MWCNT-7 administered to the lung by intratracheal instillation induces development of pleural mesothelioma in F344 rats

Cancer Sci. 2019 Aug;110(8):2485-2492. doi: 10.1111/cas.14121. Epub 2019 Jul 25.

Abstract

Multi-walled carbon nanotube-7 (MWCNT-7) fibers are biopersistent and have a structure similar to asbestos. MWCNT-7 has been shown to induce malignant mesothelioma when administered by intrascrotal or intraperitoneal injection in rats and mice, and an inhalation study demonstrated that rats exposed to respirable MWCNT-7 developed lung tumors. MWCNT-N, which is similar to MWCNT-7, was shown to induce both lung tumors and malignant mesothelioma in rats when administered by trans-tracheal intrapulmonary spraying (TIPS). The present study was performed to investigate the carcinogenicity of MWCNT-7 when administered by the TIPS method. Ten-week-old male F344/Crj rats were divided into 3 groups and administered 0.5 mL vehicle, 0.250 μg/mL MWCNT-7 or 0.250 μg/mL crocidolite once a week for 12 weeks (total doses of 1.5 mg/rat) and then observed for up to 104 weeks. Rats in the MWCNT-7 group began to die from pathologies associated with the development of malignant mesothelioma 35 weeks after the final TIPS administration. Overall, the incidence of malignant mesothelioma in the MWCNT-7 group was significantly higher than in the vehicle or crocidolite groups.

Keywords: MWCNT-7; inhalation toxicity; intra-tracheal intra-pulmonary spraying; malignant mesothelioma; rat.

MeSH terms

  • Animals
  • Asbestos, Crocidolite / adverse effects
  • Injections, Intraperitoneal / methods
  • Lung / drug effects*
  • Lung Neoplasms / chemically induced*
  • Lung Neoplasms / pathology
  • Male
  • Mesothelioma / chemically induced*
  • Mesothelioma / pathology
  • Mesothelioma, Malignant
  • Nanotubes, Carbon / adverse effects*
  • Pleural Neoplasms / chemically induced*
  • Pleural Neoplasms / pathology
  • Rats
  • Rats, Inbred F344
  • Trachea / drug effects
  • Trachea / pathology

Substances

  • Nanotubes, Carbon
  • Asbestos, Crocidolite