ARB Research Seminar
This page updated June 19, 2013
Cardiopulmonary Effects of Ultrafine, Fine and Coarse Particles in Rats: Age and Particle Size Effects
Michael T. Kleinman, Ph.D., Professor and Co-Director, Air Pollution Health Effects Laboratory, Department of Community and Environmental Medicine, University of California, Irvine
September 19, 2002
Cal EPA Headquarters, 1001 "I" Street, Sacramento, CA
Particle-induced lung injury and heart responses were measured as a function of particle size in young, adult and geriatric (senescent) rats exposed simultaneously to laboratory generated particles composed of elemental carbon and ammonium nitrate and ozone (0.2 ppm). The particle compositions and concentrations used were consistent with ambient aerosols collected and characterized in California. Three particle size ranges were tested: "ultrafine" (dp < 200 nm), fine (500nm < dp < 1000 nm) and "coarse" (2000nm < dp < 4000 nm). The biological responses studied included measures of cell replication (part of normal injury-repair processes), cellular immunological measures (related to defense mechanisms), and hemodynamic factors (changes in blood pressure, variability in heart rate and abnormal heart rhythms).
Our primary hypothesis was that particle-induced lung injury at the tissue and cellular levels, and systemic effects would be a function of particle size when composition and concentration of particles were held constant. Also, given that epidemiological studies indicated that older individuals were at greater risk of adverse particle induced health effects, we hypothesized that senescent rats would be more sensitive to the effects of particulate matter than healthy young adult rats.
Acute (six hour) exposures to mixtures of particles and ozone, at concentrations relevant to short-term peak ambient levels, caused inflammatory responses in both old and young rats exposed at high concentrations. Inflammatory effects were not significant when concentrations of the particles were reduced 50 percent (equivalent to a PM2.5 exposure of about 250 μg/m3).
The particle exposures also altered immunologic responses of lung macrophages, compared to responses measured in rats exposed to purified air. Again, these effects were significant at high concentrations but not at low concentrations.
Particle exposures caused changes in blood pressure and heart rate, compared to measurements in rats exposed to purified air. These changes were observed in both young rats and in senescent rats, but the senescent rats responded with greater sensitivity than did the younger rats. The findings suggest that senescent rats have impaired ability to compensate for hemodynamic changes induced by inhaled particles.
Exposures to "ultrafine" particles elicited greater blood pressure responses than either fine or "coarse" particles. However, ultrafine particles deposit more efficiently in the gas exchange (pulmonary) region of the lung than do either fine or coarse particles. Thus, the dose of "ultrafine" particles (estimated from a lung deposition model) was greater than the dose of particles in either of the other two size fractions, although the exposure concentrations were the same.
Michael T. Kleinman has been studying the health effects of exposures to particles and gases found in ambient air for more than 25 years. He holds a M.S. in Chemistry from the Polytechnic Institute of Brooklyn and a Ph.D. in Environmental Health Sciences from New York University. He is a Professor and Co-Director of the Air Pollution Health Effects Laboratory in the Department of Community and Environmental Medicine at the University of California, Irvine. Prior to joining the faculty at UCI in 1982, he directed the Aerosol Exposure and Analytical Laboratory at Rancho Los Amigos Hospital in Downey, California. Dr. Kleinman's research, for the most part, involves toxicological studies with human volunteers and laboratory animals. He has published 70 articles in peer-reviewed journals dealing with the uptake and dosimetry of inhaled pollutants, cardiopulmonary and immunological responses associated with inhalation of PM2.5, health effects of acidic and non-acidic aerosols, and studies of the effects of mixtures of particles with other pollutants such as ozone, formaldehyde, sulfur dioxide, and nitrogen dioxide. Dr. Kleinman's current studies focus on cardiopulmonary effects of concentrated ambient ultrafine, fine and coarse particles using geriatric rats and a mouse model of allergic airways disease. Dr. Kleinman is a consultant to the U.S. EPA Science Advisory Board and currently serves as the Chair of the California Air Quality Advisory Committee, which reviews California's air quality criteria documents.