The Time to Tumor Approach in Risk Assessment

  • Roy E. Albert
Chapter
Part of the Basic Life Sciences book series (volume 189)

Abstract

The multistage model is currently a widely used mathematical tool in carcinogen risk assessment to obtain a low-dose linear non-threshold slope for estimating cancer risks and comparing carcinogens with respect to potency. However, the multistage model is a single pathway model, whereas biological evidence indicates that carcinogenesis proceeds through multiple pathways. Furthermore, recent studies suggest that carcinogens induce a generalized increase in the susceptibility to neoplastic transformation triggered as rare events by cell proliferation. Such evidence supports the dtn = c time to tumor model in a modified form.

When assessment of carcinogenic chemicals was begun by the Carcinogen Assessment Group (CAG) at the U.S. Environmental Protection Agency in 1976, the use of low-level non-threshold linear extrapolation was taken over from the field of ionizing radiation on the basis of the mechanistic linkage between carcinogenesis and mutagenesis, the linearity of dose-response for mutagenesis, and the consistency with linearity of at least some epidemiological dose-response data for cancer1. Additional arguments were added in support of low-dose linearity for chemicals: non-threshold dose-response linearity for tumor initiation2 and virtual low-dose linearity when the mode of action of the agent in question and the background causes are the same; as indicated below, this is inherent in the multistage model of carcinogenesis.

Keywords

Mouse Skin Estimate Cancer Risk Skin Papilloma Carcinogen Risk Assessment Carcinogenic Response 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Roy E. Albert
    • 1
  1. 1.Institute of Environmental MedicineNew York University Medical CenterNew YorkUSA

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