Document B8kw8m7gdr3Gn0vNjO7rKZ3yk

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, ST1 SpBef: T* Hazcc-Hagclslcin. W. M. G. Tunbridge. ^ *. 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. Chrtien. 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 . DayhoET. 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: a /* M. O. Davhoff. in Alias Sm urare and Structure (National BiomelficalCResearah^ Foundation. Washington, D.C.. 1978). voi. 5. suppl. 3: K. Lederis et al.. Can. J. Biochem. Cell. Bit)!. 61, 602 (1983): K. C. Robbins. H. N. Antontades. S. G. Bevare, N. W. Hunkapiller. S. A. Aaronson. Nature ILondon) 305. 605 (1983). 21. The peptide corresponding to the 31-amino-acid sequence was synthesized by the solid-phase method. The purity of the synthetic peptide was established by HPLC and paper electrophoresis, and its amino acid composition was identical to the proposed sequence [R. B. Memfield, J. Am. Chem. Soc. 85. 2149 (1963): D. Yamashiro and C. H. Li. ibid. 100. 5174 (1978): C. H. Li. D. Yamashiro, K. Ramasharma. M. R. Sairam. unpublished data). 22. Supported by the Ford Foundation and the Medical Research Council of Canada. We thank C. A. Paulsen. G. Bleau, R. Vaudair. and M. O. Dayhofffor their contributions, and C. Chagnon Labelle and R. Carrire for technical assistance. * To whom correspondence should be directed. 28 November 1983: revised 17 January 1984 3. P. Honchar and W. Halperin. Lancet 1981-1.618 (1981); P. Honchar. M. Fingcrhut. W. Halperin. in preparation. 4. W. Wagner, paper presented at the SOEH Con ference. The Scientific and Social Response from Exposure to Dioxin and Related Materials (Society for Occupational and Environmental Health. Arlington. Va.. December 19831. The Environmental Protection Agency, report was originally intended to be released in November 1983. bui has not yet been released. 5. T. Sterling and A. Arundel. NCAP Nexvs. in press. 6. O. Axel son and L. Sundell. Work Environ. Health 11.21 (1974). 7. L. Hardell, M. Eriksson. P. Lenner. E. Lund- gren, Br. J. Cancer AS. 169(1981). 8. Ton That Tung. Chirurgie 99. 427 (1973). 9. A. Westing. Ed.. Proceedings. International Symposium on the Long-Term Consequences o f Chemical Warfare in Vietnam (Stockholm Inter national Peace Research Institute. Stockholm. Sweden. 1983). 10. E. Silbergeld. paper presented at the SOEH Conference, The Scientific and Social Response from Exposure to Dioxin and Related Materials (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. St e r l in 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 il ip H. A b e l s o n 26 January 1984 C03739 1202 c ripti^*' u r ti \J /iu nr , Iw i iiw w tU Monsanto Company 1101 17th Straat. N.W. Washington. 0 C 20036 Phona. (2021 452-8 680 GR TTC- / \ > 8tO A jJ W a ~ s^ _ _ y - Q03740 . NEWS/INFORMATION FROM SOUTH DAKOTA CONGRESSMAN TOM DASCHLE 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 03-334-9 439 Cannon Built Waahlnflton, O.C. 23 1-300-424 5 or 202-235-3 DOW AND DIOXIN: A STUDY S ta te m en t by Congressm an D aschle June 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 ie n c e : "T here i s a b s o lu te ly no ev id e n ce o f d io x in doing any damage to humans e x ce p t fo r som ething c a lle d c h lo ra 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 a w a r e , i n d i c a t e s H r. O re ffic e has e ith e r d e lib e ra te ly m isled th e p u b lic o r i s t o ta lly ig n o ra n t o f s tu d ie s p o ssessed by h is company. T h is s tu d y , co n d u cted by D r. M ilfo rd W ard o f th e D epartm ent o f Im m unology, R oyal H a lla n s h ir e H o s p ita l, S h e f f i e l d , E n g la n d , d o cum ents a lo n g -te rm immune s y s te breakdow n in humans ex p o sed to d io x in some te n .y e a r s , p r i o r to t h e i r e x a m in a tio n . The stu d y c o rro b o ra te s s e v e ra l s im ila r s tu d ie s on an im als and hum ans. 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 idland, M ichigan, h e a d q u a rte rs to h e a r a b o u t new s tu d ie s and re c e iv e th e company a p p r o v e d l i n e o n t h e s a f e t y o f d i o x i n . I t i s my u n d e r s t a n d i n g t h a t t h e s e j o u r n 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 th e M idland a re 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 a b o u t t h i s s t u d y d e s p i t e i t s obvious sig n ific a n c e to th e A gent O range is s u e . N or i s i t s u rp ris in g th e a u th o r o f th is study has d escrib ed i t as " c o n fid e n tia l," and "never p u b lish ed in th e s c ie n tific p re ss." These th in g s have happened, and th ey a re b u t th e tip o f th e ic e b e rg o f e f fo r ts to suppress th e fa c ts and m islead th e p u b lic about d io x in . Y et j u s t th is t i p o f d ie ic e b e r g , in th e form o f D r. W ard 's s tu d y , c a s ts th 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 Agent Orange and i t s d ead ly c o n ta m in a n t, d io x in . ...m o re ... A ccom panying C ongressm an D a sc h le in t o d a y 's News C o n fe re n c e i s D r. J o s e p h K. P r in c t a re s p e c te d im m unotoxicoL ogist who i s a R esearch A sso c ia te w ith th e U n iv e r s ity o f I l l i n o i s M edical C en ter and a T o x ic o lo g is t w ith th e E nv iro n m en tal P r o te c tio n Agenc' in C hicago (R egion V ). ; ' 1 ! : | i I * j S ta te m e n t by Congressm an D aschle --. Page 2 C o n firm a tio n o f lo n g - te r m immune sy s te m c o ll a p s e a s a r e s u l t o f d i o x in e x p o su i w ould re v o lu tio n iz e o u r th in k in g a b o u t th is e n tir e is s u e . I t w ould e x p la in th e w id e-ran g in g m aladies re p o rte d f o r y e a rs by v e te ra n s exposed to A gent O range. I t 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 c l a i m s f o r l e g a l and l e g i s l a ti v e rem edy on a p o te n tia lly m assive s c a le . And th e Ward s tu d y r a i s e s a h o s t o f im p o rta n t q u e s tio n s f o r fo llo w -u p -- q u estio n s lik e : 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 com m unity? What i s th e h e a lth s ta tu s o f th e ex p o sed v ic tim s to d ay ? Were fo llo w -u p s t u d i e s made? I f th e y w ere n o t, why n o t? I f th e y w e re, w hat d id th e y show and why have th e y rem ain ed s e c r e t? 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 l a t i n g t o d i o x i n w h ic h i t i s w ithholding?^ 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 governm ent agencies as w e ll: 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 b e e n s a i d a b o u t Was t h e W ard s t u d y show n t o t h e V e t e r a n s A d m i n i s t r a t i o n , t o t h e D e p a r t s o f D efense, o r to o th e rs concerned w ith th e A gent Orange m a tte r? I f n o t, why n o t? And i f th e V .A. was shown th e s t u d y , why h a v e n 't t e s t s f o r immune s y s t e breakdow n been in c lu d e d in th e fre e h e a lth exams g iv en th o u sa n d s o f V ietnam ve S im ila r ly , why h a s n 't th e V .A . aw arded a s in g le r e s e a r c h p ro p o s a l to s tu d y th e e f f e c t o f d io x in on th e immune s y s te m ? L eaving th e A gent Orange m a tte r e n ti r e l y a s id e , was p ro p e r a cc o u n t o f t Ward f in d in g s ta k e n in c o n s id e r in g c i v i l i a n u se o f d io x in c o n ta m in a te d d e f o l i a u se w hich c o n tin u e s to t h i s day? T hese a re b u t a few o f th e q u e s tio n s r a is e d by D r. W ard 's s tu d y . T h a t th e s e q u e s tio n s rem ain unansw ered f u l ly 20 y e a rs a f t e r th e s p ra y in g o f A gent O range in V ie and f i v e y e a r s a f t e r th e Ward s tu d y w a s , c o m p le te d s ta n d s a s an in d ic tm e n t o f a l l in volved in th is m atter. I r e l e a s e t h i s s t u 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 have b een s u p p r e s s e d , in th e hope C o n g re ss and o u r g o v e rn m e n t w i l l a t lo n g l a s t ta k e th e a c tio n s re q u ire d to com pensate th o se a f fe c te d by d io x in and p r o te c t th o se a s y e t u n a f f e c te d . I t i s s u r e l y th e v e ry l e a s t wo can d o . J Pa g e Ail LETTER FROM DR, A.'MILFORD WARD T h i s l e t t e r c o n f i r m s t h a t * h i s s t u d y -- "w r i t t e n f o r a n INDUSTRIAL COMPANY" -- WAS CONFIDENTIAL AND NEVER PUB L I S H E D IN THE S C I E N T I F I C PRESS, Pa g e s A:2-4 PORTION OF TRANSCRIPT FROM E.P.A. CANCELLATION HEARINGS 0N`2 A 5 , - T AND SILVEX (NOV. U , 1980) This transcript confirms that.Dow was aware of the Vard s t u d y . Pa g e s A:5-13 IMMUNE STUDY BY DR. A. MILFORD WARD T h i s s t u d y r e v e a l s t h e p r e s e n c e of l o n g -t e r m i m m u n e b r e a k d o w n s in a d u l t m a l e s e x p o s e d to d i o x i n . A-l LETTER'FROM DR, A. MILFORD WARD ... ' T h i s l e t t e r c o n f i r m s t h a t h i s s t u d y -- "w r i t t e n f o r a n INDUSTRIAL COMPANY" " WAS CONFIDENTIAL AND NEVER 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 rita . 54?4S Ul,hf. G. D utCiO,; Dr. A. Milford W**d AMW/JA e s : ----------------- Suprarcyional Protein Rdui once Ui Department of Immunology, Royal Hallamshire Hospital, Sheffield, S10 2JF 6 A p ril 1983 Dear 9 T h an k y o u f o r y o u r l e t t e r o f th e 2 8 th M arch 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 th e Immune c a p a b i l i t y o f W o rk ers p r e v i o u s l y e x p o se d t o 2 , 3 , 7 , 8 TCDD". I w ould be m o st i n t e r e s t e d to know how t h i s p a p e r came i n t o y o u r p o s s e s s ic I t was w ritte n f o r an in d u s t r ia l company in 1978 and was n ev er p u b lis h e d i th e s c i e n t i f i c p r e s s . As such i t was a c o n f id e n tia l docum ent and was n o t w ritte n in a form at fo r w ider d is tr ib u tio n . W h ils t t h i s w ork was done some y e a r s a g o , my i n t e r e s t i n th e s u b je c t i s s t c u r r e n t and I w ould b e i n t e r e s t e d to h e a r y o u r com m ents an d e x p e rie n c e . Hay I a ls o ask y o u r i n te r e s t o r in v o lv em en t in th e problem a re a . I n o te re fe re n c e to A gent Orange in y o u r l e t t e r head and I can o n ly assum e t h a t i t i s in th is co n n ectio n th a t your in te r e s t l i e s . K ith b e s t reg ard s Y ours s in c e re ly A MILFORD WARD - >' . w 0 V A-2 PORTION OF TRANSCRIPT FROM E.P.A. CANCELLATION HEARINGS ON 2 A 5 - T AND SILVEX (NOV. Hi, 1980). T h i s t r a n s c r i p t c o n f i r m s t h a t D r . W a r d 's s t u d y w a s d o n e f o r Dow. A-3 1 P.V MR. !)07.0r: 17221 2 > -A rc y ou a t n i l f a m i l i a r w ith t h in s tu d y ? 