Evaluating the risk of liver cancer in humans exposed in trichloroethylene using physiological models
- Armstrong Lab., Wright-Patterson AFB, OH (United States)
- Clement Assoc., Ruston, LA (United States)
Trichloroethylene (TCE) is a widespread environmental pollutant. TCE is classified as a rodent carcinogen by the U.S. Environmental Protection Agency (EPA). Using the rodent cancer bioassay findings and estimates of metabolized dose, the SPA has estimated lifetime exposure cancer risks for humans that ingest TCE in drinking water or inhale TCE. In this study, a physiologically based pharmacokinetic (PB-PK) model for mice was used to simulate selected gavage and inhalation bioassays with TCE. Plausible dose-metrics thought to be linked with the mechanism of action for TCE carcinogenesis were selected. These dose-metrics, adjusted to reflect an average amount per day for a lifetime, were metabolism of TCE (AMET, mg/kg/day) and systemic concentration of TCA (AUCTCA, mg/L/day). These dose-metrics were then used in a linearized multistage model to estimate AMET and AUCTCA values that correspond to liver cancer risks of 1 in 1 million in mice. A human PB-PK model for TCE was then used to predict TCE concentrations in drinking water and air that would provide AMET and AUCTCA values equal to the predicted mice AMET and AUCTCA values that correspond to liver cancer risks of 1 in 1 million. For the dose-metrics, AMET and AUCTCA, the TCE concentrations in air wave 10.0 and 0.1 ppb TCE (continuous exposure), respectively, and in water, 7 and 4 [mu] TCE/L, respectively.
- OSTI ID:
- 6692750
- Journal Information:
- Risk Analysis; (United States), Journal Name: Risk Analysis; (United States) Vol. 13:1; ISSN 0272-4332; ISSN RIANDF
- Country of Publication:
- United States
- Language:
- English
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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKENES
ANIMALS
BIOASSAY
BIOLOGICAL EFFECTS
CARCINOGENESIS
CARCINOMAS
CHLORINATED ALIPHATIC HYDROCARBONS
DATA
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRINKING WATER
ETHYLENE
EXPERIMENTAL DATA
HALOGENATED ALIPHATIC HYDROCARBONS
HAZARDOUS MATERIALS
HEPATOMAS
HUMAN POPULATIONS
HYDROCARBONS
HYDROGEN COMPOUNDS
INFORMATION
INGESTION
INHALATION
INTAKE
MAMMALS
MATERIALS
METABOLISM
MICE
NEOPLASMS
NUMERICAL DATA
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
OXYGEN COMPOUNDS
PATHOGENESIS
POPULATIONS
RISK ASSESSMENT
RODENTS
VERTEBRATES
WATER