Toxicology Directorate, Defense Centers for Public Health - Aberdeen, Aberdeen Proving Ground, 5158 Blackhawk Road, MD 21010, USA.
Toxicology Directorate, Defense Centers for Public Health - Aberdeen, Aberdeen Proving Ground, 5158 Blackhawk Road, MD 21010, USA.
Reprod Toxicol. 2023 Sep;120:108421. doi: 10.1016/j.reprotox.2023.108421. Epub 2023 Jun 15.
Although perfluorohexane sulfonate (PFHxS) is structurally similar to perfluorooctane sulfonate (PFOS) and also widely detected in humans and the environment, comparatively fewer toxicity data exists on this 6-chain perfluoroalkyl sulfonic acid. In this study, repeated oral doses of PFHxS were administered to deer mice (Peromyscus maniculatus) to evaluate subchronic toxicity and potential effects on reproduction and development. Maternal oral exposure to PFHxS caused increased stillbirths, which is relevant for ecological risk assessment, and resulted in a benchmark dose lower limit (BMDL) of 5.72 mg/kg-d PFHxS. Decreased plaque formation, which is relevant for human health risk assessment, occurred in both sexes of adult animals (BMDL = 8.79 mg/kg-d PFHxS). These data are the first to suggest a direct link between PFHxS and decreased functional immunity in an animal model. Additionally, female animals exhibited increased liver:body weight and animals of both sexes exhibited decreased serum thyroxine (T4) levels. Notably, since reproductive effects were used to support 2016 draft health advisories and immune effects were used in 2022 drinking water health advisories released by the United States Environmental Protection Agency for PFOS and perfluorooctanoic acid (PFOA), these novel data can potentially support advisories for PFHxS because relevant points of departure emerge at similar thresholds in a wild mammal and corroborate the general understanding of per- and polyfluoroalkyl substances (PFAS).
虽然全氟己烷磺酸（PFHxS）在结构上与全氟辛烷磺酸（PFOS）相似，并且也在人类和环境中广泛检测到，但关于这种 6 链全氟烷磺酸的毒性数据相对较少。在这项研究中，给鹿鼠（Peromyscus maniculatus）反复口服 PFHxS 剂量，以评估其亚慢性毒性以及对生殖和发育的潜在影响。母体口服 PFHxS 暴露会导致死产增加，这与生态风险评估有关，并得出 PFHxS 的基准剂量下限（BMDL）为 5.72mg/kg-d。成年动物的雌雄两性均出现斑块形成减少（这与人类健康风险评估有关），BMDL 值为 8.79mg/kg-d PFHxS。这些数据首次表明 PFHxS 与动物模型中功能性免疫下降之间存在直接联系。此外，雌性动物的肝体比增加，并且雌雄动物的血清甲状腺素（T4）水平降低。值得注意的是，由于生殖效应被用于支持 2016 年的健康建议草案，免疫效应被用于 2022 年美国环境保护署发布的针对 PFOS 和全氟辛酸（PFOA）的饮用水健康建议，这些新数据可能支持 PFHxS 的建议，因为在野生哺乳动物中，相关的起点出现在类似的阈值，并且与对全氟和多氟烷基物质（PFAS）的一般理解相一致。
