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Seung-Hyun Cho,^1,2,3 Haiyan Tong,¹ John K. McGee,¹ Richard W. Baldauf,^2,4 Q. Todd Krantz,¹ and M. Ian Gilmour¹

¹National Health and Environmental Effects Research Laboratory, and ²National Risk Management Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA; ³Research Participation Program, Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee, USA; ⁴Office of Transportation and Air Quality, U.S. Environmental Protection Agency, Ann Arbor, Michigan, USA

Abstract
Background: Epidemiologic studies have reported an association between proximity to highway traffic and increased cardiopulmonary illnesses.

Objectives: We investigated the effect of size-fractionated particulate matter (PM) , obtained at different distances from a highway, on acute cardiopulmonary toxicity in mice.

Methods: We collected PM for 2 weeks in July–August 2006 using a three-stage (ultrafine, < 0.1 µm ; fine, 0.1–2.5 µm ; coarse, 2.5–10 µm) high-volume impactor at distances of 20 m [near road (NR) ] and 275 m [far road (FR) ] from an interstate highway in Raleigh, North Carolina. Samples were extracted in methanol, dried, diluted in saline, and then analyzed for chemical constituents. Female CD-1 mice received either 25 or 100 µg of each size fraction via oropharyngeal aspiration. At 4 and 18 hr postexposure, mice were assessed for pulmonary responsiveness to inhaled methacholine, biomarkers of lung injury and inflammation ; ex vivo cardiac pathophysiology was assessed at 18 hr only.

Results: Overall chemical composition between NR and FR PM was similar, although NR samples comprised larger amounts of PM, endotoxin, and certain metals than did the FR samples. Each PM size fraction showed differences in ratios of major chemical classes. Both NR and FR coarse PM produced significant pulmonary inflammation irrespective of distance, whereas both NR and FR ultrafine PM induced cardiac ischemia–reperfusion injury.

Conclusions: On a comparative mass basis, the coarse and ultrafine PM affected the lung and heart, respectively. We observed no significant differences in the overall toxicity end points and chemical makeup between the NR and FR PM. The results suggest that PM of different size-specific chemistry might be associated with different toxicologic mechanisms in cardiac and pulmonary tissues.

Key words: cardiopulmonary, chemical composition, inflammation, ischemia–reperfusion injury, mice, motor vehicle emissions, near road, particulate matter, size fraction. Environ Health Perspect 117:1682–1689 (2009) . doi:10.1289/ehp.0900730 available via http://dx.doi.org/ [Online 29 June 2009]

Address correspondence to M.I. Gilmour, U.S. Environmental Protection Agency, 109 T.W. Alexander Dr., Mail Drop B143-04, Research Triangle Park, NC 27711 USA. Telephone: (919) 541-0015. Fax: (919) 541-0026. E-mail: gilmour.ian@epa.gov

Supplemental Material is available online (doi:10.1289/ehp.0900730.S1 via http://dx.doi.org/) .

We thank M. Daniels, E. Boykin, D. Andrews, J. Richards, and R. Jaskot for technical assistance in toxicologic analyses ; J. Lehmann for technical and editing assistance ; D.L. Costa and J. Dye for valuable comments ; E. Thoma and J. Weinstein of the Raleigh Near Road Study team for site selection and management assistance ; D. Davies, D. Terrell, and G. Hudson for mobile air sampling ; M. Hays for carbon speciation ; and D. Doerfler for guidance on statistical analyses of data. We also thank the Lions Club for the Blind for access to the monitoring sites in Raleigh, North Carolina.

S.-H.C. received fellowship support from the Research Participation Program of the U.S. Environmental Protection Agency administered by the Oak Ridge Institute for Science and Education.

The authors declare they have no competing financial interests.

Received 26 February 2009 ; accepted 29 June 2009.