2001 Progress Report: Physicochemical Parameters of Combustion Generated Atmospheres as Determinants of PM Toxicity

EPA Grant Number: R827351C005
Subproject: 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: N/A
Title: Physicochemical Parameters of Combustion Generated Atmospheres as Determinants of PM Toxicity
Investigators: Chen, Lung Chi , Nadziejko, Christine
Current Investigators: Chen, Lung Chi
Institution: New York University School of Medicine
EPA Project Officer: Chung, Serena
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) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air

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.

Table 1. Exposures Performed in the Past Year

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).

Table 2. Summary of Particulate Exposures

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 111 publications 100 publications in selected types All 88 journal articles
Type Citation Sub Project Document Sources
Journal Article 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)
  • Abstract from PubMed
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  • Supplemental Keywords:

    particulate matter, PM, cardiovascular effects, spontaneously hypertensive rats, SHR, concentrated ambient particles, CAPS., RFA, Health, PHYSICAL ASPECTS, Scientific Discipline, Air, ENVIRONMENTAL MANAGEMENT, Waste, INDUSTRY, POLLUTANTS/TOXICS, particulate matter, Environmental Chemistry, Health Risk Assessment, Chemicals, Risk Assessments, Physical Processes, Environmental Monitoring, Industrial Processes, Incineration/Combustion, Risk Assessment, ambient air quality, atmospheric particulate matter, particulates, combustion byproducts, air toxics, atmospheric particles, chemical characteristics, toxicology, ambient air monitoring, acute cardiovascular effects, airborne particulate matter, environmental risks, exposure, combustion emissions, dose response, air pollution, Sulfur dioxide, aerosol composition, atmospheric aerosol particles, human exposure, combustion, PM, exposure assessment, human health risk

    Progress and Final Reports:

    Original Abstract
  • 1999 Progress Report
  • 2000 Progress Report
  • 2002 Progress Report
  • 2003
  • 2004
  • 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