ARB Research Seminar
This page updated June 19, 2013
Mechanisms of Particulate Toxicity: An Overview
Dr. John Balmes, Department of Medicine, University of California, San Francisco
June 17, 2004
Cal EPA Headquarters, 1001 "I" Street, Sacramento, CA
- Colin Solomon, Ph.D., Health Effects in Susceptible Humans
- Karron Power, M.D., Heart Rate Variability Following Controlled Exposure to Particles and Ozone in Asthmatic Individuals
- Michael T. Kleinman, Ph.D., Inflammatory and Cardiovascular Responses to Inhaled Fine Particles
- Kent Pinkerton, Ph.D., Effects on the Respiratory System of Sensitive Animals and Asthmatic Humans
Mechanisms of Particulate Toxicity series introduction: Exposure to airborne particulate matter (PM) has been linked to thousands of deaths and to hundreds of thousands of cases of respiratory symptoms and asthma attacks in California each year. To investigate how exposure to PM might lead to these outcomes, the ARB funded a three-campus collaborative with researchers from UC San Francisco, UC Irvine, and UC Davis. The three groups used similar tissue sample collection methods, biological assays, and exposure conditions: a laboratory-generated PM mixture of ammonium nitrate and carbon black. Both human clinical studies on asthmatic volunteers and animal model studies were conducted. Investigators from each campus will present their findings and discuss how these findings help us understand the ways that particles affect human health.
Overview of Dr. Balmes' presentation: Carbon and ammonium nitrate are two of the major constituents of airborne particulate matter (PM) in California. These two types of particles, however, have traditionally been considered non-toxic to humans at concentrations typically found in California ambient air. The results of previous CARB-funded work involving rats conducted at UC Davis and UC Irvine suggested that carbon and ammonium nitrate particles at a combined total concentration range of 250-300 µg/m³ can induce proliferative changes in airway tissue and changes in blood pressure and heart rate. CARB took the unique step of funding three University of California campuses (Davis, Irvine, and San Francisco) to conduct inter-related experiments designed to further investigate how these relatively biologically inert particles might induce airway and cardiovascular toxicity in susceptible humans as well as sensitive animal models. The animal model studied at UC Davis was the ovalbumin-sensitized Brown Norway rat exposed to aerosolized ovalbumin (a model of allergic airway inflammation that has some features of human asthma). The animal model studied at UC Irvine was the senescent Fischer 344N rat (a model relevant to elderly humans). The susceptible group studied at UCSF was allergic asthmatic individuals. The results of the UC Davis experiments confirmed that carbon and ammonium nitrate particles can induce proliferation of the airway lining cells as well as augment certain allergic inflammatory responses. The results of the UC Irvine experiments confirmed that inhalational exposure to these particles can also induce changes in blood pressure and heart rate. The results of the UCSF experiments showed little evidence of toxicity of carbon and ammonium nitrate particles alone but significant effects of combined exposure to the particles and ozone on lung function, airway inflammation, and heart rate variability. Taken together, the results of the experiments at the three UC campuses suggest that exposure to carbon and ammonium nitrate particles at concentrations approximately an order of magnitude higher than ambient air can induce adverse effects in animal models of allergic airway inflammation and the elderly as well as, in combination with a high-ambient exposure to ozone, in allergic asthmatic humans.
John R. Balmes received his M.D. from the Mount Sinai School of Medicine. He is a professor in the Department of Medicine at the University of California at San Francisco, Chief of the Division of Occupational and Environmental Medicine at San Francisco General Hospital, and Director of the Northern California Center for Occupational and Environmental Health. Dr. Balmes investigates the effects of various air pollutants on airway inflammation and respiratory health in humans using controlled human exposure and epidemiologic studies.