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Fiber‐shaped particles of potassium octatitanate (tradename  TISMO ; chemical formula K 2 O·6TiO 2 ), which are morphologically similar to asbestos particles, were shown to induce severe proliferative reactions in the pleural mesothelium in a previous experiment carried out over 21 weeks. The present study aims to determine whether these fibers induce malignant mesotheliomas in rodents, and to examine chronic toxicity induced. Additionally, we investigated the specific differences observable between the biological responses to the direct infusion of the fibers alone into the pleural cavity and those induced by the co‐administration of the fibers with a known carcinogen. To detect the induction of malignant pleural mesotheliomas, two experiments were undertaken. In Experiment 1, four strains of mice, A/J, C3H,  ICR , and C57 BL , were examined for 52 weeks after experimental treatment with  TISMO . In Experiment 2, the F344 rats were treated with  TISMO  alone, the lung carcinogen  N ‐bis (2‐hydroxypropyl) nitrosamine ( DHPN ) alone, both  TISMO  and  DHPN , or left untreated and were then examined for 52 weeks. In this experiment, malignant lesion induction was expected in the co‐administration group.  TISMO  fibers were observed in the alveoli, indicating penetration through the visceral pleura in mice and rats. The histopathological detection of  TISMO  fibers in the liver and kidneys of mice and rats indicated migration of the fibers out of the pleural cavity. Atypical mesothelial cells with severe pleural proliferation were observed, but malignant mesotheliomas were not detected. Among the rats, there were no observed malignant alterations in the mesothelium induced by  DHPN – TISMO  co‐administration.

Chronic mesothelial reaction and toxicity of potassium octatitanate fibers in the pleural cavity in mice and F344 rats