3 A Y e s , I nm. 9 4 0 A re y o u f r e e t o -- w e l l , l e t ' s t u r n t o t h e 5 f ir s t page. 6 A The f a c t th a t I 'v e g o tte n to do, in e f f e c t, o r 7 have t h i s work done a g a i n , d o e s n 't i n any way i n h i b i t me 8 from s*caking about i t , no, 9 12 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 v n s e x a m i n e d , i s t h a t c o r r e c t ? 12 A Y e s . v--------------- 0 13 > And o ne 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 than ten y e a rs p r e v io u s ly , showing c l i n i c a l evidence o f to x ic ity in th e form of chloracne? * A T h a t's Croup 0 T h a t's Croup C, and I m ight say th a t th is Croup 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 Do;/ i i . t h i s m a n n e r 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 A 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 23 ` n -- numoer 2 i s C r o n j .7 an d 3 i s Group A. 24 .. 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 25 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 / ? " non jj 4 .* v ) i ' NEAL R GROSS COU1T RlPOBTial AND 18*NiC*llil I J JO VIRm ONT AVtNUt. HW w a s h i n &t o n . d c . j o o o j ' 17222 A That meant no c h lo rn c n e . I t m eant t h a t they were round about the p lace and could conceivably have 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 in te rm e d ia te 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 controls? V--------------------- ----------------------------- A T h a t's r i g h t , who were a p p a r e n tly s a id to be c e r t a i n n o t to have 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 atten tio n to. A I'v e got th a t. T h ere's a l o t of un d erlin in 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 sn ^ n B a sa 3 B B a B B n H n D a B n 3 a a a o ^ fro m Dow, 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 t h a t " T e s t 1 Group C' shows a s i g n i f i c a n t i n c a r o a j c a s e s w ith reduce*.: l e v e l s o f Icununoglobin D and Inmuno- j 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 " . J? .'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 ::! iib ite d c h lo rn c n e , d<-e::n't i t ? NEAL R. G R O S S COURT REPORTIRS ANO TRANSCRIBES 1330 VIRm ONT AVINUI. NW WASHINGTON DC. 3 0 0 0 3 - V A-5 imUNE STUDY BY DR. A. MILFORD WARD . Th i s study reveals the pr esen 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. t> o M j r c i R c u z - f t T r y v -v -v tiai INVESTIGATION OF THE IMMUNE CAPABILITY- OF WORXERS PREVIOUSLY EXPOSED TO 2 ,'3 , 7 , 8 , TETRACHLORODIBENZO p a r a - DIOXIN (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 Issu n o g lo h u lln s- Strictly 'Confidential XgSi XgAt ' Thara v u no s ig n ific a n t d if f a r tn c tb a tv a e n tha th ra a groups o r betvaen^ th a t s s t groups and th e _ la b o ra to ry ra fe ra n c a ssnga a f t e r dua sga e o rra e tio i I--------------------------- 7----- . Thara was no s ig n if ic a n t d lffsz a n e a between th e th re e groups o r between th e t e s t groupd and th e la b o ra to ry re fe re n c e range a f t e r due age corrBCtlor 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 th i s p ro p o rtio n was r e f la c ta d in each o f th e t e s t groups. . IgHi T here was no s ig n if ic a n t d lffa re n c e betw een t e s t groups A and 2 and th e leb o rato ry referen ce range. 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** and an observed range w hich was In d ia tln g u lrh a b le from th e o th e r groups b u t th a ra was a s ig n ific a n t ^----------------------------------- ( pC0.05) in c ra a s e In th e p r e p o r tion o f c a se s which gave IgK va lu e s below t he 5 th c a n t i le fo r the lab o rato ry raferanca range. - XgOt The d is tr ib u tio n o f th is Icau n o g lo b u lln in th e n o rn al p o p u latio n i s trin o d a l w ith 10% having ' u n detectable serua le v e ls . T here was no s ig n if ic a n t d iffe re n c e in th is su b set 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 ig n ific a n t d if f erence iro n the la b o rato ry referenc* p o p u la tio n {p<0.005) b u t th e r e was no s i g n i f ic a n t d iffe re n c e betw een t e s t groups 3 and 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. *. Tali lo I Inumi noe; ] o b i i t - l n r!--- n KjC A 31 g/i B 56 C 38 - Igr' g/1 A B C 31 56 38 ' e IgM 3/1' /r '. A B C 31 56 38 mediali 10.0 9.7 10.2* 1.9 2.0 ' 1.5 0.8 0.8 0.7 ' 1 obsorved* rango 6.5 - 14.0 6.5 - 15.8 5,6 - 13.1 i 0.6 - 4.8 0.4 - 4.1 0.4 - 4.8 .` 0.4 - 1.4 0.2 - 2.4 0.2 - 1.4 . No<%) below 5th contilo of roforonoo rango. 0 (-) 0 (-) 1 (2.6) N.S. 1 (3.2) T . (1.8) 1 (2.6) N.S, 2 (3.6) 7 (18.4) p<0,.05 Strictly Confideniial o T.il.la 2 (Conti IgO IU/ol A 0 C, n* 38 S3 34 aodian* 31.S U.O 13.0 . olisorvod rango* 8.5 - 85 1.0 - 88 3.0 - 131 * IflB A 31 XII/I 0 Sf c 38 40 44 37 <9 - 180 <5 - >1000 <5 -, >1000 C o o s In which aorua XflD not, dataata^ ara oxaludod. No(t)balow 5til contilo* 1 (3.3) . 13 (23.8) 8 (21.0) |K *0.005 . Ho(t) not dotoctod 3 (9.7) 4 (7.2 4 (10.5) if.B Ho(l)bolow tha 10th contilo of rofaronoa rango. . 4 (12.9) (10.9) 3 (7.9) t No(l)abovo 90th contila of roferonc rango. 3 (1.7) 8 (14.3) . 3 (3.3) H.B. Strictly Confidential I i U3 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 A-ll Tablu li liyinphucyLoa and An vitro _nltorron transformation T o tal Lymphocytes X 109/1 TO - c e l l s X 109/1 * n A 29 B 56 C 38 A 29 * B 56 C 38 10 th 'Contilo . 1.61.6 1.6 1.0 0.7 1.0 median 2.3 2.2 2.5 1.3 1.4 1.5 90th contilo' 4.3 .. 3.6 4.0 N . 2.7 . , 2 ml . 2.5 N .i B - cells X 109/1 PtW tr a n s f o rm a tio n depressed A 29 B 56 C 38 0.2 0.2 0.2 0.4 0.3 0.4 A 2/29 6.6 B 2/56 3.5 C 5/38 13.0 * Strictly Confidential. 0.9 0.6 0.9 N . 'Sv p<0.1C A-12 ( CONCLUSIONS n r.n He T<e (roup A I s in d istin g u ish a b le iro n the normal p o p u latio n w ith z a s p e c t t o re ru n Im m unoglobulins IgG* IgA* XgM* XgD and Ig 5 f and w ith re s p e c t to p e rip h e ra l blood lym phocytes and t h e i r E ltogen transform ation. X* T e s t .g_r_o u_p_C shows a s i g n i f i c a n t I n c r e a s e In t h e p ro p o r t i o n o"f c a s e s w i t h r ed u ced l e v e l s o f XgS an d I g M . ^ I h l s g ro u p shew s a n l a e r e a s e d p r o p o r t i o n o f c a s e s w i t h d e p r e s s e d PEA r e a c t i v i t y . Sa'se group B f a l l s In te rm e d ia te b etw een groups A and C w ith I n c r e a s e d p r o p o r t i o n o f c a s e s w i t h IgO l e v e l s o n ly * XgM l e v e l s nri pea r e a c t i v i t y b e in g n o rm al. i IgM l a th e a n tib o d y c l a s s a s s o c ia te d w it h th e I n i t i a t i o n o f th e j s n u n e r e s p o n s e an d w i t h Immune r e s p o n s e t o v i r a l a n d p a r t i c u l a t e a n t i g e n . XgD I s th o u g h t t o b e a s s o c i a t e d w i t h t h e t r a n s f e r o f l s a s e capabi l i t y f r e a th e T -e e ll to th e B -c e ll and w ith, a b o rt term iiscuaological m e m o r y . " "* th e s e r e s u l ts would se e n to su g g e st t h a t l e s t group C i s j r e l a t i v e l y d e f i c i e n t l b p rim a ry lem ur.* c a p a b i l i t y a n d i n T - c * l i -- B c e l l c o - o p e r a t i o n , The re d u c e d PEA t r a n s f o r m a t i o n r e s p o n s e in th is group is llfcely to be th e r e s u lt o f v ir a l Induced T -c a ll d ep ressio n a s a secondary fe a tu re o f th e reduced, hum oral ltm uue c a p a b ility ra th e r than a prim ary T -c a ll d e fe c t. 4 l T h is w ould f u r t h e r euggem t t h a t t o x i c e x p o s u re t o TCBO in d u c e s i l a s t i n g a f f e c t on B - c e l l s e n a ry and immune c a p a b i l i t y , th e In term ediate p o sitio n of t e s t group 3 being c o n s is te n t w ith p re v io u s e x p o a u r e to ZC20 b u t a t n o n ta x ic le v e l s . Strictly Confidential ' r. / a-1 3 : / C om parison o f t h i s d u w ith th e p u b lis h e d l i t e r a t u r e on TCDD exposure In ah is d i f f i c u l t in th a t com parative d ata has not y e t b e e n p u b lis h e d . The s t u d ie s by Vos a t a l l s a r e c o n fin e d to ex p erim en tal anim als w h ils t the stu d ie s on th a Savaso in c id e n t rep o rted by Tara are confined to children w ithout ex p lo ratio n of the- T c a l l - B c a l l c o -o p e ra tio n a x is and th e p o ss ib le anv o lv esen t o f t b s c y to tr o p h ic a n tib o d y , XgD. ( * i S u p e r f ic ia lly th i s d ata would seem to c o n f lic t w ith th e fin d in g s from Savaso, b u t th i s u y sim ply bV on th e method o f approach to th e p ro b la n . Tha p o s s i b i l i t y t h a t t h i s a p p a ra a t d if fe re n c e i s s o r e fundam ental and aaso elated w ith degree of exposure in an a d u lt rathe; th an p a e d ia tric population* must also be considered. Tha c o n c e p t t h a t TCDD e x p o su re can In d u ce a l a s t i n g a f f e c t on B c e l l memory and I n n a c a p a b i l i t y c o u ld be t e s t e d by e x a m in a tio n o f th a work attendance' re c o rd s o f su b je c ts o f t hi s stu d y . W hilst th e re cay be no o v e rt in c re a s e i n m ajo r i n f a c tiv e il ln e s s e s amongst Croup C, i t would b e in t e r e s t in g t o know w hether th e in d iv id u a l a r e l a t i v e l y d e f i c i e n t i n XgH and XgD o r show ing a l t e r e d lym phocyte s u b p o p u la tio n dem onstrated an Increased frequency o f minor in f la s a to z y d is o rd e rs . The exposed and contam inated groups are sm all, and th e sig n ific a n c e th e s e fin d in g s would be im proved i f th e se groups could^ be in c re a s e d . Xt would be an ad' antage to atudy f a r th e r casea r e f e r a b le to th eee two groups if- th e y co u ld be o b ta in e d , even i f i t means draw ing th an fre a an altern a tiv e In d u stria l Service. T a ilin g th i s i t would be in te r e s tin g to s t u d y w orkers exposed to o r co n tan in atad by ch an ic als related.to*TCDO, p a rtic u la rly i f th a t co n tam in atio n was a ss o c ia te d w ith th e developm ent o f ch loracne *s a toxic m anifestation. Strictly Confidential  AJ. B-l ENVIRONM ENTAL T O X IC O L O G Y P rin cip les an d Policies Edited fy SATU M. SOMANI, Ph.D. A uodalt Ptoftuor c j Pharmaceiosy and T iritelo ^ Department of Fharmacctofy Soother* lU injii V n iffttij * School ofM edium Sprinjficld, lUinoil and F IN IS L . C A V E N D E R . P h .D . Duellar, Inhalation Tootcology TanGentet Drcotor, Ulnou CHARLES C THOMAS PUBLISHER lltinmo U.S.A. 1 m w M tn J ltnKnt|T rrlalrtl tn iliwj*r Mairi. T liii aulliur fe d i that a mu Irui ut in hirmali111 lu i beni drvvlupnJ bv numi moli tir a 1 invtiigaturi lu indirle that ihr ninnine iy*iem organi ami tiiite 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 ileiertimi 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 th, 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 iyinn ap|*-ar qmle nvilivr lo chetnital*. il il veli eMjblithed thal artve 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 Irrtarv 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 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 environ menial (ln-iiiiialu TU anlliur le d i llial tlurr are Mine reiatinn dii] d u i make th tie.ii ilreaile io mmnnokuicnlugiral n v a a h pwnblv ibe mira cam m e im i (HilenIallV 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 tat 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 lUluiijl 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 th 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 leiimi*, 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- Chapter 5 IMMUNOTOXICOLOGY AND CHEMICAL CARCINOGENESIS ] d j i i K. P iin c i AHSTKACT T he influente uf rnvironnifni.il cheniical mi n u m m ilian ly v c m i hai bccii f>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 th rarly rrcugmiifin ut th 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 ntahliih an rarly m m n t iv'im i. The nij|nrui- ni th ttv d iii CarrifHuni t u ie noi lali-n min .1 culmi 1In- |Hndiility thal th im m une *\*rem n uv In- ihe nltul vi-hu lo Inr lu th hiojViali, l'or whalever rraw m . un i-Migainri lia u l ndervit ini n ed th inigiortaiirr ol Ihr im m une u u e n t ai - TV U lM fri V II M U H U .h.11 |^ l motUm di I----**ra*-. Hi 1 V i g i l i I K t M 'ih 1 4 tubili I llv M Ni tal Piar irli 7'L|*4>J |4 a |^ | U lti t*l i j li: ` r 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 Iir frtk d *kt 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 1 ^ 4 irj ^ MI |4`<r **! 