Pharmacokinetics, Metabolite Measurement, and Biomarker Identification of Dermal Exposure to Permethrin Using Accelerator Mass Spectrometry.

Autor:	Buchholz BA; Center for Accelerator Mass Spectrometry, Lawrence Livermore National laboratory, Livermore, California 94550, USA., Ahn KC; Department of Entomology, University of California, Davis, California, USA., Huang H; Department of Entomology, University of California, Davis, California, USA., Gee SJ; Department of Entomology, University of California, Davis, California, USA., Stewart BJ; Bioscience and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, California 94550, USA., Ognibene TJ; Center for Accelerator Mass Spectrometry, Lawrence Livermore National laboratory, Livermore, California 94550, USA., Hammock BD; Department of Entomology, University of California, Davis, California, USA.
Jazyk:	angličtina
Zdroj:	Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2021 Aug 30; Vol. 183 (1), pp. 49-59.
DOI:	10.1093/toxsci/kfab082
Abstrakt:	Impregnating military uniforms and outdoor clothing with the insecticide permethrin is an approach to reduce exposure to insect borne diseases and to repel pests and disease vectors such as mosquitos and sandflies, but the practice exposes wearers to prolonged dermal exposure to the pesticide. Key metabolite(s) from a low dose dermal exposure of permethrin were identified using accelerator mass spectrometry. Metabolite standards were synthesized and a high performance liquide chromatography (HPLC) elution protocol to separate individual metabolites in urine was developed. Six human subjects were exposed dermally on the forearm to 25 mg of permethrin containing 1.0 µCi of 14C for 8 h. Blood, saliva and urine samples were taken for 7d. Absorption/elimination rates and metabolite concentrations varied by individual. Average absorption was 0.2% of the dose. Serum concentrations rose until 12-24 h postdermal application then rapidly declined reaching predose levels by 72 h. Maximum saliva excretion occurred 6 h postdosing. The maximum urinary excretion rate occurred during 12-24 h; average elimination half-life was 56 h. 3-Phenoxybenzyl alcohol glucuronide was the most abundant metabolite identified when analyzing elution fractions, but most of the radioactivity was in still more polar fractions suggesting extensive degradative metabolism and for which there were no standards. Analyses of archived urine samples with the ultra performance liquid chromatography-accelerator mass spectrometry-mass spectrometry (UPLC-AMS-MS) system isolated a distinct polar metabolite but it was much diminished from the previous analyses a decade earlier. (Published by Oxford University Press on behalf of the Society of Toxicology 2021. This work is written by US Government employees and is in the public domain in the US.)
Databáze:	MEDLINE
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