Endocrine disruption in teleosts and amphibians is mediated by anthropogenic and natural environmental factors: implications for risk assessment.

Environmental variation in the Anthropocene involves several factors that interfere with endocrine systems of wildlife and humans, presenting a planetary boundary of still unknown dimensions. Here, we focus on chemical compounds and other impacts of anthropogenic and natural origins that are adversely affecting reproduction and development. The main sink of these endocrine disruptors (EDs) is surface waters, where they mostly endanger aquatic vertebrates, like teleost fish and amphibians. For regulatory purposes, EDs are categorized into EATS modalities (oestrogenic, androgenic, thyroidal, steroidogenesis), only addressing endocrine systems being assessable by validated tests. However, there is evidence that non-EATS modalities-and even natural sources, such as decomposition products of plants or parasitic infections-can affect vertebrate endocrine systems. Recently, the disturbance of natural circadian light rhythms by artificial light at night (ALAN) has been identified as another ED. Reviewing the knowledge about EDs affecting teleosts and amphibians leads to implications for risk assessment. The generally accepted WHO-definition for EDs, which focuses exclusively on 'exogenous substances' and neglects parasitic infections or ALAN, seems to require some adaptation. Natural EDs have been involved in coevolutionary processes for ages without resulting in a general loss of biodiversity. Therefore, to address the 'One Health'-principle, future research and regulatory efforts should focus on minimizing anthropogenic factors for endocrine disruption. This article is part of the theme issue 'Endocrine responses to environmental variation: conceptual approaches and recent developments'.

Metabolism-Disrupting Chemicals Affecting the Liver: Screening, Testing, and Molecular Pathway Identification.

The liver is the central metabolic organ of the body. The plethora of anabolic and catabolic pathways in the liver is tightly regulated by physiological signaling but may become imbalanced as a consequence of malnutrition or exposure to certain chemicals, so-called metabolic endocrine disrupters, or metabolism-disrupting chemicals (MDCs). Among different metabolism-related diseases, obesity and non-alcoholic fatty liver disease (NAFLD) constitute a growing health problem, which has been associated with a western lifestyle combining excessive caloric intake and reduced physical activity. In the past years, awareness of chemical exposure as an underlying cause of metabolic endocrine effects has continuously increased. Within this review, we have collected and summarized evidence that certain environmental MDCs are capable of contributing to metabolic diseases such as liver steatosis and cholestasis by different molecular mechanisms, thereby contributing to the metabolic syndrome. Despite the high relevance of metabolism-related diseases, standardized mechanistic assays for the identification and characterization of MDCs are missing. Therefore, the current state of candidate test systems to identify MDCs is presented, and their possible implementation into a testing strategy for MDCs is discussed.