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Inhalation Toxicology
International Forum for Respiratory Research
Volume 26, 2014 - Issue 11
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Research Article

The National Environmental Respiratory Center (NERC) experiment in multi-pollutant air quality health research: II. Comparison of responses to diesel and gasoline engine exhausts, hardwood smoke and simulated downwind coal emissions

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Pages 651-667 | Received 08 Apr 2014, Accepted 14 May 2014, Published online: 27 Aug 2014
 

Abstract

The NERC Program conducted identically designed exposure–response studies of the respiratory and cardiovascular responses of rodents exposed by inhalation for up to 6 months to diesel and gasoline exhausts (DE, GE), wood smoke (WS) and simulated downwind coal emissions (CE). Concentrations of the four combustion-derived mixtures ranged from near upper bound plausible to common occupational and environmental hotspot levels. An “exposure effect” statistic was created to compare the strengths of exposure–response relationships and adjustments were made to minimize false positives among the large number of comparisons. All four exposures caused statistically significant effects. No exposure caused overt illness, neutrophilic lung inflammation, increased circulating micronuclei or histopathology of major organs visible by light microscopy. DE and GE caused the greatest lung cytotoxicity. WS elicited the most responses in lung lavage fluid. All exposures reduced oxidant production by unstimulated alveolar macrophages, but only GE suppressed stimulated macrophages. Only DE retarded clearance of bacteria from the lung. DE before antigen challenge suppressed responses of allergic mice. CE tended to amplify allergic responses regardless of exposure order. GE and DE induced oxidant stress and pro-atherosclerotic responses in aorta; WS and CE had no such effects. No overall ranking of toxicity was plausible. The ranking of exposures by number of significant responses varied among the response models, with each of the four causing the most responses for at least one model. Each exposure could also be deemed most or least toxic depending on the exposure metric used for comparison. The database is available for additional analyses.

Acknowledgements

The authors thank the NERC External Scientific Advisory Committee (www.nercenter.org) for their participation in conceiving the NERC Program strategy and their continuing guidance during the conduct of this research. The authors also thank the many members of the LRRI technical staff who constructed and operated the exposure systems, cared for the animals, conducted the measurements and managed the data.

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