Assessment of the toxicity and carcinogenicity of double-walled carbon nanotubes in the rat lung after intratracheal instillation: a two-year study
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 carb...
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | Particle and Fibre Toxicology |
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| Online Access: | https://doi.org/10.1186/s12989-022-00469-8 |
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| author | Dina Mourad Saleh Shengyong Luo Omnia Hosny Mohamed Ahmed David B. Alexander William T. Alexander Sivagami Gunasekaran Ahmed M. El-Gazzar Mohamed Abdelgied Takamasa Numano Hiroshi Takase Makoto Ohnishi Susumu Tomono Randa Hussein Abd el Hady Katsumi Fukamachi Jun Kanno Akihiko Hirose Jiegou Xu Shugo Suzuki Aya Naiki-Ito Satoru Takahashi Hiroyuki Tsuda |
| author_facet | Dina Mourad Saleh Shengyong Luo Omnia Hosny Mohamed Ahmed David B. Alexander William T. Alexander Sivagami Gunasekaran Ahmed M. El-Gazzar Mohamed Abdelgied Takamasa Numano Hiroshi Takase Makoto Ohnishi Susumu Tomono Randa Hussein Abd el Hady Katsumi Fukamachi Jun Kanno Akihiko Hirose Jiegou Xu Shugo Suzuki Aya Naiki-Ito Satoru Takahashi Hiroyuki Tsuda |
| author_sort | Dina Mourad Saleh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T07:22:40Z |
| format | Article |
| id | doaj.art-ceeb9dae1f4742e590016f1f99bc6428 |
| institution | Directory Open Access Journal |
| issn | 1743-8977 |
| language | English |
| last_indexed | 2024-12-11T07:22:40Z |
| publishDate | 2022-04-01 |
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| series | Particle and Fibre Toxicology |
| spelling | doaj.art-ceeb9dae1f4742e590016f1f99bc64282022-12-22T01:16:04ZengBMCParticle and Fibre Toxicology1743-89772022-04-0119112110.1186/s12989-022-00469-8Assessment of the toxicity and carcinogenicity of double-walled carbon nanotubes in the rat lung after intratracheal instillation: a two-year studyDina Mourad Saleh0Shengyong Luo1Omnia Hosny Mohamed Ahmed2David B. Alexander3William T. Alexander4Sivagami Gunasekaran5Ahmed M. El-Gazzar6Mohamed Abdelgied7Takamasa Numano8Hiroshi Takase9Makoto Ohnishi10Susumu Tomono11Randa Hussein Abd el Hady12Katsumi Fukamachi13Jun Kanno14Akihiko Hirose15Jiegou Xu16Shugo Suzuki17Aya Naiki-Ito18Satoru Takahashi19Hiroyuki Tsuda20Nanotoxicology Lab Project, Nagoya City UniversityCollege of Basic Medical Sciences, Anhui Medical UniversityNanotoxicology Lab Project, Nagoya City UniversityNanotoxicology Lab Project, Nagoya City UniversityNanotoxicology Lab Project, Nagoya City UniversityNanotoxicology Lab Project, Nagoya City UniversityDepartment of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Alexandria UniversityDepartment of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Beni-Suef UniversityNanotoxicology Lab Project, Nagoya City UniversityCore Laboratory, Graduate School of Medicine, Nagoya City UniversityJapan Industrial Safety and Health Association, Japan Bioassay Research CenterDepartment of Microbiology and Immunology, Aichi Medical University School of MedicineDepartment of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Assuit UniversityDepartment of Neurotoxicology, Graduate School of Medical Sciences, Nagoya City UniversityNational Institute Hygienic SciencesNational Institute Hygienic SciencesNanotoxicology Lab Project, Nagoya City UniversityDepartment of Molecular Pathology, Osaka Metropolitan University Graduate School of MedicineDepartment of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City UniversityDepartment of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City UniversityNanotoxicology Lab Project, Nagoya City UniversityAbstract 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.https://doi.org/10.1186/s12989-022-00469-8Double walled carbon nanotubesTwo-year studyToxicityCarcinogenicityRats |
| spellingShingle | Dina Mourad Saleh Shengyong Luo Omnia Hosny Mohamed Ahmed David B. Alexander William T. Alexander Sivagami Gunasekaran Ahmed M. El-Gazzar Mohamed Abdelgied Takamasa Numano Hiroshi Takase Makoto Ohnishi Susumu Tomono Randa Hussein Abd el Hady Katsumi Fukamachi Jun Kanno Akihiko Hirose Jiegou Xu Shugo Suzuki Aya Naiki-Ito Satoru Takahashi Hiroyuki Tsuda 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 Double walled carbon nanotubes Two-year study Toxicity Carcinogenicity Rats |
| title | Assessment of the toxicity and carcinogenicity of double-walled carbon nanotubes in the rat lung after intratracheal instillation: a two-year study |
| title_full | Assessment of the toxicity and carcinogenicity of double-walled carbon nanotubes in the rat lung after intratracheal instillation: a two-year study |
| title_fullStr | Assessment of the toxicity and carcinogenicity of double-walled carbon nanotubes in the rat lung after intratracheal instillation: a two-year study |
| title_full_unstemmed | Assessment of the toxicity and carcinogenicity of double-walled carbon nanotubes in the rat lung after intratracheal instillation: a two-year study |
| title_short | Assessment of the toxicity and carcinogenicity of double-walled carbon nanotubes in the rat lung after intratracheal instillation: a two-year study |
| title_sort | assessment of the toxicity and carcinogenicity of double walled carbon nanotubes in the rat lung after intratracheal instillation a two year study |
| topic | Double walled carbon nanotubes Two-year study Toxicity Carcinogenicity Rats |
| url | https://doi.org/10.1186/s12989-022-00469-8 |
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