Recommended approaches to the scientific evaluation of ecotoxicological hazards and risks of endocrine-active substances

Abstract

A SETAC Pellston Workshop® “Environmental Hazard and Risk Assessment Approaches for Endocrine-Active Substances (EHRA)” was held in February 2016 in Pensacola, Florida, USA. The primary objective of the workshop was to provide advice, based on current scientific understanding, to regulators and policy makers; the aim being to make considered, informed decisions on whether to select an ecotoxicological hazard- or a risk-based approach for regulating a given endocrinedisrupting substance (EDS) under review. The workshop additionally considered recent developments in the identification of EDS. Case studies were undertaken on 6 endocrine-active substances (EAS—not necessarily proven EDS, but substances known to interact directly with the endocrine system) that are representative of a range of perturbations of the endocrine system and considered to be data rich in relevant information at multiple biological levels of organization for 1 or more ecologically relevant taxa. The substances selected were 17α-ethinylestradiol, perchlorate, propiconazole, 17β-trenbolone, tributyltin, and vinclozolin. The 6 case studies were not comprehensive safety evaluations but provided foundations for clarifying key issues and procedures that should be considered when assessing the ecotoxicological hazards and risks of EAS and EDS. The workshop also highlighted areas of scientific uncertainty, and made specific recommendations for research and methods-development to resolve some of the identified issues. The present paper provides broad guidance for scientists in regulatory authorities, industry, and academia on issues likely to arise during the ecotoxicological hazard and risk assessment of EAS and EDS. The primary conclusion of this paper, and of the SETAC Pellston Workshop on which it is based, is that if data on environmental exposure, effects on sensitive species and life-stages, delayed effects, and effects at low concentrations are robust, initiating environmental risk assessment of EDS is scientifically sound and sufficiently reliable and protective of the environment. In the absence of such data, assessment on the basis of hazard is scientifically justified until such time as relevant new information is available.

A critical review of the environmental occurrence and potential effects in aquatic vertebrates of the potent androgen receptor agonist 17β‐trenbolone

“…An intensive trenbolone literature search was conducted during the summer of 2015 using a wide variety of search terms (Matthiessen et al ), which yielded approximately 800 papers. Several additional papers from 2016 and 2017 were identified using a more targeted approach in PubMed.…”

“…In early 2016, the Society of Environmental Toxicology and Chemistry (SETAC) sponsored an international Pellston workshop focused on hazard‐ versus risk‐based approaches for the ecological assessment of endocrine‐active chemicals (Matthiessen et al ). For this comparative evaluation, workshop participants focused on several facets of endocrine‐active chemical assessments, including linkage of mechanistic data indicative of altered endocrine function to adverse outcomes (Mihaich et al ), limitations and proposed improvements in current screening and testing approaches (Coady et al ), attributes of endocrine‐active chemicals that might complicate test interpretation and prediction of hazard/risk (Parrott et al ), and population‐level effects of endocrine‐active chemicals (Marty et al ).…”

“…For this comparative evaluation, workshop participants focused on several facets of endocrine‐active chemical assessments, including linkage of mechanistic data indicative of altered endocrine function to adverse outcomes (Mihaich et al ), limitations and proposed improvements in current screening and testing approaches (Coady et al ), attributes of endocrine‐active chemicals that might complicate test interpretation and prediction of hazard/risk (Parrott et al ), and population‐level effects of endocrine‐active chemicals (Marty et al ). To support and illustrate these analyses, relatively extensive literature reviews were conducted for 6 well‐established endocrine‐active chemicals that affect different pathways, endpoints, and/or species, including an estrogen receptor agonist (17α‐ethinylestradiol), a sex steroid synthesis inhibitor (propiconazole), a compound associated with the induction of intersex in invertebrates (tributyltin), a thyroid‐active substance (perchlorate), and chemicals that interact with the vertebrate androgen receptor as an antagonist (vinclozolin) or an agonist (17β‐trenbolone; Matthiessen et al ). Several of these chemicals have been the subject of detailed and, in some cases, relatively recent reviews in the open literature concerning their environmental fate and biological effects.…”

Evaluating the credibility of histopathology data in environmental endocrine toxicity studies

“…As expressed in the meeting's executive summary, "The primary aim of the workshop was to provide objective advice, based on the current level of scientific understanding, to enable regulators/policy makers to make considered, informed decisions on whether to select a hazard-or a risk-based approach for a given endocrine-disrupting substance (EDS) under review" [8]. Invited participants for the week-long session included 49 international experts from government, industry, and academia.…”

Knotting nets: Molecular junctions of interconnecting endocrine axes identified by application of the adverse outcome pathway concept

“…For endocrine disruptors, the plausible link between the test endpoints and population‐level effects is often uncertain. To address this uncertainty, a 2016 Society of Environmental Toxicology and Chemistry (SETAC) Pellston Workshop evaluated the population relevance of toxicity endpoints from case studies with specific endocrine disruptors (Marty et al ; Matthiessen et al ). Based on the conclusions of this workshop, the AOs at the individual level described in the present review are extrapolated to the population level.…”