Pre- and postnatal oral toxicity of vinclozolin in Wistar and Long-Evans rats.

Abstract

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.

• Authors: J Hellwig, B van Ravenzwaay, M Mayer, C Gembardt
• Journal: Regulatory toxicology and pharmacology : RTP (Regul Toxicol Pharmacol) Vol. 32 Issue 1 Pg. 42-50 (Aug 2000) ISSN: 0273-2300 [Print] Netherlands
• PMID: 11029267 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright 2000 Academic Press.

Chemical References

• Androgen Antagonists
• Fungicides, Industrial
• Oxazoles
• vinclozolin

Topics

• Administration, Oral
• Androgen Antagonists (toxicity)
• Animals
• Animals, Newborn
• Female
• Fetal Death (chemically induced)
• Fetal Weight (drug effects)
• Fungicides, Industrial (toxicity)
• Genitalia, Male (drug effects, pathology)
• Male
• No-Observed-Adverse-Effect Level
• Organ Size (drug effects)
• Oxazoles (adverse effects, toxicity)
• Pregnancy
• Prenatal Exposure Delayed Effects
• Rats
• Rats, Long-Evans
• Rats, Sprague-Dawley
• Sex Characteristics
• Species Specificity
• Toxicity Tests