| Di(2-ethylhexyl) Phthalate Metabolites May Alter Thyroid Hormone Levels in Men John D. Meeker,1 Antonia M. Calafat,2 and Russ Hauser3,4 1Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan, USA; 2National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA; 3Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA; 4Vincent Memorial Obstetrics and Gynecology Service, Andrology Laboratory and In Vitro Fertilization Unit, Massachusetts General Hospital, Boston, Massachusetts, USA 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 (T4) , total triiodothyronine (T3) , 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 T4 and T3 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 T4 [95% confidence interval (CI) , –0.18 to –0.03] and a 0.05 ng/mL decrease in T3 (95% CI, –0.10 to 0.01) compared with the first (lowest) MEHP quintile. The inverse relationship between MEHP and free T4 remained when we adjusted for oxidative metabolite concentrations ; this simultaneously demonstrated a suggestive positive association with free T4. Conclusions: Urinary MEHP concentrations may be associated with altered free T4 and/or total T3 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. Key words: biomarkers, endocrine disruption, epidemiology, hormone, phthalates, thyroid, urinary metabolites. Environ Health Perspect 115:1029–1034 (2007) . doi:10.1289/ehp.9852 available via http://dx.doi.org/ [Online 12 March 2007]
Address correspondence to: J. Meeker, Department of Environmental Health Sciences, University of Michigan School of Public Health, 6635 SPH Tower, 109 S. Observatory St., Ann Arbor, MI 48109 USA. Telephone: (734) 764-7184. Fax: (734) 763-8095. E-mail: meekerj@umich.edu We gratefully acknowledge the technical assistance of M. Silva, J. Reidy, E. Samandar, and J. Preau (CDC, Atlanta, GA) in measuring the urinary concentrations of phthalate metabolites ; L. Godfrey-Bailey in subject recruitment ; and J. Frelich in data management. This work was supported by grant ES09718 from the National Institute of Environmental Health Sciences, National Institutes of Health. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the CDC. The authors declare they have no competing financial interests. Received 24 October 2006 ; accepted 12 March 2007.
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