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- Title
Cancer Risk Estimation of Genotoxic Chemicals Based on Target Dose and a Multiplicative Model.
- Authors
Granath, Fredrik N.; Vaca, Carlos E.; Ehrenberg, Lars G.; Törnqvist, Margareta A.
- Abstract
A mechanistic model and associated procedures are proposed for cancer risk assessment of genotoxic chemicals. As previously shown for ionizing radiation, a linear multiplicative model was found to be compatible with published experimental data for ethylene oxide, acrylamide,and butadiene. The validity of this model was anticipated in view ofthe multiplicative interaction of mutation with inherited and acquired growth-promoting conditions. Concurrent analysis led to rejection of an additive model (i.e. the model commonly applied for cancer riskassessment). A reanalysis of data for radiogenic cancer in mouse, dog and man shows that the relative risk coefficient is approximately the same (0.4 to 0.5 percent per rad) for tumours induced in the threespecies.Doses in vivo, defined as the time-integrated concentrationsof ultimate mutagens, expressed in millimol x kg-1 x h (mMh) are, like radiation doses given in Gy or rad, proportional to frequencies of potentially mutagenic events. The radiation dose equivalents of chemical doses are, calculated by multiplying chemical doses(in mMh) with the relative genotoxic potencies (in rad x mMh-1) determined in vitro. In this way the relative cancer incidence increments in rats and mice exposed to ethylene oxide were shown tobe about 0.4 percent per rad-equivalent, in agreement with the data for radiogenic cancer.Our analyses suggest that values of the relative risk coefficients for genotoxic chemicals are independent of species and that relative cancer risks determined in animal tests apply also to humans. If reliable animal test data are not available, cancer risks may be estimated by the relative potency. In both cases exposuredose/target dose relationships, the latter via macromolecule adducts, should be determined.
- Subjects
CANCER research; RISK assessment; ACRYLAMIDE; BUTADIENE; CHEMICALS; RADIATION; GENETIC toxicology
- Publication
Risk Analysis: An International Journal, 1999, Vol 19, Issue 2, p309
- ISSN
0272-4332
- Publication type
Article
- DOI
10.1023/A:1006933913194