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首页> 外文期刊>Journal of applied toxicology >An assessment of the impact of multi-route co-exposures on human variability in toxicokinetics: A case study with binary and quaternary mixtures of volatile drinking water contaminants
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An assessment of the impact of multi-route co-exposures on human variability in toxicokinetics: A case study with binary and quaternary mixtures of volatile drinking water contaminants

机译：多路线共同曝光对毒性饮水污染物二元和季混合物的影响对人类变异影响的评价

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ABSTRACT: This study aimed to assess the impact of multi-route co-exposures to chemicals on interindividual variability in toxicokinetics. Probabilistic physiologically based pharmacokinetic multi-route interaction models were developed for adults and four younger subpopulations. Drinking water-mediated multi-route exposures were simulated for benzene alone or in co-exposure with toluene, ethylbenzene and m-xylene, for trichloroethylene or vinyl chloride (VC), alone and in mixture. These simulations were performed for “low” and “high” exposure scenarios, involving respectively the US EPA's short-term drinking water health advisories, and 10 times these advisory values. Distributions of relevant internal dose metrics for benzene, trichloroethylene and VC were obtained using Monte Carlo simulations. Intergroup variability indexes (VI) were computed for the “low” (VIL) and “high” (VIH) exposure scenarios, as the ratio between the 95th percentile in each subpopulation over the median in adults. Thus, for benzene, parent compound's area under the curve-based VIL for single exposures vs. co-exposures correspondingly varied between 1.7 (teenagers) and 2.8 (infants) vs. 1.9 and 3.1 respectively. VIH varied between 2.5 and 3.5 vs. 2.9 and 4.1. Inversely, VIL and VIH for the amount of benzene metabolized via CYP2E1 pathway decreased in co-exposure compared to single exposure. For VC and trichloroethylene, similar results were obtained for the “high” exposure, but “low” co-exposures did not impact the toxicokinetics of individual substances. In conclusion, multi-route co-exposures can have an impact on the toxicokinetics of individual substances, but to an extent, that does not seem to challenge the default values attributed to the factors deemed at reflecting interindividual or child/adult differences in toxicokinetics. ? 2019 John Wiley & Sons, Ltd.
机译：摘要：本研究旨在评估多路线共同曝光对毒物动脉内的细胞性变异性的化学品的影响。概率基于生理基础的药代动力学多路线相互作用模型是成人和四个幼稚的群体。单独或用甲苯，乙苯和M-二甲苯，单独和混合物中的三氯乙烯或氯乙烯（VC）模拟苯均匀或与甲苯，乙苯和M-二甲苯的共接暴露的水介导的多路曝光。这些模拟是为“低”和“高”曝光情景进行，涉及美国EPA的短期饮用水健康咨询，以及这些咨询价值的10倍。使用蒙特卡罗模拟获得相关内剂量指标的分布，三氯乙烯和VC获得。对于“低”（VIL）和“高”（vIH）曝光情景计算的依法变异可变性指数（VI），作为成人中位数的每个亚贫民中的第95百分位数之间的比率。因此，对于苯，在基于曲线的VIL下的母体化合物区域，用于单曝光与共曝光相应地变化在1.7（青少年）和2.8（婴儿）与1.9和3.1之间。 VIH在2.5和3.5之间变化，2.9和4.1。与单次暴露相比，通过CYP2E1途径代谢的苯和VIH的苯的量减少。对于VC和三氯乙烯，获得了类似的结果，用于“高”暴露，但“低”共曝光没有影响各种物质的毒物动力学。总之，多路线共同曝光可能对个体物质的毒性学产生影响，但在一定程度上，这似乎并不挑战归因于认为反映毒物动脉内或儿童/成人差异的因素的违约值。还2019 John Wiley＆Sons，Ltd。

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