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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.

SUBMITTER: Kuempel ED

PROVIDER: S-EPMC5555643 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans.

Kuempel Eileen D ED Jaurand Marie-Claude MC Møller Peter P Morimoto Yasuo Y Kobayashi Norihiro N Pinkerton Kent E KE Sargent Linda M LM Vermeulen Roel C H RC Fubini Bice B Kane Agnes B AB

Critical reviews in toxicology 20160818 1

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 a ...[more]

PMID: 27537422

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Project description:BACKGROUND:Recent cross-sectional epidemiologic studies have examined the association between human health effects and carbon nanotube and nanofiber (CNT/F) workplace exposures. However, due to the latency of many health effects of interest, cohort studies with sufficient follow-up will likely be needed. The objective of this study was to identify workplace determinants that contribute to exposure and develop predictive models to estimate CNT/F exposures for future use in epidemiologic studies. METHODS:Exposure measurements were compiled from 15 unique facilities for the metrics of elemental carbon (EC) mass at both the respirable and inhalable aerosol size fractions as well as a quantitative analysis performed by transmission electron microscopy (TEM). These metrics served as the dependent variables in model development. Repeated personal samples were collected from most of the 127 CNT/F worker participants for 252 total observations. Determinants were categorized as company-level or worker-level and used to describe the exposure relationship within the dependent variables. The influence of determinants on variance components was explored using mixed linear models that utilized a backwards stepwise selection process with a lowering of the AIC for model determinant selection. Additional ridge regression models were created that examined predictive performance with and without all two-way interactions. Cross-validation was performed on each model to evaluate the generalizability of its predictive capabilities while predictive performance was evaluated according to the corresponding R2 value and root mean square error (RMSE). RESULTS:Determinants at the company-level that increased exposure included an inadequate or semi-adequate engineering control rating, increasing average CNT/F diameter/length, daily quantities of material handled from 101 g to >1 kg and >1 kg, the use of CNF materials, the industry type of hybrid producer/user, and the expert assessment of a high exposure potential. Worker-level determinants associated with higher exposure included handling the dry-powdered form of CNT/F, handling daily quantities of material >1 kg, direct/indirect exposure, having the job title of engineer, using a respirator, using a ventilated or unventilated enclosure, and the job task of powder handling. The mixed linear models explained >60% of the total variance when using all company- and worker-level determinants to create the three exposure models. The cross-validated RMSE values for each of the three mixed models ranged from 2.50 to 4.23. Meanwhile, the ridge regression models, without all two-way interactions, estimated cross-validated RMSE values of 2.85, 2.23, and 2.76 for the predictive models of inhalable EC, respirable EC, and TEM, respectively. CONCLUSIONS:The ridge regression models demonstrated the best performance for predicting exposures to CNT/F for each exposure metric, although they only provided a modest predictive capability. Therefore, it was concluded that the models alone would not be adequate in predicting workplace exposures and would need to be integrated with other methods.

Dataset Information

Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans.

Publications

Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans.

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