title: Consistent pulmonary and systemic responses from inhalation of fine concentrated ambient particles: roles of rat strains used and physicochemical properties.
abstract: Several studies have reported health effects of concentrated ambient particles (CAP) in rodents and humans; however, toxicity end points in rodents have provided inconsistent results. In 2000 we conducted six 1-day exposure studies where spontaneously hypertensive (SH) rats were exposed to filtered air or CAPs (< or = 2.5 microm, 1,138-1,765 microg/m3) for 4 hr (analyzed 1-3 hr afterward). In seven 2-day exposure studies in 2001, SH and Wistar Kyoto (WKY) rats were exposed to filtered air or CAP (< or = 2.5 microm, 144-2,758 microg/m3) for 4 hr/day times 2 days (analyzed 1 day afterward). Despite consistent and high CAP concentrations in the 1-day exposure studies, no biologic effects were noted. The exposure concentrations varied among the seven 2-day exposure studies. Except in the first study when CAP concentration was highest, lavageable total cells and macrophages decreased and neutrophils increased in WKY rats. SH rats demonstrated a consistent increase of lavage fluid gamma-glutamyltransferase activity and plasma fibrinogen. Inspiratory and expiratory times increased in SH but not in WKY rats. Significant correlations were found between CAP mass (microgram per cubic meter) and sulfate, organic carbon, or zinc. No biologic effects correlated with CAP mass. Despite low chamber mass in the last six of seven 2-day exposure studies, the levels of zinc, copper, and aluminum were enriched severalfold, and organic carbon was increased to some extent when expressed per milligram of CAP. Biologic effects were evident in those six studies. These studies demonstrate a pattern of rat strain-specific pulmonary and systemic effects that are not linked to high mass but appear to be dependent on CAP chemical composition.
authors.affiliation: Pulmonary Toxicology Branch, Experimental Toxicology Division, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. Kodavanti.urmila@epa.gov
authors.forename: Urmila P
authors.initials: UP
authors.lastname: Kodavanti
authors.forename: Mette C
authors.initials: MC
authors.lastname: Schladweiler
authors.forename: Allen D
authors.initials: AD
authors.lastname: Ledbetter
authors.forename: John K
authors.initials: JK
authors.lastname: McGee
authors.forename: Leon
authors.initials: L
authors.lastname: Walsh
authors.forename: Peter S
authors.initials: PS
authors.lastname: Gilmour
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Highfill
authors.forename: David
authors.initials: D
authors.lastname: Davies
authors.forename: Kent E
authors.initials: KE
authors.lastname: Pinkerton
authors.forename: Judy H
authors.initials: JH
authors.lastname: Richards
authors.forename: Kay
authors.initials: K
authors.lastname: Crissman
authors.forename: Debora
authors.initials: D
authors.lastname: Andrews
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Costa
mesh_terms: D000393:Air Pollutants / Q000032:analysis / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002244:Carbon / Q000032:analysis; D004391:Dust / Q000032:analysis; D005340:Fibrinogen / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D008670:Metals / Q000032:analysis; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D010316:Particle Size; D012123:Pulmonary Ventilation / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity; D013431:Sulfates / Q000032:analysis; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D004391:Dust; D008670:Metals; D013431:Sulfates; D002244:Carbon; D005340:Fibrinogen; D005723:gamma-Glutamyltransferase