Incorporation of pharmacokinetics in noncancer risk assessment: Example with chloropentafluorobenzene

Conference · Wed Jun 01 04:00:00 EDT 1994 · Risk Analysis; (United States)

OSTI ID:7008362

Clewell, III, H J ^[1]; Jarnot, B M ^[2]

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1. ICF Kaiser International, Ruston, LA (United States)
2. Wright-Patterson Air Force Base, OH (United States)

Noncancer risk assessment traditionally relies on applied dose measures, such as concentration in inhaled air or in drinking water, to characterize no-effect levels or low-effect levels in animal experiments. Safety factors are then incorporated to address the uncertainties associated with extrapolating across species, dose levels, and routes of exposure, as well as to account for the potential impact of variability of human response. A risk assessment for chloropentafluorobenzene (CPFB) was performed in which a physiologically based pharmacokinetic model was employed to calculate an internal measure of effective tissue dose appropriate to each toxic endpoint. The model accurately describes the kinetics of CPFB in both rodents and primates. The model calculations of internal dose at the no-effect and low-effect levels in animals were compared with those calculated for potential human exposure scenarios. These calculations were then used in place of default interspecies and route-to-route safety factors to determine safe human exposure conditions. Estimates of the impact of model parameter uncertainty, as estimated by a Monte Carlo technique, also were incorporated into the assessment. The approach used for CPFB is recommended as a general methodology for noncancer risk assessment whenever the necessary pharmacokinetic data can be obtained. 24 refs., 4 figs., 3 tabs.

• OSTI ID: 7008362
• Report Number(s): CONF-9304130--
• Conference Information: Journal Name: Risk Analysis; (United States) Journal Volume: 14:3
• 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.
ANIMALS
BIOLOGICAL MODELS
BODY
CALCULATION METHODS
CHLOROFLUOROCARBONS
DOSE-RESPONSE RELATIONSHIPS
HAZARDS
HEALTH HAZARDS
MAMMALS
MONTE CARLO METHOD
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
PHARMACOLOGY
PRIMATES
RISK ASSESSMENT
RODENTS
TISSUES
VERTEBRATES