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

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

The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay.

Phthalates are industrial chemicals widely used in many commercial applications. The general population is exposed to phthalates through consumer products as well as through diet and medical treatments. To determine whether environmental levels of phthalates are associated with altered DNA integrity in human sperm, we selected a population without identified sources of exposure to phthalates. One hundred sixty-eight subjects recruited from the Massachusetts General Hospital Andrology Laboratory provided a semen and a urine sample. Eight phthalate metabolites were measured in urine by using high-performance liquid chromatography and tandem mass spectrometry; data were corrected for urine dilution by adjusting for specific gravity. The neutral single-cell microgel electrophoresis assay (comet assay) was used to measure DNA integrity in sperm. VisComet image analysis software was used to measure comet extent, a measure of total comet length (micrometers); percent DNA in tail (tail%), a measure of the proportion of total DNA present in the comet tail; and tail distributed moment (TDM), an integrated measure of length and intensity (micrometers). For an interquartile range increase in specific gravity-adjusted monoethyl phthalate (MEP) level, the comet extent increased significantly by 3.6 micro m [95% confidence interval (95% CI), 0.74-6.47]; the TDM also increased 1.2 micro m (95% CI, -0.05 to 2.38) but was of borderline significance. Monobutyl, monobenzyl, monomethyl, and mono-2-ethylhexyl phthalates were not significantly associated with comet assay parameters. In conclusion, this study represents the first human data to demonstrate that urinary MEP, at environmental levels, is associated with increased DNA damage in sperm

Tracking toxins

Biomonitoring outshines the indirect assessment of exposure in determining which pollutants enter the body, and whether they cause disease or disabilit