Reuzel P G, Bruijntjes J P, Feron V J, Woutersen R A
TNO Toxicology and Nutrition Institute, Zeist, The Netherlands.
Food Chem Toxicol. 1991 May;29(5):341-54. doi: 10.1016/0278-6915(91)90205-l.
The inhalation toxicity of three amorphous silicas (Aerosil 200, Aerosil R 974 and Sipernat 22S) was compared with that of quartz dust. Rats were exposed to 1, 6 or 30 mg Aerosil 200/m3, 30 mg Aerosil R 974/m3, 30 mg Sipernat 22S/m3 or 60 mg quartz/m3 for 6 hr/day, 5 days/wk for 13 wk. Some rats were killed at the end of the exposure period and some were killed 13, 26, 39 or 52 wk after the end of exposure. Clinical signs, body weight, haematology, biochemistry, urinalyses, organ weights, retention of test material in the lungs and regional lymph nodes, collagen content of the lungs, and gross and microscopic pathology were determined in order to disclose possible adverse effects and to study the reversibility, stability or progression of the effects. All test materials induced increases in lung weight, and pulmonary lesions such as accumulation of alveolar macrophages, inflammation, alveolar bronchiolization and fibrosis. In addition, rats exposed to Aerosil 200, Aerosil R 974 or quartz developed granulomatous lesions. Silicosis was observed only in quartz-exposed animals. At the end of the exposure period, Aerosil 200 and quartz had induced the most severe changes. Quartz dust was hardly cleared from the lungs and the changes in the lungs progressed during the post-treatment period, and eventually resulted in lesions resembling silicotic nodules and in one squamous cell carcinoma. Although Aerosil 200 was very quickly cleared from the lungs and regional lymph nodes, the changes in these organs were only partly reversed during the post-exposure period in rats exposed to 30 mg/m3. Aerosil R 974 and the lower levels of Aerosil 200 resulted in less severe, and mostly reversible, changes. The slightest changes were found after exposure to Sipernat 22S, notwithstanding the persistence of this silica in the lungs during the major part of the post-treatment period. The results of this study revealed that only quartz induced progressive lesions in the lungs resembling silicotic nodules. Of the amorphous silicas examined Aerosil 200 induced the most severe changes in the lungs, which only partly recovered, whereas Sipernat 22S induced the least severe, completely reversible lung changes.
将三种无定形二氧化硅（气相二氧化硅200、气相二氧化硅R 974和超微粒硅胶22S）的吸入毒性与石英粉尘的吸入毒性进行了比较。大鼠每天暴露于1、6或30mg气相二氧化硅200/m³、30mg气相二氧化硅R 974/m³、30mg超微粒硅胶22S/m³或60mg石英/m³，每周暴露5天，每天暴露6小时，共暴露13周。在暴露期结束时处死部分大鼠，在暴露结束后13、26、39或52周处死部分大鼠。测定临床症状、体重、血液学指标、生化指标、尿液分析、器官重量、受试物在肺和局部淋巴结中的潴留情况、肺的胶原蛋白含量以及大体和显微镜下病理学变化，以揭示可能的不良反应，并研究这些影响的可逆性、稳定性或进展情况。所有受试物均导致肺重量增加，并引起肺部病变，如肺泡巨噬细胞积聚、炎症、肺泡细支气管化和纤维化。此外，暴露于气相二氧化硅200、气相二氧化硅R 974或石英的大鼠出现了肉芽肿性病变。仅在暴露于石英的动物中观察到矽肺。在暴露期结束时，气相二氧化硅200和石英引起的变化最为严重。石英粉尘很难从肺中清除，肺部变化在治疗后期间有所进展，最终导致类似矽结节的病变，并出现一例鳞状细胞癌。尽管气相二氧化硅200能很快从肺和局部淋巴结中清除，但在暴露于30mg/m³的大鼠中，这些器官的变化在暴露后期间仅部分逆转。气相二氧化硅R 974和较低剂量的气相二氧化硅200导致的变化较轻，且大多是可逆的。尽管超微粒硅胶22S在治疗后大部分时间内持续存在于肺中，但暴露于超微粒硅胶22S后发现的变化最轻微。本研究结果表明，只有石英会在肺部引起类似矽结节的进行性病变。在所检测的无定形二氧化硅中，气相二氧化硅200引起的肺部变化最为严重，且仅部分恢复，而超微粒硅胶22S引起的肺部变化最轻微，且完全可逆。
