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2001 Progress Report: Physicochemical Parameters of Combustion Generated Atmospheres as Determinants of PM Toxicity
EPA Grant Number: R827351C005Subproject: this is subproject number 005 , established and managed by the Center Director under grant R827351
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: EPA NYU PM Center: Health Risks of PM Components
Center Director: Lippmann, Morton
Title: Physicochemical Parameters of Combustion Generated Atmospheres as Determinants of PM Toxicity
Investigators: Chen, Lung Chi , Nadziejko, Christine
Current Investigators: Chen, Lung Chi
Institution: NYU School of Medicine
EPA Project Officer: Stacey Katz/Gail Robarge,
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
Project Period Covered by this Report: June 1, 2001 through May 31, 2002
RFA: Airborne Particulate Matter (PM) Centers (1999)
Research Category: Particulate Matter
Description:
Objective:The objectives of this project are to: (1) examine the time course of effects of concentrated ambient particulate matter (PM), concentrated ambient particles (CAPS) on cardiovascular function in sensitive animals to establish the biological plausibility of short lag times between PM exposure and cardiovascular effects; and (2) expose rats (both normal rats and rat models of cardiac disease) to sulfuric acid aerosols, a known irritant found in PM, to determine whether irritant aerosols cause cardiovascular changes consistent with the adverse health effects of PM. Exposure to black carbon particles was used as a non-irritant control.
This is a combined report for two Center projects that have been merged. The first project (R827351C005) is entitled "Physicochemical Parameters of Combustion Generated Atmospheres as Determinants of PM Toxicity," and the second project (R827351C006) is entitled "Effects of Particle-Associated Organic Irritants on the Cardiovascular System."
The effect of PM on the cardiovascular system is an increasingly important public health issue. However, the physical and/or chemical properties of PM responsible for these serious health effects currently are unknown. Several inextricably intertwined questions remain. What are the biologically active components of PM? What are the mechanisms by which PM affects the cardiovascular system? What are the sensitive subpopulations? Any hypothesis about a mechanism of cardiovascular effects rests on some assumptions that a certain type of constituent of PM is the culprit and vice versa.
This research has focused on particle-associated irritants, based in part on the time course of effects reported in recent epidemiological studies. There is consistent evidence from time series studies that the lag time between elevated levels of PM2.5 and increases in cardiovascular-related hospital admissions and death is very short (i.e., 1 day or less). There is one well-studied physiological mechanism that is consistent with the rapid effects of PM on both cardiovascular pulmonary function, namely the stimulation of irritant receptors in the respiratory tract. Irritant receptor activation involves a biomolecular reaction between a protein receptor in the lung and an agonist, which triggers a rapid increase in intracellular calcium (Ca++) leading to the activation of nerve fibers that send impulses to the central nervous system. Signals from the central nervous system then cause slowing of respiration and changes in blood pressure and heart rate via neural reflex pathways. The stereotypical response to an inhaled irritant is an immediate change in respiratory rate and heart rate that returns to normal soon after exposure stops.
Progress Summary:Experiments performed in the past year are summarized in Table 1 below.
Animal Model |
Animal Number |
Parameters Measured |
Number of Exposures Done |
|||
CAPS |
Fine Acid |
Ultrafine Acid |
Carbon Black |
|||
| Young Rats | 15 |
Heart rate Temperature ECG |
2 |
2 |
2 |
|
| Old Rats | 14 |
Heart rate Temperature ECG |
1 |
2 |
4 (dose response) |
2 |
| Hypertensive Rats | 7 |
Blood pressure Heart rate Respiratory rate |
2 |
4 |
4 |
|
Each group of rats (young, old, hypertensive) was randomly divided into two
groups, Group A and Group B, at the start of the study. The rats kept their
group assignment throughout the entire study. A cross-over design was used
throughout (i.e., first Group A was exposed to filtered air and Group B was
exposed to the PM, then, in the next experiment, Group B was exposed to filtered
air and Group A was exposed to the PM). The exposures were for 4 hours, and
started in the early afternoon. All exposures were at least 1 week apart.
Data from the experiments with spontaneously hypertensive rats (SHR) have been analyzed for effects during exposure. Analyses of the data obtained up to 48 hours after exposure, and results from the old and young rats, are pending. A total of 10 exposure experiments were conducted using SHR (see Table 2).
Exposure |
Dates |
Concentrations (µg/m3) |
Average Concentration |
| CAPS | Feb 2001, May 2001 | 80, 66 |
73 |
| Fine Acid | June-July 2001 | 299, 280, 119, 203 |
225 |
| Ultrafine Acid | July-August 2001 | 140, 565, 416, 750 |
468 |
Exposure of SHR rats to CAPS was found to have immediate effects on respiratory
rate and heart rate during exposure. The CAPS concentrations in these experiments
(80 and 66 µg/m3) were similar to PM levels that can occur in the Northeastern
United States. Exposure to CAPS caused a striking decrease in respiratory rate
that was apparent soon after the start of exposure, and stopped when exposure
to CAPS ceased. The decrease in respiratory rate was accompanied by a decrease
in heart rate that was statistically significant when the data from the two
CAPS exposures were combined. This acute physiological response is similar
to the effects of inhaling a sensory irritant. Exposure of the same rats to
fine particle size sulfuric acid aerosol also caused a significant decrease
in respiratory rate similar in magnitude and time course to the effects of
CAPS. Because acids have been shown to evoke sensory irritant responses in
rodents, the similarity between the effects of fine acid aerosol and CAPS seen
in this study suggests that CAPS activates airway irritant receptors during
exposure. Ultrafine acid, on the other hand, had the opposite effect on respiratory
rate as CAPS. This result is not contradictory because the concentrator used
in these studies does not enrich the ambient ultrafine particles. Also, it
is reasonable for ultrafine particles to cause a pulmonary irritant response,
characterized by an increased respiratory rate rather than a sensory irritant
response because of the greater deep lung deposition.
