Benoxacor is enantioselectively metabolized by microsomes and cytosol from the human liver

Derek Simonsen; Jacob Heffelfinger; David M. Cwiertny; Hans-Joachim Lehmler

doi:10.1016/j.emcon.2022.100198

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Benoxacor is enantioselectively metabolized by microsomes and cytosol from the human liver

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Benoxacor is enantioselectively metabolized by microsomes and cytosol from the human liver

Derek Simonsen, Jacob Heffelfinger, David M. Cwiertny and Hans-Joachim Lehmler

Emerging Contaminants, Vol.9(1), p.100198

03/2023

DOI: 10.1016/j.emcon.2022.100198

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Abstract

Benoxacor is a safener added to current-use herbicide formulations to protect the target crop from herbicidal toxicity. It is an emerging environmental contaminant that has been detected in surface waters, raising the possibility of human exposure via drinking water. Because it is not subject to the same regulations as active pesticide ingredients, its metabolism and toxicity in humans have not been studied. Here we investigate the enantioselective metabolism of benoxacor in human subcellular fractions. Pooled human liver microsomes (pHLM) and cytosol (pHLC) were incubated with racemic benoxacor for up to 30-min. Gas chromatographic analyses were used to measure the enantioselective depletion of benoxacor. pHLMs with and without nicotinamide adenine dinucleotide phosphate (NADPH, co-factor for cytochrome P450 enzymes [CYPs]) and pHLC with glutathione (GSH, co-factor for glutathione S-transferases [GSTs]) metabolized benoxacor. These results demonstrate that microsomal CYPs, microsomal carboxylesterase (CESs), and cytosolic GSTs metabolize benoxacor. Females were predicted to have a higher clearance of benoxacor by GSTs than males. Male and female pHLM incubations with NADPH showed enrichment of the first eluting benoxacor enantiomer (E1-benoxacor). pHLM incubations without NADPH and pHLC incubations with GSH showed an enrichment of the second eluting enantiomer of benoxacor (E2-benoxacor). Our results indicate that human hepatic microsomal and cytosolic enzymes enantioselectively metabolize benoxacor, a fact that needs to be considered when investigating human exposures and toxicities of benoxacor.

Details

Title: Subtitle: Benoxacor is enantioselectively metabolized by microsomes and cytosol from the human liver
Creators: Derek Simonsen - University of Iowa
Jacob Heffelfinger - Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA, 52242, United States
David M. Cwiertny - University of Iowa
Hans-Joachim Lehmler - Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA, 52242, United States
Resource Type: Journal article
Publication Details: Emerging Contaminants, Vol.9(1), p.100198
DOI: 10.1016/j.emcon.2022.100198
ISSN: 2405-6650
Publisher: Elsevier B.V
Grant note: DOI: 10.13039/100000001, name: National Science Foundation, award: CBET-1335711, CBET-1702610, CBET-1703796, CHE-1609791; DOI: 10.13039/100000002, name: National Institutes of Health; DOI: 10.13039/100000066, name: National Institute of Environmental Health Sciences, award: P30 ES005605
Language: English
Date published: 03/2023
Academic Unit: Center for Health Effects of Environmental Contamination; Civil and Environmental Engineering; Occupational and Environmental Health; Iowa Neuroscience Institute; Public Policy Center (Archive); Chemistry; Chemical and Biochemical Engineering
Record Identifier: 9984345338102771

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