Kinetics of Clearance and Relocation of Insoluble Ultrafine Iridium Particles From the Rat Lung Epithelium to Extrapulmonary Organs and Tissues (Pilot Project)

EPA Grant Number: R827354C007
Subproject: this is subproject number 007 , 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: Airborne PM - Rochester PM Center
Center Director: Oberdörster, Günter
Title: Kinetics of Clearance and Relocation of Insoluble Ultrafine Iridium Particles From the Rat Lung Epithelium to Extrapulmonary Organs and Tissues (Pilot Project)
Investigators: Kreyling, Wolfgang , Erbe, Franz , Mayer, P. , Oberdörster, Günter , Semmler, M. , Takenaka, S. , Ziesenis, A.
Institution: University of Rochester
Current Institution: GSF - Forschungszentrum fur Umwelt und Gesundheitand Ludwig Maximilian University, Neuherberg, Germany , University of Rochester
EPA Project Officer: Chung, Serena
Project Period: June 1, 1999 through May 31, 2006
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air

Objective:

The objective of this research project is to test the hypothesis that ultrafine insoluble particles may translocate from deposition sites in the lungs to systemic circulation. If such translocation occurs, it could lead to accumulation and potentially adverse reactions in critical organs such as the liver, heart, and brain, consistent with epidemiological evidence that ultrafine insoluble particles may play a role in the onset of cardiovascular diseases.

Approach:

This research project will conduct inhalation experiments on healthy young male rats. In order to study ultrafine particle translocation into secondary organs, aerosols of ultrafine iridium particles radio-labeled with Ir-192 will be produced with a spark generator using neutron-activated pure iridium electrodes. For inhalation, WKY rats will be ventilated for one hour via an endotracheal tube. After exposure, rats will be monitored in metabolic cages and excreta will be collected separately and quantitatively. Rats also will be sacrificed in time intervals ranging from 6 hours to 21 days, so that researchers can conduct a complete analysis of Ir-92 activity retained in various organs, tissues, and the remaining carcass and cleared excreta.

Expected Results:

This study will analyze the fate of retained particles in the lungs versus that of translocated particles to either the gastrointestinal tract and feces or to other organs after systemic translocation. As a result of this study, we expect to be able to explain the proportion to which ultrafine particles translocate to the systemic circulation and extrapulmonary organs.

Supplemental Keywords:

ultrafine particles, iridium, I-92, cardiovascular diseases., RFA, Health, Scientific Discipline, Air, Air Pollution, particulate matter, Toxicology, air toxics, Environmental Chemistry, Health Risk Assessment, Air Pollutants, Air Pollution Effects, Risk Assessments, Biochemistry, Atmospheric Sciences, Molecular Biology/Genetics, ambient air quality, atmospheric, biostatistics, health effects, particle size, particulates, risk assessment, sensitive populations, cardiopulmonary responses, fine particles, human health effects, lung, morbidity, ambient air monitoring, ambient air, cardiovascular vulnerability, pulmonary disease, susceptible populations, animal model, ambient monitoring, particle exposure, environmental health effects, pulmonary, lung inflamation, particulate exposure, iridium, ultrafine iridium particles, coronary artery disease, urban air pollution, inhalation toxicology, aerosol, cardiopulmonary, mortality, human health, urban environment, aerosols, cardiovascular disease, ultrafine particles

Progress and Final Reports:

  • 1999
  • 2000
  • 2001 Progress Report
  • 2002
  • 2003
  • 2004
  • Final

  • Main Center Abstract and Reports:

    R827354    Airborne PM - 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