In vivo and In vitro Assessment of Particulate Matter Toxicology

  • Umme S. AkhtarEmail author
  • Jeremy A. Scott
  • Amanda Chu
  • Greg J. Evans
Part of the Environmental Science and Engineering book series (ESE)


Exposure to ambient particulate matter (PM) can have profound adverse effects on human health. Epidemiology studies have revealed associations between ambient PM and health effects ranging from increased hospital admissions to increased mortality rate. Factors such as particle size, surface area, and composition appear to influence how the body reacts to the inhaled PM. In vivo studies using humans and animals have provided insight into the toxicity of different types of PM, in terms of lung and vascular functions as well as inflammatory and oxidative stress markers. In vitro studies using human cells are allowing elucidation of pathophysiological mechanisms underlying observed in vivo effects. The most common pathway proposed for respiratory effects is the production of reactive oxygen species (ROS) causing oxidative stress in mammalian cells. Cardiovascular effects may also be caused by release of pro-inflammatory and pro-oxidant mediators from the lungs, but autonomic imbalance and translocation of PM to systemic circulation are also postulated as potential mechanisms.


Heart Rate Variability Adverse Health Effect Airway Epithelial Cell Aerodynamic Diameter Susceptible Population 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Adamkiewicz G, Ebelt S, Syring M et al (2004) Association between air pollution exposure and exhaled nitric oxide in an elderly population. Thorax 59:204–209CrossRefGoogle Scholar
  2. Araujo JA, Barajas B, Kleinman M et al (2008) Ambient particulate pollutants in the ultrafine range promote early atherosclerosis and systemic oxidative stress. Circ Res 102:589–596CrossRefGoogle Scholar
  3. Aufderheide M (2005) Direct exposure methods for testing native atmospheres. Exp Toxicol Pathol 57:213–226CrossRefGoogle Scholar
  4. Bai Y, Suzuki AK, Sagai M (2001) The cytotoxic effects of diesel exhaust particles on human pulmonary artery endothelial cells in vitro: Role of active oxygen species. Free Radic Biol Med 30:555–562CrossRefGoogle Scholar
  5. Bakand S, Winder C, Khalil C et al (2006) An experimental in vitro model for dynamic direct exposure of human cells to airborne contaminants. Toxicol Lett 165:1–10CrossRefGoogle Scholar
  6. Bartoli CR, Wellenius GA, Diaz EA et al (2009) Mechanisms of inhaled fine particulate air pollution-induced arterial blood pressure changes. Environ Health Perspect 117:361–366Google Scholar
  7. Becker S, Soukup JM, Sioutas C et al (2003) Response of human alveolar macrophages to ultrafine, fine, and coarse urban air pollution particles. Exp Lung Res 29:29–44CrossRefGoogle Scholar
  8. Beckett WS, Chalupa DF, Pauly-Brown A et al (2005) Comparing inhaled ultrafine versus fine zinc oxide particles in healthy adults: A human inhalation study. Am J Respir Crit Care Med 171:1129–1135CrossRefGoogle Scholar
  9. Boland S, Baeza-Squiban A, Fournier T et al (1999) Diesel exhaust particles are taken up by human airway epithelial cells in vitro and alter cytokine production. Am J Physiol 276:L604–L613Google Scholar
  10. Brook RD (2008) Cardiovascular effects of air pollution. Clin Sci 115:175–187CrossRefGoogle Scholar
  11. Brook RD, Brook JR, Urch B et al (2002) Inhalation of fine particulate air pollution and ozone causes acute arterial vasoconstriction in healthy adults. Circulation 105:1534–1536CrossRefGoogle Scholar
  12. Brook RD, Brook JR, Rajagopalan S (2003) Air pollution: the “heart” of the problem. Curr Hypertens Rep 5:32–39CrossRefGoogle Scholar
  13. Brook RD, Franklin B, Cascio W et al (2004) Air pollution and cardiovascular disease. Circulation 109:2655–2671CrossRefGoogle Scholar
  14. Brook RD, Urch B, Dvonch T et al (2009) Insights into the mechanisms and mediators of the effects of air pollution exposure on blood pressure and vascular function in healthy humans. Hypertension 54:659–667CrossRefGoogle Scholar
  15. Bruijne K, Ebersviller S, Sexton KG et al (2008) Design and testing of electrostatic aerosol in vitro exposure system (EAVES): An alternative exposure system for particles. Inhalation Toxicol 20:1–11CrossRefGoogle Scholar
