Assessing the use of pharmacokinetic models in risk assessments on inhaled toxicants
The risk assessment process uses numerous assumptions when extrapolating from animal studies to estimate human health risk. Traditional risk assessment procedures for transpecies extrapolations assume that dose scales across species on a body weight or body surface area basis. This assumption is invalid when marked species differences in the pharmacokinetics of the agent exist. The incorporation of species-specific pharmacokinetic data into transpecies dose-response extrapolations should reduce some of the uncertainties in risk assessments. This study determines the degree to which specific pharmacokinetic factors influence the prediction of critical exposure concentrations and risk to humans and assesses the ability of pharmacokinetic models to provide a more accurate estimate of dose than the traditional risk assessment approach. Pharmacokinetic models which incorporate sequentially more detailed pharmacokinetic data were used to assess critical pharmacokinetic factors. Models included the US Environmental Protection Agency (1989) dosimetry approach which incorporates particle deposition and absorption factors and the Classical pharmacokinetic and the Physiologically-based pharmacokinetic (PB-PK) approaches which incorporate distribution, metabolism and elimination factors. Assessments of pharmacokinetic factors were performed by varying each factor independently and comparing predicted human equivalent concentrations (HEC) using each model to results using the traditional approach. The ability of pharmacokinetic models to predict HEC and corresponding risk more consistently than traditional methods was verified using model compounds.
- Research Organization:
- State Univ. of New York, Albany, NY (United States)
- OSTI ID:
- 5953104
- 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.
BIOLOGICAL MODELS
DOSIMETRY
FLUIDS
GASES
HAZARDOUS MATERIALS
INHALATION
INTAKE
KINETICS
MATERIALS
METABOLISM
NATIONAL ORGANIZATIONS
PARTICLES
PARTICULATES
PHARMACOLOGY
RESPIRATION
RESPIRATORY SYSTEM
RISK ASSESSMENT
SURFACE AREA
SURFACE PROPERTIES
TOXIC MATERIALS
US EPA
US ORGANIZATIONS