Evaluating the Toxicity of Airborne Particulate Matter and Nanoparticles by Measuring Oxidative Stress Potential—A Workshop Report and Consensus Statement

Background: There is a strong need for laboratory in vitro test systems for the toxicity of airborne particulate matter and nanoparticles. The measurement of oxidative stress potential offers a promising way forward. Objectives:Aworkshop was convened involving leading workers from the field in order to review the available test methods and to generate a Consensus Statement. Discussions: Workshop participants summarised their own research activities as well as discussion the relative merits of different test methods. Conclusions: In vitro test methods have an important role to play in the screening of toxicity in airborne particulate matter and nanoparticles. In vitro cell challenges were preferable to in vitro acellular systems but both have a potential major role to play and offer large cost advantages relative to human or animal inhalation studies and animal in vivo installation experiments. There remains a need to compare tests one with another on standardised samples and also to establish a correlation with the results of population-based epidemiology.

[1]  A. Wexler,et al.  Field evaluation of the versatile aerosol concentration enrichment system (VACES) particle concentrator coupled to the rapid single-particle mass spectrometer (RSMS-3) , 2005 .

[2]  R M Harrison,et al.  Particulate matter in the atmosphere: which particle properties are important for its effects on health? , 2000, The Science of the total environment.

[3]  Thomas Kuhlbusch,et al.  Hydroxyl radical generation by electron paramagnetic resonance as a new method to monitor ambient particulate matter composition. , 2003, Journal of environmental monitoring : JEM.

[4]  Julie W. Fitzpatrick,et al.  Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy , 2005, Particle and Fibre Toxicology.

[5]  G. P. Wyers,et al.  THE STEAM-JET AEROSOL COLLECTOR , 1995 .

[6]  J. Jimenez,et al.  In situ concentration of semi-volatile aerosol using water-condensation technology , 2005 .

[7]  O. Houcine,et al.  Diesel exhaust particles are taken up by human airway epithelial cells in vitro and alter cytokine production. , 1999, American journal of physiology. Lung cellular and molecular physiology.

[8]  J. Froines,et al.  The interactions of 9,10-phenanthrenequinone with glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a potential site for toxic actions. , 2005, Chemico-biological interactions.

[9]  André Nel,et al.  ATMOSPHERE: Enhanced: Air Pollution-Related Illness: Effects of Particles , 2005 .

[10]  Thomas Götschi,et al.  Comparison of Oxidative Properties, Light Absorbance, and Total and Elemental Mass Concentration of Ambient PM2.5 Collected at 20 European Sites , 2005, Environmental health perspectives.

[11]  J. Mehta,et al.  Role of oxidative stress in coronary heart disease. , 2004, Indian heart journal.

[12]  F. Kelly,et al.  Oxidative stress: its role in air pollution and adverse health effects , 2003, Occupational and environmental medicine.

[13]  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.

[14]  Andrew Saxon,et al.  Effect of glutathione-S-transferase M1 and P1 genotypes on xenobiotic enhancement of allergic responses: randomised, placebo-controlled crossover study , 2004, The Lancet.

[15]  Flemming R Cassee,et al.  Response of spontaneously hypertensive rats to inhalation of fine and ultrafine particles from traffic: experimental controlled study , 2006, Particle and Fibre Toxicology.

[16]  W. MacNee,et al.  Oxidative stress and lung inflammation in airways disease. , 2001, European journal of pharmacology.

[17]  Flemming Cassee,et al.  Atmospheric Secondary Inorganic Particulate Matter: The Toxicological Perspective as a Basis for Health Effects Risk Assessment , 2003, Inhalation toxicology.

[18]  W. Pryor,et al.  Quinoid redox cycling as a mechanism for sustained free radical generation by inhaled airborne particulate matter. , 2001, Free radical biology & medicine.

[19]  J. Seagrave,et al.  The Role of a Mitochondrial Pathway in the Induction of Apoptosis by Chemicals Extracted from Diesel Exhaust Particles1 , 2000, The Journal of Immunology.

[20]  G. Cerniglia,et al.  Microtiter plate assay for the measurement of glutathione and glutathione disulfide in large numbers of biological samples. , 1990, Analytical biochemistry.

[21]  B. Brunekreef,et al.  Double-blind intervention trial on modulation of ozone effects on pulmonary function by antioxidant supplements. , 1999, American journal of epidemiology.

