Final Report: National Environmental Respiratory Center: Health Hazards of Inhaled Gasoline Engine Emissions and Street Dust

EPA Grant Number: CR831455
Subproject: this is subproject number R831455 , established and managed by the Center Director under a main grant
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: National Environmental Respiratory Center (NERC)
Center Director: Mauderly, Joe L.
Title: National Environmental Respiratory Center: Health Hazards of Inhaled Gasoline Engine Emissions and Street Dust
Investigators: Mauderly, Joe L. , Barr, E. B. , Barrett, Edward G. , Bedrick, Edward , Belinsky, Steven A. , Campen, Matthew J. , Divine, Kevin K , Gigliotti, Andrew , Harrod, Kevin , McDonald, Jacob D. , Reed, Matthew D. , Seagrave, Jean Clare , Seilkop, Steven , Swenberg, James A. , Wise, Barry
Institution: Lovelace Respiratory Research Institute , University of New Mexico
EPA Project Officer: Chung, Serena
Project Period: September 1, 2003 through August 31, 2008
Project Amount: $969,300
RFA: Targeted Research Center (2003) Recipients Lists
Research Category: Targeted Research

Objective:

The NERC Program was initiated by Congress in 1998 explicitly to establish a multipollutant-oriented laboratory research program aimed at placing the relative health hazards of different air contaminants, their combinations, and their sources into clearer context. The program fills a gap in the nation’s predominantly single-pollutant, single-source air pollution health research portfolio. The program is based at LRRI but involves a multidisciplinary team of investigators at LRRI and several other institutions across the United States. An independent External Scientific Advisory is vested with approval authority over major program decisions to separate the conduct of research and interpretation of results from the sometimes-divergent views among sponsors. All sponsors advise in planning the research and have access to pre-publication results, but do not review or approve publications.

The NERC research strategy addresses two interrelated fundamental information gaps: 1) an exposure composition-concentration-response database adequate to support multivariate analysis of the roles of different pollutants in the various health effects; and 2) contemporary, detailed, head-to-head comparisons of the health effects of different anthropogenic combustion source emissions. The first need is met by conducting identically designed inhalation toxicology studies of several mixtures of key air contaminants having different, but overlapping compositions. The second need is met by using key combustion source emissions as the exposure “mixtures” for the studies used to construct the database. Subchronic (up to 6 months) inhalation studies have been conducted of diesel and gasoline engine exhaust, hardwood smoke, and coal combustion emissions. Recommendations from expert workshops guide the selection of methods for generating exposure atmospheres. Multiple strains of rats and mice are exposed 6 hours/day, 7 days/week. The physical-chemical compositions of the exposures are characterized in detail. Measured health responses include body and organ weight, serum hematology, serum chemistry, clearance of bacteria from the lung, heart electrophysiology, pro-atherosclerotic vascular pathology, development and exacerbation of respiratory allergic responses, micronuclei in circulating reticulocytes, and lung DNA methylation and oxidative injury.

Summary/Accomplishments (Outputs/Outcomes):

The NERC research strategy addresses two interrelated fundamental information gaps: 1) an exposure composition-concentration-response database adequate to support multivariate analysis of the roles of different pollutants in different health effects (when inhaled in mixtures); and 2) contemporary, detailed, head-to-head comparisons of the health effects of different anthropogenic combustion source emissions of significance to air quality management. The first need is being met by conducting identically designed inhalation toxicology studies of several mixtures of key air contaminants having different, but overlapping compositions (Table 1). Given such a database for which “personal” exposures and health outcomes are known precisely and in detail, several multivariate analytical approaches, such as principal component analysis (PCA), partial least squares regression (PLS; Malinowski, 2002), parallel factor analysis (PARFAC; Kiers et al., 1999), and Tucker-3 (Tucker, 1966), can be used to determine links between physical chemical species (and their combinations) and health outcomes. The feasibility and utility of this approach was demonstrated by LRRI studies using PCA/PLS to identify engine oil components, rather than fuel combustion components, as the primary drivers of lung inflammatory responses to samples of diesel, gasoline, and compressed natural gas engine emissions (McDonald et al., 2004a; Seagrave et al., 2005a) and identifying traffic and industrial emissions as important contributors to the toxicity of southeastern U.S. ambient PM samples (Seagrave et al., 2006). The need for better information on the comparative hazards of emissions from different sources is being met by using key combustion source emissions as the exposure “mixtures” for the studies used to construct the database.

