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

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.

[1]  K. Jan,et al.  Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells. , 2005, Toxicology.

[2]  B. Sanderson,et al.  Cyto- and genotoxicity of ultrafine TiO2 particles in cultured human lymphoblastoid cells. , 2007, Mutation research.

[3]  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.

[4]  J. Bemis,et al.  In vivo mutation assay based on the endogenous Pig‐a locus , 2008, Environmental and molecular mutagenesis.

[5]  Ming Jiang,et al.  Synergistic genotoxicity caused by low concentration of titanium dioxide nanoparticles and p,p′‐DDT in human hepatocytes , 2009, Environmental and molecular mutagenesis.

[6]  S. K. Sundaram,et al.  Adsorbed proteins influence the biological activity and molecular targeting of nanomaterials. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[7]  Robert A Hoke,et al.  Development of a base set of toxicity tests using ultrafine TiO2 particles as a component of nanoparticle risk management. , 2007, Toxicology letters.

[8]  David B Warheit,et al.  How meaningful are the results of nanotoxicity studies in the absence of adequate material characterization? , 2008, Toxicological sciences : an official journal of the Society of Toxicology.

[9]  Kemin Wang,et al.  Uptake of silica-coated nanoparticles by HeLa cells. , 2005, Journal of nanoscience and nanotechnology.

[10]  Csaba Varga,et al.  Lack of genotoxicity of carbon nanotubes in a pilot study. , 2008, Anticancer research.

[11]  Tae-Jong Yoon,et al.  Toxicity and tissue distribution of magnetic nanoparticles in mice. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[12]  Shareen H. Doak,et al.  Dextran Coated Ultrafine Superparamagnetic Iron Oxide Nanoparticles: Compatibility with Common Fluorometric and Colorimetric Dyes , 2011, Analytical chemistry.

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

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

[15]  M. Schladweiler,et al.  Soluble iron modulates iron oxide particle-induced inflammatory responses via prostaglandin E2 synthesis: In vitro and in vivo studies , 2009, Particle and Fibre Toxicology.

[16]  Z. Qian,et al.  Acute toxicity and genotoxicity studies on poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) nanomaterials. , 2010, Mutation research.

[17]  G. Joksiċ,et al.  Using carbon nanotubes to induce micronuclei and double strand breaks of the DNA in human cells , 2010, Nanotechnology.

[18]  Helinor Johnston,et al.  Development of in vitro systems for nanotoxicology: methodological considerations , 2009, Critical reviews in toxicology.

[19]  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.

[20]  Victor C Yang,et al.  Polyethyleneimine-modified iron oxide nanoparticles for brain tumor drug delivery using magnetic targeting and intra-carotid administration. , 2010, Biomaterials.

[21]  Mary Gulumian,et al.  The limits of testing particle-mediated oxidative stress in vitro in predicting diverse pathologies; relevance for testing of nanoparticles , 2009, Particle and Fibre Toxicology.

[22]  U. Wirnitzer,et al.  Studies on the in vitro genotoxicity of baytubes, agglomerates of engineered multi-walled carbon-nanotubes (MWCNT). , 2009, Toxicology letters.

[23]  Alexandra Kroll,et al.  Cytotoxicity screening of 23 engineered nanomaterials using a test matrix of ten cell lines and three different assays , 2011, Particle and Fibre Toxicology.

[24]  A. Gopalan,et al.  Pd (core)-Au (shell) nanoparticles catalyzed conversion of NADH to NAD+ by UV-vis spectroscopy--a kinetic analysis. , 2009, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[25]  Albrecht Poth,et al.  Genetic toxicity assessment: employing the best science for human safety evaluation part IV: Recommendation of a working group of the Gesellschaft fuer Umwelt-Mutationsforschung (GUM) for a simple and straightforward approach to genotoxicity testing. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[26]  Richard M Walmsley,et al.  Analysis of 75 marketed pharmaceuticals using the GADD45a-GFP 'GreenScreen HC' genotoxicity assay. , 2009, Mutagenesis.

[27]  H. Liber,et al.  Different capacities for recombination in closely related human lymphoblastoid cell lines with different mutational responses to X-irradiation , 1994, Molecular and cellular biology.

[28]  D. M. Roth,et al.  Occupational genotoxicity risk evaluation through the comet assay and the micronucleus test. , 2003, Genetics and molecular research : GMR.

