Issues in Risk Assessment (1993) / Chapter Skim
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4.2 Predictions Based on Mutagenicity and Acute Toxicity
4.2 Predictions Based on Mutagenicity and Acute Toxicity
Pages 132-134
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From page 132... ...
Determination of the MTD is normally based on the results of subchronic toxicity tests lasting about three-months. This observation raises the question TABLE 3 Regression of Carcinogenic Potency on the Maximum Tolerated Dose Regression Parameter Model One-Stage Multistage Weibull Intercept ± SE - 0.07 ± 0.05 - 0.10 ± 0.04 0.15 ± 0.06 Slope ± SE 1.04 ± 0.02 1.04 ± 0.02 0.99 ± 0.03 Correlation 0.952 0.964 0.903 Root Mean Square (σ)
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From page 133... ...
In addition to using the Salmonella assay to measure mutagenic potency, mutation in L5178Y mouse lymphoma cells, in vivo DNA adducts in rodent liver, and in vitro DNA repair in rodent liver were also considered. This investigation suggests that the correlation between carcinogenic potency and mutagenic potency based on each of these short-term tests is moderate, with correlation coefficients in the neighborhood of r=0.4.
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From page 134... ...
For each assay, a relative potency index was established in terms of weighted average of the potency relative to 20 reference compounds; a geometric mean of all available assays was then used to obtain an overall predictor of carcinogenicity. For some chemicals, the relative potency values based on different assays varied by as much as five orders of magnitude.
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