Document RVvJabNzeJeQro6DOaVQwXRn

Environmental Research Foundation 15 -Hoir-y 1U51 page i o Q FAX COVER SHEET To: Paul Merrell & Carol Van Strum Bradley & Merrell From: Peter Montague Environmental Research Foundation (410) 263-1584 (voice) (410) 263-8944 (fax) 4 pages (including this cover sheet) Sent on 14-Nov-93 at 18:41 Sent via FaxWorks OS/2 Environmental Research. Foundation 14-Nov-93 18:50 page 2 of 4 November 14, 1993 HI# Paul-- More thoughts on information it would be nice to get from Monsanto. The attached 1978 letter from Dow discusses the relationship between dioxin in a human now [in 1978] vs. dioxin in that same human at the time of original exposure. Such a discussion presumes some "half-life" for dioxin in humans -- some period of time that it takes for half of the original amount of dioxin to leave the body. He know today that the half-life for dioxin in humans is roughly 7 years. The Dow letter does not say what Dow believed the halflife in humans to be (as of 1978], but they clearly assumed some half-life; otherwise the letter wouldn't make any sense. Xt would be useful to know what Monsanto thought the half-life was in 1978. When they broke the Nitro cohort into "acute exposure" and "chronic exposure" that seemed to imply that an acute exposure would leave the body quickly and would not remain in the body to create an on-going chronic exposure. We now know, of course, that that was an incorrect assumption, and that an acute exposure in 1949 would remain in those exposed and would create a chronic exposure situation over the years-- so breaking the cohort into "acute" and "chronic" didn't really make any sense. If we could show that Monsanto knew something about the half-life of dioxin in humans in 1978, it would help us show that they knew (or should have known) there was no valid reason for assuming acutely-exposed people didn't thereby take on a chronic body burden that would create chronic exposure conditions for the rest of a person's life. Environmental Research Foundation 14-Nov-93 18:50 page 3 of 4 BOW CHEM ICAL U.S.a ! 6 January 1978 Dr* med. 6. Reggianx Member of the Research Board F*. Hoffman--La Roche and Co./ Ltd. Grenzacherstrasse 124 CH--4002 Basle. SWITZERLAND . Dear Dr. Reggiani/ /Thank you for the information on the levels of TCDD found in the tissues of the woman who died' 6.5 months after exposure:- I cuhcug with you that the levels appear high*. The level, in body fat suggests a daily exposure to approxi m a t e l y 0 . 0 1 H9 /k g / d a y . T o r a 75 Jig person/ this m e a n s 0.8 yg/day. If ingested via dietr the diet would have to ^ c o n t a i n a p p r o x i m a t e l y 2 ppb. Presumably/ this ,is n o t likely! S k i n >a b s o r p t i o n should: not be d i s c o u n t e d b e c ause of the f absence of~~chlogacnel First/ the age of tne woman may^have decreased the sensitivity of the aenegenic activity. Secondly, c b l o r a c n a is- likely to be a systemic rath^y than a i.rw-.n1 ^ effept m o g t gasftfi^ Therefore# the real question is whether it is possible for the woman ts* have received 0.01 ug/kg/day via ingestion plus skin absorption. _ -- ,,; A feature of the case that bothers me is why no TCDD was found in the liver in September and December of 1976* The level should have been higher than that found in the autopsy sample# 5 months later. Xs it possible that the only tissue analyzed was ,the tumor? There is evidence that liver tissue in the fetal or neonate form is unable to concentrate TCDD,. at least in rats. The only other solution seems to be that < the woman incurred much higher exposure after September than between July and September. With respect to your questions on our 3 generation reproduetivstudy, X am sdmewhat confused* Perhaps I do not understand the issue. In the study, an effect was observed in rats receiving 0.01 pg/kg/day but not in those receiving 0.001 ti?/kg- ln the first generation# dilated renal Environmental Research Foundation. 1 4 -Iio v -9 3 1 8 :5 0 page 4 of 4 Dr* Med* Reggiani G January 1978 Page 2 pelvis and a decrease in survivability were discerned in pups of females receiving 0.001' ug/kg/day upon the first mating* H o w e v e r t h e s e were not discerned in pups derived from remating the same females or in subsequent generations Therefore, the observed effects were judged to be random spontaneous o c c u r r e n c e s 'rather than treatment i n d u c e d . ' T o u r reference- to- reserpine was unknown to me. T he decrease in fertility with continued treatment as noted for r e s erpine does not.occur w i t h TCDD*. Indeed, as indicated above females of the first generated were remated. This remating resulted in an. increased fertility compared to controls. W i t h r e s p e c t to ther ^-generation study, a final report has: . been drafted and is in the process of being final typed* -As soon as i t is available/ X w i n send y o u a copy. X h o p e ray rambling has helped resolve some of your problems. However.,- X am n o t sure whether I addressed- .the c r i t i c a l issues*. 1 Respectfully yours, / * * * 1 i P. 1. Behring, p *v.M*, P h*D. Toxicology Research Laboratory Health* and Environmental. Research 1803 Building g