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

Our plain-English summary of Evaluation of respiratory toxicity and peritoneal mesothelioma induced by heat-treated and milled amosite following intratracheal and intraperitoneal injection in rats, by H. Yamauchi, A. Takata, K. Yamashita, et al (Industrial Health, 2026).

The study

• Authors: H. Yamauchi, A. Takata, K. Yamashita, M. Aminaka, T. Hitomi, N. Kohyama
• Journal: Industrial Health
• Published: 2026;64(5):421-438
• Read it: PubMed · Publisher · Free full text

Abstract

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.

In plain English

This was an animal experiment in male Wistar rats. The authors compared untreated amosite with amosite heated at 1,000°C (AM-1000) and heated amosite that was then milled (AM-1000G). In one experiment, rats received a single 2 mg dose into the trachea and were followed for up to 540 days. Amosite and AM-1000 caused acute lung inflammation and later fibrosis. AM-1000G caused less inflammation and no fibrosis. No lung adenomas, lung carcinomas or pleural mesotheliomas were found in any group (10 rats per group). In a second experiment, 25 rats in each of the three treated groups received a single 10 mg injection into the abdomen, and 35 control rats received saline; rats were observed until day 720. Peritoneal mesothelioma developed in 14 of 25 rats (56%) given amosite, 1 of 25 (4%) given AM-1000, none of 25 given AM-1000G and none of 35 saline controls. The authors concluded that AM-1000G was non-carcinogenic, and that heating to 1,000°C alone appeared insufficient. They noted that the absence of tumors in the lung model does not rule out amosite's cancer potential.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: single intratracheal injection (lung toxicity and lung tumors) and single intraperitoneal injection (peritoneal mesothelioma) in rats
• Who was studied: Male Wistar rats, 10 weeks old, studied in Japan. Intratracheal study: groups of 5 rats per time point, and 10 rats per group for lung tumor evaluation up to day 540. Intraperitoneal study: 25 rats in each of the three treatment groups and 35 saline controls, observed until day 720.
• Exposure: Three materials were tested. (1) Untreated UICC reference amosite, used as a positive control. (2) Amosite heated at 1,000°C for 1 hour (AM-1000). (3) Heated amosite then milled for 3 minutes (AM-1000G). Doses were a single 2 mg intratracheal dose or a single 10 mg intraperitoneal dose; controls received saline.
• Main results:
  • Intraperitoneal study: 56% of rats given untreated amosite (14/25) developed peritoneal mesothelioma (p<0.001 vs control).
  • Intraperitoneal study: 4% of rats given AM-1000 (1/25) developed peritoneal mesothelioma, significantly lower than the amosite group.
  • Intraperitoneal study: no peritoneal mesothelioma occurred in rats given AM-1000G (0/25).
  • Intraperitoneal study: no peritoneal mesothelioma occurred in saline controls (0/35).
  • Amosite group (intraperitoneal): median mesothelioma survival was 664 days (95% CI: 617 to 711).
  • Amosite group (intraperitoneal): the earliest mesothelioma-related death was at 358 days.
  • Intratracheal study, up to 540 days: no lung adenomas, lung carcinomas or pleural mesotheliomas in any group (0/10 in each group).
  • Intratracheal study: chronic inflammation and fibrosis persisted at day 180 in the amosite and AM-1000 groups.
  • Intratracheal study: the AM-1000G group showed no fibrosis at day 180 and reduced markers of oxidative and nitrosative stress (8-OHdG and iNOS).
  • Intratracheal study, day 3: LDH (a marker of cell damage) in lung lavage fluid was significantly increased in the amosite and AM-1000 groups compared with controls.
  • Intratracheal study: neutrophil counts in the AM-1000 group stayed raised compared with controls for up to 180 days.
  • Intratracheal study: neutrophil counts in the AM-1000G group remained significantly lower than in the amosite and AM-1000 groups.
  • Gene testing (FISH): loss of both copies of the CDKN2A/p16 gene was significantly more common in cells from the amosite group than in controls. Amosite samples came only from rats that developed mesothelioma.
  • The authors interpreted the AM-1000 and AM-1000G results as showing that heating amosite to 1,000°C alone appears insufficient to eliminate its carcinogenic potential, and that milling is also needed.
• The authors' conclusion: The authors concluded that AM-1000G was clearly non-carcinogenic, like forsterite made by heating chrysotile, and showed markedly reduced acute and chronic respiratory toxicity compared with untreated amosite.
• Limitations the authors state:
  • The absence of tumors in the intratracheal model does not negate the carcinogenic potential of amosite or the possibility of pleural mesothelioma.
  • Secondary products such as iron oxides (hematite and magnetite) formed at 1,000°C or above still need to be verified to more reliably show the safety of AM-1000G. Cristobalite, which forms at higher temperatures, also needs toxicity assessment.
  • The mechanism by which milling reduces toxicity remains unclear.
  • TNF-alpha levels rose in all four groups by day 180 for an unknown reason.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Amosite, Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Amosite, Carcinogenic, Crystal Structure, Non-Asbestiform, Aspect Ratio (Length-to-diameter ratio), Inflammation, Fibrosis.

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