat­ ed widely throughout the military. Dow Chemical apparently was con­ ducting its own research in the 1950s. It had asked Joseph V. Klauder, a Phila­ delphia dermatologist, to conduct a pe­ ChWT»«1 WwWM-y Neither the dioxin levels in finished technology, Dow did not license it im­ mediately. In early 1654. the company product during this period, nor the switched to a production teen ¡mine tra i amount of Dow's output that went into required plant process tempera: tires of domestic or military use is known. But 215 C- Measured in Di.ce in her ivu4.Tt.~P sn Air Force sampling of Agent Or­ waste streams cor.Liined dioxin Ip reti ange’s predecessor, Agent Purple, ranging from 6.0x0-lu.Ow purls per mil­ which * x i used between 1662 and 11*65. lion. according to material ir.treduced ihoweo dioxin levels as high as 45 ppm. by Dow during its recent motion fer Both Dow and Monsanto supplied 2,4,5V,' summary judgment. The Biochem re­ T to the mieiary dunng this time. Cit* port indicates that it was, inueed, the ing the ponding uLigation, Monsanto has high proefik* Urn|wr*tyre th ll por,orat­ reserved comment. ed the high dioxin levels, and led to s Dow*■ rights. In March 19£5—the tame major outbreak of chloracne st Dow. month u its meeting with other TCP Although Dow told tr.r MteH—in LV;>i. mr.kr-ra—Dow purchased licensing of Public Health about It.at prutiicin. it ngnts to Boehnncer'a low-tenqvrat'jre did not mention it to the Dt pL of LV TCP manufacturing process. From then frnse until 1967. Dow has contended tn on, Dew contends, its 2.4.5-T never concourt that "knowledge of the pre-vise tair.cJ m„re than 1 ppm of t.ox:::. Tr.e occupational hazard" that occurred in company has recently slated that 2.4.5-T 1964 is "irrelevant’’ to tin- gm eminent coni^.iniig 1 ppm or less presents no contractor defense because it “promptly human health hazards. remedied” the problem. nes oi numan experiments u> g Amre tne potential health eifecla of hertczi-les based on 2,4,5-tricldorephetiol. KU-njiT, according to publicly available docu­ ments, noted that some of the materials he was working with were “highly aller­ genic.” The documents are specific about some substances. For example, an' internal Dow report on Klaudcr's findings indicates that a herhicidal com position containing 557^ Silvex (2.4,5-TP) proposed for “control of acquatic weeds'* is irritating only in concentra­ tion^* exceeding 57>. I t ¡b not known whether Klauder, who died in 19*12, carried out any experiments using 2.4.5-T. But Boehringer clearly did. In 1955 the com­ pany wrote to all manufacturers of TCP and 2.4.5-T worldwide, warning them of problems inherent in 2,4.5,-T production and apprising them of its safer produc­ tion process. While confirming the let­ ter's existence, Boehringer declined to release a copy to Chemical Week. Insight into its contents can be gleaned from "Early Dow History of the Chloracne Problem—Blechem’s (Dow's Biochemical Research Laborato­ ry ’s] Contribution," an internal report A !*.;! m nro y."j3 knov-n ¿bout dioxin’s hBTiiJr luizares tnan many com poni¿3 v/ouid admit prepared by Dow just 13 days before its controversial Mar. 24. 1665 meeting with representatives of other TCP man­ ufacturers, including Hercules. Dia­ mond Alkali (now Diamond Shamrock) and Hooker Chemical (now Occidental). The report says that the Boehnnecr letter, which it dates to 1957, contained the "results of research on chloracne," including a description of "danger points” in the production process. report s *.i : p 3 lust lio^hnngor called for a process u-fii|v:rr.*'!re limit oT 1--J C to“avf'tn procuring ire* acne p>-*iu r in TCP a-d 2.4.5.-T. The lA'w document is annexed as an-exhibit to the records of the 1973 Federal Insecticide. Fungicide and Rodenticide Act (FlrilA) hearings to cancel the registrations of 2,4,5-T and of Siivex. Both materials contain dioxin. Slow to move. The Biochem report notes a 1955 letter from Boehringer to the Swiss firm Givaudan, in which Boehringer sought safety information. Givaudan referred the letter to Dow. which, according to the document, sent its own letter to Boehringer describing "hazards and precautions for safe han­ dling of 2,4,5-lrichiorophenol." Despite its interest in the Boehringer ______ ;______________ Still, Dow seeks to prove that govern­ ment officials were alerted to potential problems with dioxin well before 1964. In pre-tm l documents. Dow notes a 19*52 article in the Journal of Invotigjtive Dermatolngv that ; t 2.3,7,5-TCDD as a potent acin-ren article was based on res-.viren into the physiology of acne, conducted at the University of Chicago .Medical G nu-r and commissioned by the Army. Helen Knzer. a university chemist who worked on the project, recalls get­ ting the idea to use Tt'DD as a standard to R,'.oiun* the str-.T "hs of c-rJ.i-r .