[29]  Shinobu Ito,et al.  Preclinical studies on safety of fullerene upon acute oral administration and evaluation for no mutagenesis. , 2006, Toxicology.

[30]  Thomas J Webster,et al.  Bactericidal effect of iron oxide nanoparticles on Staphylococcus aureus , 2010, International journal of nanomedicine.

[31]  Qamar Rahman,et al.  Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts. , 2002, Environmental health perspectives.

[32]  David Kirkland,et al.  A core in vitro genotoxicity battery comprising the Ames test plus the in vitro micronucleus test is sufficient to detect rodent carcinogens and in vivo genotoxins. , 2011, Mutation research.

[33]  Vincent M Rotello,et al.  Toxicity of gold nanoparticles functionalized with cationic and anionic side chains. , 2004, Bioconjugate chemistry.

[34]  Richard M Walmsley,et al.  High-specificity and high-sensitivity genotoxicity assessment in a human cell line: validation of the GreenScreen HC GADD45a-GFP genotoxicity assay. , 2006, Mutation research.

[35]  X. Pan,et al.  Mutagenicity evaluation of metal oxide nanoparticles by the bacterial reverse mutation assay. , 2010, Chemosphere.

[36]  Kenji Kaneko,et al.  Modification of gold nanorods using phosphatidylcholine to reduce cytotoxicity. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[37]  M. Hande,et al.  Cytotoxicity and genotoxicity of silver nanoparticles in human cells. , 2009, ACS nano.

[38]  N. Chandrasekaran,et al.  Genotoxicity of silver nanoparticles in Allium cepa. , 2009, The Science of the total environment.

[39]  Jongheop Yi,et al.  Evaluation of the toxic impact of silver nanoparticles on Japanese medaka (Oryzias latipes). , 2009, Aquatic toxicology.

[40]  H. Autrup,et al.  PVP-coated silver nanoparticles and silver ions induce reactive oxygen species, apoptosis and necrosis in THP-1 monocytes. , 2009, Toxicology letters.

[41]  F. Veronese,et al.  PEGylated Protein Drugs: Basic Science and Clinical Applications , 2009 .

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

[43]  Min Chen,et al.  Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO2 nanoparticles. , 2005, Experimental cell research.

[44]  S. Whitehead,et al.  Heterogeneity in the bioactivity of LH secreted by peripubertal rats. , 2000, Journal of reproduction and fertility.

[45]  Moonjung Choi,et al.  Cellular uptake, cytotoxicity, and innate immune response of silica-titania hollow nanoparticles based on size and surface functionality. , 2010, ACS nano.

[46]  F. M. Gama,et al.  BC nanofibres: in vitro study of genotoxicity and cell proliferation. , 2009, Toxicology letters.

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

[48]  David Kirkland,et al.  Further analysis of Ames-negative rodent carcinogens that are only genotoxic in mammalian cells in vitro at concentrations exceeding 1 mM, including retesting of compounds of concern. , 2010, Mutagenesis.

[49]  B. Sanderson,et al.  Cytotoxicity and genotoxicity of ultrafine crystalline SiO2 particulate in cultured human lymphoblastoid cells , 2007, Environmental and molecular mutagenesis.

[50]  R. L. Jones,et al.  Unique cellular interaction of silver nanoparticles: size-dependent generation of reactive oxygen species. , 2008, The journal of physical chemistry. B.

[51]  P. Baron,et al.  Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. , 2005, American journal of physiology. Lung cellular and molecular physiology.

[52]  E. Cemeli,et al.  Genotoxicity and cytotoxicity of zinc oxide and titanium dioxide in HEp-2 cells. , 2010, Nanomedicine.

[53]  Tung-Sheng Shih,et al.  Disturbed mitotic progression and genome segregation are involved in cell transformation mediated by nano-TiO2 long-term exposure. , 2009, Toxicology and applied pharmacology.

[54]  Jim E Riviere,et al.  Surface coatings determine cytotoxicity and irritation potential of quantum dot nanoparticles in epidermal keratinocytes. , 2007, The Journal of investigative dermatology.

[55]  François Huaux,et al.  Clastogenic and aneugenic effects of multi-wall carbon nanotubes in epithelial cells. , 2008, Carcinogenesis.

[56]  Taesung Kim,et al.  Lung Function Changes in Sprague-Dawley Rats After Prolonged Inhalation Exposure to Silver Nanoparticles , 2008, Inhalation toxicology.

