For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
37
views
81
references
 Top references
cited by
38
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      1
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      In vitro genotoxicity testing strategy for nanomaterials and the adaptation of current OECD guidelines

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Highlights

          ► We consider current in vitro OECD genotoxicity tests for nanomaterials. ► Ames test does not appear to be suitable for nanomaterial assessment. ► In vitro HPRT and micronucleus assays require nanomaterial specific protocols. ► We recommend a strategic in vitro genotoxicity testing strategy for nanomaterials.

          Abstract

          There is a pressing requirement to define a hazard identification and risk management strategy for nanomaterials due to the rapid growth in the nanotechnology industry and their promise of life-style revolutions through the development of wide-ranging nano-containing consumer products. Consequently, a battery of well defined and appropriate in vitro assays to assess a number of genotoxicity endpoints is required to minimise extensive and costly in vivo testing. However, the validity of the established protocols in current OECD recognised genotoxicity assays for nanomaterials is currently being questioned. In this report, we therefore consider the in vitro OECD genotoxicity test battery including the Ames, micronucleus and HPRT forward mutation assays, and their potential role in the safety assessment of nanomaterial induced DNA damage in vitro.

          Related collections

          Most cited references81

          • Record: found
          • Abstract: found
          • Article: not found

          Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties.

          Tian Xia, Michael Kovochich, Monty Liong … (2008)
          Nanomaterials (NM) exhibit novel physicochemical properties that determine their interaction with biological substrates and processes. Three metal oxide nanoparticles that are currently being produced in high tonnage, TiO(2), ZnO, and CeO(2), were synthesized by flame spray pyrolysis process and compared in a mechanistic study to elucidate the physicochemical characteristics that determine cellular uptake, subcellular localization, and toxic effects based on a test paradigm that was originally developed for oxidative stress and cytotoxicity in RAW 264.7 and BEAS-2B cell lines. ZnO induced toxicity in both cells, leading to the generation of reactive oxygen species (ROS), oxidant injury, excitation of inflammation, and cell death. Using ICP-MS and fluorescent-labeled ZnO, it is found that ZnO dissolution could happen in culture medium and endosomes. Nondissolved ZnO nanoparticles enter caveolae in BEAS-2B but enter lysosomes in RAW 264.7 cells in which smaller particle remnants dissolve. In contrast, fluorescent-labeled CeO(2) nanoparticles were taken up intact into caveolin-1 and LAMP-1 positive endosomal compartments, respectively, in BEAS-2B and RAW 264.7 cells, without inflammation or cytotoxicity. Instead, CeO(2) suppressed ROS production and induced cellular resistance to an exogenous source of oxidative stress. Fluorescent-labeled TiO(2) was processed by the same uptake pathways as CeO(2) but did not elicit any adverse or protective effects. These results demonstrate that metal oxide nanoparticles induce a range of biological responses that vary from cytotoxic to cytoprotective and can only be properly understood by using a tiered test strategy such as we developed for oxidative stress and adapted to study other aspects of nanoparticle toxicity.
          Article 0 comments Cited 526 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Unique cellular interaction of silver nanoparticles: size-dependent generation of reactive oxygen species.

