Toxicological Profile for Plutonium



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PLUTONIUM 
E-2 
APPENDIX E 
hepatic effects ................................................................................................................................. 14, 50, 51  
hydrolysis.............................................................................................................................. 72, 84, 118, 120  
ICRP (see International Commission on Radiological Protection)...... 21, 78, 84, 85, 91, 92, 93, 94, 95, 96, 
98, 99, 100, 101, 102, 104, 105, 106, 107, 
109, 110, 112, 114, 118, 207, 208, 211, 213  
immune system ............................................................................................................................. 4, 141, 142  
immunological .............................................................................................................. 15, 16, 21, 47, 52, 53  
immunological effects................................................................................................................................. 15 
Inhalation Toxicology Research Institute (see ITRI)............................................................................ 23, 25  
International Commission on Radiological Protection (see ICRP)..................................... 21, 207, 211, 213  
ITRI (see Inhalation Toxicology Research Institute).... 23, 24, 25, 26, 35, 44, 46, 47, 48, 49, 50, 53, 61, 63  
K
ow 
.................................................................................................................................................... 148, 149  
leukemia............................................................................................................................ 12, 31, 34, 57, 126  
leukopenia............................................................................................................................................. 47, 48  
lymphatic ...................................................................................................................... 27, 29, 52, 60, 81, 92  
lymphopoietic ....................................................................................................................................... 17, 60  
lymphoreticular............................................................................................................................... 15, 52, 53  
micronuclei ............................................................................................................................... 66, 69, 70, 71  
milk ................................................................................................................................................... 182, 188  
mucociliary ................................................................................................................... 25, 73, 81, 85, 86, 99  
musculoskeletal effects ......................................................................................................................... 15, 49  
National Council on Radiation Protection (see NCRP) .............................................................................. 91 
NCRP (see National Council on Radiation Protection) .............................................. 91, 168, 170, 185, 201  
neonatal................................................................................................................................. 17, 64, 119, 127  
neoplastic ............................................................................................................................ 15, 16, 17, 50, 53  
neurobehavioral......................................................................................................................................... 124 
neutropenia.............................................................................................................................. 14, 47, 48, 142  
nuclear...................1, 2, 3, 9, 19, 32, 57, 58, 59, 76, 144, 153, 154, 155, 156, 157, 159, 161, 162, 163, 164, 
165, 166, 172, 173, 174, 175, 176, 179, 180, 181, 185, 187, 188, 191, 192, 200, 201, 213  
ocular effects................................................................................................................................... 36, 64, 65  
odds ratio................................................................................................................. 12, 13, 33, 34, 43, 57, 59  
Pacific Northwest Laboratory (see PNL).............................................................................................. 23, 25  
PBBK (see physiologically based biokinetic)..................................................................................... 91, 142  
pharmacodynamic ....................................................................................................................................... 88 
pharmacokinetic................................................................................................................ 88, 89, 90, 91, 125  
physiologically based biokinetic (see PBBK)............................................................................................. 91 
placenta ............................................................................................................................................... 82, 141  
PNL (see Pacific Northwest Laboratory).......... 23, 24, 25, 26, 35, 44, 47, 48, 49, 50, 51, 52, 53, 61, 62, 63 
pulmonary fibrosis .................................................................................................. 13, 14, 28, 43, 44, 45, 48  
rate constant .............................................................................................................................................. 112 
renal effects................................................................................................................................................. 51 
retention ........................................................... 20, 23, 25, 35, 43, 73, 74, 75, 77, 79, 80, 84, 85, 86, 88, 95, 
98, 99, 105, 110, 112, 120, 129, 130, 132, 138, 140, 211 
SD (see standard deviation) ............................................................................................................ 74, 75, 85  
SE (see standard error).............................................................................................................. 29, 33, 60, 74  
solubility ............................................................................................................... 4, 72, 73, 92, 95, 118, 167  
spermatogonia............................................................................................................................... 66, 70, 141  
standard deviation (see SD) ........................................................................................................................ 74 
standard error (see SE).......................................................................................................................... 33, 60  
T3................................................................................................................................................................ 37 
toxicokinetic...................................................................................... 13, 19, 44, 72, 123, 129, 130, 143, 144  

PLUTONIUM 
E-3 
APPENDIX E 
tumors ....................................................... 12, 15, 25, 35, 36, 49, 50, 57, 61, 62, 63, 65, 128, 129, 130, 131 
USNRC (see U.S. Nuclear Regulatory Commission).......................... 6, 7, 76, 77, 83, 84, 87, 88, 119, 122, 
154, 155, 207, 209, 210, 211 
U.S. Nuclear Regulatory Commission (see USNRC)................................................................................... 6 

