title: Soluble transition metals mediate residual oil fly ash induced acute lung injury.
abstract: Identification of constituents responsible for the pulmonary toxicity of fugitive combustion emission source particles may provide insight into the adverse health effects associated with exposure to these particles as well as ambient air particulate pollution. Herein, we describe results of studies conducted to identify constituents responsible for the acute lung injury induced by residual oil fly ash (ROFA) and to assess physical-chemical factors that influence the pulmonary toxicity of these constituents. Biochemical and cellular analyses performed on bronchoalveolar lavage fluid obtained from rats following intratracheal instillation of ROFA suspension demonstrated the presence of severe inflammation, an indicator of pulmonary injury, which included recruitment of neutrophils, eosinophils, and monocytes into the airway. A leachate prepared from ROFA, containing predominantly Fe, Ni, V, Ca, Mg, and sulfate, produced similar lung injury to that induced by ROFA suspension. Depletion of Fe, Ni, and V from the ROFA leachate abrogated its pulmonary toxicity. Correspondingly, minimal lung injury was observed in animals exposed to saline-washed ROFA particles. A surrogate transition metal sulfate solution containing Fe, V, and Ni largely reproduced the lung injury induced by ROFA. Metal interactions and pH were found to influence the severity and kinetics of lung injury induced by ROFA and soluble transition metals. These findings provide direct evidence for the role of soluble transition metals in the pulmonary injury induced by the combustion emission source particulate, ROFA.
authors.affiliation: Experimental Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. Dreher@herl45.herl.epa.gov
authors.forename: K L
authors.initials: KL
authors.lastname: Dreher
authors.forename: R H
authors.initials: RH
authors.lastname: Jaskot
authors.forename: J R
authors.initials: JR
authors.lastname: Lehmann
authors.forename: J H
authors.initials: JH
authors.lastname: Richards
authors.forename: J K
authors.initials: JK
authors.lastname: McGee
authors.forename: A J
authors.initials: AJ
authors.lastname: Ghio
authors.forename: D L
authors.initials: DL
authors.lastname: Costa
mesh_terms: D000208:Acute Disease; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D002244:Carbon / Q000633:toxicity*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005648:Fuel Oils / Q000633:toxicity*; D007249:Inflammation / Q000139:chemically induced; D008171:Lung Diseases / Q000139:chemically induced*; D008297:Male; D008670:Metals / Q000633:toxicity*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013431:Sulfates / Q000633:toxicity
chemical_list: D000393:Air Pollutants; D005648:Fuel Oils; D008670:Metals; D013431:Sulfates; D002244:Carbon