Cross-Sectional Estimation of Endogenous Biomarker Associations with Prenatal Phenols, Phthalates, Metals, and Polycyclic Aromatic Hydrocarbons in Single-Pollutant and Mixtures Analysis Approaches

Humans are exposed to mixtures of toxicants that can impact several biological pathways. We investigated the associations between multiple classes of toxicants and an extensive panel of biomarkers indicative of lipid metabolism, inflammation, oxidative stress, and angiogenesis.

This study characterizes cross-sectional endogenous biomarker signatures associated with individual and mixtures of prenatal toxicant exposures. These results can help inform the prioritization of specific pairs or clusters of endogenous biomarkers and exposure analytes for investigating health outcomes. https://doi.org/10.1289/EHP7396.

We conducted a cross-sectional study of 173 participants (median 26 wk gestation) from the LIFECODES birth cohort. We measured exposure analytes of multiple toxicant classes [metals, phthalates, phenols, and polycyclic aromatic hydrocarbons (PAHs)] in urine samples. We also measured endogenous biomarkers (eicosanoids, cytokines, angiogenic markers, and oxidative stress markers) in either plasma or urine. We estimated pair-wise associations between exposure analytes and endogenous biomarkers using multiple linear regression after adjusting for covariates. We used adaptive elastic net regression, hierarchical Bayesian kernel machine regression, and sparse-group LASSO regression to evaluate toxicant mixtures associated with individual endogenous biomarkers.

After false-discovery adjustment (<math><mrow><mi>q</mi><mo><</mo><mn>0.2</mn></mrow></math>), single-pollutant models yielded 19 endogenous biomarker signals associated with phthalates, 13 with phenols, 17 with PAHs, and 18 with trace metals. Notably, adaptive elastic net revealed that phthalate metabolites were selected for several positive signals with the cyclooxygenase (n=7<math><mrow><mi>n</mi><mo>=</mo><mn>7</mn></mrow></math>), cytochrome p450 (n=7<math><mrow><mi>n</mi><mo>=</mo><mn>7</mn></mrow></math>), and lipoxygenase (n=8<math><mrow><mi>n</mi><mo>=</mo><mn>8</mn></mrow></math>) pathways. Conversely, the toxicant classes that exhibited the greatest number of negative signals overall in adaptive elastic net were phenols (n=20<math><mrow><mi>n</mi><mo>=</mo><mn>20</mn></mrow></math>) and metals (n=21<math><mrow><mi>n</mi><mo>=</mo><mn>21</mn></mrow></math>).