Research project S4P/25/Fish4Thyroid (Research action S4P)
In the area of endocrine disruption there is an urgent need for new methods and assessment approaches to identify chemicals with thyroid hormone system disruption (THSD) potential in the context of, among others, REACH, CLP and the EU pesticides and biocides regulations, with a focus on integrated, mechanistically supported assessment strategies in a One Health approach, while reducing animal testing.
For regulatory environmental assessment of THSD, only amphibian tests are currently available. Both in vitro assays and augmented OECD fish Test Guidelines (TGs) (using protected and non-protected life stages) for the identification of chemicals with THSD properties have been developed and are currently under formal validation. This project will build upon these ongoing initiatives, and has the following objectives: (1) Further development of fish New Approach Methods (NAMs) for THSD: expanding the current set of THSD endpoints (thyroid histopathology, TH measurement, swim bladder inflation, eye development) for addition to the Fish Embryo Acute Toxicity (FET) test (OECD TG 236) with new endpoints for assessing THSD-induced developmental neurotoxicity (DNT), (2) Development of a method for measuring THs (3-3’-5-triiodothyronine [T3] and thyroxine [T4]) in the FET test using Liquid Chromatography–Mass Spectrometry (LC-MS/MS). Especially the measurement of low levels of 3-3’-5-triiodothyronine (T3) in fish embryos continues to be a challenge in the international community. (3) Development of adverse outcome pathways (AOPs) for THSD-induced DNT, building upon our existing THSD AOP network across vertebrates which will allow us to assess the potential of the use of fish to inform on both environmental and human health. (4) Development of an Integrated Approach to Testing and Assessment (IATA) for THSD: We will perform case studies that integrate in silico, in vitro and fish data for a set of regulatorily relevant chemicals that will be selected in collaboration with EU regulators and national competent authorities. On the one hand, the generated data will fill gaps for the case study chemicals. On the other hand, a decision-tree logic, aligned with the recently published ‘Application of the CLP Criteria’, will be developed to assess the different data types and conclude on the endocrine disrupting properties of a chemical within the different regulatory frameworks.
The work in this project addresses several action sheets of the National Action Plan on Endocrine Disruptors (NAPED) including the development of new scientific studies on THSD and the development of new methods for the identification of endocrine disruptors. The work builds on activities that have been performed in the first three years of the Partnership for the Assessment of Risks from Chemicals (PARC) and will be supported and co-funded by three new PARC activities running in parallel.
