Assessment of the toxicity and carcinogenicity of double-walled carbon nanotubes in the rat lung after intratracheal instillation: a two-year study

Particle and Fibre Toxicology

Shengyong Luo¹  Hiroshi Takase²  Aya Naiki-Ito³  Satoru Takahashi³  Randa Hussein Abd el Hady⁴  Ahmed M. El-Gazzar⁵  Mohamed Abdelgied⁶  Susumu Tomono⁷  Shugo Suzuki⁸  Katsumi Fukamachi⁹  Makoto Ohnishi^1,10  Omnia Hosny Mohamed Ahmed^1,11  Dina Mourad Saleh^1,11  William T. Alexander^1,11  David B. Alexander^1,11  Takamasa Numano^1,11  Sivagami Gunasekaran^1,11  Hiroyuki Tsuda^1,11  Jiegou Xu^1,11  Jun Kanno^1,12  Akihiko Hirose^1,12 

[1] College of Basic Medical Sciences, Anhui Medical University;Core Laboratory, Graduate School of Medicine, Nagoya City University;Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University;Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Assuit University;Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Alexandria University;Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Beni-Suef University;Department of Microbiology and Immunology, Aichi Medical University School of Medicine;Department of Molecular Pathology, Osaka Metropolitan University Graduate School of Medicine;Department of Neurotoxicology, Graduate School of Medical Sciences, Nagoya City University;Japan Industrial Safety and Health Association, Japan Bioassay Research Center;Nanotoxicology Lab Project, Nagoya City University;National Institute Hygienic Sciences;

关键词: Double walled carbon nanotubes;    Two-year study;    Toxicity;    Carcinogenicity;    Rats;   

DOI  :  10.1186/s12989-022-00469-8

来源: DOAJ

【 摘 要 】

Abstract Background Considering the expanding industrial applications of carbon nanotubes (CNTs), safety assessment of these materials is far less than needed. Very few long-term in vivo studies have been carried out. This is the first 2-year in vivo study to assess the effects of double walled carbon nanotubes (DWCNTs) in the lung and pleura of rats after pulmonary exposure. Methods Rats were divided into six groups: untreated, Vehicle, 3 DWCNT groups (0.12 mg/rat, 0.25 mg/rat and 0.5 mg/rat), and MWCNT-7 (0.5 mg/rat). The test materials were administrated by intratracheal-intrapulmonary spraying (TIPS) every other day for 15 days. Rats were observed without further treatment until sacrifice. Results DWCNT were biopersistent in the rat lung and induced marked pulmonary inflammation with a significant increase in macrophage count and levels of the chemotactic cytokines CCL2 and CCL3. In addition, the 0.5 mg DWCNT treated rats had significantly higher pulmonary collagen deposition compared to the vehicle controls. The development of carcinomas in the lungs of rats treated with 0.5 mg DWCNT (4/24) was not quite statistically higher (p = 0.0502) than the vehicle control group (0/25), however, the overall incidence of lung tumor development, bronchiolo-alveolar adenoma and bronchiolo-alveolar carcinoma combined, in the lungs of rats treated with 0.5 mg DWCNT (7/24) was statistically higher (p < 0.05) than the vehicle control group (1/25). Notably, two of the rats treated with DWCNT, one in the 0.25 mg group and one in the 0.5 mg group, developed pleural mesotheliomas. However, both of these lesions developed in the visceral pleura, and unlike the rats administered MWCNT-7, rats administered DWCNT did not have elevated levels of HMGB1 in their pleural lavage fluids. This indicates that the mechanism by which the mesotheliomas that developed in the DWCNT treated rats is not relevant to humans. Conclusions Our results demonstrate that the DWCNT fibers we tested are biopersistent in the rat lung and induce chronic inflammation. Rats treated with 0.5 mg DWCNT developed pleural fibrosis and lung tumors. These findings demonstrate that the possibility that at least some types of DWCNTs are fibrogenic and tumorigenic cannot be ignored.

【 授权许可】

Unknown