Uptake of acetaldehyde vapor and aldehyde dehydrogenase levels in the upper respiratory tracts of the mouse, rat, hamster, and guinea pig.
Acetaldehyde is a ubiquitous indoor and outdoor air pollutant. This vapor is a respiratory tract irritant and a rodent inhalation carcinogen. The current study was aimed at examining the upper respiratory tract (URT) deposition efficiency for this vapor at inspired concentrations of 1, 10, 100, or 1000 ppm in four rodent species: B6C3F1 mouse, Sprague-Dawley rat, Syrian hamster, and Hartley guinea pig. For measurement of vapor uptake, the URT was isolated in urethane-anesthetized animals via insertion of a polyethylene cannula in the trachea such that its tip lay at the larynx. Uptake was measured under constant velocity unidirectional inspiratory flow at flow rates of approximately 50, 100, 200, and 300% of the predicted minute ventilation of each species and also under pseudo-cyclic flow (sinusoidal flow at 100% of the predicted minute ventilation with a constant 7 ml/min bleed for analysis). In addition, aldehyde dehydrogenase (AldDH) activities were measured in whole nasal tissue homogenates from each species for comparative purposes. In all species a high-affinity (Km < 0.2 mM), low-capacity AldDH isozyme was observed. In the mouse, hamster, and rat, a low-affinity (Km > 10 mM), high-capacity isozyme was observed; this isozyme was not observed in nasal tissue homogenates of the guinea pig. In all species, URT deposition efficiency was strongly dependent on the inspired concentration, with uptake being two- to three-fold more efficient at inspired concentrations of 1 or 10 ppm than at 1000 ppm. For example, at flows approximating the twice-minute ventilation rate URT uptake efficiency averaged 43, 49, 28, and 43% in the mouse, hamster, rat, and guinea pig, respectively, at an inspired concentration of 10 ppm, compared to 27, 14, 16, and 6% at an inspired concentration of 1000 ppm. Species differences were observed in uptake efficiency. At an inspired concentration of 1000 ppm a two-factor analysis of variance followed by a Newman-Keuls test revealed that uptake was significantly higher in the mouse, rat, and hamster than in the guinea pig. In contrast, at 10 ppm uptake was significantly lower in the rat than in any other species. Thus, the rank order of these species on the basis of ability to scrub acetaldehyde from the airstream differed at high compared to low inspired concentrations. The documentation of greatly differing deposition efficiencies as well as differing relative dosimetric relationships among species at high compared to low exposure concentrations highlights the potential complexities of quantitative extrapolation of high-concentration rodent inhalation toxicity data.
Morris
J B
JB
Department of Pharmaceutical Sciences, University of Connecticut, Storrs 06269, USA.
D000079:Acetaldehyde / Q000493:pharmacokinetics*; D000445:Aldehyde Oxidoreductases / Q000378:metabolism*; D000818:Animals; D006224:Cricetinae; D006168:Guinea Pigs; D008297:Male; D008647:Mesocricetus; D051379:Mice; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013045:Species Specificity; D013047:Specific Pathogen-Free Organisms
D000445:Aldehyde Oxidoreductases; C018699:aldehyde dehydrogenase (NAD(P)+); D000079:Acetaldehyde