Chang J C, Gross E A, Swenberg J A, Barrow C S
Toxicol Appl Pharmacol. 1983 Apr;68(2):161-76. doi: 10.1016/0041-008x(83)90001-7.
Inhalation exposure for 2 years to 14.3 ppm formaldehyde (HCHO) induced a 50% incidence of squamous cell carcinoma in the nasal cavity of F-344 rats but only a 3.3% incidence in B6C3F1 mice. Since the response was concentration and species dependent, species differences in nasal cavity "dose" were examined as a possible mechanism for the differences in tumor incidence. Naive (nonpretreated) and HCHO-pretreated (6 or 15 ppm, 6 hr/day, 4 days) mice and rats were exposed to HCHO for 6 hr during which respiratory rate and tidal volume were recorded to calculate the theoretical deposition (micrograms/min/cm2) of HCHO on the nasal epithelium. Species differences in delivered "dose" were further assessed by comparative autoradiography, histopathology, and cell turnover studies. Because mice were better able to reduce minute ventilation upon repeated exposures, they had less HCHO available for deposition than rats, resulting in less tissue damage and a lower rate of cell turnover in the nasal epithelium. The correlation between calculated "dose" and observed nasal toxicity, including nasal tumor incidence, demonstrates that by normalizing the dosimetry to nasal surface area, species differences in nasal toxicity may be better understood.
对F-344大鼠鼻腔给予2年14.3 ppm甲醛（HCHO）吸入暴露，导致鳞状细胞癌发生率为50%，但在B6C3F1小鼠中仅为3.3%。由于该反应取决于浓度和物种，因此研究了鼻腔“剂量”的物种差异，作为肿瘤发生率差异的一种可能机制。将未处理（未预处理）和经HCHO预处理（6或15 ppm，每天6小时，共4天）的小鼠和大鼠暴露于HCHO 6小时，在此期间记录呼吸频率和潮气量，以计算HCHO在鼻上皮上的理论沉积量（微克/分钟/平方厘米）。通过比较放射自显影、组织病理学和细胞更新研究，进一步评估了递送“剂量”的物种差异。由于小鼠在反复暴露时更能降低分钟通气量，它们可用于沉积的HCHO比大鼠少，导致组织损伤更小，鼻上皮细胞更新率更低。计算的“剂量”与观察到的鼻腔毒性（包括鼻腔肿瘤发生率）之间的相关性表明，通过将剂量测定标准化为鼻表面积，可以更好地理解鼻腔毒性的物种差异。
