Immunotoxicity of thyroid hormone system disrupting compounds in fish

Endocrine disrupting compounds (EDCs) are among the most studied environmental pollutants in the field of (eco)toxicology, and different fish species are commonly used as model organisms, especially for studying reprotoxic effects. Despite the scientific and regulatory importance of EDCs, little attention has been given to their immunotoxic effects in fish. Basic knowledge and test systems for immune-related outcomes in fish are limited. For example, while the impact of estrogenic EDCs on the fish immune system has raised some attention in the last decade, thyroid hormone system disrupting compounds (THSDCs) and their impact on the fish immune system are less well studied. Thus, this literature review is aimed at describing the immunomodulatory roles of thyroid hormones (THs), as well as summarizing the existing research on the immunotoxicity of THSDCs in fish. A simplified potential adverse outcome pathway (AOP) was created, explaining the key events between THSD and lowered survival of fish experiencing pathogen infections along with chemical exposure. This AOP demonstrates that THSDCs can alter immune system functioning on a molecular, cellular, and organism level and, therefore, lead to reduced survival by lowering pathogen resistance of fish. However, available data were mainly limited to molecular analyses of immune-related biomarkers and included only few studies that conducted experiments demonstrating immunotoxic effects at organism level that can inform about population-relevant outcomes. Our putatively developed and simplified AOP can support the incorporation of immune-related endpoints in EDC testing guidelines and aid the development of risk assessments for THSDCs for human and environmental health.