Characterization of phthalate exposure in relation to serum thyroid and growth hormones, and estimated daily intake levels in children exposed to phthalate-tainted products: A longitudinal cohort study

Background: No information is available on the long-term effects on thyroid and growth hormones of children exposed to phthalate-tainted products, despite the infamous 2011 Taiwan phthalate episode. We investigated estimated daily intake levels and their long-term effects on serum thyroid and growth hormone levels in children. Methods: We recruited 166 children (2-18 years old) in three visits who provided specimens and filled out a questionnaire from the Risk Assessment of Phthalate Incident in Taiwan (RAPIT) project study from 2012 to 2016. Morning spot urine samples were analyzed for nine phthalate metabolites. Serum thyroid (triiodothyronine [T-3], thyroxine [T-4], and free T-4) and growth hormone (insulin-like growth factor-1 [IGF-1] and its binding protein 3 [IGF-BP3]) levels were measured. A generalized estimating equation model was used to evaluate associations between phthalate metabolite levels and children's thyroid and growth hormone levels. Results: The median metabolite levels of monomethyl phthalate (MMP), Sigma dibutyl phthalate (DBP), and Edi-(2-ethylhexyl) phthalate (DEHP) at visits 1, 2, and 3 were 6.59, 10.5, and 21.0 ng/mL, 0.15, 0.24, and 0.20 nmol/mL, and 0.15, 0.17, and 0.12 nmol/mL, respectively. After adjusting for potential confounding factors, we found that levels of urinary MMP were negatively associated with T-3 (beta = -0.013, p = 0.047), T-4 (beta = -0.016, p = 0.006), free T-4 (beta = -0.012, p = 0.002), and IGF-BP3 (beta = -0.025, p = 0.003). Urinary mono-ethyl phthalate (MEP) was negatively associated with IGF-1 (beta = -0.027, p = 0.029) and IGF-BP3 (beta = -0.016, p = 0.018). In addition, serum free T-4 was positively associated with urinary mono-2-ethyl-5-hydroxy hexyl phthalate (MEHHP) (beta = 0.016, p = 0.043), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) (beta = 0.015, p = 0.024), and EDEHPm (beta = 0.019, p = 0.020). Conclusions: Our findings support the hypothesis that specific phthalates disturb the hemostasis of thyroid and growth hormone levels in children exposed to phthalate-tainted products. (C) 2020 Elsevier Ltd. All rights reserved.