Document Outline

  • DISCLAIMER
  • UPDATE STATEMENT
  • FOREWORD
  • QUICK REFERENCE FOR HEALTH CARE PROVIDERS
  • CONTRIBUTORS
  • PEER REVIEW
  • CONTENTS
  • LIST OF FIGURES
    • 3-1  Levels of Significant Exposure to Plutonium – Inhalation
    • 3-2  Conceptual Representation of a Physiologically Based Pharmacokinetic (PBPK) Model for a Hypothetical Chemical Substance
    • 3-3  Compartment Model to Represent Particle Deposition and Time-Dependent Particle Transport in the Respiratory Tract
    • 3-4  Reaction of Gases or Vapors at Various Levels of the Gas-Blood Interface
    • 3-5  The Human Respiratory Tract Model: Absorption into Blood
    • 3-6  Schematic Representation of the ICRP (1994a) Model of Plutonium Biokinetics in Humans
    • 3-7  ICRP (1994a) Model Simulation of Elimination of an Absorbed Plutonium Dose (e.g., Intravenous) from the Body in Infants, Children, and Adults
    • 3-8  Schematic Representation of the Luciani and Polig (2000) Model of Plutonium Biokinetics in Humans
    • 3-9  Schematic Representation of the First Institute of Biophysics (FIB) Model of Plutonium Biokinetics in Humans
    • 3-10  Schematic Representation of the Leggett et al. (2005) Model of Plutonium Biokinetics in Humans
    • 3-11  Existing Information on Health Effects of Plutonium
    • 4-1  238Pu Decay Series
    • 4-2  239Pu Decay Series
    • 6-1  Frequency of NPL Sites with Plutonium and Selected Isotopes Contamination
  • LIST OF TABLES
    • 3-1  Selected Exposure Details from the ITRI and PNL Dog Studies and Conversion Procedures Used to Compare Initial Lung Burden in Common Units of kBq/kg Body Weight
    • 3-2  Summary of Human Epidemiology Studies of Health Effects of Plutonium
    • 3-3  Levels of Significant Exposure to Plutonium – Inhalation
    • 3-4  Genotoxicity of Plutonium In Vivo
    • 3-5  Genotoxicity of Plutonium In Vitro
    • 3-6  Reference Respiratory Values for a General Caucasian Population at Different Levels of Activity
    • 3-7  Reference Values of Parameters for the Compartment Model to Represent Time-dependent Particle Transport from the Human Respiratory Tract Part A
    • 3-7  Reference Values of Parameters for the Compartment Model to Represent Time-dependent Particle Transport from the Human Respiratory Tract Part B
    • 3-8  Parameters of ICRP (1994a) Model of Plutonium Biokinetics in Humans
    • 3-9  Comparison of Parameters of ICRP (1994a) Model and Luciani and Polig (2000) Model of Plutonium Biokinetics in Humans
    • 3-10  Parameters of the First Branch of the First Institute of Biophysics (FIB-1) Biokinetic Plutonium Model
    • 3-11  Parameters of Leggett et al. (2005) Model of Plutonium Biokinetics in Humans
    • 4-1  Chemical Identity of Plutonium and Selected Plutonium Compounds
    • 4-2  Physical and Chemical Properties of Plutonium and Selected Plutonium Compounds
    • 4-3  Radiological Properties of Plutonium Isotopes
    • 6-1  Common Metric Prefixes
    • 7-1  Analytical Methods for Determining Plutonium in Biological Materials
    • 7-2  Analytical Methods for Determining Plutonium in Environmental Samples
    • 8-1  Regulations, Advisories, and Guidelines Applicable to Plutonium and Plutonium Compounds
    • 8-2  Radionuclide Carcinogenicity—Slope Factors for Plutonium (Federal Guidance Report No. 13 Morbidity Risk Coefficients, in Units of Picocuries)
  • 1.  PUBLIC HEALTH STATEMENT
    • 1.1   WHAT IS PLUTONIUM?
    • 1.2   WHAT HAPPENS TO PLUTONIUM WHEN IT ENTERS THE ENVIRONMENT?
    • 1.3   HOW MIGHT I BE EXPOSED TO PLUTONIUM?
    • 1.4   HOW CAN PLUTONIUM ENTER AND LEAVE MY BODY?
    • 1.5   HOW CAN PLUTONIUM AFFECT MY HEALTH?
    • 1.6   HOW CAN PLUTONIUM AFFECT CHILDREN?
    • 1.7   HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO PLUTONIUM?
    • 1.8   IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO PLUTONIUM?
    • 1.9   WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO PROTECT HUMAN HEALTH?
    • 1.10   WHERE CAN I GET MORE INFORMATION?
  • 2.  RELEVANCE TO PUBLIC HEALTH
    • 2.1   BACKGROUND AND ENVIRONMENTAL EXPOSURES TO PLUTONIUM IN THE UNITED STATES 
    • 2.2   SUMMARY OF HEALTH EFFECTS 
    • 2.3   MINIMAL RISK LEVELS (MRLs)
  • 3.  HEALTH EFFECTS
    • 3.1   INTRODUCTION 
