Exposure to phenols, chlorophenol pesticides, phthalate and PAHs and mortality risk: A prospective study based on 6 rounds of NHANES

Human exposure to various endocrine disrupting chemicals (EDCs) is widespread and long-lasting. The primary objective of this study was to prospectively evaluate the association of combined exposure of phenols, chlorophenol pesticides, phthalate and polycyclic aromatic hydrocarbons (PAHs) and mortality risk in a representative US population. The data on urinary levels of phenols, chlorophenol pesticides, phthalates, and PAH metabolites, were collected from participants aged ≥20 years in six rounds of the National Health and Nutrition Examination Survey (NHANES) (2003–2014). NHANES-linked death records up to December 31, 2015 were used to ascertain mortality status and cause of death. Cox proportional hazards and competing risk models were mainly used for chemical and mortality risk association analysis. The weighted quantile sum (WQS) regression and the least absolute shrinkage and selection operator regression were employed to estimate the association between EDC co-exposure and mortality risk. High levels of mono-n-butyl phthalate, monobenzyl phthalate, and 1-napthol were significantly associated with increased risk of all cause, cardiovascular disease (CVD) and cancer mortality among all participants. WQS index was associated with the risks of all-cause (hazard ratio [HR] = 1.389, 95%CI: 1.155–1.669) and CVD mortality (HR = 1.925, 95%CI: 1.152–3.216). High co-exposure scores were associated with elevated all-cause (HR = 2.842, 95% CI: 1.2.094–3.858), CVD (HR = 1.855, 95% CI: 1.525–2.255), and cancer mortality risks (HR = 2.961, 95% CI: 1.468–5.972). The results of subgroup analysis, competing risk model, and sensitivity analysis were generally consistent with the findings from the main analyses, indicating the robustness of our findings. This study provided the first epidemiological evidence that co-exposure to EDC at fairly low levels contributed to elevated mortality risk among US adults. The underlying mechanisms for the effects of EDC co-exposure on human health are worthy of future exploration.