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2003 Progress Report: Particle Dosimetry
EPA Grant Number: R827352C016Subproject: this is subproject number 016 , established and managed by the Center Director under grant R827352
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Southern California Particle Center and Supersite
Center Director: Froines, John R.
Title: Particle Dosimetry
Investigators: Phalen, Robert , Oldham, Michael J.
Institution: University of California - Los Angeles
Current Institution: University of California - Irvine
EPA Project Officer: Stacey Katz/Gail Robarge,
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)
Research Category: Particulate Matter
Description:
Objective:Particle dosimetry is an essential aspect of particulate matter (PM) health-related research. Knowledge about the deposition and fate of inhaled particles is central to identifying susceptible subpopulations, extrapolation of laboratory data to humans, and designing/interpreting a wide variety of research projects. The objective of this research project is to perform: (1) original research within the guidelines set forth by the National Research Council’s (NRC) Committee on Research Priorities for Airborne Particulate Matter; and (2) service to investigators in the Southern California Particle Center and Supersite (SCPCS).
This is one of the project progress reports for the SCPCS. The progress for the other research projects conducted by the Center is reported separately (see reports for R827352, R827352C001 through R827352C009, and R827352C011 through R827352C021).
Progress Summary:In Year 5 of the project, we have senior authored two papers, coauthored three others, and are preparing another. With respect to recent laboratory activities, we have prepared 14 new mouse lung casts and performed airway morphometry on two. We also have helped prepare five research proposals and assisted four SCPCS investigators with either general or dosimetric support.
The difficult problem of establishing appropriate doses for in vitro mechanistic PM studies has been a priority in Year 5 of the project. Specifically, our calculations in support of Dr. Nel’s work on mechanisms of particle-induced asthma were incorporated in a recent publication (Li, et al., 2003). In this paper, we show that the exposures of cells in vitro that this group used were realistic for approximating in vivo environmental PM exposures at specific respiratory tract sites (airway bifurcations) in potentially susceptible subpopulations. We are preparing another paper that will provide dosimetry guidance to other researchers performing in vitro PM research, and we have been invited to address this topic at the 2005 Society of Toxicology Annual Conference.
In support of the freeway studies of Dr. Kleinman, we have characterized the exposures of mice to concentrated ambient particles (CAPS) in their cages. Our paper (Oldham, 2004) demonstrates that the mice do receive the desired doses of PM. This contribution is important for understanding the responses observed (with respect to implications to human populations). In addition, we helped substantially with several other aspects of the freeway studies, including conducting the exposures, acquiring tissues, and publishing the findings (Kleinman, 2004).
Our work on preparing replica in situ lung casts has continued. A replica cast of the nasal and tracheobronchial tree of the Brown Norway rat was supplied to Dr. Harkema; the cast has been sent to the Battelle Institute for computed tomography (CT) scanning to acquire data for particle dosimetry modeling. This important rodent model will be made more useful as a result of the CT analysis of this cast. Another rodent model, the lung tumor-susceptible A/J mouse used in PM studies at the Lovelace Respiratory Research Institute and CIIT, has been used to make 14 in situ tracheobronchial casts. Two of the casts have been subjected to initial morphometric measurements, indicating that the airways are similar to those of the BALB/c mouse.
With respect to facilitating the development of new investigators, we have been involved in the submission of five research proposals; two with Dr. Arezoo Campbell for investigating the effects of CAPs on the brain (National Institutes of Health [NIH]) and for examining the effects of exposure of Parkinson’s disease-susceptible mice to ambient air in Riverside (Health Effects Institute [HEI]) and three for Dr. Michael Oldham to develop an upper airway model for children (NIH), to perform complete airway modeling of the BALB/c mouse (HEI), and to validate CT scan-derived morphometry methods of rodent models (NIH with Case Western University). Each of these proposals are responsive to NRC’s recommendations for priority PM research, and each will help new researchers affiliated with the SCPCS research program to develop as independent investigators.
On the national/international scene, our staff have edited two dedicated peer-reviewed issues of Inhalation Toxicology that contain papers from the American Association for Aerosol Research PM Conference held in Pittsburgh in March 31-April 4, 2003. Also, the director of this research project has prepared a review paper on the current health effects research on PM (Phalen, in press, 2004); presented a workshop, “The Particulate Air Pollution Issue: Basics and an Update,” for the American Industrial Hygiene Association; and accepted an invitation by the Society of Toxicology to present a dosimetry talk as part of a session on “In Vitro Toxicity Testing of Air Pollutants: Pros and Cons.”
