Endocrine-disrupting activity in carbendazim-induced reproductive and developmental toxiclty in rats
Journal
Journal of Toxicology and Environmental Health - Part A
Journal Volume
67
Journal Issue
19
Pages
1501-1515
Date Issued
2004
Abstract
This study was designed to investigate the endocrine-disrupting activity of carbendazim-induced reproductive and developmental toxicity in Sprague-Dawley rats treated orally with the fungicide. Cotreatment of male rats with 675 mg/kg carbendazim and 50 or 100 mg/kg flutamide, an androgen receptor antagonist, once daily for 28 d blocked decrease of testis weight induced by treatment with carbendazim alone. The cotreatment prevented losses of spermatozoa and cell morphology and decrease of sperm concentration induced by carbendazim. Premating treatment of male and female rats with 200 mg/kg carbendazim for 28 d produced androgenic effects including incomplete development of uterine horn, enlargement of uretha, absence of vagina, and induction of seminal vesicles in female offspring, without marked effects in male offspring. Premating treatment with 100 mg/kg benomyl, the parent compound of carbendazim, resulted in incomplete development of uterine horn and absence of vagina in female offspring and produced testis and epidydimis atropy in male offspring. Treatment of male rats with 25, 50, 100, 200, 400, and 800 mg/kg carbendazim for 56 d produced dose-dependent increases of androgen receptor concentrations in testis and epididymis. Additions of 5, 50, and 500 μM carbendazim to testis extract from untreated rats replaced binding of [3H]-5α-dihydrotestosterone to androgen receptor in a concentration-dependent manner. The present study demonstrates that reproductive toxicity induced by carbendazim is blocked by an androgen receptor antagonist in male rats and developmental toxicity of the fungicide shows androgenic properties in female offspring. These results suggest that androgen- and androgen receptor-dependent mechanisms are possibly involved in carbendazim-induced toxicity.
SDGs
Other Subjects
androgen receptor; androstanolone; antiandrogen; benomyl; carbendazim; flutamide; animal cell; animal experiment; animal tissue; article; cell loss; cell structure; concentration response; controlled study; developmental disorder; dose response; drug receptor binding; epididymis disease; female; histopathology; male; nonhuman; priority journal; rat; rat strain; reproductive toxicity; seminal vesicle; spermatozoon; spermatozoon density; testis; testis atrophy; testis weight; urethra disease; uterus horn; vagina aplasia; Abnormalities, Drug-Induced; Androgen Antagonists; Animals; Benomyl; Benzimidazoles; Carbamates; Dose-Response Relationship, Drug; Endocrine System Diseases; Female; Flutamide; Fungicides, Industrial; Genital Diseases, Female; Genital Diseases, Male; Genitalia; Humans; Male; Maternal Exposure; Models, Animal; Paternal Exposure; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Animalia
Type
journal article