Thyroid hormone system disruption (THSD) is a growing concern in chemical hazard assessment due to its impact on human and environmental health and the scarce methods available for assessing the THSD potential of chemicals. In particular, the general lack of validated in silico and in vitro methods for assessing THS activity is of high concern. This manuscript provides an inventory of test methods relevant to THSD. Building on the Organisation for Economic Co-operation and Development (OECD) Guidance Document 150 and recent international developments, we highlight progress in in silico and in vitro methods, as well as in vivo assays. The provided inventory categorizes available methods according to the levels of the OECD Conceptual Framework, with an assessment of the validation status of each method. At Level 1, 12 in silico models that have been statistically validated and are directly related to THSD have been identified. At Level 2, 67 in vitro methods have been listed including those assessed in key initiatives such as the European Union Network of Laboratories for the Validation of Alternative Methods (EU-NETVAL) validation study to identify potential thyroid disruptors. At Levels 3-5, THSD-sensitive endpoints are being included in existing fish-based OECD Test Guidelines to complement amphibian assays. In total, the inventory counts 108 entries comprising established methods (e.g., OECD Test Guidelines) as well as citable methods that are under further development and in some cases are ready for validation or in the initial stages of validation. This work aims to support the ongoing development of strategies for regulatory hazard assessment, such as integrated approaches to testing and assessment (IATAs), for endocrine disruptors, addressing critical gaps in the current testing landscape for THSD in both human and environmental health contexts.

Endocrine disruption - the potential of chemicals, such as industrial chemicals or pesticides, to disrupt hormonal systems and cause adverse health effects - is of growing concern due to its impact on human and environmental health and the scarce methods available for assessing such hazards. In particular, the limited methods available for assessing disruption of the thyroid hormone system, is of high concern. This manuscript provides an inventory of test methods relevant for the assessment of thyroid hormone system disruption. We highlight progress in different types of methods such as computer simulations, cell-based methods, non-mammalian embryo-based methods and animal methods and include an assessment of the readiness of each method for implementation in chemical evaluations. In total, the inventory counts 108 entries comprising already established methods as well as recent developments. This work aims to support the ongoing development of strategies for evaluating endocrine disruption, addressing critical gaps in the current testing landscape for thyroid hormone system disruption in both human and environmental health contexts.

• Klíčová slova
• One Health, Thyroid hormone system disruption, endocrine disruption, new approach methods,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The prevalence of polymer usage in everyday activities has emerged as a detriment to both human life and the environment. A large number of studies describe severe impacts of micropolymers (MP) and nanopolymers (NP) on various organ systems, including the endocrine system. Additionally, plasticizers utilized as additives have been identified as endocrine-disrupting chemicals (EDCs). MP/NP, along with associated plasticizers, affect principal signalling pathways of endocrine glands such as the pituitary, thyroid, adrenal, and gonads, thereby disrupting hormone function and metabolic processes crucial for maintaining homeostasis, fertility, neural development, and fetal growth. This review delves into the sources, distribution, and effects of micropolymers, nanopolymers, and associated plasticizers acting as EDCs. Furthermore, it provides a detailed review of the mechanisms underlying endocrine disruption in relation to different types of MP/NP.

• Klíčová slova
• Endocrine disrupting chemical, Hormones, Hypothalamus-pituitary axis, Microplastic, Nanoplastic, Plasticizers,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Nonalcoholic fatty liver disease (NAFLD) is a growing concern worldwide, affecting 25% of the global population. NAFLD is a multifactorial disease with a broad spectrum of pathology includes steatosis, which gradually progresses to a more severe condition such as nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and eventually leads to hepatic cancer. Several risk factors, including exposure to environmental toxicants, are involved in the development and progression of NAFLD. Environmental factors may promote the development and progression of NAFLD by various biological alterations, including mitochondrial dysfunction, reactive oxygen species production, nuclear receptors dysregulation, and interference in inflammatory and immune-mediated signaling. Moreover, environmental contaminants can influence immune responses by impairing the immune system's components and, ultimately, disease susceptibility. Flame retardants (FRs) are anthropogenic chemicals or mixtures that are being used to inhibit or delay the spread of fire. FRs have been employed in several household and outdoor products; therefore, human exposure is unavoidable. In this review, we summarized the potential mechanisms of FRs-associated immune and inflammatory signaling and their possible contribution to the development and progression of NAFLD, with an emphasis on FRs-mediated interferon signaling. Knowledge gaps are identified, and emerging pharmacotherapeutic molecules targeting the immune and inflammatory signaling for NAFLD are also discussed.

• Klíčová slova
• cytokines, flame retardants, interferon, metabolic disruption, metabolism-disrupting chemicals, nonalcoholic fatty liver disease,
• MeSH
• biologické markery MeSH
• cílená molekulární terapie MeSH
• cytokiny metabolismus   MeSH
• interferony metabolismus   MeSH
• játra účinky léků   metabolismus   patologie   MeSH
• lidé MeSH
• mediátory zánětu metabolismus   MeSH
• náchylnost k nemoci * MeSH
• nealkoholová steatóza jater etiologie   metabolismus   patologie   MeSH
• objevování léků MeSH
• retardanty hoření škodlivé účinky   MeSH
• signální transdukce * MeSH
• zánět etiologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH
• cytokiny MeSH
• interferony MeSH
• mediátory zánětu MeSH
• retardanty hoření MeSH