| Sample Characterization of Automobile and Forklift Diesel Exhaust Particles and Comparative Pulmonary Toxicity in Mice Pramila Singh,1 David M. DeMarini,1 Colin A.J. Dick,2 Dennis G. Tabor,3 Jeff V. Ryan,3 William P. Linak,3 Takahiro Kobayashi,4 and M. Ian Gilmour1 1National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA; 2Center for Environmental Medicine and Lung Biology, University of North Carolina, Chapel Hill, North Carolina, USA; 3National Risk Management Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA; 4Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Japan Abstract
Two samples of diesel exhaust particles (DEPs) predominate in health effects research: an automobile-derived DEP (A-DEP) sample and the National Institute of Standards Technology standard reference material (SRM 2975) generated from a forklift engine. A-DEPs have been tested extensively for their effects on pulmonary inflammation and exacerbation of allergic asthmalike responses. In contrast, SRM 2975 has been tested thoroughly for its genotoxicity. In the present study, we combined physical and chemical analyses of both DEP samples with pulmonary toxicity testing in CD-1 mice to compare the two materials and to make associations between their physicochemical properties and their biologic effects. A-DEPs had more than 10 times the amount of extractable organic material and less than one-sixth the amount of elemental carbon compared with SRM 2975. Aspiration of 100 µg of either DEP sample in saline produced mild acute lung injury ; however, A-DEPs induced macrophage influx and activation, whereas SRM 2975 enhanced polymorphonuclear cell inflammation. A-DEPs stimulated an increase in interleukin-6 (IL-6) , tumor necrosis factor  , macrophage inhibitory protein-2, and the TH2 cytokine IL-5, whereas SRM 2975 only induced significant levels of IL-6. Fractionated organic extracts of the same quantity of DEPs (100 µg) did not have a discernable effect on lung responses and will require further study. The disparate results obtained highlight the need for chemical, physical, and source characterization of particle samples under investigation. Multidisciplinary toxicity testing of diesel emissions derived from a variety of generation and collection conditions is required to meaningfully assess the health hazards associated with exposures to DEPs. Key words: automobile, diesel exhaust particles, forklift, mice, pulmonary toxicity, SRM 2975. Environ Health Perspect 112:820-825 (2004) . doi:10.1289/ehp.6579 available via http://dx.doi.org/ [Online 22 December 2003]
Address correspondence to P. Singh, U.S. Environmental Protection Agency, MD:B143-01, Research Triangle Park, NC 27711 USA. Telephone: (919) 541-7808. Fax: (919) 541-4284. E-mail: singh.pramila@epa.gov We thank J.A. Dye, M.C. Madden, D.L. Costa, and L.S. Birnbaum for their comments on the manuscript. We also thank M.J. Daniels, E.H. Boykin, D.L. Andrews, J.H. Richards, D.L. Doerfler, M.J. Calvi, T. Shinagawa, and A. Miller for their technical assistance and analyses, and Y.Y. Kostetski, L.E. Yu, and N.M. Kocherginsky from the National University of Singapore for performing electron paramagnetic resonance analysis. P.S. was supported by National Institutes of Health grant ES11245-01, and C.A.J.D. was supported by U.S. EPA/University of North Carolina cooperative agreement CR824915. This article was reviewed by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency (EPA) , and approved for publication. The authors declare they have no competing financial interests. Received 11 July 2003 ; accepted 22 December 2003.
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