Grantee Research Project Results
Final Report: Assessing Toxicity of Local and Transported Particles Using Animal Models Exposed to CAPs
EPA Grant Number: R832416C003Subproject: this is subproject number 003 , established and managed by the Center Director under grant R832416
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Health Effects Institute (2015 - 2020)
Center Director: Greenbaum, Daniel S.
Title: Assessing Toxicity of Local and Transported Particles Using Animal Models Exposed to CAPs
Investigators: Godleski, John J. , Koutrakis, Petros
Institution: Harvard University
EPA Project Officer: Chung, Serena
Project Period: October 1, 2005 through September 30, 2010 (Extended to September 30, 2011)
RFA: Particulate Matter Research Centers (2004) RFA Text | Recipients Lists
Research Category: Human Health , Air
Objective:
The main objective of this project was to differentiate the toxicological effects of locally emitted and transported particles. Toward this end short-term 5-hour animal exposures to concentrated ambient fine particles (CAPs) were conducted during the time periods of 5:00 -10:00 am and 10:30 am-3:30 pm. Starting the early morning inhalation exposures at 5 am, before significant vertical mixing takes place, captured particles predominantly from local sources. This exposure interval coincides with the highest density morning commuter traffic. The mid-day exposures, which started about 10:30 am and ended prior to the evening rush hour, were relatively more enriched in transported particles. Specific biologic outcomes investigated in this study included: breathing patterns, indicators of pulmonary and systemic inflammation, and in vivo oxidant responses in the heart and lung. We also monitored blood pressure and heart rate over repeated exposures. These exposures were conducted using normal male Sprague-Dawley (SD) rats, which we have used in many previous CAPs studies.
The second objective of this project was to determine whether spontaneously hypertensive rats, a genetically susceptible population, would have enhanced vascular responses to exposure to locally emitted and transported particles, as compared to normal rats. For this part of the study, we used Spontaneously Hypertensive Rats (SHR), a sensitive model in many studies, and Wistar Kyoto (WKY) the strain control for SHR rats.
To control for circadian variations during both morning and mid-day exposure periods, all outcomes were assessed in relation to those of filtered air (Sham) exposures. Animal exposures were characterized using continuous measurements of particle mass, number, and black carbon. Integrated measurements of particle mass, sulfate, elements, and elemental and organic carbon also were made.
Summary/Accomplishments (Outputs/Outcomes):
Findings of the Research Project
Exposure Characterization. The early morning and mid-day CAPs mass and composition for all early and mid-day exposures are shown in Table 1 below. Overall, CAPs mass concentrations for both the early morning and mid-day exposure periods were slightly higher than previously published CAPs exposure studies from our laboratory. The average CAPs mass concentrations in the early morning and mid-day exposures were not significantly different from each other using a paired two-tailed t-test. There were some modest, but statistically significant, differences in composition between the early and mid-day CAPs. For example, elemental carbon was slightly but significantly higher in the early morning CAPs exposure than the mid-day exposure, supporting the premise that the early exposure was more influenced by local (primarily traffic) sources. In addition, iron, nickel, and copper levels also were significantly higher in the early morning. These differences were even more pronounced in the fractional composition (e.g., the ratio of a specific component to the total CAPs mass). The mid-day CAPs also had several components that were slightly but significantly greater in concentration (or fractional composition) than the morning CAPs, including sulfur, potassium, magnesium, manganese, and silicon. In general, these morning/mid-day CAPs differences were consistent through both the normal and SHR rat exposures, and for the short-term and repeated exposures.
