Current limitations and a path forward to improve testing for the environmental assessment of endocrine active substances

Katherine K. Coady, Ronald C. Biever, Nancy D. Denslow, Melanie Gross, Patrick D. Guiney, Henrik Holbech, Natalie K. Karouna-Renier, Ioanna Katsiadaki, Henry O. Krueger, Steven L. Levine, Gerd Maack, Mike Williams, Jeffrey Wolf, G.T. Ankley

Publikation: Konferencebidrag uden forlag/tidsskriftPosterForskning


To assess the hazards and risks of possible endocrine active chemicals (EACs) there is a need for robust, validated test methods that detect perturbation of endocrine pathways of concern and provide insights reliable information as to assess to potential adverse effects on apical endpoints. One issue of significant concern to for current EACS screening/testing programs involves resources in regard such as to cost, time, trained personnel, and animal use. This is especially problematic when considering the number of chemicals that some regulatory authorities need to assess. One way to address this challenge is to prioritize chemicals for possible in vivo testing using in vitro high throughput (HTP) assays focused on a suite of endocrine molecular initiating events (MIEs) of concern. Additional challenges associated with the design and conduct of in vivo EAC screening and testing include selection of appropriate species (i.e., sensitive and amenable to laboratory testing), endpoints and life-stages. A component of this involves experience gained using existing tests to determine, for example, those that have been shown to be exceptionally sensitive to perturbation of a given MIE of concern. However, there is the opportunity for strategic use of HTP data and/or early screening level information to help guide the selection of existing assays that can further evaluate a given EAC modality. Further challenges for EAC screening and testing involve guidance and optimization in several areas, such as concentration setting, statistical power to detect biologically significant adverse effects, delivery and analytical measurement of test substances, availability of technical expertise, and study interpretation, including linking mechanistic and apical effects. Some of these areas can be addressed by the lessons learned and best practices developed through recent experiences conducting EAC screening/testing. Additionally, the collective assessment of EAC screening and testing data (e.g. compilation of historical control data) can be leveraged to refine test designs and performance criteria to maximize the power and utility of EAC screening/testing. Finally, a number of recommendations are provided for longer term research to address areas of uncertainty, including identifying potentially sensitive species for which test methods currently do not exist (e.g., invertebrates) and key endocrine pathways in addition to estrogen, androgen and thyroid signalling.

Katherine Coady, Ronald Biever, Nancy Denslow, Melanie Gross, Patrick Guiney, Henrik Holbech, Natalie Karouna-Renier, Ioanna Katsiadaki, Henry Krueger, Steven Levine, Gerd Maack, Mike Williams, Jeffrey Wolf, Gerald Ankley
Publikationsdato25. maj 2016
Antal sider1
StatusUdgivet - 25. maj 2016
BegivenhedSETAC Europe 26th annual meeting: Environmental contaminants from land to sea: continuities and interface in environmental toxicology and chemistry - Nantes, Frankrig
Varighed: 22. maj 201626. jul. 2016


KonferenceSETAC Europe 26th annual meeting


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