ECETOC Task Force proposes a science-based testing strategy to predict if a chemical has the potential to disrupt the thyroid hormone system in humans

The ECETOC Thyroxine (T4) Task Force has developed a new science-based tiered testing strategy that aims to predict if substances have the potential to significantly disrupt the thyroid hormone system in pregnant women. Severe changes in thyroid hormone homeostasis may be associated with neurodevelopmental effects in their children.

A comprehensive, structured approach to assess such effects is currently unavailable. This has created uncertainty in the EU regulatory environments for plant protection products, biocides and REACH chemicals. The ECETOC T4 Task Force was launched in Summer 2018 in response to this uncertainty.

The Task Force has now published its Proposal for a Thyroid Function-Related Neurodevelopmental Toxicity Testing and Assessment Scheme (Thyroid-NDT-TAS) as the fourth in a series of scientific papers. For this publication, the Task Force collaborated with technical experts from Crop Life Europe.The first publication in 2020 looked at which parameters from human studies were most relevant for toxicological assessments; the second, in 2021, looked at how key events of relevant adverse outcome pathways could be addressed in toxicological assessments; and the third, in 2022, investigated which patterns of thyroid- and brain-related effects could be seen in rats resulting from gestational or lactational exposure to 14 substances that cause thyroid hormone imbalance

The Thyroid-NDT-TAS is based on the state-of-the-science; it has been developed to make human safety assessments more accurate while at the same time minimising animal testing, in line with the 3Rs principle to replace, reduce and refine animal testing. It is also designed to comply with current EU legislation on the identification of endocrine disrupting properties of substances.

The proposed testing strategy identifies (1) if a substance has the ability to elicit maternal and/or offspring thyroid hormone imbalance and potentially also neurodevelopmental effects in the progeny; and (2) if effects observed in rodents are relevant for humans.

The Task Force is recommending that registrants and regulators now apply the new Thyroid-NDT-TAS for all future regulatory assessments.