Benomyl- or Carbendazim-Induced Androgen Receptor Disrupting Might Lead to Spinal and Bulbar Muscular Atrophy in Multi-Generations of Rats

We have reported that benomyl and its metabolite carbendazim induced reproductive and developmental toxicity and endocrine-disrupting activity in rats. The exactly underlying mechanism of reproductive and developmental toxicity and endocrine-disrupting activity still remain unclear. This manuscript aimed to review and infer the conclusion based on some research, our unpublished data and previous reports. Androgen receptor plays an important role in benomyl- and carbendazim-induced reproductive and developmental toxicity and endocrine-disrupting activity. The evidences were (1) androgen- and androgen receptor-dependent mechanisms are possibly involved in carbendazim-induced toxicity; (2) Our unpublished data showed that the antiandrogen flutamide can completely recover the reproductive and developmental toxicity including embryolethality induced by in utero exposure to benomyl and carbendazim in rats. Based on the previous reports of relationship between androgen receptor expression and spinal and bulbar muscular atrophy (SBMA) or Kennedy's disease, our unpublished data supported this hypothesis by showing carbendazim-induced spinal and bulbar muscular atrophy in Wistar offspring rats. The molecular underlying mechanism of reproductive and developmental toxicity, endocrine-disrupting activity and spinal and bulbar muscular atrophy induced by benomyl and carbendazim through androgen receptor need to be further investigated.