Letter from the Methyl Bromide Industry Panel to US EPA Submitting Supplemental Information Concerning the 8ehq-1189-0844 s Submission on Methyl Bromide with Attachments

摘要

Methyl bromide (CAS No. 74-83-9) was evaluated for developmental toxicity in 2-part study with artificially inseminated rabbits (26/group) administered whole-body exposures to 0, 20, 40, or 80 ppm for 6 hours/day on gestational days 6-19. The initial trial reported significant maternal toxicity in 80 ppm does, and significant developmental toxicity (fetal malformations) consisting of agenesis of caudal lung lobes and gall bladders, and fused sternebrae. Potential confounding factors in assessing developmental toxicity included hereditary predisposition to malformations via the females or a common source of semen inseminating the 8 females of litters lacking gall bladders. In a second study, groups of 18 pregnant does (not inseminated with suspect semen) were exposed to either 0 or 80 ppm and 18 does (inseminated only with suspect semen) were an unexposed control group. Treatment-related maternal toxicity and reduced fetal bodyweights per litter were not associated with increased percent fetal malformation (fetal skeletal exams were not done) in the 80 ppm group, although incidence of missing gall bladders in 80 ppm fetuses was nearly 5X that in negative controls; the naive control group litters had fewer malformations than either the negative control or 80 ppmgroup litters. The protocol and findings were evaluated and validated by Dr. Rochelle Tyl, Senior Program Director, Reproductive and Developmental Toxicology, Research Triangle Institute. Both the study authors and Dr. Tyl concluded that fetal effects might be attributed to maternal toxicity at 80 ppm, as such fetal effects and maternal toxicity were not observed at lower concentrations. Dr. Tyl additionally provided historical control data regarding fetal fused sternebrae associated with maternal toxicity (irrespective of chemical, route, or dose). A NOAEL for both does and conceptuses was 40 ppm under the conditions of this study, and neither study authors nor reviewer considered the results indicative of developmental toxicity per se.