the log10(TD50) and log10(MDT) reported in Figure 2 for the multistage and Weibull models. As further confirmation of this, we used the analytical approach in annex D to determine the correlation as a function of the shape parameter k in the Weibull model for a spontaneous tumor response rates of P(0) = 0.10 (Table 2). These results indicate that the correlation remains high for all values of k, increasing from about 0.9 for k near zero to almost 1 for large values of k.
3.5 Genotoxic vs. Nongenotoxic Carcinogens
Goodman & Wilson (1992) compared the dependence of the TD50 on the MTD for 217 genotoxic and nongenotoxic chemicals subjected to rodent bioassay within the U.S. National Toxicology Program. In this study, segregation of genotoxic and nongenotoxic carcinogens was done primarily on the basis of structural alerts and mutagenicity in Salmonella as described by Ashby & Tennant (1988). This analysis demonstrated that the TD50 for both genotoxic and nongenotoxic rodent carcinogens was highly correlated with the MTD. The authors found that the variability
TABLE 2 Correlationa Between Carcinogenic Potency and the Maximum Tolerated Dose as a Function of the Weibull Shape Parameter k
Weibull Shape Parameter k |
ρ = Corr (log10TD50, log10MTD) |
0.0b |
0.944 |
0.5 |
0.946 |
1.0 |
0.965 |
3.0 |
0.994 |
5.0 |
0.998 |
∞b |
1.000 |
aBased on assumptions in annex D. bLimiting cases as k → 0, ∞. |