Evaluation of respiratory toxicity and peritoneal mesothelioma induced by heat-treated and milled amosite following intratracheal and intraperitoneal injection in rats

Amoste is highly carcinogenic, and its incomplete removal from the environment continues to pose significant health risks. High temperatures are known to alter the crystal structure of asbestos. In this study, we evaluated the carcinogenicity and respiratory toxicity of heat-treated amosite (AM-1000; heated at 1,000 °C) and its milled derivative (AM-1000G; heat-treated at 1,000 °C and milled), using untreated amosite as a positive control. Physicochemical analyses confirmed that AM-1000G predominantly consisted of non-asbestiform structures with an aspect ratio of less than 3. In a single intratracheal administration study in rats (2 mg; observation period up to 540 d), AM-1000G induced much less severe acute and chronic pulmonary inflammation than amosite or AM-1000 and did not cause fibrosis. No pulmonary adenoma, lung cancer, or pleural mesothelioma was observed in any group. Following intraperitoneal administration (10 mg; two-year observation period), peritoneal mesotheliomas developed in 56% (14/25) of rats in the amosite group, whereas only one (1/25) rat in the AM-1000 group developed mesotheliomas. In contrast, no peritoneal mesothelioma was observed in the AM-1000G group. This study demonstrated that AM-1000G is non-carcinogenic and exhibits markedly reduced acute and chronic respiratory toxicity. These findings provide the first scientific evidence supporting the feasibility of amosite detoxification through heat treatment, based on its biological evaluation. .