Molinate: A Metabolic Explanation 95

Molinate: A Metabolic Explanation for Species Differences in Suscepti- bility to Male Reproductive Toxicity-95
Project Leader and Principal UC Investigators Marion G. Miller, professor, Department of Environmental Toxicology, UC Davis Will Jewel, graduate student, Department of Environmental Toxicology, UC Davis Bruce Winder, postgraduate researcher, Department of Environmental Toxicology, UC Davis	The rice herbicide molinate has been shown to cause toxicity in the reproductive organs of male rats. Since rats are often used in risk assessment studies, wouldn't it stand to reason that molinate might pose a similar threat to humans? Environmental toxicologists working on this project think not. Researchers suspect that molinate is metabolized differently in humans and rats. In this study environmental toxicologists sought to identify how different metabolic pathways lead to toxic metabolites forming readily in rats but not in humans. A metabolite of molinate, formed through what researchers call "the sulfoxidation metabolic pathway," has been implicated as the chemical agent responsible for testicular damage. Preliminary in vitro studies of human and rat liver preparations indicate that humans have less ability to form these toxic metabolites and a threefold greater capacity to form nontoxic metabolites. Their research supports the contention that rats are a more susceptible species and humans are relatively insensitive to reproductive toxicity from molinate. The toxicologists say that further work is necessary to make a more quantitative assessment of the relative susceptibility of humans to male reproductive damage.

Molinate: A Metabolic Explanation
for Species Differences in Suscepti-
bility to Male Reproductive Toxicity-95

Project Leader and Principal UC Investigators

Marion G. Miller, professor, Department of Environmental Toxicology, UC Davis

Will Jewel, graduate student, Department of Environmental Toxicology, UC Davis

Bruce Winder, postgraduate researcher, Department of Environmental Toxicology, UC Davis

The rice herbicide molinate has been shown to cause toxicity in the reproductive organs of male rats. Since rats are often used in risk assessment studies, wouldn't it stand to reason that molinate might pose a similar threat to humans? Environmental toxicologists working on this project think not.

Researchers suspect that molinate is metabolized differently in humans and rats. In this study environmental toxicologists sought to identify how different metabolic pathways lead to toxic metabolites forming readily in rats but not in humans.

A metabolite of molinate, formed through what researchers call "the sulfoxidation metabolic pathway," has been implicated as the chemical agent responsible for testicular damage. Preliminary in vitro studies of human and rat liver preparations indicate that humans have less ability to form these toxic metabolites and a threefold greater capacity to form nontoxic metabolites.

Their research supports the contention that rats are a more susceptible species and humans are relatively insensitive to reproductive toxicity from molinate. The toxicologists say that further work is necessary to make a more quantitative assessment of the relative susceptibility of humans to male reproductive damage.