Systemic Translocation of Particulate Matter–Associated Metals Following a Single Intratracheal Instillation in Rats

• Published in: Toxicological sciences Vol. 98; no. 1; pp. 231 - 239
• Main Authors: Wallenborn, J. Grace, McGee, John K., Schladweiler, Mette C., Ledbetter, Allen D., Kodavanti, Urmila P.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.07.2007
• Subjects: Administration, Inhalation; Animals; bioavailability; cardiovascular injury; Intubation, Intratracheal; Male; metals; Metals - administration & dosage; Metals - metabolism; Metals - pharmacokinetics; particulate matter; Particulate Matter - administration & dosage; Particulate Matter - metabolism; Particulate Matter - pharmacokinetics; Rats; Rats, Inbred WKY; Solubility; Tissue Distribution; translocation; particulate matter; metals; translocation; cardiovascular injury; bioavailability
• ISSN: 1096-6080; 1096-0929
• DOI: 10.1093/toxsci/kfm088

Respirable ambient particulate matter (PM) exposure has been associated with an increased risk of cardiovascular disease. Direct translocation of PM-associated metals from the lungs into systemic circulation may be partly responsible. We measured elemental content of lungs, plasma, heart, and liver of healthy male WKY rats (12–15 weeks old) 4 or 24 h following a single intratracheal (IT) instillation of saline or 8.33 mg/kg of oil combustion PM (HP-12) containing a variety of transition metals with differing water and acid solubility. Tissues were digested with a combination of quaternary acid, amine, and nitric acid and analyzed using inductively coupled plasma-atomic emission spectroscopy. Lung levels of metals were lower at 24 h than at 4 h. Metals with high water solubility and relatively high concentration in HP-12 were increased in extrapulmonary organs. Water-soluble nonessential metals, like vanadium and nickel, were increased in plasma, hearts, and livers of exposed animals at both time points. Exposure-related small increases in essential metals, like zinc and manganese, were also noted in extrapulmonary tissues at both time points. Lead, with low water solubility but high acid solubility, was detected in liver only at 24-h postinstillation. Elements with low water or acid solubility, like silicon and aluminum, were not detected in extrapulmonary tissues despite decreased levels in the lung suggesting mucociliary clearance. We have shown that HP-12–associated metals translocate to systemic circulation and extrapulmonary organs following IT exposure. This translocation is dependent upon their relative levels and water solubility. Thus, following inhalation, PM-associated metals deposited in the lung may be released into systemic circulation at different rates depending on their water/acid solubility, thereby providing a means by which metals may elicit direct extrapulmonary effects.