Identification of potential chemical biomarkers of hexaconazole using in vitro metabolite profiling in rat and human liver microsomes and in vivo confirmation through urinary excretion study in rats

• Published in: Chemosphere (Oxford) Vol. 358; p. 142123
• Main Authors: Yahavi, C., Pandey, Anushka, Bhateria, Manisha, Warkad, Balabhau Vaijinathrao, Trivedi, Ravi Kumar, Singh, Sheelendra Pratap
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2024
• Subjects: Animals; Biological Monitoring; Biomarkers - metabolism; Biomarkers - urine; Biomonitoring; Chemical biomarker; Fungicide; Fungicides, Industrial - metabolism; Fungicides, Industrial - urine; Hexaconazole; Human health risk assessment; Humans; Male; Metabolite profiling; Microsomes, Liver - metabolism; Rats; Rats, Sprague-Dawley; Triazoles - metabolism; Triazoles - urine; Biomonitoring; Hexaconazole; Metabolite profiling; Fungicide; Chemical biomarker; Human health risk assessment
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2024.142123

Hexaconazole (HEX) is an azole fungicide widely used in agricultural practices across various countries and numerous studies have reported the toxic effects of HEX, such as endocrine disruption, immunotoxicity, neurotoxicity and carcinogenicity. Despite its widespread agricultural use and toxic effects, the metabolism of HEX is not completely understood, and information on urinary elimination of HEX or its metabolites is limited. Therefore, in the present study, we aimed to identify HEX metabolites in rat and human liver microsomes followed by their in vivo confirmation using a urinary excretion study in rats to identify potential candidate for exposure biomarkers for human biomonitoring studies. From the in vitro assay, a total of 12 metabolites were observed, where the single oxidation metabolites (M5 and M6) were the most abundant metabolites in both rat and human liver microsomes. The triple oxidation followed by dehydration metabolite, M8 (which could also be hexaconazole acid or hydroxy keto-hexaconazole), and the double oxidation metabolite (M9) were the major metabolites found in rat urine and were detectable in rat urine longer than the parent. These metabolites increased with decreasing concentrations of HEX in the rat urine samples. Therefore, metabolites M8, M9 and M5 could be pursued further as potential biomarkers for assessing and monitoring human exposure to HEX. [Display omitted] •Hexaconazole underwent phase-1 metabolism, oxidation was found to be the major pathway.•A total of 12 metabolites of hexaconazole identified in rat and human liver microsomes using HRMS.•Identified hexaconazole metabolites also confirmed in the rat in vivo urine samples.•The oxidative metabolites (M8.M9 and M5) were suggested as potential chemical biomarkers for hexaconazole.