Metals in PM associated with Cardiac Toxicity

BrooklynDodger(s) comment: Risk assessments for particulate exposure in the workplace, and also community, typically ignore cardiac effects. Cohort studies in workplace populations are typically null for associations with chemical exposure, probably resulting from the healthy worker effect. This endpoint needs more work. Good to see EPA in the science game.

Toxicology and Applied Pharmacology
Volume 241, Issue 1, 15 November 2009, Pages 71-80

Differential pulmonary and cardiac effects of pulmonary exposure to a panel of particulate matter-associated metals

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J. Grace Wallenborn^{a, ,} , Mette J. Schladweiler^b, , Judy H. Richards^b, and Urmila P. Kodavanti^b,

^aDepartment of Environmental Sciences and Engineering, UNC School of Public Health, Chapel Hill, NC 27599, USA

^bPulmonary Toxicology Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, ORD, Environmental Protection Agency, Durham, NC 27711, USA

Received 28 May 2009;

revised 29 July 2009;

accepted 3 August 2009.

Available online 11 August 2009.

Abstract

Biological mechanisms underlying the association between particulate matter (PM) exposure and increased cardiovascular health effects are under investigation. Water-soluble metals reaching systemic circulation following pulmonary exposure are likely exerting a direct effect. However, it is unclear whether specific PM-associated metals may be driving this. We hypothesized that exposure to equimolar amounts of five individual PM-associated metals would cause differential pulmonary and cardiac effects. We exposed male WKY rats (14 weeks old) via a single intratracheal instillation (IT) to saline or 1 μmol/kg body weight of zinc, nickel, vanadium, copper, or iron in sulfate form. Responses were analyzed 4, 24, 48, or 96 h after exposure. Pulmonary effects were assessed by bronchoalveolar lavage fluid levels of total cells, macrophages, neutrophils, protein, albumin, and activities of lactate dehydrogenase, γ-glutamyl transferase, and n-acetyl glucosaminidase. Copper induced earlier pulmonary injury/inflammation, while zinc and nickel produced later effects. Vanadium or iron exposure induced minimal pulmonary injury/inflammation. Zinc, nickel, or copper increased serum cholesterol, red blood cells, and white blood cells at different time points. IT of nickel and copper increased expression of metallothionein-1 (MT-1) in the lung. Zinc, nickel, vanadium, and iron increased hepatic MT-1 expression. No significant changes in zinc transporter-1 (ZnT-1) expression were noted in the lung or liver; however, zinc increased cardiac ZnT-1 at 24 h, indicating a possible zinc-specific cardiac effect. Nickel exposure induced an increase in cardiac ferritin 96 h after IT. This data set demonstrating metal-specific cardiotoxicity is important in linking metal-enriched anthropogenic PM sources with adverse health effects.