Interspecies Extrapolation Animal-to-Human Summary and

5 Interspecies Extrapolation (Animal-to-Human) Summary and Recommendations 

The rationale for extrapolation of toxicity data across species is founded in the commonality of anatomic characteristics and the universality of physiological functions and biochemical reactions, despite the great diversity of sizes, shapes, and forms of mammalian species. 

For extrapolation of data from animal studies to humans, account should be taken of species-specific differences between animals and humans. 

Ideally, the interspecies extrapolation should be based on substance-specific information however, for most substances, only limited or no data are available. Therefore, an assessment factor is usually applied in the interspecies extrapolation. The traditionally used default interspecies assessment factor is 10, possibly divided into a sub-factor of 4 for differences in toxicokinetics and a sub-factor of 2.5 for differences in toxicodynamics as proposed by Renwick (1993) and adopted by the WHO/IPCS (1994). The validity of the interspecies default factor of 4 for toxicokinetics has been assessed by Walton et al. (2001a,b) for each of the test species (dog, rabbit, rat, and mouse) the authors concluded that their assessment supports the need to replace the generic default factor by a compound-related value derived from specific, relevant, quantitative data. 

Systematic differences can be accounted for by means of allometric scaring. The reasons for the variability in sensitivity may be due to both toxicokinetic and toxicodynamic characteristics of a species and may imply both higher and lower sensitivity for man when compared to experimental 

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