[22]  A. Aust,et al.  Iron-catalyzed reactions may be responsible for the biochemical and biological effects of asbestos. , 1991, BioFactors.

[23]  B. Ersek,et al.  Impact of body iron status on myocardial perfusion, left ventricular function, and angiographic morphologic features in patients with hypercholesterolemia. , 2002, American heart journal.

[24]  B. Fubini.  Surface chemistry and quartz hazard. , 1998, The Annals of occupational hygiene.

[25]  B. Britigan,et al.  Iron sequestration by macrophages decreases the potential for extracellular hydroxyl radical formation. , 1993, The Journal of clinical investigation.

[26]  R. Crystal,et al.  Normal alveolar epithelial lining fluid contains high levels of glutathione. , 1987, Journal of applied physiology.

[27]  Brian J. Johnson,et al.  A high performance liquid chromatography method for determination of gas-phase hydrogen peroxide in ambient air using Fenton's chemistry. , 2003, Chemosphere.

[28]  Thomas Sandström,et al.  Recent outcomes in European multicentre projects on ambient particulate air pollution. , 2005, Toxicology and applied pharmacology.

[29]  Constantinos Sioutas,et al.  Redox activity of airborne particulate matter at different sites in the Los Angeles Basin. , 2005, Environmental research.

[30]  T. Sandström,et al.  Altered lung antioxidant status in patients with mild asthma , 1999, The Lancet.

[31]  A. Nel,et al.  Chemicals in diesel exhaust particles generate reactive oxygen radicals and induce apoptosis in macrophages. , 1999, Journal of immunology.

[32]  Y. Kikkawa,et al.  Ascorbic acid in bronchoalveolar wash , 2007, Lung.

[33]  C. Ward,et al.  Virulence and the Role of Iron in Pseudomonas aeruginosa Infection , 1974, Infection and immunity.

[34]  C. Venkataraman,et al.  Particle and Fibre Toxicology Combustion of Dried Animal Dung as Biofuel Results in the Generation of Highly Redox Active Fine Particulates , 2022 .

[35]  C. Gujuluva,et al.  Induction of Heme Oxygenase-1 Expression in Macrophages by Diesel Exhaust Particle Chemicals and Quinones via the Antioxidant-Responsive Element1 , 2000, The Journal of Immunology.

[36]  B. Ferger,et al.  Comparison of two independent aromatic hydroxylation assays in combination with intracerebral microdialysis to determine hydroxyl free radicals , 2001, Journal of Neuroscience Methods.

[37]  A. Nel,et al.  Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage. , 2002, Environmental health perspectives.

[38]  C. Pepine,et al.  Inflammation in atherosclerosis: some thoughts about acute coronary syndromes. , 2006, Circulation.

[39]  D K Stevenson,et al.  Heme oxygenase activity as measured by carbon monoxide production. , 1988, Analytical biochemistry.

[40]  J. Pennings,et al.  Ozone induces clear cellular and molecular responses in the mouse lung independently of the transcription-coupled repair status. , 2007, Journal of applied physiology.

[41]  Walter John,et al.  Characteristics of the Berner Impactor for Sampling Inorganic Ions , 1988 .

[42]  E. Ford,et al.  Diabetes and serum ferritin concentration among U.S. adults. , 1999, Diabetes care.

[43]  Ning Li,et al.  Nrf2 Is a Key Transcription Factor That Regulates Antioxidant Defense in Macrophages and Epithelial Cells: Protecting against the Proinflammatory and Oxidizing Effects of Diesel Exhaust Chemicals1 , 2004, The Journal of Immunology.

[44]  J. Pennings,et al.  Gene Expression Pattern in Spontaneously Hypertensive Rats Exposed to Urban Particulate Matter (EHC-93) , 2005, Inhalation toxicology.

[45]  J. Froines,et al.  Versatile aerosol concentration enrichment system (VACES) for simultaneous in vivo and in vitro evaluation of toxic effects of ultrafine, fine and coarse ambient particles Part I: Development and laboratory characterization , 2001 .

[46]  Andre E Nel,et al.  Particulate air pollutants and asthma. A paradigm for the role of oxidative stress in PM-induced adverse health effects. , 2003, Clinical immunology.