1^ fm*d< *4 tu faMHdL<4 *1 dii tatig, *>!v 71 /aiaiaacaciai-J*e r ad CkrmHol (la iw i^ n r u 7 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-g. *ljti*ln . m rsp o la fin n i o l jdia rmai illogica i iin*c rr*]Hiii*e Mutili**, lile nm tiple ip ecie end target oigan hhiawayt, mirrnhi d ,'h iu th rin :i. Uu diri, a n d d iem u a l iln tc lu ir re lalimi* hip*. `*'* 1 lu-*e toni*, -e* nnlH iuily, have ie ri rii u i very a ril. IJnai-M-r. ilio lavi llu t lumia dala ii lacking in a majority uf die ca*e* ha* Invi a m u n- > con vieri ialion. 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|Hilaunti* 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*. ................. j i . 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 jiiiI t:.n polen lial fnr rapid pini tei alinn m a lli them an ilea I vehicle !-. the ilud e of jMlenlial loicilv. I mimine Ceti A niliiel Olir alea llut lu i mu I n v i nell io*e*ligaleil hm i l ile* allei e u ri th 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 vieni irli*. A m I i Im h Iv i i I j Ii * 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 lirari ivi resinanti* tn lurtetial inleiliun Inni* U-eo I i|n r l n i . llwn ir vii-" *. Immune Deficiency and Malignancy O ik- ul the m od 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 <h>non who wrre neoplastic or within 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 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 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. Drrsv An Cairi Thrrapi Vis .Vo Cue* CaartrTxpx f u n Psoriasis 24 Mrthoim a te Ami mips rr in Other 23 Lvsnphoma 1 3 IjukrmLl 1 H Skin 5 Mise. 16 ttrsial U iv a v tthmiualuid Art hrit is 13 AralliHijiriin- 7 Cycluphosphaimdr 7 Other in 10 Cyclnphosphamidc s Othrr 8 Skin Lymphoma Mise. Lymphoma Leukemia Lymphoma Mbc. 3 1 6 5 3 2 4 Systemr Lupus Erylltematosui 7 Cyclophosphamide 3 Amiheoprine 6 Other 6 Kaposi'* Sareuma 1 Other In Itam i lory Disease* 16 tr- \ Agent* C w i 31 |i* above, alune ur X* combi unp Cancers 16 | Lymphoma s.. Leu- krntiai, Hodgkins. and cancer pf tlin. blackIrr. culn, brunchu*.) s . a- . - - * t . .. 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 ; miniumsitppressive 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. UnsuIIan. O-meirapiopui me. /nniMiikti(ol'*(l tmChinimiCarriflOfMeiil 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 aIso 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 ....................... ................................................. L y m p h o m a ........................................................................................ (Including 1 plasma cell lymphoma). Lymphosarcoma............................................................................... Lymphorclicular m alignancy....................................................... lludgLins D is e a s e .......................................................................... Histiocytic Reticulosis (.').............................................................. amtiChrmnal C-r<IS--V- 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 iihiiiIivI 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 o d g k in s iIivmju- .......... 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 befanajih thyfamine. It ha* causes I bladder cancer in aniline worker.) Leukemia and Chemical Immune Modulation 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 jiiiIJi-nkt-uoa1 condorted 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 rPa* well as Viglialo aml 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 M h n ' i u n n i k i TnMXnltifr 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 duralbin 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 ispifion that Iten/eue is a powerful bone marrow ix iiso o . '1 OoltfM ein' 1has written an excellent review o f the lo tic henijwwilie 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 /minaatitaitenbft aa j Ckimitaf Gtrnsi'ersrui t has rojionrd that in mice (hionicallv cx|>otxJ 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 cytorha lasin B. Many nl these 1ailer rttm|uniiuLs have been, useeIi 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. \VoImanMhas 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 1li-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. Anenploiifv and thromnsomc hirakagi occurred seven and eight lim n mure (rtxpieully in treated tells. fnmmocJiniiicili and C onfer 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 IrealixI with auiilivpvnviisixc. au lu ri vllnutr a-genl as w ell as amubercolar or anitsouvnlsise agents have shown to In si 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 anllH H ties s lim n la le il hy th 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 im i le a i r lr iu e iiis . li alti-1 Is sai m in lissues, an d Ila ' a (alai torni. O n e n i th n ijjn i liiuliiigs in diagnosi has b u i il ir* |iiis a x n i' <>l a ll 1,h i eli 11*ilvmir| .|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 ila lile ilo* mix lia iro n i insolves (he ly m p lim y lir m u li) (hai reatts wiili th antiliuh-. I.ym pluHyli-s lux urne saturale! un Iheir ai u v e ilrs, am i l'M S relfs ulne lo coglili th "so ilei! lymphiwyii-s. Iligi-sting jw ay fjih a co e y to ss) ih* le m a im h -r u t th ly m p im s v ir. lite l'M N p a c k age-. th n u ilix tp ro ie m m aterial as a resid u ai hoaly calteli Lh. A h lin n g h ib is itiwasi- is u su allv v irjlly iiuhicixL lb i-ra|w iiitr agi-ms sut h a sili piteli Ihyt tanni) il. iwimazid. In ib aiai inv. am i p m t jiiiam nUh a v r in d u iix l th svio In im e th al g r n rr a lly disap]n-arx u{tnn w ilhdraw al n f th r clrug. T h ese m echatiism s th at in d u ce rh e M.K xvnd ro n o - ars* n o i s e t s r l l uiki is IlkxI; huwevsT, C hem ical m lh ie n c e c o th im m one xsximi has produred atiiibotfrs ihat m cluile amiUNA. anlinucltxiprolcin. antihistoues. an liiiu rlru lar KNA. and anlihodies to fibrous o r particulale nucivopruleins. Ih e im jsirl 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 or inllueiice b io lo g iiat syslenis, bave im ii'tu l v llix l' Ihal are noi alwavx rvatlly ap]>areni. llo w this ini|soruM i ihdense m i-cnam 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* bilile nl bjnhigh al ilsstuii/iiini, 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 iin y c hulic drugs. T h r malli Iihsrrsaiion Was lite |>IVVJ. lente nf in unlimilo);! 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 levaIni parteutsi. wlivrea* con Imi luti !*; I I, jm l nor ma! is oii'iiUiixl lo u n g e ! ohi lo 2*xl palienls wIn, e ie g veli rombi ned Iherapv, chl>ii)oumazine plnv amnlier bug. for th san ie leu gl h nf lim e show ixl levelsnl -rum IgM jt fi.l * 7Y Olhcr / 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|iri*lil. lillu um . an d a m ili s p illin o 1 bis gin. alo n e itili lini p io v itli-aiis -ig in liu iil dilli toni es w ln-n ii.n iju w tiis w e r r in aile Im Iw 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 u n u-asixl h -s rls >! I g \ l n i s i n atoaig s u iti ||iiiii1i>plaslui lim o s o li- n niixl in i i ljii- o i lo ib<w- ai ilo tal ino o l d iri apv. Itolli g n u i|is h a d a )Misti ivo anim ili b a r an b u l y tt-sl |li't'A). Im lh li.ul o h ihxipioToin aulii*hi* | ' n ', ). ai tassali g n m p s Uail a n lila iih e s to n a liv e UNA | tu'). Il is in le ri's im g lo nolo Ilio ani Imi s` i u n i Im im i. " Ilio Ig M w us il cxugulalion iuhihilur.' am i was dotiliInvi ilirn n g h mimiiuo n e o n . (Zalioii alili iln m iiim g lo h u lit) Isolai ion h x lin iip io s. A prmlm I n f il immunologo al analyses was th linding ihal Ihe |M -|ienlage nf Iv m p h m x i-s wi-rohi4iTW- m in ia i in llurtccii uni uf Im im n i- |>.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-aiincni ilev rlo p etl sp lenuniegaly. Recemfy. Docliir 1. Fidlrr'* al lite iJelrich M arsljiul (la m i Research Center, working wiih macronhages lunn munse jwr toneum . fouiitl thal Ior vome ihl 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?ing 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 hixin 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 <as*s. ihe piixixlnre niiahli.x bccau.se thr Vk.Ms w n e lonm l in havv Invi dir rvtniostr rapaluliiv A aietnl i-sjniiiiaiioii ol ih e viicci im* ol Invi ai u t :> 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 n i n o Ii j i I a i h lm o io tev el o f a ls n il iwolv- h Sixtlx tl |s jl l s ]Mr 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 - Ii .iiios ,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? 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 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 mihim.*. On co n o tti li ve weeks. I'KM Jrieltl int erased |m m MiriniMini mite, but tinte mi liv*r<liluriiian*d water hail n-dured I'KM' nr remaneil liiw r th in rnnirols. Mire ilia! were m riving lap Haler yielded mat mphages Miai when limolateti were mmnrdilal in ei/ni In IIIn melanoma cell* ttr to L'V 112 fihw sariunta whett attivateti by Cmicauavalm A-MAF*. ai measured hy releaw nl radioactivity. T h e mire drinking liyfieu him inaliti walt-r r\luhiu*l Inwrrrcl levels o f cytntuxfi ability tur the fin i two s i t K ami. be the emt of (he third week til ireatmeiit. the cell*, abbim eli Mimutated by Con A -M A f. were not itimurititlal. T h e v ludir* vliow that hyprrchtunnalcd water produrr* pro fetimi alterations in the im itilets and Uinmru.iilal capacity ol PKMs. Lower leseli ppm) may also exert such influence tlhough user a Iont i e pcrinal of lime. * .Supponine these effiets was a report by Fuller that showctl that patients tilt long-term hemodialysis tles*eb>[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 iis id.it IiLe pal lot s 11It*sow* mom jihnspliale sliiiiitj ol n il blond rei Is |Kl>(ls|. T he iLmiago to Kilt!