TOXICOLOGICAL PROFILE FOR 

PLUTONIUM
 


 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service 

Agency for Toxic Substances and Disease Registry 

November 2010 
 

PLUTONIUM ii 

DISCLAIMER 

The use of company or product name(s) is for identification only and does not imply endorsement by the 

Agency for Toxic Substances and Disease Registry. 
 


 


 


 


 


 


 


 


 


 


 


 


 

PLUTONIUM iii 

UPDATE STATEMENT
 

A Toxicological Profile for Plutonium, Draft for Public Comment was released in October 2007. This 

edition supersedes any previously released draft or final profile. 

Toxicological profiles are revised and republished as necessary. For information regarding the update 

status of previously released profiles, contact ATSDR at: 

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology and Environmental Medicine/Applied Toxicology Branch
 

1600 Clifton Road NE
 

Mailstop F-62
 

Atlanta, Georgia 30333
 
PLUTONIUM iv 

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FOREWORD 


This toxicological profile is prepared in accordance with guidelines* developed by the Agency for 

Toxic Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA). The 

original guidelines were published in the Federal Register on April 17, 1987. Each profile will be revised 

and republished as necessary. 

The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health 

effects infonnation for these toxic substances described therein. Each peer-reviewed profile identifies and 

reviews the key literature that describes a substance's toxicologic properties. Other pertinent literature is 

also presented, but is described in less detail than the key studies. The profile is not intended to be an 

exhaustive document; however, more comprehensive sources of specialty information are referenced. 

The focus ofthe profiles is on health and toxicologic infonnation; therefore, each toxicological 

profile begins with a public health statement that describes, in nontechnical language, a substance's 

relevant toxicological properties. Following the public health statement is infonnation concerning levels 

of significant human exposure and, where known, significant health effects. The adequacy of infonnation 

to detennine a substance's health effects is described in a health effects summary. Data needs that are of 

significance to protection of public health are identified by ATSDR. 

Each profile includes the following: 

(A) The examination, summary, and interpretation ofavailable toxicologic infonnation and 

epidemiologic evaluations on a toxic substance to ascertain the levels of significant human 

exposure for the substance and the associated acute, subacute, and chronic health effects; 

(B) 	A determination ofwhether adequate infonnation on the health effects of each substance is 

available or in the process of development to detennine levels ofexposure that present a 

significant risk to human health ofacute, subacute, and chronic health effects; and 

(C) Where appropriate, identification oftoxicologic testing needed to identifY the types or levels 

ofexposure that may present significant risk of adverse health effects in humans. 

The principal audiences for the toxicological profiles are health professionals at the Federal, State, 

and local levels; interested private sector organizations and groups; and members ofthe public. 

This profile reflects ATSDR's assessment ofall relevant toxicologic testing and infonnation that 

has been peer-reviewed. Staffs ofthe Centers for Disease Control and Prevention and other Federal 

scientists have also reviewed the profile. In addition, this profile has been peer-reviewed by a 

nongovernmental panel and was made available for public review. Final responsibility for the contents 

and views expressed in this toxicological profile resides with ATSDR. 

// 7\\ /) ;/A~-'0/.L.-- /r:../C~--(Xj 

Thomas R. Frieden, M.D., M.P.H. 


Administrator 


Agency for Toxic Substances and 


Disease Registry 

"Legislative Background 

The toxicological profiles are developed under the Comprehensive Environmental Response, 

Compensation, and Liability Act of 1980, as amended (CERCLA or Superfund). CERCLA section 

104(i)(1) directs the Administrator of ATSDR to " ...effectuate and implement the health related 

authorities" ofthe statute. This includes the preparation oftoxicological profiles for hazardous 

substances most commonly found at facilities on the CERCLA National Priorities List and that pose the 

most significant potential threat to human health, as determined by ATSDR and the EPA. Section 

104(i)(3) ofCERCLA, as amended, directs the Administrator ofATSDR to prepare a toxicological profile 

for each substance on the list. In addition, A TSDR has the authority to prepare toxicological profiles for 

substances not found at sites on the National Priorities List, in an effort to " ...establish and maintain 

inventory of literature, research, and studies on the health effects oftoxic substances" under CERCLA 

Section 104(i)(IXB), to respond to requests for consultation under section 104(i)(4), and as otherwise 

necessary to support the site-specific response actions conducted by A TSDR. 
 

 

 

 

 

 

 

 

 

 


 


 


 


 


 

PLUTONIUM vii 

QUICK REFERENCE FOR HEALTH CARE PROVIDERS 

Toxicological Profiles are a unique compilation of toxicological information on a given hazardous 

substance. Each profile reflects a comprehensive and extensive evaluation, summary, and interpretation 

of available toxicologic and epidemiologic information on a substance. Health care providers treating 

patients potentially exposed to hazardous substances will find the following information helpful for fast 

answers to often-asked questions. 

Primary Chapters/Sections of Interest 

Chapter 1: Public Health Statement: The Public Health Statement can be a useful tool for educating 

patients about possible exposure to a hazardous substance. It explains a substance’s relevant 

toxicologic properties in a nontechnical, question-and-answer format, and it includes a review of 

the general health effects observed following exposure. 

Chapter 2: Relevance to Public Health: The Relevance to Public Health Section evaluates, interprets, 

and assesses the significance of toxicity data to human health. 

Chapter 3: Health Effects: Specific health effects of a given hazardous compound are reported by type 

of health effect (death, systemic, immunologic, reproductive), by route of exposure, and by length 

of exposure (acute, intermediate, and chronic). In addition, both human and animal studies are 

reported in this section. 

NOTE: Not all health effects reported in this section are necessarily observed in the clinical 

setting. Please refer to the Public Health Statement to identify general health effects observed 

following exposure. 