[47]  C. Sioutas,et al.  Development and Evaluation of a Compact Facility for Exposing Humans to Concentrated Ambient Ultrafine Particles , 2004 .

[48]  W. MacNee,et al.  Combustion-derived nanoparticles: A review of their toxicology following inhalation exposure , 2005, Particle and Fibre Toxicology.

[49]  V. Castranova,et al.  Critical Issues in the Evaluation of Possible Adverse Pulmonary Effects Resulting from Airborne Nanoparticles , 2007 .

[50]  G. Walsh.  Targeting airway inflammation: novel therapies for the treatment of asthma. , 2006, Current medicinal chemistry.

[51]  Garry M Walsh.  Levocetirizine: an update. , 2006, Current medicinal chemistry.

[52]  Freya Q. Schafer,et al.  Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. , 2001, Free radical biology & medicine.

[53]  D. Dockery,et al.  Epidemiology of Particle Effects , 1999 .

[54]  W. MacNee,et al.  Adverse health effects of PM10 particles: involvement of iron in generation of hydroxyl radical. , 1996, Occupational and environmental medicine.

[55]  Ning Li,et al.  Comparison of the Pro-Oxidative and Proinflammatory Effects of Organic Diesel Exhaust Particle Chemicals in Bronchial Epithelial Cells and Macrophages1 , 2002, The Journal of Immunology.

[56]  R. Barouki,et al.  Organic compounds from diesel exhaust particles elicit a proinflammatory response in human airway epithelial cells and induce cytochrome p450 1A1 expression. , 2001, American journal of respiratory cell and molecular biology.

[57]  Roel P F Schins,et al.  Inhaled particles and lung cancer. Part A: Mechanisms , 2004, International journal of cancer.

[58]  I. Romieu,et al.  Antioxidant supplementation and lung functions among children with asthma exposed to high levels of air pollutants. , 2002, American journal of respiratory and critical care medicine.

[59]  E. Stephanou,et al.  Collection of gas and particle semi-volatile organic compounds: use of an oxidant denuder to minimize polycyclic aromatic hydrocarbons degradation during high-volume air sampling , 2003 .

[60]  V. Castranova,et al.  Systemic Microvascular Dysfunction and Inflammation after Pulmonary Particulate Matter Exposure , 2005, Environmental health perspectives.

[61]  Black Rd,et al.  Glutathione concentrations in rat lung bronchoalveolar lavage fluid: effects of hyperoxia. , 1988 .

[62]  C. Sioutas,et al.  A Methodology for Measuring Size-Dependent Chemical Composition of Ultrafine Particles , 2002 .

[63]  Lundin Lg,et al.  Iron-catalyzed reactions may be responsible for the biochemical and biological effects of asbestos. , 1991 .

[64]  M. Kodama,et al.  Biological effects of diesel exhaust particles. I. In vitro production of superoxide and in vivo toxicity in mouse. , 1993, Free radical biology & medicine.

[65]  R. Barouki,et al.  Involvement of reactive oxygen species in the metabolic pathways triggered by diesel exhaust particles in human airway epithelial cells. , 2003, American journal of physiology. Lung cellular and molecular physiology.

[66]  Kevin R. Smith,et al.  Particle characteristics responsible for effects on human lung epithelial cells. , 2002, Research report.

[67]  Antonella Zanobetti,et al.  The concentration-response relation between PM(2.5) and daily deaths. , 2002, Environmental health perspectives.

[68]  F. Cassee,et al.  Field evaluation of a mobile high-capacity particle size classifier (HCPSC) for separate collection of coarse, fine and ultrafine particles , 2001 .

[69]  A. Nel,et al.  Use of a fluorescent phosphoprotein dye to characterize oxidative stress‐induced signaling pathway components in macrophage and epithelial cultures exposed to diesel exhaust particle chemicals , 2005, Electrophoresis.

[70]  Joachim Heinrich,et al.  Metal-rich ambient particles (particulate matter 2.5) cause airway inflammation in healthy subjects. , 2004, American journal of respiratory and critical care medicine.

[71]  J. Mauderly,et al.  Responses to Subchronic Inhalation of Low Concentrations of Diesel Exhaust and Hardwood Smoke Measured in Rat Bronchoalveolar Lavage Fluid , 2005, Inhalation toxicology.

