Feasibility and reliability of a downsized comparative thyroid assay for evaluating thyroid hormone disrupting activity in maternal rats and their offspring: reproducibility study with sodium phenobarbital

<p>As thyroid hormones (THs) are essential for brain development, concern has been raised that mild THs disrupting chemicals may have potential to interfere with the developing brain. Since guideline studies to evaluate developmental neurotoxicity require significant resources, a simple screening assay would be valuable. The Comparative Thyroid Assay (CTA) is a candidate screening test, but it requires several animals and advanced techniques of sampling and THs measurements. We are currently attempting to develop a downsized CTA that reduces the animal number, while adding extra parameters in offspring (brain THs levels and histology). We had shown that 6-propylthiouracil (10 ppm) induced severe (> 50%) reduction of THs and offspring brain abnormalities, while phenobarbital (PB, 1000 ppm) induced mild (approx. 30%) reduction of THs but did not induce brain abnormalities. Here we investigated suitability of doses tested and reproducibility of the findings with PB. 1000 and 1500 ppm PB were fed to 10 pregnant rats/group from (1) gestational days (GD)6 to 20, and (2) from GD6 to lactation day 21. THs levels and brain histology were examined. The previous findings at 1000 ppm were reproduced. Compared to 1000 ppm, 1500 ppm revealed similar or slightly more potent THs suppression but was an excessive dose as evidenced by neurological signs in all dams and reduced pup survival. These findings suggest that the modified CTA is feasible and reliable and mild suppression of THs may have little impact on offspring brain development. Further studies should be investigated.</p>