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.
Arch Toxicol. 2024 Nov;98(11):3763-3775. doi: 10.1007/s00204-024-03846-8. Epub 2024 Aug 28.
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), area under the curve (AUC) and peak concentration (C) 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.
氯氟吡氧乙酸是一种新型的广谱杀虫剂，来源于链霉菌属产生的天然吡咯衍生物。它作为一种前体杀虫剂，经代谢转化为活性代谢物，三氯吡氧乙酸。氯氟吡氧乙酸中毒以其迟发性神经症状和高死亡率而闻名。不幸的是，关于氯氟吡氧乙酸和三氯吡氧乙酸的毒代动力学、代谢和组织分布的信息仍然缺乏。在这项研究中，我们研究了在小鼠中毒剂量口服给予氯氟吡氧乙酸和三氯吡氧乙酸后的代谢谱、毒代动力学和组织分布。在血浆、尿液和粪便中鉴定出 20 种代谢物，主要通过脱烷基化、氧化脱氯和还原脱氯形成。毒代动力学结果表明，氯氟吡氧乙酸给药后迅速转化为三氯吡氧乙酸，三氯吡氧乙酸的体内半衰期（t）、曲线下面积（AUC）和峰浓度（C）值明显高于氯氟吡氧乙酸（P < 0.05）。组织分布实验证实，与氯氟吡氧乙酸相比，代谢物三氯吡氧乙酸半衰期更长，清除率更低，在不同器官和组织中的分布更广。它还能够穿过血脑屏障，这表明它可能与脑损伤有关。此外，还建立了一种灵敏、快速的 LC-MS/MS 分析方法，用于检测氯氟吡氧乙酸和三氯吡氧乙酸。总之，本研究提供了有价值的代谢、毒代动力学和组织分布信息，有助于今后对氯氟吡氧乙酸中毒的风险评估和法医鉴定。我们建议考虑评估三氯吡氧乙酸的水平，这可能在氯氟吡氧乙酸中毒的治疗中更为重要。
