Nearly 500 years ago, Paracelsus coined the phrase "the dose makes the poison” and even today the relationship between dose and health effects remains a fundamental concept of toxicology. All chemical substances will exhibit an adverse effect if given a large enough dose. Conversely, if the dose is sufficiently low, even a toxic substance will cease to cause a harmful effect. Thus, potency of a chemical is ultimately defined by the dose. Quantifiable risk assessment was initially developed to assess human health risks associated with exposure to chemicals (NAS 1983). As defined by the National Academies, risk management in its most basic form consists of three phases as outlined in this figure.
Over the last decade, scientific initiatives toward more realistic risk assessment have greatly expanded to include new techniques and methods including “-omics” technologies (e.g., genomics, proteomics), high throughput toxicity assays, sensitive new analytical chemistry techniques, and PBPK modeling methods. However, to date these efforts have largely focused on hazard assessment, and the methodology necessary to determine how to best incorporate the results from this new science into quantitative risk assessment lags behind. In addition, many of the new testing methods need to be validated as reliable tools for use in hazard assessments, especially those that rely upon in vitro models. Thus, proactive scientific engagement in this new era of toxicology is crucial.