Pediatrics: Four new sections have been added to each Toxicological Profile to address child health 

issues: 

Section 1.6 How Can (Chemical X) Affect Children?
 

Section 1.7 How Can Families Reduce the Risk of Exposure to (Chemical X)?
 

Section 3.8 Children’s Susceptibility
 

Section 6.6 Exposures of Children
 

Other Sections of Interest: 

Section 3.9 Biomarkers of Exposure and Effect 

Section 3.12 Methods for Reducing Toxic Effects 

ATSDR Information Center 

Phone: 1-800-CDC-INFO (800-232-4636) or 1-888-232-6348 (TTY) Fax: (770) 488-4178 

E-mail: cdcinfo@cdc.gov Internet: http://www.atsdr.cdc.gov 

The following additional material can be ordered through the ATSDR Information Center: 

Case Studies in Environmental Medicine: Taking an Exposure History—The importance of taking an 

exposure history and how to conduct one are described, and an example of a thorough exposure 

history is provided. Other case studies of interest include Reproductive and Developmental 

Hazards; Skin Lesions and Environmental Exposures; Cholinesterase-Inhibiting Pesticide 

Toxicity; and numerous chemical-specific case studies. 
PLUTONIUM viii 

Managing Hazardous Materials Incidents is a three-volume set of recommendations for on-scene 

(prehospital) and hospital medical management of patients exposed during a hazardous materials 

incident. Volumes I and II are planning guides to assist first responders and hospital emergency 

department personnel in planning for incidents that involve hazardous materials. Volume III— 

Medical Management Guidelines for Acute Chemical Exposures—is a guide for health care 

professionals treating patients exposed to hazardous materials. 

Fact Sheets (ToxFAQs) provide answers to frequently asked questions about toxic substances. 

Other Agencies and Organizations 

The National Center for Environmental Health (NCEH) focuses on preventing or controlling disease, 

injury, and disability related to the interactions between people and their environment outside the 

workplace. Contact: NCEH, Mailstop F-29, 4770 Buford Highway, NE, Atlanta, 

GA 30341-3724 • Phone: 770-488-7000 • FAX: 770-488-7015. 

The National Institute for Occupational Safety and Health (NIOSH) conducts research on occupational 

diseases and injuries, responds to requests for assistance by investigating problems of health and 

safety in the workplace, recommends standards to the Occupational Safety and Health 

Administration (OSHA) and the Mine Safety and Health Administration (MSHA), and trains 

professionals in occupational safety and health. Contact: NIOSH, 200 Independence Avenue, 

SW, Washington, DC 20201 • Phone: 800-356-4674 or NIOSH Technical Information Branch, 

Robert A. Taft Laboratory, Mailstop C-19, 4676 Columbia Parkway, Cincinnati, OH 45226-1998 

• Phone: 800-35-NIOSH. 

The National Institute of Environmental Health Sciences (NIEHS) is the principal federal agency for 

biomedical research on the effects of chemical, physical, and biologic environmental agents on 

human health and well-being. Contact: NIEHS, PO Box 12233, 104 T.W. Alexander Drive, 

Research Triangle Park, NC 27709 • Phone: 919-541-3212. 

Radiation Emergency Assistance Center/Training Site (REAC/TS) provides support to the U.S. 

Department of Energy, the World Health Organization, and the International Atomic Energy 

Agency in the medical management of radiation accidents. A 24-hour emergency response 

program at the Oak Ridge Institute for Science and Education (ORISE), REAC/TS trains, 

consults, or assists in the response to all kinds of radiation accidents. Contact: Oak Ridge 

Institute for Science and Education, REAC/TS, PO Box 117, MS 39, Oak Ridge, TN 37831-0117 • 

Phone 865-576-3131 • FAX 865-576-9522 • 24-Hour Emergency Phone 865-576-1005 (ask for 

REAC/TS) • e-mail: cooleyp@orau.gov • website (including emergency medical guidance): 

http://www.orau.gov/reacts/default.htm 

Referrals 

The Association of Occupational and Environmental Clinics (AOEC) has developed a network of clinics 

in the United States to provide expertise in occupational and environmental issues. Contact: 

AOEC, 1010 Vermont Avenue, NW, #513, Washington, DC 20005 • Phone: 202-347-4976 

• FAX: 202-347-4950 • e-mail: AOEC@AOEC.ORG • Web Page: http://www.aoec.org/. 
PLUTONIUM ix 

The American College of Occupational and Environmental Medicine (ACOEM) is an association of 

physicians and other health care providers specializing in the field of occupational and 

environmental medicine. Contact: ACOEM, 25 Northwest Point Boulevard, Suite 700, Elk 

Grove Village, IL 60007-1030 • Phone: 847-818-1800 • FAX: 847-818-9266. 
PLUTONIUM x 

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PLUTONIUM xi 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHOR(S): 

Sam Keith, M.S., C.H.P.
 

Eugene Demchuk, Ph.D.
 

Robert L. Williams, Ph.D.
 

Erik Aufderheide, M.D., M.P.H.
 

Charleton Coles, Ph.D.
 

ATSDR, Division of Toxicology and Environmental Medicine, Atlanta, GA
 

David W. Wohlers, Ph.D.
 

Gary L. Diamond, Ph.D.
 

Julie M. Klotzbach, Ph.D.
 

Lara L. Chappell, Ph.D.
 

Amy Hueber, M.L.S.
 

SRC, Inc., North Syracuse, NY
 

THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS: 

1.	 Health Effects Review. The Health Effects Review Committee examines the health effects 

chapter of each profile for consistency and accuracy in interpreting health effects and classifying 

end points. 

