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Cardiopulmonary toxicity of peat wildfire particulate matter and the predictive utility of precision cut lung slices
Kim, Y., H. Tong, E. Boykin, Todd Krantz, J. Mcgee, M. Hays, K. Kovalcik, J. Dye, AND I. Gilmour. Cardiopulmonary toxicity of peat wildfire particulate matter and the predictive utility of precision cut lung slices. Particle and Fibre Toxicology. BioMed Central Ltd, London, Uk, 11:29, (2014).
Background: Emissions from a large peat fire in North Carolina were associated with increased hospital admissions for asthma and the rate of heart failure in the exposed population. Peat fires often produce larger amounts of smoke and last longer than forest fires, however few studies have reported on their toxicity. Moreover, reliable alternatives to traditional animal toxicity testing are needed to reduce the number of animals required for hazard identification and risk assessments. Methods: Size-fractionated particulate matter (PM; ultrafine, fine, and coarse) were obtained from a peat fire in Eastern North Carolina in the summer of 2008 when the fire was smoldering (ENCF-1), or when the fire was almost extinguished (ENCF-4). The PM samples were extracted, analyzed for a suite of elements, ions and carbon speciation, and then instilled into female CD-1 mice at 100 µg. Additional samples were cultured with mouse lung slices at a dose of 11 µg/slice. At 4 h and 24 h post-exposure, biomarkers of lung injury and inflammation were assessed in bronchoalveolar lavage fluids from mice, and in the conditioned medium from the lung slices. Lung slices were also exposed to PM pre-treated with an endotoxin inhibitor (polymyxin B). Results: Minimal effects were seen with any of the fine or ultrafine particles from either sampling period. The coarse PM had greater endotoxin content than the smaller size fractions and both fractions increased neutrophil numbers at 4 h, and more substantially at 24 h. Cytokine responses were also higher in the coarse PM at 4 h but then diminished by 24 h. Responses were generally greater in the ENCF-1 sample compared to those seen with the ENCF-4 sample. A similar pattern of cytokine production was seen in the lung slice system and pre-treatment with polymyxin B significantly attenuated this response. Conclusions: The findings suggest that exposure to peat fire coarse PM caused inflammatory effects in the mouse lung in association with endotoxin content while the fine and ultrafine samples had little to no effect. The lung tissue slices were shown to be a predictive, alternative assay platform to in vivo lung toxicity tests.
Identifies components of a wildfire PM that cause health effects.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
ENVIRONMENTAL PUBLIC HEALTH DIVISION
CARDIOPULMONARY AND IMMUNOTOXICOLOGY BRANCH