US EPA

The US EPA National Center for Environmental Assessment has developed a methodology to derive acute inhalation toxicity benchmarks, called acute reference exposures (AREs), for noncancer effects. The methodology provides guidance for the derivation of chemical-specific benchmarks that can be used to estimate the potential health risks of accidental and routine acute releases of chemicals to the environment. Chemical-specific AREs are analogous to inhalation reference concentrations (RfCs) for chronic noncancer effects, but apply to exposure durations of 24 hours or less. AREs will be publicly available via incorporation into chemical-specific files in U.S. EPA's Integrated Risk Information System (IRIS). The methodology for ARE development provides a framework for choosing an optimal derivation approach, based on the amount and type of data available, from one of three approaches (1) identification of an experimental no-observed-adverse-effect level (NOAEL), (2) benchmark concentration (BMC) analysis, or (3) categorical regression analysis. Although the NOAEL and BMC approaches require duration adjustments if the experimental exposure duration is not the duration of interest, the categorical regression approach models the change in response with duration of exposure. Uncertainty factors are applied to the point of departure obtained from one of the three approaches to derive the ARE. Due to the capability to use more exposure-response information than the NOAEL approach, exposure-response analyses such as BMC and categorical regression are favored as methods to derive the point of departure when the available database will support such analyses. The NOAEL approach may be used when the data are insufficient to support exposure-response modeling. Example AREs will be provided.

Strickland, J. U.S. EPA's Acute Reference Exposure Methodology For Acute Inhalation Exposures. Presented at 2001 EPA/DOD Conference on Issues and Applications in Toxicology and Risk Assessment, Fairborn, OH, April 23-26, 2001.