Dose response considerations in risk assessment--an overview of recent ILSI activities.
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 undertaken by various components of the International Life Sciences Institute (ILSI). 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.
Holsapple
Michael P
MP
International Life Sciences Institute, Health and Environmental Sciences Institute, One Thomas Circle, NW, Ninth Floor, Washington, DC 20005-5802, USA. mholsapple@ilsi.org
Wallace
Kendall B
KB
D000047:Academies and Institutes; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019055:No-Observed-Adverse-Effect Level; D018570:Risk Assessment; D014116:Toxicology / Q000639:trends