title: Variable pulmonary responses from exposure to concentrated ambient air particles in a rat model of bronchitis.
abstract: Chronic bronchitis may be considered a risk factor in particulate matter (PM)-induced morbidity. We hypothesized that a rat model of human bronchitis would be more susceptible to the pulmonary effects of concentrated ambient particles (CAPs) from Research Triangle Park, NC. Bronchitis was induced in male Sprague-Dawley rats (90-100 days of age) by exposure to 200 ppm sulfur dioxide (SO2), 6 h/day x 5 days/week x 6 weeks. One day following the last SO2 exposure, both healthy (air-exposed) and bronchitic (SO2-exposed) rats were exposed to filtered air (three healthy; four bronchitic) or CAPs (five healthy; four bronchitic) by whole-body inhalation, 6 h/day x 2 or 3 days. Pulmonary injury was determined either immediately (0h) or 18 h following final CAPs exposure. The study protocol involving 0 h time point was repeated four times (study #A, November, 1997; #B, February, 1998; #C and #D, May, 1998), whereas the study protocol involving 18 h time point was done only once (#F). In an additional study (#E), rats were exposed to residual oil fly ash (ROFA), approximately 1 mg/ m(3)x6 h/day x 3 days to mimic the CAPs protocol (February, 1998). The rats allowed 18 h recovery following CAPs exposure (#F) did not depict any CAPs-related differences in bronchoalveolar lavage fluid (BALF) injury markers. Of the four CAPs studies conducted (0 h time point), the first (#A) study (approximately 650 microg/m3 CAPs) revealed significant changes in the lungs of CAPs-exposed bronchitic rats compared to the clean air controls. These rats had increased BALF protein, albumin, N-acetyl glutaminidase (NAG) activity and neutrophils. The second (#B) study (approximately 475 microg/m3 CAPs) did not reveal any significant effects of CAPs on BALF parameters. Study protocols #C (approximately 869 microg/m3 CAPs) and #D (approximately 907 microg/m3 CAPs) revealed only moderate increases in the above mentioned BALF parameters in bronchitic rats exposed to CAPs. Pulmonary histologic evaluation of studies #A, #C, #D, and #F revealed marginally higher congestion and perivascular cellularity in CAPs-exposed bronchitic rats. Healthy and bronchitic rats exposed to ROFA (approximately 1 mg/m3) did not show significant pulmonary injury (#E). Analysis of leachable elemental components of CAPs revealed the presence of sulfur, zinc, manganese, and iron. There was an apparent lack of association between pulmonary injury and CAPs concentration, or its leachable sulfate or elemental content. In summary, real-time atmospheric PM may result in pulmonary injury, particularly in susceptible models. However, the variability observed in pulmonary responses to CAPs emphasizes the need to conduct repeated studies, perhaps in relation to the season, as composition of CAPs may vary. Additionally, potential variability in pathology of induced bronchitis or other lung disease may decrease the ability to distinguish toxic injury due to PM.
authors.affiliation: Pulmonary Toxicology Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina, USA. kodavanti.urmila@epa.gov
authors.forename: U P
authors.initials: UP
authors.lastname: Kodavanti
authors.forename: R
authors.initials: R
authors.lastname: Mebane
authors.forename: A
authors.initials: A
authors.lastname: Ledbetter
authors.forename: T
authors.initials: T
authors.lastname: Krantz
authors.forename: J
authors.initials: J
authors.lastname: McGee
authors.forename: M C
authors.initials: MC
authors.lastname: Jackson
authors.forename: L
authors.initials: L
authors.lastname: Walsh
authors.forename: H
authors.initials: H
authors.lastname: Hilliard
authors.forename: B Y
authors.initials: BY
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Richards
authors.forename: D L
authors.initials: DL
authors.lastname: Costa
mesh_terms: D000118:Acetylglucosaminidase / Q000032:analysis; D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D000418:Albumins / Q000032:analysis; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001991:Bronchitis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002244:Carbon / Q000633:toxicity; D060729:Coal Ash; D004195:Disease Models, Animal; D007220:Industrial Waste; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D052638:Particulate Matter; D051381:Rats; D017207:Rats, Sprague-Dawley; D013458:Sulfur Dioxide / Q000633:toxicity
chemical_list: D000393:Air Pollutants; D000418:Albumins; D015415:Biomarkers; D060729:Coal Ash; D007220:Industrial Waste; D052638:Particulate Matter; D013458:Sulfur Dioxide; D002244:Carbon; D007770:L-Lactate Dehydrogenase; C033079:alpha-N-acetyl-D-glucosaminidase; D000118:Acetylglucosaminidase