Uptake of Acrolein in the Upper Respiratory Tract of the F344 Rat

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Abstract
To provide inhalation dosimetric information for acrolein vapor, the uptake of this irritant was measured during a 40-min exposure period in the surgically isolated upper respiratory tract (URT) of the anesthetized male F344 rat at selected unidirectional inspiratory (50–300 ml/min) or pseudo-cyclic (1 ml volume, 100 cycles/min with 7 ml/min being continuously bled off for analysis) flow conditions. In addition, the effect of acrolein on URT uptake of acetone vapor was studied via this approach to determine if this irritant was capable of altering the uptake of other vapors. In contrast to numerous other vapors, URT uptake of acrolein did not attain or maintain a steady state during the exposure, but rather slowly decreased throughout the 40-min exposure period. Average URT acrolein deposition efficiency (between 20 and 40 min of exposure) was significantly dependent (p < .001) on the inspired concentrations, with average deposition efficiencies of 62, 38, and 28% being observed at inspired concentrations of 2, 10, and 20 μg/L respectively (inspiratory flow rate 200 ml/min). Similar effects were seen under both unidirectional and pseudo-cyclic flow conditions. The mechanisms for this effect are not known. These results indicate that caution must be used in extrapolating dosimetry data from high-exposure scenarios to predict effects at lower, more environmentally relevant levels. Although uptake of acetone normally attains a steady state during 40-min exposure, simultaneous exposure to acrolein resulted in non-steady-state acetone uptake behavior. Acrolein also enhanced average URT acetone deposition efficiency. Specifically, acetone deposition efficiency (between 20 and 40 min of exposure) averaged 13% in animals exposed to acetone alone (200 ml/min inspiratory flow rate), compared to 21% in animals simultaneously exposed to 20 μg/L acrolein (p < .001). Enhanced acetone uptake was observed after 12 min from the start of exposure, indicating the response to acrolein was quite rapid. These results indicate that the nasal dosimetry of acrolein is complex and that this irritant can rapidly alter the uptake of other vapors.