THE EFFECTS OF PERINATAL JUVENILE METHOXYCHLOR EXPOSURE ON ADULT-RAT NERVOUS, IMMUNE, AND REPRODUCTIVE-SYSTEM FUNCTION/

In order to address data gaps identified by the NAS report Pesticides in the Diets of Infants and Children, a study was performed using meth oxychlor (MXC). Female rats were gavaged with MXC at 0, 5, 50, or 150 mg/kg/day for the week before and the week after birth, whereupon the pups were directly dosed with MXC from postnatal day (pnd) 7. Some dam s were killed pnd7 and milli and plasma were assayed for MXC and metab olites. For one cohort of juveniles, treatment stopped at pnd21; a mod ified functional observational battery was used to assess neurobehavio ral changes. Other cohorts of juveniles were dosed until pnd42 and eva luated for changes to the immune system and for reproductive toxicity. Dose-dependent amounts of MXC and metabolites were present in milk an d plasma of darns and pups. The high dose of MXC reduced litter size b y approximate to 17%. Ano-genital distance was unchanged, although vag inal opening was accelerated in all treated groups, and male prepuce s eparation was delayed at the middle and high doses by 8 and 34 days, r espectively. In the neurobehavioral evaluation, high-dose males were m ore excitable, but other changes were inconsistent and insubstantial. A decrease in the antibody plaque-forming cell response was seen in ma les only. Adult estrous cyclicity was disrupted at 50 and 150MXC, dose s which also showed reduced rates of pregnancy and delivery. Uterine w eights (corrected for pregnancy) were reduced in all treated pregnant females. High-dose males impregnated fewer untreated females; epididym al sperm count and testis weight were reduced at the high, or top two, doses, respectively. All groups of treated females showed uterine dys plasias and less mammary alveolar development; estrous levels of folli cle stimulating hormone were lower in all treated groups, and estrus p rogesterone levels were lower at 50 and 150 MXC, attributed to fewer c orpora lutea secondary to ovulation defects. These data collectively s how that the primary adult effects of early exposure to MXC are reprod uctive, show that 5 mg/kg/day is not a NO(A)EL in rats with this expos ure paradigm (based on changes in day of vaginal opening, pubertal ova ry weights, adult uterine and seminal vesicle weights, and female horm one data) and imply that the sites of action are both central and peri pheral. (C) 1997 Society of Toxicology.