TY - JOUR
T1 - Toward a science-based testing strategy to identify maternal thyroid hormone imbalance and neurodevelopmental effects in the progeny - part I
T2 - which parameters from human studies are most relevant for toxicological assessments?
AU - Sauer, Ursula G.
AU - Asiimwe, Alex
AU - Botham, Philip A.
AU - Charlton, Alex
AU - Hallmark, Nina
AU - Jacobi, Sylvia
AU - Marty, Sue
AU - Melching-Kollmuss, Stephanie
AU - Palha, Joana A.
AU - Strauss, Volker
AU - van Ravenzwaay, Bennard
AU - Swaen, Gerard
N1 - Funding Information:
We would like to thank the members of the ECETOC Scientific Committee for their critical comments. Also, we would like to thank all members of the ECETOC Special T4 Task Force as well as all participants of the November 2019 Extended Task Force Meeting for valuable discussions that contributed to the basis for this review. We are indebted to Olivier de Matos, Secretary General of ECETOC, and his team at ECETOC (Alice Brousse, Andreea Cuciureanu, Lisa Wingate, Virginie van der Steeg) for organisational and technical assistance to the ECETOC Special T4 Task Force and for support in preparing and holding the November 2019 Extended Task Force Meeting. A special thank you for the preparation and holding of that meeting also goes to Ursel Blum and Christine Gahn (BASF SE, Germany). The authors also extend a note of appreciation to the three reviewers selected by the Editor and anonymous to the authors of the paper. The comments of these reviewers were very useful in improving the manuscript.
Publisher Copyright:
© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2020/12/11
Y1 - 2020/12/11
N2 - 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.
AB - 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.
KW - Free thyroxine (fT4)
KW - thyroid stimulating hormone (TSH)
KW - thyroid disruption
KW - developmental neurotoxicity
KW - uridine diphosphate glucuronyltransferase (UGT)
KW - adverse outcome pathway (AOP)
KW - brain development
KW - pregnancy
KW - European Union guidelines
KW - endocrine disruptors
U2 - 10.1080/10408444.2020.1839380
DO - 10.1080/10408444.2020.1839380
M3 - (Systematic) Review article
C2 - 33305658
SN - 1040-8444
VL - 50
SP - 740
EP - 763
JO - Critical Reviews in Toxicology
JF - Critical Reviews in Toxicology
IS - 9
ER -