A pragmatic approach for human risk assessment of chemical mixtures

Humans are continuously exposed to complex chemical mixtures from foods and the environment. Due to our inadequate understanding of mixture effects, tools to assess the combined risk of mixed chemical exposures have been difficult to develop. In recent years, regulatory authorities across the world have made considerable progress towards developing pragmatic frameworks to deal with combined exposure to multiple chemicals for risk assessment purposes. These approaches require a high level of information about chemical exposures and toxicities, information that often is lacking. We see this data gap as delaying urgently needed improvements in chemical safety. Herein, we present a pragmatic step-by-step procedure for mixture risk assessment and propose tools for grouping of chemicals. Until we have a better understanding of adverse outcome pathways, we suggest that grouping of chemicals for mixture risk assessment be based on integrated in vivo and in vitro data, read-across as well as computational methods such as QSAR models or integrative systems biology. These latter methods can be used to predict inherent hazards or modes/mechanisms of action and to group the chemicals in cases where no experimental data exist.