Department of Occupational and Environmental Health, School of Public Health, Université de Montréal, Montreal, Canada; Centre de Recherche en Santé Publique, Université de Montréal and CIUSSS du Centre-Sud-de-l'Île-de-Montréal, Canada.
Department of Occupational and Environmental Health, School of Public Health, Université de Montréal, Montreal, Canada; Centre de Recherche en Santé Publique, Université de Montréal and CIUSSS du Centre-Sud-de-l'Île-de-Montréal, Canada.
Environ Int. 2023 Sep;179:108170. doi: 10.1016/j.envint.2023.108170. Epub 2023 Aug 23.
Perfluorooctanoic acid (PFOA) is detected in the blood of virtually all biomonitoring study participants. Assessing health risks associated with blood PFOA levels is challenging because exposure guidance values (EGVs) are typically expressed in terms of external dose. Biomonitoring equivalents (BEs) consistent with EGVs could facilitate health-based interpretations.
To i) derive BEs for serum/plasma PFOA corresponding to non-cancer EGVs of the U.S. Environmental Protection Agency (U.S. EPA), the Agency for Toxic Substances and Disease Registry (ATSDR) and Health Canada, and ii) compare with PFOA concentrations from national biomonitoring surveys.
Starting from EGV points of departure, we employed pharmacokinetic data/models and uncertainty factors. Points of departure in pregnant rodents (U.S. EPA 2016, ATSDR) were converted into fetus and pup serum concentrations using an animal gestation/lactation pharmacokinetic model, and equivalent human fetus and child concentrations were converted into BEs in maternal serum using a human gestation/lactation model. The point of departure in adult rodents (Health Canada) was converted into a BE using experimental data. For epidemiology-based EGVs (U.S. EPA 2023, draft), BEs were directly based on epidemiological data or derived using a human gestation/lactation pharmacokinetic model. BEs were compared with Canadian/U.S. biomonitoring data.
Non-cancer BEs (ng/mL) were 684 (Health Canada, 2018) or ranged from 15 to 29 (U.S. EPA, 2016), 6-10 (ATSDR, 2021) and 0.2-0.8 (U.S. EPA, 2023, draft). Ninety-fifth percentiles of serum levels from the 2018-2019 Canadian Health Measures Survey (CHMS) and the 2017-2018 National Health and Nutrition Examination Survey (NHANES) were slightly below the BE for ATSDR, and geometric means were above the non-cancer BEs for the U.S. EPA (2023, draft).
Non-cancer BEs spanned three orders of magnitude. The lowest BEs were for EGVs based on developmental endpoints in epidemiological studies. Concentrations in Canadian/U.S. national surveys were higher than or close to BEs for the most recent non-cancer EGVs.
几乎所有生物监测研究参与者的血液中都能检测到全氟辛酸 (PFOA)。评估与血液中 PFOA 水平相关的健康风险具有挑战性，因为暴露指导值 (EGV) 通常以外部剂量表示。与 EGV 一致的生物监测等效物 (BE) 可以促进基于健康的解释。
i) 推导与美国环境保护署 (U.S. EPA)、疾病控制与预防中心毒物和疾病登记处 (ATSDR) 和加拿大卫生部的非癌症 EGV 相对应的血清/血浆 PFOA 的 BE，ii) 并与国家生物监测调查中的 PFOA 浓度进行比较。
从 EGV 起点开始，我们使用了药代动力学数据/模型和不确定性因素。妊娠啮齿动物（美国环保署 2016 年，ATSDR）的起点通过动物妊娠/哺乳期药代动力学模型转化为胎儿和幼崽的血清浓度，并用人类妊娠/哺乳期模型将相当于人类胎儿和儿童的浓度转化为母体血清中的 BE。成年啮齿动物（加拿大卫生部）的起点使用实验数据转化为 BE。对于基于流行病学的 EGV（美国环保署 2023 年，草案），BE 直接基于流行病学数据或使用人类妊娠/哺乳期药代动力学模型推导。BE 与加拿大/美国的生物监测数据进行了比较。
非癌症 BE（ng/mL）为 684（加拿大卫生部，2018 年）或范围为 15-29（美国环保署，2016 年）、6-10（ATSDR，2021 年）和 0.2-0.8（美国环保署，2023 年，草案）。2018-2019 年加拿大健康测量调查（CHMS）和 2017-2018 年全国健康和营养检查调查（NHANES）的血清水平第 95 百分位数略低于 ATSDR 的 BE，几何平均值高于美国环保署（2023 年，草案）的非癌症 BE。
非癌症 BE 跨越了三个数量级。最低的 BE 是基于流行病学研究中发育终点的 EGV。加拿大/美国国家调查中的浓度高于或接近最新非癌症 EGV 的 BE。
