A 2-generation reproduction study was completed in 2001 by our NTP RACB contractor, TherImmune, in which the pups from high dose PTU treated rats all died within 4 days following weaning. It was determined that the cause of death was starvation since the incisors of these pups failed to erupt. The pups also exhibited a malformation phenotype similar to that of a knockout mouse known as """"""""toothless"""""""". The gene knocked out in this mouse is known as the Colony Stiimulating Factor 1 (aka Macrophage Stimulating Factor 1). This Project proposes to investigate the relationship between the effects of exposure of rats to 0.0015% w/v PTU in drinking water and alterations of CSF-1 and related genes in PND 10-28 day pups. Since PTU induced thyroid hormone disruption is known to be associated with neurological defects, the brains of these rats will also be examined.
