Pre- and Postnatal Oral Toxicity of Vinclozolin in Wistar and Long–Evans Rats

Vinclozolin administered to pregnant Wistar and Long–Evans rats from day 14 postcoitum to day 3 postpartum at 200 mg/kg body wt/day was maternally toxic (reduced food consumption and body weight gain) and increased perinatal mortality; major adverse effects on sex-specific organs in male offspring were seen (reduced anogenital distance and index; persistence of nipples/areolas into adulthood; hypospadic penis; penile hypoplasia or development of a vaginal pouch; transient paraphimosis; hypoplasia and chronic inflammation of epididymides, prostate, seminal vesicles, and coagulating glands; and also testicular tubular atrophy and chronic inflammation of the urinary bladder in some Long–Evans) with isolated inflammation-related deaths due to pyelonephritis. At 12 mg/kg, prevalence of female areola/nipple anlagen in immature (preweaning) male offspring was increased in both strains; these persisted to adulthood in a few treated Long–Evans but not Wistar offspring. Adult Long–Evans but not Wistar at this dose also had hypoplasia of prostate, seminal vesicles, and coagulating glands, and a minority had testicular tubular atrophy. The no-observed-adverse-effect levels (NOAEL) were 12 and 6 mg/kg body wt in Wistar and Long–Evans rats, respectively, in these studies. The data suggest that both the Long–Evans and the Wistar rats are comparably sensitive to the antiandrogenic effects of vinclozolin. At dose levels below the NOAEL (1 and 3 mg/kg, respectively), there were no indications of any test-substance-related effects.