Adapting existing toxicokinetic models to relate perfluoroalkyl and polyfluoroalkyl intake to biomarkers in humans.

IF 4.1 3区 医学 Q2 TOXICOLOGY
Kara J Dean, Régis Pouillot, Jane M Van Doren, Sofia M Santillana Farakos
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Abstract

Exposures to per- and polyfluoroalkyl substances (PFAS) are associated with various adverse health outcomes, and a wide range of PFAS compounds have been detected in human serum, the environment, and food. Toxicokinetic models, however, have been developed for only a subset of the compounds of interest. To facilitate reverse dosimetry and risk assessment for the less studied PFAS compounds in food, we developed and evaluated an approach to adapt existing toxicokinetic models for nonhuman primates to predict human serum levels. The approach was validated with perfluorooctanoic acid and perfluorooctanesulfonic acid data and applied to perfluorohexanesulfonate. Results indicate that the approach yields similar dosimetry estimates to those of other models, particularly those used for regulatory purposes, suggesting the methodology can be leveraged to inform decision-making in data-sparse spaces. Applying and adapting the framework will improve our ability to connect dietary PFAS exposures to endpoints of concern for a wide range of PFAS compounds.

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调整现有的毒物动力学模型,将全氟烷基和多氟烷基摄入量与人体生物标志物联系起来。
暴露于全氟烷基和多氟烷基物质(PFAS)与各种不良健康后果有关,在人类血清、环境和食物中已检测到各种PFAS化合物。然而,毒性动力学模型只针对部分感兴趣的化合物建立。为了便于对食品中较少研究的PFAS化合物进行反向剂量测定和风险评估,我们开发并评估了一种方法,以适应现有的非人类灵长类动物毒性动力学模型来预测人类血清水平。用全氟辛酸(PFOA)和全氟辛烷磺酸(PFOS)数据验证了该方法,并将其应用于全氟己酸(PFHxS)。结果表明,该方法产生的剂量学估计值与其他模型相似,特别是用于监管目的的模型,这表明该方法可以用于数据稀疏空间的决策。应用和调整该框架将提高我们将膳食PFAS暴露与广泛的PFAS化合物的关注端点联系起来的能力。
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来源期刊
Toxicological Sciences
Toxicological Sciences 医学-毒理学
CiteScore
7.70
自引率
7.90%
发文量
118
审稿时长
1.5 months
期刊介绍: The mission of Toxicological Sciences, the official journal of the Society of Toxicology, is to publish a broad spectrum of impactful research in the field of toxicology. The primary focus of Toxicological Sciences is on original research articles. The journal also provides expert insight via contemporary and systematic reviews, as well as forum articles and editorial content that addresses important topics in the field. The scope of Toxicological Sciences is focused on a broad spectrum of impactful toxicological research that will advance the multidisciplinary field of toxicology ranging from basic research to model development and application, and decision making. Submissions will include diverse technologies and approaches including, but not limited to: bioinformatics and computational biology, biochemistry, exposure science, histopathology, mass spectrometry, molecular biology, population-based sciences, tissue and cell-based systems, and whole-animal studies. Integrative approaches that combine realistic exposure scenarios with impactful analyses that move the field forward are encouraged.
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