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Title: Cancer risk estimation of genotoxic chemicals based on target dose and a multiplicative model

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. Concurrent analysis led to rejection of an additive model. A reanalysis of data for radiogenic cancer in mouse, dog and man shows that the relative risk coefficient is approximately the same for tumors induced in the three species. Doses in vivo, defined as the time-integrated concentrations of ultimate mutagens, expressed in millimol x kg[sup [minus]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 determined in vitro. In this way the relative cancer incidence increments in rats and mice exposed to ethylene oxide were shown to be about 0.4% per rad-equivalent, in agreement with the data for radiogenic cancer. The 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. Ifmore » reliable animal test data are not available, cancer risks may be estimated by the relative potency. In both cases exposure dose/target dose relationships, the latter via macromolecule adducts, should be determined.« less
Authors:
 [1] ;  [2] ; ;  [3]
  1. (Stockholm Univ. (Sweden). Dept. of Mathematical Statistics Karolinska Inst., Stockholm (Sweden). Dept. of Medical Epidemiology)
  2. (Stockholm Univ. (Sweden). Dept. of Radiobiology Casco Products AB, Stockholm (Sweden))
  3. (Stockholm Univ. (Sweden))
Publication Date:
OSTI Identifier:
6277640
DOE Contract Number:
FG02-89ER60784
Resource Type:
Journal Article
Resource Relation:
Journal Name: Risk Analysis; Journal Volume: 19:2
Sponsoring Org:
DOE; USDOE, Washington, DC (United States)
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; ACRYLAMIDE; BIOLOGICAL MODELS; BUTADIENE; CARCINOGENESIS; ETHYLENE; EXPERIMENTAL NEOPLASMS; MATHEMATICAL MODELS; RISK ASSESSMENT; ALKENES; AMIDES; DIENES; HYDROCARBONS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; PATHOGENESIS; POLYENES 560300* -- Chemicals Metabolism & Toxicology