In a research article published online on August 4, 2021, in the peer-reviewed journal Environment International, Arash Derakhshan from the Academic Center for Thyroid Diseases, Rotterdam, Netherlands, and co-authors reported how exposure to phthalates during early pregnancy interferes with the thyroid system and by which underlying mechanisms.
The study was embedded in the Swedish Environmental Longitudinal Mother and Child, Asthma and Allergy (SELMA) study. Since 2007, scientists associated with the ongoing population-based pregnancy cohort study have been analyzing the effects of potential endocrine-disrupting chemicals (EDCs) on pregnancy, the health of mothers and infants, as well as on child development (FPF reported). For their study, Derakhshan and colleagues collected blood and urine samples from 1,996 pregnant mothers with a median gestational age of 10 weeks, all without thyroid disease and thyroid medication use. Subsequently, they measured 14 plasticizer metabolites in the urine and biomarkers in the blood serum to assess the maternal thyroid function, including the thyroid-stimulating hormone (TSH), free and total thyroxine (FT4 and TT4), and free and total triiodothyronine (FT3 and TT3).
The study found an association between the biomarker levels and plasticizer metabolites which indicates that exposure to di-ethyl-hexyl phthalate (DEHP, CAS 117-81-7) metabolites in particular, but also to di-iso-nonyl phthalate (DINP, CAS 28553-12-0), dibutyl phthalate (DBO; CAS 84-72-2), butyl-benzyl phthalate (BBzP; CAS 85-68-7), and diisononyl cyclohexane dicarboxylate (DINCH, CAS 166412-78-8) metabolites during pregnancy may disrupt maternal thyroid functioning. According to the researchers, this study is the first to analyze DINCH association with thyroid system effects in humans. The scientists reported that higher DINCH metabolite concentration was associated with a higher TT3 level indicating that DINCH affects the peripheral thyroid hormone metabolism. DINCH is a widely-used alternative to phthalates like DEHP but already previous studies linked DINCH metabolites to metabolic disruption such as the induction of fat cell formation (FPF reported). A recently conducted study by Alexandra Schaffert from the Helmholtz-Centre for Environmental Research (UFZ), Leipzig, Germany, and co-authors found that DINCH and its metabolite monoisononylcyclohexane-1,2-dicarboxylic acid ester (MINCH) can induce “cellular stress and pro-inflammatory effects in macrophages, which may lead to adverse health effects.” The research article was published on September 10, 2021, in the journal Cells.
The study by Derakhshan et al. further observed an inverted U-shaped association between DEHP metabolites’ concentration and thyroxine (TT4) levels, supporting previous findings on the non-monotonic dose-response effects of EDCs (FPF reported and here).
The authors concluded that exposure to phthalates as well as some substitutes of known harmful phthalates “may interfere with the thyroid system during pregnancy.” They also emphasized the need for future human longitudinal studies, that include repeated analysis of urinary phthalate concentrations and thyroid function analysis, to verify their results and “to better investigate the potential underlying mechanisms of thyroid disruption by phthalates.” Carl-Gustaf Bornehag from Karlsrad University, Sweden, who is one of the co-authors of the study will speak about their work at the 2021 Food Packaging Forum (FPF) Workshop which takes place online on October 6-8.
Since July 2020, EU’s REACH has restricted the use of four phthalates, including DEHP, in consumer products but the restriction does not apply to food contact materials (FPF reported). A study by the German Environment Agency (UBA) demonstrated that the total concentration of plasticizers in the environment has barely changed between the mid-2000s and 2017 (FPF reported), and, according to the outcomes of the European Human Biomonitoring Initiative (HBM4EU) in 2019, concentrations of phthalate-alternatives like DINCH are even increasing (FPF reported).
Derakhshan, A., et al. (2021). „Association of phthalate exposure with thyroid function during pregnancy.” Environment International. DOI: 10.1016/j.envint.2021.106795
Schaffert A., et al. (2021): “The emerging plasticizer alternative DINCH and its metabolite MINCH induce oxidative stress and enhance inflammatory responses in human THP-1 macrophages.” Cells. DOI: https://doi.org/10.1007/s00204-021-03152-7