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Interspecies Extrapolation

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Computational Toxicology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 929))

Abstract

Interspecies extrapolation encompasses two related but distinct topic areas that are germane to quantitative extrapolation and hence computational toxicology—dose scaling and parameter scaling. Dose scaling is the process of converting a dose determined in an experimental animal to a toxicologically equivalent dose in humans using simple allometric assumptions and equations. In a hierarchy of quantitative extrapolation approaches, this option is used when minimal information is available for a chemical of interest. Parameter scaling refers to cross-species extrapolation of specific biological processes describing rates associated with pharmacokinetic (PK) or pharmacodynamic (PD) events on the basis of allometric relationships. These parameters are used in biologically based models of various types that are designed for not only cross-species extrapolation but also for exposure route (e.g., inhalation to oral) and exposure scenario (duration) extrapolation. This area also encompasses in vivo scale-up of physiological rates determined in various experimental systems. Results from in vitro metabolism studies are generally most useful for interspecies extrapolation purposes when integrated into a physiologically based pharmacokinetic (PBPK) modeling framework. This is because PBPK models allow consideration and quantitative evaluation of other physiological factors, such as binding to plasma proteins and blood flow to the liver, which may be as or more influential than metabolism in determining relevant dose metrics for risk assessment.

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Disclaimer

This manuscript has been reviewed in accordance with the policy of the National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.

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Authors and Affiliations

  1. Pharmacokinetics Branch, Integrated Systems Toxicology Division, MD B105-03, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA

    Elaina M. Kenyon

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  1. Elaina M. Kenyon
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Correspondence to Elaina M. Kenyon .

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Editors and Affiliations

  1. School of Biomedical Engineering, Chemical & Biological Engineering, Colorado State University, Campus Delivery 1370, Fort Collins, 80523-1370, Colorado, USA

    Brad Reisfeld

  2. , Chemical & Biological Engineering, Colorado State University, Campus Delivery 1370, Fort Collins, 80523-1370, Colorado, USA

    Arthur N. Mayeno

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Kenyon, E.M. (2012). Interspecies Extrapolation. In: Reisfeld, B., Mayeno, A. (eds) Computational Toxicology. Methods in Molecular Biology, vol 929. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-050-2_19

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  • DOI: https://doi.org/10.1007/978-1-62703-050-2_19

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  • Publisher Name: Humana Press, Totowa, NJ

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