In: Ecotoxicology and environmental safety: EES ; official journal of the International Society of Ecotoxicology and Environmental safety, Band 224, S. 112657
In: Ankley , G T , Coady , K K , Gross , M , Holbech , H , Levine , S L , Maack , G & Williams , M 2018 , ' A critical review of the environmental occurrence and potential effects in aquatic vertebrates of the potent androgen receptor agonist 17β-trenbolone ' , Environmental Toxicology and Chemistry , vol. 37 , no. 8 , pp. 2064-2078 . https://doi.org/10.1002/etc.4163
Trenbolone acetate is widely used in some parts of the world for its desirable anabolic effects on livestock. Several metabolites of the acetate, including 17β-trenbolone, have been detected at low nanograms per liter concentrations in surface waters associated with animal feedlots. The 17β-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 17β-trenbolone, with an emphasis on potential risks to aquatic animals. In vitro studies indicate that, although 17β-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 17β-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 17β-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 17β-trenbolone in sensitive species. Environ Toxicol Chem 2018;37:2064-2078. Published 2018 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.
In: Ecotoxicology and environmental safety: EES ; official journal of the International Society of Ecotoxicology and Environmental safety, Band 284, S. 116995
In: Audouze , K M L , Zgheib , E , Abass , K , Baig , A H , Forner-Piquer , I , Holbech , H , Knapen , D , Leonards , P E G , Lupu , D I , Palaniswamy , S , Rautio , A , Sapounidou , M & Martin , O V 2021 , ' Evidenced-Based Approaches to Support the Development of Endocrine-Mediated Adverse Outcome Pathways: Challenges and Opportunities ' , Frontiers in Toxicology , vol. 3 , 787017 . https://doi.org/10.3389/ftox.2021.787017
A transformation of regulatory toxicology is underway to meet the demands of testing increasing numbers of chemicals whilst reducing reliance on in vivo models. This transformation requires a shift from chemical safety assessment largely based on direct empirical observation of apical toxicity outcomes in whole organisms to predictive approaches in which outcomes and risks are inferred from accumulated mechanistic understanding. In the last decade, Adverse Outcome Pathways (AOPs) (Ankley et al., 2010; Ankley and Edwards, 2018) have captured the attention of regulators and researchers alike as a systematic approach for organizing knowledge that may support such inferences (Wittwehr et al., 2017). An AOP is a conceptual structured representation of existing toxicological knowledge describing the causally connected sequence of events, across different levels of biological organization, required to produce an adverse effect when an organism is exposed to a stressor. Specifically, AOPs depict a series of key events (KEs) linking a molecular initiating event (MIE, an interaction between a stressor (e.g., endogenous ligand, xenobiotic) and a biomolecule) to an adverse outcome (AO, at organism or population levels). The causal links between 2 KEs are referred to as key event relationships (KERs). AOPs provide a useful framework to connect mechanistic data to adverse effects on human health or wildlife populations as a basis for the identification of cell- or biochemical-based tests that could fit in Integrated Approaches to Testing and Assessment (IATAs), identifying KEs that could be targeted for the development of New Approach Methods (NAMs), as well as investigating similarities in mechanistic pathways between species. AOPs are also particularly salient for identifying potential Endocrine Disruptors (EDs). Indeed, both the World Health Organization (WHO) and the International Programme on Chemical Safety (IPCS) definition and the scientific criteria adopted by the European Union in 2017 are articulated around three ...