2002 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, 2002 through May 31, 2003
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air

Objective:

The primary objective of the project "Physicochemical Parameters of Combustion Generated Atmospheres as Determinants of Particulate Matter Toxicity" is to determine the influence of physicochemical parameters of combustion generated PM on the time course, dose response, and persistence of particle-induced cardiopulmonary effects.

The objectives of the closely related project, "Effects of Particulate-Associated Irritants on the Cardiovascular System," are to: (1) examine the time course of effects of concentrated ambient PM (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 rate 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.

Physicochemical Parameters of Combustion Generated Atmospheres as Determinants of PM Toxicity

Combustion generated particles often make up a significant portion of ambient PM in many regions. This study examines the hypothesis that the toxicological effects associated with combustion-generated PM depend upon specific physicochemical characteristics of the particles. PM effluents from high-temperature processes, such as fossil fuel combustion and pyrometallurgical systems, consist of inorganic materials having a wide size range and chemical composition, including H2SO4 and unreacted SO2. Such effluents have been shown to be toxicologically active. Freshly formed acidic fly ash atmospheres (containing SO2 and ultrafine particles with transition metals on their surface) produce decrements in lung function (Amdur, et al., 1986; Chen, et al., 1990). Furthermore, sulfuric acid as a coating on particle surfaces has been shown to be 10 fold more potent in producing pulmonary effects than are pure acid droplets of the same H+ concentration (Amdur and Chen, 1989). Epidemiological data have indicated increased daily mortality to be associated with particulate air pollution indices, and a significant contribution from SO2 could not be ruled out (Health Effects Institute, 1995). SO2, by itself, has low toxicity, therefore it is reasonable to speculate that a synergistic interaction between SO2 and particles may have been responsible for these observed effects (Amdur and Chen, 1989; Amdur, et al., 1986).

Several human panel studies in the United States and the MONICA study in Europe (Gold, et al., 1998; Pope, et al., 1998; Shy, et al., 1998; Peters, et al., 1998), as well as animal studies (Watkinson, et al., 1998; Lovett, et al., 1998; Nadziejko, et al., 1997) have suggested an association between PM and changes in host homeostasis. In this study, cardiopulmonary effects are measured in healthy and compromised animals exposed by inhalation to laboratory-generated particle atmospheres having precisely defined physicochemical characteristics.

This study examines the hypothesis that the toxicological effects associated with combustion-generated PM depend upon specific physicochemical characteristics of the particles. This project determines the influence of physicochemical parameters of combustion-generated PM on the time course, dose response, and persistence of particle-induced cardiopulmonary effects.

The Effects of Particle-Associated 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 and a number of unanswered 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? These three questions are inextricably intertwined. Any hypothesis about a mechanism of cardiovascular effects rests on some assumptions that a certain type of constituent of PM is the culprit.

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 times-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 rapid effects of PM on both cardiovascular and pulmonary function, namely stimulation of irritant receptors in the respiratory tract. Irritant receptor activation involves a bimolecular reaction between a protein receptor in the lung and an agonist, which triggers a rapid increase in intracellular calcium (Ca++) leading to 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, which returns to normal soon after exposure stops.

Progress Summary:

Physicochemical Parameters of Combustion Generated Atmospheres as Determinants of PM Toxicity

Progress in Years 1-3 of the Project. There is close collaboration between this project and the efforts of Dr. C. Nadziejko in the measurement of cardiopulmonary effects upon exposures to various PM atmospheres.

We have developed two furnace systems to produce realistic combustion effluents. We have successfully produced a mixture of carbon, SO2, and metal (iron or copper). This allows determination of specific components, especially metals, which may be responsible for adverse health effects, and an assessment of whether any effects could be nonspecific, i.e., they follow inhalation of any type of particle.

