1999 Progress Report: Clinical Studies of Ultrafine Particle Exposure in Susceptible Human Subjects

EPA Grant Number: R827354C003
Subproject: this is subproject number 003 , established and managed by the Center Director under grant R827354
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Rochester PM Center
Center Director: Oberd√∂rster, G√ľnter
Title: Clinical Studies of Ultrafine Particle Exposure in Susceptible Human Subjects
Investigators: Frampton, Mark W. , Beckett, William , Morrow, P. E. , Utell, Mark J.
Current Investigators: Frampton, Mark W. , Utell, Mark J.
Institution: University of Rochester
Current Institution: University of Rochester
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, 1999 through May 31, 2000
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air

Objective:

These studies utilize controlled human exposures to examine, in healthy and potentially susceptible subjects, the deposition and fate of inhaled ultrafine carbon particles (UFP), and the role of UFP and ultrafine carbon particles containing trace metals (UMP) in inducing health effects.

Progress Summary:

We have developed a facility for experimental exposure of humans to ultrafine particles, which permits the quantitative determination of the exposure levels, respiratory intakes, and depositions of the aerosol. A detailed description of the facility was presented at the Third Colloquium on Particulate Air Pollution and Human Health in Durham, NC, in June 1999 (Chalupa, 1999). Because our initial exposure mass concentrations are within the range of PM10 measurements outdoors, it was important to know numbers and mass concentrations of particles within the Clinical Research Center and the Environmental Chamber where the facility is located, as well as in the intake air for the exposure facility. These measurements were performed, and the ambient measurement results also were reported at the Third Colloquium on Particulate Air Pollution and Human Health (Riesenfeld, 1999).

For our initial studies, exposures were conducted at rest with a relatively low concentration of pure carbon UFP (~10 ?g/m3, ~2 x 106 particles/cm3, count median diameter 26.4 nm, GSD 2.3). Twelve healthy nonsmoking subjects (6 female) inhaled either filtered air or UFP by mouthpiece for 2 hours at rest, with a 10 minute break after the first hour. Exposures were double blinded, randomized, and separated by at least 2 weeks. The total respiratory tract deposition fraction (DF) was determined for six different particle size fractions after correction for system losses, and the overall DF was calculated for both number and mass for each subject. Respiratory symptoms, spirometry, blood pressure, pulse-oximetry, and exhaled NO were assessed before and at intervals after the exposure. Sputum induction was performed 18 hours after exposure. Continuous 24-hour, 12-lead Holter monitoring was performed on the day of the exposure and analyzed for changes in heart rate variability and repolarization phenomena.

The overall deposition fraction (DF) was 0.66 ? 0.12 (mean ? SD) by number, and 0.58 ? 0.14 by mass. The number of DFs during the first and second hours of exposure was similar within subjects, but the average overall DF varied from 0.43 to 0.79 among subjects. The DF decreased with increasing particle size in the UFP range, from 0.76 ? 0.11 at 7.5 nm to 0.47 ? 0.17 at 133.4 nm.

Preliminary analysis indicated no significant differences in respiratory symptoms, blood pressure, pulse-oximetry, spirometry, exhaled NO, blood markers of coagulation and endothelial activation, leukocyte activation, or sputum cell differential counts (Frampton, 2000).

Analysis of heart rate variability (HRV) showed exposure-related increases for both air and UFP in the RR interval, the standard deviation of the RR intervals in the 24-hour period (SDNN, an overall time-domain measure of HRV), and in the square root of the mean sum of squares of differences between adjacent N-N intervals (rMSSD, a short-term time-domain measure of HRV). There was a small but significant elevation of the ST segment, in V5 only, associated with UFP vs. air (see Table 1).