At the outset of the program, the ESAC proposed 12 different exposure atmospheres, including multiple variants of some source emissions (e.g., emissions from both on-road and off-road gasoline engines). Emissions vary considerably among sources within each source category; however, it is both implausible and strategically unnecessary to study all of the permutations of each source emission. The key is to include a range of physical-chemical classes of air contaminants at a range of ratios among classes, rather than attempting to encompass all variations of source emissions. The database is therefore being constructed using a representative case of each source emission that includes the key distinguishing features of each source type.

The strategy for generating each source emission is based on consensus of scientific and technical experts, achieved by NERC workshops convened for that purpose. Exploratory multivariate analyses of the database containing results from the first three studies began in 2007, and detailed analyses of data from four studies will begin in late 2008 when the final results from the coal emission study are complete. However, it is not expected that multivariate analytical approaches will gain substantive power until six exposure cases are accumulated in the database. Planning for the study of residual oil (marine heavy fuel oil, HFO) emissions is underway at the time of this Report. The ESAC has recommended that studies of respirable paved road dust and secondary organic aerosols follow, and strategies for generating those exposure atmospheres have already been established in preliminary studies. It is expected that the composition-concentration-response relationships revealed by multivariate analyses will provide a foundation for designing more focused (limited-scale) studies to test hypotheses directly. Such follow-on research could be an extension of the NERC Program, but it is more likely to be accomplished by multiple laboratories using a range of funding mechanisms. NERC is envisioned as the benchmark lead initiative.

Separate subchronic inhalation studies are conducted for each exposure atmosphere using a consistent protocol that allows not only direct comparisons of effects among atmospheres (sources) but also combining data from all studies into a single database for analysis. Each study contributes a “layer” of composition-concentration-response data to the aggregate database. The database will support analyses of the contributions of individual physical-chemical pollutant species, classes, and combinations to the health outcomes across studies. The underlying hypothesis is that composition-response relationships can be identified that hold true regardless of the source of the pollutants. If this proves true on a program scale, as it has in our hands on a smaller study scale (McDonald et al., 2004a; Seagrave et al., 2006), the results of the program will be an important step toward a more integrated, multipollutant understanding of air quality-health relationships.

For the study of each atmosphere (source emission), animals are exposed in whole-body chambers 6 hours/day, 7 days/week for up to 6 months to one of three concentrations of the mixture, to the highest concentration with PM removed by filtration, or to clean air as controls. In the first two studies (diesel exhaust and hardwood smoke), the four exposure atmospheres were all dilutions of whole emissions. In the subsequent gasoline and coal emissions studies, the exposures included three dilutions and both filtered and unfiltered emissions at the highest concentration, as a direct test of the relative importance of PM and non-PM components. This approach proved very informative, and we have now repeated studies of the diesel and wood smoke atmospheres to compare effects of filtered versus unfiltered exposures on selected health outcomes (not the full protocol). All exposure levels are intended to fall within the range of plausible human exposures, although the higher levels represent occupational or “hot spot” conditions rather than widespread environmental exposures. Including multiple exposure levels in each study allows testing the significance of exposure-response trends and provides a glimpse of the nature of the exposure- response curve, including potential identification of no-effects levels. Indeed, the lowest exposure level has proven to be a “no observed effects level” for nearly all health endpoints. This is useful information aside from the other products of the Program.

The NERC exposures are characterized at the greatest practical level of detail. Characterization encompasses the general physical-chemical classes summarized in Table 2 (McDonald et al., 2004b; 2006a,b; 2008), but most classes contains many species. The analyses employ current state-of-the-art, research-grade methods. Of course, it is acknowledged that the complete speciation of the PM-borne organic matter is beyond current analytical methods; thus, the majority of PM organic mass is unresolved. Health responses are measured using the animal models and endpoints described in detail in publications (Campen et al., 2003; Harrod et al., 2005; Barrett et al., 2005, 2008; Seagrave et al., 2005b; Reed et al., 2006b, 2008; Lund et al., 2007). The goal is to employ outcome models and endpoints that span the general categories of health outcomes that have been associated statistically with air pollution by epidemiology.

