Department of Environmental and Occupational Health, Chair in Toxicological Risk Assessment and Management, and Public Health Research Center (CReSP), University of Montreal, Montreal, Quebec, Canada.
PLoS One. 2024 Oct 23;19(10):e0309803. doi: 10.1371/journal.pone.0309803. eCollection 2024.
A toxicokinetic model of the pyrethroid insecticide lambda-cyhalothrin (LCT) was developed to relate absorbed doses to urinary cis-3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (CFMP) metabolite levels used as a biomarker of exposure. The model then served to reconstruct absorbed doses in agricultural workers and their probability of exceeding the EFSA Acceptable occupational Exposure Level (AOEL). The toxicokinetic model was able to reproduce the temporal profiles of CFMP in the urine of operators spraying pesticides using the optimized model parameters (adjusted to human volunteer data). Modeling also showed that simulation of an inadvertent oral exposure mainly was the exposure scenario giving the best fit to CFMP urinary time-course data in applicators. With the dermal model parameters optimized from data in volunteers, simulation of a dermal exposure in applicators did not allow to reproduce the observed peak excretions and urinary metabolite levels; extremely high applied dermal doses would be required but still simulated dermal penetration rate would remain too slow. Simulation of an inhalation exposure allowed to reproduce the observed time-courses, but with unrealistic air concentrations. For applicators with the highest urinary concentrations, there was a probability of exceeding the AOEL at some points during the biomonitoring period [>50% probability of exceeding for 27% of 24-h samples]; for non-applicator workers the probability of exceeding the AOEL value was very low [corresponding value of 5%]. Furthermore, the median [95% CI] estimates of 10 000 Monte Carlo simulations led to a biological reference value corresponding to the AOEL of 116 [113-119] ng/kg bw/d and 7.5 [7.3-7.7] μg/L. Overall, 7% of applicators and 1% of workers performing weeding and strawberry picking had a probability of exceeding this biological reference value. As a next step, it would be interesting to apply these methods to multiple exposure to various contaminants.
建立了拟除虫菊酯杀虫剂氯氟氰菊酯（LCT）的毒代动力学模型，以将吸收剂量与用作暴露生物标志物的尿中环丙烷羧酸顺-3-（2-氯-3,3,3-三氟-1-丙烯-1-基）-2,2-二甲基（CFMP）代谢物水平相关联。该模型随后用于重建农业工人的吸收剂量及其超过 EFSA 可接受职业暴露水平（AOEL）的可能性。毒代动力学模型能够重现使用优化模型参数（调整至人类志愿者数据）对喷洒农药的操作人员尿液中 CFMP 的时间曲线。建模还表明，在施药者中，模拟意外口服暴露主要是与 CFMP 尿液时间过程数据拟合最好的暴露情况。使用从志愿者数据中优化的皮肤模型参数，在施药者中模拟皮肤暴露无法再现观察到的峰排泄和尿代谢物水平；需要极高的应用皮肤剂量，但模拟的皮肤穿透率仍然太慢。模拟吸入暴露可以再现观察到的时间过程，但空气浓度不切实际。对于尿液浓度最高的施药者，在生物监测期间某些点超过 AOEL 的可能性很大[24 小时样本中 27%的可能性超过 AOEL>50%]；对于非施药者工人，超过 AOEL 值的可能性非常低[相应值为 5%]。此外，10000 次蒙特卡罗模拟的中位数[95%CI]估计值导致与 AOEL 对应的生物参考值为 116[113-119]ng/kg bw/d 和 7.5[7.3-7.7]μg/L。总体而言，7%的施药者和 1%从事除草和草莓采摘的工人有超过该生物参考值的可能性。下一步将有趣的是将这些方法应用于对多种污染物的多重暴露。