The electronics for temperature regulations of both furnace systems were updated. To produce iron (or copper) and sulfur-coated carbon particles, sucrose solutions containing varying concentrations of Fe(NO3)3 (or Cu(NO3)2) were produced by a nebulizer and burned in the furnace system previously used to produce coal fly ash. The mass median diameters (MMD), determined by a Mercer impactor, of particles produced by a Collison nebulizer (before combustion) using 10 sucrose solutions (each containing 1,117 ppm Fe) were 0.9 µm. When 10 percent sucrose solution containing 1,117 ppm Fe (or Cu) was burned in the furnace at 750°C in the presence of 1 ppm SO2, ultrafine particles with a median diameter of 32 ± 1.3 nm (34.0 ± 7.4 nm for Cu) and sg of 1.55 were produced. Number concentrations as high as 1.9 x 107 particles/cc were achieved. X-ray fluorescence was used to measure the concentrations of iron, copper, and sulfur in these particles. At this combustion condition, the particles produced from this furnace contained 35.1 percent and 3.6 percent by mass of iron and sulfur, respectively (30.6 percent copper and 6.9 percent sulfur when copper was used). It appeared that copper is almost twice as efficient (6.9 percent versus 3.6 percent) in converting sulfur dioxide gas to particle-associated sulfur.

Sprague Dawley rats were exposed to furnace gas or 450 µg/m3 of these particles for 3 hours and their lungs were lavaged 24-hours post-exposure. A lead oxide diffusion denuder was used to remove SO2 from the exposure atmospheres. None of the exposure atmospheres produce changes in lactic dehydrogenase levels in the lavage fluid. However, those aerosols containing a mixture of iron, SO2, and carbon produced a 6.8-fold increase over the furnace gas control for the total number of cells in the lavage, whereas particles containing copper, SO2, and carbon did not produce any change in this parameter. The results are shown in Table 1.

Table 1. Effects of Ultrafine Particles in Rats

Exposure Atmospheres
Total Cell Counts (106)
LDH (BB unit)
Furnace Gas
0.70 ± 0.14
95.5 ± 10.2
SO2 + carbon
1.52 ± 0.31
78.7 ± 6.3
Copper + SO2 + carbon
1.52 ± 0.23
80.0 ± 13.5
Iron + SO2 + carbon
4.77 ± 0.41*
113.7 ± 28.2
Values were mean ± standard error, (n = 4 to 7 per exposure group).
* Significantly different than furnace gas control (p < 0.0001).

Progress in Years 4-5 of the Project. We are determining the irritant potency as well as the cardiopulmonary effects of these particles. Healthy animals will be used first, followed by compromised animals. The morphology of these particles will be investigated using the atomic force microscopy as well as transmission and scanning electron microscopes.

The Effects of Particle-Associated Irritants on the Cardiovascular System

Progress in Years 1-3 of the Project. We examined the effects of various PM air pollutants on rats with surgically implanted electrocardiogram (ECG) and blood pressure (BP) transmitters to determine whether inhaled PM causes immediate physiological effects. Spontaneously hypertensive rats (SHRs) with BP transmitters (which measure BP, heart rate, and respiratory rate) were exposed to CAPS for 4 hours. The SHRs also were exposed to fine and ultrafine sulfuric acid aerosols because acid is one of the components of PM that could potentially activate irritant receptors and cause effects during exposure. Young and old (> 20 months) Sprague Dawley (SD) rats with ECG transmitters (which measure heart rate and core temperature) were exposed to fine and ultrafine acid aerosols and to resuspended carbon black. Inhalation of CAPS by the SHRs caused a striking decrease in respiratory rate that was apparent soon after the start of exposure and that stopped when exposure to CAPS ceased. The decrease in respiratory rate was accompanied by a decrease in heart rate. Exposure of the same SHRs to fine particle size sulfuric acid aerosol also caused a significant decrease in respiratory rate similar to the effects of CAPS. Ultrafine acid had the opposite effect on respiratory rate in SHRs as CAPS. In both old and young SD rats, inhalation of fine acid aerosol caused an immediate increase in temperature (compared to air-exposed rats) that ceased when exposure stopped. Ultrafine acid caused an immediate decrease in heart rate and temperature during exposure in young SD rats and no significant effect on old SD rats. Carbon black inhalation had no significant effect on heart rate or temperature during exposure in either old or young rats. This study showed that inhalation of ambient PM and acid aerosols has immediate effects on cardiopulmonary function during exposure. The pattern of the response to inhaled PM is consistent with activation of irritant receptors in the respiratory tract. Telemetry data from these experiments are being analyzed to determine whether significant cardiovascular effects from PM or acid persist after exposure stops.

