Integrative toxicogenomics-based approach to risk assessment of heavy metal mixtures/complexes: strategies and challenges

Human exposure to metallic elements ranging from single metal ionic salt, metal compounds, and metal mixtures that may occur naturally, as well as from human activities and industrial applications. Some metals including arsenic, cadmium, chromium, lead, mercury, and nickel in both single element and mixture forms render confounding health effects and ultimately cause cancer. Studies of heavy metal-mediated global aberration using non-targeted multiple toxicogenomic technologies might help to elucidate environmentally relevant disorders, as well as to monitor biomarker of exposure and predict the health risk toward environmental toxicants. We describe recent toxicogenomic studies on heavy metal mixtures as well as relevant mechanism of toxicity and molecular signatures. On the basis of system toxicology approach, integrative toxicogenomic and bioinformatic tools might represent the biological pathways linked to disorders. We also strongly suggest that the toxicogenomic data can be adopted to risk assessment process. Furthermore, we mention challenges in utility of toxicogenomic studies data to risk assessment process of toxicity of metal mixtures. Overall, we realize that application and interpretation of toxicogenomic data regarding to their strengths and weaknesses would potentiate chemical risk assessment.