  16. Calderon-Garciduenas L, Reed W, Maronpot RR et al (2004) Brain inflammation and Alzheimer’s-like pathology in individuals exposed to severe air pollution. Toxicol Pathol 32:650–658CrossRefGoogle Scholar
  17. Canadian Medical Association (CMA) (2008) No breathing room National illness costs of air pollution. Accessed 29 August 2009
  18. Carter JD, Ghio AJ, Samet JM et al (1997) Cytokine production by human airway epithelial cells after exposure to an air pollution particle is metal-dependent. Toxicol Appl Pharmacol 146:180–188CrossRefGoogle Scholar
  19. Carter JM, Corson N, Driscoll KE et al (2006) A comparative dose-related response of several key pro- and anti-inflammatory mediators in the lungs of rats, mice, and hamsters after subchronic inhalation of carbon black. J Occup Environ Med 48:1265–1278CrossRefGoogle Scholar
  20. Cohen AJ, Anderson HR, Ostro B et al (2005) The global burden of diseases due to outdoor air pollution. J Toxicol Environ Health 68:1301–1307CrossRefGoogle Scholar
  21. Delfino RJ, Sioutas C, Malik S (2005) Potential role of ultrafine particles in associations between airborne particle mass and cardiovascular health. Environ Health Perspect 113:934–946CrossRefGoogle Scholar
  22. Delfino RJ, Staimer N, Gillen D et al (2006) Personal and ambient air pollution is associated with increased exhaled nitric oxide in children with asthma. Environ Health Perspect 114:1736–1743Google Scholar
  23. Devlin RB, Frampton ML, Ghio AJ (2005) In vitro studies: what is their role in toxicology? Exp Toxicol Pathol 57:183–188CrossRefGoogle Scholar
  24. Di Pietro A, Visalli G, Munaò F et al (2009) Oxidative damage in human epithelial alveolar cells exposed in vitro to oil fly ash transition metals. Int J Hyg Environ Health 212:196–208CrossRefGoogle Scholar
  25. Dominici F, Peng RD, Bell ML et al (2006) Fine particulate air pollution and hospital admission for cardiovascular and respiratory diseases. J Am Med Assoc 295:1127–1134CrossRefGoogle Scholar
  26. Dormans JAMA, Steerenberg PA, Arts JHE et al (1999) Pathological and immunological effects of respirable coal fly ash in male Wister rats. Inhalation Toxicol 11:51–69CrossRefGoogle Scholar
  27. Dubowsky SD, Suh H, Schwartz J et al (2006) Diabetes, obesity, and hypertension may enhance associations between air pollution and markers of systemic inflammation. Environ Health Perspect 114:992–998CrossRefGoogle Scholar
  28. Fairley D (1999) Daily mortality and air pollution in Santa Clara County, California: 1989–1996. Environ Health Perspect 107:637–641CrossRefGoogle Scholar
  29. Fakhri AA, Ilic LM, Wellenius GA et al (2009) Autonomic effects of controlled fine particulate exposure in young healthy adults: effect modification by ozone. Environ Health Perspect 117:1287–1292Google Scholar
  30. Fischer HC, Fournier-Bidoz S, Pang KS et al (2007) Quantitative detection of engineered nanoparticles in tissues and organs: an investigation of efficacy and linear dynamic ranges using ICP-AES. NanoBiotechnology 3:46–54CrossRefGoogle Scholar
  31. Fujii T, Hayashi S, Hogg JC et al (2001) Particulate matter induces cytokine expression in human bronchial epithelial cells. Am J Respir Cell Mol Biol 25:265–271Google Scholar
  32. Fukano Y, Yoshimura H, Yoshida T (2006) Heme oxygenase-1 gene expression in human alveolar epithelial cells (A549) following exposure to whole cigarette smoke on a direct in vitro exposure system. Exp Toxicol Pathol 57:411–418CrossRefGoogle Scholar
  33. Ghio AJ, Devlin RB (2001) Inflammatory lung injury after bronchial instillation of air pollution particles. Am J Respir Crit Care Med 164:704–708Google Scholar
  34. Ghio AJ, Kim C, Devlin RB (2000) Concentrated ambient air particles induce mild pulmonary inflammation in healthy human volunteers. Am J Respir Crit Care Med 162:981–988Google Scholar
  35. Gold DR, Litonjua A, Schwartz J et al (2000) Ambient pollution and heart rate variability. Circulation 101:1267–1273CrossRefGoogle Scholar
  36. Goldberg MS, Bailar JC III, Burnett RT et al. (2000) Identifying subgroups of the general population that may be susceptible to short-term increases in particulate air pollution: a time-series study in Montreal, Quebec. Cambridge, MA: Health Effects Institute; Research Report 97. Accessed 27 June 2009
