Dose response considerations in risk assessment-An overview of recent ILSI activities

Michael P. Holsapple, Kendall B. Wallace

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)85-92
Number of pages8
JournalToxicology Letters
Volume180
Issue number2
DOIs
StatePublished - Aug 15 2008

Bibliographical note

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

Keywords

  • Dose response
  • Regulatory toxicology
  • Risk assessment

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