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.
Hellwig
J
J
Department of Product Safety Regulations, Toxicology and Ecology, BASF, Ludwigshafen, 67056, Germany.
van Ravenzwaay
B
B
Mayer
M
M
Gembardt
C
C
D000284:Administration, Oral; D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D020567:Fetal Weight / Q000187:drug effects; D005659:Fungicides, Industrial / Q000633:toxicity*; D005837:Genitalia, Male / Q000187:drug effects / Q000473:pathology; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D010080:Oxazoles / Q000009:adverse effects / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013045:Species Specificity; D018675:Toxicity Tests
D000726:Androgen Antagonists; D005659:Fungicides, Industrial; D010080:Oxazoles; C025643:vinclozolin