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USING CHIRALITY TO INFORM THE METABOLISM OF TRIADIMEFON TO TRIADIMENOL: A CROSS-SPECIES EXAMINATION
Citation:
OVERMYER, J. P., J. F. KENNEKE, C. S. MAZUR, J. K. AVANTS, A. W. GARRISON, M. DELORENZO, AND P. KEY. USING CHIRALITY TO INFORM THE METABOLISM OF TRIADIMEFON TO TRIADIMENOL: A CROSS-SPECIES EXAMINATION. Presented at Society for Environmental Toxicology and Chemistry Annual Meeting, Milwaukee, WI, November 11 - 15, 2007.
Impact/Purpose:
To determine the environmental occurrences, fate, and effects of the enantiomers of selected chiral pesticides and other chiral pollutants.
Description:
Triadimefon is a systemic agricultural fungicide of the conazole class whose metabolite, triadimenol, provides the majority of the actual fungicidal activity; i.e. inhibition of steroid demethylation. Triadimenol is also registered and used as a fungicide. Both chemicals are chiral: triadimefon has one chiral center with two enantiomers while its enzymatic reduction to triadimenol produces a second chiral center and four enantiomers (two diastereomers). Our research involves treatment of microsomes prepared from a variety of mammalian, fish and invertebrate species with triadimefon, followed by analysis of the triadimenol metabolites using a chiral BGB-172 column in a GC-MS system. The two triadimefon enantiomers and the four triadimenol enantiomers are separated from each other so that the stereoselectivity of loss of the parent and formation of the metabolite can be observed. In vitro exposure of microsomes from seven species with subsequent chiral analysis shows that the (+)-enantiomer of triadimefon is transformed to triadimenol faster than the (-)-enantiomer in all these microsomes, but that the pattern of stereoselectivity of formation of the latter differs for all species. Since it is known that the diastereomers of triadimenol differ in their toxicities, the resulting biological activity of this metabolite most likely depends on the pattern of stereoisomers formed. Interspecies comparison by chiral analysis may be useful in probing the metabolism of pesticide-exposed organisms as well as improving cross-species extrapolation for risk assessment.