ECETOC task force studies the relationship between thyroid hormone imbalance in pregnant rats and neurodevelopmental effects in their pups

The third in a series of four reports on developing a science-based testing strategy for maternal thyroid disruption and neurodevelopmental effects on offspring has now been published in the medical journal Critical Reviews in Toxicology (read the full manuscript here).

The thyroid gland plays a critical role in mammalian neurodevelopment, as well as, more generally, in reproduction and development. The scientific and regulatory communities are concerned about a potential connection between chemicals that reduce the blood levels of thyroid hormones, in particular thyroxine (T4), and impaired mental development in children. However, a science-based testing strategy to determine such effects is currently unavailable, and this has caused uncertainty in the EU regulatory environments for plant protection products, biocides and REACH chemical regulations.

The review, by the Centre for chemical safety assessment (ECETOC) T4 Task Force, investigated which patterns of thyroid- and brain-related effects can be seen in rats resulting from gestational or lactational exposure to 14 substances that cause thyroid hormone imbalance.

From the rat data reviewed, maternal thyroid hormone levels were generally not useful to predict neurodevelopmental effects in their progeny. However, thyroid hormone levels in the rat pups did appear to be relevant for predicting the likelihood of statistically significant neurodevelopmental effects. Measurements of brain thyroid hormone levels also appear to be relevant.

For rats, observed neurodevelopmental effects commonly include alterations in learning and memory, motor activity, hearing or specific brain structures. Similarly, studies on humans have shown that thyroid hormone imbalance in pregnant mothers can cause reduced intelligence, impaired learning and memory, motor deficits as well as other neurobehavioural changes including attention deficits and hyperactivity in the child. However, all these deficits can also be caused by factors unrelated to thyroid function.

The first study by ECETOC’s T4 Task Force 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.

Now the findings from all three studies will be used in a final fourth review that presents a tiered testing strategy to determine whether gestational and/or lactational substance exposure may cause thyroid hormone imbalance and potentially also neurodevelopmental effects. The testing strategy will help ensure that man-made substances are safe to humans while at the same time avoiding animal testing.