ABSTRACT
The dose–response assessment or toxicity assessment provides a means of understanding whether the magnitude of human exposure to environmental contaminants is sufficient to produce adverse health effects. A major effort is underway to develop and validate results from high-throughput in vitro testing for use in risk assessment and ideally supplant animal testing. The changing nature of societal concerns, considerations of animal welfare, and our ever-increasing knowledge of the biological basis of disease are changing the manner in which toxicity and dose-response are assessed. The identification of activation by metabolism as a key event may permit a powerful counterfactual demonstration that strongly supports the identification of metabolism as a key event. The mode of action (MOA) framework was originally developed over a decade ago by the World Health Organization International Program for Chemical Safety and specifically focused on chemical carcinogenesis. The European Commission has also incorporated using MOA in its risk assessment guidance for industrial chemicals and biocides.
