Evaluation of Developmental Toxicity, Developmental Neurotoxicity, and Tissue Dose in Zebrafish Exposed to GenX and Other PFAS
Evaluation of Developmental Toxicity, Developmental Neurotoxicity, and Tissue Dose in Zebrafish Exposed to GenX and Other PFAS
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DOI：
10.1289/ehp5843
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发表时间：
2020-04-01
影响因子：
10.4
通讯作者：
Tal, Tamara
中科院分区：
文献类型：
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作者：
Gaballah, Shaza;Swank, Adam;Tal, Tamara
背景：全氟烷基和多氟烷基物质（PFAS）是一种广泛存在于环境中的工业化学品。暴露于长链PFAS与发育毒性有关，促使它们被短链和氟醚化合物取代。公众越来越关注PFAS替代品的安全性。目的：我们的目的是根据共有的毒性表型对PFAS进行分组。方法：斑马鱼发育暴露于4，8-二氧杂-3H-全氟壬酸（ADONA），全氟-2-丙氧基丙酸（GenX游离酸）、全氟-3，6-二氧杂-4-甲基-7-辛烯-1-磺酸（PFESA 1）、全氟己烷磺酸（PFHxS）、全氟己酸（PFHxA）、全氟正辛酸（PFOA）、全氟辛烷磺酸（PFOS）或0.4%二甲基亚砜（DMSO），从灭菌后0-5天（dpf）开始每日给药。在6 dpf时，进行发育毒性和发育神经毒性试验，并使用靶向分析化学测量培养基和组织剂量。为了测试脂肪族磺酸PFAS是否引起相同的毒性表型，（PFBS; 4-碳），全氟戊磺酸（PFPeS; 5-碳），PFHxS（6-碳），全氟庚磺酸（PFHpS; 7-碳）和全氟辛烷磺酸（8-碳）进行了评价。在非致畸浓度下，PFHxS或PFOS暴露会导致鱼鳔充气失败、尾巴异常前屈以及活动过度。暴露于PFHxA导致了独特的多动症特征。ADONA、PFESA 1或PFOA暴露导致幼虫组织中母体化合物的可检测水平，但产生阴性毒性结果。GenX在DMSO中不稳定，但在去离子水中稀释时稳定且毒性呈阴性。暴露于PFPeS，PFHxS，PFHpS，或全氟辛烷磺酸导致在一个共享的毒性表型，其特征在于体轴和鱼鳔缺陷和hyperactivity.CONCLUSIONS：所有新兴的氟醚PFAS测试是负面的评估结果。两个独特的毒性签名被确定产生的结构不同的PFAS。在磺酸脂肪族PFAS中，化学效价与发育神经毒性的碳链长度增加相关，但与发育毒性无关。这项研究确定了化学结构和体内表型之间的关系，可能产生的共同机制PFAS毒性。这些数据表明，发育神经毒性是这类广泛存在的环境化学品的一个重要终点。
BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a diverse class of industrial chemicals with widespread environmental occurrence. Exposure to long-chain PFAS is associated with developmental toxicity, prompting their replacement with short-chain and fluoroether compounds. There is growing public concern over the safety of replacement PFAS.OBJECTIVE: We aimed to group PFAS based on shared toxicity phenotypes.METHODS: Zebrafish were developmentally exposed to 4,8-dioxa-3H-perfluorononanoate (ADONA), perfluoro-2-propoxypropanoic acid (GenX Free Acid), perfluoro-3,6-dioxa-4-methyl-7-octene-1-sulfonic acid (PFESA1), perfluorohexanesulfonic acid (PFHxS), perfluorohexanoic acid (PFHxA), perfluoro-n-octanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), or 0.4% dimethyl sulfoxide (DMSO) daily from 0-5 d post fenilization (dpf). At 6 dpf, developmental toxicity and developmental neurotoxicity assays were performed, and targeted analytical chemistry was used to measure media and tissue doses. To test whether aliphatic sulfonic acid PFAS cause the same toxicity phenotypes, perfluorobutanesulfonic acid (PFBS; 4-carbon), perfluoropentanesulfonic acid (PFPeS; 5-carbon), PFHxS (6-carbon), perfluoroheptanesulfonic acid (PFHpS; 7-carbon), and PFOS (8-carbon) were evaluated.RESULTS: PFHxS or PFOS exposure caused failed swim bladder inflation, abnormal ventroflexion of the tail, and hyperactivity at nonteratogenic concentrations. Exposure to PFHxA resulted in a unique hyperactivity signature. ADONA, PFESA1, or PFOA exposure resulted in detectable levels of parent compound in larval tissue but yielded negative toxicity results. GenX was unstable in DMSO, but stable and negative for toxicity when diluted in deionized water. Exposure to PFPeS, PFHxS, PFHpS, or PFOS resulted in a shared toxicity phenotype characterized by body axis and swim bladder defects and hyperactivity.CONCLUSIONS: All emerging fluoroether PFAS tested were negative for evaluated outcomes. Two unique toxicity signatures were identified arising from structurally dissimilar PFAS. Among sulfonic acid aliphatic PFAS, chemical potencies were correlated with increasing carbon chain length for developmental neurotoxicity, but not developmental toxicity. This study identified relationships between chemical structures and in vivo phenotypes that may arise from shared mechanisms of PFAS toxicity. These data suggest that developmental neurotoxicity is an important end point to consider for this class of widely occurring environmental chemicals.