  37. Gong H Jr, Linn WS, Sioutas C et al (2003) Controlled exposures of healthy and asthmatic volunteers to concentrated ambient fine particles in Los Angeles. Inhalation Toxicol 15:305–325CrossRefGoogle Scholar
  38. Gong H Jr, Linn WS, Clark KW et al (2005) Respiratory responses to exposures with fine particulates and nitrogen dioxide in the elderly with and without COPD. Inhalation Toxicol 17:123–132CrossRefGoogle Scholar
  39. Graff DW, Cascio WE, Rappold A et al (2009) Exposure to concentrated coarse air pollution particles causes mild cardiopulmonary effects in healthy young adults. Environ Health Perspect 117:1089–1094CrossRefGoogle Scholar
  40. Hetland RB, Cassee FR, Refsnes M et al (2004) Release of inflammatory cytokines, cell toxicity and apoptosis in epithelial lung cells after exposure to ambient air particles of different size fractions. Toxicol In Vitro 18:203–212CrossRefGoogle Scholar
  41. Karoly ED, Li Z, Dailey LA et al (2007) Up-regulation of tissue factor in human pulmonary artery endothelial cells after ultrafine particle exposure. Environ Health Perspect 115:535–540CrossRefGoogle Scholar
  42. Katsouyanni K, Touloumi G, Samoli E et al (2003) Sensitivity analysis of various models of short-term effects of ambient particles on total mortality in 29 cities in APHEA2. In: Revised analyses of time-series of Air Pollution and Health. Special Report, Health Effects Institute, Boston, pp 157–164Google Scholar
  43. Knebel JW, Ritter D, Aufderheide M (2002) Exposure of human lung cells to native diesel motor exhaust-development of an optimized in vitro test strategy. Toxicol In Vitro 16:185–192CrossRefGoogle Scholar
  44. Kok TMCM, Driece HAL, Hogervorst JGF (2006) Toxicological assessment of ambient and traffic-related particulate matter: A review of recent studies. Mutat Res 613:103–122CrossRefGoogle Scholar
  45. Kunzli N, Jerrett M, Mack WJ et al (2005) Ambient air pollution and atherosclerosis in Los Angeles. Environ Health Perspect 113:201–206CrossRefGoogle Scholar
  46. La Rovere MT, Pinna GD, Maestri R et al (2003) Short-term heart rate variability strongly predicts sudden cardiac death in chronic heart failure patients. Circulation 107:565–570CrossRefGoogle Scholar
  47. Li N, Venkatesan MI, Miguel A et al (2000) Induction of heme oxygenase-1 expression in macrophages by diesel exhaust particle chemicals and quinones via the antioxidant-responsive element. J Immunol 165:3393–3401Google Scholar
  48. Li N, Kim S, Wang M et al (2002) Use of a stratified oxidative stress model to study the biological effects of ambient concentrated and diesel exhaust particulate matter. Inhalation Toxicol 14:459–486CrossRefGoogle Scholar
  49. Li N, Sioutas C, Cho A et al (2003) Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage. Environ Health Perspect 111:455–460CrossRefGoogle Scholar
  50. Li N, Xia T, Nel AE (2008) The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles. Free Radic Biol Med 44:1689–1699CrossRefGoogle Scholar
  51. Maier KL, Alessandrini F, Beck-Speier I et al (2008) Health effects of ambient particulate matter- biological mechanisms and inflammatory responses to in vitro and in vivo particle exposures. Inhalation Toxicol 20:319–337CrossRefGoogle Scholar
  52. Mauad T, Rivero DHRF, de Oliveira RC et al (2008) Chronic exposure to ambient levels of urban particles affects mouse lung development. Am J Respir Crit Care Med 178:721–728CrossRefGoogle Scholar
  53. Mazzarella G, Ferraraccio F, Prati MV et al (2007) Effects of diesel exhaust particles on human lung epithelial cells: An in vitro study. Respir Med 101:1155–1162CrossRefGoogle Scholar
  54. McClellan RO (2000) Particle interactions with the respiratory tract. In: Gehr P, Heyder J (eds) Particle-lung interactions, 1st edn. Marcel Dekker Inc., New YorkGoogle Scholar
  55. Mills NL, Törnqvist H, Gonzalez MC et al (2007) Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men with coronary heart disease. N Engl J Med 357:1075–1082CrossRefGoogle Scholar