The research is conducted by a team of LRRI and non-LRRI investigators who produce, analyze, interpret, and publish data .  No team member works in isolation; each necessarily coordinates with others. Thus, the Center does not consist of research cores supporting multiple individual projects as is typical of most programs; rather, it is a completely integrated program in which all investigators participate in the same studies.

The NERC Program emphasizes incorporating the best current thinking and broad scientific and stakeholder consensus into the design of the research. This is done not only by open discussion with the ESAC and sponsor representatives at the annual meeting, but also by conducting peer expert workshops to review options and develop recommendations for key components of the program. The first workshop optimized the experimental design to facilitate analysis of the resulting database, followed by workshops to define the health assessment protocol, the generation of each exposure atmosphere, and strategies for statistical analyses.

Conclusions:

Studies of the four source emissions listed above have been completed and most have been published, although results of the coal emission study are still being analyzed. Integrated analysis of the results has begun, and will be a major effort over the coming year. All exposures have caused health effects, but the pattern of effects differed among the studies. Although the mass concentration of particulate matter (PM) has been the most comparable exposure metric among the studies, inclusion of filtered atmospheres demonstrated that non-PM components dominated many effects.

References:

Barrett, E G., M.D. Reed, T. Espindola and R. Henson. 2002a. Diesel Exhaust Exposure in

Conjunction with Periodic Allergen Challenge Does Not Lead to Allergic Sensitization. Am. J. Respir. Crit. Care Med. 165: A303.

 

Barrett, E.G., M.D. Reed, T. Espindola and R. Henson. 2002b. Allergic Airway Responses Following Diesel Exhaust Exposure: Exacerbation vs. Attenuation. Am. J. Respir. Crit. Care Med. 165: A414.

Barrett, E.G., R.D. Henson, B. Welsh, S.K. Seilkop, J.D. McDonald, and M.D. Reed. 2006. Effects of Hardwood Smoke Exposure on Allergic Airway Inflammation in Mice. Inhal. Toxicol. 18: 33-43. 

Burchiel, S.W., F.T. Lauer, J.D. McDonald, and M.D. Reed. 2004. Systemic Immunotoxicity in AJ Mice following 6-Month Whole Body Inhalation Exposure to Diesel Exhaust. Toxicol. Appl. Pharmacol. 196: 337-345. 

Burchiel, S.W., F.T. Lauer, S.L. Dunaway, J. Zawadzki, J.D. McDonald, and M.D. Reed. 2005. Hardwood Smoke Alters Murine Splenic T Cell Responses to Mitogens Following a Six Month Whole Body Inhalation Exposure. Toxicol. Appl. Pharmacol. 202(3): 229-236. 

Campen, M.J., J.D. McDonald, A.P. Gigliotti, S.K. Seilkop, M.D. Reed, and J.M. Benson. 2003. Cardiovascular Effects of Inhaled Diesel Exhaust in Spontaneously Hypertensive Rats. Cardiovasc. Toxicol. 3(4): 353-361. 

Campen, M.J., J.D. McDonald, M.D. Reed, and JC. Seagrave. 2006. Fresh Gasoline Emissions, Not Paved Road Dust, Trigger Alterations in Cardiac Repolarization in ApoE-/- Mice. Cardiovasc. Toxicol. 6: 199-210. 

Day, K. C., M.D. Reed, J.D. McDonald, S.K. Seilkop, and E.G. Barrett. 2008. Effects of  Gasoline Emissions on Pre-Existing Allergic Airway Responses in Mice. Inhal. Toxicol. (in  press). 

Gilliland, F.D., K. Berhane, Y-F. Li, E.B. Rappaport, and J.M. Peters. 2003. Effects of Early Onset Asthma and In Utero Exposure to Maternal Smoking on Childhood Lung function. Am J. Respir. Crit. Care Med. 167: 917-924.  

Goksör, E., M. Amark, B. Alm, P. Gustafsson, and G. Wennergren. 2007. The Impact of Pre-and Post-Natal Smoke Exposure on future Asthma and Brochial Hyper-Responsiveness. Acta  Paediatr. 96: 1030-1035. 

Harrod, K.S., R.J. Jaramillo, C.L. Rosenberger, S.Z. Wang, J.A. Berger, and M.D. Reed. 2003. Increased Susceptibility to RSV Infection by Exposure to Inhaled Diesel Engine Emissions. Am. J. Respir. Cell Mol. Biol. 28: 451-463. 