* wiis fm nol 11.* ninnila lit e 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 mis ) i.iills ni. 'Iliis lias hern simun he llih lis and Weioberi;'' whereliy inhibition o l die lisn sim al n o vines of ihe marmphages ntturs by addi ion of irypun blue, and siali il iralion o f (hr IvMeannat nieiutoaues nenie with the addition of hyttro- cortiannr, and the cytotoxic a n iv iiy is iup|>ressnL /n n iin a n a i^ r tati Chrmtiat ('itntnfrirui tn * M aim p lu gis that b a ie U n i attivali*! )! lim pbknies bave m ilit im i bai lei ipiai 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 <onlrols. Siili e Miei Mot ilo* i<ninfa niiulsf in hihi|s Mie IIM I'.U |'atliHav'J* libai is Mie major palli Ini liio n e m u tu im i in ibi* Kilt'. Sj.Mirre iva |*t".ibililV Miai Idnroieand-t.r ils cumjmnmls mav stililiivnilv itiliiliii slm iw * tn u in n i lo Mie poi ili wliriche mi rnpliagrs llu l bave lei lutisi limiiiiim u b i >-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 hrtiugn-, bin degratLiimi produci'um l/iir lam e inniilieisiil ih iw ip il K ilt>. Ctn supjHess mai mpliagr liinioinlii j) ai ls ilv, Rrgardlfs* f th misbanistu hy w lidi 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 alsu 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 tllkcrcl 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 cghl 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. pitUi liloinnun luoortte. pfa-rnns I bniosiile, im seil ps it-ilo iiis. ami ir so m lu io h ir r adulili siri tsl iniigatti n aiti [ In* .nom ais tven- esam ini i1 ! ali etiti Jabot ol **li |llti*ss and sws-lhng~ tullaiiiiualoi 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 aunials w u e tirsi iss-n an m ps litui ol lluotest eo i labelisi ovai bum in. alloweil olile waler atf ith liti 1 rlll v 'Ioni Imins. ami Ihet) g veli a lailus 111 baiti wilh ih e pest ile lv inliaga-li ii Im imi; tube twenty-lour Inmrs alli-r Mie iniinim i/aliou. Ilo* musi *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 lime liirin, DlJ I*. Malalliiini. M nex. ami Jiatalhiim. a single dose <il |a-slniili* was gtssti orally al ihe l.l]'" or th II.I l. l )'** live t b n lafore. ta o ilass lie lo re. or Ino dass illi-r imiti un baio m hi Mi shts-p ervllinirs'les. Assgvs wen* Men rom lio lisi using anllaaly jtlatpie lorniing tells loor iLtss later. {I'taijoe Inrniing li l i s -- ani ila aly Jiitaliii tog tells Miai u n lim n a lieniolylic plaijne in lite preseorr of ronijilemenl ami eryih na yli s.) A ll jn o u is res l iving tht* higher Arse eshilnitsl sigiti lit ani depressions in spinile platjne Ini tiling te li minila*s. Low do*, animals rcrrivitig Mie iIom* {or eli ber righi or Iwvnly-vighl days prior lo inimu m u lion exhibited no sign ifiran n s tori ion in the arwilxxlv plarjue forming cell num bers. T h e author indcales that a lack til information prevens x etniciusimi as i the rifu at y nf ilese iim t|aiuuds un nualiilaimg the inumili t*system. Soirr Me niel limb dogy unis uses one test for ih e erylhrnryte rise) itnr. little fan be emit Indisi. 1hit is whv m ultiple Jvjraturter assays arc lust-ssary. Faith and Lustri have iH-rtormitl extensive investiga lions on the jin --and jBisunta! efbsrts of Tetrachhirodibemraliosm I'i CDU) ml Ihe ininiutii* ssslem atol have Inumi that VO 111 apia-.in a relatively e s fe llm i immmoitupprt-s'tse in the f ischer* Wi-lar rat strains, llu* H*rlu*r strain is repuud lo In* less of a ri|uidtr Iban its Fischer/Wtstar cm isin. Ilnwevrr. dosing ut nursing (ritiales Ins shown Miai ihe TO M ) lias the rajtahdilv o l causing iinmuuosiipjiressimt in lutermaies. Tin* cl Irei s has e Ij-lrd as Imi as *27(1 Mass. Irum IIIr tf tloses tu Mie moMier al itavs /ero. seven, aim foul Ut o . applied ai five micrograms f*cr kilogram lugrkgi tawtv wrigbl. Ai days eighteen ami ihirlv-lis-c. both Iemale and malt* Itir rinate* showiti ilr|>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 smil t*l ni Ihew same rat strains, h] dente cells taken hunt /M n tn a tw .^ t* rta ( ( ( a i , ih.* a - ** i. 7^i it 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' si 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 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 tsil 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 i n g Mie t i ll n te to b ts n e . or lltal in ser ioti ol lite 1O i l ) in i Ilo- m em brant* i j n s .i l sol lati a ltm tio n s . aliti ibis ih an g e in lite teli m iatilieil ils m u tu ai Inno lo g paItern s. Vai im is tiisi-.iig an .rs f u s e show 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 Inni ies[am se. wlit'll suli'etpieU t e \| is n re 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 i slm w n lo taiiM* s u ii h o j h * in th s u s c e p lib lily 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 well as sii p |i ressi mi 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 iy 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 imciit 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 icaIs 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 binassavs and microbial UNA Minile lor human use. ami emisi ilulr major source of cuntroveri* am one predictive lexicologists. A major su-p forward in resilvini; neh pm hlenn rtmlil he allained with th e uh *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 syu*m aie an integral pail nl the drfene 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 ci tu proceed iti usrrptibh* individual. T lir iic* of imiiiimosiippiessivr clierapv Ita shimvi there 1 an increased Ircipirtii y ol arimi tvjie ol malignant disease a tateil with continued ue 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|>nne in a given host may in Ian be vety <*nonly ikqieniti-ni ii(>ii an immune system that lias Invi 01nel low t ompiunuwvL ini /arim iirilif Jiniulut fa rt/m ami in o tiulies iisiug (tesiliiili-s. inelatlo-oig.iuis ami vai il11' phaimat nlngiial agi-nl'. Itavi* show 11 ilial teriain allivid* ol 1volpinoli celi' arr modulateli liv th pri'wiue o l mane n i il k m - rtinl|sutmK. l.yiiipliooyto haiv* heen either nppivvvl r limolateti, ami ri il ter lomlitiim niay In* alliviiug iminniu* n*s)H>n*. Hit* lit o t i monnevie, wliich play a viial tuie in th |1h i-II/Ih oli iun-i ar iso. are showii 111 he vrrv rv*n*lv disturbivi In*esresssv* amonili of chlnriue nf hcmogtnbin ib-gradalimi proaluti. So. direct or in d im i filivi can modulale th iiunmuc rrsjimiw. howilig ihr srnsiliviiy of tlie lympiloni (stipulatimi lo em immne-iilal infili' cure. T h e celi tlienueUv nuy bivom e ilekviive tlinuigh riirtvl action, or th iiu<* in whtrh divy mature ami itilereinaic n i be nmdifii-iU poalm ing au im|<oieoi celi. T he celi may Ite alfrvtivl al th intace, v illin i th r*ip!am wbere amigrine ilcirrminaitl are synihrir rvLor williin ihe nnrlrar prolei 11 aml/or dironiowima1It-veK. Tini tlierr e.vi'is a crii lor all casini; mnrpliidngisl. hiochemii. immuimlogisis. pure chi-in* bis. pure biologi!, all will liuti an abinubncrof stillatile materiaI lo investigate. The musi rrwarding porttnn ul mir wnrk may v e li be that v e v ili be closer lo cffrrtisv* o.vlrapnlalinn (or human exposure. Conclusimi The mechanism when-bv chemical influence the ininmnolugical surveillame sysiem arr not iiiulir*<o.nl. In lad. thrrr ate man* who hav* asked questions that mav dull tlir csriit-mcnl over the im m uiiusiirveillaiice theory. However, the* have not been 11Ilicienllv subslalitialivl. W lul ha been eliiclilauvi 111 ibis peenia- lion is that we CJinnu deny the influence rvlrrnji rlu-mii a)s have on the celts and products id liue Irom Ihe Ivmpliniil-immiiiic tysicm. The rote of chemically induced malignancy m the immune loppi evsed (salients Tecci tng Ilu-rapv or the esce nrrurirm es of -- ;n nini>Mii..L>lirirnt Imlivufuals is sigmliraul and >amml be igiuuml 1he com plrsiis ol 1I11- im m im e lem. details of niv\lijnims. 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* H a ie il) ti* ell lum inelli Jill! tlu-y ilo li.ne niiiiinuouxlnljlii eth-cls. I low ik a s tln m ie ni iimtimuitnodiilat >u alltv I ioti 1pi 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 n.i i>-(mii*i-d 011 malignancy lo a 1 ariinogenii Im-iuii al* Ila s e those mi lidaini 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 <ao i-s|.ilmli Compromised posti inn when making ionchii"ii a in lii-llu anv rhrmical Inudii Ite allowed in tln* hunta 11 ens noiinteiil. Mii 1 n t c hamster. and guinea pig bave vanaiib- svsti ms. ] ijv 1)1 rbemiral li-.Iivi u im -d a ik-priwsimi of die S'ti-ui d u i allo*som e'viro in indoli- a lam er.' Or ha ilu* annual politati distressed inm uine yti-m. due lo rrpi essimi of gem-lit ev(tiessili due In inbrrvitng thal now alluvs a i>ntplaltt re|j>uie 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.itology. however. I would ugge* the following, Btvacisf immutwiutvititlngy mav bring alam i ai additional dimension in rv trapoial 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 penplu-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 riufiils-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 n 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*rttrw <enrl in tlim itb ii lr p H M ii|fn t|tiim in *VfT MIIX I1*: L Ulilh. |. Ks! (dhiTurtimf 1V4 CMmti Idtr h Iiwri'4xm| (  /. 1 i '.S V >.^.1* 1.^ *ai*tntty*f *J fi s S* 3 r. ; u 1I3-rp 3J flliflFy _ i- E rir 3t k- l;t m i i w? , ir C 3 Fy *r m mP K I f lil'i J;pi l i ? !S U n i "i 5s = j p r 3. 5 ?.s t * % v ? 9 ? -3 / j L fM 5. 1 1 S r-l ? i ? a5 f3 *" A*i- s?*3 f ra a r; ;i ^3 ?3 "- I >i f I g J S { .> . H .! z. ^ j n i 1 9.1 C 3 ' 2 i- 5 : -r r<i E: .3s 32 -i 1 T y= i t ->Ii ; ;T 3-, : Ii ?i A %l g$ s3Is-;?r I ; tf ?- i - : *i 3 --1 2 :=. ilHK3 ? ? ' f HV3. s H 1 iri !?i^ lt < tr *5' =J1. 31 3 54 ?! P i- ; I. fuliI ? i 1- 3i :i- i! i H I U N i i l i i t ? r f V J 3 i, I i3! % s 3# i ? f S ? ? t r t r * c ^ ? r i ' i 3 I r 5 2.14 Fi ^ " ; 1 f L; i i= r "; r* :'l 3 - j l fH ;i j ? : i ! 2. 3 $a il i. -=' L; ' T ! i t 73 J ;>;> 2 S - >e P f 3> 3 ; Ji ii rt j U? 21-A A' i 3t ? H1 3 ?3 3 U. 3 \ i I ? ? A s f* ft fr 3 sP tf *' Sill I * Si?:^5 B.5i ?9 ? H 5 Sfc- TL ' '1- A l sl l\ " i A 3* . 3? ?i I .ou*ww/ t . y ? y" ? n, H n p Ml-i T ;3 ? J-1s iL i ri i: T Z hi i f i*j ? i j= l, F *1 L ^i > fF* i 3 ''!i1- V*3 5 1fh'ri^* `3 i r--,,*j* 3 jr <l il i iX* ; i ;T : i si 3 ?i i.* ^ ^" Sr ? 1--3 3 = i. . 