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Abstract
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.
Acknowledgements
The authors, IARC Mechanisms Subgroup members, gratefully acknowledge the IARC Secretariat and Monograph 111 Working Group members for their scientific review and input on the mechanistic evidence sections that we drafted for the monograph. This manuscript is based on, and updates, the material that we originally prepared for the carbon nanotubes section of the monograph, and it is also informed by the review comments and discussions before and during the monograph meeting. We would especially like to thank the IARC/WHO Secretariat members Dr. Yann Grosse, Dr. Kathryn Guyton, and Dr. Kurt Straif for their insightful review comments on an earlier draft of this paper. Special thanks go to the IARC staff for their administrative support during the monograph meeting, and to Ms Suzette Smiley-Jewell, University of California, Davis, and Ms Ellen Galloway, NIOSH, for editorial assistance on this article. We thank Ms Vanessa B. Williams and Ms Nicole M. Romero, NIOSH, for preparing the final version of the figures. Finally, we would like to thank the four anonymous peer reviewers for their critical review comments which were helpful in improving the final version of this paper.
Declaration of interest
The affiliation of the authors is as shown on the cover sheet. The authors were all originally selected by IARC to participate in the review of the carcinogenic hazard of carbon nanotubes held in October 2014, a review they participated in as independent scientists. As noted in the manuscript, that review will be published by IARC as Monograph 111. This paper was prepared by the authors as an independent endeavor. This review, the interpretations, the conclusions drawn, and the recommendations made are exclusively those of the authors and are not necessarily those of their employers or IARC. None of the authors have appeared in either legal or regulatory proceedings related to the contents of the paper.
The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health.
Supplemental material
Supplemental material for this article is available online here.