Herbert R A, Hailey J R, Grumbein S, Chou B J, Sills R C, Haseman J K, Goehl T, Miller R A, Roycroft J H, Boorman G A
Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Toxicol Pathol. 1996 Sep-Oct;24(5):539-48. doi: 10.1177/019262339602400502.
To evaluate the toxicity and carcinogenic potential of long-term exposure to ozone, B6C3F1 mice were exposed by whole-body inhalation to 0, 0.12, 0.5, or 1.0 ppm and 0, 0.5, or 1.0 ppm ozone for 24 or 30 mo (lifetime), respectively. The incidence of alveolar/ bronchiolar adenomas and carcinomas (combined) increased (p < 0.05) in female mice exposed to 1.0 ppm for 24 or 30 mo and marginally increased (p > 0.05) in male mice exposed to concentrations of 0.5 or 1.0 ppm. An increased incidence of nonneoplastic lesions were observed in the nasal cavities and in the centriacinar region of the lung of mice exposed to 0.5 or 1.0 ppm for 24 and 30 mo. Nasal cavity lesions were mild and included hyaline degeneration, hyperplasia, squamous metaplasia, fibrosis and suppurative inflammation of the transitional and respiratory epithelium of the lateral wall, and atrophy of the olfactory epithelium. Lung lesions included replacement of the epithelium of the alveolar ducts and adjacent alveolar septa with epithelium similar to that normally found in terminal bronchioles (metaplasia) and associated alveolar histiocytosis. Based on the results of these studies, we conclude that inhalation exposure of B6C3F1 mice to ozone for 24 or 30 mo (a) is carcinogenic in female B6C3F1 mice exposed to 1.0 ppm of ozone based on an increased incidence of alveolar/bronchiolar adenoma or carcinoma and (b) results in mild, site-specific, nonneoplastic lesions in the nasal cavity and centriacinar lung of male and female mice exposed to 0.5 or 1.0 ppm of ozone for 2 yrs, which persist with continued exposure to 30 mo. It is uncertain whether or not the marginal increase (p > 0.05) of alveolar/bronchiolar neoplasms in male B6C3F1 mice resulted from exposure to ozone.
为评估长期暴露于臭氧环境中的毒性和致癌潜力，将B6C3F1小鼠分别通过全身吸入的方式暴露于0、0.12、0.5或1.0 ppm以及0、0.5或1.0 ppm的臭氧环境中，时长分别为24个月或30个月（终生）。暴露于1.0 ppm臭氧环境24个月或30个月的雌性小鼠中，肺泡/细支气管腺瘤和癌（合并计算）的发生率有所增加（p < 0.05），而暴露于浓度为0.5或1.0 ppm臭氧环境的雄性小鼠中，该发生率略有增加（p > 0.05）。在暴露于0.5或1.0 ppm臭氧环境24个月和30个月的小鼠的鼻腔和肺的终末腺泡区域，观察到非肿瘤性病变的发生率有所增加。鼻腔病变较轻，包括透明变性、增生、鳞状化生、纤维化以及外侧壁过渡和呼吸上皮的化脓性炎症，以及嗅上皮萎缩。肺部病变包括肺泡导管和相邻肺泡间隔的上皮被类似于终末细支气管中正常发现的上皮（化生）所取代，以及相关的肺泡组织细胞增多症。基于这些研究结果，我们得出结论：B6C3F1小鼠吸入臭氧24个月或30个月，(a) 对于暴露于1.0 ppm臭氧的雌性B6C3F1小鼠具有致癌性，依据是肺泡/细支气管腺瘤或癌的发生率增加；(b) 对于暴露于0.5或1.0 ppm臭氧达2年的雄性和雌性小鼠，会在鼻腔和肺终末腺泡区域导致轻度的、特定部位的非肿瘤性病变，持续暴露至30个月时这些病变依然存在。尚不确定雄性B6C3F1小鼠肺泡/细支气管肿瘤的轻微增加（p > 0.05）是否由臭氧暴露所致。
