Mesothelioma carcinogenesis of chrysotile and forsterite compared and validated by intraperitoneal injection in rat

Asbestos, especially chrysotile, continues to be exposed to humans globally. Hence, it should be disposed properly to prevent asbestos-related diseases, including mesothelioma and lung cancer. This study aimed to verify whether forsterite, a heating product of chrysotile, can cause carcinogenicity, particularly mesothelioma. Forsterite (FO-1000) and enstatite (EN-1500) produced by heating chrysotile at 1,000°C and 1,500°C, respectively, were subjected. We injected 10 mg of chrysotile, FO-1000, or EN-1500 in rats intraperitoneally and observed the development of peritoneal mesothelioma until 24 months. The incidence of peritoneal mesothelioma in the chrysotile group was 91.2%, whereas in the FO-1000 and EN-1500 groups, peritoneal mesothelioma did not develop. Urinary 8-hydroxy-2'-deoxyguanosine and serum N-ERC/mesothelin concentrations significantly increased in the chrysotile group that developed peritoneal mesothelioma, while they only temporarily changed in the FO-1000 or EN-1500 groups during early treatment. Furthermore, there was a significant homozygous deletion of the CDKN2A/p16 gene in the chrysotile group compared to the control group, in contrast to no significant difference in the FO-1000 and EN-1500 groups. Therefore, this study provides clear evidence that forsterite is a nonmesothelioma carcinogen and suggests that forsterite and enstatite are sufficient substances for chrysotile detoxification.