3JC.7 1 : :r 1 .3-. '7-rI3 f Sj I - - F ' t ; s 7. i1 * >r -jiia 7 ? rsrF2. "i i I f :S p ?3 f 1" Si s> ir *j 1 t ! " ? r ? " r 7 ; 1 1 1 ! i" L 33 ''" *' i%2M", 5r ?I n^ * r r = s f ? I XI 1 -f;53l*irrt_r3;!2?-ii-. ?i't1i"i-, SH1-FaIi(Ss$Hr>rir.J.*t--f=' "at '--i .S*. rr- U --39 Mf L iIa --U 1 i=5_, V 2. -i j?, . tHs m? .5 a' Fi t r ? ; vr, .M. 3-S3.'.5is=5r 3 .i- 5=' s X yTa"H?31 - a*. .j t ; tni t y"n ? IC -* 41 3_+k^ rS y j . *. sj I IJ i li l-i 1a1s- a ? s JF a - 3 4 rS,f i ,4 S 3 e* 5- i. n,; c j I3 ; at s Snft- - *33! r i l : ;9 3? 4 .H ,3 - I 5_ l ?; fi V ? - 3 t l5 > - I!' ! -l |h =*5.c. s Z SSL i " ^j7 *> t n f; . :i ^ *i i p :. - ..aS.miu*j Q BACKGROUND 1NFQRHAT1QN The a t t a c h ed r eprints- from p e ri o d ic a l s and the Co n g r e s s i o n a l Re c o r d a r e i n t e n d e d t o p r o v i d e BACKGROUND INFORMATION REGARDING AGENT ORANGE, d i o x i n ,, D o w , a n d r e l a t e d t o p i c s . The l a s t p a g e in t h i s g r o u p is a c o p y o f t h e Agent O range b i ll introduced by Co n gr e s sm a n D a s c h l e (H.R. 1961), a n d h i s r e m a r k s a t t h e TIME OF INTRODUCTION. W ASHINGTON, TU ESD A Y . A PRIL 19, 1983 DOW CHEMICAL CO., AND DIOXIN public because the situation might- "ex plode" and generate a new wave of govern HON. THOMAS A. DASCHLE ment regulation for the nhpm imi industry Another scientist noted that Dow official OP SOUTH DAKOTA had disclosed at the meeting a study whlci showed that dioxin caused "severe" livej IN THE HOUSE OF REPRESENTATIVES damage in rabbits. . Tuesday; April 19, 1983 Dioxin, which has also been linked tc 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 what many of us` have been saying for some time; th at the Dow Chemical Co. was aware of the health hazards and toxicity of dioxin, th contam inant found in agent orange slvely. Since the Midland session, various studies have yielded conflicting evidence or whether dioxin Increases the risk of cancel In humans. Although It has been known for man; years that Dow held the IS65 meeting with an d o th 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 Asia and in the United States. Dow of course, made no effort to notify the TJSDA, DOD, or any other m ajor gov ernm ental purchaser of dioxin con tam inated herbicides of their con now beginning to emerge as a result of i lawsuit filed in 1979 against Dow and sever ai other chemical companies. The memoran duns raise the possibility that Dow scien lists have been saying one thing in privatt about dioxin while the company's manage 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 form ation revealed in the Times arti cle today further damages the claims of Dow, the Veterans' Administration and others th a t dioxin is relatively safe and th at veterans in Vietnam are something called chloracne," Paul F. Orel fice, the president of Dow, said last montt on NBC's "Today" show.'"it's a rash." Do^ has performed medical tests on individual: suffering from chloracne for "over 2C years." he added, "and. there is no evidenc* of -any damage oLher than this rash which unlikely to be suffering unusual went away soon after." h e a lth effects as a result of th eir ex Dow's critics" challenge the accuracy o: posure to dioxin contaminated chemi cals. I submit this article for the R ecord and hope th a t aD Members and staff will take the time to read it. Mr. Oreffice's flat assertion that there is nr evidence that dioxin causes human damage other Lhan chloracne and also charge t-hnj Dow has failed to publish all the Informa Lion it has collected in its own dioxin' re T h e article follows: search. Furthermore, they say,*Dow has sys [From the New York Times, Apr. 19, 1983] 1965 Memos Show Dow's A anO T on D ioxxh (By David Burnham) tematicaily resisted Federal and state ei forts to learn about and regulate rflnrin. Accordlngto a pretrial motion filed bj Yannacone dz Associates, the iegal organiza 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 manufactured. Chemical Company was invited but did noi Shortly after the meeting tn Midland. attend Mich., on March 24. 1965. one of those at Donald R. Frayer, a spokesman for Dow 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 compa 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 INVITATION TO MEETING The pretrial motion filed by Yannacong & Associates quoted a number of documents. the material In the Agent Orange case h, been sealed by the Judge. The documen were sealed at the chemical companies' z quest. V. K. Rowe, then director of Dow's Bio chemical Research Laboratory, said in his GROUP 07 75 COMPOUNDS. Invitation to tne^ meeting-that Dow had Dioxin Is the name given to any of 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; 2,4,5- ly owned toxicology labs. 1s one of the two major components ( Two days after the meeting. C. L. Dunn, a. Agent Orange. chemist who was manager for regulatory af Proving the specific effects of toxic chem fairs for Hercules, summarized in-writing* cals on humans la; extremely difiicul what he had been told. "Dow says that their examination of their own and competitors' 2,4,5-T products con tain what they call `surprisingly high* amnpnts of the toxic Impurities," he wrote. "In addition to the skin effect," he wrote, describing the results of tests on rabbits, human experiments are generally promo:; ed by medical ethics. Animal tests, whic are universally accepted by scientists as pre viaing essential guidance on appropriate e> posure levels for humans, are not a perfec guide because various species react diffei 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 : evidence it is systemic." group of agriculture workers In souther; THAR OH SITUATION . Dr. John Prawley, the chief toxicologist for Hercules, who had also attended the March meeting, got a follow-up telephone r-aTi four months later from Earl Famum, a Dow executive. -Dr. Frawley immediately wrote a confidential memorandum to the file. Sweden, point to a possible association be tween exposure to herbicides contaminate) with dioxin and an' increased risk of soft tissue cancers. Other studies, however, m eluding one in New Zealand, show no highe risk of cancers for a group of farmers, for esters and fisherman exposed to dioxin tha; in men in other occupations. Mr. Famum, he wrote, said he was calling W ARNING ON D IO X IN STUD IES on behalf of a Dow vice president, Donald Dr. Samuel S. Epstein, a*physician who i Baldwin, and "stated that Dow was ex tremely frightened that this situation might professor of occupational and enviromnen tal medicine at the University of Illinoi explode." "They are aware that their competitors are marketing 2,4.5-T which contains 'alarming amounts' of acnegcn," Dr. Fraw ley continued, referring to dioxin, "and if the Government learns about this the whole industry will suffer. They are particularly fearful of a Congressional investigation and excessive restrictive legislation on the man ufacture of pesticides which might result." A second memorandum Tilton - by Dr. Frawley, and quoted In part by lawyers for the veterans, said he had just received new .information about health effects of dioxin fro m Monsanto, which did not sent a repre sentative to the meeting. "From the data provided, a sample which contained 5 parts Medical Center in Chicago, cites the Swea ish studies and other research on such ques tlons as reproductive abnormalities to chal lenge the statement of Dow's president tha there is no evidence that dioxin causes an; more damage than a skin rash; "For Mr Oreffice to make that statement is absurd,' he said in a recent Interview. . On March 23. Dr. Perry J. Gehrig, Dow*; vice president for agricultural research an; development and director of health and en vironraental science, cautioned the Housi Subcommittee on Natural Resources, Agri culture 'Research ana Environment again;: "overinterpreting" the Swedish studies. Tin reports, he argued, "are too incomplete 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 spontaneous abortions, stillbirths. Infant Billions of dollars !are zit stake in thi 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 had been directly exposed to dioxin. The addition to the tens of thousands of veter oris who have sued the chemical companic; study concluded there were few differences in the.number and kind of birth abnormali because of their exposure to Agent Orangf 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<ew York, chars the study. . ing that the dioxin contained in the 2.4^5- j "Initially," Dr. Legator went on, "Dow sprayed In Vietnam was a cause of canee: planned on comparing the birth defects and other diseases among tneir member: among the wives of Dow dioxin workers and had resulted in genetic damage-and tin with two controls. First, a group of wives of birth of severely deformed children. Dow workers in Midland who had not been Victor John Tannacene, Jr, a principa 'directly exposed to dioxin, and second, some organizer of the association of lawyers han wives of workmen who lived outside the dling the class-action suit, said in a recen Midland area. This second control group interview that the croup r^w represent was Important because the Midland area is 20.000 Vietnam veterans, widows and chi] quite polluted and the general population dren of veterans who are seeking damage has a relatively high level of congenital ab against the chemical ccmDanies that pre normalities. But when they published the study the second control group was not In cluded." * vided the Government with Agent Orange. The suit against Dow and the other maio manufacturers of 2.4.5-T is scheculed to g to trial in the Uniondale. LA., court of Fee A "SAMPLING PROBLEM" era! District Judge Cpeorge C. Pratt Jr. L Mr. Frayer, the Dow spokesman, said the second group had been deleted because of "sampling problems." "The women could not be compared with those in the first two groups, and they were questioned in a different way." Mr. Frayer said. June. In an annual report filed with the Secur ties and-Exchange CommLxdon in V/ashin; ton called a IO-K, Dow said it waa one of ti chemical companies who were defendants i the suit. "Dow believes it has not been sc entifically demonstrated that the in June claimed by th plaintiffs were caused c Information compiled by Dr. Alvin Young, could have been caused 07 exposure t an expert at the Veterans Administration, Agent Orange." the report said. indicates that from 1361 to 63 American The -Dow. report also noted that Lh companies made & total o f 154.5 million chemical company was opposing a move b pounds of 2.4,5-T. * * - - the Environmental Protection Agency init Of that total. 44 million pounds were ap ated during the Carter Administration U12 plied to the jungles of Vietnam. 23.4 million would totally ban the use of 2,-L5-T*in tb pounds were exported to other countries United States. The hemidde therefore and 78.1 million pounds were used comesU- still being used onrice lie ha. on range lane eajly. The balance. 