Human Health Effects of Exposure to Ultrafine Particles

EPA Grant Number: R826781
Title: Human Health Effects of Exposure to Ultrafine Particles
Investigators: Frampton, Mark W. , Marder, Victor J. , Oberdörster, Günter , Utell, Mark J. , Zareba, Wojciech
Institution: University of Rochester
EPA Project Officer: Hunt, Sherri
Project Period: October 1, 1998 through September 30, 2001 (Extended to September 30, 2002)
Project Amount: $736,260
RFA: Health Effects of Particulate Matter and Associated Air Pollutants (1998) RFA Text |  Recipients Lists
Research Category: Air , Health Effects , Particulate Matter , Air Quality and Air Toxics

Description:

Ultrafine particles (UFP) may contribute to the health effects of ambient particle exposure because of their high number concentration and surface area, a high deposition efficiency in the pulmonary region, and a high propensity to penetrate the epithelium. Our objective is to initiate clinical studies of exposure to UFP in healthy human subjects and in subjects with asthma. These studies will determine the deposition efficiency of UFP in healthy and asthmatic humans, and will compare exposure to air, ultrafine carbon, and ultrafine iron oxide with regard to: 1) the induction of airway inflammation, 2) leukocyte and endothelial adhesion molecule expression in the blood, 3) activation and inflammatory cytokine profile of blood and airway T lymphocytes, 4) alterations in blood coagulability, and 5) alterations in cardiac electrical activity.

Approach:

Healthy and asthmatic subjects will be exposed for two hours with exercise, using a mouthpiece system, to air, ultrafine carbon, and ultrafine iron oxide particles (25 to 30 nm) on separate occasions, separated by at least 3 weeks. The exposure concentration will be 10 µg/m3, equal to one-fifth of the new EPA PM2.5 24-hour Standard. Airway inflammation will be assessed using sputum induction and airway nitric oxide production. Blood will be obtained for measurement of changes in leukocyte expression of LFA-1, Mac-1, VLA-4, ICAM-1, and L- selectin using flow cytometry. Serum levels of soluble ICAM-1, VCAM-1, L-selectin, and E- selectin will be determined using ELISA. Blood lymphocyte cytokine expression will be determined 18 hours after exposure using the RNAse protection assay and intracellular cytokine staining, and lymphocyte activation and memory phenotype will be measured in both blood and sputum using flow cytometry. Blood will be analyzed for markers of the acute phase response (IL-6, C-reactive protein, serum amyloid A, fibrinogen) and for markers of hypercoagulability (prothrombin1+2, PAI-1, von Willebrand factor, and fibrinopeptide A). Changes in blood monocyte expression of tissue factor and IL-6 will be assessed using quantitative RT-PCR. High resolution digital EKGs will be obtained before and after exposure, and continuous 24-hour cardiac monitoring will be performed with each exposure.

Expected Results:

UFP exposure will result in mild airway inflammation, preceded by sequential expression and shedding of endothelial and leukocyte adhesion molecules, and accompanied by a transient acute phase response and increased blood coagulability.

Improvement in Risk Assessment or Risk Management: By identifying mechanisms, and non- invasive markers, for UFP-induced respiratory and systemic effects in healthy and asthmatic subjects, these studies will assist in establishing rational environmental standards.

Publications and Presentations:

Publications have been submitted on this project: View all 26 publications for this project

Journal Articles:

Journal Articles have been submitted on this project: View all 11 journal articles for this project

Supplemental Keywords:

Ambient air, atmosphere, sensitive populations, susceptibility, particulates, metals, dosimetry,, RFA, Health, Scientific Discipline, Air, particulate matter, Health Risk Assessment, Chemistry, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Allergens/Asthma, genetic susceptability, Atmospheric Sciences, ambient air quality, asthma, particle size, particulates, cardiopulmonary responses, human health effects, ultrafine iron oxide, cardiovascular vulnerability, exposure, airway disease, Lymphocytes, airway inflammation, human exposure, inhalation, clinical studies, environmental chemistry, analytical chemistry, Acute health effects, metals, ultrafine particles, ultrafine carbon, air quality

Progress and Final Reports:

1999 Progress Report
2000 Progress Report
2001 Progress Report
Final Report