Progress in Year 4 of the Project. Over the course of the first 3 years of this project, we did more than 50 experiments exposing rats to CAPS, irritant aerosols, particulate matter surrogates, and even some irritant gases. Every experiment involved monitoring of cardiovascular functional data in an air-exposed and pollutant-exposed group before exposure, during exposure, and for 48-72 hours post-exposure. We did extensive exploratory data analysis while experiments were being performed and solved a number of issues related to quantifying telemetric data. However, it was apparent that there was no suitable statistical method for determining whether there was a significant difference between the treated and control groups because the onset and duration of the effects were unknown. In the past year, Dr. Nadziejko collaborated with Dr. Jing-Shiang Hwang, a visiting scientist (and statistician) in the PM Center, and Dr. Arthur Nádas, a mathematical statistician in the Department of Environmental Medicine. This collaboration resulted in a simple but powerful method of analyzing repeated measures data when the time course of the effect is not known a priori. This method, which is called the Fishing License method, currently is being used to analyze all of the telemetry data from the last few years.

Future Activities:

We will continue to determine the irritant potency as well as the cardiopulmonary effects of combustion particles. Healthy animals will be used first, followed by compromised animals. The morphology of these particles will be investigated using the atomic force microscopy as well as transmission and scanning electron microscopes. We also will complete the analysis of telemetry data from the experiments to determine whether significant cardiovascular effects from PM or acid persist after exposure stops. In addition, we will continue to use the Fishing License method to analyze all of the telemetry data from the last few years.


Journal Articles on this Report : 3 Displayed | Download in RIS Format

Other subproject views: All 5 publications 5 publications in selected types All 5 journal articles
Other center views: All 112 publications 101 publications in selected types All 89 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
  • Abstract: SpringerLink-Abstract
    Exit
  • Journal Article Nadziejko C, Fang K, Chen LC, Gordon T, Nadas A. Quantitative analysis of cardiac data from rats monitored by telemetry: reducing within-and between-animal variability. Cardiovascular Toxicology 2002;2(4):237-244. R827351 (2003)
    R827351 (Final)
    R827351C005 (2002)
    R827351C005 (Final)
    R827351C006 (2003)
    R827351C006 (Final)
  • Abstract from PubMed
  • Abstract: SpringerLink-Abstract
    Exit
  • Journal Article Narciso SP, Nadziejko E, Chen LC, Gordon T, Nadziejko C. Adaptation to stress induced by restraining rats and mice in nose-only inhalation holders. Inhalation Toxicology 2003;15(11):1133-1143. R827351 (2001)
    R827351 (Final)
    R827351C005 (2002)
    R827351C005 (Final)
    R827351C006 (2003)
    R827351C006 (Final)
  • Abstract from PubMed
  • Abstract: Taylor and Francis-Abstract
    Exit
  • Supplemental Keywords:

    air pollution, air pollutants, particulate matter, PM, fine particles, PM2.5, health effects, PM toxicity, cardiovascular effects, pulmonary effects, lung disease, lung function, irritant potency, cardiopulmonary effects, combustion, combustion effluents, combustion-generated PM, metals, iron, copper, Fe, Cu, carbon, SO2, electrocardiogram, ECG, blood pressure, heart rate, respiratory rate, irritant aerosols, particulate matter surrogates, irritant gases, exposure, hypertensive rats., RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Air, ENVIRONMENTAL MANAGEMENT, Waste, INDUSTRY, POLLUTANTS/TOXICS, particulate matter, Environmental Chemistry, Health Risk Assessment, Chemicals, Risk Assessments, Environmental Monitoring, Physical Processes, 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

    Relevant Websites:

    http://charlotte.med.nyu.edu/epa-pm-center/ Exit

    Progress and Final Reports:

    Original Abstract
  • 1999 Progress Report
  • 2000 Progress Report
  • 2001 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