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Current limitations and a path forward to improve testing for the environmental assessment of endocrine active substances-presentation
Citation:
Coady, K., R. Biever, N. Denslow, M. Gross, P. Guiney, H. Holbech, N. Karouna-Renier, I. Katsiadaki, H. Krueger, S. Levine, G. Maack, M. Williams, J. Wolf, AND G. Ankley. Current limitations and a path forward to improve testing for the environmental assessment of endocrine active substances-presentation. SETAC North America, Orlando, FL, November 06 - 10, 2016.
Impact/Purpose:
not applicable
Description:
To assess the hazards and risks of possible endocrine active chemicals (EACs), there is a need for robust, validated test methods that detect perturbations of endocrine pathways and provide reliable information for evaluating potential adverse effects on apical endpoints. One issue of significant concern for current EACS screening/testing programs involves resources such as 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 by using in vitro high throughput (HTP) assays focused on a suite of endocrine molecular initiating events (MIEs). Additional challenges associated with the design and conduct of in vivo EAC screening and testing include the selection of appropriate species (i.e., sensitive and amenable to laboratory testing), endpoints and life-stages. A component of this involves experience gained in the use of existing tests to determine, for example, assays that have demonstrated exceptional sensitivity to perturbation of a given MIE. However, the strategic use of HTP data and/or early screening level information may 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 to 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.