Harrod, K.S., R.J. Jaramillo, J.A. Berger, A.P. Gigliotti, S.K. Seilkop, and M.D. Reed. 2005.  Inhaled Diesel Engine Emissions Reduce Bacterial Clearance and Exacerbate Lung Disease to  Pseudomonas aeruginosa Infection. Toxicol. Sci. 83: 155-165. 

Kiers, H.A.L., J.M.F. ten Berge, and R. Bro. 1999. PARAFAC2 - Part I. A direct fitting algorithm for the PARAFAC2 model. J. Chemom. 13: 275-294. 

Lund , A.K., T.L. Knuckles, C.O. Akata, R. Shohet, J.D. McDonald, A. Gigliotti, JC. Seagrave, and M.J. Campen. 2007. Gasoline Exhaust Emissions Induce Vascular Remodeling Pathways Involved in Atherosclerosis. Toxicol. Sci. 95: 485-494. 

Lund , A.K., J. Lucero, S. Lucas, M.C. Madden, J.D. McDonald, J. Seagrave, T.L. Knuckles, and M.J. Campen. 2008. Vehicular Emissions Induce Vascular MMP-9 Expression and Activity via Endothelin-1 Mediated Pathways. Arterio. Thrombosis Vasc. Biol. (submitted). 

Malinowski, E.R. 2002. Factor Analysis in Chemistry, Third Edition. John Wiley & Sons, New  York , 414 pp. Mauderly, J.L. 2003. Health Effects of Air Pollution: The Struggle for Context. Environmental Progress 22(3): 2-4. 

Mauderly, J.L. 2004. Health Effects of Complex Mixtures: Where Are We and Where Do We  Need to Be? In: Effects of Air Contaminants on the Respiratory Tract – Interpretations from  Molecules to Meta Analysis, INIS Monographs, Fraunhofer IRB Verlag, pp. 43-52. 

Mauderly, J.L., J.D. McDonald, JC. Seagrave, S.K. Seilkop, and E.J. Bedrick. 2007. Effect of Chemical and biological composition on the In Vitro Toxicity of Fine and Coarse Respirable  Paved Road Dust. Am. J. Respir. Crit. Care. Med. 175 (abstract issue):A174. 

Mauderly, J.L., and J.M. Samet. 2008. Is There Evidence for Synergy Among Air Pollutants in Causing Health Effects? Environ. Health Perspect. (in press). 

Mauderly, J L., R. Burnett, M. Castillejos, H. Ozkaynak, J. Samet, D. Stieb, S. Vedal, and R.  Wyzga. 2008a. Health Assessment Aspects of Multipollutant, Results-Based Air Quality  Management. Chapter 4 in: Technical Challenges of Applying Accountability-Based Air Quality Management Within a Multipollutant Framework, J. Brook, K. Demerjian, G. Hidy, and R. Scheffe, Eds. NARSTO, Pasco . WA, (submitted). 

Mauderly, J.L., E.G. Barrett, M.J. Campen, A.P. Gigliotti, J.D. McDonald, J. Seagrave, M.D.  Reed, and S.K. Seilkop. 2008b. Comparative Effects of Subchronic Inhalation Exposure of   Rodents to Diesel and Gasoline Engine Emissions, Hardwood Smoke, and Simulated Downwind  Coal Emissions. The Toxicologist 102 (1): 221 (abstract 1071). 

McDonald, J.D., I. Eide, JC. Seagrave, B. Zielinska, K. Whitney, D.R. Lawson, and J.L.  Mauderly. 2004a. Relationship Between Composition and Toxicity of Engine Emission Samples. Environ. Health Perspect. 112: 1527-1538. 

McDonald, J.D., E.B. Barr, R.K. White, J.C. Chow, J.J. Schauer, B. Zielinska, and E. Grosjean. 2004b. Generation and Characterization of Four Dilutions of Diesel Engine Exhaust for a  Subchronic Inhalation Study. Environ. Sci. Technol. 38(9): 2513-2522. 

McDonald, J. D. and J. Costanzo. 2006a. Particle Size and Organic Phase Distribution of Four  Dilutions of Diesel Engine Emissions. Atmospheric Environ. (in press). 

