Britton Katy N, Judson Richard S, Hill Bridgett N, Jarema Kimberly A, Olin Jeanene K, Knapp Bridget R, Lowery Morgan, Feshuk Madison, Brown Jason, Padilla Stephanie
Oak Ridge Associated Universities Research Participation Program Hosted by EPA, Center for Computational Toxicology and Exposure, Biomolecular and Computational Toxicology Division, Rapid Assay Development Branch, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Center for Computational Toxicology and Exposure, Computational Toxicology and Bioinformatics Branch, Research Triangle Park, NC 27711, USA.
Toxics. 2024 Jul 10;12(7):501. doi: 10.3390/toxics12070501.
Per- and polyfluoroalkyl substances (PFAS) are found in many consumer and industrial products. While some PFAS, notably perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), are developmentally toxic in mammals, the vast majority of PFAS have not been evaluated for developmental toxicity potential. A concentration-response study of 182 unique PFAS chemicals using the zebrafish medium-throughput, developmental vertebrate toxicity assay was conducted to investigate chemical structural identifiers for toxicity. Embryos were exposed to each PFAS compound (≤100 μM) beginning on the day of fertilization. At 6 days post-fertilization (dpf), two independent observers graded developmental landmarks for each larva (e.g., mortality, hatching, swim bladder inflation, edema, abnormal spine/tail, or craniofacial structure). Thirty percent of the PFAS were developmentally toxic, but there was no enrichment of any OECD structural category. PFOS was developmentally toxic (benchmark concentration [BMC] = 7.48 μM); however, other chemicals were more potent: perfluorooctanesulfonamide (PFOSA), N-methylperfluorooctane sulfonamide (N-MeFOSA), ((perfluorooctyl)ethyl)phosphonic acid, perfluoro-3,6,9-trioxatridecanoic acid, and perfluorohexane sulfonamide. The developmental toxicity profile for these more potent PFAS is largely unexplored in mammals and other species. Based on these zebrafish developmental toxicity results, additional screening may be warranted to understand the toxicity profile of these chemicals in other species.
全氟和多氟烷基物质（PFAS）存在于许多消费品和工业产品中。虽然一些PFAS，特别是全氟辛酸（PFOA）和全氟辛烷磺酸（PFOS），对哺乳动物具有发育毒性，但绝大多数PFAS尚未评估其发育毒性潜力。使用斑马鱼中通量发育脊椎动物毒性试验对182种独特的PFAS化学品进行了浓度-反应研究，以调查毒性的化学结构标识符。从受精当天开始，将胚胎暴露于每种PFAS化合物（≤100μM）。在受精后6天（dpf），两名独立观察者对每个幼虫的发育标志进行评分（例如，死亡率、孵化率、鳔充气、水肿、脊柱/尾巴异常或颅面结构）。30%的PFAS具有发育毒性，但没有任何经合组织结构类别富集。PFOS具有发育毒性（基准浓度[BMC]=7.48μM）；然而，其他化学物质毒性更强：全氟辛烷磺酰胺（PFOSA）、N-甲基全氟辛烷磺酰胺（N-MeFOSA）、（（全氟辛基）乙基）膦酸、全氟-3,6,9-三氧杂十三烷酸和全氟己烷磺酰胺。这些毒性更强的PFAS在哺乳动物和其他物种中的发育毒性概况在很大程度上尚未得到研究。基于这些斑马鱼发育毒性结果，可能有必要进行额外的筛选，以了解这些化学物质在其他物种中的毒性概况。
