Estrogenic Activity of Perfluoro Carboxylic and Sulfonic Acids in Rainbow Trout Estrogen Receptor Binding and Liver Slice Vtg mRNA Expression Assays.

Q2 Health Professions Applied In Vitro Toxicology Pub Date : 2023-03-17 DOI:10.1089/aivt.2022.0013
Mark A Tapper, Jeffrey S Denny, Barbara R Sheedy, Ben Johnson, Richard C Kolanczyk
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Abstract

Perfluoroalkylated substances (PFAS) such as carboxylic acids, and sulfonic acids were manufactured in high quantities and are ubiquitous environmental contaminants. These chemicals persist in the environment and tend to bioaccumulate. In the current study, the estrogenic potential of a series of perfluoro carboxylic acids and select perfluoro sulfonic acids were assessed in an in vitro rainbow trout estrogen receptor (rtER) binding assay and an ex vivo rtER dependent vitellogenin (Vtg) expression rainbow trout liver slice assay. Perfluoro carboxylic acids with perfluoroalkyl chain lengths of four to six did not significantly bind to the rtER or induce Vtg expression in liver slices. Perfluoro carboxylic acids with chain lengths of seven to ten, and sulfonic acids with seven and eight carbon chains bound to the rtER, but with low relative binding affinities. While affinity for the rtER increased with increasing chain length the highest affinity measured was only 0.0025% relative to the endogenous hormone 17ß-estradiol at 100%. Both the eight-carbon carboxylic acid and eight-carbon sulfonic acid induced Vtg expression in ex vivo liver slices. However, toxicity did not allow expression to achieve maximum efficacy relative to estradiol.

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全氟羧酸和磺酸对虹鳟雌激素受体结合和肝切片Vtg mRNA表达的影响
羧酸和磺酸等全氟烷基化物质 (PFAS) 被大量生产,是无处不在的环境污染物。这些化学物质会在环境中持续存在,并有生物累积的趋势。本研究通过体外虹鳟鱼雌激素受体(rtER)结合试验和体内外依赖于 rtER 的卵黄素(Vtg)表达虹鳟鱼肝切片试验,评估了一系列全氟羧酸和部分全氟磺酸的雌激素潜力。全氟烷基链长度为 4 至 6 的全氟羧酸与 rtER 结合不明显,也不能诱导肝切片中 Vtg 的表达。链长为 7 至 10 的全氟羧酸以及碳链为 7 和 8 的磺酸与 rtER 结合,但相对结合亲和力较低。虽然与 rtER 的亲和力随着链长的增加而增加,但相对于 100%的内源性激素 17ß-estradiol 而言,测得的最高亲和力仅为 0.0025%。八碳羧酸和八碳磺酸都能诱导体内外肝脏切片中 Vtg 的表达。然而,与雌二醇相比,毒性并不能使表达达到最大效果。
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来源期刊
Applied In Vitro Toxicology
Applied In Vitro Toxicology Health Professions-Medical Laboratory Technology
CiteScore
2.70
自引率
0.00%
发文量
13
期刊介绍: Applied In Vitro Toxicology is a peer-reviewed journal providing the latest research on the application of alternative in vitro testing methods for predicting adverse effects in the pharmaceutical, chemical, and personal care industries. This Journal aims to address important issues facing the various chemical industries, including regulatory requirements; the reduction, refinement, and replacement of animal testing; new screening methods; evaluation of new cell and tissue models; and the most appropriate methods for assessing safety and satisfying regulatory demands. The Journal also delivers the latest views and opinions of developers of new models, end users of the models, academic laboratories that are inventing new tools, and regulatory agencies in the United States, Europe, Latin America, Australia and Asia. Applied In Vitro Toxicology is the journal that scientists involved with hazard identification and risk assessment will read to understand how new and existing in vitro methods are applied, and the questions for which these models provide answers. Applied In Vitro Toxicology coverage includes: -Applied in vitro toxicology industry standards -New technologies developed for applied in vitro toxicology -Data acquisition, cleaning, distribution, and best practices -Data protection, privacy, and policy -Business interests from research to product -The changing role of in vitro toxicology -Visualization and design principles of applied in vitro toxicology infrastructures -Physical interfaces and robotics -Opportunities around applied in vitro toxicology
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