Di(2-ethylhexyl) Phthalate Metabolites May Alter Thyroid Hormone Levels in Men

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Abstract
Phthalates are used extensively in many personal-care and consumer products, resulting in widespread nonoccupational human exposure through multiple routes and media. A limited number of animal studies suggest that exposure to phthalates may be associated with altered thyroid function, but human data are lacking. Concurrent samples of urine and blood were collected from 408 men. We measured urinary concentrations of mono(2-ethylhexyl) phthalate (MEHP), the hydrolytic metabolite of di(2-ethylhexyl) phthalate (DEHP), and other phthalate monoester metabolites, along with serum levels of free thyroxine (T(4)), total triiodothyronine (T(3)), and thyroid-stimulating hormone (TSH). Oxidative metabolites of DEHP were measured in urine from only 208 of the men. We found an inverse association between MEHP urinary concentrations and free T(4) and T(3) serum levels, although the relationships did not appear to be linear when MEHP concentrations were categorized by quintiles. There was evidence of a plateau at the fourth quintile, which was associated with a 0.11 ng/dL decrease in free T(4) [95% confidence interval (CI), -0.18 to -0.03] and a 0.05 ng/mL decrease in T(3) (95% CI, -0.10 to 0.01) compared with the first (lowest) MEHP quintile. The inverse relationship between MEHP and free T(4) remained when we adjusted for oxidative metabolite concentrations; this simultaneously demonstrated a suggestive positive association with free T(4). Urinary MEHP concentrations may be associated with altered free T(4) and/or total T(3) levels in adult men, but additional study is needed to confirm the observed findings. Future studies must also consider oxidative DEHP metabolites relative to MEHP as a potential marker of metabolic susceptibility to DEHP exposure.

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