Cancer-risk prediction for carbon tetrachloride using pharmacokinetic and cell-kinetic multistage models

Conference · Wed Feb 01 04:00:00 EST 1989

OSTI ID:6459562

Bogen, K T

Multistage cancer risk models that account for clonal growth of intermediate, premalignant cell populations have been successfully used to describe age-specific incidence trends for human and experimentally induced animal tumors. Currently there is keen and growing interest in applying ''cell-kinetic multistage'' (CKM) models, which distinguish mutations and cell population kinetics as separate processes influencing the rate of tumor formation, to the problem of predicting human cancer risk that may be posed by environmental agents. This paper illustrates the application of such models to cancer-risk prediction for carbon tetrachloride (CCl/sub 4/), using data from rodent cancer bioassays and information on CCl/sub 4/ pharmacokinetics in rodents and humans. The presumption, made in most CKM models considered to date, that preneoplastic cell growth is exponential over time is critically evaluated along with the impact on predicted CCl/sub 4/-induced cancer risk of using a more biologically realistic cell-growth model. Equations describing modeled exponential and geometric CKM-based risk from multiple exposure scenarios are developed and applied to the problem of risk population for CCl/sub 4/. It is shown that if CCl/sub 4/ is assumed to be a ''pure'' promoter of carcinogenesis (i.e., to have no cancer-initiating capacity), the CKM approach predicts a low-dose carcinogenic potency for CCl/sub 4/ that is up to four orders of magnitude less than that predicted using a widely used standard approach that does not take into account the impact of induced cell proliferation. 46 refs., 6 figs.

• Research Organization: Lawrence Livermore National Lab., CA (USA)
• DOE Contract Number: W-7405-ENG-48
• OSTI ID: 6459562
• Report Number(s): UCRL-98748; CONF-8810249-4; ON: DE89008609
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BIOASSAY
BIOLOGICAL EFFECTS
CARBON TETRACHLORIDE
CELL PROLIFERATION
CHLORINATED ALIPHATIC HYDROCARBONS
DISEASES
DOSE-RESPONSE RELATIONSHIPS
GENETIC EFFECTS
GROWTH
HALOGENATED ALIPHATIC HYDROCARBONS
HAMSTERS
MAMMALS
MATHEMATICAL MODELS
MICE
MUTATIONS
NEOPLASMS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
RATS
RISK ASSESSMENT
RODENTS
TOXICITY
TUMOR CELLS
VERTEBRATES