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

Journal Article · Thu Apr 01 00:00:00 EST 1999 · Risk Analysis

DOI:https://doi.org/10.1023/A:1006933913194· OSTI ID:6277640

Granath, F N ^[1]; Vaca, C E ^[2]; Ehrenberg, L G; Toernqvist, M A ^[3]

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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)

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. If 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.

• Sponsoring Organization: USDOE; USDOE, Washington, DC (United States)
• DOE Contract Number: FG02-89ER60784
• OSTI ID: 6277640
• Journal Information: Risk Analysis, Vol. 19:2; ISSN 0272-4332
• Country of Publication: United States
• Language: English

Related Subjects

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