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Toxicology and Applied Pharmacology
Volume 197, Issue 2, 1 June 2004, Pages 125-136
 
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doi:10.1016/j.taap.2004.02.007    How to Cite or Link Using DOI (Opens New Window)
Copyright © 2004 Elsevier Inc. All rights reserved.

Review

Hormesis: from marginalization to mainstream A case for hormesis as the default dose-response model in risk assessment

Edward J. CalabreseCorresponding Author Contact Information, E-mail The Corresponding Author

Environmental Health Sciences, University of Massachusetts, Morrill I, N344, Amherst, MA 01003, USA

Received 2 January 2004; 
accepted 17 February 2004. 
Available online 28 March 2004.

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Abstract

The paper provides an account of how the hormetic dose response has emerged in recent years as a serious dose-response model in toxicology and risk assessment after decades of extreme marginalization. In addition to providing the toxicological basis of this dose-response revival, the paper reexamines the concept of a default dose model in toxicology and risk assessment and makes the argument that the hormetic model satisfies criteria (e.g., generalizability, frequency, application to risk assessment endpoints, false positive/negative potential, requirements for hazard assessment, reliability of estimating risks, capacity for validation of risk estimates, public health implications of risk estimates) for such a default model better than its chief competitors, the threshold and linear at low dose models. The selection of the hormetic model as the default model in risk assessment for noncarcinogens and specifically for carcinogens would have a profound impact on the practice of risk assessment and its societal implications.

Author Keywords: Hormesis; U-shaped; J-shaped; Dose response; Biphasic; Carcinogen; Adaptive response

Article Outline

• Introduction
• Quantitative features of the hormetic dose response
• Frequency of hormesis in the toxicological literature
• Mechanistic foundations
• What is a default dose-response model
• Acceptance of the threshold dose-response model
• Criteria in the selection of a default dose-response model
• Generalizability according to biological model, endpoints measured and range of chemical classes and physical agents
• Frequency of model responses in the toxicological literature
• Application of dose-response model for endpoints of relevance to risk assessment
• Capacity for false positive and negative estimates of dose-response model
• How dose-response models impact hazard assessment study requirements
• Reliability of estimating risk with the proposed dose-response model
• Capacity to validate estimates of risk
• Public health implications of risk assessment estimates
• Final perspectives
• Acknowledgements
• References


 
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