Objective: We reviewed studies on pulmonary, reproductive, and developmental toxicity caused by carbon nanotubes (CNTs). In paricular, we analyzed how CNT exposure affects the several processes of pulmonary toxicity, including inflammation, injury, fibrosis, and pulmonary tumors. Methods: In pulmonary toxicity, there are various processes, including inflammation, injury, fibrosis, respiratory tumor in the lungs, and biopersistence of CNTs and genotoxicity as tumor-related factors, to develop the respiratory tumor. We evaluated the evidence for the carcinogenicity of CNTs in each process. In the fields of reproductive and developmental toxicity, studies of CNTs have been conducted mainly with mice. We summarized the findings of reproductive and developmental toxicity studies of CNTs. Results: In animal studies, exposure to CNTs induced sustained inflammation, fibrosis, lung cancer following long-term inhalation, and gene damage in the lung. CNTs also showed high biopersistence in animal studies. Fetal malformations after intravenous and intraperitoneal injections and intratracheal instillation, fetal loss after intravenous injection, behavioral changes in offsprings after intraperitoneal injection, and a delay in the delivery of the first litter after intratracheal instillation were reported in mice-administered multi-walled carbon nanotubes (MWCNTs). Single-walled carbon nanotubes (SWCNTs) appeared to be embryolethal and teratogenic in mice when given by intravenous injection; moreover, the tubes induced death and growth retardation in chicken embryos. Conclusion: CNTs are considered to have carcinogenicity and can cause lung tumors. However, the carcinogenicity of CNTs may attenuate if the fiber length is shorter. The available data provide initial information on the potential reproductive and developmental toxicity of CNTs.
Multi-walled carbon nanotubes (MWCNTs), dispersed in suspensions consisting mainly of individual tubes, were used for intratracheal instillation and inhalation studies. Rats intratracheally received a dose of 0.2 mg, or 1 mg of MWCNTs and were sacrificed from 3 days to 6 months. MWCNTs induced a pulmonary inflammation, as evidenced by a transient neutrophil response in the low-dose groups, and presence of small granulomatous lesion and persistent neutrophil infiltration in the high-dose groups. In the inhalation study, rats were exposed to 0.37 mg/m(3) aerosols of well-dispersed MWCNTs (>70% of MWCNTs were individual fibers) for 4 weeks, and were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. The inhalation exposures delivered less amounts of MWCNTs into the lungs, and therefore less pulmonary inflammation responses was observed, as compared to intratracheal instillation. The results of our study show that well-dispersed MWCNT can produce pulmonary lesions, including inflammation.
In an evaluation of carbon nanotubes (CNTs) for the IARC Monograph 111,
the Mechanisms Subgroup was tasked with assessing the strength of evidence on
the potential carcinogenicity of CNTs in humans. The mechanistic evidence was
considered to be not strong enough to alter the evaluations based on the animal
data. In this paper, we provide an extended, in-depth examination of the
in vivo and in vitro experimental studies
according to current hypotheses on the carcinogenicity of inhaled particles and
fibers. We cite additional studies of CNTs that were not available at the time
of the IARC meeting in October 2014, and extend our evaluation to include carbon
nanofibers (CNFs). Finally, we identify key data gaps and suggest research needs
to reduce uncertainty. The focus of this review is on the cancer risk to workers
exposed to airborne CNT or CNF during the production and use of these materials.
The findings of this review, in general, affirm those of the original evaluation
on the inadequate or limited evidence of carcinogenicity for most types of CNTs
and CNFs at this time, and possible carcinogenicity of one type of CNT
(MWCNT-7). The key evidence gaps to be filled by research include: investigation
of possible associations between in vitro and early-stage
in vivo events that may be predictive of lung cancer or
mesothelioma, and systematic analysis of dose–response relationships
across materials, including evaluation of the influence of physico-chemical
properties and experimental factors on the observation of nonmalignant and
malignant endpoints.
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