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Mixture Effects of Metals, PCBs, Dioxins, and Furans on Liver Function
Bolanle Akinyemi1,2, Emmanuel Obeng-Gyasi1,2
1Department of Built Environment, North Carolina A&T State University, Greensboro, NC 27411, USA.
Toxics
|May 27, 2026
Summary
This study reveals how mixtures of heavy metals, PCBs, dioxins, and furans impact liver health in US adults. Specific chemical mixtures were linked to altered liver biomarkers, highlighting potential hepatobiliary vulnerability.
Area of Science:
- Environmental Health Sciences
- Toxicology
- Biostatistics
Background:
- Assessing the health impacts of chemical mixtures is complex due to correlated components and nonlinear dose-response relationships.
- The liver, a primary site for toxicant metabolism, is vulnerable to damage from circulating chemicals.
- Subclinical organ dysfunction can result from exposure to complex chemical mixtures.
Purpose of the Study:
- To evaluate combined and component-specific associations of heavy metals, PCBs, dioxins, and furans with liver biomarkers in U.S. adults.
- To compare concentration-based mixture analysis with toxic equivalent (TEQ) potency weighting for dioxin-like compounds.
- To identify specific chemical contributors and patterns associated with liver biomarkers using multiple statistical methods.
Main Methods:
- Utilized data from U.S. adults (n=947) in NHANES 2003-2004.
- Analyzed heavy metals (cadmium, lead, mercury), PCBs, dioxins, and furans in relation to eight liver biomarkers.
- Applied multi-exposure linear regression, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR), including TEQ-based models.
Main Results:
- Total bilirubin showed consistent positive associations with the mixture, driven by PCBs and dioxin-like compounds.
- Albumin exhibited inverse associations, with dioxin-like components identified as key drivers.
- Other biomarkers (ALT, ALP, AST, GGT, LDH, total protein) often showed attenuated or null effects, suggesting counterbalancing within sub-mixtures. Specific metals and PCBs were identified as dominant predictors for certain biomarkers.
Conclusions:
- Multiple methods identified outcome-specific mixture patterns indicating hepatobiliary vulnerability.
- Toxic equivalent (TEQ) concordance supports the toxicological relevance of the dioxin-like chemical axis.
- Heavy metals and non-dioxin-like mechanisms likely contribute through additional pathways to liver biomarker alterations.
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