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

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 nanot...

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Autores principales: Saleh, Dina Mourad, Luo, Shengyong, Ahmed, Omnia Hosny Mohamed, Alexander, David B., Alexander, William T., Gunasekaran, Sivagami, El-Gazzar, Ahmed M., Abdelgied, Mohamed, Numano, Takamasa, Takase, Hiroshi, Ohnishi, Makoto, Tomono, Susumu, Hady, Randa Hussein Abd el, Fukamachi, Katsumi, Kanno, Jun, Hirose, Akihiko, Xu, Jiegou, Suzuki, Shugo, Naiki-Ito, Aya, Takahashi, Satoru, Tsuda, Hiroyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9026941/
https://www.ncbi.nlm.nih.gov/pubmed/35449069
http://dx.doi.org/10.1186/s12989-022-00469-8
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author Saleh, Dina Mourad
Luo, Shengyong
Ahmed, Omnia Hosny Mohamed
Alexander, David B.
Alexander, William T.
Gunasekaran, Sivagami
El-Gazzar, Ahmed M.
Abdelgied, Mohamed
Numano, Takamasa
Takase, Hiroshi
Ohnishi, Makoto
Tomono, Susumu
Hady, Randa Hussein Abd el
Fukamachi, Katsumi
Kanno, Jun
Hirose, Akihiko
Xu, Jiegou
Suzuki, Shugo
Naiki-Ito, Aya
Takahashi, Satoru
Tsuda, Hiroyuki
author_facet Saleh, Dina Mourad
Luo, Shengyong
Ahmed, Omnia Hosny Mohamed
Alexander, David B.
Alexander, William T.
Gunasekaran, Sivagami
El-Gazzar, Ahmed M.
Abdelgied, Mohamed
Numano, Takamasa
Takase, Hiroshi
Ohnishi, Makoto
Tomono, Susumu
Hady, Randa Hussein Abd el
Fukamachi, Katsumi
Kanno, Jun
Hirose, Akihiko
Xu, Jiegou
Suzuki, Shugo
Naiki-Ito, Aya
Takahashi, Satoru
Tsuda, Hiroyuki
author_sort Saleh, Dina Mourad
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12989-022-00469-8.
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spelling pubmed-90269412022-04-23 Assessment of the toxicity and carcinogenicity of double-walled carbon nanotubes in the rat lung after intratracheal instillation: a two-year study Saleh, Dina Mourad Luo, Shengyong Ahmed, Omnia Hosny Mohamed Alexander, David B. Alexander, William T. Gunasekaran, Sivagami El-Gazzar, Ahmed M. Abdelgied, Mohamed Numano, Takamasa Takase, Hiroshi Ohnishi, Makoto Tomono, Susumu Hady, Randa Hussein Abd el Fukamachi, Katsumi Kanno, Jun Hirose, Akihiko Xu, Jiegou Suzuki, Shugo Naiki-Ito, Aya Takahashi, Satoru Tsuda, Hiroyuki Part Fibre Toxicol Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12989-022-00469-8. BioMed Central 2022-04-22 /pmc/articles/PMC9026941/ /pubmed/35449069 http://dx.doi.org/10.1186/s12989-022-00469-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Saleh, Dina Mourad
Luo, Shengyong
Ahmed, Omnia Hosny Mohamed
Alexander, David B.
Alexander, William T.
Gunasekaran, Sivagami
El-Gazzar, Ahmed M.
Abdelgied, Mohamed
Numano, Takamasa
Takase, Hiroshi
Ohnishi, Makoto
Tomono, Susumu
Hady, Randa Hussein Abd el
Fukamachi, Katsumi
Kanno, Jun
Hirose, Akihiko
Xu, Jiegou
Suzuki, Shugo
Naiki-Ito, Aya
Takahashi, Satoru
Tsuda, Hiroyuki
Assessment of the toxicity and carcinogenicity of double-walled carbon nanotubes in the rat lung after intratracheal instillation: a two-year study
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 Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9026941/
https://www.ncbi.nlm.nih.gov/pubmed/35449069
http://dx.doi.org/10.1186/s12989-022-00469-8
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