Exposure to environmental chemicals such as phthalates has been linked to numerous adverse pregnancy outcomes, potentially through an oxidative stress mediated mechanism. Most research examined urinary 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) as the oxidative stress biomarker. However, 8-iso-PGF 2α also originates from enzymatic sources linked to inflammation. Therefore, associations between phthalates and 8-iso-PGF 2α could have been misinterpreted. To clarify this, the 8-iso-PGF 2α /prostaglandin F 2α ratio approach was used to quantitatively distinguish between inflammation or oxidative stress derived 8-iso-PGF 2α and estimate their associations with phthalate metabolites in a cohort of 758 pregnant women from The Infant Development and Environment Study (TIDES). Most urinary phthalate metabolites were associated with a significant increase in 8-iso-PGF 2α . For example, a 22.4% higher 8-iso-PGF 2α concentration (95% confidence interval = 14.4, 30.9) was observed with an interquartile range increase in mono-n-butyl phthalate. For most metabolites, associations were observed solely with oxidative stress derived 8-iso-PGF 2α . In contrast, monocarboxy-isononyl phthalate and monoisononyl phthalate (MNP) were associated with both sources of 8-iso-PGF 2α . Metabolites of the phthalate alternative 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH), were only associated with inflammation-derived 8-iso-PGF2 α , which is interesting because DINCH metabolites and MNP have structural similarities . In conclusion, phthalates metabolites are not exclusively associated with oxidative stress derived 8-iso-PGF 2α . Depending on the metabolite structure, some are also associated with inflammation derived sources, which provides interesting insights in the toxicology of phthalates.
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