-u>pocteu aciicgens ire;» ¿cnuil's ar’_. ,e m Chemical Abstracts, knzer c-mnot r— call whether she mi-fitiimed Schulz's work in her own a im -J n-purL»*to the Army prior to 1662. But she does say that “it's possible.” Q livers were severely.damaged As one par­ ticipant in the 1965 meeting later wrote, the Dow scientists reported that "even vigorous washing of the (rabbit's 1 skin 15 M emos o f 1965 meeting hint at company‘s fears minutes after application Iof dioxinl will not prevent damage and mav possibly en­ n a.chilly morning in March 1965.a j ing ihe preliminary legal maneuvering in hance the absorption of the material." highly unusual gathering took place aL j a class-action lawsuit that has been Now. 18 years after the private parley DowChemical Co.’s headquarters in Mid- | brought on bchairof 20.000 Viet Nam vet- 1 of scientists, the Midland area is still land. Mich. Without any corporate fan* j erans. their widow's and children against wrestling with dioxin. It continues to fare, Dow scientists met with colleagues j Dow and ether producers of Agent Or* show up m tainted water from Dow's from three rival firms. Hooker Chemical. ! ange. Scheduled for rnaj on Long Island Midland plant, has been found in fish in Diamond Alkali and Hercules Powair. I next month before U.S. District Court ten Michigan rivers and is the source of On theagenda that day wasa discussion of | Judge George C. Pratt, the suit charges considerable anxiety among local resi­ the effects on human health of a family cf j that the dioxin contained tn Agent Or- dents'. Says Diane Herbert, a young moth­ chemicals known as dioxin. The chemj- i anse caused cancer and other ailments er two children: "Almost everyone cals, including Agent Orange, later used ; among me soldiers and genetic defects in seems to have thyroid proolcmsi and by the U.S. to defoliate the jungles of Viet i their children. Dow has resolutely denied ' there are a lot of skin tumors and allergies Nam. are an unwanted byproduct in the I the charges In a television interview, 'in pels." To assess those fears. Michigan's making of herbicides. At the time, most I Dow President Paul F. Ore nice said, state health department is seeking state or chemists were only vaguely aware of | "There is absolutely no evidence of dioxin federal money for a major suuy of diox­ in's effects on residents. Whatever the pnvate concerns of the Dow scientists at the 1965 meeting, they did not lead to public action. As a compa­ ny spokesman said last week. "We found we had a problem. We corrected it. We re­ ported it to the appropriate authorities, i We called in our competitors, urged them i to adopt our practice. This was reaily an : attempt by industry to police itself." The i Viet Nam veterans' lawyer. Victor Yan- : nacone, has a harsher view. He calls the ; backstage parleying nothing less than “a 1 conspiracy of silence." ■ ; D io x in P u i s D o w o n i h s S p o t O TIME MAGAZINE May 2 , 1983 Sittin g along the TiUabawassa* fin er. Dow’i sprawling m ia i la lion in Midland. Mich. Ghostsfrom what seemed tike a corporate gesture o/gooa wtii w competitors. dioxin, or its problems. But Dow had.just I doing any damage to humans, except experienced an outbreak of dioxin guison- j something caued cnieracnc. li'sa rash." tng among workers in Midland, it warned j Many scientists du r.ot take The chemi­ to sound a private alert to prevent similar j cal so lightly. They say that even concen­ incidents at other chemical plants, mclud- j trations as low as 5 parts per trillion can ing those of its competitors. Cause birth defects, cancer and Ciner seri­ Last week this seemingly generous ous illness in laboratory animals Last I gesture of good will came back to haunt week the Centers for Disease Control in I Dow. According to a report in the New Atlanta reported that 1¡2 of 130 residents i York Times, memorandums from partici­ tested in Impend. Mo. near dioxin- I pants in that almost forgotten session in­ con laminated Times Bcuen. showed ab- | dicate that Dows objective may not have normalities in b'oed, liver orikidnev func* I been corporate benevolence. Rather, the lions. Says Dr. Irwng Schkotf. director of ! documents show, the meeting appears to the environmental-science lab at Mount I have been part of an etlort to keep discov­ Sinai Medical Center in