ABSTRACT

The 2018 ATSDR mixture framework recommends three approaches including the hazard index (HI) for environmental mixture toxicity assessment. Per- and polyfluoroalkyls (PFAS) are found in our environment and general populations. Recent experimental mixture toxicity studies of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) and an assessment of 17 PFAS indicate the use of additivity for their joint toxicity assessment. The aim of this investigation was to detail the stepwise procedures and examine the extent and use of the HI approach for PFAS mixture assessment. Using estimated general public lifetime exposures (high, medium, and low), binary mixtures of PFOS and PFOA yielded, respectively, hazard indices (HIs) of 30.67, 8.33, and 3.63 for developmental toxicity; 10.67, 5.04, and 2.34 for immunological toxicity; 3.57, 1.68, and 0.78 for endocrine toxicity; 4.51, 1.73, and 0.79 for hepatic toxicity; and 15.08, 2.29, and 0.88 for reproductive toxicity. A heterogeneous mixture of PFOA, PFAS, dioxin (CDD), and polybrominated compounds (PBDE) for high exposure scenario yielded HIs of 30.99 for developmental, 10.77 for immunological, 3.64 for endocrine, 4.61 for hepatic, and 17.36 for reproductive effects. The HI values are used as a screening tool; the potential concern for exposures rises as HI values increase. For HI values >1, a follow-up including further analysis of specific exposures, use of internal dosimetry, and uncertainty factors is conducted before recommending appropriate actions. The HI approach appears suitable to address present-day PFAS public health concerns for initial assessment of multiple health effects, until further insights are gained into their mechanistic toxicology.

The findings and conclusions in this article are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry.

摘要

2018 年 ATSDR 混合物框架推荐了三种方法，包括用于环境混合物毒性评估的危险指数 (HI)。全氟烷基和多氟烷基 (PFAS) 存在于我们的环境和一般人群中。最近对全氟辛烷磺酸 (PFOS) 和全氟辛酸 (PFOA) 的实验性混合物毒性研究以及对 17 种 PFAS 的评估表明，在它们的联合毒性评估中使用了可加性。这项调查的目的是详细说明逐步程序，并检查 HI 方法在 PFAS 混合物评估中的范围和使用。使用估计的一般公众终生暴露量（高、中和低），全氟辛烷磺酸和全氟辛酸的二元混合物产生的发育毒性危害指数 (HI) 分别为 30.67、8.33 和 3.63；免疫毒性为 10.67、5.04 和 2.34；3.57, 1.68, 内分泌毒性为 0.78；肝毒性为 4.51、1.73 和 0.79；生殖毒性分别为 15.08、2.29 和 0.88。PFOA、PFAS、二恶英 (CDD) 和多溴化合物 (PBDE) 的异质混合物在高暴露情景下产生的 HI 为 30.99 的发育影响、10.77 的免疫影响、3.64 的内分泌影响、4.61 的肝影响和 17.36 的生殖影响。HI 值用作筛选工具；随着 HI 值的增加，对暴露的潜在担忧也会增加。对于 HI 值 >1，在建议采取适当措施之前，将进行后续行动，包括对特定暴露的进一步分析、内部剂量测定的使用和不确定因素。HI 方法似乎适合解决当前 PFAS 公共卫生问题，以初步评估多种健康影响，

本文中的发现和结论是作者的结论，并不一定代表疾病控制和预防中心/有毒物质和疾病登记局的官方立场。