Standard Article

Empirical Methods and Default Approaches in Consideration of Exposure Duration in Dose–Response Relationships

Issues Relevant to Toxicology

  1. George M. Woodall PhD1,
  2. Jeffrey S. Gift PhD2,
  3. Gary L. Foureman PhD3

Published Online: 15 DEC 2009

DOI: 10.1002/9780470744307.gat173

General, Applied and Systems Toxicology

General, Applied and Systems Toxicology

How to Cite

Woodall, G. M., Gift, J. S. and Foureman, G. L. 2009. Empirical Methods and Default Approaches in Consideration of Exposure Duration in Dose–Response Relationships. General, Applied and Systems Toxicology. .

Author Information

  1. 1

    US Environmental Protection Agency, Research Triangle Park, North Carolina

  2. 2

    US Environmental Protection Agency, Research Triangle Park, North Carolina

  3. 3

    US Environmental Protection Agency, Research Triangle Park, North Carolina

Publication History

  1. Published Online: 15 DEC 2009

Abstract

This contribution is concerned with exploring the relationship of the duration or time and concentration components of exposure. Under many exposure scenarios, especially those characterized as acute (i.e. brief duration to high concentrations), both components are critical in eliciting the toxic response. Historical guidance on the inter-relationship of these components has been based in large part on mathematical models and theory (e.g. the ‘Haber’ C × t  =  k relationship and toxic load or TL phenomenon) and limited to lethality as the toxic response. This report features a suite of methods and approaches accommodating empirical data that characterize both lethal and nonlethal responses. Case studies are used to demonstrate the flexibility of these methods with regard to the type and amount of available data, as well as providing examples and insight into other aspects, including how variability arises, its consequences and how it may be addressed.

Keywords:

  • concentration × time;
  • duration;
  • duration extrapolation;
  • categorical regression;
  • acute inhalation