Manhattan: "No | eries about dioxin's perils from exploding j question aooul it. dtox-n is harmful to j into a public scandal, which could have i humans. It is man-made. As a result, the | brought a new outcry for governmental | human body doesn’t know how io break | regulation of the chemical industry, j it down. We store it in cur bodies and Wrote a participant from Hercules Pow- j 'accumulate it." In 1964. after 64 workers at its Mid- ! den “They (Dow I are particularly fearful j of ». congressional investigation and ex- i Land plant developed caloracne following j cessive restrictive legislation on Ihe man- I exposure to dioxin, Dow began a full- i ufacture of pesticides. " j scale investigation of ns criects. When I The documents were unearthed dur- | dioxin was administered to rabbits. Iheir | '• * - NEW DISCLOSURES*REGARDING AGENT ORANGE HON. THOMAS A. DASCHLE OF BOtJTH DAKOTA IK THE HOOSC O r RCTRUCKTAnTZS t I Tuesday, May '-f- 3383 • Mr.* DASCHLE. Mr. Speaker. a recent news story In the Robinson. 111.. Dally News, present strilurig evidence of the link between the dioxin In agent orange. to which many servicemen were exposed In Vietnam, and the ill­ ness th a t many of those servicemen have suffered. 1 commend the writer. Tony Gordon, for his extensive rescorcn. and I rec­ ommend hfs article to m y colleagues for their understanding of this signifi­ cant Issue: {From th e R o b lm o n till.) D rily M e n . U ay *. 1S83J A rocaL T M t L atxt? "O aancr-H oT " C o n ra o v e tsT (B y T o n y G ordon I A m edical s p ecialist Ln C hicago h as diagnosed a n u m b e r o f phyetcxl alim ent* in W e st York r e n d e n t S am m y D an * and an ­ o th e r V ietnam v e teran as being related U th e d efo lian t A g en t O range. T h e diagnosis Is believed to be th e l i n t tim e a physician h a s draw n a connection be­ tw e e n Illness an d th e exposure of U,5. aervIcem en Ln V ietnam to th e d angers of dioxin, a n Ingredient of A gent O range. D avis, w ho w as aw arded th e M edal of H o n o r for te r r ie r In V irim an . was cu e of t h e U ral th re e V ietnam veteran* to be ex ­ am in ed fo r possible dio x in -related Illnesses by D r. B e rtra m C am ow . p resid e n t and se n io r scientist f o r C im o v . Coni b ear and A ssociate*. Ltd. Carr.ow la th e d ire cto r o f o ccu cx tio n ri and en v iro n m en tal m edicine a t th e University of Illinois School of P ublic H ealth , a n atten d ­ ing physician a t th re e C hicago hospital* and th e a u th o r of m ore th a n SO articles and p u blications o n Lhe « (.'ecu o t th e environ­ m e n t on h u m a n h e a lth . An advisor to th e th r e e v eteran s. Irv W ells. Is c h a irm an of th e V ietnam Veterans C o n fed eratio n of M ilw aukee and a licensed surgical physician'* assistan t. He arranged to have th e th re e m en see C im c v to r a n ex­ am ination. “ We w arned to h av e -jur guys exam ined by th e fin e st e x p e rt * , ‘'c co u n try and a review of th e ruse a r t '. dioxin led m to D r. C am ow . H e's p u re p .iy jic lin . a r.cn-po-UUcai anim al, and was wilhng to look for th e reason th e se m en are c-lX." Weils said. C am ow perfo rm e d a I'i-n o u r wine* of te s ts and physical ex am in atio n on th e th ree v e te ra n s ln M arch . C am o w * Hn-Jires are m arkedly, d iffe re n t from in fo rm s tier, the m e n received following ex am inations by V eterans A dm inistratio n do cto * T h r resu lts of C araow 's u rd ep eu o rn l tests show Davis and fellow v eteran J o h n Cromow skl of M ilw aukee su ffer from asnorm all ties In th e ir blood an d vascular ijv tem . liv er disorder«, nervous sy stem e ffe c ts a n d —A low ered level of liver fu n ctio n s and a severe depression. w h ite blood cell c o u n t p aL tem th a t is sim i­ N o n e of th e se m aladies w ere d ia g n o se d la r to one Ln a p e rs o n w hose im m u n e system th r o u g h te sts th e m en h a d ta th e V A's Is depressed. —N orm al k id n e y fu n ctio n s, b u t a n tnA g en t O ran g e screen in g pro g ram . D avis was to ld by VA d octors h e r e c o r d s u rg e ry o n crea.se tn u ric a d d level th a t could lead to nerve* ln his w rist and sh o u ld u n d erg o p s y ­ kidney dam age an d b o u ts w ith r o u t o r ch o logical counseling. O tom ow akl. w h o h a s g o u tty a rth n U a . D ari* h a s h a d a tta c k s o f s u ffe re d from seizures since 1571. a rid VA g o u t since 1SJS. one y e a r a f te r h e re tu rn e d d octors w ere u n ab le to Id en tify th e ir cause. from 1)11 V ietnam service. —A'■variety