Upper respiratory tract deposition of inspired acetaldehyde.
Inhalation exposure of rodents to high concentrations of acetaldehyde produces lesions in the upper respiratory tract (URT, all regions of the respiratory tract anterior to and including the larynx). Information on the inhalation dosimetric relationships for this vapor are needed for a comprehensive understanding of its inhalation toxicity. Toward this end, uptake of acetaldehyde was measured in the surgically isolated URT of the urethane-anesthetized male F344 rat under unidirectional (50, 100, 200, or 300 ml/min) and cyclic (100 ml/min) flow conditions at inspired concentrations of 1, 10, 100, or 1000 ppm. Under all flow conditions URT deposition efficiency was strongly dependent on inspired concentration. URT deposition efficiency (under cyclic flow) averaged 76, 48, 41, and 26% at 1, 10, 100, and 1000 ppm, respectively. Nasal acetaldehyde dehydrogenase activity averaged 1.2 micrograms/min. Absolute acetaldehyde deposition rates (micrograms/min) at 100 and 1000 ppm exceeded this activity by 5- to 100-fold, suggesting a possible mechanism for the reduced deposition efficiency at high concentrations. URT deposition under unidirectional flow was strongly dependent on the inspiratory flow rate. The effect of flow rate on deposition was reasonably predicted by the mass-transfer model of Aharonson et al. (J. Appl. Physiol. 37, 654-657, 1974). The uptake coefficients determined from the unidirectional flow studies were used to predict uptake under cyclic flow by integration of the model. The predicted cyclic deposition efficiencies differed from the observed efficiencies by 2.3 +/- 4.3% (mean +/- SEM), suggesting this model might provide a reasonable first approximation for acetaldehyde uptake under cyclic breathing conditions.
Morris
J B
JB
Toxicology Program, School of Pharmacy, University of Connecticut, Storrs 06269-2092.
Blanchard
K T
KT
D000079:Acetaldehyde / Q000008:administration & dosage / Q000378:metabolism*; D000280:Administration, Inhalation; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007830:Larynx / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009297:Nasal Mucosa / Q000378:metabolism*; D010614:Pharynx / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D015657:Respiratory Transport
D000079:Acetaldehyde