2.	 Minimal Risk Level Review. The Minimal Risk Level Workgroup considers issues relevant to 

substance-specific Minimal Risk Levels (MRLs), reviews the health effects database of each 

profile, and makes recommendations for derivation of MRLs. 

3.	 Data Needs Review. The Applied Toxicology Branch reviews data needs sections to assure 

consistency across profiles and adherence to instructions in the Guidance. 

4.	 Green Border Review. Green Border review assures the consistency with ATSDR policy. 
PLUTONIUM xii 

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PLUTONIUM xiii 

PEER REVIEW
 

A peer review panel was assembled for plutonium. The panel consisted of the following members: 

1.	 Lynn Anspaugh, Ph.D., Research Professor, Department of Radiology, Radiobiology Division, 

University of Utah, Salt Lake City, Utah; 

2.	 Fletcher Hahn, D.V.M., Ph.D., Scientist Emeritus, Lovelace Respiratory Research Institute, 

Albuquerque, New Mexico; 

3.	 Richard Leggett, Ph.D., Research Scientist, Life Sciences Division, Oak Ridge National 

Laboratory, Oak Ridge, Tennessee; 

4.	 Nicholas Priest, Ph.D., Head, Radiobiology Section, AECL Chalk River Laboratory, Chalk River, 

Ontario, Canada; and 

5.	 Ethel Gilbert, Ph.D., M.P.H., Expert (biostatistician), Radiation Epidemiology Branch, Division 

of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. 

These experts collectively have knowledge of plutonium’s physical and chemical properties, 

toxicokinetics, key health end points, mechanisms of action, human and animal exposure, and 

quantification of risk to humans. All reviewers were selected in conformity with the conditions for peer 

review specified in Section 104(I)(13) of the Comprehensive Environmental Response, Compensation, 

and Liability Act, as amended. 

Scientists from the Agency for Toxic Substances and Disease Registry (ATSDR) have reviewed the peer 

reviewers' comments and determined which comments will be included in the profile. A listing of the 

peer reviewers' comments not incorporated in the profile, with a brief explanation of the rationale for their 

exclusion, exists as part of the administrative record for this compound. 

The citation of the peer review panel should not be understood to imply its approval of the profile's final 

content. The responsibility for the content of this profile lies with the ATSDR. 
PLUTONIUM xiv 

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PLUTONIUM xv 

CONTENTS
 

DISCLAIMER ..............................................................................................................................................ii
 

UPDATE STATEMENT .............................................................................................................................iii
 

FOREWORD ................................................................................................................................................v
 

QUICK REFERENCE FOR HEALTH CARE PROVIDERS....................................................................vii
 

CONTRIBUTORS.......................................................................................................................................xi
 

PEER REVIEW .........................................................................................................................................xiii
 

CONTENTS................................................................................................................................................xv
 

LIST OF FIGURES ...................................................................................................................................xix
 

LIST OF TABLES.....................................................................................................................................xxi
 

1. PUBLIC HEALTH STATEMENT..........................................................................................................1
 

1.1 WHAT IS PLUTONIUM? .............................................................................................................2
 

1.2 WHAT HAPPENS TO PLUTONIUM WHEN IT ENTERS THE ENVIRONMENT? ................2
 

1.3 HOW MIGHT I BE EXPOSED TO PLUTONIUM? ....................................................................3
 

1.4 HOW CAN PLUTONIUM ENTER AND LEAVE MY BODY?..................................................4
 

1.5 HOW CAN PLUTONIUM AFFECT MY HEALTH?...................................................................4
 

1.6 HOW CAN PLUTONIUM AFFECT CHILDREN?......................................................................5
 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO PLUTONIUM?..................5
 

1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED
 

TO PLUTONIUM? ........................................................................................................................6
 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? ...................................................................................................6
 

1.10 WHERE CAN I GET MORE INFORMATION?..........................................................................7
 

2. RELEVANCE TO PUBLIC HEALTH ...................................................................................................9
 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO PLUTONIUM IN THE
 

UNITED STATES .........................................................................................................................9
 

2.2 SUMMARY OF HEALTH EFFECTS.........................................................................................10
 

2.3 MINIMAL RISK LEVELS (MRLs) ............................................................................................17
 

3. HEALTH EFFECTS..............................................................................................................................19
 

3.1 INTRODUCTION........................................................................................................................19
 

3.2 DISCUSSION OF HEALTH EFFECTS OF PLUTONIUM BY ROUTE OF EXPOSURE.......21
 

3.2.1 Inhalation Exposure ..............................................................................................................22
 

3.2.1.1 Death..............................................................................................................................26
 

3.2.1.2 Systemic Effects.............................................................................................................36
 

3.2.1.3 Immunological and Lymphoreticular Effects................................................................52
 

3.2.1.4 Neurological Effects ......................................................................................................54
 

3.2.1.5 Reproductive Effects......................................................................................................54
 

3.2.1.6 Developmental Effects...................................................................................................54
 

3.2.1.7 Cancer............................................................................................................................54
 

3.2.2 Oral Exposure........................................................................................................................64
 

3.2.2.1 Death..............................................................................................................................64
 

3.2.2.2 Systemic Effects.............................................................................................................64
 

3.2.2.3 Immunological and Lymphoreticular Effects................................................................65
 

3.2.2.4 Neurological Effects ......................................................................................................65
 

3.2.2.5 Reproductive Effects......................................................................................................65
 

3.2.2.6 Developmental Effects...................................................................................................65
 

3.2.2.7 Cancer............................................................................................................................65
 
 

 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 

3.2.3 Dermal Exposure...................................................................................................................65
 

3.2.3.1 Death..............................................................................................................................65
 

3.2.3.2 Systemic Effects.............................................................................................................65
 

