Population-relevant endpoints in the evaluation of endocrine-active substances (EAS) for ecotoxicological hazard and risk assessment

Marty, M. Sue; Blankinship, Amy; Chambers, Janice E.; Constantine, Lisa A.; Kloas, Werner; Kumar, Anu; Lagadic, Laurent; Meador, James P.; Pickford, Daniel B.; Schwarz, Tamar; Verslycke, Tim

doi:10.1002/ieam.1887

Cited by 33 publications

(39 citation statements)

References 70 publications

(72 reference statements)

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“…Finally, issues were identified that aid in distinguishing between endocrineversus nonendocrine-specific responses. These crosscutting issues are broadly outlined below and discussed in detail in the associated companion papers (Coady et al this issue; Marty et al this issue; Mihaich et al this issue; Parrott et al this issue). …”

Section: Crosscutting Issues Relevant To the Evaluation Of Hazards Anmentioning

confidence: 99%

“…This lack of definition is a source of major uncertainty for both hazard and risk assessment. The companion paper by Marty et al. (this issue) used data from the EAS case studies (Supplemental Data S1–S6) to evaluate the population relevance of collected study endpoint data in the context of ecotoxicological hazard and risk assessment for various taxa (invertebrates, fish, amphibians, birds, and mammals).…”

Section: Crosscutting Issues Relevant To the Evaluation Of Hazards Anmentioning

confidence: 99%

“…However, until an established linkage between these endpoints and subsequent population changes are evident, such endpoints should not be used to drive the risk assessment of EDS. Marty et al. (this issue) have, in addition, examined recovery in endpoint responses, which may be particularly important when evaluating effects of EDS on populations.…”

Section: Crosscutting Issues Relevant To the Evaluation Of Hazards Anmentioning

confidence: 99%

“…It should be noted that the flow chart is intended for use in situations where a substance has already been clearly identified as an EDS, and therefore decisions about whether or not to initiate ecotoxicological risk assessment need to be made. The issues underpinning these decisions have been discussed more fully in the section entitled Cross-Cutting Issues Relevant to the Evaluation of Hazards and Risks of EAS/EDS, and at length in the accompanying papers (Coady et al this issue; Marty et al this issue; Mihaich et al this issue; Parrott et al this issue). …”

Section: Proposed Decision-making Strategy To Support Endocrine Disrumentioning

confidence: 99%

“…Several areas where further research is needed were identified at the workshop, and the main points are highlighted here; for more detail, see the companion papers in this series (Coady et al this issue; Marty et al this issue; Mihaich et al this issue; Parrott et al this issue). Many of these areas involve the need for fundamental biological research, but there is also a need for the development of new testing methods.…”

Section: Knowledge Gaps In Endocrine Screening and Testingmentioning

confidence: 99%

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

Matthiessen¹,

Ankley

Biever

et al. 2017

Integr Environ Assess Manag

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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.

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Section: Crosscutting Issues Relevant To the Evaluation Of Hazards Anmentioning

confidence: 99%

Section: Crosscutting Issues Relevant To the Evaluation Of Hazards Anmentioning

confidence: 99%

Section: Crosscutting Issues Relevant To the Evaluation Of Hazards Anmentioning

confidence: 99%

Section: Proposed Decision-making Strategy To Support Endocrine Disrumentioning

confidence: 99%

Section: Knowledge Gaps In Endocrine Screening and Testingmentioning

confidence: 99%

See 3 more Smart Citations

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

Matthiessen¹,

Ankley

Biever

et al. 2017

Integr Environ Assess Manag

Self Cite

View full text Add to dashboard Cite

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

Brüggemann

Licht

Fetter

et al. 2017

Enviro Toxic and Chemistry

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To be defined as an endocrine disruptor, a substance has to meet several criteria, including the induction of specific adverse effects, a specific endocrine mode of action, and a plausible link between both. The latter criterion in particular might not always be unequivocally determined, especially because the endocrine system consists of diverse endocrine axes. The axes closely interact with each other, and manipulation of one triggers effects on the other. The present review aimed to identify some of the many interconnections between these axes. The focus was on fish, but data obtained in studies on amphibians and mammals were considered if they assisted in closing data gaps, because most of the endocrine mechanisms are evolutionarily conserved. The review includes data both from ecotoxicological studies and on physiological processes and gives information on hormone/hormone receptor interactions or gene transcription regulation. The key events and key event relationships identified provide explanations for unexpected effects on one axis, exerted by substances suspected to act specifically on another axis. Based on these data, several adverse outcome pathway (AOP) segments are identified, describing connections between the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-thyroid (HPT) axes, the HPG and hypothalamic-pituitary-adrenal/interrenal (HPA/I) axes, and the HPT and HPA/I axes. Central key events identified across axes were altered aromatase activity as well as altered expression and function of the proteins 11b-hydroxysteroid dehydrogenase (11b-HSD) and steroidogenic acute regulatory (StAR) protein. Substance classes that act on more than one endocrine axis were, for example, goitrogens or aromatase inhibitors. Despite the wealth of information gathered, the present review only provides a few insights into the molecular nets of endocrine axes, demonstrating the complexity of their interconnections.

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

Ankley

Coady

Gross³

et al. 2018

Enviro Toxic and Chemistry

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Trenbolone acetate is widely used in some parts of the world for its desirable anabolic effects on livestock. Several metabolites of the acetate, including 17b-trenbolone, have been detected at low nanograms per liter concentrations in surface waters associated with animal feedlots. The 17b-trenbolone isomer can affect androgen receptor signaling pathways in various vertebrate species at comparatively low concentrations/doses. The present article provides a comprehensive review and synthesis of the existing literature concerning exposure to and biological effects of 17b-trenbolone, with an emphasis on potential risks to aquatic animals. In vitro studies indicate that, although 17b-trenbolone can activate several nuclear hormone receptors, its highest affinity is for the androgen receptor in all vertebrate taxa examined, including fish. Exposure of fish to nanograms per liter water concentrations of 17b-trenbolone can cause changes in endocrine function in the short term, and adverse apical effects in longer exposures during development and reproduction. Impacts on endocrine function typically are indicative of inappropriate androgen receptor signaling, such as changes in sex steroid metabolism, impacts on gonadal stage, and masculinization of females. Exposure of fish to 17b-trenbolone during sexual differentiation in early development can greatly skew sex ratios, whereas adult exposures can adversely impact fertility and fecundity. To fully assess ecosystem-level risks, additional research is warranted to address uncertainties as to the degree/breadth of environmental exposures and potential population-level effects of 17b-trenbolone in sensitive species.

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Population-relevant endpoints in the evaluation of endocrine-active substances (EAS) for ecotoxicological hazard and risk assessment

Cited by 33 publications

References 70 publications

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

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

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

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

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