title: Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans.
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.
authors.affiliation: a National Institute for Occupational Safety and Health , Cincinnati , OH , USA.
authors.forename: Eileen D
authors.initials: ED
authors.lastname: Kuempel
authors.affiliation: b Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche , UMR 1162 , Paris , France.|c Labex Immuno-Oncology, Sorbonne Paris Cité, University of Paris Descartes , Paris , France.|d University Institute of Hematology, Sorbonne Paris Cité, University of Paris Diderot , Paris , France.|e University of Paris 13, Sorbonne Paris Cité , Saint-Denis , France.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Jaurand
authors.affiliation: f Department of Public Health , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Møller
authors.affiliation: g Department of Occupational Pneumology , University of Occupational and Environmental Health , Kitakyushu City , Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morimoto
authors.affiliation: h National Institute of Health Sciences , Tokyo , Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: i Center for Health and the Environment, University of California , Davis , California , USA.
authors.forename: Kent E
authors.initials: KE
authors.lastname: Pinkerton
authors.affiliation: j National Institute for Occupational Safety and Health , Morgantown , West Virginia , USA.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Sargent
authors.affiliation: k Institute for Risk Assessment Sciences, Utrecht University , Utrecht , The Netherlands.
authors.forename: Roel C H
authors.initials: RC
authors.lastname: Vermeulen
authors.affiliation: l Department of Chemistry and "G.Scansetti" Interdepartmental Center , Università degli Studi di Torino , Torino , Italy.
authors.forename: Bice
authors.initials: B
authors.lastname: Fubini
authors.affiliation: m Department of Pathology and Laboratory Medicine , Brown University , Providence , RI , USA.
authors.forename: Agnes B
authors.initials: AB
authors.lastname: Kane
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests; D006801:Humans; D057139:Nanofibers / Q000633:toxicity*; D037742:Nanotubes, Carbon / Q000633:toxicity*
chemical_list: D037742:Nanotubes, Carbon
keywords: Cancer mechanisms; carbon nanofibers; carbon nanotubes; cell proliferation; fibrosis; genotoxicity; inflammation; lung cancer; mesothelioma; particle retention; pulmonary; translocation