ToxSci Advance Access published online on April 13, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm088
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Published by Oxford University Press 2007.
Systemic Translocation of Particulate Matter-Associated Metals Following a Single Intratracheal Instillation in Rats
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* Department of Environmental Sciences and Engineering, UNC School of Public Health, Chapel Hill, NC 27599, USA
Pulmonary Toxicology Branch, MD B143-01, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, ORD, Environmental Protection Agency, Research Triangle Park, NC 27711, USA
To whom correspondence should be addressed at Pulmonary Toxicology Branch, MD B143-01, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711. Phone: (919) 541-4963. Fax: (919) 541-0026. Email address: kodavanti.urmila{at}epa.gov
Received January 30, 2007; revision received April 6, 2007; accepted April 10, 2007
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Abstract |
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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 wks 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 post instillation. 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 intratracheal 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.
Key Words: particulate matter; cardiovascular injury; metals; translocation; bioavailability.
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