of n erv o u s s y u e m d y sfu n c­ T h e th ird v eteran In Lhe gro u p . M edal of H o n o r recip ien t J o h n U se s o f S p rin g fie ld . tions. T h e m eida n erv e ln h is rig h t h a n d Is l i » H will req u ire f u r th e r ex a m in atio n b efo re Inflam ed and Interfere* w ith sen so ry conduel! on. a co n d itio n o fte n a.xiociiLrd w ith a a diagnosis can be m ace. W elts said. B o th C a n s and G rom ow tki w en t th r o u g h d e g e n e ra tiv e process. H e also s tif f e n from th e V A 'i A gent O ran g e screen in g a t th e VA p e tty ra ril seizures, w h ich m ake h im n a u ­ B o sp lta l a t W ood. W ise , a M ilw aukee seous. d ^ z y and b lu r h is vtslon. —A b h crm riitlea la h is rep ro d u ctiv e s u b u rb . A t Lhe conclusion of text* th e re , th e y w ere sen t le tte rs signed by D r. M ichael sy stem w hich, a lth o u g h It Is still possible O . O 'G rad y , th e s ta ff en v iro n m en tal pnysl- f» r h im to la th e r c h ild ren , p ro d u ce sp erm ciao . th a t said th e resu lts of th e ir in itia l form s t h a t are n e t n o rm a l In th e ir ab ility to Im p re g n ate or a re m u ta te d . te sts w ere “sat is facto ry ." —A n o rganically-baseo severe dep ressio n T h e D aily News a tte m p te d to c o n ta c t O 'G rad y c n W ednesday. b u t w as to ld h e p o in tin g to a n Im balance of n o u ris h m e n t in som e of th e celts ID h is b rain . D avis said co u ld n o t sp eak to th e p re ts and w as re­ fe rre d to pu o u c relatio n s i to a c t m a n Y . C. C arr.ow told h im h e h a s n o t su ffered b rain P a ris h . A w oman In P a ris h 's o ffice s a id h e dam age, b u t som e of th e cells a re d am ag ed to th e p o in t w h e re th e y a r e u n a b le to w ould n o t re tu rn to work u n til M onday. II Is th e p re se n t policy of th e V ete ra n s ab so rb c * 7 Btn. —zits botty also h a s d ifficu lty In D ie proc­ A d m ln istratio n -to d en y -an y d isab ility claim s b ased on dzosln'i effects. T h e VA provides ess of en erg y p ro d u c tio n an d tra n sfe r, w hich b rin g s o n o cru rrrrrce s of e x trem e free.p h y sic al cx *.t .: ha *.:o rs to v - u w ho /•—! th e y m ay h av e su ffered id ie.-ae ti r a .th e f­ w * y js e is D a .is said i n - re.its in d trv .rd th e body p r o d u trs a n to iu th l th e fects from exposure to A gent O ran g e. T h e VA said V* eiln rie a y 263.000 V ietnam dioxin cm .tarn in a n o n w inch sw.-Hs th e nucirux of ci Its and re ta rd s th e flow of en e rg y v ets have gone to VA r;uspiL—s com p lain in g of illnesses th e y tn o u g h t could be n e s te d to LPrcju^h h is bt>uy. G rem o w sal said C am o w to ld h im a likely A g en t O ran g e i s th e la st y ea r an d S.40u of th e m w ere 111 en o u g h to be h o sp ita ltsed . cause of his seizures Is d am ag e to h ts b rain caused by m alfo rm ed ceils, ills liv er and n o n e fo r any illness th e VA say* is ca u sed c e n tra l n erv o u s sy stem are d am aged, th e re by A gent O range. V cm R ogers, a sp o k esm an fo r th e VA Is a blockage in h ts lu n g s an d ab n o rm al Hies In h ts blood. O ffice of P ublic and C o n su m er A il aim in “Dc. C am ow to ld m e th e d iseases I h av e C hicago, la s t w teg said th e ag en cy a* “p ro ­ are all a re s u lt of ex p o su re tn th e d io x in tn viding m e d c a l screen in g fo r any v e te ra n s A gent O ran g e." G rornr'w rxi raid. who th in k th e y b is ; have a pro b lem an d we T h e disg.-.psia of G ru ru iw ss j m ay be esp e­ a r e doing so w ith o u t an y tn -c io ri p ro o f in cially sig n ifican t b-.-vausc w h ile D avis w as th e e n tire w on a u r n * u n i b etw een A g en t a-.-.:g,-.ed to a co rn ea l u r.:t In are a s of VietO ran g e and m edicaj pro b lem s ex ists. T h e re ra m »prayed w :;n a x- n t ' -»range. G rois no piece of pap er by any ciicto r an y w n e re r a i v i ' i was m il H r t v ar.'lv n ed as a c o o l Chat say s a n y th Jig a t all is caused by A s c o t tn D a Nar.g ha^- c a m p f.vr mx m o n th A a n d O ran g e. was n ev er sunt in to a s p ra t rd area . R esu lts from C am ow '* te stin g and ex a m i­ "T n e d.*g.-iu,is of J o h n p u la us in m e po­ n atio n s m ay prov.de th a t piece of p ap e r. r t i o n to re th in k m e d isease ." trlflio n to eaeh of t l r..:.;'>ad w o r s e n in ­ volved In an e x p o su re re la te d suit. T h e w o r s e n c h a rg e d In th e su it th e y h a d s u ffe re d c e n tra l nervou* sy'.u.