[57]  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.

[58]  Sabine Neuss,et al.  Gold nanoparticles of diameter 1.4 nm trigger necrosis by oxidative stress and mitochondrial damage. , 2009, Small.

[59]  S. G. Shankar,et al.  Effect of Nano-Silver on Cell Division and Mitotic Chromosomes : A Prefatory Siren , 2007 .

[60]  S. Hussain,et al.  Evaluation of genotoxic effects of oral exposure to aluminum oxide nanomaterials in rat bone marrow. , 2009, Mutation research.

[61]  Vincent Castranova,et al.  Single-walled Carbon Nanotubes: Geno- and Cytotoxic Effects in Lung Fibroblast V79 Cells , 2007, Journal of toxicology and environmental health. Part A.

[62]  Katie Smith,et al.  Reduction of misleading ("false") positive results in mammalian cell genotoxicity assays. I. Choice of cell type. , 2012, Mutation research.

[63]  Stefano Bellucci,et al.  Multi-walled carbon nanotubes: Lack of mutagenic activity in the bacterial reverse mutation assay. , 2009, Toxicology letters.

[64]  D. Bowman,et al.  Hitting the mark or falling short with nanotechnology regulation? , 2009, Trends in biotechnology.

[65]  David Kirkland,et al.  Clastogenicity, photo-clastogenicity or pseudo-photo-clastogenicity: Genotoxic effects of zinc oxide in the dark, in pre-irradiated or simultaneously irradiated Chinese hamster ovary cells. , 2006, Mutation research.

[66]  E Sabbioni,et al.  Comparative genotoxicity of cobalt nanoparticles and ions on human peripheral leukocytes in vitro. , 2008, Mutagenesis.

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

[68]  Andrea Magrini,et al.  Carbon nanotubes induce oxidative DNA damage in RAW 264.7 cells , 2010, Environmental and molecular mutagenesis.

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

[70]  S. Fukushima,et al.  Genotoxicity and Cytotoxicity of Multi‐wall Carbon Nanotubes in Cultured Chinese Hamster Lung Cells in Comparison with Chrysotile A Fibers , 2010, Journal of occupational health.

[71]  P. Taupin,et al.  PEG and PEG conjugates toxicity: towards an understanding of the toxicity of PEG and its relevance to PEGylated biologicals , 2009 .

[72]  N. Başaran,et al.  Monitoring of DNA damage in foundry and pottery workers exposed to silica by the alkaline comet assay. , 2003, American journal of industrial medicine.

[73]  C. Case,et al.  The in vitro genotoxicity of orthopaedic ceramic (Al2O3) and metal (CoCr alloy) particles. , 2010, Mutation research.

[74]  Benjamin Gilbert,et al.  Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties. , 2008, ACS nano.

[75]  M. Fenech.  Cytokinesis-block micronucleus assay evolves into a "cytome" assay of chromosomal instability, mitotic dysfunction and cell death. , 2006, Mutation research.

[76]  Timothy J Shaw,et al.  Cellular uptake and cytotoxicity of gold nanorods: molecular origin of cytotoxicity and surface effects. , 2009, Small.

[77]  Ritesh K Shukla,et al.  DNA damaging potential of zinc oxide nanoparticles in human epidermal cells. , 2009, Toxicology letters.

[78]  J. Bacri,et al.  Intracellular uptake of anionic superparamagnetic nanoparticles as a function of their surface coating. , 2003, Biomaterials.

[79]  Jennifer A. Higgins,et al.  DNA damage of macrophages at an air-tissue interface induced by metal nanoparticles , 2009 .

[80]  Maxime Robin,et al.  DNA-damaging activity and mutagenicity of 16 newly synthesized thiazolo[5,4-a]acridine derivatives with high photo-inducible cytotoxicity. , 2008, Mutation research.

[81]  Alok Dhawan,et al.  Cellular uptake and mutagenic potential of metal oxide nanoparticles in bacterial cells. , 2011, Chemosphere.

[82]  Hong Yin,et al.  Effects of surface chemistry on cytotoxicity, genotoxicity, and the generation of reactive oxygen species induced by ZnO nanoparticles. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[83]  B. Sanderson,et al.  Ultrafine Quartz-Induced Damage in Human Lymphoblastoid Cells in vitro Using Three Genetic Damage End-Points , 2007, Toxicology mechanisms and methods.