Currie Seth D, Benson David Blake, Xie Zhong-Ru, Wang Jia-Sheng, Tang Lili
Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602, USA.
Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, GA 30602, USA.
J Xenobiot. 2025 Feb 2;15(1):24. doi: 10.3390/jox15010024.
Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in various products, such as firefighting foams and non-stick cookware, due to their resistance to heat and degradation. However, these same properties make them persistent in the environment and human body, raising public health concerns. This study selected eleven PFAS commonly found in drinking water and exposed Caenorhabditis elegans to concentrations ranging from 0.1 to 200 µM to assess neurodevelopmental toxicity using a high-throughput, high-content screening (HTS) platform coupled with artificial intelligence for image analysis. Our findings showed that PFAS such as 6:2 FTS, HFPO-DA, PFBA, PFBS, PFHxA, and PFOS inhibited dopaminergic neuron activity, with fluorescence intensity reductions observed across concentrations from 0.1 to 100 µM. PFOS and PFBS also disrupted synaptic transmission, causing reduced motility and increased paralysis in aldicarb-induced assays, with the most pronounced effects at higher concentrations. These impairments in both neuron activity and synaptic function led to behavioral deficits. Notably, PFOS was one of the most toxic PFAS, affecting multiple neurodevelopmental endpoints. These results emphasize the developmental risks of PFAS exposure, highlighting the impact of both individual compounds and mixtures on neurodevelopment. This knowledge is essential for assessing PFAS-related health risks and informing mitigation strategies.
全氟和多氟烷基物质（PFAS）是用于各种产品的合成化学品，如消防泡沫和不粘锅炊具，因为它们具有耐热性和抗降解性。然而，这些相同的特性使它们在环境和人体中持久存在，引发了公众对健康的担忧。本研究选择了饮用水中常见的11种PFAS，并将秀丽隐杆线虫暴露于0.1至200μM的浓度下，使用高通量、高内涵筛选（HTS）平台结合人工智能图像分析来评估神经发育毒性。我们的研究结果表明，6:2 FTS、HFPO-DA、PFBA、PFBS、PFHxA和PFOS等PFAS抑制多巴胺能神经元活性，在0.1至100μM的浓度范围内均观察到荧光强度降低。PFOS和PFBS还破坏了突触传递，在涕灭威诱导的试验中导致运动能力下降和麻痹增加，在较高浓度下影响最为明显。神经元活性和突触功能的这些损伤导致了行为缺陷。值得注意的是，PFOS是毒性最强的PFAS之一，影响多个神经发育终点。这些结果强调了PFAS暴露的发育风险，突出了单个化合物和混合物对神经发育的影响。这些知识对于评估与PFAS相关的健康风险和为缓解策略提供信息至关重要。
