5P42ES027706 Sources, Transport, Exposure, and Effects of PFASs (STEEP) SRP

5P42ES027706 PFAS (STEEP) SRP 的来源、传输、暴露和影响

• 批准号: 10381901
• 负责人: Rainer Lohmann
• 金额: $ 1.6万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-19 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10381901
• 关键词: Acids; Acute; Address; Alkanesulfonates; Attention; Body Burden; Carboxylic Acids; Characteristics; Chemicals; Chromatography; Chronic; Development; Dose; Electroplating; Environment; Exposure to; Film; Follow-Up Studies; Health; Hepatic; Human; Human Milk; Human body; Immunologics; In Vitro; Infrastructure; Ions; Link; Lipids; Liquid Chromatography; Liver; Mass Spectrum Analysis; Measures; Metabolic Pathway; Modeling; Mothers; Mus; Oral; Organ; Outcome; Phospholipids; Production; Proteins; Resolution; Risk Assessment; Serum; Signal Recognition Particle; Source; Tissues; Toxicokinetics; anthropogenesis; aqueous; bioaccumulation; chemical property; ground water; postnatal; pregnant; pup; response; uptake; wasting

Per- and polyfluoroalkyl substances (PFAS) are a chemical class of highly fluorinated anthropogenic chemicals. Exposures to perfluoroalkyl compounds have been linked to numerous adverse hepatic and immunological outcomes. Polyfluoroalkyl compounds, which can degrade into perfluoroalkyl compounds and share similar chemical properties, have received minimal scientific and regulatory attention. Extensive use of the polyfluoroalkyl 6:2 fluorotelomer sulfonate (6:2 FTSA) and its precursors (6:2 FT) in aqueous film-forming foams (AFFF) and mist suppressants used in metal plating has resulted in widespread contamination of groundwater and waste infrastructure. Critical gaps in understanding of the disposition of these chemicals in vitro, their metabolites, possible health effects, and potential contributions to the human body burden of perfluoroalkyl carboxylic acids (PFCA) hinder ongoing risk assessment. This proposal aims to address these gaps by measuring these compounds, and their metabolites, in CD-1 mice exposed to 6:2 FTSA and 6:2 FT mixtures used in AFFF. Our team will first evaluate PFAS bioaccumulation and metabolic pathways for PFCA production in these mice. The mice will be exposed for 28 days to 10 µM F 6:2 FTSA or AFFF via oral gavage and levels of PFAS and extractable organofluorine (EOF) will be quantified in serum, liver, and other organs using liquid chromatography tandem mass spectroscopy and combustion ion chromatography. Total protein, lipids, and phospholipids will be simultaneously measured to assess distribution among tissues using a mixed effects model. Nontargeted analysis using high resolution mass spectroscopy will be performed to identify unknown metabolites and degradation mechanisms. A follow-up study will be performed to assess dose-response relationships during developmental and chronic exposure to 6:2 FTSA in the mice. Pregnant mice will be exposed to 0 to 1 µM F as 6:2 FTSA via oral gavage and their pups will be split into acute (PFAS free) or chronic (0.001 µM F as 6:2 FTSA) exposure groups. PFAS and EOF will be quantified in the mothers’ breast milk and the pup’s serum and liver at postnatal day 4, 21, and 126.

每种和多氟烷基物质（PFA）是一类化学类的高度氟化 人为化学物质。对全氟烷基化合物的暴露已与众多 不良肝和免疫学结果。多氟烷基化合物，可以降解 进入全氟烷基化合物并具有相似的化学特性，获得了最低 科学和法规关注。多流氟烷基6：2氟烷基的广泛使用 在水性膜形成泡沫（AFFF）和 金属镀金中使用的雾化物已导致地下水的宽度污染 和废物基础设施。了解这些化学物质在 体外，其代谢产物，可能的健康影响以及对人体的潜在贡献 全氟烷基羧酸（PFCA）的负担阻碍了持续的风险评估。这个建议 旨在通过测量CD-1小鼠中的这些化合物及其代谢物来解决这些差距 暴露于AFFF中使用的6：2 FTSA和6：2英尺的混​​合物。我们的团队将首先评估PFA 这些小鼠的PFCA产生的生物积累和代谢途径。老鼠会 暴露于28天至10 µm F 6：2 ftsa或通过口服膨胀以及PFA的水平和AFFF。 可提取的有机氟（EOF）将使用液体在血清，肝脏和其他器官中进行量化 色谱串联质谱和组合离子色谱。总蛋白质， 脂质和磷脂将简单地测量以评估组织之间的分布 使用混合效应模型。使用高分辨率质谱法分析将 进行以识别未知代谢物和降解机制。后续研究 将进行发育和慢性期间评估剂量反应关系 在小鼠中暴露于6：2 ftsa。怀孕的小鼠将暴露于6：2 ftsa的0至1 µm F 通过口服饲料及其幼崽将分为急性（不含PFA）或慢性（0.001 µm F AS 6：2） FTSA）暴露组​​。 PFA和EOF将在母亲的母乳中进行量化 PUP在产后第4、21和126天的血清和肝脏。