3.2.3.3 Immunological and Lymphoreticular Effects ................................................................65
 

3.2.3.4 Neurological Effects ......................................................................................................65
 

3.2.3.5 Reproductive Effects......................................................................................................65
 

3.2.3.6 Developmental Effects...................................................................................................65
 

3.2.3.7 Cancer............................................................................................................................65
 

3.2.4 Other Routes of Exposure .....................................................................................................65
 

3.3 GENOTOXICITY........................................................................................................................66
 

3.4 TOXICOKINETICS.....................................................................................................................72
 

3.4.1 Absorption.............................................................................................................................72
 

3.4.1.1 Inhalation Exposure .......................................................................................................72
 

3.4.1.2 Oral Exposure ................................................................................................................75
 

3.4.1.3 Dermal Exposure ...........................................................................................................77
 

3.4.2 Distribution ...........................................................................................................................78
 

3.4.2.1 Inhalation Exposure .......................................................................................................78
 

3.4.2.2 Oral Exposure ................................................................................................................83
 

3.4.2.3 Dermal Exposure ...........................................................................................................83
 

3.4.2.4 Other Routes of Exposure..............................................................................................83
 

3.4.3 Metabolism............................................................................................................................84
 

3.4.4 Elimination and Excretion.....................................................................................................84
 

3.4.4.1 Inhalation Exposure .......................................................................................................85
 

3.4.4.2 Oral Exposure ................................................................................................................87
 

3.4.4.3 Dermal Exposure ...........................................................................................................87
 

3.4.4.4 Other Routes of Exposure..............................................................................................87
 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models.............88
 

3.5 MECHANISMS OF ACTION ...................................................................................................118
 

3.5.1 Pharmacokinetic Mechanisms.............................................................................................118
 

3.5.2 Mechanisms of Toxicity......................................................................................................122
 

3.5.3 Animal-to-Human Extrapolations.......................................................................................123
 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS...........................124
 

3.7 CHILDREN’S SUSCEPTIBILITY............................................................................................125
 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT .....................................................................127
 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Plutonium......................................128
 

3.8.2 Biomarkers Used to Characterize Effects Caused by Plutonium........................................128
 

3.9 INTERACTIONS WITH OTHER CHEMICALS .....................................................................129
 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE ............................................132
 

3.11 METHODS FOR REDUCING TOXIC EFFECTS................................................................133
 

3.11.1 Reducing Peak Absorption Following Exposure.............................................................134
 

3.11.2 Reducing Body Burden ...................................................................................................134
 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects..........................................135
 

3.12 ADEQUACY OF THE DATABASE.....................................................................................135
 

3.12.1 Existing Information on Health Effects of Plutonium.....................................................136
 

3.12.2 Identification of Data Needs............................................................................................138
 

3.12.3 Ongoing Studies ..............................................................................................................144
 

4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION.............................................145
 

4.1 CHEMICAL IDENTITY............................................................................................................ 145
 

4.2 PHYSICAL, CHEMICAL, AND RADIOLOGICAL PROPERTIES .......................................145
 

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5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL..........................................................153
 

5.1 PRODUCTION ..........................................................................................................................153
 

5.2 IMPORT/EXPORT ....................................................................................................................154
 

5.3 USE ............................................................................................................................................154
 

5.4 DISPOSAL.................................................................................................................................155
 

6. POTENTIAL FOR HUMAN EXPOSURE .........................................................................................157
 

6.1 OVERVIEW...............................................................................................................................157
 

6.2 RELEASES TO THE ENVIRONMENT...................................................................................159
 

6.2.1 Air .......................................................................................................................................161
 

6.2.2 Water...................................................................................................................................163
 

6.2.3 Soil ......................................................................................................................................164
 

6.3 ENVIRONMENTAL FATE ......................................................................................................166
 

6.3.1 Transport and Partitioning...................................................................................................166
 

6.3.2 Transformation and Degradation ........................................................................................170
 

6.3.2.1 Air................................................................................................................................170
 

6.3.2.2 Water............................................................................................................................170
 

6.3.2.3 Sediment and Soil ........................................................................................................171
 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT..................................171
 

6.4.1 Air .......................................................................................................................................172
 

6.4.2 Water...................................................................................................................................174
 

6.4.3 Sediment and Soil ...............................................................................................................176
 

6.4.4 Other Environmental Media................................................................................................182
 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE ........................................ 185
 

6.6 EXPOSURES OF CHILDREN..................................................................................................188
 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES ..............................................189
 

6.8 ADEQUACY OF THE DATABASE ........................................................................................189
 

6.8.1 Identification of Data Needs ...............................................................................................190
 

6.8.2 Ongoing Studies..................................................................................................................193
 

7. ANALYTICAL METHODS................................................................................................................195
 

7.1 BIOLOGICAL MATERIALS....................................................................................................196
 

7.2 ENVIRONMENTAL SAMPLES ..............................................................................................201
 

7.3 ADEQUACY OF THE DATABASE ........................................................................................205
 

7.3.1 Identification of Data Needs ...............................................................................................205
 

7.3.2 Ongoing Studies..................................................................................................................206
 

8. REGULATIONS, ADVISORIES, AND GUIDELINES.....................................................................207
 

9. REFERENCES ....................................................................................................................................215
 

10. GLOSSARY ......................................................................................................................................255
 

APPENDICES 

A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS .............................................................A-1
 

B. USER’S GUIDE.................................................................................................................................. B-1
 

C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS...................................................................... C-1
 

D. OVERVIEW OF BASIC RADIATION PHYSICS, CHEMISTRY, AND BIOLOGY .....................D-1
 

E. INDEX................................................................................................................................................. E-1
 

