Decisive new endpoints indicative of abnormal neurodevelopment
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Some standardized developmental and reproductive toxicity studies suggest or require serum thyroxine (T4) measures in pregnant, lactating, and developing rats, to screen for a chemical’s thyroid disrupting activity. However, the developing brain is not often examined concurrently by either histopathology or neurobehavior, making it is unclear when a serum T4 reduction is adverse. To address this knowledge gap, we have worked to identify potential endpoints indicative of thyroid disruption in the brain. In a series of hypothesis-driven investigations, abnormal cell migration and brain barrier disruption are two reproducible effects of TH interference in vivo. Importantly, these mechanisms can be evaluated using specific histopathology or molecular approaches, which could complement serum T4 measures in toxicology studies. In all, directed evaluation of TH targets in the developing rat brain could strengthen the interpretation of serum T4 measures, thus improving chemical assessment. This work does not reflect US EPA policy.