Toward a science-based testing strategy to identify maternal thyroid hormone imbalance and neurodevelopmental effects in the progeny – part I: which parameters from human studies are most relevant for toxicological assessments?. (20th October 2020)

• Record Type: Journal Article
• Authors: Sauer, Ursula G.; Asiimwe, Alex; Botham, Philip A.; Charlton, Alex; Hallmark, Nina; Jacobi, Sylvia; Marty, Sue; Melching-Kollmuss, Stephanie; Palha, Joana A.; Strauss, Volker; van Ravenzwaay, Bennard; Swaen, Gerard
• Is Part Of: Critical reviews in toxicology. Volume 50:Number 9(2020)
• Page Start: 740
• Page End: 763
• Publication Date: 2020-10-20
• Subjects: Free thyroxine (fT4) -- thyroid stimulating hormone (TSH) -- thyroid disruption -- developmental neurotoxicity -- uridine diphosphate glucuronyltransferase (UGT) -- adverse outcome pathway (AOP) -- brain development -- pregnancy -- European Union guidelines -- endocrine disruptors; Toxicology -- Periodicals; Poisons -- Physiological effect -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1080/10408444.2020.1839380
• Languages: English
• ISSNs: 1040-8444

Abstract

Abstract: The 2018 European Food Safety Authority/European Chemicals Agency Guidance on the Identification of Endocrine Disruptors lacks clarity on how the presence or absence of substance-induced maternal thyroid hormone imbalance, or the potential for subsequent deleterious consequences in child neurodevelopment, should be established by toxicological assessments. To address these uncertainties, this narrative review evaluates human evidence on how altered maternal thyroid function may be associated with child neurodevelopmental outcomes; and seeks to identify parameters in human studies that appear most relevant for toxicological assessments. Serum levels of free thyroxine (fT4) and thyroid stimulating hormone (TSH) are most frequently measured when assessing thyroid function in pregnant women, whereas a broad spectrum of neurodevelopmental parameters is used to evaluate child neurodevelopment. The human data confirms an association between altered maternal serum fT4 and/or TSH and increased risk for child neurodevelopmental impairment. Quantitative boundaries of effects indicative of increased risks need to be established. Moreover, it is unknown if altered serum levels of total T4, free or total triiodothyronine, or parameters unrelated to serum thyroid hormones might be more relevant indicators of such effects. None of the human studies established a link between substance-mediated liver enzyme induction and increased serum thyroid hormone clearance, let alone further to child neurodevelopmental impairment. This review identifies research needs to contribute to the development of toxicity testing strategies, to reliably predict whether substances have the potential to impair child neurodevelopment via maternal thyroid hormone imbalance.