Potassium octatitanate fibers (K2O•8TiO2, POT fibers) are used as an asbestos substitute. Their physical characteristics suggest that respirable POT fibers are likely to be carcinogenic in the lung and pleura. However, previous 2-year inhalation studies reported that respired POT fibers had little or no carcinogenic potential. In the present study ten-week old male F344 rats were left untreated or were administered vehicle, 0.25 or 0.5 mg rutile-type nano TiO2 (r-nTiO2), 0.25 or 0.5 mg POT fibers, or 0.5 mg MWCNT-7 by intra-tracheal intra-pulmonary spraying (TIPS), and then observed for 2 years. There were no differences between the r-nTiO2 and control groups. The incidence of bronchiolo-alveolar cell hyperplasia was significantly increased in the groups treated with 0.50 mg POT and 0.50 mg MWCNT-7. The overall incidence of lung tumors, however, was not increased in either the POT or MWCNT-7 treated groups. Notably, the carcinomas that developed in the POT and MWCNT-7 treated rats were accompanied by proliferative fibrous connective tissue while the carcinomas that developed in the untreated rats and the r-nTiO2 treated rats were not (carcinomas did not develop in the vehicle control rats). In addition, the carcinoma that developed in the rat treated with 0.25 mg POT was a squamous cell carcinoma, a tumor that develops spontaneously in about 1 per 1700 rats. The incidence of mesothelial cell hyperplasia was 4/17, 7/16, and 10/14 and the incidence of malignant mesothelioma was 3/17, 1/16, and 2/14 in the 0.25 mg POT, 0.5 mg POT, and MWCNT-7 treated groups, respectively. Neither mesothelial cell hyperplasia nor mesothelioma developed in control rats or the rats treated with r-nTiO2. Since the incidence of spontaneously occurring malignant mesothelioma in rats is extremely low, approximately 1 per 1000 animals (Japan Bioassay Research Center [JBRC] historical control data), the development of multiple malignant mesotheliomas in the POT and MWCNT-7 treated groups was biologically significant. The incidence of pleural mesotheliomas in male F344 rats administered POT fibers and MWCNT-7 was significantly higher than the JBRC historical control data, indicating that the incidence of pleural mesothelioma in the groups administered POT fibers and MWCNT-7 fibers via the airway using TIPS was biologically significant. The incidence of type II epithelial cell hyperplasia and the histology of the carcinomas that developed in the POT treated rats also indicates that respirable POT fibers are highly likely to be carcinogenic in the lungs of male F344 rats.

中文翻译：

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肺内给药后八丁烷酸钾（POT）纤维对Fischer 344雄性大鼠肺和胸膜的致癌作用

八ati钛酸钾纤维（K2O•8TiO2，POT纤维）用作石棉替代品。它们的物理特征表明，可吸入的POT纤维在肺和胸膜中可能具有致癌性。但是，以前的2年吸入研究报告说，呼吸的POT纤维几乎没有或没有致癌潜力。在本研究中，十周大的雄性F344大鼠未经治疗或接受媒介物，0.25或0.5毫克金红石型纳米TiO2（r-nTiO2），0.25或0.5毫克POT纤维或0.5毫克MWCNT-7。气管内喷雾（TIPS），然后观察2年。r-nTiO2与对照组之间没有差异。在0.50 mg POT和0.50 mg MWCNT-7处理的组中，细支气管肺泡细胞增生的发生率显着增加。但是，肺部肿瘤的整体发病率 在POT或MWCNT-7处理组中均未升高。值得注意的是，在POT和MWCNT-7治疗的大鼠中发展的癌伴有增殖性纤维结缔组织，而在未治疗的大鼠和r-nTiO2治疗的大鼠中则没有（在载体对照大鼠中未发展癌）。 ）。此外，用0.25 mg POT治疗的大鼠中发展的癌是鳞状细胞癌，即每1700只大鼠中约有1例自发发展的肿瘤。在0.25 mg POT，0.5 mg POT和MWCNT中，间皮细胞增生的发生率分别为4 / 17、7 / 16和10/14，恶性间皮瘤的发生率分别为3 / 17、1 / 16和2/14。 -7个治疗组。在对照大鼠或r-nTiO2处理的大鼠中，均未出现间皮细胞增生或间皮瘤。由于大鼠自发发生的恶性间皮瘤的发病率极低，每1000只动物中约有1例（日本生物测定研究中心[JBRC]历史对照数据），因此在POT和MWCNT-7治疗组中发生多种恶性间皮瘤具有生物学意义。雄性F344大鼠给予POT纤维和MWCNT-7的胸膜间皮瘤的发生率明显高于JBRC的历史对照数据，表明使用TIPS经气道给予POT纤维和MWCNT-7纤维的组的胸膜间皮瘤的发生率较高。具有生物学意义。