Difference in carcinogenicities of two different vapor grown carbon fibers with different physicochemical characteristics induced by intratracheal instillation in rats

Our plain-English summary of Difference in carcinogenicities of two different vapor grown carbon fibers with different physicochemical characteristics induced by intratracheal instillation in rats, by K. Sato, H. Fukui, Y. Hagiwara, et al (Particle and Fibre Toxicology, 2023).

The study

• Authors: K. Sato, H. Fukui, Y. Hagiwara, R. Ogawa, A. Nishioka, T. Numano, T. Sugiyama, M. Kawabe, Y. Mera, T. Yoneda
• Journal: Particle and Fibre Toxicology
• Published: 2023;20(1):37
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Carbon fibers are high aspect ratio structures with diameters on the submicron scale. Vapor grown carbon fibers are contained within multi-walled carbon tubes, with VGCF™-H commonly applied as a conductive additive in lithium-ion batteries. However, several multi-walled carbon fibers, including MWNT-7, have been reported to induce lung carcinogenicity in rats. This study investigated the carcinogenic potential of VGCF™-H fibers in F344 rats of both sexes with the vapor grown carbon fibers VGCF™-H and MWNT-7 over 2 years. The carbon fibers were administered to rats by intratracheal instillation at doses of 0, 0.016, 0.08, and 0.4 mg/kg (total doses of 0, 0.128, 0.64, and 3.2 mg/kg) once per week for eight weeks and the rats were observed for up to 2 years after the first instillation.

Results: Histopathological examination showed the induction of malignant mesothelioma on the pleural cavity with dose-dependent increases observed at 0, 0.128, 0.64, and 3.2 mg/kg in rats of both sexes that were exposed to MWNT-7. On the other hand, only two cases of pleural malignant mesothelioma were observed in the VGCF™-H groups; both rats that received 3.2 mg/kg in male. The animals in the MWNT-7 groups either died or became moribund earlier than those in the VGCF™-H groups, which is thought related to the development of malignant mesothelioma. The survival rates were higher in the VGCF™-H group, and more carbon fibers were observed in the pleural lavage fluid (PLF) of the MWNT-7 groups. These results suggest that malignant mesothelioma is related to the transfer of carbon fibers into the pleural cavity.

Conclusions: The intratracheal instillation of MWNT-7 clearly led to carcinogenicity in both male and female rats at all doses. The equivocal evidence for carcinogenic potential that was observed in male rats exposed to VGCF™-H was not seen in the females. The differences in the carcinogenicities of the two types of carbon fibers are thought due to differences in the number of carbon fibers reaching the pleural cavity. The results indicate that the carcinogenic activity of VGCF™-H is lower than that of MWNT-7.

© 2023. BioMed Central Ltd., part of Springer Nature.

