Variability and epistemic uncertainty in water ingestion rates and pharmacokinetic parameters, and impact on the association between perfluorooctanoate and preeclampsia in the C8 Health Project population.
Variability and epistemic uncertainty in water ingestion rates and pharmacokinetic parameters, and impact on the association between perfluorooctanoate and preeclampsia in the C8 Health Project population.
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DOI：
10.1016/j.envres.2016.01.011
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发表时间：
2016-04
影响因子：
8.3
通讯作者：
Bartell SM
中科院分区：
文献类型：
--
作者：
Avanasi R;Shin HM;Vieira VM;Bartell SM
我们最近利用一套环境命运和运输模型以及综合暴露和药代动力学模型来估计个体全氟辛酸 (PFOA) 血清浓度，并评估了 C8 健康项目（一项横断面研究，对位于西弗吉尼亚州的美国主要含氟聚合物生产设施附近环境中暴露于 PFOA 的 69,000 多人）参与者的这些浓度与先兆子痫的关联。然而，该集成模型的暴露估计依赖于关键独立暴露参数的默认值，包括水摄入率、血清 PFOA 半衰期和 PFOA 分布体积。本研究的目的是评估这些参数的个体差异和认知不确定性对暴露估计的影响，以及随后的 PFOA 暴露与先兆子痫之间的流行病学关联。我们使用蒙特卡罗模拟来传播暴露评估中的个体间变异性/认知不确定性，并重新分析流行病学关联。这些参数的个体间变异对血清 PFOA 浓度预测有轻微影响（我们研究中估计血清浓度与原始预测血清浓度之间的最低平均等级相关性为 0.95），并且对与先兆子痫的流行病学关联的影响可以忽略不计（平均调整比值比 (AOR) 没有变化，暴露不确定性对总不确定性的贡献（包括采样变异性）为 7%）。然而，当认知不确定性与个体间变异一起添加时，血清 PFOA 浓度预测及其与先兆子痫的关联受到中度影响（先兆子痫发生的平均 AOR 从 1.12 降低至 1.09，暴露不确定性对总不确定性的贡献增加至 33%）。总之，我们的研究表明，由于独立暴露参数的变异性和认知不确定性，研究参与者的排名暴露变化足够大，足以导致 25% 的零偏差。这表明该人群中 PFOA 与先兆子痫之间关联的真实 AOR 可能高于最初报告的 AOR，并且比最初报告的置信区间具有更多的不确定性。
We recently utilized a suite of environmental fate and transport models and an integrated exposure and pharmacokinetic model to estimate individual perfluorooctanoate (PFOA) serum concentrations, and also assessed the association of those concentrations with preeclampsia for participants in the C8 Health Project (a cross-sectional study of over 69,000 people who were environmentally exposed to PFOA near a major U.S. fluoropolymer production facility located in West Virginia). However, the exposure estimates from this integrated model relied on default values for key independent exposure parameters including water ingestion rates, the serum PFOA half-life, and the volume of distribution for PFOA. The aim of the present study is to assess the impact of inter-individual variability and epistemic uncertainty in these parameters on the exposure estimates and subsequently, the epidemiological association between PFOA exposure and preeclampsia. We used Monte Carlo simulation to propagate inter-individual variability/epistemic uncertainty in the exposure assessment and reanalyzed the epidemiological association. Inter-individual variability in these parameters mildly impacted the serum PFOA concentration predictions (the lowest mean rank correlation between the estimated serum concentrations in our study and the original predicted serum concentrations was 0.95) and there was a negligible impact on the epidemiological association with preeclampsia (no change in the mean adjusted odds ratio (AOR) and the contribution of exposure uncertainty to the total uncertainty including sampling variability was 7%). However, when epistemic uncertainty was added along with the inter-individual variability, serum PFOA concentration predictions and their association with preeclampsia were moderately impacted (the mean AOR of preeclampsia occurrence was reduced from 1.12 to 1.09, and the contribution of exposure uncertainty to the total uncertainty was increased up to 33%). In conclusion, our study shows that the change of the rank exposure among the study participants due to variability and epistemic uncertainty in the independent exposure parameters was large enough to cause a 25% bias towards the null. This suggests that the true AOR of the association between PFOA and preeclampsia in this population might be higher than the originally reported AOR and has more uncertainty than indicated by the originally reported confidence interval.