Issues in Risk Assessment (1993)
Chapter: 6. INTERSPECIES EXTRAPOLATION
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 |
Correlation | 0.944 | 0.961 |
Root Mean Square (s) | 0.462 | 0.386 |
Factor 102s 95% Prediction Intervalb | 8.4 | 5.9 |
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
