Genotoxicity of nanomaterials: Refining strategies and tests for hazard identification

A workshop addressing strategies for the genotoxicity assessment of nanomaterials (NMs) was held on October 23, 2010 in Fort Worth Texas, USA. The workshop was organized by the Environmental Mutagen Society and the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute. The workshop was attended by more than 80 participants from academia, regulatory agencies, and industry from North America, Europe and Japan. A plenary session featured summaries of the current status and issues related to the testing of NMs for genotoxic properties, as well as an update on international activities and regulatory approaches. This was followed by breakout sessions and a plenary session devoted to independent discussions of in vitro assays, in vivo assays, and the need for new assays or new approaches to develop a testing strategy for NMs. Each of the standard assays was critiqued as a resource for evaluation of NMs, and it became apparent that none was appropriate without special considerations or modifications. The need for nanospecific positive controls was questioned, as was the utility of bacterial assays. The latter was thought to increase the importance of including mammalian cell gene mutation assays into the test battery. For in‐vivo testing, to inform the selection of appropriate tests or protocols, it was suggested to run repeated dose studies first to learn about disposition, potential accumulation, and possible tissue damage. It was acknowledged that mechanisms may be at play that a standard genotoxicity battery may not be able to capture. Environ. Mol. Mutagen. 54:229–239, 2013. © 2013 Wiley Periodicals, Inc.

[1]  Alexandra Kroll,et al.  Testing Metal‐Oxide Nanomaterials for Human Safety , 2010, Advanced materials.

[2]  M L Kashon,et al.  Induction of aneuploidy by single‐walled carbon nanotubes , 2009, Environmental and molecular mutagenesis.

[3]  H. Norppa,et al.  Genotoxicity testing of nanomaterials – Conclusions , 2010, Nanotoxicology.

[4]  M. Kirsch‐Volders,et al.  Adaptations of the in vitro MN assay for the genotoxicity assessment of nanomaterials. , 2011, Mutagenesis.

[5]  S. Doak,et al.  NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. , 2009, Biomaterials.

[6]  Stefan Pfuhler,et al.  Silica nanoparticles administered at the maximum tolerated dose induce genotoxic effects through an inflammatory reaction while gold nanoparticles do not. , 2012, Mutation research.

[7]  A Elhajouji,et al.  Indications for a threshold of chemically‐induced aneuploidy in vitro in human lymphocytes , 1995, Environmental and molecular mutagenesis.

[8]  R. Grimalt,et al.  OPINION ON SAFETY OF NANOMATERIALS IN COSMETIC PRODUCTS , 2008 .

[9]  Shigehisa Endoh,et al.  In vitro and in vivo genotoxicity tests on fullerene C60 nanoparticles. , 2009, Toxicology letters.

[10]  S. Maenosono,et al.  Mutagenicity of water-soluble ZnO nanoparticles in Ames test. , 2007, The Journal of toxicological sciences.

[11]  M. Kirsch‐Volders,et al.  Induction of chromosome malsegregation by nanomaterials. , 2010, Biochemical Society transactions.

[12]  Stephen Mann,et al.  Nanoparticles can cause DNA damage across a cellular barrier. , 2009, Nature nanotechnology.

[13]  Markus Schulz,et al.  Genotoxicity investigations on nanomaterials: methods, preparation and characterization of test material, potential artifacts and limitations--many questions, some answers. , 2009, Mutation research.

[14]  G. Jenkins,et al.  Mechanistic influences for mutation induction curves after exposure to DNA-reactive carcinogens. , 2007, Cancer research.

[15]  G. Jenkins,et al.  In vitro genotoxicity testing strategy for nanomaterials and the adaptation of current OECD guidelines , 2012, Mutation research.

[16]  S. Hussain,et al.  In vitro mutagenicity assessment of aluminium oxide nanomaterials using the Salmonella/microsome assay. , 2010, Toxicology in vitro : an international journal published in association with BIBRA.

[17]  F. Oesch,et al.  Gene toxicity studies on titanium dioxide and zinc oxide nanomaterials used for UV-protection in cosmetic formulations , 2010, Nanotoxicology.

[18]  A. Collins.  Investigating oxidative DNA damage and its repair using the comet assay. , 2009, Mutation research.

[19]  Paramjit Grover,et al.  In vivo genotoxicity assessment of aluminium oxide nanomaterials in rat peripheral blood cells using the comet assay and micronucleus test. , 2009, Mutagenesis.

[20]  S. Maenosono,et al.  Mutagenicity of water-soluble FePt nanoparticles in Ames test. , 2007, The Journal of toxicological sciences.

[21]  J. Carter,et al.  Effects of particle exposure and particle-elicited inflammatory cells on mutation in rat alveolar epithelial cells. , 1997, Carcinogenesis.

[22]  P. M. Williams,et al.  Confounding experimental considerations in nanogenotoxicology. , 2009, Mutagenesis.

[23]  J. Schnekenburger,et al.  Not ready to use – overcoming pitfalls when dispersing nanoparticles in physiological media , 2008 .

[24]  M. Reigosa,et al.  Comparative study of the cytotoxic and genotoxic effects of titanium oxide and aluminium oxide nanoparticles in Chinese hamster ovary (CHO-K1) cells. , 2010, Journal of hazardous materials.

[25]  Minnamari Vippola,et al.  Genotoxicity of nanomaterials: DNA damage and micronuclei induced by carbon nanotubes and graphite nanofibres in human bronchial epithelial cells in vitro. , 2009, Toxicology letters.

[26]  Laetitia Gonzalez,et al.  Genotoxicity of engineered nanomaterials: A critical review , 2008 .