Comparative Thyroid Assay: Current situation of a short-term <i>in vivo</i> assay for thyroid hormone disrupting activity in maternal rats and their offspring as prescreen for potential developmental neurotoxicity

<p>Some xenobiotic substances disrupt thyroid homeostasis including on thyroid hormone (TH) signaling, synthesis, metabolism and excretion. Since THs are essential for normal brain development in human and animals, concern has been raised that TH disrupting chemicals may have potential to interfere with the developing brain. In contrast to strong anti-thyroid agents such as 6-propylthiouracil (PTU), suppression by liver enzyme inducers (e.g., phenobarbital, PB) is generally mild. Effects of mild suppression of maternal THs on the neonatal brain development is not fully understood. Since standardized guideline studies to identify developmental neurotoxicity requires significant resources, a simple screening test for investigating whether maternal chemical exposure reduces brain THs levels (a necessary precursor event for brain developmental disorders) in offspring would be valuable. Recently, we began verifying the feasibility and reliability of the Comparative Thyroid Assay (CTA; US.EPA, 2005) but downsizing the number of rats but with additional examination of brain THs levels and histology. Our findings suggest that the modified CTA is feasible and reliable as a short-term in vivo assay for THs disruption in offspring. The PB data indicate that mild reduction of THs in maternal rats by enzyme inducers may have little impact on brain development of offspring in contrast to the PTU-like phenotype in brain THs and morphology. Further study with similar substances to evaluate reproducibility is needed. I will present a summary and perspective of our research.</p>