Exposure to phthalates and their alternatives in relation to biomarkers of inflammation and oxidative stress in adults: Evidence from NHANES 2017-2018

Abstract

Abstract Phthalates and their alternatives are considered significant environmental risk factors that potentially influence inflammation and oxidative stress. However, their impact on biomarkers of inflammation and oxidative stress was inconsistent. This study aimed to explore the associations between phthalates and high-sensitivity C-reactive protein (hsCRP), gamma-glutamyl transferase (GGT), and white blood cell (WBC) counts, employing both univariate exposure and multivariate co-exposure models. For this analysis, a total of 1619 individuals aged 18 years and above, sourced from the National Health and Nutrition Examination Survey (NHANES) conducted between 2017 and 2018, were selected as subjects. We explored the associations between hsCRP, GGT, and WBC counts and eighteen different phthalate metabolites. Multiple linear regression analysis revealed significant associations between hsCRP and two specific metabolites: MCNP (β = 0.060, P = 0.034) and MEHP (β = -0.054, P = 0.049). We observed negative correlations of MCOP, MCPP, MHBP, and MONP with GGT (β = -0.036, P = 0.027; β = -0.045, P = 0.019; β = -0.046, P = 0.023; β = -0.053, P = 0.001, respectively). Conversely, MEHHP and MEHTP exhibited positive correlations with GGT (β = 0.048, P = 0.011; β = 0.029, P = 0.009). Furthermore, MECPTP and MEHTP showed positive correlations with WBC (β = 0.011, P = 0.026; β = 0.017, P = 0.001). Notably, we identified a non-linear relationship between phthalates and inflammation and oxidative stress markers. The Bayesian kernel machine regression (BKMR) analysis demonstrated a negative joint effect of the phthalates mixture on GGT, particularly at lower concentrations. The BKMR model also found that MEOHP and MHiBP were negatively associated with GGT. In contrast, MEHHP showed a significant positive association with GGT. Moderating effect analysis suggested that increased dietary inflammatory index (DII), income-to-poverty ratio (PIR), age, BMI, and less physical activity strengthened the association between phthalates and inflammation and oxidative stress. These findings contribute to a deeper understanding of the relationships between phthalates and inflammation and oxidative stress.