PMID- 36372265 OWN - NLM STAT- MEDLINE DCOM- 20221220 LR - 20221222 IS - 1096-0295 (Electronic) IS - 0273-2300 (Linking) VI - 137 DP - 2023 Jan TI - Feasibility study for a downsized comparative thyroid assay with measurement of brain thyroid hormones and histopathology in rats: Case study with 6-propylthiouracil and sodium phenobarbital at high dose. PG - 105283 LID - S0273-2300(22)00170-2 [pii] LID - 10.1016/j.yrtph.2022.105283 [doi] AB - Concern has been raised that thyroid hormone disruptors (THDs) may potentially interfere with the developing brain, but effects of mild suppression of maternal THs by environmental contaminants on neonatal brain development are not fully understood. The comparative thyroid assay (CTA) is a screening test for offspring THDs, but it requires several animals and is criticized that reliance on serum THs alone as predictive markers of brain malfunction is inadequate. To verify feasibility of the downsized CTA but additional examination of brain THs levels and histopathology, we commenced internal-validation studies. This paper presents the data of the study where 6-propylthiouracil (6-PTU, 10 ppm) and sodium phenobarbital (NaPB, 1000 ppm) were dosed by feeding from gestational days (GD)6-20, and from GD6 to lactation day 21. The modified CTA detected 6-PTU-induced severe (>70%) suppression of serum THs in dams, with >50% suppressed serum/brain TH levels in offspring and brain heterotopia in postnatal day 21 pups. The modified CTA also detected NaPB-induced mild (<35%) suppression of serum THs in dams, with mild (<35%) reduction of serum/brain TH levels in fetuses but not in pups. These findings suggest that the modified CTA may have a potential as a screening test for offspring THDs. CI - Copyright (c) 2022 Elsevier Inc. All rights reserved. FAU - Minami, Kenta AU - Minami K AD - Environmental Health Science Laboratory, Sumitomo Chemical Company, Ltd., 3-1-98, Kasugade-naka 3-chome, Konohana-ku, Osaka, 554-8558, Japan. FAU - Suto, Hidenori AU - Suto H AD - Environmental Health Science Laboratory, Sumitomo Chemical Company, Ltd., 3-1-98, Kasugade-naka 3-chome, Konohana-ku, Osaka, 554-8558, Japan. FAU - Sato, Akira AU - Sato A AD - Institute of Environmental Toxicology, 4321, Uchimoriya-machi, Joso-shi, Ibaraki, 303-0043, Japan. FAU - Ogata, Keiko AU - Ogata K AD - Environmental Health Science Laboratory, Sumitomo Chemical Company, Ltd., 3-1-98, Kasugade-naka 3-chome, Konohana-ku, Osaka, 554-8558, Japan. FAU - Kosaka, Tadashi AU - Kosaka T AD - Institute of Environmental Toxicology, 4321, Uchimoriya-machi, Joso-shi, Ibaraki, 303-0043, Japan. FAU - Hojo, Hitoshi AU - Hojo H AD - Institute of Environmental Toxicology, 4321, Uchimoriya-machi, Joso-shi, Ibaraki, 303-0043, Japan. FAU - Takahashi, Naofumi AU - Takahashi N AD - Institute of Environmental Toxicology, 4321, Uchimoriya-machi, Joso-shi, Ibaraki, 303-0043, Japan. FAU - Tomiyama, Naruto AU - Tomiyama N AD - Institute of Environmental Toxicology, 4321, Uchimoriya-machi, Joso-shi, Ibaraki, 303-0043, Japan. FAU - Fukuda, Takako AU - Fukuda T AD - Bioscience Research Laboratory, Sumitomo Chemical Company, Ltd., 3-1-98 Kasugade-naka, Konohana-ku, Osaka, 554-8558, Japan. FAU - Iwashita, Katsumasa AU - Iwashita K AD - Environmental Health Science Laboratory, Sumitomo Chemical Company, Ltd., 3-1-98, Kasugade-naka 3-chome, Konohana-ku, Osaka, 554-8558, Japan. FAU - Aoyama, Hiroaki AU - Aoyama H AD - Institute of Environmental Toxicology, 4321, Uchimoriya-machi, Joso-shi, Ibaraki, 303-0043, Japan. FAU - Yamada, Tomoya AU - Yamada T AD - Environmental Health Science Laboratory, Sumitomo Chemical Company, Ltd., 3-1-98, Kasugade-naka 3-chome, Konohana-ku, Osaka, 554-8558, Japan. Electronic address: yamadat8@sc.sumitomo-chem.co.jp. LA - eng PT - Journal Article DEP - 20221111 PL - Netherlands TA - Regul Toxicol Pharmacol JT - Regulatory toxicology and pharmacology : RTP JID - 8214983 RN - 721M9407IY (Propylthiouracil) RN - 0 (Thyroid Hormones) RN - YQE403BP4D (Phenobarbital) RN - 9NEZ333N27 (Sodium) SB - IM MH - Female MH - Animals MH - Rats MH - *Propylthiouracil/toxicity MH - *Thyroid Gland MH - Feasibility Studies MH - Thyroid Hormones MH - Phenobarbital/pharmacology MH - Brain MH - Sodium/pharmacology OTO - NOTNLM OT - 6-Propylthiouracil OT - Comparative thyroid assay OT - Developmental neurotoxicity OT - Endocrine disruption OT - Heterotopia OT - Hypothyroidism OT - Screening OT - Sodium phenobarbital OT - Thyroid hormone OT - Uridine diphosphate glucuronyltransferase (UGT) COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/11/14 06:00 MHDA- 2022/12/21 06:00 CRDT- 2022/11/13 19:33 PHST- 2022/06/14 00:00 [received] PHST- 2022/10/12 00:00 [revised] PHST- 2022/10/29 00:00 [accepted] PHST- 2022/11/14 06:00 [pubmed] PHST- 2022/12/21 06:00 [medline] PHST- 2022/11/13 19:33 [entrez] AID - S0273-2300(22)00170-2 [pii] AID - 10.1016/j.yrtph.2022.105283 [doi] PST - ppublish SO - Regul Toxicol Pharmacol. 2023 Jan;137:105283. doi: 10.1016/j.yrtph.2022.105283. Epub 2022 Nov 11.