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

Abstract

Background: 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. Methods: 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. Results: 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\(_4\). Conclusions: 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.