Role of metabolism in testicular toxicity of molinate (Ordram) in male rats.
Toxicologist 1996 Mar; 30(1)(Part 2):53
Molinate is a thiocarbamate herbicide widely used in rice culture. Studies conducted for regulatory purposes have indicated that molinate exposure results in reproductive damage in male rats. The present study investigated the hypothesis that a metabolite of molinate causes testicular toxicity. A single dose acute model of molinate toxicity was established. Molinate was administered to Sprague-Dawley rats (100-400 mg/kg, ip) and testes were evaluated histopathologically at 48hrs, 1 and 3 weeks after administration. Dose-response relationships were observed in testicular histopathological endpoints with vacuolization, atrophy and multinucleated giant cells being seen. The lesion increased markedly with time until, at three weeks, germ cells in the seminiferous tubules were almost completely absent. When molinate sulfoxide was administered, it was a more potent testicular toxicant than the parent compound. HPLC analysis, of in vitro rat liver microsomal metabolism indicates sulfoxidation as the primary metabolic pathway. Interestingly, human epidemiological studies have shown no adverse effects after molinate exposure. Further analysis will compare rat and human liver microsomal metabolic capabilities and will determine whether metabolic differences can offer an explanation for species differences in susceptibility to molinate's testicular toxicity.
Metabolism; Testes; Laboratory-animals; Animals; Animal-studies; Herbicides; Exposure-levels; Exposure-assessment; Reproductive-system-disorders; Reproductive-hazards; Models; Toxins; Toxic-effects; Dose-response
The Toxicologist. Society of Toxicology 35th Annual Meeting, March 10-14,1996, Anaheim, California
University of California - Davis