    • 3.2   DISCUSSION OF HEALTH EFFECTS OF PLUTONIUM BY ROUTE OF EXPOSURE 
      • 3.2.1   Inhalation Exposure 
        • 3.2.1.1   Death 
        • 3.2.1.2   Systemic Effects 
        • 3.2.1.3   Immunological and Lymphoreticular Effects 
        • 3.2.1.4   Neurological Effects 
        • 3.2.1.5   Reproductive Effects 
        • 3.2.1.6   Developmental Effects 
        • 3.2.1.7   Cancer 
      • 3.2.2   Oral Exposure 
        • 3.2.2.1   Death 
        • 3.2.2.2   Systemic Effects 
        • 3.2.2.3   Immunological and Lymphoreticular Effects 
        • 3.2.2.4   Neurological Effects 
        • 3.2.2.5   Reproductive Effects 
        • 3.2.2.6   Developmental Effects 
        • 3.2.2.7   Cancer 
      • 3.2.3   Dermal Exposure 
        • 3.2.3.1   Death
        • 3.2.3.2   Systemic Effects
        • 3.2.3.3   Immunological and Lymphoreticular Effects 
        • 3.2.3.4   Neurological Effects 
        • 3.2.3.5   Reproductive Effects 
        • 3.2.3.6   Developmental Effects 
        • 3.2.3.7   Cancer 
      • 3.2.4 Other Routes of Exposure
    • 3.3   GENOTOXICITY 
    • 3.4   TOXICOKINETICS 
      • 3.4.1   Absorption 
      • 3.4.2   Distribution 
        • 3.4.2.1   Inhalation Exposure 
        • 3.4.2.2   Oral Exposure 
        • 3.4.2.3   Dermal Exposure 
        • 3.4.2.4   Other Routes of Exposure
      • 3.4.3   Metabolism 
      • 3.4.4   Elimination and Excretion 
        • 3.4.4.1   Inhalation Exposure 
        • 3.4.4.2   Oral Exposure 
        • 3.4.4.3   Dermal Exposure 
        • 3.4.4.4   Other Routes of Exposure
      • 3.4.5   Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models 
    • 3.5   MECHANISMS OF ACTION 
      • 3.5.1   Pharmacokinetic Mechanisms 
      • 3.5.2   Mechanisms of Toxicity 
      • 3.5.3   Animal-to-Human Extrapolations 
    • 3.6   TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS 
    • 3.7   CHILDREN’S SUSCEPTIBILITY 
    • 3.8   BIOMARKERS OF EXPOSURE AND EFFECT 
      • 3.8.1   Biomarkers Used to Identify or Quantify Exposure to Plutonium
      • 3.8.2   Biomarkers Used to Characterize Effects Caused by Plutonium 
    • 3.9   INTERACTIONS WITH OTHER CHEMICALS 
    • 3.10   POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 
    • 3.11   METHODS FOR REDUCING TOXIC EFFECTS 
      • 3.11.1   Reducing Peak Absorption Following Exposure 
      • 3.11.2   Reducing Body Burden 
      • 3.11.3   Interfering with the Mechanism of Action for Toxic Effects 
    • 3.12   ADEQUACY OF THE DATABASE 
      • 3.12.1   Existing Information on Health Effects of Plutonium
      • 3.12.2   Identification of Data Needs 
      • 3.12.3   Ongoing Studies 
  • 4.  CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION
  • 5.  PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL
    • 5.1   PRODUCTION
    • 5.2   IMPORT/EXPORT 
    • 5.3   USE 
    • 5.4   DISPOSAL 
  • 6.  POTENTIAL FOR HUMAN EXPOSURE
    • 6.1   OVERVIEW 
    • 6.2   RELEASES TO THE ENVIRONMENT 
      • 6.2.1   Air 
      • 6.2.2   Water 
      • 6.2.3   Soil 
    • 6.3   ENVIRONMENTAL FATE 
      • 6.3.1   Transport and Partitioning 
      • 6.3.2   Transformation and Degradation 
    • 6.4   LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 
      • 6.4.1   Air 
      • 6.4.2   Water 
      • 6.4.3   Sediment and Soil 
      • 6.4.4   Other Environmental Media 
    • 6.5   GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 
    • 6.6   EXPOSURES OF CHILDREN 
    • 6.7   POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 
    • 6.8   ADEQUACY OF THE DATABASE 
      • 6.8.1   Identification of Data Needs 
      • 6.8.2   Ongoing Studies 
  • 7.  ANALYTICAL METHODS
    • 7.1   BIOLOGICAL MATERIALS 
    • 7.2   ENVIRONMENTAL SAMPLES 
    • 7.3   ADEQUACY OF THE DATABASE 
      • 7.3.1   Identification of Data Needs 
      • 7.3.2   Ongoing Studies 
  • 8.  REGULATIONS, ADVISORIES, AND GUIDELINES
  • 9.  REFERENCES
  • 10.  GLOSSARY
  • APPENDIX A.  ATSDR MINIMAL RISK LEVELS AND WORKSHEETS
  • APPENDIX B.  USER'S GUIDE
  • APPENDIX C.  ACRONYMS, ABBREVIATIONS, AND SYMBOLS
  • APPENDIX D.  OVERVIEW OF BASIC RADIATION PHYSICS, CHEMISTRY, AND BIOLOGY
  • APPENDIX E.  INDEX

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