Urinary phthalate metabolites in relation to biomarkers of inflammation and oxidative stress: NHANES 1999–2006

Phthalate esters are a class of compounds utilized extensively in widely-distributed consumer goods, and have been associated with various adverse health outcomes in previous epidemiologic research. Some of these health outcomes may be the result of phthalate-induced increases in oxidative stress or inflammation, which have been demonstrated in animal studies. The aim of this study was to explore the relationship between urinary phthalate metabolite concentrations and serum markers of inflammation and oxidative stress (C-reactive protein (CRP) and gamma glutamyltransferase (GGT), respectively). Subjects were participants in the National Health and Nutrition Examination Survey (NHANES) between the years 1999 and 2006. In multivariable linear regression models, we observed significant positive associations between CRP and mono-benzyl phthalate (MBzP) and mono-isobutyl phthalate (MiBP). There were CRP elevations of 6.0% (95% confidence interval (CI) 1.7–10.8%) and 8.3% (95% CI 2.9–14.0%) in relation to interquartile range (IQR) increases in urinary MBzP and MiBP, respectively. GGT was positively associated with mono(2-ethylhexyl) phthalate (MEHP) and an MEHP% variable calculated from the proportion of MEHP in comparison to other di(2-ethylhexyl) phthalate (DEHP) metabolites. IQR increases in MEHP and MEHP% were associated with 2.5% (95% CI 0.2–4.8%) and 3.7% (95% CI 1.7–5.7%) increases in GGT, respectively. CRP and GGT were also inversely related to several phthalate metabolites, primarily oxidized metabolites. In conclusion, several phthalate monoester metabolites that are detected in a high proportion of urine samples from the US general population are associated with increased serum markers of inflammation and oxidative stress. On the other hand, several oxidized phthalate metabolites were inversely associated with these markers. These relationships deserve further exploration in both experimental and observational studies.

Research highlights► Multiple urinary phthalate metabolites are detected in the majority of NHANES participants. ► Metabolites of di-butyl phthalate and benzylbutyl phthalate were associated with increased serum C-reactive protein (CRP), a marker of inflammation. ► The monoester metabolite of di-(2-ethylhexyl) phthalate (DEHP) was associated with increased gamma glutamyltransferase (GGT), a marker of oxidative stress. ► There was evidence for potential metabolic susceptibility to DEHP exposure in relation to CRP and GGT based on DEHP metabolite ratios. ► Several oxidized phthalate metabolites were inversely associated with CRP and GGT.