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

IF 4.8 2区 医学 Q1 TOXICOLOGY Archives of Toxicology Pub Date : 2024-08-28 DOI:10.1007/s00204-024-03846-8
Shunjie Zhang, Xin wang, Xia yang, Ziyang Ma, Peng Liu, Shiyuan Tang, Min Zhao, Haijun Chen, Qiang Qiu, Minghai Tang, Aihua Peng, Yu Cao
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Abstract

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 (t1/2), area under the curve (AUC) and peak concentration (Cmax) 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.

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氯虫苯甲酰胺在小鼠体内的毒代动力学、体内代谢分析和组织分布。
Chlorfenapyr 是一种新型广谱杀虫剂,源自链霉菌属(Streptomyces spp)产生的天然吡咯衍生物。氯虫苯甲酰胺中毒以其迟发性神经症状和高死亡率而闻名。遗憾的是,有关氯虫苯甲酰胺和 tralopyril 的毒代动力学、新陈代谢和组织分布的信息仍然缺乏。本研究调查了小鼠口服毒性剂量的氯虫苯甲酰胺和 tralopyril 的代谢概况、毒物动力学和组织分布。在血浆、尿液和粪便中发现了 20 种代谢物,主要由脱烷基、氧化脱氯和还原脱氯形成。毒代动力学结果表明,氯虫苯甲酰胺在给药后会迅速转化为曲唑草胺,曲唑草胺的体内半衰期(t1/2)、曲线下面积(AUC)和峰浓度(Cmax)值明显高于氯虫苯甲酰胺(P<0.05)。
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来源期刊
Archives of Toxicology
Archives of Toxicology 医学-毒理学
CiteScore
11.60
自引率
4.90%
发文量
218
审稿时长
1.5 months
期刊介绍: Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.
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