-m oarr.aite an d c a n c e n because th e N j i l u n arid W rs ic m R ailw ay h a j ta ^ r d to pr^-r-ct th em wrren th e y w ere Involved In a J lv itr i c tra n u p o p ­ e ra tio n a f te r a rail accid en t In lv 79. C am o w te stifie d o n b e h a lf of th e w orkers a n d described th e m rtlira l p ro b lem s h e h a s d e te c te d la th e m th ro u g h h ts Irsi* . A fter 10 d a)* -•* h i. :iv * : v .Lv.Z rd th e w orkers hxd b een aiir*te<1 arid beg ait m aking th e fu ian c.al » an ts. l n h ts im erv irw a i m m e Daily N r a s . C a m o * s a .J l.e w as . C o n g r e s s i o n a l R e co rd May 2 4 , 1983 : *.. :■ ;.g a n , o i li e r d o cto rs of n r tltg r n c c even th o u g h th e r e ­ sult* of his lest* on P * .tx k ill *¡ri-m.iw.vai ■how d tltrii-iii ri-s-:.‘s IJ.,;i th e re ir.v “ I do n o t th in k an y o n e U fakir-g th e te sts, b u t th e y may n o t be all U m e m an d m ay n o t be viewing th e re s u lts th e sam e way We have e;i:> r* » :j.:n rd th r e e p»-op,e and w h rn and if we do 30 or m ure. w.r w ill • Mr. DASCHLE. Mr. Bpexker. Mr, K D flW Ja O A K P a w e t ia as vice chalnr-aa of the Viet­ nam veterans 1a Ccr.grcss. and myself us chairman, are lmroOucias legisla­ tion th a t will to an extent provide fi­ nancial relief for a limited group of Vietnam veterans suffering from the effects of toxic chemical exposure from their service In Vietnam; 111 of my colleagues from both sides of the able have Joined with me In this effort. I believe this legislation Is even more compelling after the administration's decision to compensate the residents of Times Beach. Mo. Though the extent of Federal Government culpa­ bility at T im » Beach Is still somewhat unclear, the decision to purchase the property In the community implies an acknowledgment that dioxin, the same conlalnant In the herbicide agent orange. Is dangerous enough to pay for the evacuation of an entire community of 2.500 people. If this Government Is willing to accept this responsibility for Times Beach. It has even more of a rexponMblllly to provide compensatory relief to Individuals It was a u x .c tly re­ sponsible for cxsujlng to the very aame chemical In Vietnam. My colleagues may be Interested to learn th a t dioxin levels at Times Beach, averaging ICO parts per billion. are approximately 20 times less than th e mean level of dioxin In agent orange, 2 parts per million. Dioxin levels In agent purple averaged 32 parts per million and In agents green and pink they averaged 65 parts per million. Herbicides pink, purple, and green used primarily before KrS5. thus had dioxin levels hundreds of times higher than levels discovered at Times Beach and tho'isar.ds of tunes above the EPA danger level of 1 part per bil­ lion for domestic use of herbicides con­ taining the coiitamlnanL We thus believe It especially appro­ priate to Introduce legislation which would compensate certain Vietnam veterans for Illnesses and disabilities which may be related to their service In Vietnam. Current law allows for the establishment of presumptions. and the payment of compensation, when there is doubt as to whether a specific illness originated during a veteran's service or not. Thla legislation would establish three new presumptions for compensation purposes in section 312 of title 33, United States Cede. The new presumptions are for sofL tissue sarcomas, a liver condition Known as porphyria cutanea tarda, and a sain affliction called chloracne. Scientific studies presently show a strong corre­ lation between these illnesses and dioxin exposure. There would be no presumptive period applicable to these Illnesses, but In recognition of the largesL and probably most costly epi­ demiological study ever undertaken, there Is a sunset provision which would terminate benefits within 1 year of the first report from Lhe Centers Jor Disease Control epidemiology study unless the results ol the study Indicate that there continues to be a significant correlation between service in Vietnam and cerium neaiih cllecis. Since the CDC study is expeu'-td lo have Initial findings by 1£37. the ‘sunset provision would likely become effective sometime In lSfCH. A few vei.-rans suffering from soft tissue nuiccrs ana p^rpnyr.a cutanea tarda will benefit from this legislation as would some 2.5u0 veter­ ans with chloracne or chloraiuiefuna lesions should Veterans' AiiininisLratlon extrapolations of current chlor­ acne cases prove accurate. Tills R*gi.