McDonald, J.D., R.K. White, E.B. Barr, B. Zielinska, J.C. Chow, and E. Grosjean. 2006b.  Generation and Characterization of Hardwood Smoke Inhalation Exposure Atmospheres.  Aerosol. Sci. Technol. 40: 573-584. 

McDonald, J.D., E.B. Barr, R. K. White, D. Kracko, J.C. Chow, B. Zielinska, and E. Grosjean. 2008. Generation and Characterization of Gasoline Engine Exhaust Inhalation Exposure Atmospheres. Inhal. Toxicol. (in press). 

Mitchell, L. A., J. Gao, R. V. Wal, A. Gigliotti, S. W. Burchiel, and J. D. McDonald. 2007.  Pulmonary and systemic immune responses to Inhaled Multiwalled Carbon Nanotubes. Toxicol. Sci. 100: 203-214. 

NRC (National Research Council). 2004a. Air Quality Management in the United States.  National Academies Press, Washington, D.C. NRC (National Research Council). 2004b. Research Priorities for Airborne Particulate Matter  IV. Continuing Research Progress. National Academy Press, Washington, D. C Reed, M.D., A.P. Gigliotti, J.D. McDonald, JC Seagrave, S.K. Seilkop, and J.L. Mauderly. 2004. Health Effects of Subchronic Exposure to Environmental Levels of Diesel Exhaust. Inhal. Toxicol. 16: 177-193. 

Reed, M.D. and J.A. Berger. 2006a. Real Time RT-PCR Assessment of Clearance of Respiratory Syncytial Virus Altered by Exposure to Diesel Exhaust and Hardwood Smoke. The Toxicologist 90: 232 (abstract). 

Reed, M.D., M.J. Campen, A.P. Gigliotti, K.S. Harrod, J.D. McDonald, JC. Seagrave, S.K.   Seilkop, and J.L. Mauderly. 2006b. Health Effects of Subchronic Exposure to Environmental  Levels of Hardwood Smoke. Inhal. Toxicol. 18: 523-539. 

Reed, M.D., E.G. Barrett, M.J. Campen, K.K. Divine, A.P. Gigliotti, J.D. McDonald, JC.   Seagrave, S.K. Seilkop, J.A. Swenberg, and J.L. Mauderly. 2008. Health Effects of Subchronic Inhalation Exposure to Gasoline Engine Emissions. Inhal. Toxicol. (in press).  

Seagrave, JC., A. Gigliotti, J.D. McDonald, S.K. Seilkop, K.A. Whitney, B. Zielinska, and J.L. Mauderly. 2005a. Composition, Toxicity, and Mutagenicity of Particulate and Semivolatile  Emissions from Heavy-Duty Compressed Natural Gas-Powered Vehicles. Toxicol. Sci. 87: 232

Seagrave, JC., J.D. McDonald , M.D. Reed, S.K. Seilkop, and J.L. Mauderly. 2005b. Responses to Subchronic Inhalation of Low Concentrations of Diesel Exhaust and Hardwood Smoke Measured in Rat Bronchoalveolar Lavage Fluid. Inhal. Toxicol. 17: 657-670.  

Seagrave, JC., J.D. McDonald, and J.L. Mauderly. 2005c. In Vitro versus In Vivo Exposure to Combustion Emissions. Exp. Toxicol. Pathol. 57: 233-238. 

Seagrave, JC., J.D. McDonald, E. Bedrick, E.S. Edgerton, A.P. Gigliotti, J.J. Jansen, L. Ke, L.P. Naeher, S.K. Seilkop, M. Zheng, and J.L. Mauderly. 2006. Lung Toxicity of Ambient Particulate Matter from Southeastern U.S. Cities with Different Contributing Sources: Relationships Between Composition and Effects. Environ. Health Perspect. 114: 1387-1394. 

Seagrave, JC., S. Dunaway, P. Hayden, J. D. McDonald, C. Stidley, and J. L. Mauderly. 2007. Responses of Differentiated Primary Human Lung Epithelial Cells to Exposure to Diesel Exhaust at an Air-Liquid Interface. Exper. Lung Res. 33:27-51. 

