Plasticisers chemical mixture, vitamin status, and mortality in US adults: a prospective population-based cohort

BACKGROUND: Plastic pollution is a major environmental and health issue. To cover knowledge gaps, this study aimed to examine the association between population exposure to plasticiser mixtures and mortality, estimate the attributable public health burden, and explore potential nutritional mitigation measures. METHODS: This prospective population-based study included non-pregnant US adults aged 20 years or older free from cardiovascular diseases and cancer at baseline from the US National Health and Nutrition Examination Survey 2005-16. The main outcome was mortality status and cause of death, which was confirmed using ICD-9 and ICD-10 codes. Baseline urinary concentrations of eight phthalate metabolites and bisphenol A were selected a priori based on a comprehensive review of the toxicological and epidemiological evidence and modelled as a plasticiser mixture by quantile-based g-computation. Vitamin concentrations were examined as effect modifiers. FINDINGS: 8378 adults were included. Over 71 127 person-years of follow-up (average 8·5 years per person), 633 deaths occurred. Each tertile increase in the mixture concentration was positively associated with all-cause mortality (hazard ratio 1·35, 95% CI 1·02-1·78), cancer mortality (1·79, 1·06-3·03), and cardiovascular disease mortality (1·83, 1·04-3·22). An estimated 10·31% (95% CI 0·78-20·38) of total deaths were attributable to a tertile increase in the mixture, equating to 256 471 annual excess deaths in the USA. The mixture association with all-cause, cancer, or cardiovascular disease mortality was observed only in individuals with serum vitamin D or red blood cell folate concentrations in the lowest tertile, but not in the upper tertiles. INTERPRETATION: Exposure to a mixture of common plasticisers was associated with increased all-cause, cancer, and cardiovascular disease mortality risk. Vitamin D and folate appeared to mitigate these associations. The findings underscore the need to reduce plasticiser exposure, optimise vitamin intake, and regulate chemicals by class. FUNDING: Instituto de Salud Carlos III (Spain) and NextGeneration EU.