Arash Derakhshan1, Huan Shu2, Maarten A C Broeren3, Christian H Lindh4, Robin P Peeters1, Andreas Kortenkamp5, Barbara Demeneix6, Carl-Gustaf Bornehag7, Tim I M Korevaar8. 1. Academic Center for Thyroid Diseases, Erasmus MC, Dr. Molewaterplein 15, 3051 GE Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus MC, Dr. Molewaterplein 15, 3051 GE Rotterdam, the Netherlands. 2. Department of Health Sciences, Karlstad University, 651 88 Karlstad, Sweden. 3. Laboratory of Clinical Chemistry and Haematology, Máxima Medical Centre, Veldhoven, De Run 4600, the Netherlands. 4. Division of Occupational and Environmental Medicine, Lund University, Lund, 22363 Lund, Sweden. 5. Division of Environmental Sciences, College of Health, Medicine and Life Sciences, Brunel University, London, Uxbridge, UK. 6. Laboratoire d'Evolution des Régulations Endocriniennes, CNRS/Muséum National d'Histoire Naturelle, 57 Rue Cuvier, 75005 Paris, France. 7. Department of Health Sciences, Karlstad University, 651 88 Karlstad, Sweden; Icahn School of Medicine at Mount Sinai, New York City, NY 10029-6574, USA. 8. Academic Center for Thyroid Diseases, Erasmus MC, Dr. Molewaterplein 15, 3051 GE Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus MC, Dr. Molewaterplein 15, 3051 GE Rotterdam, the Netherlands. Electronic address: t.korevaar@erasmusmc.nl.
Abstract
BACKGROUND: The extent of thyroid disruptive effects of phthalates during pregnancy remains unclear. AIM: To investigate the association of maternal urinary phthalates with markers of the thyroid system during early pregnancy. METHODS: 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. 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. 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. CONCLUSIONS: 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.
BACKGROUND: The extent of thyroid disruptive effects of phthalates during pregnancy remains unclear. AIM: To investigate the association of maternal urinary phthalates with markers of the thyroid system during early pregnancy. METHODS: 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. 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. 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. CONCLUSIONS: 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.
Authors: Diana C Pacyga; Diana K Haggerty; Megan Nicol; Melissa Henning; Antonia M Calafat; Joseph M Braun; Susan L Schantz; Rita S Strakovsky Journal: Environ Int Date: 2022-03-02 Impact factor: 9.621