Singh, S.P., E.G. Barrett, R. Kalra, S. Rasani-Boroujerdi, R.J. Langley, V. Kurup, Y. Tesfaigzi, and M.L. Sopori. 2003. Prenatal Cigarette Smoke Decreases Lung cAMP and Increases Airway Hyperresponsiveness. Am. J. Respir. Crit. Care Med. 168: 342-347. 

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Tesfaigzi, Y., S.P. Singh, J.E. Foster, J. Kubatko, E.B. Barr, P.M. Fine, J.D. McDonald, F.F. Hahn, and J.L. Mauderly. 2002. Health Effects of Subchronic Exposure to Low Levels of Wood Smoke in Rats. Toxicol. Sci. 65: 115-125. 

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Journal Article Barrett EG, Rudolph K, Bowen LE, Muggenburg BA, Bice DE. Effect of inhaled ultrafine carbon particles on the allergic airway response in ragweed-sensitized dogs. Inhalation Toxicology 2003;15(2):151-165. CR831455 (Final)
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  • Journal Article Barrett EG, Henson RD, Seilkop SK, McDonald JD, Reed MD. Effects of hardwood smoke exposure on allergic airway inflammation in mice. Inhalation Toxicology 2006;18(1):33-43. CR831455 (2006)
    CR831455 (Final)
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  • Journal Article Burchiel SW, Lauer FT, McDonald JD, Reed MD. Systemic immunotoxicity in AJ mice following 6-month whole body inhalation exposure to diesel exhaust. Toxicology and Applied Pharmacology 2004;196(3):337-345. CR831455 (Final)
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  • Journal Article Burchiel SW, Lauer FT, Dunaway SL, Zawadzki J, McDonald JD, Reed MD. Hardwood smoke alters murine splenic T cell responses to mitogens following a 6-month whole body inhalation exposure. Toxicology and Applied Pharmacology 2005;202(3):229-236. CR831455 (2004)
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  • Journal Article Campen MJ, McDonald JD, Gigliotti AP, Seilkop SK, Reed MD, Benson JM. Cardiovascular effects of inhaled diesel exhaust in spontaneously hypertensive rats. Cardiovascular Toxicology 2003;3(4):353-361. CR831455 (Final)
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  • Journal Article Campen MJ, McDonald JD, Reed MD, Seagrave JC. Fresh gasoline emissions, not paved road dust, alter cardiac repolarization in ApoE-/- mice. Cardiovascular Toxicology 2006;6(3-4):199-209. CR831455 (Final)
    R830839 (2005)
    R830839 (Final)
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  • Journal Article Chow JC, Watson JG, Mauderly JL, Costa DL, Wyzga RE, Vedal S, Hidy GM, Altshuler SL, Marrack D, Heuss JM, Wolff GT, Pope III CA, Dockery DW. Health effects of fine particulate air pollution:lines that connect (critical review discussion). Journal of the Air & Waste Management Association 2006;56(10):1368-1380. CR831455 (Final)
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  • Journal Article Day KC, Reed MD, McDonald JD, Seilkop SK, Barrett EG. Effects of gasoline engine emissions on preexisting allergic airway responses in mice. Inhalation Toxicology 2008;20(13):1145-1155. CR831455 (Final)
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  • Journal Article Harrod KS, Jaramillo RJ, Rosenberger CL, Wang S-Z, Berger JA, McDonald JD, Reed MD. Increased susceptibility to RSV infection by exposure to inhaled diesel engine emissions. American Journal of Respiratory Cell and Molecular Biology 2003;28(4):451-463. CR831455 (Final)
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  • Journal Article Harrod KS, Jaramillo RJ, Berger JA, Gigliotti AP, Seilkop SK, Reed MD. Inhaled diesel engine emissions reduce bacterial clearance and exacerbate lung disease to Pseudomonas aeruginosa infection in vivo . Toxicological Sciences 2005;83(1):155-165. CR831455 (2004)
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  • Journal Article Lund AK, Knuckles TL, Akata CO, Shohet R, McDonald JD, Gigliotti A, Seagrave JC, Campen MJ. Gasoline exhaust emissions induce vascular remodeling pathways involved in atherosclerosis. Toxicological Sciences 2007;95(2):485-494. CR831455 (Final)
    R830839 (2005)
    R830839 (Final)
    R831860 (2007)
    R831860 (Final)
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  • Journal Article Lund AK, Lucero J, Lucas S, Madden MC, McDonald JD, Seagrave J-C, Knuckles TL, Campen MJ. Vehicular emissions induce vascular MMP-9 expression and activity associated with endothelin-1–mediated pathways. Arteriosclerosis, Thrombosis, and Vascular Biology 2009;29(4):511-517. CR831455 (Final)
