Title: Pharmacokinetics, Metabolite Measurement and Biomarker Identification of Dermal Exposure to Permethrin Using Accelerator Mass Spectrometry (AMS).
Authors: Buchholz, Bruce A; Ahn, KiChang; Huang, Huazhang; Gee, Shirley J; Stewart, Benjamin; Ognibene, Ted J; Hammock, Bruce D
Published In Toxicol Sci, (2021 Jun 21)
Abstract: 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 an 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 post dermal application then rapidly declined reaching predose levels by 72 h. Maximum saliva excretion occurred 6 h post dosing. 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 UPLC-AMS-MS system isolated a distinct polar metabolite but it was much diminished from the previous analyses a decade earlier.
PubMed ID: 34152416
MeSH Terms: No MeSH terms associated with this publication