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Evaluation of Toxicological Interactions for the Dose-Response Assessment of Chemical Mixtures

Basic Science

  1. Kannan Krishnan PhD, DABT, FATS1,
  2. Sastry Isukapalli PhD2,
  3. Jonathan Boyd PhD3

Published Online: 15 DEC 2009

DOI: 10.1002/9780470744307.gat009

General, Applied and Systems Toxicology

General, Applied and Systems Toxicology

How to Cite

Krishnan, K., Isukapalli, S. and Boyd, J. 2009. Evaluation of Toxicological Interactions for the Dose-Response Assessment of Chemical Mixtures. General, Applied and Systems Toxicology. .

Author Information

  1. 1

    Université de Montréal, Départmente de Santé environnementale et Santé au Travail, Pavillon Marguerite d'Youville, Montreal, Quebec, Canada

  2. 2

    The State University of New Jersey, Environmental and Occupational Health Sciences Institute (EOHSI), a joint institute of UMDNJ RW Johnson Medical School and Rutgers, Piscataway, New Jersey, USA

  3. 3

    Johns Hopkins University, Applied Physics Laboratory, Baltimore, Maryland, USA

Publication History

  1. Published Online: 15 DEC 2009

Abstract

Dose-response assessment for chemical mixtures involves the characterization of the relationship between administered dose (or more appropriately target tissue dose) and tissue response, in order to facilitate the determination of safe exposure levels for humans. When interactions among chemicals occur, the consideration of mechanisms would be necessary for the conduct of scientifically sound dose-response assessment for mixtures. The present chapter focusses on the current approaches for evaluating toxicological interactions for the dose-response assessment of chemical mixtures. The approaches described in this chapter include: (i) interaction matrix method, (ii) interaction weighting ratio method and (iii) physiologically based pharmacokinetic (PBPK) modelling. The unique use of PBPK models in predicting the change in tissue dose of mixture components as a function of dose, route, exposure scenario and mixture complexity is highlighted. Finally, the interaction-based dose-response analysis of chemical mixtures is described, along with illustrative examples.

Keywords:

  • toxic interactions;
  • PBPK modeling;
  • chemical mixtures;
  • interaction matrix;
  • interaction weighting ratio;
  • metabolic interactions