Project 1 Researchers Find that Exposure to Phthalate Mixtures is Associated with Oxidative Stress Biomarker

Dec 8, 2021 | Project 1 (Targeted Epidemiology), PROTECT Research

PROTECT Project 1 researchers have found that exposure to a mixture of phthalate metabolites has a strong positive association with oxidative stress. This work, published in a paper in Environment International in September 2021, contributes to a better understanding of why exposure to phthalates is linked to an increased risk of preterm birth.

Phthalates are a class of synthetic plasticizers commonly used in the manufacturing of consumer products such as personal care products and plastic food packaging. Since the use of phthalates is so common, everyone has detectable levels of at least several phthalates in their body throughout every stage of life. Unfortunately, exposure to phthalates is also linked to adverse health and pregnancy outcomes such as increased risk of preterm birth.

It is known that exposure to phthalates is linked to increased risk of preterm birth is known, but the mechanisms behind the link are not entirely clear. One possible explanation is that exposure to phthalate mixtures may increase levels of oxidative stress, a state that occurs when there is an excess of free radicals in the body’s cells, which can lead to damage in cells, proteins, and DNA.

Past PROTECT research demonstrates a strong association between exposure to single phthalates and oxidative stress. Project 1 researchers built on this work to investigate if exposure to a mixture of phthalates had a positive association with oxidative stress. Researchers took urinary biomarker measurements from 775 pregnant women in the PROTECT cohort at three different points during gestation. They then used lipid peroxidation biomarker 8-Iso-postaglandin-F2α (8-Iso-PGF2α) to measure levels of oxidative stress. This biomarker is commonly used to measure oxidative stress, but it can be derived through either chemical or enzymatic lipid peroxidation pathways. Researchers used quantitative methods to assess the concentration of the biomarker coming from either pathway to further understand how phthalate exposures affect the physiological pathways that contribute to preterm birth.

The biomarker 8-Iso-PGF2α indicated that exposure to a mixture of phthalates has a strong positive association with oxidative stress. Through observations of the interactions between the various metabolites in the phthalate mixture, researchers also found that metabolites have different effects on oxidative stress when they occur together compared to when they occur separately, meaning exposure to mixtures affects the body differently than exposure to single contaminants. When observing the difference between chemical lipid peroxidation and enzymatic lipid peroxidation, researchers also saw that different phthalate components of the mixture were important for each pathway. These findings suggest that exposure to a mixture of phthalate compounds can increase levels of oxidative stress and may in turn increase the risk of preterm delivery.

This publication continues Project 1’s push to study contaminant mixtures rather than single chemicals. People will continue to have detectable levels of multiple phthalates at once, so future research will focus more on how exposure to mixtures physiologically affects the body rather than how single phthalates do. Knowledge of how these phthalate mixtures interact and why they affect human health remains important to understanding health endpoints.

This graph displays the total percent change in 8-Iso-PGF2α with varying quantiles of exposure to the phthalate mixtures, relative to the median.

The portion of change in 8-Iso-PGF2α that came from chemical lipid peroxidation.

The portion of change in 8-Iso-PGF2α that came from enzymatic lipid peroxidation.