Future Activities:We will focus on three major projects in Year 6.
Project 1: Dose Calculations for Geriatric Rats . The SCPCS-related freeway study of Drs. Kleinman and Sioutas will use aged rats as a potential model for elderly humans. The use of such compromised models, and research on their PM doses, is a priority in the NRC- recommended research portfolio. We hypothesize that age, per se, is associated with dilation of bronchial airways (resulting from loss of muscle tone) that leads to uneven PM deposition (resulting from airflow distribution inhomogeneity). In situ casting of airways using physiological saline replacement followed by detailed morphometry will allow us to test our hypothesis.
Project 2: Transfer Coefficient Study for Rats in Mobile Exposure Unit . This research project involves using fluorescent monodisperse polystyrene-latex particles to quantify the exposure of rats used in the freeway study. The hypothesis is that the freeway exposure cage will deliver different PM doses than a nose-only system. A publication is planned.
Project 3: Workshop on the Potential Effects of Particle Electrical Charge on Toxicity . Although much is known regarding the distribution of electrical charge on laboratory particles and the effect of such charge on the deposition of inhaled particles, there is a clear need to explore this topic further. Specifically, the charge states of aerosols in the Los Angeles Basin and the implications to their toxicity are largely unknown. As a start, we propose to organize a 1-day workshop at the University of California at Los Angeles to define the state of current knowledge, assess the implications to SCPCS research projects, and define future research needs.
Journal Articles:No journal articles submitted with this report: View all 6 publications for this subproject
Supplemental Keywords:particulate matter, quinones, polycyclic aromatic hydrocarbons, PAHs, aldehydes, ketones, metals, allergic airway disease, human exposure studies, asthma, cardiovascular effects, aerosol sampling, atmospheric aerosol, environmental monitoring, environmental statistics, California, acute exposure, aerosols, air pollution, air quality, air toxics, airway disease, allergen, allergic response, ambient aerosol, assessment of exposure, asthma triggers, atmospheric chemistry, bioaerosols, biological response, childhood respiratory disease, children, dosimetry, environmental hazard exposures, environmental health hazard, environmental triggers, environmentally caused disease, epidemiology, exposure assessment, health effects, home, household, human exposure, human health effects, indoor air quality, inhaled particles, lead, outdoor air, particle concentrator, particle transport, particulate exposure, particulates, sensitive populations, toxicology, toxics,
Relevant Websites:
Progress and Final Reports:
2002 Progress Report
Original Abstract
2004 Progress Report
Final Report
Main Center Abstract and Reports:
R827352 Southern California Particle Center and Supersite
Subprojects under this Center:
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R827352C001 The Chemical Toxicology of Particulate Matter
R827352C002 Pro-inflammatory and the Pro-oxidative Effects of Diesel Exhaust Particulate in Vivo and in Vitro
R827352C003 Measurement of the “Effective” Surface Area of Ultrafine and Accumulation Mode PM (Pilot Project)
R827352C004 Effect of Exposure to Freeways with Heavy Diesel Traffic and Gasoline Traffic on Asthma Mouse Model
R827352C005 Effects of Exposure to Fine and Ultrafine Concentrated Ambient Particles near a Heavily Trafficked Freeway in Geriatric Rats (Pilot Project)
R827352C006 Relationship Between Ultrafine Particle Size Distribution and Distance From Highways
R827352C007 Exposure to Vehicular Pollutants and Respiratory Health
R827352C008 Traffic Density and Human Reproductive Health
R827352C009 The Role of Quinones, Aldehydes, Polycyclic Aromatic Hydrocarbons, and other Atmospheric Transformation Products on Chronic Health Effects in Children
R827352C010 Novel Method for Measurement of Acrolein in Aerosols
R827352C011 Off-Line Sampling of Exhaled Nitric Oxide in Respiratory Health Surveys
R827352C012 Controlled Human Exposure Studies with Concentrated PM
R827352C013 Particle Size Distributions of Polycyclic Aromatic Hydrocarbons in the LAB
R827352C014 Physical and Chemical Characteristics of PM in the LAB (Source Receptor Study)
R827352C015 Exposure Assessment and Airshed Modeling Applications in Support of SCPC and CHS Projects
R827352C016 Particle Dosimetry
R827352C017 Conduct Research and Monitoring That Contributes to a Better Understanding of the Measurement, Sources, Size Distribution, Chemical Composition, Physical State, Spatial and Temporal Variability, and Health Effects of Suspended PM in the Los Angeles Basin (LAB)