Mixture analysis of associations between environmental and workplace toxins and liver damage and telomere length, stratified by race/ethnicity

This study aimed to identify the worst "bad actors" in mixtures of pollutants contributing to liver damage and shorter telomeres in the U.S. population, using Weighted Quantile Sum (WQS) modeling with stratification by race/ethnicity. We conducted a comprehensive cross-sectional analysis of mixtures of pollutants in National Health and Nutrition Examination Survey datasets: a) 33,979 adults with blood levels of cadmium (Cd), lead (Pb), and mercury, including subsets with measurements of per-/polyfluoroalkyl substances (PFAS), and polychlorinated biphenyls (PCBs)/polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs); and b) 7360 adults with measurements of telomeres, Cd, and Pb. Multivariable-adjusted WQS regression examined associations between WQS mixture indices and liver injury [alanine aminotransferase (ALT)-elevation], advanced liver-fibrosis (LF), and telomere length. WQSmetal indices were associated with advanced-LF in all racial/ethnic groups. The top contributor was Cd in the total population and in non-Hispanic Whites (NHW), while Pb was the top contributor in non-Hispanic Blacks (NHB). The WQSmetal-PCB-PCDD/F index was associated with ALT-elevation, with PCB126, Cd and Pb as main contributors; the odds ratio (OR) per decile was 1.50 (95 %CI, 1.26–1.78), while the OR per decile of the WQSmetal-PFAS index was 1.03 (95 %CI, 0.98–1.05), not significant. WQSmetal indices were associated with shorter telomeres. Cd was main contributor associated with advanced-LF in NHW, while Pb was the major bad actor in NHB, suggesting that NHB may be especially susceptible to Pb toxicity. Metals were associated with shorter telomeres. Metal and PCB/PCDD/F mixtures were associated with ALT-elevation. Heavy metals and organic chemicals may contribute to liver-related morbidity and healthcare disparities.