Interim methods for development of inhalation reference concentrations. Draft report
An inhalation reference concentration (RfC) is an estimate of continuous inhalation exposure over a human lifetime that is unlikely to pose significant risk of adverse noncancer health effects and serves as a benchmark value for assisting in risk management decisions. Derivation of an RfC involves dose-response assessment of animal data to determine the exposure levels at which no significant increase in the frequency or severity of adverse effects between the exposed population and its appropriate control exists. The assessment requires an interspecies dose extrapolation from a no-observed-adverse-effect level (NOAEL) exposure concentration of an animal to a human equivalent NOAEL (NOAEL(HBC)). The RfC is derived from the NOAEL(HBC) by the application of generally order-of-magnitude uncertainty factors. Intermittent exposure scenarios in animals are extrapolated to chronic continuous human exposures. Relationships between external exposures and internal doses depend upon complex simultaneous and consecutive processes of absorption, distribution, metabolism, storage, detoxification, and elimination. To estimate NOAEL(HBC)s when chemical-specific physiologically-based pharmacokinetic models are not available, a dosimetric extrapolation procedure based on anatomical and physiological parameters of the exposed human and animal and the physical parameters of the toxic chemical has been developed which gives equivalent or more conservative exposure concentrations values than those that would be obtained with a PB-PK model.
- Research Organization:
- Environmental Protection Agency, Research Triangle Park, NC (USA). Environmental Criteria and Assessment Office
- OSTI ID:
- 6409660
- Report Number(s):
- PB-90-238890/XAB; EPA-600/8-90/066A
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
XENOBIOTICS
METABOLISM
BIOLOGICAL MODELS
CHRONIC EXPOSURE
DOSE-RESPONSE RELATIONSHIPS
INHALATION
LABORATORY ANIMALS
MAN
RISK ASSESSMENT
TOXICITY
ANIMALS
INTAKE
MAMMALS
PRIMATES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology