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Regul Toxicol Pharmacol. 2019 Apr;103:10-20. doi: 10.1016/j.yrtph.2019.01.020. Epub 2019 Jan 8.
Perfluorohexanoic acid (PFHxA) is a short-chain, six-carbon PFAA and is a primary impurity, degradant, and metabolite associated with the short-chain fluorotelomer-based chemistry used in the United States, Europe and Japan today. With the shift towards short-chain PFAA chemistry, uncertainties remain regarding human health risks associated with current exposure levels. Here, we present a critical review and assessment of data relevant to human health risk assessment to today's short-chain PFAA chemistry. Human biomonitoring surveys indicate that PFHxA is infrequently detected in the environment as well as in human serum and urine; however, human health concerns may persist in locations where PFHxA is detected. In a companion paper (Luz et al., 2019) we comprehensively evaluate the available toxicity data for PFHxA, and derive a chronic human health-based reference dose (RfD) for PFHxA of 0.25 mg/kg-day based on benchmark dose modeling of renal papillary necrosis in chronically exposed female rats. In this paper, we apply this RfD in human health-based screening levels calculations, and derive a drinking water lifetime health advisory of 1400 μg/L and a residential groundwater screening level for children of 4000 μg/L. Compared to environmental concentration data, even sites with more elevated concentrations of PFHxA in the environment are at least an order of magnitude lower than these screening levels. Available PFHxA human serum and urine biomonitoring data, used as a biomarker for general population exposure, demonstrates that the general human population exposures to PFHxA are low. Previous estimates of daily intake rates for infants exposed to PFHxA through breast milk, formula, and baby foods (Lorenzo et al., 2016) combined with the most conservative PFHxA peer-reviewed toxicity value (Luz et al., 2019) demonstrate that the margin of safety for PFHxA is high. Therefore, PFHxA and related fluorotelomer precursors currently appear to present negligible human health risk to the general population and are not likely to drive or substantially contribute to risk at sites contaminated with PFAS mixtures. PFHxA may also represent a suitable marker for the safety of fluorotelomer replacement chemistry used today.
全氟己酸（PFHxA）是一种短链六碳全氟羧酸，是当今美国、欧洲和日本使用的短链含氟调聚物化学物质的主要杂质、降解产物和代谢物。随着短链全氟羧酸化学物质的使用，目前接触水平相关的人类健康风险仍存在不确定性。在这里，我们对当今短链全氟羧酸化学物质的人类健康风险评估相关数据进行了批判性评估和审查。人体生物监测调查表明，PFHxA 在环境以及人血清和尿液中很少被检出；然而，在 PFHxA 被检出的地方，人类健康问题可能仍然存在。在一篇相关的论文中（Luz 等人，2019 年），我们全面评估了 PFHxA 的现有毒性数据，并基于慢性暴露雌性大鼠肾乳头坏死的基准剂量建模，得出 PFHxA 的慢性人类健康参考剂量（RfD）为 0.25mg/kg-day。在本文中，我们将该 RfD 应用于基于人类健康的筛查水平计算，并得出终生饮用水健康咨询值为 1400μg/L，儿童居住用地下水筛查水平为 4000μg/L。与环境浓度数据相比，即使在环境中 PFHxA 浓度较高的地方，其浓度也至少低一个数量级。可用的 PFHxA 人血清和尿液生物监测数据可作为一般人群暴露的生物标志物，表明一般人群对 PFHxA 的暴露水平较低。此前对通过母乳、配方奶和婴儿食品暴露于 PFHxA 的婴儿的日摄入量估计值（Lorenzo 等人，2016 年）与最保守的 PFHxA 同行评议毒性值（Luz 等人，2019 年）相结合，表明 PFHxA 的安全裕度很高。因此，PFHxA 及其相关的全氟调聚物前体目前似乎对一般人群没有造成显著的人类健康风险，并且不太可能在含有 PFAS 混合物的污染地点驱动或显著增加风险。PFHxA 也可能是当今使用的全氟调聚物替代化学物质安全性的合适标志物。
