Association of phthalate exposure with thyroid function during pregnancy.

Arash Derakhshan,Carl-Gustaf Bornehag,Christian H Lindh,Robin P Peeters,Maarten A.C Broeren,Tim I.M Korevaar,Andreas Kortenkamp,Huan Shu,Barbara Demeneix

doi:10.1016/j.envint.2021.106795

Abstract

The extent of thyroid disruptive effects of phthalates during pregnancy remains unclear. To investigate the association of maternal urinary phthalates with markers of the thyroid system during early pregnancy. Urinary concentrations of phthalate metabolites and serum concentrations of thyroid stimulating hormone (TSH), free and total thyroxine (FT4 and TT4) and free and total triiodothyronine (FT3 and TT3) were measured in pregnant women in early pregnancy in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study (2007-ongoing), a population-based prospective cohort. In the 1,996 included women, higher di-ethyl-hexyl phthalate (DEHP) metabolites were associated with a lower FT4 (β [SE] for the molar sum: -0.13 [0.06], P=0.03) and a higher TSH/FT4 ratio (0.003 [0.001], P=0.03). Higher concentrations of di-iso-nonyl phthalate (DINP) metabolites were associated with a lower TT4 (β [SE] for the molar sum: 0.93 [0.44], P=0.03) as well as with lower TT4/FT4 and TT4/TT3 ratios. Higher metabolites of both dibutyl and butyl-benzyl phthalate (DBP and BBzP) were associated with lower T4/T3 ratio (free and total) and higher FT4/TT4 and FT3/TT3 ratios. A higher diisononyl cyclohexane dicarboxylate (DINCH) metabolite concentration was associated with a higher TT3. These results translate results from experimental studies suggesting that exposure to phthalates may interfere with the thyroid system during pregnancy. This is also true for compounds that have been introduced to replace known disruptive phthalates. Further experimental studies should take into account the human evidence to better investigate the potential underlying mechanisms of thyroid disruption by phthalates.

Highlights

Phthalates are pseudo-persistent synthetic chemical compounds widely used in plastic and personal care products such as food packaging and cosmetics
Experimental studies have shown that phthalates interfere with the thyroid system by altering expression of genes involved in hypothalamic-pituitary-thyroid (HPT) axis, thyroid hormone transport, metabolism and action (Sun et al, 2018; Kim et al, 2018; Ye et al, 2017; Dong et al, 2017; Jia et al, 2016; Liu et al, 2015; Wenzel et al, 2005; Duan et al, 2018; Ishihara et al, 2003; O’Connor et al, 2002)
The aim of this study is to fill this gap by investigating associations of maternal phthalate exposure with a wide spectrum of maternal thyroid function measurements dur ing early pregnancy

Summary

Introduction

Phthalates are pseudo-persistent synthetic chemical compounds widely used in plastic and personal care products such as food packaging and cosmetics. Results: In the 1,996 included women, higher di-ethyl-hexyl phthalate (DEHP) metabolites were associated with a lower FT4 (β [SE] for the molar sum: − 0.13 [0.06], P = 0.03) and a higher TSH/FT4 ratio (0.003 [0.001], P = 0.03). Higher concentrations of di-iso-nonyl phthalate (DINP) metabolites were associated with a lower TT4 (β [SE] for the molar sum: 0.93 [0.44], P = 0.03) as well as with lower TT4/FT4 and TT4/TT3 ratios. Conclusions: These results translate results from experimental studies suggesting that exposure to phthalates may interfere with the thyroid system during pregnancy. This is true for compounds that have been introduced to replace known disruptive phthalates. Further experimental studies should take into account the human evidence to better investigate the potential underlying mechanisms of thyroid disruption by phthalates

Objectives

Methods

Results