Dose Response Considerations in Risk Assessment—An Overview of Recent Activities

Toxicology Letters. 2008;180(2):85-92

Abstract: This paper will provide some perspective on the role that a consideration of the dose–response has played (past), is playing (present) and will play (future) in human risk assessment with special emphasis on a number of recent activities. The dose–response is a critically important concept in every aspect of biomedical science, including toxicology. A characterization of the dose response has been recognized as one of the four essential components of risk assessment since the release of the NRC/NAS report in 1983, and understanding the dose–response curve is the basis for regulatory toxicology. The introduction of concepts such as hormesis, thresholds of toxicological concern (TTC), and dose-dependent transitions in mechanisms of toxicity have emphasized the complexities associated with a characterization of the dose–response. The transitions to emphasizing predictive toxicology, systems biology, the new ‘omics technologies, and high-throughput screening (HTS) have provided a new vision for toxicity testing. One impact of fully integrating these new concepts and technologies is that we will have unprecedented capabilities to explore the dose–response relationship, especially at low doses. How these new insights into the dose–response will affect our definition of threshold, and our understanding of the distinction between adverse and adaptive effects remain to be determined.

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