Table 1. Changes from baseline for heart rate variability and ST segment position

Parameter
During Exposure
P1
P2
P3
RR (ms) Air
20?42
169?34
-4?25
-32?35
UFP
16?40
140?31
-37?45
34?27
SDNN Air
29?12
16?17
-7?8
-6?10
UFP
34?13
26?8
13?12
34?11*
rMSSD Air
19?15
20?21
10?9
-12?11
UFP
30?19
27?9
2?11
27?12
TP Air
9030?2447
3505?3705
-1714?1405
-1425?2122
UFP
8720?3155
3556?1554
2026?2092
4923?1775
ST in V5 Air
-1?4
-3?3
-16?6
-10?7
UFP
7?2*
4?2*
-7?2
4?4
2. p<0.05, Air compared with UFP

 

These results will be presented at the ATS International Conference in Toronto (Boscia, 2000; Frampton, 2000).

We conclude that exposure to 10 g/m3 pure carbon UFP at rest does not cause significant respiratory or cardiac effects in healthy nonsmokers.

Future Activities:

We have initiated concentration-response exposures (10 and 25 µg/m3 UFP) of healthy subjects with exercise; if these also show no significant effects, exposures to UFP with trace metals will be initiated.


Journal Articles on this Report : 1 Displayed | Download in RIS Format

Other subproject views: All 27 publications 26 publications in selected types All 24 journal articles
Other center views: All 104 publications 98 publications in selected types All 90 journal articles
Type Citation Sub Project Document Sources
Journal Article Daigle CC, Chalupa DC, Gibb FR, Morrow PE, Oberdorster G, Utell MJ, Frampton MW. Ultrafine particle deposition in humans during rest and exercise. Inhalation Toxicology 2003;15(6):539-552. R827354 (2004)
R827354 (Final)
R827354C003 (1999)
R827354C003 (2000)
R827354C003 (2001)
R827354C003 (2002)
R827354C003 (2003)
R827354C003 (2004)
R827354C003 (Final)
R827354C004 (Final)
R826781 (2001)
R826781 (Final)
R832415 (2010)
R832415 (2011)
R832415 (Final)
R832415C003 (2011)
R832415C004 (2011)
  • Abstract from PubMed
  • Abstract: Taylor and Francis-Abstract
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  • Supplemental Keywords:

    pollution prevention, atmosphere, particulates, metals, sensitive population., RFA, Health, Scientific Discipline, Air, particulate matter, air toxics, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Biochemistry, Atmospheric Sciences, Molecular Biology/Genetics, ambient air quality, cytokine production, particle size, particulates, sensitive populations, health effects, risk assessment, cardiopulmonary responses, fine particles, human health effects, morbidity, ambient air monitoring, lung, cardiovascular vulnerability, pulmonary disease, susceptible populations, animal model, carbon particles, environmental health effects, particle exposure, ambient monitoring, human exposure, particulate exposure, lung inflamation, pulmonary, coronary artery disease, inhalation toxicology, urban air pollution, mortality, urban environment, aerosol, cardiopulmonary, human health, aerosols, cardiovascular disease, ultrafine particles, pathophysiological mechanisms

    Relevant Websites:

    http://www2.envmed.rochester.edu/envmed/pmc/indexpmc.html Exit

    Progress and Final Reports:

    Original Abstract
  • 2000 Progress Report
  • 2001 Progress Report
  • 2002 Progress Report
  • 2003 Progress Report
  • 2004 Progress Report
  • Final Report

  • Main Center Abstract and Reports:

    R827354    Rochester PM Center

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R827354C001 Characterization of the Chemical Composition of Atmospheric Ultrafine Particles
    R827354C002 Inflammatory Responses and Cardiovascular Risk Factors in Susceptible Populations
    R827354C003 Clinical Studies of Ultrafine Particle Exposure in Susceptible Human Subjects
    R827354C004 Animal Models: Dosimetry, and Pulmonary and Cardiovascular Events
    R827354C005 Ultrafine Particle Cell Interactions: Molecular Mechanisms Leading to Altered Gene Expression
    R827354C006 Development of an Electrodynamic Quadrupole Aerosol Concentrator
    R827354C007 Kinetics of Clearance and Relocation of Insoluble Ultrafine Iridium Particles From the Rat Lung Epithelium to Extrapulmonary Organs and Tissues (Pilot Project)
    R827354C008 Ultrafine Oil Aerosol Generation for Inhalation Studies