Cardiopulmonary Responses of Intratracheally Instilled Tire Particles and Constituent Metal Components

National Research Council, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA.
Inhalation Toxicology (Impact Factor: 2.26). 03/2008; 20(5):473-84. DOI: 10.1080/08958370701858427
Source: PubMed


Tire and brake wear particles contain transition metals, and contribute to near-road PM. We hypothesized that acute cardiopulmonary injury from respirable tire particles (TP) will depend on the amount of soluble metals. Respirable fractions of two types of TP (TP1 and TP2) were analyzed for water and acid-leachable metals using ICP-AES. Both TP types contained a variety of transition metals, including zinc (Zn), copper (Cu), aluminum, and iron. Zn and Cu were detected at high levels in water-soluble fractions (TP2 > TP1). Male Wistar Kyoto rats (12-14 wk) were intratracheally instilled, in the first study, with saline, TP1 or TP2 (5 mg/kg), and in the second study, with soluble Zn, Cu (0.5 micromol/kg), or both. Pulmonary toxicity and cardiac mitochondrial enzymes were analyzed 1 d, 1 wk, or 4 wk later for TP and 4 or 24 h later for metals. Increases in lavage fluid markers of inflammation and injury were observed at d 1 (TP2 > TP1), but these changes reversed by wk 1. No effects on cardiac enzymes were noted with either TP. Exposure of rats to soluble Zn and Cu caused marked pulmonary inflammation and injury but temporal differences were apparent (Cu effects peaked at 4 h and Zn at 24 h). Instillation of Zn, Cu, and Zn + Cu decreased the activity of cardiac aconitase, isocitrate dehydrogenase, succinate dehydrogenase, cytochrome-c-oxidase and superoxide dismutase suggesting mitochondrial oxidative stress. The observed acute pulmonary toxicity of TP could be due to the presence of water soluble Zn and Cu. At high concentrations these metals may induce cardiac oxidative stress.