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PLUTONIUM xviii
 

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PLUTONIUM xix 

LIST OF FIGURES
 

3-1. Levels of Significant Exposure to Plutonium – Inhalation................................................................. 42
 

3-2. Conceptual Representation of a Physiologically Based Pharmacokinetic (PBPK) Model for a
 

Hypothetical Chemical Substance ......................................................................................................90
 

3-3. Compartment Model to Represent Particle Deposition and Time-Dependent Particle Transport
 

in the Respiratory Tract ......................................................................................................................93
 

3-4. Reaction of Gases or Vapors at Various Levels of the Gas-Blood Interface......................................96
 

3-5. The Human Respiratory Tract Model: Absorption into Blood........................................................100
 

3-6. Schematic Representation of the ICRP (1994a) Model of Plutonium Biokinetics in Humans ........104
 

3-7. ICRP (1994a) Model Simulation of Elimination of an Absorbed Plutonium Dose
 

(e.g., Intravenous) from the Body in Infants, Children, and Adults.................................................106
 

3-8. Schematic Representation of the Luciani and Polig (2000) Model of Plutonium Biokinetics
 

in Humans.........................................................................................................................................108
 

3-9. Schematic Representation of the First Institute of Biophysics (FIB) Model of Plutonium 

Biokinetics in Humans......................................................................................................................111
 

3-10. Schematic Representation of the Leggett et al. (2005) Model of Plutonium Biokinetics
 

in Humans.......................................................................................................................................115
 

3-11. Existing Information on Health Effects of Plutonium....................................................................137
 

4-1. 238Pu Decay Series............................................................................................................................151
 

4-2. 239Pu Decay Series............................................................................................................................152
 

6-1. Frequency of NPL Sites with Plutonium and Selected Isotopes Contamination..............................158
 
PLUTONIUM xx 

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PLUTONIUM xxi 

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 ........................... 24
 

3-2. Summary of Human Epidemiology Studies of Health Effects of Plutonium ..................................... 27
 

3-3. Levels of Significant Exposure to Plutonium – Inhalation ................................................................. 37 

3-4. Genotoxicity of Plutonium In Vivo..................................................................................................... 67
 

3-5. Genotoxicity of Plutonium In Vitro.................................................................................................... 68
 

3-6. Reference Respiratory Values for a General Caucasian Population at Different Levels of 

Activity ............................................................................................................................................... 94
 

3-7. Reference Values of Parameters for the Compartment Model to Represent Time-dependent 

Particle Transport from the Human Respiratory Tract Part A ............................................................ 97
 

3-7. Reference Values of Parameters for the Compartment Model to Represent Time-dependent 

Particle Transport from the Human Respiratory Tract Part B ............................................................ 98
 

3-8. Parameters of ICRP (1994a) Model of Plutonium Biokinetics in Humans ...................................... 102
 

3-9. Comparison of Parameters of ICRP (1994a) Model and Luciani and Polig (2000) Model of
 

Plutonium Biokinetics in Humans .................................................................................................... 109
 

3-10. Parameters of the First Branch of the First Institute of Biophysics (FIB-1) Biokinetic 

Plutonium Model ............................................................................................................................ 113
 

3-11. Parameters of Leggett et al. (2005) Model of Plutonium Biokinetics in Humans .......................... 116
 

4-1. Chemical Identity of Plutonium and Selected Plutonium Compounds ............................................ 146
 

4-2. Physical and Chemical Properties of Plutonium and Selected Plutonium Compounds ................... 148
 

4-3. Radiological Properties of Plutonium Isotopes ................................................................................ 150
 

6-1. Common Metric Prefixes .................................................................................................................. 160
 

7-1. Analytical Methods for Determining Plutonium in Biological Materials ........................................ 197
 

7-2. Analytical Methods for Determining Plutonium in Environmental Samples ................................... 202
 

8-1. Regulations, Advisories, and Guidelines Applicable to Plutonium and Plutonium Compounds..... 208
 

8-2. Radionuclide Carcinogenicity—Slope Factors for Plutonium (Federal Guidance Report No. 13
 

Morbidity Risk Coefficients, in Units of Picocuries) ....................................................................... 213
 
PLUTONIUM xxii 

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PLUTONIUM 1 

1. PUBLIC HEALTH STATEMENT 

This public health statement tells you about plutonium and the effects of exposure to it. 

The Environmental Protection Agency (EPA) identifies the most serious hazardous waste sites in the 

nation. These sites are then placed on the National Priorities List (NPL) and are targeted for long-term 

federal clean-up activities. Plutonium has been found in at least 16 of the 1,689 current or former NPL 

sites. Although the total number of NPL sites evaluated for this substance is not known, strict regulations 

make it unlikely that the number of sites at which plutonium is found would increase in the future as more 

sites are evaluated. This information is important because these sites may be sources of exposure and 

exposure to this substance may be harmful. 

When a substance is released from a large area, such as an industrial plant, or from a container, such as a 

drum or bottle, it enters the environment. This release does not always lead to exposure. You are 

normally exposed to a substance only when you come in contact with it. You may be exposed by 

breathing, eating, or drinking the substance, or by skin contact. However, since plutonium is radioactive, 

you can also be exposed to its radiation if you are near it. 

External exposure to radiation may occur from natural or man-made sources. Naturally occurring sources 

of radiation are cosmic radiation from space or radioactive materials in soil or building materials. Manmade sources of radioactive materials are found in consumer products, industrial equipment, atom bomb 

fallout, and to a smaller extent from hospital waste and nuclear reactors. 

