Association of Endocrine-Disrupting Chemicals with All-Cause and Cause-Specific Mortality in the U.S.: A Prospective Cohort Study

Abstract

Wide exposure to endocrine-disrupting chemicals (EDCs) poses a great risk on human health. However, few large-scale cohort studies have comprehensively estimated the association between EDCs exposure and mortality risk. This study aimed to investigate the association of urinary EDCs exposure with mortality risk and quantify attributable mortality and economic loss. Multivariable Cox proportional hazards regression models were performed to investigate the association of 38 representative EDCs exposure with mortality risk in the National Health and Nutrition Examination Survey (NHANES). During a median follow-up of 7.7 years, 47,279 individuals were enrolled. All-cause mortality was positively associated with 1-hydroxynaphthalene, 2-hydroxynaphthalene, cadmium, antimony, cobalt, and monobenzyl phthalate. Cancer mortality was positively associated with cadmium. Cardiovascular disease (CVD) mortality was positively associated with 1-hydroxynaphthalene, 2-hydroxynaphthalene, and 2-hydroxyfluorene. Nonlinear U-shaped relationships were found between all-cause mortality and cadmium and cobalt, which was also identified between 2-hydroxyfluorene and CVD mortality. J-shaped association of cadmium exposure with cancer mortality was also determined. EDCs exposure may cause 56.52% of total deaths (1,528,500 deaths) and around 1,897 billion USD in economic costs. Exposure to certain phthalates, polycyclic aromatic hydrocarbons, phytoestrogens, or toxic metals, even at substantially low levels, is significantly associated with mortality and induces high economic costs.

Keywords: NHANES; death burden; dose−response; economic cost; endocrine-disrupting chemicals (EDCs); mortality.