            C. Carlson, S. Hussain, A M Schrand … (2008)
            The rapid advancement of nanotechnology has created a vast array of engineered nanomaterials (ENMs) which have unique physical (size, shape, crystallinity, surface charge) and chemical (surface coating, elemental composition and solubility) attributes. These physicochemical properties of ENMs can produce chemical conditions to induce a pro-oxidant environment in the cells, causing an imbalanced cellular energy system dependent on redox potential and thereby leading to adverse biological consequences, ranging from the initiation of inflammatory pathways through to cell death. The present study was designed to evaluate size-dependent cellular interactions of known biologically active silver nanoparticles (NPs, Ag-15 nm, Ag-30 nm, and Ag-55 nm). Alveolar macrophages provide the first defense and were studied for their potential role in initiating oxidative stress. Cell exposure produced morphologically abnormal sizes and adherence characteristics with significant NP uptake at high doses after 24 h. Toxicity evaluations using mitochondrial and cell membrane viability along with reactive oxygen species (ROS) were performed. After 24 h of exposure, viability metrics significantly decreased with increasing dose (10-75 microg/mL) of Ag-15 nm and Ag-30 nm NPs. A more than 10-fold increase of ROS levels in cells exposed to 50 microg/mL Ag-15 nm suggests that the cytotoxicity of Ag-15 nm is likely to be mediated through oxidative stress. In addition, activation of the release of traditional inflammatory mediators were examined by measuring levels of cytokines/chemokines, including tumor necrosis factor (TNF-alpha), macrophage inhibitory protein (MIP-2), and interleukin-6 (IL-6), released into the culture media. After 24 h of exposure to Ag-15 nm nanoparticles, a significant inflammatory response was observed by the release of TNF-alpha, MIP-2, and IL-1beta. However, there was no detectable level of IL-6 upon exposure to silver nanoparticles. In summary, a size-dependent toxicity was produced by silver nanoparticles, and one predominant mechanism of toxicity was found to be largely mediated through oxidative stress.
            Article 0 comments Cited 412 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Cellular uptake and cytotoxicity of gold nanorods: molecular origin of cytotoxicity and surface effects.

              Alaaldin Alkilany, Pratik K Nagaria, Cole R Hexel … (2009)
              Gold nanorods of different aspect ratios are prepared using the growth-directing surfactant, cetyltrimethylammonium bromide (CTAB), which forms a bilayer on the gold nanorod surface. Toxicological assays of CTAB-capped nanorod solutions with human colon carcinoma cells (HT-29) reveal that the apparent cytotoxicity is caused by free CTAB in solution. Overcoating the nanorods with polymers substantially reduces cytotoxicity. The number of nanorods taken up per cell, for the different surface coatings, is quantitated by inductively coupled plasma mass spectrometry on washed cells; the number of nanorods per cell varies from 50 to 2300, depending on the surface chemistry. Serum proteins from the biological media, most likely bovine serum albumin, adsorb to gold nanorods, leading to all nanorod samples bearing the same effective charge, regardless of the initial nanorod surface charge. The results suggest that physiochemical surface properties of nanomaterials change substantially after coming into contact with biological media. Such changes should be taken into consideration when examining the biological properties or environmental impact of nanoparticles.
              Article 0 comments Cited 212 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                S.H. Doak
                Journal
                Journal ID (nlm-ta): Mutat Res Genet Toxicol Environ Mutagen
                Journal ID (iso-abbrev): Mutat Res Genet Toxicol Environ Mutagen
                Title: Mutation Research. Genetic Toxicology and Environmental Mutagenesis
                Publisher: Elsevier
                ISSN (Print): 1383-5718
                ISSN (Electronic): 1879-3592
                Publication date PMC-release: 14 June 2012
                Publication date (Print): 14 June 2012
                Volume: 745
                Issue: 1-2
                Pages: 104-111
                Affiliations
                Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, Wales, UK
                Author notes
                [* ]Corresponding author. Tel.: +44 1792 295388. s.h.doak@ 123456swansea.ac.uk
                Article
                Publisher ID: S1383-5718(11)00278-6
                DOI: 10.1016/j.mrgentox.2011.09.013
                PMC ID: 4028084
                PubMed ID: 21971291
                SO-VID: 8a133f65-bbb5-4103-9acc-608413528e76
                Copyright © © 2012 Elsevier B.V.
                License:

                This document may be redistributed and reused, subject to certain conditions.

                History
                Date received : 9 September 2011
                Date accepted : 12 September 2011
                Categories
                Subject: Article

                Keywords: nanoparticles,nanotubes,nanomaterials,genotoxicity,micronucleus assay,ames test
                Data availability:
                Keywords: nanoparticles, nanotubes, nanomaterials, genotoxicity, micronucleus assay, ames test

                Comments

                Comment on this article

                scite_

                Similar content1

                See all similar

                Cited by30

                See all cited by