When you are exposed to plutonium, many factors will determine whether you will be harmed. These 

factors include the dose (how much), the duration (how long), and how you come in contact with it. You 

must also consider any other chemicals you are exposed to and your age, sex, diet, family traits, lifestyle, 

and state of health. 
 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 2 

1. PUBLIC HEALTH STATEMENT 

1.1 WHAT IS PLUTONIUM? 

Radioactive metal Plutonium is a radioactive element. Pure plutonium is a silvery-white metal. 

Most plutonium is found combined with other substances, for example, 

plutonium dioxide (plutonium with oxygen) or plutonium nitrate (plutonium 

with nitrogen and oxygen). 

Plutonium is usually measured in terms of its radioactivity (curies or 

becquerels). Both the curie (Ci) and the becquerel (Bq) tell us how much a 

radioactive material decays every second. 

Exists in various 

forms called 

isotopes 

The most common plutonium isotope is plutonium-239. 

Plutonium is not 

stable 

Each radioactive isotope of an element constantly gives off radiation, which 

changes it into an isotope of a different element or a different isotope of the 

same element. This process is called radioactive decay. 

Plutonium-238 and plutonium-239 give off alpha particles (sometimes 

referred to as alpha radiation) and transform into uranium-234 and 

uranium-235, respectively. 

The half-life is the time it takes for half of the atoms of a radionuclide to 

undergo radioactive decay and change it into a different isotope. The halflife of plutonium-238 is 87.7 years. The half-life of plutonium-239 is 

24,100 years. The half-life of plutonium-240 is 6,560 years. 

Produced in Very small amounts of plutonium occur naturally. Plutonium-239 and 

nuclear power plutonium-240 are formed in nuclear power plants when uranium-238 

plants and used captures neutrons. Plutonium is used to produce nuclear weapons. 

in nuclear 

weapons and Plutonium-238 is used as a heat source in nuclear batteries to produce 

batteries electricity in devices such as unmanned spacecraft and interplanetary 

probes. 

More information about the properties and uses of plutonium can be found in Chapters 4, 5, and 6. 

1.2 WHAT HAPPENS TO PLUTONIUM WHEN IT ENTERS THE ENVIRONMENT? 

Released during 

testing of 

nuclear weapons 

Plutonium released during atmospheric testing of nuclear weapons, which 

ended in 1980, is the source of most of the plutonium in the environment 

worldwide. The plutonium released during these tests was deposited on land 

and water. The small amount that remains in the atmosphere continues to be 

deposited as it slowly settles out. 

Plutonium is also released to the environment from research facilities, waste 

disposal, nuclear fuel reprocessing facilities, nuclear weapons production 

facilities, and accidents at facilities where plutonium is used. 
 

 

 

 

 

 

 

 

 

PLUTONIUM 3 

1. PUBLIC HEALTH STATEMENT 

Deposited in 

water or soil 

Plutonium can be transported in the atmosphere usually when it is attached to 

particles in the air. It can be deposited on land or water by settling or by rain. 

Plutonium can stick to particles in soil, sediment, and water. 

Plutonium isotopes will undergo radioactive decay in the environment. 

For more information on plutonium in the environment, see Chapter 6. 

1.3 HOW MIGHT I BE EXPOSED TO PLUTONIUM? 

You may be exposed to plutonium by breathing air, drinking water, or eating food containing plutonium; 

however, the levels of plutonium in air, water, soil, and food are very low. 

Soil Average plutonium levels in surface soil from fallout range from 0.01 to 

0.1 picocuries (pCi) per gram of soil (1 picocurie equals one-trillionth [10-12] 

of a curie). 

Air Plutonium concentrations in air are generally low. Baseline plutonium-239 

concentrations in air ranging from 1.6x10-6 to 3.8x10-6 pCi per cubic meter of 

air (pCi/m3

) have been reported. 

Workplace Persons who work at nuclear fuel and weapons production facilities have a 

greater chance of being exposed than individuals in the general population. 

Accident You could be exposed to plutonium if there was an accidental release of 

plutonium during use. It is very unlikely you would be exposed as the result 

of a traffic accident or disposal. Plutonium transport containers are virtually 

indestructible by accident or fire. The disposal site is deep underground and 

away from the public. 

Further information on how you might be exposed to plutonium is given in Chapter 6. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 4 

1. PUBLIC HEALTH STATEMENT 

1.4 HOW CAN PLUTONIUM ENTER AND LEAVE MY BODY? 

Plutonium can When you breathe air that contains plutonium, some of it will get trapped in 

enter your body your lungs. Some of the trapped plutonium will move to other parts of your 

when it is inhaled body, mainly your bones and liver. The amount of plutonium that stays in 

or swallowed your lungs depends on the solubility of the plutonium that is in the air you 

breathe. 

A small amount of the plutonium you swallow (much less than 1%) will enter 

other parts of your body (mainly your bones and liver). 

If plutonium gets onto your healthy skin, very little, if any, plutonium will enter 

your body. More plutonium will enter your body if gets onto injured skin, 

such as a cut or burn. 

Plutonium in your Plutonium leaves your body very slowly in the urine and feces. If plutonium 

body will remain were to enter your lungs today, much of the plutonium would still be in your 

there for many body 30–50 years later. 

years 

Further information on how plutonium enters and leaves the body is given in Chapter 3. 

1.5 HOW CAN PLUTONIUM AFFECT MY HEALTH? 

Plutonium may remain in the lungs or move to the bones, liver, or other body organs. It generally stays in 

the body for decades and continues to expose the surrounding tissues to radiation. 

Lung, liver, and 

bone cancer 

You may develop cancer depending on how much plutonium is in your body 

and for how long it remains in your body. The types of cancers you would 

most likely develop are cancers of the lung, bones, and liver. These types 

of cancers have occurred in workers who were exposed to plutonium in air 

at much higher levels than is in the air that most people breathe. 

