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 as prescreening for potential of developmental neurotoxicity.
Principal Investigator:
Tomoya Yamada, DVM, PhD (Fellow, Environmental Health Science Laboratory, Sumitomo
Chemical Company, Ltd.)
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, Environmental Health Science Laboratory, Sumitomo
Chemical Company, Ltd.,)
3-1-98 Kasugadenaka, Konohanaku, Osaka 554-8558, Japan(e-mail) sutoh@sc.sumitomo-chem.co.jp
Summary of Research:
As thyroid hormones (THs) are essential for brain development, concern has been raised that mildTHs 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 (PTU, 10 ppm) induced severe (> 50%) reduction of THs andoffspring brain abnormalities (heterotopia), while phenobarbital (PB, 1000 ppm) induced mild(approx. 30%) reduction of THs but did not induce brain abnormalities. Recently, the previousfindings at PB 1000 ppm were reproduced, and detection of heterotopia was improved by stepsection. 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.
Timeline:
March 1, 2021 – February 28, 2022.
Topics:Oral presentation at JCIA LRI Annual Workshop 2021 “Development of a short-term in vivo assayfor thyroid hormone disrupting activity in maternal rats and their fetuses/pups as prescreening forpotential of developmental neurotoxicity.” (On-line, August 20th, 2021)
Publications:〇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 maternal rats
and their fetuses/pups as prescreening for potential developmental neurotoxicity: Propylthiouraciland phenobarbital examples. I. Findings in maternal rats and their fetuses”. The 48th Annual
Meeting of the Japanese Society of Toxicology, Kobe, Japan, July 9th, 2021.
〇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 maternal rats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 Meetingof the Japanese Society of Toxicology, Kobe, Japan, July 9th, 2021.
Tomoya Yamada (Sumitomo Chemical Company, Ltd.)“A short-term in vivo assay for thyroid hormone disrupting activity in maternal rats and theirfetuses/pups as prescreening for potential developmental neurotoxicity”. The 61st Annual Meetingof the Japanese Society Teratology, On-line, August 8th, 2021.
Tomoya Yamada (Sumitomo Chemical Company, Ltd.)“Comparative Thyroid Assay: Current situation of a short-term in vivo assay for thyroid hormone
disrupting activity in maternal rats and their offspring as prescreening for potential developmentalneurotoxicity”. The 49th Annual Meeting of the Japanese Society of Toxicology, Sapporo, Japan,July 2022.
Kenta Minami1, 〇Hidenori Suto1, Akira Sato2, Keiko Ogata1, Kenta Minami1, Tadashi Kosaka2,
Hitoshi Hojo2, Naofumi Takahashi2, Naruto Tomiyama2, Hiroaki Aoyama2, Tomoya Yamada1 (1Sumitomo Chemical Company, Ltd. 2 The Institute of Environmental Toxicology)“Feasibility and reliability of a downsized comparative thyroid assay for evaluating thyroid hormone
disrupting activity in maternal rats and their offspring: reproducibility study with sodiumphenobarbital”. The 49th Annual Meeting of the Japanese Society of Toxicology, Sapporo, Japan,July 2022.