| Measurement | Early Morning Mean ± SE | Mid-Day Mean ± SE | p value |
| CAPs Mass | 465.9 ± 42.9 | 425.6 ± 38.2 | 0.233 |
| *Elemental Carbon | 21.7 ± 2.1 | 16.8 ± 1.9 | 0.020 |
| Organic Carbon | 82.7 ± 6.6 | 83.6 ± 6.1 | 0.910 |
| Total Carbon | 104.4 ± 8.3 | 100.3 ± 7.6 | 0.652 |
| Sodium | 8.5 ± 2.6 | 9.2 ± 1.5 | 0.348 |
| *Magnesium | 1.12 ± 0.15 | 1.34 ± 0.15 | 0.015 |
| Aluminum | 3.3 ± 0.4 | 3.7 ± 0.4 | 0.251 |
| Silicon | 8.9 ± 0.9 | 9.8 ± 0.9 | 0.329 |
| Sulfur | 38.7 ± 5.5 | 44.3 ± 6.1 | 0.243 |
| Chlorine | 6.0 ± 1.8 | 8.3 ± 2.9 | 0.136 |
| Potassium | 2.7 ± 0.2 | 3.0 ± 0.2 | 0.167 |
| Calcium | 5.8 ± 0.7 | 5.9 ± 0.4 | 0.946 |
| Titanium | 0.43 ± 0.04 | 0.44 ± 0.05 | 0.713 |
| Vanadium | 0.25 ± 0.20 | 0.04 ± 0.01 | 0.280 |
| *Iron | 11.4 ± 1.1 | 9.3 ± 0.7 | 0.039 |
| Nickel | 0.07 ± 0.01 | 0.05 ± 0.01 | 0.078 |
| *Copper | 0.41 ± 0.07 | 0.25 ± 0.02 | 0.021 |
| Zinc | 0.91 ± 0.08 | 0.95 ± 0.10 | 0.709 |
| Lead | 0.14 ± 0.03 | 0.19 ± 0.07 | 0.587 |
| *Elemental Carbon percent of mass | 5.1 ± 0.4 | 4.0 ± 0.3 | 0.007 |
| *Organic Carbon percent of mass | 20.4 ± 1.1 | 22.4 ± 1.3 | 0.049 |
| Total Carbon percent of mass | 25.5 ± 1.4 | 26.4 ± 1.5 | 0.468 |
| Sodium percent of mass | 2.6 ± 0.5 | 2.9 ± 0.5 | 0.165 |
| *Magnesium percent of mass | 0.31 ± 0.04 | 0.40 ± 0.05 | 0.006 |
| Aluminum percent of mass | 0.91 ± 0.11 | 1.02 ± 0.11 | 0.072 |
| *Silicon percent of mass | 2.52 ± 0.27 | 2.86 ± 0.27 | 0.040 |
| *Sulfur percent of mass | 7.66 ± 0.53 | 8.97 ± 0.70 | 0.029 |
| Chlorine percent of mass | 1.65 ± 0.49 | 2.44 ± 0.70 | 0.066 |
| *Potassium percent of mass | 0.73 ± 0.06 | 0.83 ± 0.05 | 0.008 |
| Calcium percent of mass | 1.62 ± 0.19 | 1.81 ± 0.20 | 0.084 |
| Titanium percent of mass | 0.12 ± 0.01 | 0.13 ± 0.01 | 0.519 |
| Vanadium percent of mass | 0.08 ± 0.06 | 0.01 ± 0.00 | 0.285 |
| Iron percent of mass | 3.0 ± 0.3 | 2.7 ± 0.2 | 0.081 |
| *Nickel percent of mass | 0.02 ± 0.00 | 0.01 ± 0.00 | 0.036 |
| *Copper percent of mass | 0.10 ± 0.02 | 0.07 ± 0.01 | 0.030 |
| Zinc percent of mass | 0.24 ± 0.02 | 0.27 ± 0.03 | 0.343 |
| Lead percent of mass | 0.04 ± 0.06 | 0.06 ± 0.03 | 0.431 |
Breathing Patterns. Twenty one repetitions of the paired early morning and mid-day exposures were carried out, and animals were studied for breathing pattern, bronchoalveolar lavage (BAL), and in vivo chemiluminescence (IVCL) outcomes, in each treatment group for each strain. The numbers of animals studied provided sufficient power to examine differences between groups, based on our previous studies.
The control (Sham-exposed) animals showed a diurnal difference in breathing pattern between the early morning and mid-day exposures. The difference in respiratory parameters between all early morning and mid-day Sham exposed animals is summarized in Table 2. Because there are significant differences, it is important to control for diurnal variation in analyses of respiratory parameters. All breathing pattern data reported in this study are thus presented as continuous differences in parameter measurements between CAPs and Sham animal exposures to compensate for this diurnal variability.