In plain English

In this animal experiment, the authors compared two multi-walled carbon fibers, VGCF™-H and MWNT-7, in male and female F344 rats. The fibers, not asbestos, were delivered into the windpipe (intratracheal instillation) weekly for eight weeks, for total doses of 0.128, 0.64 or 3.2 mg/kg body weight, and the rats were followed for 104 weeks. In rats given MWNT-7 at those three doses, malignant mesothelioma of the chest (thoracic) cavity developed in 1 of 30, 18 of 30 and 37 of 39 males, and in 2 of 30, 1 of 30 and 22 of 30 females. With VGCF™-H it occurred only in 2 of 30 males at the highest dose, which was not statistically different from controls, and in no females. Survival was lower in the higher-dose MWNT-7 groups, and fewer VGCF™-H fibers were found in fluid washed from the chest cavity. Neither fiber significantly increased lung adenoma or adenocarcinoma. The authors concluded that MWNT-7 was clearly carcinogenic, that the evidence for VGCF™-H in males at the highest dose was equivocal, and that the carcinogenic activity of VGCF™-H was clearly lower. They said an inhalation study of VGCF™-H is still needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Two-year animal carcinogenicity experiment comparing two carbon fibers given by intratracheal instillation to rats
• Who was studied: Male and female F344/DuCrlCrlj rats, 10 weeks old at group assignment: 40 rats each in the untreated and vehicle (control) groups and 50 in each VGCF™-H and MWNT-7 dose group, per sex. Histopathology tables list 30 animals per group (39 in the male 3.2 mg/kg MWNT-7 group). The work was done at the DIMS Institute of Medical Science in Japan; study dates are not given.
• Exposure: Two vapor grown multi-walled carbon fibers, VGCF™-H and MWNT-7. No asbestos was tested. Single doses were 0 (control), 0.016, 0.08 and 0.4 mg/kg body weight, given once a week for 8 weeks, for total doses of 0.128, 0.64 and 3.2 mg/kg. VGCF™-H fibers were 148 ± 52 nm in diameter and 5.2 ± 2.7 μm long. MWNT-7 fibers were 75 ± 20 nm in diameter and 9.0 ± 6.1 μm long.
• Main results:
  • Male rats given MWNT-7: malignant mesothelioma in the thoracic cavity in 1 in 30 (3.3%), 18 in 30 (60.0%) and 37 in 39 (94.9%) at total doses of 0.128, 0.64 and 3.2 mg/kg. Controls had 0. Table 10 marks the 0.64 and 3.2 mg/kg groups as significantly different from controls.
  • Male rats given VGCF™-H: malignant mesothelioma in the thoracic cavity in 0 in 30, 0 in 30 and 2 in 30 (6.7%) at 0.128, 0.64 and 3.2 mg/kg. These were not statistically different from controls.
  • Female rats given MWNT-7: malignant mesothelioma in the thoracic cavity in 2 in 30 (6.7%), 1 in 30 (3.3%) and 22 in 30 (73.3%) at 0.128, 0.64 and 3.2 mg/kg. Table 10 marks the 3.2 mg/kg group as significantly different from controls.
  • Female rats given VGCF™-H: no malignant mesothelioma at any dose.
  • Final survival in males was 70.0%, 40.0% and 2.5% in the 0.128, 0.64 and 3.2 mg/kg MWNT-7 groups. In the matching VGCF™-H groups it was 65.0%, 87.5% and 75.0%.
  • Final survival at week 104 in females was 70.0%, 65.0% and 35.0% in the MWNT-7 groups and 72.5%, 77.5% and 77.5% in the VGCF™-H groups, at 0.128, 0.64 and 3.2 mg/kg.
  • Fewer VGCF™-H fibers than MWNT-7 fibers were counted in the pleural lavage fluid (fluid washed from the chest cavity). At week 104, VGCF™-H counts were less than 1/8 of MWNT-7 counts at total doses of 0.128 and 0.64 mg/kg.
  • Neither fiber produced a significant increase in lung or bronchial adenoma or adenocarcinoma in either sex. Adenosquamous carcinoma was seen in one male and one female in the 3.2 mg/kg MWNT-7 groups and in no VGCF™-H rats.
• The authors' conclusion: The authors concluded that, under the conditions of this study, MWNT-7 showed clear carcinogenic properties in both sexes. They found equivocal evidence of carcinogenic potential for VGCF™-H in male rats at the highest dose, but not in females. They attributed the difference to the number of fibers in the pleural cavity and judged the carcinogenic activity of VGCF™-H to be clearly lower than that of MWNT-7.
• Limitations the authors state:
  • The authors stated that a whole-body inhalation study of VGCF™-H is needed, in addition to this instillation study, to clearly evaluate its carcinogenic potential.
  • Because most male rats in the 3.2 mg/kg MWNT-7 group had died by week 104, the week-104 pleural fluid measurements for that group came from only one rat.
  • Doses were calculated per body weight, so males received more fiber per dose than females. The authors believed this dosage difference affected the incidence of mesothelioma.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Aspect Ratio (Length-to-diameter ratio), Carcinogenic, Mesothelioma, Pleural Cavity.

Related studies

• Two-year intermittent exposure of a multiwalled carbon nanotube by intratracheal instillation induces lung tumors and pleural mesotheliomas in F344 rats — M. Hojo, A. Maeno, et al. (2022)
• MWCNT-7 administered to the lung by intratracheal instillation induces development of pleural mesothelioma in F344 rats — T. Numano, H. Higuchi, et al. (2019)
• Dose-Response 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 — A. Maeno, M. Hojo, et al. (2026)
• Pulmonary inflammatory and fibrotic responses in Fischer 344 rats after intratracheal instillation exposure to Libby amphibole — D.J. Padilla-Carlin, M.C. Schladweiler, et al. (2011)
• A single intratracheal instillation of single-walled carbon nanotubes induced early lung fibrosis and subchronic tissue damage in mice — E.J. Park, J. Roh, et al. (2011)
• Absence of in vivo mutagenicity of multi-walled carbon nanotubes in single intratracheal instillation study using F344 gpt delta rats — K. Horibata, A. Ukai, et al. (2017)

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