title: Current limitations and recommendations to improve testing for the environmental assessment of endocrine active substances.
abstract: In the present study, existing regulatory frameworks and test systems for assessing potential endocrine active chemicals are described, and associated challenges are 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 to 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 with 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 to 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 assays 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. Integr Environ Assess Manag 2017;13:302-316. © 2016 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
authors: The Dow Chemical Company, Toxicology and Environmental Research and Consulting, Midland, Michigan, USA.
authors: Katherine K
authors: KK
authors: Coady
authors: Smithers Viscient Laboratories, Wareham, Massachusetts, USA.
authors: Ronald C
authors: RC
authors: Biever
authors: Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, Florida, USA.
authors: Nancy D
authors: ND
authors: Denslow
authors: wca, Faringdon, United Kingdom.
authors: Melanie
authors: M
authors: Gross
authors: Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, Madison, Wisconsin, USA.
authors: Patrick D
authors: PD
authors: Guiney
authors: Department of Biology, University of Southern Denmark, Odense M, Denmark.
authors: Henrik
authors: H
authors: Holbech
authors: USGS Patuxent Wildlife Research Center, Beltsville, Maryland.
authors: Natalie K
authors: NK
authors: Karouna-Renier
authors: Centre for Environment Fisheries and Aquaculture Science, Dorset, United Kingdom.
authors: Ioanna
authors: I
authors: Katsiadaki
authors: Wildlife International, Division of EAG Laboratories, Easton, Maryland, USA.
authors: Hank
authors: H
authors: Krueger
authors: Global Regulatory Sciences, Monsanto Company, St Louis, Missouri, USA.
authors: Steven L
authors: SL
authors: Levine
authors: German Environment Agency, Dessau-Roßlau, Germany.
authors: Gerd
authors: G
authors: Maack
authors: CSIRO Land and Water, South Australia, Australia.
authors: Mike
authors: M
authors: Williams
authors: Experimental Pathology Laboratories, Sterling, Virginia, USA.
authors: Jeffrey C
authors: JC
authors: Wolf
authors: US Environmental Protection Agency, Duluth, Minnesota.
authors: Gerald T
authors: GT
authors: Ankley
mesh_terms: D000818:Animals; D001681:Biological Assay; D054750:Ecotoxicology; D052244:Endocrine Disruptors / Q000032:analysis* / Q000633:toxicity; D004784:Environmental Monitoring / Q000379:methods* / Q000592:standards; D004785:Environmental Pollutants / Q000032:analysis* / Q000633:toxicity; D006801:Humans; D018570:Risk Assessment; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D052244:Endocrine Disruptors; D004785:Environmental Pollutants
keywords: Endocrine disruption; High-throughput assays; Regulatory tests; Risk and hazard assessment