| Respiratory Parameter | Difference Mean ± SE | P value |
| Frequency | 20.7 ± 4.52 | <0.0001 |
| TV | 0.06 ± 0.20 | NS |
| Ti | -0.03 ± 0.01 | 0.0001 |
| Te | -0.02 ± 0.00 | <0.0001 |
| Penh | -0.22 ± 0.05 | <0.0001 |
| EIP | 0.26 ± 0.31 | NS |
| EEP | -16.4 ± 4.37 | 0.0002 |
| EF50 | 0.51 ± 1.27 | NS |
| PEF | 1.88 ±2.05 | NS |
| PIF | 4.23 ± 2.39 | NS |
For all rat strains, regardless of exposure period (early morning vs. mid-day) breathing pattern showed significant differences between CAPs and Sham exposures. Overall, there was an increase in respiratory frequency accompanied by a decrease in the time of inspiration and expiration. The increase of frequency was seen in all groups/strains with CAPs exposure compared to controls (13.081±3.139 breaths per minute, p<0.0001). The increase in frequency also was significant in early morning CAPs exposures for all three strains (SD, SHR and WKY; p≤0.01). Inspiratory and expiratory times were decreased overall with CAPs exposure compared to controls (-0.007±0.003 and -0.013±0.005 respectively; p≤0.05).
There were very few significant differences in breathing pattern between animals exposed to CAPs in early morning and those exposed at mid-day. Although responses for animals exposed in the early morning often were greater than those of animals exposed at mid-day, this difference was only significant for frequency in the SHR rats (p=0.0393). In the overall analysis, tidal volumes tended to increase and there were no early morning-mid-day differences that were significant. Inspiratory and expiratory flows had some statistically significant differences, but these tended to be increases. The pause parameters also showed little change between the early morning and mid-day exposures. The changes in breathing pattern (e.g., increases in tidal volumes and flows) in these experiments do not appear to be toxicologically significant changes. The rapid shallow pattern, which was more pronounced in the morning than the mid-day exposure, suggests that the animals sensed the exposure to be sufficiently irritative to cause a change in the breathing pattern, but this difference is not significant. Further, the overall change in breathing pattern with CAPs exposure was not accompanied by decrease in volume or flow suggesting that there was neither bronchoconstrictive change nor inflammatory change in the airways. The lack of change in these parameters was corroborated by BAL and histological findings, which also did not show any significant changes.
In vivo Chemiluminescence (IVCL). As with the breathing pattern results, there was a definite CL response to CAPs exposure compared to Sham, regardless of exposure period, for all rat strains. IVCL data, summarized in Table 3, show that there was significant increase in spontaneous chemiluminescence (CL) in the lungs of rats exposed to CAPs, whereas increases in IVCL in the heart did not reach significance.
| SITE | Effect Tested | CAPs-Sham Difference Mean ± SE | P value |
| Heart | CAPs Effect All Exposures | 5.47 ± 4.20 | 0.197 |
| CAPs Effect Different for 3 Species | -- | 0.644 | |
| CAPs Effects Different for Early Morning vs Mid-day | -- | 0.366 | |
| Lung | CAPs Effect All Exposures | 10.28 ± 3.07 | 0.001 |
| CAPs Effect Different for 3 Species | -- | 0.640 | |
| Early Morning Exposure | 12.28 ± 4.41 | 0.007 | |
| Mid-Day Exposure | 8.38 ± 4.31 | 0.055 | |
| CAPs Effects Different for Early Morning vs Mid-day | -- | 0.529 |
-- Differences tested were not CAPs-Sham
Because there were significant changes with both early morning and mid-day exposures, and these changes did not differ by rat strain, the overall effects of particle components on the heart and lung CL were estimated using the pooled data. Table 4 shows the components that have significant univariate relationships to lung CL, but none of these were significant in multivariate analyses. No significant cardiac effects were found using univariate or multivariate analyses.
