ENDOCRINE-DISRUPTING ACTIVITY IN CARBENDAZIM-INDUCED REPRODUCTIVE AND DEVELOPMENTAL TOXICITY IN RATS

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 675mg/kg carbendazim and 50 or 100mg/kg flutamide, an androgen receptor antagonist, once daily for 28d 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 200mg/kg carbendazim for 28d 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 100mg/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 800mg/kg carbendazim for 56d produced dose-dependent increases of androgen receptor concentrations in testis and epididymis. Additions of 5, 50, and 500μM 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.

This study was supported in part by a grant (92AS-1.2.1-FD-Z1, T.-H. Ueng) from the Council of Agriculture, Executive Yuan, Republic of China.