Affect ability to 

fight infections 

In laboratory animals, plutonium affected the animal’s ability to resist 

disease (immune system). 

More information on the health effects of plutonium is presented in Chapters 2 and 3. 
 

 

 

 

 

 

 

 

PLUTONIUM 5 

1. PUBLIC HEALTH STATEMENT 

1.6 HOW CAN PLUTONIUM AFFECT CHILDREN? 

This section discusses potential health effects in humans from exposures during the period from 

conception to maturity at 18 years of age. 

There are Studies in young animals have shown that a larger amount of the plutonium 

differences deposited in the lung will move to growing bones. Therefore, it is possible 

between children that the bones of children could be more severely affected by plutonium 

and adult than the bones of adults; however, this has not been shown in humans or 

laboratory animals. 

Studies in animals have also shown that a larger amount of plutonium that 

enters the gut of newborn animals is absorbed into the body. 

Effects in unborn 

children 

We do not know if plutonium causes birth defects or affects the ability to 

have children, although some plutonium that reaches the blood can be 

found in ovaries and testes. 

A large portion of the plutonium in the body of adults is in bone. It is 

possible that plutonium in the bones of a pregnant woman may move to the 

fetus, when the calcium from the mother’s bone is being used to build the 

bones of the fetus. 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO PLUTONIUM? 

Exposure of the general population to plutonium will be small. Plutonium levels in water, air, and food 

are generally low in areas that have not been contaminated by accidents or other releases of radioactive 

materials. 

Risk for working 

adults 

People working at facilities using plutonium that is not highly contained will be 

more highly exposed to plutonium than the general population. 

Risk near the 

home 

People do not generally live near facilities that use plutonium in their 

operations. Some people may be slightly more exposed to plutonium due to 

releases of plutonium through filtered stack-emissions or waste water. Any 

releases are to be within regulatory limits. Disposal sites are deep 

underground and away from the public. 

Risk in the air you 

breathe 

Breathing plutonium-contaminated air is the most dangerous way to be 

exposed to plutonium. If you know or suspect that plutonium has been 

released to the air, you should leave the area immediately. 
 

 

 

 

 

 

 

 

PLUTONIUM	 	 6 

1. PUBLIC HEALTH STATEMENT 

1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO 

PLUTONIUM? 

Can be measured 

in urine and feces 

Plutonium can be measured in the urine and feces even at very low levels. 

These measurements can be used to estimate the total amount of 

plutonium that has entered the body. 

The levels of plutonium in body can be used to predict the kind of health 

effects that might develop from that exposure. 

Plutonium inside 

the body can be 

detected from 

outside the body 

Some sensitive equipment can measure the weak gamma rays that travel 

to the outside of the body after they are released from plutonium and other 

radioactive materials inside the body. In the United States, this equipment 

is only available in a few locations. 

Further information on how plutonium can be measured in exposed humans is presented in 

Chapters 3 and 7. 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? 

The federal government develops regulations and recommendations to protect public health. Regulations 

can be enforced by law. Federal agencies that develop regulations for toxic substances include the 

Environmental Protection Agency (EPA), the Occupational Safety and Health Administration (OSHA), 

the Food and Drug Administration (FDA), and the U.S. Nuclear Regulatory Commission (USNRC). 

Recommendations provide valuable guidelines to protect public health but cannot be enforced by law. 

Federal organizations that develop recommendations for toxic substances include the Agency for Toxic 

Substances and Disease Registry (ATSDR), the National Institute for Occupational Safety and Health 

(NIOSH), and the FDA. 

Regulations and recommendations can be expressed as “not-to-exceed” levels, that is, levels of a toxic 

substance in air, water, soil, or food that do not exceed a critical value that is usually based on levels that 

affect animals; they are then adjusted to levels that will help protect humans. Sometimes these not-toexceed levels differ among federal organizations because they used different exposure times (an 8-hour 

workday, a 24-hour day, or a work-year), different animal studies, or other factors. 

Recommendations and regulations are also updated periodically as more information becomes available. 

For the most current information, check with the federal agency or organization that provides it. 
 

 

 

 

 

 

 

 

PLUTONIUM 7 

1. PUBLIC HEALTH STATEMENT 

The USNRC has recommended the following radiation exposure limits for the general public and for 

workers: 

General public 0.1 rem/year for the general public and 0.5 rem/year for people who work 

with medical patients. These regulations are for all forms of radiation 

combined, so they are not only for plutonium. 

Workers 5 rem/year for workers in industries where exposure to radiation may occur 

and 0.5 rem for the pregnancy period following the declaration of pregnancy 

by a woman in an industry where exposure to radiation may occur. 

These recommended radiation exposure limits are for all forms of radiation combined and are not specific 

to plutonium. The limits are expressed in units called rem (roentgen equivalent man). A rem is a 

radiation unit that expresses the radiation equivalent dose to a particular organ or tissue. The limits on 

equivalent dose are used to calculate the limits on the amount of radioactive substances that can be 

inhaled or ingested. 

Additional information on governmental regulations regarding plutonium can be found in Chapter 8. 

1.10 WHERE CAN I GET MORE INFORMATION? 

If you have any more questions or concerns, please contact your community or state health or 

environmental quality department, or contact ATSDR at the address and phone number below. 

ATSDR can also tell you the location of occupational and environmental health clinics. These clinics 

specialize in recognizing, evaluating, and treating illnesses that result from exposure to hazardous 

substances. 

