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Benoxacor Is Enantioselectively Metabolized By Rat Liver Subcellular Fractions

preprint
submitted on 08.03.2020 and posted on 09.03.2020 by Derek Simonsen, David M. Cwiertny, Hans-Joachim Lehmler
This study investigated the enantioselective metabolism of benoxacor, an ingredient of herbicide formulations, in rats in vitro. Benoxacor was incubated for ≤ 30 minutes with microsomes or cytosol from female or male rat livers, and its enantioselective depletion was measured using gas chromatographic methods. Benoxacor was depleted in incubations with active microsomes, suggesting its metabolism by hepatic cytochrome P450 enzymes. In the presence of glutathione, benoxacor was also depleted in cytosolic incubations, consistent with its metabolism by glutathione S-transferases. The depletion of benoxacor was faster in incubations with cytosols from male than female rats, whereas no statistically significant sex-differences was observed in microsomal incubations. Microsomal incubations showed an enrichment of the first eluting benoxacor enantiomer (E1-benoxacor). A greater enrichment occurred in incubations with microsomes from female (EF=0.67±0.01) than male rats (EF=0.60±0.01). Cytosolic incubations from female rats resulted in enrichment of E1-benoxacor (EF=0.54±0.01), while cytosolic incubations from male rats displayed enrichment of the second eluting enantiomer (E2-benoxacor; EF=0.43±0.01). Sex-dependent differences in the metabolism of benoxacor in rats could significantly impact ecological risks and mammalian toxicity. Our results also suggest changes in the enantiomeric enrichment of benoxacor may be a powerful tool for source apportionment and environmental fate and transport studies.

Funding

P30 ES005605

CBET-1703796

CBET-1702610

CBET-1335711

CHE-1609791

History

Email Address of Submitting Author

hans-joachim-lehmler@uiowa.edu

Institution

University of Iowa

Country

USA

ORCID For Submitting Author

0000-0001-9163-927X

Declaration of Conflict of Interest

No conflict of interest

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