| Element/Component | Estimate ± SE | P value |
| CAPs Mass | 0.012±0.005 | 0.027 |
| Organic Carbon | 0.106±0.038 | 0.0064 |
| Elemental Carbon | 0.298±0.121 | 0.016 |
| Aluminum | 1.573±0.739 | 0.036 |
| Silicon | 0.577±0.267 | 0.034 |
| Sulfur | 0.132±0.061 | 0.033 |
| Iron | 0.509±0.218 | 0.022 |
Cardiovascular Outcomes in Repeated Exposures with Spontaneously Hypertensive (SH) and Wistar Kyoto (WKY) Rats. SH and WKY rats, surgically implanted with telemetry transmitters to monitor blood pressure and heart rate, were exposed either to CAPs or filtered air (Sham) 1 day per week for 32 weeks. Animals were exposed either in the early morning or at mid-day throughout the study. Blood pressure (BP), heart rate and breathing pattern were monitored during exposure. Linear mixed effects models were used to assess how responses change over time and whether the response trajectories over 32 weeks of exposures were different for blood pressure outcomes due to rat species (WKY vs SHR), exposure (Sham vs CAPs), time of day (early morning vs mid-day), and the different concentrations of various exposure components. The model used either a linear or a quadratic form for trend over 32 weeks (depending on the shape of the trajectory), and the interactions related to the changes in the trend across the factors. Seven predictors (mass, EC, Na, S, Si, V, and particle count) were used in the model to examine which components were associated with CAPs/Sham differences, and whether the time trend differs as a function of the concentration of these elements during exposure. Examples of the results of the time trend analysis and the impact of exposure are presented for particle count in Table 5 below.
| RAT STRAIN | Parameter | Time Trend Type | Difference in Time Trend between AM and PM | Difference in Time Trend among particle count concentrations | ||
| Overall | AM only | PM only | ||||
| WKY | Systolic Pressure | Linear (<0.0001)* | YES (0.0054) | YES (0.0133) | NO | Borderline (0.0509) |
| Diastolic Pressure | Linear (0.0005) | YES (0.0068) | YES (0.0004) | NO | YES (0.0008) | |
| Mean Pressure | Linear (<0.0001) | YES (0.0119) | YES (0.0011) | NO | YES (0.0032) | |
| Pulse Pressure | Linear (<0.0001) | NO | NO | NO | NO | |
| Heart Rate | Quadratic (<0.0001) | NO | Borderline (0.0511) | NO | YES (0.0035) | |
| SHR | Systolic Pressure | Quadratic (0.0004) | YES (<0.0001) | Borderline (0.0578) | NO | YES (0.0028) |
| Diastolic Pressure | Quadratic (0.0014) | YES (<0.0001) | NO | NO | YES (0.0145) | |
| Mean Pressure | Quadratic (0.0003) | YES (<0.0001) | NO | NO | YES (0.0071) | |
| Pulse Pressure | Quadratic (<0.0001) | YES (<0.0001) | NO | NO | YES (0.0257) | |
| Heart Rate | Quadratic (<0.0001) | YES (0.0001) | YES (0.0030) | YES (0.0473) | YES (0.0092) | |
*(Values) are p-values for the corresponding hypothesis test.
For the SH rats, there were significant differences in the quadratic time trend of heart rate, diastolic, mean, and pulse pressures between the early morning and mid-day exposure periods (p<0.001). These differences were similar for the CAPs and Sham exposures, as shown for diastolic blood pressure in Figure 1. For SH rats exposed to CAPs or filtered air, across 32 weeks of early morning exposures, BP parameters initially increased then plateaued at very high diastolic and systolic levels. CAPs exposure did not enhance this response. The SH rat BP parameters had a very different shape over 32 weeks in the mid-day exposures, but also were very high. These results may indicate that BP levels were already so high that they were beyond other influences.
Figure 1. Effect of CAPs exposures on diastolic BP in early morning and mid-day over 32 weeks for SH rats.
(Red=CAPs, Blue=Sham)
For the WKY rats, the species quadratic time trend difference between CAPs and Sham was significant for heart rate. Over 32 weeks of exposure, systolic, diastolic, mean and pulse pressure linearly increased over time, but not significantly (p<0.1). Overall, systolic and diastolic blood pressures in WKY rats were much lower than in SH rats. The overall change in BP parameters across 32 weeks in the early morning exposure period was different from that observed for the mid-day exposure. For both exposure periods, WKY rat BP increases were continuous over time. Compared to the SH rats, there was a greater CAPs influence on WKY rats, especially in the afternoon. This increase was found to be associated with Si, which is related to road dust components, and Na, which was seasonally (winter and spring) correlated with road dust elements in these data, as shown in Figure 2 for diastolic pressure.
Figure 2. Effect of components of CAPs exposures on diastolic BP in WKY rats over 32 weeks.
