Linking indoor air and pharmacokinetic models to assess tetrachloroethylene risk
Physiologically based pharmacokinetic (PBPK) models describing the uptake, metabolism, and excretion of xenobiotic compounds are now proposed for use in regulatory health-risk assessments. In this study the authors investigate the extent of PCE metabolism arising from domestic respiratory exposure to tetrachloroethylene (PCE) from ground water, as predicted using a PBPK model. Indoor exposure patterns they use as input to the PBPK model are realistic ones generated from a three-compartment model describing volatilization of PCE from domestic water into household air. Values they use for the metabolic parameters of the PBPK model are estimated from data on urinary metabolites in workers exposed to PCE. It is shown that for respiratory PCE exposure due to typical levels of PCE in ground water, use of time-weighted average air concentrations with a steady-state PBPK model yields estimates of total metabolized PCE similar to those obtained using completely dynamic modeling, despite considerable uncertainty in key exposure- and metabolic-model parameters. These findings suggest that, for PCE, risk estimation taking pharmacokinetics into account may be accomplished using a simple analytic approach.
- Research Organization:
- Lawrence Livermore National Lab., CA (USA)
- DOE Contract Number:
- W-7405-ENG-48
- OSTI ID:
- 6277761
- Journal Information:
- Risk Anal.; (United States), Vol. 8:4
- Country of Publication:
- United States
- Language:
- English
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Prediction of risk from indoor exposure to tetrachloroethylene; Pharmacokinetic considerations under steady-state and dynamic exposure conditions
Prediction of risk from indoor exposure to tetrachloroethylene: Pharmacokinetic considerations under steady-state and dynamic exposure conditions
Related Subjects
54 ENVIRONMENTAL SCIENCES
CHLORINATED ALIPHATIC HYDROCARBONS
RISK ASSESSMENT
MATHEMATICAL MODELS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
CARCINOGENS
COMPUTERIZED SIMULATION
DATA COVARIANCES
DOSE-RESPONSE RELATIONSHIPS
ENVIRONMENTAL EXPOSURE PATHWAY
EXCRETION
GROUND WATER
HEALTH HAZARDS
HUMAN POPULATIONS
INDOOR AIR POLLUTION
INHALATION
METABOLISM
METABOLITES
OCCUPATIONAL EXPOSURE
PHARMACOLOGY
RESPIRATION
UPTAKE
WATER POLLUTION
AIR POLLUTION
CLEARANCE
HALOGENATED ALIPHATIC HYDROCARBONS
HAZARDS
HYDROGEN COMPOUNDS
INTAKE
KINETICS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
OXYGEN COMPOUNDS
POLLUTION
POPULATIONS
REACTION KINETICS
SIMULATION
WATER
560300* - Chemicals Metabolism & Toxicology
500200 - Environment
Atmospheric- Chemicals Monitoring & Transport- (-1989)
520200 - Environment
Aquatic- Chemicals Monitoring & Transport- (-1989)