Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, USA.
Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, USA.
Food Chem Toxicol. 2020 Feb;136:111114. doi: 10.1016/j.fct.2020.111114. Epub 2020 Jan 3.
Perfluorooctanoic acid (PFOA) is a per- and polyfluoroalkyl substance (PFAS) once used as a surfactant in the polymerization of chemicals. Because of its ubiquitous nature and long half-life, PFOA is commonly detected in the environment, wildlife, and humans. While skin exposure to PFOA is of concern, studies evaluating the immunotoxicity of dermal exposure are lacking. These studies evaluated the immunotoxicity of PFOA (0.5-2% w/v, or 12.5-50 mg/kg/dose) following dermal exposure using a murine model. PFOA (0.5-2%) was not identified to be an irritant or sensitizer using the local lymph node assay. The IgM antibody response to sheep red blood cell. was significantly reduced in the spleen following 4-days of dermal exposure (2%). PFOA exposure produced a significant decrease in thymus (1 and 2%) and spleen (0.5-2%) weight along with an increase in liver weight (0.5-2%). Immune cell phenotyping identified a reduction in the frequency (1 and 2%) and number (0.5-2%) of splenic B-cells. To further define the mechanism of immunotoxicity, gene expression was also evaluated in the skin. The findings support a potential involvement of the nuclear receptor PPARα. These results demonstrate that dermal exposure to PFOA is immunotoxic and raise concern about potential adverse effects from dermal exposure.
全氟辛酸(PFOA)是一种全氟和多氟烷基物质(PFAS),曾用作化学品聚合中的表面活性剂。由于其普遍存在和半衰期长,PFOA 通常在环境、野生动物和人类中被检测到。虽然人们关注皮肤接触 PFOA 的问题,但缺乏评估皮肤接触 PFOA 的免疫毒性的研究。这些研究使用小鼠模型评估了 PFOA(0.5-2%w/v,或 12.5-50mg/kg/剂量)经皮暴露后的免疫毒性。局部淋巴结测定法未发现 PFOA(0.5-2%)具有刺激性或致敏性。皮肤接触 4 天后,脾脏中对绵羊红细胞的 IgM 抗体反应明显降低(2%)。PFOA 暴露导致胸腺(1%和 2%)和脾脏(0.5-2%)重量减轻,肝脏重量增加(0.5-2%)。免疫细胞表型鉴定表明,脾脏 B 细胞的频率(1%和 2%)和数量(0.5-2%)减少。为了进一步确定免疫毒性的机制,还评估了皮肤中的基因表达。研究结果支持核受体 PPARα 的潜在参与。这些结果表明,PFOA 的经皮暴露具有免疫毒性,并引起对经皮暴露潜在不良影响的关注。