MOLINATE - RODENT REPRODUCTIVE TOXICITY AND ITS RELEVANCE TO HUMANS -A REVIEW

Molinate is a thiocarbamate herbicide used on rice. During the evaluat ion of the compound for regulatory compliance, an adverse effect on ma le reproduction in rats was observed. This Led to extensive investigat ions in rats, mice, rabbits, dogs, monkeys, and humans, resulting in a description of the cause of the effect and establishing an empirical case for rodent specificity. More recent investigations have also show n an effect on the ovaries in rodents. A series of investigations into the mechanism of action to support the view that the effect was speci fic to rodents has been concluded. The results from this investigation are drawn together and show that the mode of action is via a metaboli te, the sulfoxide, which is primarily found in rodents, and that the l esion in both rodent sexes is elicited via inhibition of the enzyme ne utral cholesterol ester hydrolase, resulting in interference with mobi lization of cholesterol from high-density lipoprotein, a path specific to rodents. Thus, the mechanism of action is such that the effect can not be elicited in other species including humans. (C) 1998 Academic P ress.