Hayes et al

A. Wallace Hayes

University of South Florida College of Public Health, Tampa, FL USA

Humans are exposed to multiple chemicals, and various sources contribute to simultaneous and sequential exposure via multiple exposure routes. The effects of mixtures, however, are largely unknown.  Risk assessments for regulatory purposes rarely take into account the “real-life” exposure to multiple substances, but most often rely on the assessment of individual compounds. Because mixtures are often undefined, assessing the potential hazard is challenging.   The complex toxicology of many chemical mixtures and the diversity of the routes of exposure make it a multistep process that should begin by mining the published literature and by characterizing the physical-chemical nature of the mixture. This effort may include integration of historical data, comprehensive analytical characterization of the mixture, comparison with the toxicity of other mixtures with similar composition, and robust in silico modeling. Consideration of new testing concepts, such as novel in vitro models, adverse outcome pathways, and PBPK and computational models may help identify potential untoward health effects associated with mixtures without the use of classical animal approaches. The nature of the assessment may require different approaches, often determined on a case-by-case basis, which is particularly pertinent for the safety assessment of botanicals.