-Ialion Is expected to cost only 13 to i t million a year. The following chart provided by the Veterans' Administra­ tion lists the number of agent orange related compensation claims filed with O — • rr* > rv Jit w * t t mft ft hm JcrffW V l n f hraW r i/ Cwa r t a «1 ______ 1 O n »A t a n a oagnag ■li-bK* « n* Ua . _ IUU I XI LSI 1U) 1X1 m at SI LM IX* —n ______ _ 1l o j t t m i f H ptari v IJUf < c* fc*J U K t>—a M it kfti tf u Ukj I ) i *4 uari IM b a v m u t fni^n BKTMM 4V4 M • i « t >.* cm*mW | m lf t a i Um H S i artrj-» fcj< m k o . m L c n __ h rom • a i m a M m i r v r a g u n i ___ lu m »cvnm, »ftiTift. i q u i ML). nu i;t ;a %x i% ra m As my colleagues can see, veterans have filed claims for a number of ad­ verse health effects from agent orange exposure. Virtually ail of these condi­ tions have been described in scientific 'literature on phenoxy herbicides and dioxins. For reference purposes, I would refer my colleagues to chapter 5 of the Review of Literature on Herbi­ cides, Including Phenoxy Herbicides and Associated Dioxins, ordered by Congress In Public I.aw 95-151. and completed In September 1981. An up­ dated review should be available In several months. This document, as well as a bibliography with over 1.110 references on the Bublect is available from the Government Pruning Office. Certainly, there is ho snortage of in­ formation on this subject. Despite the large number of adverse ell eels no­ ticed In exposed populations to oioxm. I felt that at this time the legislation should be limited to those illnesses which arc most lncisputable. The efforts of the Army Agent Orange Task Force will also enable us to verify in most cases whether or not a veteran was actually exposed to her­ bicides. The task force, which has been busy Identifying cohort groups of veterans who were exposed, not ex­ posed. as well as those who old not serve In Vietnam for the two Centers lor Disease Control epidemiology stud­ ies on the Vietnam experience and ef­ fects of agent orange exposure. Is a most capable and credible source to ^conduct this research and Is complete­ ly willing to assist the Congress and Veterans’ Administration with this particular effort. Mr. Speaker, the alleged scientific uncertainly surrounding all the defini­ tive effects of agenl orange exposure in my opinion will continue to be ex­ pressed lor some time. After all. LI we have been unable to find conclusive evidence after publication of over 1.100 studies and reports on Uie chemical spanning decades of worx. what can we expect those studies r.ow underway to add to the current knowl­ edge that has not already been re­ vealed. I personally believe Uial declsions can and must be made on Lhe rvltlencc which Is already available and there Is sufficient evidence to do so. The nodal policy Implications of agent orange poisoning have been Ignored too long. Regardless of whether agent orange can be dt luuteiy lutM-d to *n Illness or Is merely correlative, there are over 16.500 Vietnam veterans with severe Illnesses they believe arr caused by their exposure to agent or&uge. To hold their fate In the balance while Congress, the VA. and the svirnttftc community deliberate the conclusiveness of the science is a mockery of their service to Lhls Nation and to their suffering. The leg Linden 1 anr now Introducing la a tightly crafted MU win*-fc ......... . - - — •- — * diseases to compensatory relief cur­ rently not available^ If compensation can be provided to residents of Times Beach, and I think It snould. It defi­ nitely should be provided certain Viet­ nam v eteran as well. Following Is .the text of the legislation: J L R .1 M I A b ill to am en d title IS. U nited S u t r a Code, to p ro n d e a p re su m p tio n of service co n ­ n ec tio n f o r t h e o ccu rren ce of c e rta in dis­ ease« t r i l l e d to exposure to Hero If. ties o f o tb e r en v iro n m en tal h az ard s or condition» in v eteran s w ho served in S o u th e a s t Asia d u rin g th e V ietn am e ra Be f t enacted b y tVe Senate and House a f R ep ream to f i l 'd 0 / (Ae Untied Stale* q f A m erica m C o n p rau o zrem ew t TliaL Lhtl A ct m ay be cited as th e "V ietn am V cteranc A g en t O ran g e R elief A ct". Roc. 3. T h e C ongress fLnot t h a t — (1) c e rta in A th e n e h eal Lb Effects o ccur­ rin g am ong p erso n s who served In th e A rm ed F o rces In S o u th e a s t A sia d u rin g th e V ietn am era. an d c e rta in birth d efects oc­ c u rrin g am ong th e cull d ie s o l su ch p erso n s, m ay be tr.e re s u lt of lh e ex p o su re o f su ch p erro n s d u rin g spoil service to p h rn o x y h erblciccs i u-.l in g th e h e rsic ia * t n o v n as A gent O range* and th e class of rh e m iro ls know u s s Lae tu o sin s p ro d u ced d u n n g