Current limitations and recommendations to improve testing for the environmental assessment of endocrine active substances
Autor: | Patrick D. Guiney, Jeffrey C. Wolf, Ronald C. Biever, Gerd Maack, Gerald T. Ankley, Melanie Gross, Nancy D. Denslow, Katherine K. Coady, Hank Krueger, Natalie K. Karouna-Renier, Mike Williams, Steven L. Levine, Henrik Holbech, Ioanna Katsiadaki |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Engineering business.industry Adverse outcomes Geography Planning and Development General Medicine 010501 environmental sciences 01 natural sciences In vivo tests Hazard Reliability engineering 03 medical and health sciences 030104 developmental biology Resource (project management) Risk analysis (engineering) Endocrine system Environmental impact assessment Adverse effect business Hormone signaling 0105 earth and related environmental sciences General Environmental Science |
Zdroj: | Integrated Environmental Assessment and Management. 13:302-316 |
ISSN: | 1551-3777 |
Popis: | In this paper existing regulatory frameworks and test systems for assessing potential endocrine-active chemicals are described, and associated challenges discussed, along with proposed approaches to address these challenges. Regulatory frameworks vary somewhat across geographies, but all basically evaluate whether a chemical possesses endocrine activity and whether this activity can result in adverse outcomes either to humans or the environment. Current test systems include in silico, in vitro and in vivo techniques focused on detecting potential endocrine activity, and in vivo tests that collect apical data to detect possible adverse effects. These test systems are currently designed to robustly assess endocrine activity and/or adverse effects in the estrogen, androgen, and thyroid hormone signaling pathways; however, there are some limitations of current test systems for evaluating endocrine hazard and risk. These limitations include a lack of certainty regarding: 1) adequately sensitive species and life-stages, 2) mechanistic endpoints that are diagnostic for endocrine pathways of concern, and 3) the linkage between mechanistic responses and apical, adverse outcomes. Furthermore, some existing test methods are resource intensive in regard to time, cost, and use of animals. However, based on recent experiences, there are opportunities to improve approaches to, and guidance for existing test methods, and reduce uncertainty. For example, in vitro high throughput screening could be used to prioritize chemicals for testing and provide insights as to the most appropriate assay(s) for characterizing hazard and risk. Other recommendations include adding endpoints for elucidating connections between mechanistic effects and adverse outcomes, identifying potentially sensitive taxa for which test methods currently do not exist, and addressing key endocrine pathways of possible concern in addition to those associated with estrogen, androgen and thyroid signaling. This article is protected by copyright. All rights reserved |
Databáze: | OpenAIRE |
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