    R830839 (2005)
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  • Journal Article March TH, Barr EB, Finch GL, Nikula KJ, Seagrave JC. Effects of concurrent ozone exposure on the pathogenesis of cigarette smoke-induced emphysema in B6C3F1 mice. Inhalation Toxicology 2002;14(12):1187-1213. CR831455 (Final)
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  • Journal Article Mauderly JL. An evolution of perspectives: summary of the Third Colloquium on Particulate Air Pollution and Human Health, Durham, North Carolina, June 6-8, 1999. Inhalation Toxicology 2000;12(Suppl 1):7-12. CR831455 (Final)
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  • Journal Article Mauderly JL. Animal models for the effect of age on susceptibility to inhaled particulate matter. Inhalation Toxicology 2000;12(9):863-900. CR831455 (Final)
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  • Journal Article Mauderly JL. Diesel emissions: is more health research still needed? Toxicological Sciences 2001;62(1):6-9. CR831455 (Final)
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  • Journal Article Mauderly JL. Health effects of air pollution: the struggle for context. Environmental Progress 2003;22(3):2-4. CR831455 (2004)
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  • Journal Article Mauderly JL. Health hazards of complex environmental exposures: a difficult challenge to inhalation toxicology. Inhalation Toxicology 2006;18(2):137-141. CR831455 (2006)
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  • Journal Article Mauderly JL, Chow JC. Health effects of organic aerosols. Inhalation Toxicology 2008;20(3):257-288. CR831455 (Final)
    R831086 (Final)
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  • Journal Article Mauderly JL, Samet JM. Is there evidence for synergy among air pollutants in causing health effects? Environmental Health Perspectives 2009;117(1):1-6. CR831455 (Final)
    R832417 (Final)
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  • Abstract from PubMed
  • Associated PubMed link
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  • Journal Article McDonald JD, Barr EB, White RK, Chow JC, Schauer JJ, Zielinska B, Grosjean E. Generation and characterization of four dilutions of diesel engine exhaust for a subchronic inhalation study. Environmental Science & Technology 2004;38(9):2513-2522. CR831455 (Final)
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  • Journal Article McDonald JD, White RK, Barr EB, Zielinska B, Chow JC, Grosjean E. Generation and characterization of hardwood smoke inhalation exposure atmospheres. Aerosol Science & Technology 2006;40(8):573-584. CR831455 (2006)
    CR831455 (Final)
  • Full-text: Taylor & Francis-Full Text HTML
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  • Abstract: Taylor & Francis-Abstract
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  • Journal Article McDonald JD, Barr EB, White RK, Kracko D, Chow JC, Zielinska B, Grosjean E. Generation and characterization of gasoline engine exhaust inhalation exposure atmospheres. Inhalation Toxicology 2008;20(13):1157-1168. CR831455 (Final)
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  • Abstract: Informa-Abstract
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  • Journal Article Muggenburg BA, Benson JM, Barr EB, Kubatko J, Tilley LP. Short-term inhalation of particulate transition metals has little effect on the electrocardiograms of dogs having preexisting cardiac abnormalities. Inhalation Toxicology 2003;15(4):357-371. CR831455 (Final)
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  • Abstract: Informa-Abstract
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  • Journal Article Redman TK, Rudolph K, Barr EB, Bowen LE, Muggenburg BA, Bice DE. Pulmonary immunity to ragweed in a Beagle dog model of allergic asthma. Experimental Lung Research 2001;27(5):433-451. CR831455 (Final)
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  • Abstract: Informa-Abstract
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  • Journal Article Reed MD, Gigliotti AP, McDonald JD, Seagrave JC, Seilkop SK, Mauderly JL. Health effects of subchronic exposure to environmental levels of diesel exhaust. Inhalation Toxicology 2004;16(4):177-193. CR831455 (Final)
  • Abstract from PubMed
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  • Abstract: Informa-Abstract
