US EPA

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 managmement decisions. erivation 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. his assessment requires an interspecies dose extrapolaton from a no-observed-adverse effect level (NOAEL) exposure concentration of an animal to a human equivalent NOAEL (NOAEL). he RfC is derived from the NOAEL by the application of generally order-of-magnitude uncertainty factors. ntermittent exposure scenarios in animals are extrapolated to chronic continuous human exposures. elationships between external exposures and internal doses depend upon complex simultaneous and consecutive processes of absorpton, distributon, metabolism, storage, detoxification, and elimination. o estimate NOAEL 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.

Jarabek, A., M. Dourson, AND J. Overton. INTERIM METHODS FOR DEVELOPMENT OF INHALATION REFERENCE CONCENTRATIONS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/8-90/066A (NTIS PB90238890).