10 minion pounds, was and in industrial areas such as refineries. 1 destroyed by the Government after it was control weeds. decided to halt the Vietnam defoliation pro The company's repealed public stab gram. meats about the comparative safety, c Dr. Young estimates that 1.700 pounds of dioxin. Including testimony to* Consrressioi dioxin a year were produced in the United al committees, press releases and scienti!: States from the mid-1950*s to about 1975, papers, have been accompanied by effon when steps were taken to limit if through on its part, particularly In live Jteagan A; changing the manufacturing process. ministration, to block the Government fro: There is broad. Agreement chat a substan collecting information about ( lq contain tial portion of dioxin-conraminated wasLea riant. - - are buried in thousands of dumps around Evidence of the repeated contacts belwee the country. The Environ mental Protection Dow and EJ?_A. officials in Washington, Agency recently said there were* 12.000 of these dumps. Other experts have estimated the n u m b e r may be closer to 6J.CJO. not of the subject of the meetings, Is coi tained in the calendars and travel records 1 these officials that have been ootciried t the House subcommittees Investigating tf agency. - (Over Dow releasing toxic substances New studies by the Environmental Pro Dow officials said the new studies were of analyzing such small concentrations tection Agency(EPA) show that the Dow not consistent with pievious data, some An eailier report by the EPA legional Chemical Co. is releasing dioxin and at of which had been provided bv Dow. and office ted to the forced resignation of least 40 other toxic substances into waters that contamination levels were small. Acting EPA Administrator |ohn W. Her downstream from its Midland, Mich,, The newly reported study also found nandez last month. Adamkus. in congres plant site, agency officials have reported. traces of more than 40 toxic compounds sional hearings, had said that Hernandez Catfish placed in cages in th e Tit* in water samples taken downriver from had ordered the altering of the earlier tabawassee River just downstream from the Dow plant, including m ethylene report to eliminate conclusions that Dow the Dow plant for four weeks were found chloride, chloroform, various pesticides, was the source of contaminants in the to have become contaminated with con PCBs, and herbicides such as Silvex. The downstream,rivers. centrations of the most potent form of dioxin found was in the form of 2.3.7.8-T, dioxin o f l 10 pans per trillion. or TCDD, considered by many experts to That level is nearly 14 times the con be the most potent toxic chemical known. AMERICAN MEDICAL ASSOCIATIC centration found in fish tested in a similar The levels detected were extremely NEWS V. manner just upstream from the Dow small -- 50 parts per quadrillion of TCDD A p r i l 1 5 , 1983 plant, indicating that site as the likely in water downstream from the plant -- source ol the contaminant. but the EPA analysis extrapolated from its The downstream concentrations are findings the estim ate that som e 35 more than twice as high as the 50 parts per pounds of toxic chemicals were released trillion level labeled by the Food and Drug from the Dow plant every day. The.p1ant Administration (FDA) as the "level of discharges more than 61 million gallons of concern" for human consumption. waste water daily. Officials pointed out, however, that The water level study was conducted in comparisons may be inappiopriate, since 1931, Adamkus said, but results w ere the EPA tested dioxin levels in the whoie delayed so long because of the.difficulty fish, while the FDA standard refers only to edible portions, which may not be comparable. Regional EPA officials in Chicago long had charged that the Dow plant was a significant source of to u r c ..ruination in downstream waters, im.100.04 :he Tu- tabawassee and Saginaw Rivers and Saginaw Bay-- where catfishand carpare harvested commercially. Earlier evidence had been ambiguous, however, and was disputed by Dow. EPA officials said. The new study "confirms for us the problem is th ere," said EPA Regional Administrator Valdus Adamkus. "Now we've got very good and clear w uionte that dioxin and other toxicants are being released from the plant. The levels are ol concern to us. It has to be controlled." I.-nnrs TO GOVERNMENT Anne McGill Burford, for example, made at least two trips to Midland, Mich., in her 22 months as the head of the Environmen* tal Protection Agency. Rita M. Lavelle, the former head of the Government program to clean up toxic waste dumps, met at least 14 times with Dow officials in the 11 months she held office. x* .Mrs. Burford, Miss Lavelle and 11 other political appointees*' recently resigned or were dismissed amid Congressional inquiries on alTeditions that the agency's toxic waste (Continued from previous page) program had been mishandled. y y According to the public testimony of some officials of the agency, Dow used its connec tions with the top echelon of the agency's Washington officials to get its way on sever al Important matters relating to the regula tion of dioxin. Three weeks ago, for example, agency of ficials In Chicago told the Investigations Subcommittee of the House Committee on Energy and Commerce that their superiors in Washington ordered them to change an inportant report on dioxin to comply with the wishes o i Do*-. The key deletion from the report was the folloTing central conclusion about Dow's Midland plant: "Dow's discharge represent ed the major source, if not the only source, of TCDD contamination found in the Tit- tabawasse and Saginaw Rivers and Saginaw \ Bay in Micbigban." /V VaWJ fa4 Vqs>^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 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 nes oi numan experiments u> gAmre 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 poni3 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 :p3 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 4 ChWT1 WwWM-y ______ ;______________ technology, Dow did not license it im mediately. In early 1654. the company switched to a production teenmine tra i required plant process tempera: tires of 215 C- Measured in Di.ceinher ivu4.Tt.~P waste streams cor.Liined dioxin Ipreti ranging from 6.0x0-lu.Ow purls per mil lion. according to material ir.treduced by Dow during its recent motion fer summary judgment. The Biochem re port indicates that it was, inueed, the high proefik* Urn|wr*tyre th ll por,orat ed the high dioxin levels, and led to s major outbreak of chloracne st Dow. Although Dow told tr.r MteH--in LV;>i. of Public Health about It.at prutiicin. it did not mention it to the Dt pL of LV frnse until 1967. Dow has contended tn court that "knowledge of the pre-vise occupational hazard" that occurred in 1964 is "irrelevant'' to tin- gm eminent contractor defense because it "promptly remedied" the problem. Neither the dioxin levels in finished product during this period, nor the amount of Dow's output that went into domestic or military use is known. But sn Air Force sampling of Agent Or ange's predecessor, Agent Purple, which * x i used between 1662 and 11*65. ihoweo dioxin levels as high as 45 ppm. Both Dow and Monsanto supplied 2,4,5V,' T to the mieiary dunng this time. Cit* ing the ponding uLigation, Monsanto has reserved comment. Dow* rights. In March 195--the tame month u its meeting with other TCP mr.kr-ra--Dow purchased licensing ngnts to Boehnncer'a low-tenqvrat'jre TCP manufacturing process. From then on, Dew contends, its 2.4.5-T never contair.cJ m,,re than 1 ppm of t.ox:::. Tr.e company has recently slated that 2.4.5-T coni^.iniig 1 ppm or less presents no human health hazards. 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 Invotigj- tive 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 D ioxin P u is D o w on ih s S p o t ticipant in the 1965 meeting later wrote, the Dow scientists reported that "even vigorous washing of the (rabbit's 1skin 15 M emos o f 1965 meeting hint at company`sfears minutes after application Iof dioxinl will not prevent damage and mav possibly en On 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. Orenice 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 1conspiracy of silence." ; TIME MAGAZINE May 2 , 1983 Sittin g along the TiUabawassa* fin er. Dow'i sprawling m ia i lalion 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 12 of 130 residents i York Times, memorandums from partici tested in Impend. Mo. near dioxin- I pants in that almost forgotten session in conlaminated 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." den "They (DowI are particularly fearful j In 1964. after 64 workers at its Mid- ! 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 | ' * - 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 hite blood cell count paL 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. NEW DISCLOSURES*REGARDING AGENT ORANGE A gent O range screening program . D avis was --Norm al kidney functions, b u t an tnto ld by VA doctors he re c o rd su rg ery o n crea.se tn uric a d d level th a t could lead to nerve* ln his wrist and should undergo psy kidney dam age and bouts with ro u t or HON. THOMAS A. DASCHLE chological counseling. Otomowakl. w ho has goutty arthnU a. Dari* has had attacks of 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 OF BOtJTH DAKOTA IK THE HOOSC O r RCTRUCKTAnTZS d octors w ere u n ab le to Id en tify th e ir cause. from 1)11 V ietnam service. T h e th ird v eteran In Lhe gro u p . M edal of --A'variety of n erv o u s s y u e m d y sfu n c 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 Tuesday, May '-f- 3383 l i Hwill require fu rth e r exam ination before Inflam ed and Interfere* w ith sensory con- 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 a diagnosis can be m ace. Welts said. B oth C a n s and Gromowtki w ent th ro u g h th e V A 'i A gent O ran g e screen in g a t th e VA B ospltal a t Wood. W ise, a M ilwaukee s u b u rb . A t Lhe conclusion of text* th e re , duel! on. a condition often a.xiociiLrd w ith a degenerative process. He also stiffe n from petty raril seizures, which make him n au seous. d^zy and b lu r his vtslon. --A b h crm riitlea la h is rep ro d u ctiv e orange. to which many servicemen th e y w ere sen t le tte rs signed by D r. M ichael system which, a lth o u g h It Is still possible were exposed In Vietnam, and the ill O . O 'G rady, th e sta ff en v iro n m en tal pnysl- fr h im to la th e r ch ild ren , p roduce sperm t I 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 ciao. th a t said the results of th eir initial te sts w ere "sat is facto ry ." T h e D aily News a ttem p ted to c o n ta c t O 'G rady cn Wednesday. b u t was told h e could not speak to the prets and was re ferred to puouc relations i toa c tm an Y. C. P arish. A woman In P arish 's office said he form s th a t are n e t norm al In th e ir ab ility to Im pregnate or are m utated. --A n o rganically-baseo severe dep ressio n pointing to an Im balance of n o u rish m e n t in som e of th e celts ID h is b rain . D avis said Carr.ow told him he has not suffered brain damage, bu t some of th e cells are dam aged cant Issue: would n o t return to work until M onday. to the point w here they are unable to {From the R oblm on till.) D rily M en . Uay *. 1S83J A rocaL T M t Latxt? "O aancr-H oT " C o n rao v e tsT (By Tony Gordon I A m edical s p ecialist Ln C hicago h as diagnosed a nu m b er o f phyetcxl alim ent* in W est York re n d e n t Samm y D an* and an o th e r Vietnam veteran as being related U th e defoliant A gent Orange. T h e diagnosis Is believed to be th e l i n t tim e a physician h as drawn 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, an Ingredient of Agent Orange. Davis, who was awarded th e Medal of H onor for te rrie r In V irim an. was cue of th e Ural th ree Vietnam veteran* to be ex am ined fo r possible dioxin-related Illnesses by Dr. B ertram Camow. president and senior scientist for C im o v . Coni bear and II Is th e p re se n t policy of th e V ete ra n s A dm lnistration-to deny-any disability claim s b ased on dzosln'i effects. T h e VA provides fre e .p h y s ic a l cx*.t .:ha*.:ors to v - u w ho /--! they may have suffered idie.-ae tira .th ef fects from exposure to Agent O range. T h e VA said V*eiln rie a y 263.000 V ietnam v ets have gone to VA r;uspiL--s com p lain in g of illnesses they tnought could be n e ste d to A gent O range is th e last y ear an d S.40u of th e m w ere 111 en o u g h to be h o sp ita ltsed . n o n e fo r any illness th e VA say* is ca u sed by Agent Orange. Vcm Rogers, a spokesm an fo r th e VA Office of Public and C onsum er A il aim in C hicago, la s t w teg said th e ag en cy a* "p ro viding m ed cal screening for any veterans who th in k they bis; have a problem and we a re doing so w ithout any tn-ciori proof in the entire won a u r n * u n i between Agent O range and medicaj problem s exists. T here is no piece of paper by any ciictor anyw nere absorb c * 7 Btn. --zits botty also h a s d ifficu lty In D ie proc ess of energy production and transfer, which brings on ocrurrrrrces of extrem e w * y jseis D a.is said in - re.its in d trv .rd th e body produtrs an to iuthl the dioxin cm .tarn in a n o n w inch sw.-Hs th e nu- cirux of ci Its and re ta rd s th e flow of en e rg y LPrcju^h h is bt>uy. Grem ow sal said Cam ow told him a likely cause of his seizures Is d am ag e to h ts b rain caused by m alform ed ceils, ills liver and central nervous system are damaged, there Is a blockage in h ts lu n g s an d ab n o rm al Hies In hts blood. "Dc. Cam ow told me th e diseases I have are all a result of exposure tn th e dioxin tn Agent O range." G rornr'w rxi raid. T h e disg.-.psia of G ru ru iw ss j m ay be esp e cially sig n ifican t b-.-vausc w h ile D avis w as a-.-.:g,-.ed to a co rn ea l u r.:t In are a s of Viet- ra m prayed w :;n a x- n t ' -range. G ro- r a i v i 'i was m il H r t v ar.'lvned as a cool Associate*. Ltd. Carr.ow la th e d ire cto r o f o ccu cx tio n ri and environm ental medicine a t th e University of Chat say s a n y th Jig a t all is caused by A s c o t O range. R esults from Cam ow'* testing and exam i tn D a Nar.g ha^- ca m p f.vr mx m o n th A a n d was never sunt in to a sp ra t rd area. "T n e d.*g.-iu,is of J o h n p u la us in m e po Illinois School of Public H ealth, an attend nations may prov.de th a t piece of paper. r tio n to reth in k m e <rr; omitx ol exposure ing physician a t th re e Chicago hospital* and A lthough Cam ow said " 1 have no in te n to Included arra s of tw iitti V ietnam previ th e a u th o r of m ore th a n SO articles and tio n of becom ing involved in th e p o litics of ously u n su sp ected of posing a th r e a t." W ells p u blications o n Lhe (.'ecu o t th e environ th is L-ivue." h e said tus diaer.nzis of C av ts " is said. m ent on hum an health. a m a tte r of in lore re ration of studies of Cam ow said his le s u 'c n th e th re e veier- An advisor to th e th re e veterans. Irv people w ho have th e same things." ans involved " a s tu d y of th e p s ti- n t 's htV.o- W ells. Is c h a irm an of th e V ietnam Veterans " I t comes down to a question of w hether ry. a com plete pnys:ral r u m and laboratory C o n fed eratio n of M ilw aukee and a licensed you believe so m ething th a t look* like a te sts to m easu re tn e fu n ctio n * of various surgical physician'* assistant. He arranged duck, walks like a duca and talks l.ae a duck organ systems: th e liver, centra: and periph to have th e th re e men see C im c v tor a n ex is a cuck. Thr.-e may be o th e r vnim ais w ith eral nervous system s. carciuv si-cunr arid re am ination. fe a th e rs th a t spend tim e In th e w ater, b u t a productive system s. We s.ro do a ju rie s of " We w arned to h av e -jur guys exam ined d uck 1* one specific an im al an d people blood te sts to d e te rm in e blood co u n ts tn th e by th e fin e st e x p e rt * , `'c co u n try and a sh o u ld be able to d eterm in e t h a t from inves liver an d x iin e y s ." review of th e rusea r t'. dioxin led m to tigation." Camow said in annexing th e Una He sard nil firm em ploys "th e state of th e D r. C am ow . H e's p u re p .iy jic lin . a r.cn-po- betw een dioxin an d th e h e a lth of th e tw o a r t In clinical m ed icin e." b u t h e h a s n o -UUcai anim al, and was wilhng to look for v eteran s. equipm ent or procedures not available to th e reason th e se m en are c-lX." Weils said. in a n interview restricted to Lhe re s u lts of tb e VA. C am ow perform ed a I'i-nour wine* of th e Dis h exam ination and general in fo rm a "T h e V eterans A dm inistration has th e ca te s ts and physical ex am in atio n on th e th ree tio n ab o u t his procedures. C am o w to ld Lhe p ab ility to do a n y th in g we ca n . b u t n o t veterans ln M arch. C am ow * Hn-Jires are D ady News " M r. Davis displays Lhe n o t having th e results of M r. D avis' tests th rre . m arkedly, d iffe re n t from inform s tier, the sym ptom s traditionally found in peODie who I d o n 't know w h at ty p e of ex am in atio n th e y m e n received following ex am inations by h av e b een exposed to d ioxin, an d th e r e it ccn d u cL T h e VA h a s a tw o-volum e book o n Veterans Administration docto*- ab solutely n o th in g else tn h is b ack g ro u n d to th e researc h in to d io x in , th e y know w h a t ix T h r resu lts of C araow 's u rd ep eu o rn l tests su g g est any o th e r ex p o su re to d ioxin m a n being done. T h e y h av e Lhe lo x o lo g tsu , bio- show Davis and fellow veteran Jo h n Cro- th e A gent O range in Vietnam." 9Utist:c:an* and laboratory physicians capa mowskl of M ilwaukee suffer from asnor- According to both th e coctor and patient. ble o f doing these sam e text*. It becom es a m allties In th e ir blood and vascular ijvtem . C iir.o v i exam ination of Davis d etected Lhe question of w hether Or Dot th e y agree w ith follow ing;. m e." Cam ow said. --H igh ch o lestero l, h ig h trig ly cerid es a n d O ne group of p eo p le believed to h av e a larg e concentration of fa tty celt* tn his agreed v i 'h C am ow and hts In n s for a d blood, a condition norm ally found tn people verse tirxitn effretj eaused by dioxin expo m u c h o ld er th a n Davis. T h e se facto rs. su re a re th e 12 m r m tv r s of a M ad tu rn C am o w arid , poee " a very h ig h risk of h e a r t Civunty Jury w ho In A u g i^ t t'- c a n g ra n tin g disease ." JU dgm rnts of betw een 11 m i.tiun ar.d 11.> trlflion to eaeh of t l r..:.;'>ad w o rse n in volved In an exposure related suit. T h e w o rse n ch arg ed In th e su it th e y h ad s u ffe re d c e n tra l nervou* sy'.u.-m oarr.aite an d ca n cen because th e N jilu n arid W rsicm Railw ay h a j ta ^ rd to pr^-r-ct them wrren th ey w ere Involved In a J lv itri ctran u p op e ra tio n a f te r a rail accid en t In lv 79. Cam ow testified on behalf of the workers and described the m rtliral problems he has 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.Zrd th e w orkers hxd b een aiir*te<1 arid beg ait m aking the fuianc.al ants. ln h ts im ervirw a im m e Daily N ras. C a m o * s a .J l.e w as . : *.. : ;.g a n , o i li e r doctors of nrtltgrncc even though the re sult* of his lest* on P * .tx k ill *ri-m.iw.vai C o n g re ssio n a l Record May 2 4 , 1983 how d tltrii-iii ri-s-:.`s IJ.,;i th e re ir.v " I do not think anyone U fakir-g the tests, but they may not be all U m em and may n o t be viewing th e results 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, P a w etia 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 137. 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' AiiininisLra- tlon extrapolations of current chlor acne cases prove accurate. Tills R*gi.-Ia- lion 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 KDflW JaO AK hraW ri/ Cwa r t a IUU I XI 1 . LSI ______ _ 1U) 1 O n A t a n a oagnag li-bK* _n_* _Ua___--n_ LM 1X1 m at SI IX* kf1tlio j t t m i f tHf uptari v IM b a v m u t IJUfUfnk<ij^c*nI fc)*BJKUTKMitM>--*4a4uMVar4i it 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 ___ l u 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: JLR .1M I A bill to am end title IS. United S u tr a Code, to p ro n d e a presum ption of service con nection fo r th e occurrence of certain dis ease tr ille d to exposure to Hero If.ties of otb er environm ental hazards or condition in veterans who served in S outheast Asia during th e Vietnam era Be ft enacted by tVe Senate and House a f R ep ream to f i l 'd 0 / (Ae Untied Stale* qf A m erica m C onprau ozrem ew t TliaL Lhtl Act may be cited as th e "V ietnam Vcteranc A gent O range Relief Act". Roc. 3. T h e Congress fLnot th a t-- (1) c e rta in A th e n e h eal Lb Effects o ccur ring am ong persons who served In th e Armed Forces In S outheast Asia d u ring th e V ietn am era. an d c e rta in birth d efects oc curring among the culld ie s ol such persons, may be tr.e result of lhe exposure of such perrons during spoil service to phrnoxy herblciccs i u-.lin g th e h e rsic ia * t n o v n as A gent Orange* and the class of rhem irols knowu ss Lae tuosins produced d u n n g tn c m anufacture of such hertiieiaesor to other [sev en involved to such service Including ex posure to o th e r herbicide*, chem icals, caedi- cai-a ns. or environm ental bosom s o r condi tions: and (3/ a com prehensive review and scientific analys'-i of live lite r a tu r e covering a lu d its relating to w hether there may be long-term advene h ealth effects In hum ans freru ex- fiorare to a n y cl m e class ol chem icals known os th e dioxins produced during Uie m anufacture of the various phenoxy h erb i cide vu.ciL.ibng th e h erb icid e k n o w n as A grat Orange), os required by section of P uhbc Law -111. h a s been com pleted and suocuttcd to th e V eterans' A 'fm inutrat.'oa. 