Adverse Outcome Pathway on inhibition of Thyroperoxidase and subsequent adverse neurodevelopmental outcomes in mammals

Kevin M. Crofton, Mary Gilbert, Katie Paul Friedman, Barbara Demeneix, Mary Sue Marty and R. Thomas Zoeller
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Kevin M. Crofton: R3Fellows LLC
Mary Gilbert: US Environmental Protection Agency (EPA)
Katie Paul Friedman: US Environmental Protection Agency (EPA)
Barbara Demeneix: National History Museum
Mary Sue Marty: Dow Chemical Company
R. Thomas Zoeller: University of Massachusetts

No 13, OECD Series on Adverse Outcome Pathways from OECD Publishing

Abstract: This AOP describes one adverse outcome that may result from the inhibition of thyroperoxidase (TPO) during mammalian development. Chemical inhibition of TPO results in decreased thyroid hormone (TH) synthesis, and subsequent reduction in circulating concentrations of THs. THs are essential for normal human brain development, both prenatally and postnatally, modulating genes critical for a normal neuroanatomical development, with subsequent effects on neurophysiology, and finally neurological function. Therefore, chemicals that interfere with TH synthesis have the potential to cause TH insufficiency that may result in adverse neurodevelopmental effects in offspring. Herein, we discuss the implications of developmental TPO inhibition for hippocampal anatomy, function, and ultimately neural function. The hippocampus is known to be critically involved in cognitive, emotional, and memory function. The adverse consequences of TH insufficiency depend both on severity and developmental timing, indicating that exposure to TPO inhibitors may produce different effects at different developmental windows of exposure.

Date: 2019-07-30
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Persistent link: https://EconPapers.repec.org/RePEc:oec:envaad:13-en

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