Pharmacokinetic modeling of trichloroethylene and trichloroacetic acid in humans
- Clement International Corp. Ruston, LA (United States)
- Armstrong Lab, Wright-Patterson AFB, OH (United States)
The development and application of appropriate physiologically based pharmaocokinetic (PBPK) models of chemical contaminants will provide a rational basis for risk assessment extrapolation. Trichloroethylene (TCE) is a widespread contaminant found in soil, groundwater, and the atmosphere. Exposures to TCE and its metabolities have been found to be carcinogenic in rodents. In this study, a PBPK model for TCE and its major metabolite, trichloracetic acid (TCA), is developed for humans. The model parameters, estimated from the relevant published literature on human exposures to TCE and its metabolites, are described. Key parameters describing the metabolism of TCE and the kinetics of TCA were estimated by optimization. The optimization was accomplished by simultaneously matching model predictions to observations of TCE concentrations in blood and exhaled breath, TCA plasma concentrations, and urinary TCA excretin from five published studies. The optimized human PBPK model provides an excellent description of TCE and TCA kinetics. The predictions were especially good for TCA plasma concentrations following repeated TCE inhalation, an exposure scenario similar to that occurring in the workplace. The human PBPK model can be used to estimate dose metrics resulting from TCE exposures and is therefore useful when considering the estimation of human health risks associated with such exposures.
- OSTI ID:
- 6692765
- 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.
AIR
ALDEHYDES
ALKENES
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BODY FLUIDS
BREATH
CHLORAL
CHLORINATED ALIPHATIC HYDROCARBONS
DOSE-RESPONSE RELATIONSHIPS
ETHYLENE
EXTRAPOLATION
FLUIDS
GASES
GROUND WATER
HALOGENATED ALIPHATIC HYDROCARBONS
HAZARDOUS MATERIALS
HUMAN POPULATIONS
HYDROCARBONS
HYDROGEN COMPOUNDS
INHALATION
INTAKE
KINETICS
MAMMALS
MATERIALS
METABOLISM
NUMERICAL SOLUTION
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
OXYGEN COMPOUNDS
PLASMA
POPULATIONS
RISK ASSESSMENT
RODENTS
SOILS
TOXICITY
VERTEBRATES
WATER