A method for measuring upper respiratory tract vapor uptake and its applicability to quantitative inhalation risk...

A thorough understanding of the toxicity of any substance requires knowledge of the relationships between exposure concentration and dose delivered to the critical target site. This is particularly true for inhalation exposures because inspired particles and vapors do not deposit uniformly in the respiratory tract. The current report describes in detail a methodology for measuring upper respiratory tract (URT) uptake of vapors in the rat. A urethane-anesthetized animal model is utilized in which two endotracheal tubes are inserted: one leading toward the lung to facilitate respiration, and the other toward the nose to allow air sampling through the nasal passages. The animal is placed in a nose-only exposure chamber and test vapor is drawn through the nose for periods up to 1 h. Uptake efficiency is calculated from the difference in vapor concentration between the inspired (chamber) air and air exiting the URT. Uptake data are provided for acetaldehyde and nicotine vapors, and a suggested experimental design that includes multiple air flow regimes and inspired concentrations is described. The data obtained by this methodology are not necessarily reflective of uptake efficiencies in normally breathing animals due to the nonphysiologic airflow regimes and the invasiveness of the procedure. The data so obtained are best utilized to support and validate state-of-the-art mathematical simulation models of regional vapor uptake. These models increase scientific rigor and reduce uncertainty in quantitative risk assessments for inhaled materials.