tn c m a n u fa c tu re of su ch h e r tiie ia e s o r to o th e r [s e v e n involved to su ch service Including ex­ p o su re to o th e r herbicide*, chem icals, caedicai-a ns. o r en v iro n m en tal b o s o m s o r co n d i­ tio n s: an d (3 / a com p reh en siv e review a n d scie n tific analys'-i of live lite r a tu r e covering a lu d its relatin g to w h e th e r th e re m ay be lo n g -term a d v e n e h e a lth effec ts In h u m a n s freru exfiorare to a n y cl m e class ol chem icals know n os th e d ioxins p ro d u ced d u rin g Uie m a n u factu re of th e various p h en o x y h e r b i­ cide» vu.ciL.ibng th e h erb icid e k n o w n as A g ra t O range), os req u ired by section of P u h b c Law ¡¿-111. h a s been com pleted an d s u o c u ttc d to th e V ete ra n s' A 'fm in u trat.'o a. f-BC. 3. Gev-ucm 313 of title 38, U n ite d S tate» C ade, is am en d ed t v ad d in g a t th e a n d the fuiiaw lng new tu mu-el ion: ■*ts-puit r*q u-red Ct scetio n f i K o H h of Lit; Vi-lrrorvi H eal Lb ih iig ro m s A atetisiun an d lm p ru rep e n t A ct of 1BT9 (P u b lic Law SB-151; S3 S U L 1093L"A i MARCH 8, 1983 » Dioxin rii ad a Human Wreck C l o c ii h O j / Of Ton ah Trackm i 1 MrJieot Tnt>\t*c firp.irt “ 1 saw some c he m:!u n •n csee nee stud­ kO.'-! THE RKCKONING of St. Joseph’s 1 Dr. Gc'.!::cy, a team ut Mis­ ies he did with n e u t r o p h i l c o m m e n t e d souri doctors spent a total uf about -JO St. Luuis U. ’%Dr. Slavjn. But did lie incu­ hours examining the Times Beach test bate lymphocytes with rniiocrns?“ population of 120. Dr. Carr.ow* said cnch Yes. Dr. Prince averred. he did — w ith of the 47 railroaJ trackmen spent a total of phylohc mu git!ut in in. poke weed mitogen 16 or 18 hours seeing ms team of 12 spe­ and concanasulm-A. Moreover, he found cialists. Tne croup were examined starting the generation of luperoxide radical> wjs 10 months after the accident, and reexa­ affected. He said the chances indicate a change in hone marrow at the sretti cel! mined at interval* until last November. ‘‘The stuff, which included phenol and level. He speculates that with the iymch- rorrhochlorphenoi. affected every major prohferutive ability of the tody impaired, organ system and numerous enzyme sys­ the freshly transformed neoplastic cells tems, “ according to this specialist. His may no longer be swept away in time. colleague in these studies was his associ­ Dr. Camow added that in animals, ate, Dr. Shirley A. Conibear. # - the dioxin is a cocarcinogen beyond be-, “ Many of the wouters had diabetes. lief. For example, 3-n.ethyIcholar.threne Four had Peyronie's disease. A number on its own is known to stimulate oroduchad complete urinary obstruction. Five, or ticn of ary ih.v droxyhsdroxylase and there­ about 10 percent. d r * by, tumor grow tn. But when dioxin is veloped skin cancer. ; • ..s added, the carcino­ One had a l .400 tri- i i m :.J 1 genic process is en­ glytcride. Eighteen!? had abnormally low i . hanced thue*ap.ds of ¿ 'A -A ^ : h- ^• H u t - ; \ times. testosterone, usually ¡i ». Such inferential with a marked ce- j | v. risks aside, to fully crease in libido. In \ assess the individual many. peripheral i nsks in the Times neuropathv, a numb- : Beach population, ness and l.r.giing. be- !i professional inter­ came deeply painful viewers las; January at niebr. causing in­ somnia. There were changes in muscle reached yOO or 9*0 residents with caesmetabolism, an ATPase ar.d CPK. abnor­ tionnaires eliciting data on lifestyle and mality.’ • •• possible exposure of nil types from all dif­ “ Anotlier major problem was a com­ ferent sources. From the answers, ir.vestiplex of extensive neurobeh.n u>r.ii abnor­ gatorTdrew the test group of 120. A leading environmental specialist, the malities. often characterized by a severe depression. It was i,onp>ycl:ogenic and in Palo Alto iCulit l Medical Clime'* Cr. some cases amounted to u h.r. me Ibav.ians David Di vl.-.r, made tin. plea: "Wo very call a ncuro\c,cot.,,i\e state. There were much need C D C ' expertise here, to do the seveie personality divom.eis. narked t y a longitudinal ep.demnoiocic {’•.»I’owun ’.hut > tendency to fly otf the handle..“ ^ ^ ... is needed, and with its experience tuilowdiNperving them­ In 20 of !’*; -I? aiiro-.t two xc.’.rs ing p.•ml itioiis ibet alter the diovm 'Pui. L mvetsity oi tiiu.oi* selves .now.id li e nation, ¡•.••diii.c j w;idv inimuiioioMc» •loots; Jo>cpn Prmce.. that everyb.nly c.m live wuli. We should I'h l) . Ik oi.d i.;:; an i;:e:it ..i i ui r , np: »i 1 |*.it onl li i: »1 m C DC u> do ih.s. . • and l y t e i.,:\t:.'