[72]  S. Boland,et al.  Mechanisms of GM-CSF increase by diesel exhaust particles in human airway epithelial cells. , 2000, American journal of physiology. Lung cellular and molecular physiology.

[73]  P. Baron,et al.  Exposure to Carbon Nanotube Material: Assessment of Nanotube Cytotoxicity using Human Keratinocyte Cells , 2003, Journal of toxicology and environmental health. Part A.

[74]  S. Kennedy,et al.  Persistence of external chloride and DIDS binding after chemical modification of Glu-681 in human band 3. , 1999, American Journal of Physiology.

[75]  W. MacNee,et al.  Free radical activity of PM10: iron-mediated generation of hydroxyl radicals. , 1997, Environmental health perspectives.

[76]  T. Reponen,et al.  Design and Collection Efficiency of a New Electrostatic Precipitator for Bioaerosol Collection , 2002 .

[77]  C. Cross,et al.  Determination of low-molecular-mass antioxidant concentrations in human respiratory tract lining fluids. , 1999, American journal of physiology. Lung cellular and molecular physiology.

[78]  A. Baulig,et al.  Biological effects of atmospheric particles on human bronchial epithelial cells. Comparison with diesel exhaust particles. , 2003, Toxicology in vitro : an international journal published in association with BIBRA.

[79]  I. Beverland,et al.  Soluble transition metals in welding fumes cause inflammation via activation of NF-kappaB and AP-1. , 2005, Toxicology letters.

[80]  M. Kaliner,et al.  Uric acid is a major antioxidant in human nasal airway secretions. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[81]  Hui Li,et al.  Hydroxyl-radical-dependent DNA damage by ambient particulate matter from contrasting sampling locations. , 2006, Environmental research.

[82]  C. Sioutas,et al.  Reduction of nitrate losses from filter and impactor samplers by means of concentration enrichment , 2000 .

[83]  R. Djukanović,et al.  Inflammatory cells in the airways in COPD , 2006, Thorax.

[84]  J. Carter,et al.  ANTIOXIDANT DEFENSE MECHANISMS AND THE TOXICITY OF FIBROUS AND NONFIBROUS PARTICLES , 2002, Inhalation toxicology.

[85]  Ning Li,et al.  Role of the Nrf2-mediated signaling pathway as a negative regulator of inflammation: implications for the impact of particulate pollutants on asthma. , 2006, Antioxidants & redox signaling.

[86]  Vicki Stone,et al.  Oxidative stress and calcium signaling in the adverse effects of environmental particles (PM10). , 2003, Free radical biology & medicine.

[87]  V. Castranova,et al.  Particles and Cellular Oxidative and Nitrosative Stress , 2006 .

[88]  Steffen Loft,et al.  Oxidative stress-induced DNA damage by particulate air pollution. , 2005, Mutation research.

[89]  Reinhard Niessner,et al.  Polycyclic aromatic hydrocarbons in urban air particulate matter: decadal and seasonal trends, chemical degradation, and sampling artifacts. , 2003, Environmental science & technology.

[90]  Thomas Sandström,et al.  An in vitro and in vivo investigation of the effects of diesel exhaust on human airway lining fluid antioxidants. , 2004, Archives of biochemistry and biophysics.

[91]  T. Xia,et al.  Toxic Potential of Materials at the Nanolevel , 2006, Science.

[92]  V. Castranova,et al.  Direct and indirect effects of single walled carbon nanotubes on RAW 264.7 macrophages: role of iron. , 2006, Toxicology letters.

[93]  F. Kelly,et al.  Modeling the interactions of particulates with epithelial lining fluid antioxidants. , 1999, American journal of physiology. Lung cellular and molecular physiology.

[94]  A. Zanobetti,et al.  Air Conditioning and Source-Specific Particles as Modifiers of the Effect of PM10 on Hospital Admissions for Heart and Lung Disease , 2001 .

[95]  A. Baulig,et al.  Fine particulate matter induces amphiregulin secretion by bronchial epithelial cells. , 2004, American journal of respiratory cell and molecular biology.

[96]  Mark R Wiesner,et al.  Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. , 2006, Nano letters.

[97]  Antonella Zanobetti,et al.  Air conditioning and source-specific particles as modifiers of the effect of PM(10) on hospital admissions for heart and lung disease. , 2001, Environmental health perspectives.