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  • Journal Article Reed MD, Campen MJ, Gigliotti AP, Harrod KS, McDonald JD, Seagrave JC, Mauderly JL, Seilkop SK. Health effects of subchronic exposure to environmental levels of hardwood smoke. Inhalation Toxicology 2006;18(8):523-539. CR831455 (2006)
    CR831455 (Final)
  • Abstract from PubMed
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  • Abstract: Informa-Abstract
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  • Journal Article Reed MD, Barrett EG, Campen MJ, Divine KK, Gigliotti AP, McDonald JD, Seagrave JC, Mauderly JL, Seilkop SK, Swenberg JA. Health effects of subchronic inhalation exposure to gasoline engine exhaust. Inhalation Toxicology 2008;20(13):1125-1143. CR831455 (Final)
  • Abstract from PubMed
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  • Abstract: Informa-Abstract
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  • Journal Article Rowan III WH, Campen MJ, Wichers LB, Watkinson WP. Heart rate variability in rodents: uses and caveats in toxicological studies. Cardiovascular Toxicology 2007;7(1):28-51. CR831455 (Final)
    R830839 (2005)
    R830839 (Final)
  • Abstract from PubMed
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  • Journal Article Seagrave J, McDonald JD, Mauderly JL. In vitro versus in vivo exposure to combustion emissions. Experimental and Toxicologic Pathology 2005;57(Suppl 1):233-238. CR831455 (2006)
    CR831455 (Final)
  • Abstract from PubMed
  • Abstract: ScienceDirect-Abstract
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  • Journal Article Seagrave J, McDonald JD, Reed MD, Seilkop SK, Mauderly JL. Responses to subchronic inhalation of low concentrations of diesel exhaust and hardwood smoke measured in rat bronchoalveolar lavage fluid. Inhalation Toxicology 2005;17(12):657-670. CR831455 (2004)
    CR831455 (2006)
    CR831455 (Final)
  • Abstract from PubMed
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  • Journal Article Seagrave J, Dunaway S, McDonald JD, Mauderly JL, Hayden P, Stidley C. Responses of differentiated primary human lung epithelial cells to exposure to diesel exhaust at an air-liquid interface. Experimental Lung Research 2007;33(1):27-51. CR831455 (Final)
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  • Journal Article Seagrave J, Campen MJ, McDonald JD, Mauderly JL, Rohr AC. Oxidative stress, inflammation, and pulmonary function assessment in rats exposed to laboratory-generated pollutant mixtures. Journal of Toxicology and Environmental Health, Part A 2008;71(20):1352-1362. CR831455 (Final)
  • Abstract from PubMed
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  • Journal Article Seagrave J, Barr EB, March TH, Nikula KJ. Effects of cigarette smoke exposure and cessation on inflammatory cells and matrix metalloproteinase activity in mice. Experimental Lung Research 2004;30(1):1-15. CR831455 (Final)
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  • Journal Article Tesfaigzi Y, Singh SP, Foster JE, Kubatko J, Barr EB, Fine PM, McDonald JD, Hahn FF, Mauderly JL. Health effects of subchronic exposure to low levels of wood smoke in rats. Toxicological Sciences 2002;65(1):115-125. CR831455 (Final)
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  • Journal Article Tesfaigzi Y, McDonald JD, Reed MD, Singh SP, De Sanctis GT, Eynott PR, Hahn FF, Campen MJ, Mauderly JL. Low-level subchronic exposure to wood smoke exacerbates inflammatory responses in allergic rats. Toxicological Sciences 2005;88(2):505-513. CR831455 (2006)
    CR831455 (Final)
  • Abstract from PubMed
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  • Supplemental Keywords:

    RFA, Health, Scientific Discipline, Air, particulate matter, Environmental Chemistry, Health Risk Assessment, Epidemiology, Risk Assessments, Biology, copollutant exposures, fine particles, acute lung injury, airway epithelial cells, cardiopulmonary responses, epidemelogy, exposure, susceptible subpopulations, street dust, air pollution, endothelial function, diesel exhaust, chronic health effects, lung inflammation, oxidant gas, particulate exposure, human exposure, inhaled, Acute health effects, concentrated particulate matter, road dust, airborne urban contaminants

    Progress and Final Reports:

    Original Abstract
  • 2004 Progress Report
  • 2005
  • 2006 Progress Report
  • 2007