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    • "Tests were done with administered saline, the two tire dusts and soluble zinc, copper or both. At very high dose levels (5 mg/kg rat), the exposures induced cardiac oxidative stress (Gottipolu et al., 2008), which was associated with the water-soluble zinc and copper. Whilst it is unlikely that transition metals can explain all of the health effects observed in epidemiological studies at present ambient levels, these components remain a group of components for which reduction measures will most likely lead to improving the health status of the population. "
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    ABSTRACT: Abstract Particulate matter (PM) is regulated in various parts of the world based on specific size cut offs, often expressed as 10 or 2.5 µm mass median aerodynamic diameter. This pollutant is deemed one of the most dangerous to health and moreover, problems persist with high ambient concentrations. Continuing pressure to re-evaluate ambient air quality standards stems from research that not only has identified effects at low levels of PM but which also has revealed that reductions in certain components, sources and size fractions may best protect public health. Considerable amount of published information have emerged from toxicological research in recent years. Accumulating evidence has identified additional air quality metrics (e.g. black carbon, secondary organic and inorganic aerosols) that may be valuable in evaluating the health risks of, for example, primary combustion particles from traffic emissions, which are not fully taken into account with PM2.5 mass. Most of the evidence accumulated so far is for an adverse effect on health of carbonaceous material from traffic. Traffic-generated dust, including road, brake and tire wear, also contribute to the adverse effects on health. Exposure durations from a few minutes up to a year have been linked with adverse effects. The new evidence collected supports the scientific conclusions of the World Health Organization Air Quality Guidelines and also provides scientific arguments for taking decisive actions to improve air quality and reduce the global burden of disease associated with air pollution.
    Inhalation Toxicology 12/2013; 25(14):802-12. DOI:10.3109/08958378.2013.850127 · 2.26 Impact Factor
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    • "Many of these components are known to have significant toxicity, though they were thought mainly to be associated with larger particles. This is particularly true of redox active metals, such as Fe and Al, which have been shown to be associated with oxidative damage in a number of studies (Ohyama et al., 2007; Gottipolu et al., 2008; Castro-Giner et al., 2009; Shinyashiki et al., 2009; Verma et al., 2009). Several studies have investigated the components of near-roadway exposures using other metrics – such as BC, CO, and NOx – as proxy measurements for exposure near roadways, but to date, these associations have not been consistently strong. "
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    ABSTRACT: We describe spatial and temporal patterns of seven chemical elements commonly observed in fine particulate matter (PM) and thought to be linked to roadway emissions that were measured at residential locations in New York City (NYC). These elements, that is, Si, Al, Ti, Fe, Ba, Br, and black carbon (BC), were found to have significant spatial and temporal variability at our 10 residential PM(2.5) sampling locations. We also describe pilot study data of near-roadway samples of both PM(10-2.5) and PM(2.5) chemical elements of roadway emissions. PM(2.5) element concentrations collected on the George Washington Bridge (GWB) connecting NYC and New Jersey were higher that similar elemental concentration measured at residential locations. Coarse-particle elements (within PM(10-2.5)) on the GWB were 10-100 times higher in concentration than their PM(2.5) counterparts. Roadway elements were well correlated with one another in both the PM(2.5) and PM(10-2.5) fractions, suggesting common sources. The same elements in the PM(2.5) collected at residential locations were less correlated, suggesting either different sources or different processing mechanisms for each element. Despite the fact that these elements are only a fraction of total PM(2.5) or PM(10-2.5) mass, the results have important implications for near-roadway exposures where elements with known causal links to health effects are shown to be at elevated concentrations in both the PM(2.5) and PM(10-2.5) size ranges.
    Journal of Exposure Science and Environmental Epidemiology 04/2011; 21(5):484-94. DOI:10.1038/jes.2011.15 · 3.19 Impact Factor
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    • "Our findings build upon results obtained on the effects of this material on an in vitro cell line (Camatini et al., 2003, Gualtieri et al., 2005c; Beretta et al., 2007) and of the eluates obtained from similar material on non mammalian in vivo systems (Gualtieri et al, 2005a,b; Mantecca et al., 2007). To our knowledge, except for the paper of Gottipolu et al. (2008), the current study represents the first in vivo evidence of the impact of TPs -which comprise 5-7% of ambient PM 10 -on the mammalian respiratory system. "
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    ABSTRACT: Tire particles (TP) represent a significant component of urban air pollution (PM), constituting more than 10% of PM10 mass at urban locations with heavy traffic. The purpose of this study was to evaluate the effects of size-fractionated TP in an animal exposure model frequently used to assess the health effects of air pollutants. Potential pro-inflammatory and toxic effects of TP2.5 (<2.5 microm) and TP10 (<10 microm) were investigated through instillation of suspensions of these materials in BALB/c mice. Bronchoalveolar lavage fluid (BALF) was screened for total protein, lactate dehydrogenase (LDH), alkaline phosphatase (AP), and beta-glucuronidase (B-Gluc) as markers of cytotoxicity; glutathione (GSH) and superoxide dismutase (SOD) as markers of oxidative potential; and tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2), and inflammatory cells as markers of inflammation. Concomitantly, histological analysis of TP-exposed lungs was performed. A single intratracheal instillation of 10 microg/100 microl, 100 microg/100 microl or 200 microg/100 microl was performed, and after 24h mice were euthanized and BALF examined. Inflammatory cellular profiles showed dose-dependent responses after TP10 exposure, while strong cytotoxic effects, including increases in total protein, LDH and AP, were observed to be associated to TP2.5 exposure. Histologically, TP10-treated lungs mainly showed inflammatory tissue infiltration, in contrast to TP2.5-treated lungs, where lysis of the alveolar barrier appeared to be the most characteristic lesion. Our biochemical, cytological, and histological results indicated differential lung toxicity mechanisms elicited by size-fractionated TP, in agreement with other studies performed in in vivo systems that have shown that lung responses to inhaled or instilled particles are affected by particle size. We conclude that lung toxicity induced by TP10 was primarily due to macrophage-mediated inflammatory events, while toxicity induced by TP2.5 appeared to be related more closely to cytotoxicity.
    Toxicology Letters 06/2009; 189(3):206-14. DOI:10.1016/j.toxlet.2009.05.023 · 3.26 Impact Factor
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