Morris J B, Blanchard K T
Toxicology Program, School of Pharmacy, University of Connecticut, Storrs 06269-2092.
Toxicol Appl Pharmacol. 1992 May;114(1):140-6. doi: 10.1016/0041-008x(92)90106-3.
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.
使啮齿动物吸入高浓度乙醛会导致上呼吸道（URT，呼吸道中喉部及喉部之前的所有区域）出现损伤。要全面了解乙醛的吸入毒性，需要掌握该蒸气的吸入剂量关系信息。为此，在单向（50、100、200或300毫升/分钟）和循环（100毫升/分钟）流动条件下，对经氨基甲酸乙酯麻醉的雄性F344大鼠的手术分离上呼吸道进行了研究，测定了在1、10、100或1000 ppm的吸入浓度下乙醛的摄取情况。在所有流动条件下，上呼吸道沉积效率都强烈依赖于吸入浓度。在循环流动条件下，1、10、100和1000 ppm时的上呼吸道沉积效率分别平均为76%、48%、41%和26%。鼻腔乙醛脱氢酶活性平均为1.2微克/分钟。在100和1000 ppm时，乙醛的绝对沉积速率（微克/分钟）超过该活性5至100倍，这表明在高浓度下沉积效率降低可能存在一种机制。单向流动条件下的上呼吸道沉积强烈依赖于吸气流量。Aharonson等人（《应用生理学杂志》37，654 - 657，1974）的传质模型合理预测了流量对沉积的影响。通过对该模型进行积分，利用单向流动研究确定的摄取系数来预测循环流动下的摄取情况。预测的循环沉积效率与观察到的效率相差2.3 +/- 4.3%（平均值 +/- 标准误），这表明该模型可能为循环呼吸条件下乙醛的摄取提供合理的初步近似值。
