Abstract：
Per- and polyfluoroalkyl substances (PFAS) are a large group of synthetic surfactants of over 12,000 compounds that are incorporated into numerous products for their chemical and physical properties. Studies have associated PFAS with adverse health effects. Although there is a high potential for dermal exposure, these studies are lacking. The present study evaluated the systemic and immunotoxicity of subchronic 28- or 10-days of dermal exposure, respectively, to PFHpS (0.3125-2.5% or 7.82-62.5 mg/kg/dose) or PFOS (0.5% or 12.5 mg/kg/dose) in a murine model. Elevated levels of PFHpS were detected in the serum and urine, suggesting that absorption is occurring through the dermal route. PFHpS induced significantly increased relative liver weight, significantly decreased relative spleen and thymus weight, altered serum chemistries, and altered histopathology. Additionally, PFHpS significantly reduced the humoral immune response and altered immune subsets in the spleen, suggesting immunosuppression. Gene expression changes were observed in the liver, skin, and spleen of genes involved in fatty acid metabolism, necrosis, and inflammation. Immune-cell phenotyping identified significant decreases in B-cells and CD11b+ monocyte and/or macrophages in the spleen along with decreases in eosinophils and dendritic cells in the skin. These findings support PFHpS absorption through the skin leading to liver damage and immune suppression.
摘要：
全氟烷基和多氟烷基物质(PFAS)是一大组超过12,000种化合物的合成表面活性剂,其由于其化学和物理性质而被掺入到许多产品中。研究已经将PFAS与不良健康影响相关联。尽管皮肤暴露的可能性很高，这些研究是缺乏的。本研究评估了亚慢性28天或10天皮肤暴露的全身和免疫毒性，分别,小鼠模型中的PFHpS（0.3125-2.5％或7.82-62.5mg/kg/剂）或PFOS（0.5％或12.5mg/kg/剂）。在血清和尿液中检测到PFHpS水平升高，这表明吸收是通过皮肤途径进行的。PFHpS诱导的相对肝脏重量显著增加，显著降低相对脾脏和胸腺重量，改变血清化学，改变了组织病理学.此外,PFHpS显著降低体液免疫应答，改变脾脏中的免疫亚群，提示免疫抑制。在肝脏中观察到基因表达变化，皮肤,和脾脏的基因参与脂肪酸代谢，坏死,和炎症。免疫细胞表型鉴定了脾脏中B细胞和CD11b单核细胞和/或巨噬细胞的显着减少，以及皮肤中嗜酸性粒细胞和树突状细胞的减少。这些发现支持PFHpS通过皮肤吸收导致肝损伤和免疫抑制。
