Molinate Research - 97


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Project Leader and Principal UC Investigators

Marion G. Miller Associate Professor - Department of Environmental Toxicology, UC Davis

Will Jewell - Graduate Student, Department of Environmental Toxicology UC Davis

Bruce Winder - Postgraduate Researcher Department of Environmental Toxicology, UC Davis


Environmental toxicologists continued a third year of research into the rice herbicide molinate (Ordram®). Because this important chemical has been shown to cause toxicity in the reproductive organs of male rats, there has been some concern about its potential to affect humans. As researchers learn more about differences in the "metabolic pathways' in humans and rats, however, these scientists are allaying some of those concerns.

In previous work toxicologists determined that humans and rats metabolize molinate differently. What causes toxicity in rats is a toxic sulfoxide byproduct or "metabolite" of molinate. Research has shown that humans have less ability to form this toxic metabolite and a much greater capacity to form nontoxic metabolites.

Researchers had also previously determined that metabolic activation takes place in the liver. Additional in vivo studies in 1997 have led researchers to believe that some of this activation is also taking place in the testis of rats. Observations also suggest that the blood plays an important role in transporting the toxic sulfoxide compound to the testis. In vitro studies last year compared the capacity of human and rat liver slices to metabolize molinate through nontoxic and detoxification pathways, as well as the toxic pathway. This research showed that human livers have five times the ability to metabolize molinate through nontoxic pathways as rats. Toxicologist also confirmed previous observations that the human liver is less capable of forming the toxic sulfoxide metabolite.

Toxicologists also identified a protein found in both liver and testis that is influenced by molinate and suggest further research to develop a better understanding of biological thresholds. Toxicologists stress the importance of an understanding of both the metabolic parameters and the mechanisms leading to toxicity to best estimate the risk posed to humans.

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