化学物質の周産期曝露による甲状腺ホルモンかく乱と脳発達障害

抄録

Thyroid hormones (THs) are essential for proper nervous system development. Environmental chemicals that disrupt the thyroid system are of regulatory concern for potential adverse effects on the developing brain. However, since quantitative relationships between chemical-induced perinatal TH insufficiency and abnormal brain development have not been fully understood, OECD test guidelines were revised in 2018 to make measurement of peripheral TH levels mandatory in toxicity studies. If test chemical disrupts TH levels, then developmental neurotoxicity (DNT) should be assessed. Since studies to identify DNT are comprehensive and require substantial resources, a simple screening test is needed. We focused on a weight-of-evidence approach based on mode of action using a short-term in vivo study, the “Comparative Thyroid Assay (CTA)” in rats, and began verifying the feasibility of an augmented CTA by adding parameters (brain TH levels and brain histopathology) but reducing the number of rats. Our findings suggest that the augmented CTA can be a potential short-term in vivo assay for sorting perinatal TH disruptors. In addition to this, the augmented CTA can also be used for collecting data to build a model of physiologically based pharmacokinetics (PBPK) in the perinatal period, intended to utilizing new approach methodologies (NAMs).