{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T04:27:36Z","timestamp":1787372856688,"version":"build-2736575974"},"reference-count":106,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health Labour and Welfare","award":["21KD2004"],"award-info":[{"award-number":["21KD2004"]}]},{"award":["21KD2004"],"award-info":[{"award-number":["21KD2004"]}],"id":[{"id":"https:\/\/ror.org\/03mwa7s65","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>The multiwalled carbon nanotube, MWCNT-7, is carcinogenic to rat lungs when inhaled over the course of 2 years, but does not induce pleural mesothelioma. In contrast, intratracheal instillation of MWCNT-7 causes both lung tumors and pleural mesotheliomas. To explore the possibility of the use of the intratracheal instillation technique in risk characterization, we administered this widely used reference material using instillation to male F344 rats at doses of 0.0175, 0.07, 0.28, or 0.42 mg\/kg once per week for 13 weeks, followed by an observation period of 91 weeks and compared the dose\u2013response toxicological data with the 2-year inhalation study. Lung tumors and pleural mesotheliomas were induced in a dose-dependent manner (the 0.42 mg\/kg group was excluded from analysis of lung tumor formation). The lung burden of MWCNT-7 at week 13 was dose-dependent: 0.0302, 0.191, 0.98, and 1.369 mg\/lung in the 0.0175, 0.07, 0.28, and 0.42 mg\/kg groups, respectively. The number of fibers in the pleural lavage fluid was also dose-dependent. The no-observed-adverse-effect-level (NOAEL) of MWCNT-7\u2019s carcinogenicity was 0.0302 mg\/lung based on no significant lung tumor induction and no mesothelioma induction in the 0.0175 mg\/kg group. When compared based on lung burden, the dose\u2013response relationship and NOAEL of lung tumor induction resembled those in the 2-year inhalation study, offering the possibility of the application of this protocol for risk characterization.<\/jats:p>","DOI":"10.3390\/nano16161039","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:05:19Z","timestamp":1787241919000},"page":"1039","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dose\u2013Response Relationships for Lung Tumor and Pleural Mesothelioma Induction by Repetitive Intratracheal Instillation of a Multiwalled Carbon Nanotube, MWCNT-7, in Rats: Comparison with Inhalation Carcinogenicity Based on Lung Burden"],"prefix":"10.3390","volume":"16","author":[{"given":"Ai","family":"Maeno","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical and Environment Health, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunincho, Shinjuku-Ku, Tokyo 169-0073, Japan"},{"name":"Laboratory of Veterinary Pathology, Graduate School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Chuo-Ku, Sagamihara 252-0206, 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 Environment Health, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunincho, Shinjuku-Ku, Tokyo 169-0073, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimitsu","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Environment Health, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunincho, Shinjuku-Ku, Tokyo 169-0073, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Environment Health, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunincho, Shinjuku-Ku, Tokyo 169-0073, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyomi","family":"Ikushima","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Environment Health, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunincho, Shinjuku-Ku, Tokyo 169-0073, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Igarashi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Environment Health, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunincho, Shinjuku-Ku, Tokyo 169-0073, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7660-6303","authenticated-orcid":false,"given":"Satoshi","family":"Yokota","sequence":"additional","affiliation":[{"name":"Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences, 3-25-26 Tono-Machi, Kawasaki-Ku, Kawasaki 210-9501, 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 and Research, National Institute of Health Sciences, 3-25-26 Tono-Machi, Kawasaki-Ku, Kawasaki 210-9501, 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Mizuho-Cho, Mizuho-Ku, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takamasa","family":"Numano","sequence":"additional","affiliation":[{"name":"National Institute of Occupational Safety and Health, Japan Organization of Occupational Health and Safety, 2-26-1 Muraokahigashi, Fujisawa 251-0012, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Kanno","sequence":"additional","affiliation":[{"name":"Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences, 3-25-26 Tono-Machi, Kawasaki-Ku, Kawasaki 210-9501, 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 Assessment and Research Center, Chemicals Evaluation and Research Institute, Japan, 1-4-25 Koraku, Bunkyo-Ku, Tokyo 112-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7111-4791","authenticated-orcid":false,"given":"Akiko","family":"Inomata","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Environment Health, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunincho, Shinjuku-Ku, Tokyo 169-0073, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0228-9007","authenticated-orcid":false,"given":"Junichi","family":"Kamiie","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Graduate School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Chuo-Ku, Sagamihara 252-0206, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5895-3830","authenticated-orcid":false,"given":"Dai","family":"Nakae","sequence":"additional","affiliation":[{"name":"Department 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