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Abstract
BACKGROUND AND AIM: Researchers are increasingly using innovative statistical methods to understand how exposure to real-world metal mixtures may affect human health. Although these new statistical approaches, such as Bayesian Kernel Machine Regression and Weighted Quantile Sums Regression, allow for researchers to include a wide panel of metals in their analysis, metals have unique sources and routes of exposure, different adsorption and elimination pathways and not all biomarkers are effective measures of exposure. This review aims to move the field of metal epidemiology forward by summarizing the most up-to-date research available on several metals, particularly highlighting the strengths and limitations of metal biomarkers and discussing potential existing evidence of interactions with other metals and environmental exposures. METHODS: We reviewed observational and experimental studies from database searches and citations regarding exposure to 12 different metals, including 8 non-essential elements (arsenic, barium, cadmium, lead, mercury, nickel, tin, uranium) and 4 essential trace elements (manganese, molybdenum, selenium, and zinc). We included more than 500 studies. RESULTS:In this review, we discuss in depth major environmental sources of exposure, biotransformation and elimination, biomarkers of exposure, and known interactions with other metals and environmental exposures for 12 metals increasingly used in metal-mixtures analyses. CONCLUSIONS:As metal epidemiology moves towards embracing a multi-metal approach it is important for researchers to have a strong knowledge base about the metals they are including in their analysis. This review provides researchers with sufficient background knowledge on several metals to appropriately inform their analysis planning, statistical approach, and interpretation of results. KEYWORDS: Heavy metals, Chemical exposures, Biomarkers of exposure, Mixtures, Toxicology
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