Toxicokinetics, in vivo metabolic profiling and tissue distribution of chlorfenapyr in mice.

Autor: Zhang S; Department of Emergency Medicine, Institute of Disaster Medicine, Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.; Disaster Medical Center, Sichuan University, Chengdu, 610041, China., Wang X; Department of Emergency Medicine, Institute of Disaster Medicine, Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.; Disaster Medical Center, Sichuan University, Chengdu, 610041, China., Yang X; Department of Emergency Medicine, Institute of Disaster Medicine, Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.; Disaster Medical Center, Sichuan University, Chengdu, 610041, China., Ma Z; Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China., Liu P; Department of Emergency Medicine, Institute of Disaster Medicine, Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.; Disaster Medical Center, Sichuan University, Chengdu, 610041, China., Tang S; Department of Emergency Medicine, Institute of Disaster Medicine, Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.; Disaster Medical Center, Sichuan University, Chengdu, 610041, China., Zhao M; Department of Emergency Medicine, Institute of Disaster Medicine, Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.; Disaster Medical Center, Sichuan University, Chengdu, 610041, China., Chen H; School of Mechanical Engineering, Sichuan University, Chengdu, 610065, China., Qiu Q; Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China., Tang M; Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. tangminghai1982@126.com., Peng A; Department of Emergency Medicine, Institute of Disaster Medicine, Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China. peng_aihua@163.com.; Disaster Medical Center, Sichuan University, Chengdu, 610041, China. peng_aihua@163.com., Cao Y; Department of Emergency Medicine, Institute of Disaster Medicine, Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.; Disaster Medical Center, Sichuan University, Chengdu, 610041, China.
Jazyk: angličtina
Zdroj: Archives of toxicology [Arch Toxicol] 2024 Nov; Vol. 98 (11), pp. 3763-3775. Date of Electronic Publication: 2024 Aug 28.
DOI: 10.1007/s00204-024-03846-8
Abstrakt: Chlorfenapyr is a novel broad-spectrum insecticide derived from natural pyrrole derivatives produced by Streptomyces spp. It acts as a pro-insecticide and is metabolically converted to the active metabolite, tralopyril. Chlorfenapyr poisoning is known for its delayed neurological symptoms and high mortality. Unfortunately, information on the toxicokinetics, metabolism and tissue distribution of chlorfenapyr and tralopyril is still lacking. In this study, the metabolic profile, toxicokinetics and tissue distribution of chlorfenapyr and tralopyril after oral administration at a toxic dose in mice were investigated. Twenty metabolites were identified in plasma, urine and feces, which were mainly formed by dealkylation, oxidative dechlorination and reductive dechlorination. Toxicokinetic results showed that chlorfenapyr was rapidly converted to tralopyril after administration, and the in vivo half-life (t 1/2 ), area under the curve (AUC) and peak concentration (C max ) values of tralopyril were significantly higher than those of chlorfenapyr (P < 0.05). Tissue distribution experiments confirmed that the metabolite tralopyril had a longer half-life, a lower clearance and a wide distribution in different organs and tissues compared to chlorfenapyr. It was also able to cross the blood-brain barrier, suggesting a potential association with brain lesions. In addition, a sensitive and rapid LC-MS/MS analytical method was established for the detection of chlorfenapyr and tralopyril. In conclusion, this study provided valuable metabolic, toxicokinetic and tissue distribution information, contributing to future risk assessment and forensic identification in cases of chlorfenapyr poisoning. We recommend considering the assessment of tralopyril levels, which may be of greater therapeutic importance in the management of chlorfenapyr poisoning.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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