[98]  L. Arab,et al.  Effect of antioxidant supplementation on ozone-induced lung injury in human subjects. , 2001, American journal of respiratory and critical care medicine.

[99]  K. Donaldson,et al.  Free radical activity associated with the surface of particles: a unifying factor in determining biological activity? , 1996, Toxicology letters.

[100]  Ning Li,et al.  USE OF A STRATIFIED OXIDATIVE STRESS MODEL TO STUDY THE BIOLOGICAL EFFECTS OF AMBIENT CONCENTRATED AND DIESEL EXHAUST PARTICULATE MATTER , 2002, Inhalation toxicology.

[101]  Vincent Castranova,et al.  Improved method to disperse nanoparticles for in vitro and in vivo investigation of toxicity , 2007 .

[102]  B. Brunekreef,et al.  Antioxidant supplementation and respiratory functions among workers exposed to high levels of ozone. , 1998, American journal of respiratory and critical care medicine.

[103]  A. Peters,et al.  Respiratory effects are associated with the number of ultrafine particles. , 1997, American journal of respiratory and critical care medicine.

[104]  G. Buettner,et al.  Catalytic metals, ascorbate and free radicals: combinations to avoid. , 1996, Radiation research.

[105]  Delbert J. Eatough,et al.  Semi-volatile secondary organic aerosol in urban atmospheres: meeting a measurement challenge , 2003 .

[106]  R. Lefèvre,et al.  Physicochemical characteristics and biological activities of seasonal atmospheric particulate matter sampling in two locations of Paris. , 2004, Environmental science & technology.

[107]  A. Favier,et al.  Determination of salicylate hydroxylation products as an in vivo oxidative stress marker. , 2000, Free radical biology & medicine.

[108]  Y. Ozaki,et al.  Simultaneous determination of uric and ascorbic acids in human serum by reversed-phase high-performance liquid chromatography with electrochemical detection. , 1984, Analytical biochemistry.

[109]  T. Noll,et al.  Role of Redox Signaling in the Autonomous Proliferative Response of Endothelial Cells to Hypoxia , 2003, Circulation research.

[110]  D. Díaz-Sánchez,et al.  Biology of diesel exhaust effects on respiratory function. , 2005, The Journal of allergy and clinical immunology.

[111]  Jian Cai,et al.  Acrylonitrile irreversibly inactivates glyceraldehyde-3-phosphate dehydrogenase by alkylating the catalytically active cysteine 149. , 2002, Chemico-biological interactions.

[112]  J. Weiss,et al.  Quinones and Aromatic Chemical Compounds in Particulate Matter Induce Mitochondrial Dysfunction: Implications for Ultrafine Particle Toxicity , 2004, Environmental health perspectives.

[113]  Keiko Taguchi,et al.  Oxidation of proximal protein sulfhydryls by phenanthraquinone, a component of diesel exhaust particles. , 2002, Chemical research in toxicology.

[114]  R. Willis,et al.  Ascorbic acid in rat lung. , 1974, Biochemical and biophysical research communications.

[115]  M. Green.  Air pollution and health , 1995 .

[116]  A. Ghio,et al.  Disruption of Iron Homeostasis as a Mechanism of Biologic Effect by Ambient Air Pollution Particles , 2005, Inhalation toxicology.

[117]  J Schwartz,et al.  Confounding and Effect Modification in the Short-Term Effects of Ambient Particles on Total Mortality: Results from 29 European Cities within the APHEA2 Project , 2001, Epidemiology.

[118]  Meiying Wang,et al.  Use of Proteomics to Demonstrate a Hierarchical Oxidative Stress Response to Diesel Exhaust Particle Chemicals in a Macrophage Cell Line* , 2003, Journal of Biological Chemistry.

[119]  Roy M. Harrison,et al.  A pragmatic mass closure model for airborne particulate matter at urban background and roadside sites , 2003 .

[120]  S. Friedlander,et al.  Versatile aerosol concentration enrichment system (VACES) for simultaneous in vivo and in vitro evaluation of toxic effects of ultrafine, fine and coarse ambient particles Part II: Field evaluation , 2001 .

[121]  V. Castranova,et al.  Oxidative stress and inflammatory response in dermal toxicity of single-walled carbon nanotubes. , 2009, Toxicology.