Risk Assessment Department, French Agency for Food, Environmental and Occupational Health & Safety (ANSES), 14 rue Pierre et Marie Curie, Maisons-Alfort F-94701, France.
Department of Environmental and Occupational Health, Chair in Toxicological Risk Assessment and Management, Institute of Research in Public Health, University of Montreal, Roger-Gaudry Building, U424, P.O. Box 6128, Main Station, Montreal, Quebec H3C 3J7, Canada.
Toxicol Appl Pharmacol. 2018 Jul 15;351:21-31. doi: 10.1016/j.taap.2018.05.007. Epub 2018 May 9.
The French Nutrition and Health Survey (ENNS) reported higher biomarker levels of exposure to pyrethroids than those observed in North American and German biomonitoring studies. The authors therefore investigated aggregate exposure to permethrin as an initial case study because this compound is one of the most widely-used pyrethroid insecticides. We assessed several contamination sources-such as indoor and outdoor air, settled dust and diet-and several pathways, including oral, inhalation and dermal routes. We used permethrin exposure level estimations (computed from ENNS data) and a PBPK model calibrated with human kinetic data (from 6 individuals) to simulate an internal dose of cis- and trans-3-(2,2 dichlorovinyl)-2,2-dimethyl-(1-cyclopropane) carboxylic acid (cis- or trans-DCCA) in a population of 219 individuals. The urinary concentrations of cis- and trans -DCCA predicted by the PBPK model according to three permethrin exposure scenarios ("lower", "intermediate", and "upper"), were compared to the urinary levels measured in the ENNS study. The ENNS levels were between the levels simulated according to permethrin exposure scenarios "lower" and "intermediate". The "upper" scenario led to an overestimation of the predicted urinary concentration levels of cis - and trans -DCCA compared to those measured in the ENNS study. The most realistic scenario was the "lower" one (permethrin concentration of left-censored data considered as 0). Using PBPK modeling, we estimated the contribution of each pathway and source to the internal dose. The main route of permethrin exposure was oral (98%), diet being the major source (87%) followed by dust (11%) then the dermal route (1.5%) and finally inhalation (0.5%).
法国营养与健康调查(ENNS)报告称,接触拟除虫菊酯的生物标志物水平高于北美和德国生物监测研究中观察到的水平。因此,作者研究了拟除虫菊酯的总体暴露情况,作为初始案例研究,因为这种化合物是使用最广泛的拟除虫菊酯杀虫剂之一。我们评估了几种污染来源,如室内和室外空气、沉降灰尘和饮食,以及几种途径,包括口服、吸入和皮肤途径。我们使用从 ENNS 数据中计算得出的拟除虫菊酯暴露水平估计值和经过人体动力学数据(来自 6 个人)校准的 PBPK 模型,模拟了 219 个人群中顺式和反式 3-(2,2-二氯乙烯基)-2,2-二甲基-(1-环丙烷)羧酸(顺式或反式-DCCA)的内部剂量。根据三种拟除虫菊酯暴露情景(“低”、“中”和“高”),PBPK 模型预测的顺式和反式-DCCA 尿浓度与 ENNS 研究中测量的尿浓度进行了比较。ENNS 水平介于根据拟除虫菊酯暴露情景“低”和“中”模拟的水平之间。与 ENNS 研究中测量的水平相比,“高”情景导致顺式-DCCA 和反式-DCCA 预测尿浓度水平的高估。最现实的情景是“低”情景(考虑到左删失数据的拟除虫菊酯浓度为 0)。使用 PBPK 模型,我们估计了每种途径和来源对内部剂量的贡献。拟除虫菊酯暴露的主要途径是口服(98%),饮食是主要来源(87%),其次是灰尘(11%),然后是皮肤途径(1.5%),最后是吸入途径(0.5%)。