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Genotoxicity and carcinogenic potential of carbon nanomaterials

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  • Description:
    Engineered carbon nanomaterials (ECNMs) have undergone broad technological developments in fields such as electronics, energy storage, structural materials, cosmetics, environmental remediation, medical diagnostics, and drug delivery. With such widespread incorporation into numerous products and uses, ECNMs' potential human exposure is to be expected during manufacturing, incorporation into other products, use, disposal, and release into the environment. Carbon nanotubes (CNTs), a major group of carbon nanomaterials, exhibit a fibrous morphology and biopersistence similar to asbestos, a known human carcinogen, and potentially harbor asbestos-like lung cancer and mesothelioma risks associated with their long-term exposure. Several ECNMs are known to induce irreversible damage to exposed tissue (e.g., fibrosis) in animal models or cause genetic damage (i.e., genotoxicity) upon exposure to sensitive tissues/cells, a key first step at initiating tumorigenesis. In addition, ultrafine carbon black (UFCB) and multiwalled carbon nanotubes (MWCNTs) have been identified as potential human carcinogens. It raises urgent occupational, public, and environment safety and health concerns, and therefore a critical need exists to understand specific carbon nanomaterial-induced carcinogenesis potential as well as screen and evaluate methods based on that knowledge. Lung cancer is the leading cause of cancer-related mortality, and has been largely associated with smoking and environmental carcinogen exposures. With a decrease in the smoking population in developed countries as a result of increased regulations and better control of atmospheric industrial particulates, the incidence of squamous lung carcinoma in the developed countries has seen a decline. However, the rate of adenocarcinoma in these countries has continued to increase, suggesting the rise of unknown environmental factors contributing to such occurrence. Outdoor air pollution, a byproduct of anthropogenic activity, is responsible for a significant fraction of ultrafine carbon particulates (PM 2.5), which are considered a human carcinogen and may contribute to lung adenocarcinoma. Furthermore, exposure to man-made nanomaterials such as ECMNs may contribute to this development. ECNMs possess novel and unique physicochemical properties that provide technological advantage over conventional materials, but they may also generate unknown health consequences (e.g., carcinogenesis) following their exposure. Assessing the carcinogenic effect of nanomaterials is a huge undertaking due to their rapid growth and great variety of nanomaterials. Guidelines for establishing a material's carcinogenic potential rely on human epidemiological data, confirmed cases in clinical reports, and animal studies. Studies can be qualitative and explorative in nature (i.e., yes or no) or quantitative (i.e., dose-response) to identify the lowest observed and non-observable effective concentrations (i.e., LOEC and NOEC, respectively). At present, there is no human case of ECNM-induced cancer, and ECNM carcinogenic studies in animal models have only been conducted on a case-by-case basis. These animal studies have used historical data with similar particles (i.e., fine TiO2 and asbestos fibers) to justify their assessment of nano-sized TiO2 and MWCNT. Very few engineered nano-materials (ENMs) have undergone qualitative assessment for their carcinogenic potential (i.e., nano-TiO2, MWCNT), and no published studies have assessed their quantitative risk through expected exposure routes. The U .S. National Institute for Occupational Safety and Health (NIOSH) is currently conducting dose-response studies with MWCNTs, a known lung cancer and mesothelioma tumor promotor, in a mouse model. With the exponential increase in novel ECNM development, there is an overwhelming and critical need to assess emerging ECNMs for their carcinogenic potential. With very few documented cases of chronic disease in humans linked to prolonged ECNM exposure, the best data sets at present are in sensitive animal models of tumor development and relevant in vitro screening models to investigate the unique physicochemical characteristics of ECNMs that can result in specific interactions and detrimental effects in exposed tissues. The main objective of this chapter is to provide an overview of ECNM genotoxicity, neoplastic transformation, and tumorigenic potential, and how future ECNM carcinogenesis risk assessment can use current and developing cancer cell biology techniques to quickly screen and assess emerging nanomaterials. Here, we highlight key findings that form the basis of our current understanding of ENM-induced carcinogenesis and raise important issues that need to be addressed in future research. Focus of this chapter is on the pulmonary targets and related pulmonary responses, since the majority of human exposures to ENMs are via inhalation. Secondary effects as a result of ENMs' translocation into other tissues are also discussed. Subsequently, we describe how advances in in vitro neoplastic transformation and in vivo carcinogenesis models may be employed to screen suspected ENMs for neoplastic transformation and carcinogenic potential. Such information could be used to promote safe-by-design and prevention-by-design strategies that eventually enhance protection for occupational and environmental exposures and for long-term protection of the nanotechnology industry. [Description provided by NIOSH]
  • Subjects:
  • Keywords:
  • ISBN:
    9783527338719
  • Publisher:
    Wiley-VCH Verlag GmbH & Co. KGaA
  • Document Type:
    Text
  • Genre:
    Book
  • Place as Subject:
  • CIO:
    National Institute for Occupational Safety and Health (NIOSH)
  • Division:
    HELD - Health Effects Laboratory Division
  • Topic:
    Workplace Safety & Health
  • Location:
    North America
  • Pages in Document:
    267-331
  • NIOSHTIC Number:
    nn:20048012
  • Citation:
    Biomedical applications and toxicology of carbon nanomaterials. Chen C, Wang H, eds. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2016 May; :267-331
  • Contact Point Address:
    Todd A. Stueckle, National Institute for Occupational Safety and Health, Health Effects Laboratory Division, Allergy and Clinical Immunology Branch, 1095 Willowdale Road, Morgantown, WV, 26505, USA
  • CAS Registry Number:
  • Editor(s):
    Chen C; Wang H
  • Federal Fiscal Year:
    2016
  • NORA Priority Area:
    Manufacturing
  • Peer Reviewed:
    False
  • Source Full Name:
    Biomedical applications and toxicology of carbon nanomaterials
  • Collection(s):
  • Main Document Checksum:
    urn:sha-512:74598c59d1ee7fc157226d4c853c68fff2b45202a86e488d34f1fcbb400214a70234679519ca0a4460508cd857632171920dcec26d71aafc9972e9956941cd04
  • Download URL:
  • File Type:
    Filetype[PDF - 955.21 KB ]
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