(*=p<0.05; **=p<0.01)
Findings of Additional Center-Supported Research within this Project
The PM Center provided support to additional studies under this project. These studies included pilot CAPs exposure studies using a rat model of social stress, as well as mechanistic investigations of biological response to CAPs exposure. In addition, supported publications included: further analyses of studies completed in the previous Center; reviews of the cardiovascular effects of air particulate on the cardiovascular system; or development statistical methods (in collaboration with the statistical core). Conclusions from supported CAPs exposure studies are summarized below.
Mechanistic studies using IVCL and continuous ECG. Previous CAPs studies suggested that ambient particles modulate autonomic tone leading to cardiovascular oxidant stress and dysfunction. Studies supported by the Center within this project directly investigated the relationship between inhaled CAPs, neurogenic signals from the lung, and effects on cardiac oxidative stress (Ghelfi, et al., 2008). In these studies, Capsazepine (CPZ), a specific antagonist of vanilloid receptor 1 (TRPV1), was administered immediately before exposure to either CAPs or filtered air. At the end of the exposure, cardiac oxidative stress was measured using IVCL, lipid peroxidation (TBARS), and tissue edema. CPZ was found to decrease CAPs-induced CL. Similar effects on TBARS and edema in the heart indicated that blocking TRP receptors, systemically or locally, decreased heart CL.
Cardiac function also was monitored throughout the exposure. Changes in cardiac rhythm and ECG morphology due to CAPs exposure were prevented by CPZ. In control rats, CAPs exposure led to significant decreases in HR and in the length of the RT, Pdur, QT and Tpe intervals. These changes were observable immediately upon exposure and were maintained throughout exposure. In the CPZ treated rats, these changes were not observed. This suggests that cardiac conduction current abnormalities in CAPs-exposed rats alter action potentials leading to changes in conduction velocity and ventricular repolarization.
Taken together, these results suggest that inhaled CAPs stimulated TRVP1 (and possibly other pulmonary irritant receptors), thereby activating autonomic nervous system reflexes. This ultimately resulted in increased cardiac oxidative stress and functional cardiac electrophysiological changes. Thus, CAPs exposure results in cardiac current abnormalities leading to changes in conduction velocity and ventricular repolarization. Further, triggering of TRPV1-mediated autonomic reflexes in the lung is essential for the observed changes in conduction, repolarization and cardiac rhythms.
In other mechanistic studies, Rhoden, et al. (2008), used a specific blocker of superoxide anion to assess the role of this oxidant in induction of pulmonary inflammation with instilled ambient particles. The findings of this study indicate that superoxide anion plays a significant role in the development of inflammation.
Effects of Chronic Stress in Susceptibility to CAPs exposures. A pilot study of the effect of chronic stress on the response to CAPs exposures (Clougherty, et al., 2010) was supported by the Center within this project. In this study, chronic stress rats and non-stress control rats were exposed to CAPs. Blood-borne markers of systemic inflammation (C-reactive protein, TNF-α, and WBC counts) were elevated under chronic stress, compared to non-stress controls. The effect of CAPs exposure on respiratory measures differed significantly, and substantively, by stress group. In chronically stressed rats, CAPs exposures were associated with increased respiratory frequency, reduced flows, and reduced volumes, indicating a rapid, shallow breathing pattern. Results from this study are consistent with epidemiologic findings that chronic stress may exacerbate respiratory response to particulate air pollution.
References:
Clougherty JE, Rossi CA, Lawrence J, Long MS, Diaz EA, Lim RH, McEwen B, Koutrakis P, Godleski JJ. Chronic social stress and susceptibility to concentrated ambient fine particles in rats. Environmental Health Perspectives 2010;118(6):769-775.
Ghelfi E, Rhoden C, Wellenius GA, Lawrence J, González-Flecha B. Cardiac oxidative stress and electrophysiological changes in rats exposed to concentrated air particles are mediated by TRP-dependent pulmonary reflexes. Toxicological Sciences 2008;102:328-336.
Rhoden CR, Ghelfi E, González-Flecha B. Pulmonary inflammation by ambient ai particles is mediated by superoxide Anion. Inhalation Toxicology 2008;20:11-15.
