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.

Capillary electrophoresis analysis of affinity to assess carboxylation of multi-walled carbon nanotubes

“…A substantial number of studies aimed at exploring the health effects of carbon nanotube toxicity have been reported. Currently, the toxicity of carbon nanotubes is conflicting or poorly understood for a variety of reasons [3–5], although a specific type of multi-walled carbon nanotube has been demonstrated to be carcinogenic in mice and rats [3, 6]. Modifying carbon nanotubes by functionalizing them may reduce toxicity and improve the aqueous solubility.…”

Particle emissions from laboratory activities involving carbon nanotubes

“…The results from toxicological studies should not be generalized to humans since no incidence related to exposure to CNTs has been reported so far. Recently, one type of multi-walled CNTs (CNT 7) were classified by the International Agency for Research on Cancer (IARC) as a 2B carcinogen, “possibly carcinogenic to humans” (Grosse et al 2014; IARC 2016; Kuempel et al 2016). …”

Effect of surface functionalizations of multi-walled carbon nanotubes on neoplastic transformation potential in primary human lung epithelial cells

“…In most instances, MWCNT exposures are expected to occur over long time frames at low levels (Kuempel et al, 2017). Once MWCNTs move downstream from their manufacturing site into additive manufacturing, modifications to their surface, structural integrity, and other physicochemical properties are expected due to their wide spread use in numerous applications, each with their own physical and chemical requirements.…”

“…Changes or elimination of surface functionalization will not only change the technological abilities, but possibly the transport, transformation, and toxicological effect of MWCNTs if released into the environment (Petersen et al, 2011). To date, few studies have examined the changes in physicochemical properties of MWCNTs across their life cycle (Dahm et al, 2012; Hedmer et al, 2014), and how these changes potentially impact worker pulmonary health (Bishop et al, 2016; Kuempel et al, 2017). No studies have evaluated the life cycle impacts on MWCNT tumorigenic potential.…”