Title of Research:
20-3-02

Development of a short-term in vivo assay for thyroid hormone
disrupting activity in maternal rats and their fetus/pups asprescreening for potential of developmental neurotoxicity.
Principal Investigator:
Tomoya Yamada, DVM, PhD (Fellow, Sumitomo Chemical Company, Ltd., Environmental HealthScience Laboratory)
3-1-98 Kasugadenaka, Konohanaku, Osaka 554-8558, Japan(e-mail) yamadat8@sc.sumitomo-chem.co.jp
Collaborators:
Hiroaki Aoyama, PhD (Executive Director, Toxicology Division, The Institute of EnvironmentalToxicology)
4321 Uchimoriya-machi, Joso-shi, Ibaraki 303-0043, Japan(e-mail) aoyama@iet.or.jp
Hidenori Suto, PhD (Research Associate, Sumitomo Chemical Company, Ltd., Environmental
Health Science Laboratory)
3-1-98 Kasugadenaka, Konohanaku, Osaka 554-8558, Japan(e-mail) sutoh@sc.sumitomo-chem.co.jp
Summary of Research:
While thyroid hormones (THs) are essential for brain development, effects of mild suppression ofmaternal blood THs by hepatic enzyme inducers on the infant brain developments is not fully
understood. Conducting guideline study to identify of developmental neurotoxicity induced bychemicals requires significant resources (animals, time and costs). A simple screening test forinvestigating whether maternal chemical exposure reduces brain THs in fetal and neonatal rats
would be valuable. To verify reliability of the Comparative Thyroid Assay with additional
examination of the brain, THs and histology, propylthiouracil (PTU, 10 ppm) and phenobarbital (PB,1000 ppm) were dosed by feeding. Clearly suppressed brain THs in rat fetuses and pups andbrain abnormality (heterotopia) in pups were noted with PTU but not with PB. Reproducibility andeffects of PB at higher dose level will be examined in further study.
Timeline:
March 1, 2020 – February 28, 2021.
Topics:Oral presentation at JCIA LRI Annual Workshop 2020 “Development of a short-term in vivo assay
for thyroid hormone disrupting activity in maternal rats and their fetuses/pups as prescreening forpotential of developmental neurotoxicity.” (On-line, August 21st, 2020)
Publications:
1. Hidenori Suto1, Akira Sato2, Keiko Ogata1, Kenta Minami1, Tadashi Kosaka2, Hitoshi Hojo2,Naofumi Takahashi2, Naruto Tomiyama2, Katsumasa Iwashita1, Hiroaki Aoyama2, TomoyaYamada1 (1 Sumitomo Chemical Company, Ltd. 2 The Institute of Environmental Toxicology)“Development of a short-term in vivo assay for thyroid hormone disrupting activity in maternalrats and their fetuses/pups as prescreening for potential developmental neurotoxicity:
Propylthiouracil and phenobarbital examples. I. Findings in maternal rats and their fetuses”.
The 48th Annual Meeting of the Japanese Society of Toxicology, Kobe, Japan, July 2021.
2.

Akira Sato1, Hidenori Suto2, Keiko Ogata2, Kenta Minami2, Tadashi Kosaka1, Hitoshi Hojo1,Naofumi Takahashi1, Naruto Tomiyama1, Katsumasa Iwashita2, Hiroaki Aoyama1, Tomoya
Yamada2 (1 The Institute of Environmental Toxicology 2 Sumitomo Chemical Company, Ltd.)“Development of a short-term in vivo assay for thyroid hormone disrupting activity in maternalrats and their fetuses/pups as prescreening for potential developmental neurotoxicity:Propylthiouracil and phenobarbital examples. II. Findings in maternal rats and their pups”.
The 48th Annual Meeting of the Japanese Society of Toxicology, Kobe, Japan, July 2021.