Although CAPS and fine particle size sulfuric acid both caused sensory irritant-like effects on respiratory rate, it is unlikely that sulfuric acid present in PM was responsible for the immediate effects of CAPS. The concentrations of sulfuric acid used in the acid aerosol exposures are many times higher than what would be encountered in PM exposures. However, PM does contain a wide variety of organic constituents that have structural similarities to known irritants. Also, decreased pH has been shown to increase the sensitivity of irritant receptors to organic irritants. Thus, acid constituents in PM may enhance the effects of PM-associated irritants.
Conclusion. This study showed that inhalation of CAPS and acid aerosols by SHR does have immediate effects on cardiopulmonary function during exposure. The pattern of the response to inhaled CAPS is consistent with activation of irritant receptors in the respiratory tract.
Future Activities:Future activities of this research project are to continue to study the PM to obtain a better understanding of the biologically active components of PM and the cardiovascular effects of PM.
Journal Articles on this Report: 1 Displayed | Download in RIS Format
| Other subproject views: | All 5 publications | 5 publications in selected types | All 5 journal articles |
| Other center views: | All 95 publications | 86 publications in selected types | All 74 journal articles |
| Type | Citation | ||
|---|---|---|---|
|
|
Nadziejko C, Fang K, Nadziejko E, Narciso SP, Zhong M, Chen LC. Immediate effects of particulate air pollutants on heart rate and respiratory rate in hypertensive rats. Cardiovascular Toxicology 2002;2(4):245-252. |
R827351 (2003) R827351 (Final) R827351C005 (2001) R827351C005 (2002) R827351C005 (Final) R827351C006 (2003) R827351C006 (Final) |
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particulate matter, PM, cardiovascular effects, spontaneously hypertensive rats, SHR, concentrated ambient particles, CAPS. , POLLUTANTS/TOXICS, ENVIRONMENTAL MANAGEMENT, INDUSTRY, Air, Scientific Discipline, Waste, Health, RFA, PHYSICAL ASPECTS, Risk Assessment, Risk Assessments, Health Risk Assessment, Industrial Processes, Physical Processes, Incineration/Combustion, Chemicals, particulate matter, Environmental Chemistry, Environmental Monitoring, exposure assessment, heavy metals, ambient air quality, chemical characteristics, combustion byproducts, combustion, human health risk, acute cardiovascular effects, air toxics, particulates, Sulfur dioxide, toxicology, atmospheric particles, air pollution, dose response, environmental risks, ambient air monitoring, atmospheric particulate matter, exposure, atmospheric aerosol particles, airborne particulate matter, human exposure, PM, combustion emissions
Progress and Final Reports:
1999 Progress Report
2000 Progress Report
Original Abstract
2002 Progress Report
Final Report
Main Center Abstract and Reports:
R827351 EPA NYU PM Center: Health Risks of PM Components
Subprojects under this Center:
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R827351C001 Exposure Characterization Error
R827351C002 X-ray CT-based Assessment of Variations in Human Airway Geometry: Implications for Evaluation of Particle Deposition and Dose to Different Populations
R827351C003 Asthma Susceptibility to PM2.5
R827351C004 Health Effects of Ambient Air PM in Controlled Human Exposures
R827351C005 Physicochemical Parameters of Combustion Generated Atmospheres as Determinants of PM Toxicity
R827351C006 Effects of Particle-Associated Irritants on the Cardiovascular System
R827351C007 Role of PM-Associated Transition Metals in Exacerbating Infectious Pneumoniae in Exposed Rats
R827351C008 Immunomodulation by PM: Role of Metal Composition and Pulmonary Phagocyte Iron Status
R827351C009 Health Risks of Particulate Matter Components: Center Service Core
R827351C010 Lung Hypoxia as Potential Mechanisms for PM-Induced Health Effects
R827351C011 Urban PM2.5 Surface Chemistry and Interactions with Bronchoalveolar Lavage Fluid (BALF)
R827351C012 Subchronic PM2.5 Exposure Study at the NYU PM Center
R827351C013 Long Term Health Effects of Concentrated Ambient PM2.5
R827351C014 PM Components and NYC Respiratory and Cardiovascular Morbidity
R827351C015 Development of a Real-Time Monitoring System for Acidity and Soluble Components in Airborne Particulate Matter
R827351C016 Automated Real-Time Ambient Fine PM Monitoring System