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Issues in Risk Assessment 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