{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:23:53Z","timestamp":1787498633752,"version":"build-2736575974"},"reference-count":27,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MHLW Association","award":["H25-kagaku-ippan-004"],"award-info":[{"award-number":["H25-kagaku-ippan-004"]}]},{"name":"MHLW Association","award":["H27-kagaku-shitei-004"],"award-info":[{"award-number":["H27-kagaku-shitei-004"]}]},{"name":"MHLW Association","award":["H28-kagaku-ippan-004"],"award-info":[{"award-number":["H28-kagaku-ippan-004"]}]},{"name":"MHLW Association","award":["H30-kagaku-shitei-004"],"award-info":[{"award-number":["H30-kagaku-shitei-004"]}]},{"name":"MHLW Association","award":["JPMH19KD0101"],"award-info":[{"award-number":["JPMH19KD0101"]}]},{"name":"MHLW Association","award":["JPMH20KD0201"],"award-info":[{"award-number":["JPMH20KD0201"]}]},{"name":"MHLW Association","award":["JPMH21KD2004"],"award-info":[{"award-number":["JPMH21KD2004"]}]},{"name":"MHLW Association","award":["JPMH23KD0101"],"award-info":[{"award-number":["JPMH23KD0101"]}]},{"name":"YOG Specified Nonprofit Corporation"},{"DOI":"10.13039\/100016642","name":"Japan Chemical Industry Association","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100016642","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Cultural Affairs and Missions Sector, Ministry of higher education of the Arab republic of Egypt"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>We previously carried out an in vivo 2-year study to assess the potential toxicity\/carcinogenicity of double-walled carbon nanotubes (DWCNTs) in a rat lung. We found that administration of DWCNTs by intratracheal\u2013intrapulmonary spraying (TIPS) at a dose of 0.5 mg\/rat induced the development of lung tumors in 7 of 24 treated rats while 1 of 21 untreated rats and 1 of 25 vehicle treated rats developed lung tumors. In the current study, we administered DWCNTs of different lengths, 1.5 \u00b5m, 7 \u00b5m, and 15 \u00b5m, to rats by TIPS to investigate the possible effect of the length of this thin, flexible CNT on toxicity\/carcinogenicity in rat lungs. Rats were administered DWCNTs with lengths of 1.5 \u00b5m (D1.5), 7 \u00b5m (D7), and 15 \u00b5m (D15) by TIPS once every other day over the course of two weeks for a total of eight administrations. The total dose administered was approximately 22 \u00d7 1012 fibers per rat, corresponding to 0.0504 mg for D1.5, 0.232 mg for D7, and 0.504 mg for D15. Another group of rats was administered 0.5 mg MWCNT-7, a known carcinogen. Animals were killed at weeks 6 and 104 (4 and 102 weeks after the final TIPS administration). The mean survival time of the rats in the untreated, vehicle, D1.5, D7, and D15 groups was 99 to 104 weeks. One rat in the D1.5 group and one rat in the D15 group died before week 75. The remaining rats in the untreated, vehicle, D1.5, D7, and D15 groups were included in the final assessment of lung toxicity\/carcinogenicity. In contrast, 11 rats in the MWCNT-7 group died before week 75 due to the development of malignant mesothelioma. Due to the much shorter survival time of the rats treated with MWCNT-7, accurate assessment of lung proliferative lesions in this group was not possible. At week 6, an increase in alveolar macrophages and granulation tissue foci in the alveoli was observed in all DWCNT administered groups. The alveolar epithelial cell PCNA index was also significantly increased in the D7 and D15 groups. Increases in alveolar macrophages, granulation tissue foci, and the alveolar epithelial cell PCNA index were observed in all DWCNT-treated groups at the final sacrifice. The incidences of lung tumors were 0\/13, 0\/12, 4\/12, 3\/8, and 2\/10 in the untreated, vehicle, D1.5, D7, and D15 groups, respectively. In agreement with our previous study, the DWCNTs tested in the present study were carcinogenic in the rat lung. In addition, we present evidence that DWCNT fiber length may possibly have an effect on DWCNT-induced carcinogenicity in rat lungs.<\/jats:p>","DOI":"10.3390\/nano15181402","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T07:52:28Z","timestamp":1757663548000},"page":"1402","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Comparative Carcinogenicity of Double-Walled Carbon Nanotubes of Different Lengths Administered by Intratracheal Installation into Rat Lungs"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5241-2195","authenticated-orcid":false,"given":"Omnia Hosny Mohamed","family":"Ahmed","sequence":"first","affiliation":[{"name":"Nanotoxicology Project, Nagoya City University, Nagoya 467-8603, Japan"},{"name":"Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 461-8601, Japan"},{"name":"Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Aswan University, Aswan 81528, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8848-6708","authenticated-orcid":false,"given":"Dina Mourad","family":"Saleh","sequence":"additional","affiliation":[{"name":"Nanotoxicology Project, Nagoya City University, Nagoya 467-8603, Japan"},{"name":"Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William T.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Nanotoxicology Project, Nagoya City University, Nagoya 467-8603, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Takase","sequence":"additional","affiliation":[{"name":"Core Laboratory, Graduate School of Medical Sciences, Nagoya City University, Nagoya 461-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4612-0652","authenticated-orcid":false,"given":"Yuhji","family":"Taquahashi","sequence":"additional","affiliation":[{"name":"Division of Cellular and Molecular Toxicology, Center for Biological Safety & Research, National Institute of Health Sciences, Kawasaki 210-0821, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5386-5110","authenticated-orcid":false,"given":"Motoki","family":"Hojo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, Tokyo 169-0073, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai","family":"Maeno","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, Tokyo 169-0073, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsumi","family":"Fukamachi","sequence":"additional","affiliation":[{"name":"Department of Neurotoxicology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 461-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1642-8127","authenticated-orcid":false,"given":"Min","family":"Gi","sequence":"additional","affiliation":[{"name":"Department of Environmental Risk Assessment, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1703-4883","authenticated-orcid":false,"given":"Akihiko","family":"Hirose","sequence":"additional","affiliation":[{"name":"Chemicals Evaluation and Research Institute (CERI), Tokyo 112-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Tsuruoka","sequence":"additional","affiliation":[{"name":"Research Institute for Supra-Materials, Shinshu University, Nagano 380-8553, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8139-8158","authenticated-orcid":false,"given":"Satoru","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 461-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Tsuda","sequence":"additional","affiliation":[{"name":"Nanotoxicology Project, Nagoya City University, Nagoya 467-8603, Japan"},{"name":"Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 461-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0828-2033","authenticated-orcid":false,"given":"Aya","family":"Naiki-Ito","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 461-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1743-8977-11-3","article-title":"Promotion of lung adenocarcinoma following inhalation exposure to multi-walled carbon nanotubes","volume":"11","author":"Sargent","year":"2014","journal-title":"Part. 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