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SYSTEMIC TRANSLOCATION OF PARTICULATE MATTER (PM)-ASSOCIATED METALS FOLLOWING A SINGLE INTRATRACHEAL (IT) INSTILLATION IN WKY RATS
Citation:
WALLENBORN, G., J. K. MCGEE, M. SCHLADWEILER, A. D. LEDBETTER, AND U. P. KODAVANTI. SYSTEMIC TRANSLOCATION OF PARTICULATE MATTER (PM)-ASSOCIATED METALS FOLLOWING A SINGLE INTRATRACHEAL (IT) INSTILLATION IN WKY RATS. Presented at Society of Toxicology Annual Meeting, Charlotte, NC, March 25 - 29, 2007.
Description:
Ambient PM contains transition metals with differing water solubilities. Epidemiological studies show a link between PM exposure and an increased risk of cardiovascular disease. Direct translocation of PM-associated metals from the lung into systemic circulation may be partly responsible for this. We measured levels of various metals in lung, plasma, heart and liver of healthy male WKY rats (12-15 wks old) 4 and 24 h after a single IT instillation of saline or oil combustion PM (8.33 mg/kg). IT instillation was used to control for pulmonary deposited dose and nasal absorption. The selected PM contains moderate levels of metals including zinc, vanadium, nickel, aluminum, silica, iron, copper, manganese and lead, each with differing water and acid solubility. Tissues were digested in acid and analyzed for elemental content using Inductively Coupled Plasma-Atomic Emission Spectroscopy. Most PM-associated metals were detected in the lung at both time points, with lower concentrations at 24 h than at 4 h. Both essential and nonessential metals with high water solubility were translocated into extrapulmonary organs. Detection of PM-associated vanadium and nickel in plasma, heart and liver at both time points demonstrates soluble metal translocation following pulmonary exposure. Increased levels of zinc and manganese were also observed in plasma and other organs. Metals with low water solubility were not detected in extrapulmonary tissues despite their decreased level in the lung, suggesting mucociliary clearance. We have demonstrated that PM-associated water soluble metals are rapidly translocated to systemic circulation and extrapulmonary organs following an acute IT instillation, likely via vascular absorption. This process is dependent on the relative water solubility of metals. Inhalation of metal rich PM may elicit a direct effect on pulmonary and extrapulmonary organs. (Abstract does not represent USEPA policy. This research was supported in part by UNC/EPA CT829471.)