National Academies Press: OpenBook

Issues in Risk Assessment (1993)

Chapter: 3.5 Genotoxic vs. Nongenotoxic Carcinogens

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Suggested Citation:"3.5 Genotoxic vs. Nongenotoxic Carcinogens." National Research Council. 1993. Issues in Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/2078.
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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, ∞.

Suggested Citation:"3.5 Genotoxic vs. Nongenotoxic Carcinogens." 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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