  56. Mills NL, Robinson SD, Fokkens PHB et al (2008) Exposure to concentrated ambient particles does not affect vascular function in patients with coronary heart disease. Environ Health Perspect 116:709–715CrossRefGoogle Scholar
  57. Mitschik S, Schierl R, Nowak D et al (2008) Effects of particulate matter on cytokine production in vitro: a comparative analysis of published studies. Inhalation Toxicol 20:399–414CrossRefGoogle Scholar
  58. Möller W, Felten K, Sommerer K et al (2008) Deposition, retention, and translocation of ultrafine particles from the central airways and lung periphery. Am J Respir Crit Care Med 177:426–432CrossRefGoogle Scholar
  59. Narciso SP, Nadziejko E, Chen LC et al (2003) Adaptation to stress induced by restraining rats and mice in nose-only inhalation holders. Inhalation Toxicol 15:1133–1143Google Scholar
  60. National Institute of Standards and Technology (NIST). Accessed 17 September 2009
  61. Nemmar A, Hoet PHM, Vanquickenborne B et al (2002) Passage of inhaled particles into the blood circulation in humans. Circulation 105:411–414CrossRefGoogle Scholar
  62. Nemmar A, Hoylaerts MF, Hoet PHM et al (2004) Possible mechanisms of the cardiovascular effects of inhaled particles: systemic translocation and prothrombotic effects. Toxicol Lett 149:243–253CrossRefGoogle Scholar
  63. Oberdörster G (1996) Significance of particle parameters in the evaluation of exposure-dose-response relationships of inhaled particles. Inhalation Toxicol 8(Suppl):73–89Google Scholar
  64. Oberdörster G (2001) Pulmonary effects of inhaled ultrafine particles. Int Arch Occup Environ Health 74:1–8CrossRefGoogle Scholar
  65. Oberdörster G, Sharp Z, Atudorei V et al (2004) Translocation of inhaled ultrafine particles to the brain. Inhalation Toxicol 16:437–445CrossRefGoogle Scholar
  66. Peretz A, Sullivan JH, Leotta DF et al (2008) Diesel exhaust inhalation elicits vasoconstriction in vivo. Environ Health Perspect 116:937–942CrossRefGoogle Scholar
  67. Peters A, Wichmann HE, Tuch T et al (1997) Respiratory effects are associated with the number of ultrafine particles. Am J Respir Crit Care Med 155:1376–1383Google Scholar
  68. Peters A, Dockery D, Muller J et al (2001) Increased particulate air pollution and the triggering of myocardial infarction. Circulation 103:2810–2815CrossRefGoogle Scholar
  69. Politis M, Pilinis C, Lekkas TD (2008) Ultrafine particles (UFP) and health effects. Dangerous. Like no other PM? Review and analysis. Glob NEST J 10:439–452Google Scholar
  70. Pope CA III, Ezzati M, Dockery DW (2009) Fine-particulate air pollution and life expectancy in the Unites States. N Engl J Med 360:376–386CrossRefGoogle Scholar
  71. Quinlan T, Spivack S, Mossman BT (1994) Regulation of antioxidant enzymes in lung after oxidant injury. Environ Health Perspect 102(Suppl 2):79–86CrossRefGoogle Scholar
  72. Ritter D, Knebel JW, Aufderheide M (2001) In vitro exposure of isolated cells to native gaseous compounds- development and validation of an optimized system for human lung cells. Exp Toxicol Pathol 53:373–386CrossRefGoogle Scholar
  73. Rothen-Rutishauser B, Kiama SG, Gehr P (2005) A three-dimensional cellular model of the human respiratory tract to study the interaction with particles. Am J Respir Cell Mol Biol 32:281–289CrossRefGoogle Scholar
  74. Rothen-Rutishauser B, Blank F, Mühlfeld C et al (2008) In vitro models of the human epithelial airway barrier to study the toxic potential of particulate matter. Expert Opin Drug Metab Toxicol 4:1075–1089CrossRefGoogle Scholar
  75. Rundell KW, Hoffman JR, Caviston R et al (2007) Inhalation of ultrafine and fine particulate matter disrupts systemic vascular function. Inhalation Toxicol. doi: 10.1080/08958370601051727
  76. Saldiva PH, Clarke RW, Coull BA et al (2002) Lung inflammation induced by concentrated ambient air particles is related to particle composition. Am J Respir Crit Care Med 165:1610–1617CrossRefGoogle Scholar
  77. Schins RPF, Hei TK (2007) Genotoxic effects of particles. In: Donaldson K, Borm P (eds) Particle toxicology, 1st edn. CRC Press, New YorkGoogle Scholar
  78. Schwartz J (1994) Air pollution and daily mortality: a review and meta analysis. Environ Res 64:36–52CrossRefGoogle Scholar