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-elion: *ts<l) Ycr Lhe p u rp a a ra of le c tio n 310 of th is title and s u u jn rt in Lhe provisions c l sectio n 313 of li t title , m th e case of v et era n who served La S o u th e a s t A sia d u rin g tn e Vietnam era and who after such service ra fte r from a case sat d ra c n o e d In p a r a g rap h *SXA) c f th is ruoseetton. su ch dtw-ase ahaU be considered to have been Incurred in or aggravated by such service, n o tw ith stan d ing m a t th e re Is no record o f evidence of such duease during tile period cf vem ce. "liX A l T h e diseases referred to In p ara graph (1) of this subjection are th e foJlov- tnx: "ll) Scft-lUrue sarcomas. "ill) P rcp h y n a euLanea tarda. `(Ill) A euve a n d resid u al efilo rsen e a n d ch lo ro ccelo ra lesions. "tiv i A disease listed In a reg u latio n p re scribed by th e A dm inistrator under su b p ara g rap h CDI of Litis p arag ra p h . "(B ) T h e A dm in L ir a ta r tr.xy d e te rm in e , an d c re s c p b e by re g u la tio n diseases t:n a d dition to those lu ted in suo p arag rap n (A) of this para* ra c n ) th a t meoioaJ r o v a re n h as shown may be due to exposure to h erb i cides, chem icals, medications, or environ m ental hacarus o r conditions. T he Adminis- -LraLor t r . i h include tn su ch re g u la tio n s . a ip e c d te a iio a of Lhe ita a d a r d s used by tn c Aclfr.inuL.-qlew Lh m a tin g xucb d e te in u n a - tion. Ti; T a m g rap h (1) of m ix aubsecLlon hail te rm in a te on Lhe first day of th e U n i m onth beginning after th e end of th e c:;r- y ra r p -n o d b e rm n m g on th e d ate Lhe A 1- m in ls t-itu r lu o m it* L) th e a ru ri-iin a te O-itumitvee oi Co::zr.--a th e firs t i>-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 re- p e n t A ct of 1BT9 (P u b lic Law SB-151; S3 SU L 1093L"A i MARCH 8, 1983  > pr- Dioxin riiad a Human Wreck Cl Of Ton ah Trackm i 1 o c i i h O j / MrJieot Tnt>\t*c firp.irt FkO.'-! THE RKCKONING of St. Joseph's " 1 saw some che m:!un ncsee nee stud 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 -- with of the 47 railroaJ trackmen spent a total of phylohc mu git!ut inin. 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 mined at interval* until last November. change in hone marrow at the sretti cel! ``The stuff, which included phenol and level. He speculates that with the iymch-r- orrhochlorphenoi. 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 oroduc- had complete urinary obstruction. Five, or ticn of ary ih.v droxyhsdroxylase and there about 10 percent. d r* - by, tumor grow tn. veloped skin cancer. ; But when dioxin is One had a l .400 tri- i i glytcride. Eighteen!? ..s m : . J 1 added, the carcino genic process is en had abnormally low i . - A testosterone, usually i . ^ ' A hanced thue*ap.ds of : h- ^H u t - ; \ times. with a marked ce- j | crease in libido. In \ v. Such inferential risks aside, to fully many. peripheral i assess the individual neuropathv, a numb- : nsks in the Times ness and l.r.giing. be- !i Beach population, came deeply painful professional inter at niebr. causing in viewers las; January somnia. There were changes in muscle reached yOO or 9*0 residents with caes- metabolism, 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.vesti- plex of extensive neurobeh.n u>r.ii abnor gatorTdrew the test group of 120. malities. often characterized by a severe A leading environmental specialist, the 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 tuilow- In 20 of !'*; -I? aiiro-.t two xc.'.rs ing p.ml itioiis ibet diNperving them 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) . Ikoi.d i.;:; an i;:e:it ..i iuir, 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 . with that in age-Miatche.l no rm aN l lie D yinrj Ircm d 'o x in : n h n ". on nn lirr- 'rl- P"lime move : * ol h**l ie ist.iuce no I m r v i nl. M o. (arm I h o n n h/volu tn n r irt.y i.m l had full i tuwi i*l the fnemy. were 3?,CH'0 pt*k>. j ..totowide hujli. -V; .wV^i.T > , OVV' ' Cl,;C.V|rt 1.mmt -X^ -- 7 r;b*jn->-.--S--u-o--o--.t--/.n Ma--rr-crh--,2 7,-,--1--;-t7 T 'h ; * < i i t >h s i ' V / *k 4. !S ]T $ Q iliid / P pi ('*.* y XIs -XV f > r| :,, c l /ft > r r > : ; ? j . o - v >. / U ... L' i *r'j.1 71 ,\ ? ( * > . v -i v ) i V L 1 [ j . s'* v i '. , i n *.- 't h i : i n \ i j : m \ m i ; n t m . i -.!-.*(i n n A i t . \ i.-. . . . i i ( l ! o h u ; t l i * l o w M o f T > > l : i T. M i* ec,ii il li '' Ii,il 4 *1. : . ; . i . n : i . . o '. ; ' I r n l i . i l i V h . i / n i d , u s d os o l c *: ; e . 11M i i : i I n. Ii 'ii 1S ' i - , I I I . -o. I I m i . T i ' s *f t l l i m .1. *. ; . tln in m M o lit] 'id I:.ivo M ies M is .ilsu l i 1; i \ | - 'il !< I I c o n t l o x i - - i . i l i I n - I t i t c.i! 1- si I f *I* I* . : i : m u ; * ! > . i | i - n \ i t h e >! i i *i- n i i!. 1;i i i iii*I i!' |u* *,n >1 11I ,.i. I ' . r r i ni\v I o .uliii ,i * v\ ! ' ! I \ . . . I . i l . . 1.1r t i t i i s in ." o;;; f - ' \ j .1! i i - I* \ . i y . m u . i l l i * i t o it i i n i 4i ! . - m . i v . i i I i . I t i ' ; i . | * ' i -. . - n ' s j i l u l n y I n v . ' o i l i s . .- I**: ` .<!"*!)<I<()|*v .lo*i*11!i1*1issi'0, rn i.:'? i.1 ,'t( 111* University 1 :i-;i. o'i'i.T - liow vul.lly 11:.i\ni (ifi .!I*.s' li. Ii:-:i;r.i liirk ..mi m.iy rt|*ti"re; .-n*-.ii-.v,,irmi.<'ss'toii. `f.,r I'..1<Mil fill's eaU'-C'l l.v Ilit* loxie c n . .i! 4i x r I \ ' .' M i ' l i f i l l N l i n o , ; t h i s l i m e , " hr . i j ( ! .............' / ' : il l S M l I ' Y , i n i r o l I In* I ' r w 111 . . i l i . i . v s i : I ' V j i i i n . i l : I n > : : i i s , i . * >. ^ i . . -il | n 1 i \111 M ! i o i l . m i . i l i i . I I <*)) * i . i i t , i I s p i l l i n 11:11I a i ' u ; . ' i ' i I . , n . . t i m e v . u . s The if'.i :i w c . e > | n . . . - - l ! n m u , i l l a m o u n t . . o f 111 11( i ' . i i i I* : | -K ra h ^ im ; finiu few Ch:X' to u:>to 1::mi >.$. 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 1 11 1h ! t o li i . : i v > o f t A o l h i i d s ni lie normal function of nouliuph'l.s. "I'ac man'-type rell:; Hi,it semiy ;i!ioi:| 11*1 l i n d v ' '. M i n i ; ' h a i l e i ' i a ; i m l f e i e i p . n l i e - hiIS. Also fotiii'lwas a (Inrea.se in the mini Inrof1usinophils,<ellsthat plus a role in cm lidlliuj' alh-rp.ic reactions, ami a reInilion in the eonmnlralion of oxvpmi cans ill]' heiiinp.lahin 111 the led hlood halaneed 1i**;iil;j|<*% opm atu.i,*' I'nnco said. `W hen you pet too ii*;.u\ ofone kind of cell and not Olinuyh ol another, it cnmplef'ly ni'-NelsIr.ememal iespot.se A compioini ed irnriiunc system is ir.capa* lfaie.loilonliphtinj;Ifclialunys in a normal "This is a very sohtle and complex riaction " ells. I'l nic.-e s a i d h i s s t u d y l o a u l t s a r e e o n s i s - AMh*n,"h viiIfly 1rcop.ni/nl a:; .1 |o\m, h n i w i t h t h o s e d o n e i n . ' i v i d m i w h e r e the exact extent ofd.-.no.erj(.(<Ih\ diox 1m e n w o f k i l . p i n l o r e s ! : p r a y e d w i t h ; in in the environment .1 in.dim of\^ Iii 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 iin!in.ei:y aninnif .`.1lenl1-Is. I ; . m p h o n i a * ; . I h i i i o i - o ! fa ll I r e n e , a t a 'It11:IHim :hlood mils l-iimr Ktiufiii? MillInfillV WilltcslIIIy (-.nil11ons <illsthat regularly occur in Ilie liiunan hmiy ,-is well ish;u'ten;ianil<.lh<'ll'o|cij;u111.ihri als II the cells (.ail lo 1eiupni/.e ami iiisi1ny inth/'.'ian! cells,a pm m.'s 1isl;of d;celopinitcancer v.ii! inciease <h.nip.o cells may .ahlisonoirmillii.ciallehhiam*la*amchaonfe.Mesooidn the hone maildw wh'Te hlood cell-; arc 1, t i e s i \ l i n n s ; r e . i t ` T ; l s m N o r m a l . It:.haul Wilson, chan in.m of tin- phy sic., depfuIlm nt at Jl.ii'.nrd tnivcrsiiy wl.o has studied dioxin and has written a nmnher ol hooks 1 - iunain:;j levels of d;.m'<T> asfoeiated with h xi'is, said the st1rIn , dot.-* m liMm'.Ns. inI11!a1i ll.o S*.edr h .sliiiIv cited hy I`line:, have I.lik'd lo establish Ih.d chioiiiv cxpusure tosmall ammintfi oldn-xin e.mse-,cauccr. mniiiil.itturcil, l'micc said Such <hanp.es could mean .a/'.ratcr ;i.skof levelojnni; Imil.i-nna. a cancer of the hlood. The cli.u.pes l*inice fmiiiil in Illinois woikiurn aic consistent with studiesdone in ini,he '..ud Inmire <xposed tolaip<* aiuonnis of dins111. the natural unmum.* system shuts down. When mice arcexpos SOMi: STl'blKS` s i i j m ; " .( c h r o n i c t o x i c i t y i s c a i c i i r w . t 'n i c ' I c a n c e r - c a u s i n g I a n d 11 1o t h e r s s u c h * s t il i s ; . i e a r e i n o f . ' . c n k ' . " W i l s o n s a i d " S l u d i f " ; h a v e s h m v n it c a n 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 I C a i r o * I n s ! li d e f e c t s | .s' i i i p l i ( M i s i 'S. I t i s tilMil'S."M u s t y .`i t h i p . h ( l o s e s , h u t s o a r e l o t s o f ed to liny amounts of the fsti.n.n. tfi.'ir white IiiikI cell production actually is slimul iicd, hut iunction of those Cills is alleic<J. W1I..011 said Hint us: of Ai'.eiii Mr.inj;e in Vietnam hy U S. militai v forces to clear vepa'tntion was done without normal s.ilefjuanis for human e.vpo.siire and with C'l thes i . ' n i t i r o N 11 "Kvcn lions, w t l v In 'In : t h a n t h o s e 11uriiidi-h'T.j.t-ia1i,t--.-*ha': haven't ce.'.i c.,m yet ft.'ld n 'p o M c.r..'i e;i dleviiis'aeid(.,f1:fliatm.i:ivtl11m'.vr.tht.e*.(t.er.x::-'i's..i.n.-' he snp,|| A stialy i f iniro \ p !:,*-.'.e fa:,'i'i: re|H,iler| !a!We*!'eha'N th.*! *; Tli.it :.l'.!d,y. un :-.rt-don !_ V;e'r..a 140,eirisnnt. rn:.led that A*" : who-e In-hat.!- a*,! ip the .V chirmp. th'- war 1*: r..'.ear*ly >, r ol h.*vnut Ill'-e!t1i1. . f.I.a.r'i.s chddimi v,.Hi a-:*.}:: than v.:r: v.ii. li:rh.m Is mav e men e.x;ei-* to A',eiitOr.ifiyi'i:i.l.osi.nto 1 theP I U \ ( l x S . M V i i 't i u i n fin d fim '* arc* "ci.u.. tiiit would c.xpmt i* wTli:t.hs t};*.. (I . a -di n m hl.i>d..c'.uc i . h i l i l i e s o l i n t o , : t n r . , ; a :*.:i . d l k . r . d -. n o r m .il ;ic' iviliv> AiKilliiT l.'iuvetsity of Ilia.*-:.-. nisi, John Fiederkn. h*s *.i-1 he "i km I:* of a (!i'!fi c. c t j .r . . 1 h m h.c 'J sprayed a'.ei'ie:/ y -n :*:il V.'a.<-or..:r farmland more than a ci a :> A classic ;.yi.ph.ni oCi.d'-d w;*} dioxin exoos'i'n i- .a .,**.) r.'ssh r.If*, chlnr.iei r. I.id loi.h-fra :.! #*-! t-:ol-\joiissympfim',1 1 ;,er,r,.(u-r.t.y "Few ' than .Vi j rc'e*.o f 1 j ;-r (.xj/OsC'd to dic/X.;r. w;il sv<.,.v a r. h. lc.asl very soon," Ijed-T:: '.id n i a skin cancer in the se-.-e 'hat it r-. 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 <lclliatly coiuaminaiU levels of dioxin that were pears." V l` ij v\ siV