Blogs

This blog was written by Talia Sager.

At the 2026 SOT Workshop Session “Endocrine Disruption Safety Assessment Approaches for Cosmetics,” Katie Paul Friedman, UL Research Institutes’ Chemical Insights, presented, “Interpretation of Thyroid-Relevant Bioactivity Data.” Her talk emphasized the importance of understanding and identifying chemicals that may disrupt thyroid hormone (TH) function, particularly during early brain development when even minor to moderate TH insufficiencies can lead to permanent neurological effects.

Regulatory programs in the US, Canada, and the EU continue to emphasize endocrine disruption as a priority; yet, current guideline studies offer limited mechanistic insights into TH-disruption–specific modes of action and provide no effective path for screening the thousands of data-poor chemicals. High-Throughput screening (HTS) programs like ToxCast help address this gap by enabling the development of assays targeting molecular initiating events (MIEs) relevant to thyroid function at scale. Within the thyroid adverse outcome pathway (AOP) network, 26 MIEs have been identified, with 19 covered by about 100 assay endpoints in ToxCast. Despite this coverage, many assays have known sources of interference and no orthogonal HTS assays available for validation. Retrospective and prospective strategies to advance screening were explored.

One retrospective example used ToxCast data on the inhibition of deiodinase (DIO) enzymes, key regulators of TH activation and inactivation. These data were combined with high-throughput toxicokinetic (HHTK) modeling to derive targeted bioactivity exposure ratios (BERs), taking a pool of over 2,000 screened chemicals down to 58 with targeted BER values below 1,000. Of note, a first-trimester toxicokinetic model was developed, since disruption most relevant to the human population occurs at this phase, and incorporated into the R library httk, enabling simulation of a full-term pregnancy. By calculating an administered equivalent dose and comparing it against thyroid-relevant bioactivity in tissues where DIO activity occurs during sensitive developmental windows, the method improves biological relevance.

Importantly, the targeted BER, focused on thyroid-specific tissues and pregnancy physiology, reduced the number of chemicals requiring deeper evaluation by about 50% compared with a systemic BER from a non-pregnant model. With a narrowed list of prioritized chemicals, it was proposed to move screening into models with greater biological relevance, such as TSH-responsive 3D thyroid microtissues. Because these microtissues express the TSH receptor and exhibit growth responses similar to actual thyroid tissue, they help confirm that the bioactivity is relevant.

On the prospective side, the expansion of quantitative structure–activity relationship (QSAR) models that predict interactions across multiple thyroid-relevant MIEs were discussed. Challenges include the extensive expertise required for data curation and the limited chemical diversity of existing datasets, which may not encompass all chemicals of interest. Still, an in silico screen can be used to replace or reduce primary screening needs, help distinguish genuine mechanisms from assay interference, and guide implementation of orthogonal screens.

Stepping back, the work shared in this presentation highlights how quickly the science around thyroid disruption is evolving. With so many chemicals still lacking data, developing better ways to organize, interpret, and apply what is known is essential. The integration of high-throughput testing and models that consider early pregnancy physiology brings the field closer to understanding real-world human relevance. At the same time, the presentation underscored that no single assay or model can fully capture the complexity of thyroid biology. Each new tool adds another layer of understanding but also reminds us how much more there is to learn.

This blog reports on a presentation in the Workshop Session “Endocrine Disruption Safety Assessment Approaches for Cosmetics” that was held during the 2026 SOT Annual Meeting and ToxExpo. An on-demand recording of this session is available for meeting registrants on the SOT Online Planner and SOT Event App.

This blog was prepared by an SOT Reporter and represents the views of the author. SOT Reporters are SOT members who volunteer to write about sessions and events in which they participate during the SOT Annual Meeting and ToxExpo. SOT does not propose or endorse any position by posting this article. If you are interested in participating in the SOT Reporter program in the future, please email SOT Headquarters.