This status report provides a review of advances in the state of the science for interspecies inhalation gas dosimetry related to extrathoracic (ET) or upper respiratory tract (URT), tracheobronchial (TB), pulmonary (PU), and extrarespiratory (systemic, SYS) effects.
The RfC Methods document (Methods for Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry; EPA/600/8-90/066F, October 1994) provides the basis for EPA extrapolation of data from animal toxicology studies to estimate delivered dose in humans as part of the development of inhalation reference values (i.e., RfC values). This report evaluates and summarizes the pertinent scientific developments and advancements in gas dosimetry focusing on extrathoracic (ET) or upper respiratory tract (URT), tracheobronchial (TB), pulmonary (PU), and extrarespiratory (systemic, SYS) effects as they relate to the current methodology used by EPA. Particular emphasis is placed on the use of data from animal studies to estimate a comparable dose in humans for inhaled chemicals. In addition, this report summarizes available data pertaining to inhalation dosimetry throughout the respiratory tract of children as it relates to derivation of an RfC. This report provides the scientific foundation necessary for ensuring that methods and guidance used and implemented by EPA in inhalation risk assessment of gases reflects the state of the science.