Ratelle Mylène, Côté Jonathan, Bouchard Michèle
Department of Environmental and Occupational Health, Chair in Toxicological Risk Assessment and Management, and University of Montreal Public Health Research Institute (IRSPUM), University of Montreal, Roger-Gaudry Building, U424, P.O. Box 6128, Main Station, Montreal, Quebec H3C 3J7, Canada.
Department of Environmental and Occupational Health, Chair in Toxicological Risk Assessment and Management, and University of Montreal Public Health Research Institute (IRSPUM), University of Montreal, Roger-Gaudry Building, U424, P.O. Box 6128, Main Station, Montreal, Quebec H3C 3J7, Canada.
Toxicol Lett. 2015 Jan 22;232(2):369-75. doi: 10.1016/j.toxlet.2014.12.003. Epub 2014 Dec 8.
Permethrin is a widely used pyrethroid insecticide for which the toxicokinetics of exposure biomarkers in humans is not fully documented. The time courses of key biomarkers of permethrin exposure were thus assessed in accessible biological matrices of orally exposed volunteers. Six volunteers ingested 0.1 mg/kg body weight of permethrin (60:40 trans/cis). Blood samples were withdrawn at fixed periods over 72 h following ingestion and complete timed-urine voids were collected over 84 h post-dosing. Cis-and trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropane-1-carboxylic acids (cis-and trans-DCCA) and 3-phenoxybenzoic acid (3-PBA) were quantified in samples. In plasma, peak concentrations of cis-DCCA, trans-DCCA and 3-PBA were reached about ≈7 h post-dosing, and elimination appeared monophasic with a mean apparent elimination half-life (t½) of 6.2, 7.1 and 6.5 h, respectively. In urine, elimination rate time courses of cis-DCCA, trans-DCCA and 3-PBA evolved in parallel with plasma, with respective mean apparent elimination t½ of 4.5, 5.4 and 5.7 h. Over the 84 h period post-treatment, 43-46% of administered molar dose were excreted in urine as trans-DCCA (molar % of trans-permethrin) and 3-PBA. Results show similarities in the different metabolite profiles and a rapid equilibrium between urine and plasma levels; data should help interpret the significance of biological measurements and optimal sampling strategies.
氯菊酯是一种广泛使用的拟除虫菊酯类杀虫剂，其在人体中暴露生物标志物的毒代动力学尚未得到充分记录。因此，在口服暴露志愿者易于获取的生物基质中评估了氯菊酯暴露关键生物标志物的时间进程。六名志愿者摄入了0.1 mg/kg体重的氯菊酯（反式/顺式比例为60:40）。摄入后72小时内定期采集血样，并在给药后84小时内收集完整的定时尿液。对样品中的顺式和反式-3-(2,2-二氯乙烯基)-2,2-二甲基环丙烷-1-羧酸（顺式和反式-DCCA）以及3-苯氧基苯甲酸（3-PBA）进行定量。在血浆中，顺式-DCCA、反式-DCCA和3-PBA的峰值浓度在给药后约7小时达到，消除呈单相，平均表观消除半衰期（t½）分别为6.2、7.1和6.5小时。在尿液中，顺式-DCCA、反式-DCCA和3-PBA的消除速率时间进程与血浆平行，平均表观消除t½分别为4.5、5.4和5.7小时。在治疗后的84小时内，43%-46%的给药摩尔剂量以反式-DCCA（反式氯菊酯的摩尔百分比）和3-PBA的形式经尿液排出。结果显示不同代谢物谱具有相似性，且尿液和血浆水平之间存在快速平衡；这些数据应有助于解释生物测量的意义和最佳采样策略。