Journal Articles on this Report : 9 Displayed | Download in RIS Format
| Other subproject views: | All 14 publications | 12 publications in selected types | All 12 journal articles |
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| Other center views: | All 206 publications | 199 publications in selected types | All 199 journal articles |
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Bartoli CR, Wellenius GA, Coull BA, Akiyama I, Diaz EA, Lawrence J, Okabe K, Verrier RL, Godleski JJ. Concentrated ambient particles alter myocardial blood flow during acute ischemia in conscious canines. Environmental Health Perspectives 2009;117(3):333-337. |
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Bartoli CR, Wellenius GA, Diaz EA, Lawrence J, Coull BA, Akiyama I, Lee LM, Okabe K, Verrier RL, Godleski JJ. Mechanisms of inhaled fine particulate air pollution-induced arterial blood pressure changes. Environmental Health Perspectives 2009;117(3):361-366. |
R832416 (2008) R832416 (2009) R832416C003 (2009) R832416C003 (Final) R827353 (Final) |
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Bartoli CR, Nadar MM, Godleski JJ. Capsule thickness correlates with vascular density and blood flow within foreign-body capsules surrounding surgically implanted subcutaneous devices. Artificial Organs 2010;34(10):857-861. |
R832416 (Final) R832416C003 (Final) R827353 (Final) R831917 (Final) |
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Bartoli CR, Godleski JJ, Verrier RL. Mechanisms mediating adverse effects of air pollution on cardiovascular hemodynamic function and vulnerability to cardiac arrhythmias. Air Quality, Atmosphere & Health 2011;4(1):53-63. |
R832416 (Final) R832416C003 (Final) R827353 (Final) R831917 (Final) |
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Clougherty JE, Rossi CA, Lawrence J, Long MS, Diaz EA, Lim RH, McEwen B, Koutrakis P, Godleski JJ. Chronic social stress and susceptibility to concentrated ambient fine particles in rats. Environmental Health Perspectives 2010;118(6):769-775. |
R832416 (Final) R832416C003 (Final) |
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Ghelfi E, Wellenius GA, Lawrence J, Millet E, Gonzalez-Flecha B. Cardiac oxidative stress and dysfunction by fine concentrated ambient particles (CAPs) are mediated by angiotensin-II. Inhalation Toxicology 2010;22(11):963-972. |
R832416 (Final) R832416C003 (Final) |
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Imrich A, Ning YY, Lawrence J, Coull B, Gitin E, Knutson M, Kobzik L. Alveolar macrophage cytokine response to air pollution particles:oxidant mechanisms. Toxicology and Applied Pharmacology 2007;218(3):256-264. |
R832416 (2008) R832416 (Final) R832416C003 (Final) |
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Nikolov MC, Coull BA, Catalano PJ, Diaz E, Godleski JJ. Statistical methods to evaluate health effects associated with major sources of air pollution: a case-study of breathing patterns during exposure to concentrated Boston air particles. Journal of the Royal Statistical Society Series C-Applied Statistics 2008;57(3):357-378. |
R832416 (Final) R832416C003 (Final) |
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Nikolov MC, Coull BA, Catalano PJ, Godleski JJ. Multiplicative factor analysis with a latent mixed model structure for air pollution exposure assessment. Environmetrics 2011;22(2):165-178. |
R832416 (2009) R832416 (Final) R832416C003 (2009) R832416C003 (Final) |
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Supplemental Keywords:
RFA, Health, Scientific Discipline, Air, particulate matter, Environmental Chemistry, Health Risk Assessment, Risk Assessments, ambient air quality, atmospheric particulate matter, human health effects, chemical characteristics, automobile exhaust, airborne particulate matter, cardiovascular vulnerability, chemical composition, biological mechanism , biological mechanisms, ambient particle health effects, mobile sources, human exposure, autonomic dysfunction, oxidative stressProgress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R832416 Health Effects Institute (2015 - 2020) Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R832416C001 Cardiovascular Responses in the Normative Aging Study: Exploring the Pathways of Particle Toxicity
R832416C002 Cardiovascular Toxicity of Concentrated Ambient Fine, Ultrafine and Coarse Particles in Controlled Human Exposures
R832416C003 Assessing Toxicity of Local and Transported Particles Using Animal Models Exposed to CAPs
R832416C004 Cardiovascular Effects of Mobile Source Exposures: Effects of Particles and Gaseous Co-pollutants
R832416C005 Toxicological Evaluation of Realistic Emission Source Aerosol (TERESA): Investigation of Vehicular Emissions
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.