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Issues in Risk Assessment (1993)


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Suggested Citation:"6. INTERSPECIES EXTRAPOLATION." National Research Council. 1993. Issues in Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/2078.

TABLE 4 Regression of Upper Bounds on Low Dose Slopes on the Maximum Tolerated Dosea

Regression Parameter

Extrapolation Method

Multistage Model

Model-Free Extrapolation

Intercept ± SE

0.01 ± 0.05

0.11 ± 0.04

Slope ± SE

-1.05 ± 0.03

-1.07 ± 0.02




Root Mean Square (s)



Factor 102s 95% Prediction Intervalb



aBased on simple linear regression of log slope on log MDT.

bUpper limit is 102s x MDT; lower limit is 10-2s x MDT.

approximate 95% prediction intervals for the low dose slope encompass a range of about 8 × 8 = 64-fold about the MDT with the LMS model, and a range of about 36-fold for MFX. Given an upper bound on the low dose slope ß, the corresponding 10-6 RSD is simply 10-6/ß.

6. Interspecies Extrapolation

Since mammalian species share many common physiological characteristics it is expected that they may respond in a somewhat similar manner to toxic substances. While many differences exist between species (Oser, 1981), allometric relationships among physiological parameters have suggested different metrics for quantitative interspecies extrapolation: heat loss, for example, appears to be proportional to the surface area of mammals, whereas metabolism is related to body weight to the 3/4 power (Schmidt-Nielsen, 1984). Such considerations have led to suggestions that allometric equations of the form

Suggested Citation:"6. INTERSPECIES EXTRAPOLATION." National Research Council. 1993. Issues in Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/2078.
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The scientific basis, inference assumptions, regulatory uses, and research needs in risk assessment are considered in this two-part volume.

The first part, Use of Maximum Tolerated Dose in Animal Bioassays for Carcinogenicity, focuses on whether the maximum tolerated dose should continue to be used in carcinogenesis bioassays. The committee considers several options for modifying current bioassay procedures.

The second part, Two-Stage Models of Carcinogenesis, stems from efforts to identify improved means of cancer risk assessment that have resulted in the development of a mathematical dose-response model based on a paradigm for the biologic phenomena thought to be associated with carcinogenesis.

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