-i w :..••• com:*.wedI F > p r- with that in age-Miatche.l n o rm a N l lie lime move:* ol h»**l ie ist.iuce no I m r vi P" nl. M o . (arm I h o n n h/volu tn n r irt.y i.m l had full were 3?,CH'0 pt*k>. j •..totowide hujli. •i tuwi i*l the fnemy. D yinrj Irc m d 'o x in : n h n " .« on nn lir r - 'r l- -V; .wV^i.T > , •V V' O' ★ T 'h ; * < i « i t >h !S ]T $ Q iliid s i ' V / *k 4. Cl, ;C.V|rt 7 r;b*jn«-------■ >. Suoo . t/. March 2 7 , 1°;t7 1.mmt -X»^ — ■ ------n — r-r—, ,------ /P p i I ¿ ¡f> r| ('*.* y Xs -XV 71 /» ft > r r > : ; ? j . o - v :„ c l >. / U ... L' i *r'j.1 v ) ,\ •? ( * > . v -i i« V L ¿1 normal function of nouliuph'l.s. "I’ac halaneed 1i**;iil;j|<»»*% opm atu.i»,*’ I’nnco s i . ' n i t i r o N t l v I n ’ I n : t h a n t h o s e y e t n ’ p o M man'-type rell:; Hi,it semiy ;i!ioi:| 11*1• said. ‘W hen you pet too ii*;.u\ of one kind C'l 11«the 11iiih’.j .-•ait-.-* 't : \ : \ ; . •»-«.!•-.*(i n n of cell and not Olinuyh ol another, it "Kvcn urid-T ti1,-»• ha'»:« ft.’ld c.»r..'i lindv ' «’. M i n i ; ' h a i l e i ' i a ;im l feieip.n liee;i A i t •». \ • i.-. . • . . i i » ( l ! o hu ; tli«* l o w M o f cnmplef'ly ni'-Nels Ir.e memal iespot.se A lions, w haven't ce.’.i c».,m hiIS. T > > l : i T. M • i* ec,ii «• il li «'' I•«■i,il iiv 11 vr. t.*.«•ex:«’... Also fotiii'l was a (In rea.se in the mini compioini ed irnriiunc system is ir.capa* deiii’e (,f «■f 4. : . ; . i . n : i . . *1 o ’. ; • ' I r n l i . i l i V h . i / n i d « , u s Inr of 1usinophils, . | - n \ • i t h e the exact extent of d.-.no.er j•(••.(•!• i i »*i - n i i!. •1; i i i • i ii *I i!' • |u* *,n in in the environment \^ . 1 in.dim of I i i r h i c i i l ” ( a m l . i i n i i i i t d u » . \ i n e x p e r i e n c e d chirmp. th'- war 1¡*: r ..’.ear *ly >, r • I ,.i. I ' . r r i n i\v I o .uliii > 1 , i 11*• v\ i•in!in.ei:y aninnif . ol h.*vnut Ill’-e!t1i1. • . f.I.a.r’i.s I;.m phonia*;. I ! fa ll I r e n e , a t a ‘.1lenl1-Is. !' !« I ■\ . .. I . ¡ i l . . « r t i t i 1.1 i s i n . ” o ; ; ; v,.¡Hi a- •:*.}■:: than v.:•r: 1 ,t i e s i \ l i n n s ;» re .it‘T ; l s m N o rm a l. 'It11:IHim :hlood mils l-iimr Ktiufiii? It:.•haul Wilson, chan in.m of tin- phy­ chddimi I s mav e men f - ■' • \ j » ! i i - I«* \ . i y . . i l l i * i t o it i i .1■ n i v . i i . l i : rh.m MillInfillV Will «tcslIIIy (-.nil11ons asfoeiated with h xi'is, said the would c.xpm t i* Tl:.s ( I -d h.i> c.c . .’ian! cells, a pm •m.'s 1isl;of d;.m’ «1 »:i-;i . o' i’i.T - liow vul.lly 11:.i\ni iiisi1ny in th/’ s t 1 r I n , d o t . * m l i M m ' . N s . i n « I • 11!a1»i ll.o h i l i l i e s o l i n t o , : t n r . , ; : *. : .dl k.r.d» -. (•ifi .»!I*.•s' li.• Ii:-:i;r.i liirk ..mi m.iy d;celopinit cancer v.ii! inciease S*. edr h .sliiiIv cited hy I‘line«:, have n o r m . i l ; i c ’ i v i l i v > < h . n i p . o h i n o r i l i . i l him lam o f Mood rt|*ti”re; .-n ■*-.•ii-. v,,irmi.<’ss'toii. ‘f.,r cells may .also imlicale ha*a* chane.es in I.lik’d lo establish Ih.d chioiiiv cxpusure liiT l.’iuvetsity of Ilia.*-:.-. I'. .1 Imil.i-nna. a cancer of the hlood. o t h e r s * st il is ; 11. 1i e a r e i n o f . ' . c n k ' . " l S M l I'Y , inir ol I In* I'rw The c l i . u . p e s l * i n i c e f m i i i i l i n I l l i n o i s A cla s s i c ; . y i . p h . n i • o C i . d'-d w ;*} W ils o n s a id " S l u d i f ”; h a v e s h m v n it c a n ( ! • • • .............' •» . . i l i . i . v s i : I ’ V j i i i n . »• i l : I n 111> : : i i s , dioxin exoos'i'n i- .a .,*•*.) r.'ssh r. If*, /' :• • i l • ■i . * >.• ^ i . . «- i l | n « 1 i • \111 woikiurn aic consistent with studies done p M ’d n c e c a n m r m r a h ; a t h u l l d o s e s a n d in ini«••,he '..ud In mire |n...--l !n ,ill a m o u n t . . of "Few« »’ than .Vi j» rc'e*. o f 1 j ;«r (i • ' . i i i I* : | 111- K r a h ^ i m ; f i n i u 11 f e w ed to liny amounts of the fsti.n.n. tfi.’ir W1I..011 said Hint us«: of Ai’.eiii Mr.inj;e in (.•xj/OsC’d to dic/X.;r. w;il sv<., . v a r . « h . white Iiii•»kI cell production actually is Vietnam hy U S. militai v forces to clear lc.asl very soon," Ijed-T»::« '. id Ch:X' to u:> to 1::mi ■>.$. • ni 1' n r . r c ; . . i t . I a h i . . m a l i H r : ; i n D i e ’. l u t e slimul iicd, hut iunction of those Cills is vepa’tntion was done without normal a skin cancer in the se-.-e ’hat it r-. a l l e i c < J . h ! « 1 t o li ¡ i . : i v 11> of t A o l h i i d s ni 1l i e s.ilefjuanis for human e.vpo.siire and with take years after exposure before ii ap n ' . i :i A m n . ^ t h e m w a s a r e d u c t i o n i:i t h e "Till-: I.MMUNK h).stem is a