  79. Sioutas C, Koutrakis P, Burton RM (1995) A technique to expose animals to concentrated fine ambient aerosols. Environ Health Perspect 103:172–177CrossRefGoogle Scholar
  80. Sioutas C, Delfino RJ, Singh M (2005) Exposure assessment for atmospheric ultrafine particles (UFPs) and implications in epidemiologic research. Environ Health Perspect 113:947–955CrossRefGoogle Scholar
  81. Southern Ontario Centre for Atmospheric Aerosol Research (SOCAAR) (2007) Facilities- Concentrated Ambient Particle Exposure Facility (CAPEF). Accessed 21 September 2009
  82. Squadrito GL, Cueto R, Dellinger B et al (2001) Quinoid redox cycling as a mechanism for sustained free radical generation by inhaled airborne particulate matter. Free Radic Biol Med 31:1132–1138CrossRefGoogle Scholar
  83. Suwa T, Hogg JC, Quinlan KB et al (2002) Particulate air pollution induces progression of atherosclerosis. J Am Coll Cardiol 39:935–942CrossRefGoogle Scholar
  84. Thomson EM, Williams A, Yauk CL et al (2009) Impact of nose-only exposure system on pulmonary gene expression. Inhalation Toxicol 21(Suppl 1):74–82CrossRefGoogle Scholar
  85. Törnqvist H, Mills NL, Gonzalez M et al (2007) Persistent endothelial dysfunction in humans after diesel exhaust inhalation. Am J Respir Crit Car Med 176:395–400CrossRefGoogle Scholar
  86. Ulrich MMW, Alink GM, Kumarathasan P et al (2002) Health effects and time course of particulate matter on the cardiopulmonary system in rats with lung inflammation. J Toxicol Environ Health 65:1571–1595CrossRefGoogle Scholar
  87. United States Environmental Protection Agency (USEPA) (2004) Air quality criteria for particulate matter Volume II. Accessed 10 May 2009
  88. Urch B, Silverman F, Corey P et al (2005) Acute blood pressure responses in healthy adults during controlled air pollution exposures. Environ Health Perspect 113:1052–1055CrossRefGoogle Scholar
  89. Utell MJ, Frampton MW (2000) Toxicologic methods: controlled human exposures. Environ Health Perspect 108:605–613Google Scholar
  90. Valavanidis A, Fiotakis K, Vlachogianni T (2008) Airborne particulate matter and human health: Toxicological assessment and importance of size and composition of particles for oxidative damage and carcinogenic mechanisms. J Environ Sci Health Part C 26:339–362Google Scholar
  91. Valentine R, Kennedy GL (2008) Inhalation toxicology. In: Hayes AW (ed) Principles and methods of toxicology, 5th edn. CRC Press, New YorkGoogle Scholar
  92. Vincent R, Kumarathasan P, Goegan P et al (2001) Inhalation toxicology of urban ambient particulate matter: Acute cardiovascular effects in rats. Res Rep Health Effects Inst 104:5–54Google Scholar
  93. Watterson TL, Sorensen J, Martin R et al (2007) Effects of PM2.5 collected from Cache Valley Utah on genes associated with the inflammatory response in human lung cells. J Toxicol Environ Health A 70:1731–1744CrossRefGoogle Scholar
  94. Weiss ST, Utell MJ, Samet JM (1999) Environmental tobacco smoke and asthma in adults. Environ Health Perspect 107:891–895Google Scholar
  95. Wellenius GA, Coull BA, Godleski JJ et al (2003) Inhalation of concentrated ambient air particles exacerbates myocardial ischemia in conscious dogs. Environ Health Perspect 111:402–408CrossRefGoogle Scholar
  96. Wittmaack K (2007) In search for the most relevant parameter for quantifying lung inflammatory response to nanoparticle exposure: particle number surface area or what? Environ Health Perspect 115:187–194CrossRefGoogle Scholar
  97. World Health Organization (WHO) (2006) Air quality guidelines global update 2005. . Accessed 2 July 2009
  98. Zanobetti A, Schwartz J (2005) The effect of particulate air pollution on emergency admissions for myocardial infarction: a multi-city case-crossover analysis. Environ Health Perspect 113:978–982CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Umme S. Akhtar
    • 1
    • 3
    Email author
  • Jeremy A. Scott
    • 2
    • 3
  • Amanda Chu
    • 1
    • 3
  • Greg J. Evans
    • 1
    • 3
  1. 1.Department of Chemical Engineering and Applied ChemistryUniversity of TorontoTorontoCanada
  2. 2.Department of MedicineUniversity of TorontoTorontoCanada
  3. 3.Southern Ontario Centre for Atmospheric Aerosol Research (SOCAAR)TorontoCanada

Personalised recommendations