Grantee Research Project Results
2001 Progress Report: 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: R827354C007Subproject: 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: Health Effects Institute (2000 — 2005)
Center Director: Greenbaum, Daniel S.
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 , Ziesenis, A. , Erbe, Franz , Oberdörster, Günter , Semmler, M. , Mayer, P. , Takenaka, S.
Institution: GSF - Forschungszentrum fur Umwelt und Gesundheitand Ludwig Maximilian University , University of Rochester
EPA Project Officer: Chung, Serena
Project Period: June 1, 1999 through May 31, 2006
Project Period Covered by this Report: June 1, 2000 through May 31, 2001
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.
Progress Summary:
To study ultrafine particle translocation into secondary organs, aerosols of ultrafine iridium particles radio-labeled with Ir-192 (count median diameter 15 nanometer (nm) and 80 nm; geometric standard deviation 1.6 each) are produced with a spark generator using neutron-activated pure iridium electrodes. For inhalation, healthy young male WKY rats are ventilated for 1 hour via an endotracheal tube. After exposure, rats are maintained in metabolic cages and excreta are collected separately and quantitatively. At time points ranging from 6 hours to 21 days, rats have been sacrificed, and a complete balance of Ir-192 activity retained in various organs, tissues, and the remaining carcass and cleared by excretion, have been determined gamma spectroscopically.
Our study results from this year found that 7 days after soluble Ir-192 administration, 60 percent was excreted via urine, 8 percent stayed in the lungs, and 10 percent fractions were retained in both soft tissue and bone; little was left in other organs. Auxiliary in vivo studies confirmed in vitro studies on the very low solubility of ultrafine iridium particles (<1 percent per 7 days). Both, inhaled 15 nm and 80 nm ultrafine iridium particles continued to be exclusively retained in the lungs for 1 week after fast tracheobronchial clearance was complete. Only about 0.5 percent of the particles were retained in bone and soft tissue, <0.1 percent in the liver, and even less in the heart and brain.
Balancing the entire deposited Ir-92 activity and the negligible solubility of the particles allowed a sensitive and quantitative analysis of 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 this study indicates, only a tiny fraction of ultrafine iridium particles have access to systemic circulation and extrapulmonary organs. However, chemical particle composition and the properties of the particulate surface may provide other important determinants.
Future Activities:
We will continue to test the hypothesis that ultrafine insoluble particles may translocate from deposition sites in the lungs to systemic circulation.
Supplemental Keywords:
ultrafine particles, iridium, I-92, cardiovascular diseases., RFA, Scientific Discipline, Health, Air, particulate matter, Air Pollution, Toxicology, Air Pollutants, air toxics, Environmental Chemistry, Health Risk Assessment, Air Pollution Effects, Risk Assessments, Biochemistry, Atmospheric Sciences, Molecular Biology/Genetics, ambient air quality, particle size, particulates, sensitive populations, biostatistics, atmospheric, health effects, risk assessment, cardiopulmonary responses, fine particles, human health effects, morbidity, ambient air monitoring, lung, cardiovascular vulnerability, pulmonary disease, susceptible populations, animal model, ambient air, environmental health effects, particle exposure, ambient monitoring, iridium, particulate exposure, lung inflamation, ultrafine iridium particles, pulmonary, coronary artery disease, inhalation toxicology, urban air pollution, mortality, urban environment, aerosol, cardiopulmonary, human health, aerosols, cardiovascular disease, ultrafine particlesProgress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R827354 Health Effects Institute (2000 — 2005) 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
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.