Reuzel P G, Wilmer J W, Woutersen R A, Zwart A, Rombout P J, Feron V J
TNO-CIVO Toxicology and Nutrition Institute, Zeist, The Netherlands.
J Toxicol Environ Health. 1990;29(3):279-92. doi: 10.1080/15287399009531391.
The combined effects on the nasal epithelium of mixtures of ozone and formaldehyde at cytotoxic and noncytotoxic concentrations were examined. Male Wistar rats were exposed by inhalation during 22 h/d for 3 consecutive days to 0.3, 1.0, or 3.0 ppm formaldehyde, or to 0.2, 0.4, or 0.8 ppm ozone, or to mixtures of 0.4 ppm ozone and 0.3, 1.0, or 3.0 ppm formaldehyde, or to 1.0 ppm formaldehyde and 0.2, 0.4, or 0.8 ppm ozone, or they were sham-exposed to clean air. The noses were examined for pathological changes at six standard cross levels by light microscopy and for epithelial cell proliferation by counting [3H-methyl]thymidine-labeled cells at cross levels II and III. Ozone at 0.4 ppm or 0.8 ppm or formaldehyde at 3 ppm enhanced cell proliferation at cross level II at all locations, except for the epithelium of the septum, which was not affected by ozone. At cross level III ozone alone did not induce cell proliferation, but formaldehyde at 0.3 and 1 ppm tended to reduce cell proliferation while at 3 ppm proliferation was slightly stimulated. The combined exposure to 0.4 ppm ozone and 0.3 ppm formaldehyde induced less cell proliferation at cross levels II and III when compared with that of 0.4 ppm ozone alone. Less cell proliferation was also seen at cross level II when animals were exposed to 0.4 or 0.8 ppm ozone in combination with 1 ppm formaldehyde than when exposed to these ozone concentrations alone. A more than additive increase in cell proliferation was found at cross level II after exposure to 0.4 ppm ozone in combination with 3 ppm formaldehyde, and at cross level III in animals exposed to 0.4 ppm ozone and 1 or 3 ppm formaldehyde. Treatment-related histopathological nasal changes, such as disarrangement, loss of cilia, and hyper/metaplasia of the epithelium were seen at 0.2, 0.4, and 0.8 ppm ozone and at 3 ppm formaldehyde. Simultaneous exposure to both materials did not noticeably affect type, degree, and size of the microscopic nasal lesions.
研究了细胞毒性和非细胞毒性浓度的臭氧与甲醛混合物对鼻上皮的联合作用。将雄性Wistar大鼠每天22小时连续3天吸入0.3、1.0或3.0 ppm的甲醛，或0.2、0.4或0.8 ppm的臭氧，或0.4 ppm臭氧与0.3、1.0或3.0 ppm甲醛的混合物，或1.0 ppm甲醛与0.2、0.4或0.8 ppm臭氧的混合物，或假暴露于清洁空气中。通过光学显微镜在六个标准横断水平检查鼻子的病理变化，并通过计数横断水平II和III处的[3H-甲基]胸苷标记细胞来检测上皮细胞增殖。0.4 ppm或0.8 ppm的臭氧或3 ppm的甲醛在所有位置的横断水平II处均增强了细胞增殖，但鼻中隔上皮除外，其不受臭氧影响。在横断水平III处，单独的臭氧不会诱导细胞增殖，但0.3和1 ppm的甲醛倾向于减少细胞增殖，而3 ppm时增殖受到轻微刺激。与单独的0.4 ppm臭氧相比，同时暴露于0.4 ppm臭氧和0.3 ppm甲醛在横断水平II和III处诱导的细胞增殖较少。当动物同时暴露于0.4或0.8 ppm臭氧与1 ppm甲醛时，在横断水平II处也比单独暴露于这些臭氧浓度时观察到更少的细胞增殖。在暴露于0.4 ppm臭氧与3 ppm甲醛后，横断水平II处以及暴露于0.4 ppm臭氧和1或3 ppm甲醛的动物的横断水平III处发现细胞增殖有超过相加的增加。在0.2、0.4和0.8 ppm的臭氧以及3 ppm的甲醛下观察到与治疗相关的鼻组织病理学变化，如上皮排列紊乱、纤毛丧失和上皮增生/化生。同时暴露于两种物质并未明显影响微观鼻病变的类型、程度和大小。
