Cover Image

PAPERBACK
$49.00



View/Hide Left Panel

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, ∞.



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page 130
APPENDIX F 130 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. 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, ∞.