Particle Induced Toxicity in Relation to Transition Metal and

The PRA and DUI FPM samples were selected to determine the putative effects of transition metal content of the PM on cardiovascular end points since t...
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Environ. Sci. Technol. 2009, 43, 4729–4736

Particle Induced Toxicity in Relation to Transition Metal and Polycyclic Aromatic Hydrocarbon Contents M I R I A M E . G E R L O F S - N I J L A N D , * ,3 MELINA RUMMELHARD, A. JOHN F. BOERE,3 DAAN L. A. C. LESEMAN, R O D G E R D U F F I N , ‡,§ R O E L P . F . S C H I N S , § ¨A ¨ ,⊥ PAUL J. A. BORM,| MARKUS SILLANPA RAIMO O. SALONEN,# AND FLEMMING R. CASSEE3 National Institute for Public Health and the Environment, Bilthoven, The Netherlands, University of Edinburgh, Scotland, United Kingdom, Institut fu ¨ r Umweltmedizinische Forschung, Du ¨ sseldorf, Germany, Centre of Expertise in Life Sciences, Heerlen, The Netherlands, Finnish Meteorological Institute, Helsinki, Finland, and National Institute for Health and Welfare, Kuopio, Finland

Received November 10, 2008. Revised manuscript received February 14, 2009. Accepted February 24, 2009.

Exposure to ambient particulate matter (PM) is statistically significantlyassociatedwithmorbidityandmortality.Theobjectives of this study were (a) to investigate in vivo pulmonary and systemic cytotoxicity and inflammatory activity in compromised animals exposed to PM and (b) to investigate the relationships of the outcomes to the chemical compositions of particular polycyclic aromatic hydrocarbons (PAH) and transition metals in the PM. The PM samples were collected in European cities representing contrasting situations. Exposure of spontaneously hypertensive rats (7 mg of PM/kg) resulted in pulmonary inflammation, cellular toxicity and the induction of blood fibrinogen. Coarse PM generally caused stronger effects per mg than fine particles. Positive correlations between lactate dehydrogenase, proteins, and some inflammation parameters and the particle metal and PAH content were found. PM rich in PAH also led to increased blood fibrinogen. Removal of particles but not the organics (i.e., PAH) of a sample led to reduced inflammation in the lungs. The present study highlights the importance of metals as well as PMbound PAH in particle biological outcomes. It supports the hypothesis that, on an equal mass basis, particle health effects differ due to differences in compositions and size.

Introduction It has become evident in the past decades that elevated exposure to ambient particulate matter (PM) is associated with respiratory and cardiovascular morbidity and mortality (1-4). Both animal toxicology studies and studies with human volunteers support these findings. Inhalation studies have * Corresponding author e-mail: [email protected]. 3 National Institute for Public Health and the Environment. ‡ University of Edinburgh. § Institut fu ¨ r Umweltmedizinische Forschung. | Centre of Expertise in Life Sciences. ⊥ Finnish Meteorological Institute. # National Institute for Health and Welfare. 10.1021/es803176k CCC: $40.75

Published on Web 03/25/2009

 2009 American Chemical Society

shown that short-term exposure to diesel engine particles or concentrated ambient particles at levels that people encounter in polluted areas results in acute lung inflammation (5, 6). Animal studies have also revealed an association between particle exposure and cardiovascular abnormalities (7, 8). It has become increasingly clear that toxicology studies cannot rely on PM mass alone to describe the health effects of particles. Indeed, urban air inhalable particles (PM10: PM with an aerodynamic diameter