Toxicological profiles are also available on-line at www.atsdr.cdc.gov and on CD-ROM. You may 

request a copy of the ATSDR ToxProfilesTM CD-ROM by calling the toll-free information and technical 
 

 

 

 

 

 

 

 

 

 

 

 

 


 


 


 


 


 


 


 


 


 


 


 

PLUTONIUM 8 

1. PUBLIC HEALTH STATEMENT 

assistance number at 1-800-CDCINFO (1-800-232-4636), by e-mail at cdcinfo@cdc.gov, or by writing 

to: 

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology and Environmental Medicine
 

1600 Clifton Road NE
 

Mailstop F-62
 

Atlanta, GA 30333
 

Fax: 1-770-488-4178
 

Organizations for-profit may request copies of final Toxicological Profiles from the following: 

National Technical Information Service (NTIS)
 

5285 Port Royal Road
 

Springfield, VA 22161
 

Phone: 1-800-553-6847 or 1-703-605-6000
 

Web site: http://www.ntis.gov/
 
 

 

 

 

 

 

 

 

 


 

PLUTONIUM 9 

2. RELEVANCE TO PUBLIC HEALTH
 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO PLUTONIUM IN THE 

UNITED STATES 

Plutonium is primarily a human-made radioactive element of the actinide series and was the first humanmade element to be synthesized in weighable amounts. Plutonium was first synthesized by the 

bombardment of uranium with deuterons (2

H) by Seaborg and co-workers in 1940. Although 20 isotopes 

of plutonium (228-247Pu) have been identified, the alpha-emitting 238Pu and 239Pu isotopes are the ones most 

commonly encountered and widely studied for potential adverse health effects. The isotope 239Pu was 

first used in fission weapons beginning in 1945 and is produced during the bombardment of uranium 

(

235U) by neutrons in nuclear reactors. Approximately one-third of the total energy produced in a typical 

commercial nuclear power plant comes from the fission of 239Pu produced from 235U. The isotope 238Pu 

has been used as a heat source in nuclear batteries to produce electricity in devices such as unmanned 

spacecraft and interplanetary probes. Plutonium is a carefully regulated material under government and 

International Atomic Energy Agency (IAEA) control and has no commercial usage, with the exception of 

small quantities used in research laboratories. Approximately 1,855 metric tons of plutonium was 

estimated to exist worldwide at the end of 2003; most of which was found in spent fuel from nuclear 

power plants. A plutonium production rate of 70–75 metric tons/year was estimated for reactors 

worldwide in 2003. 

The main sources of plutonium in the environment are releases from research facilities, nuclear weapons 

testing, waste disposal, nuclear weapons production facilities, and accidents. Atmospheric testing of 

nuclear weapons, which ended in 1980, is the source of most of the plutonium in the environment 

worldwide, which released approximately 10,000 kilograms of plutonium. Trace amounts of plutonium 

(including 238Pu, 239Pu, 240Pu, and 241Pu) are found worldwide, mostly due to fallout from atmospheric 

nuclear testing. Trace amounts of 239Pu are found in naturally occurring uranium ores, although in such 

small amounts that extraction is not practical. Small amounts of 244Pu also exist in nature from remnants 

of primordial stellar nucleosynthesis and from “natural” reactors such as the Oklo natural reactor in the 

African nation of Gabon, which existed about 2 billion years ago. Plutonium released to the atmosphere 

reaches the earth's surface through wet and dry deposition to the soil and surface water. Once in these 

media, soluble plutonium can sorb to soil and sediment particles or bioaccumulate in terrestrial and 

aquatic food chains. 
 

 

 

 

 

 

 

 

PLUTONIUM 10 

2. RELEVANCE TO PUBLIC HEALTH 

Humans may be exposed to plutonium by breathing air, drinking water, or eating food containing 

plutonium; however, the levels of plutonium in air, water, soil, and food are generally very low, and of 

little health consequence. Average plutonium levels in surface soil from fallout range from 0.01 to 

0.1 picocuries (pCi) per gram of soil (1 picocurie equals one-trillionth [10-12] of a curie). In general, 

plutonium concentrations in air are low. Baseline 239Pu concentrations in air ranging from 1.6x10-6 to 

3.8x10-6 pCi per cubic meter of air (pCi/m3

) have been reported. 

2.2 SUMMARY OF HEALTH EFFECTS 

Risks for adverse outcomes of plutonium exposures are strongly dependent on radiation doses received by 

specific tissues and organ systems. Most of the body burden of plutonium resides in the skeleton and 

liver, and following inhalation exposures, in the lung and lung-associated lymph nodes. As a result, these 

tissues receive relatively high radiation doses following exposures to plutonium. Radiation-induced 

toxicity to these tissues has been documented in human epidemiological studies and in animal models. 

The relatively high radiation doses received by bone, liver, and lung lend greater credibility to the 

epidemiological findings for these tissues than for outcomes in other tissues that receive much smaller 

radiation doses. All epidemiological studies that have reported adverse outcomes in these tissues have 

studied populations (i.e., workers in plutonium production and processing facilities) that experienced 

exposures and radiation doses that greatly exceed those experienced by the general public. Accordingly, 

risks for these outcomes in the general population are substantially lower than reported for these more 

highly exposed worker populations. 

Death. Possible associations between exposure to plutonium and mortality have been examined in 

studies of workers at the U.S. plutonium production and/or processing facilities (Hanford, Los Alamos, 

Rocky Flats), as well as facilities in Russia (e.g., Mayak) and the United Kingdom (e.g., Sellafield). The 

Mayak studies provide relatively strong evidence for an association between cancer mortality (bone, liver, 

lung) and exposure to plutonium. Plutonium dose-response relationships for lung cancer mortality have 

been derived from studies of Mayak workers, who received much higher uptakes of plutonium compared 

to other epidemiological cohorts (i.e., mean body burdens 0.09–9.2 kBq, with much higher individual 

exposures [up to 470 kBq] in relatively large numbers of these workers). Excess relative risk (ERR) 

estimated in three studies (adjusted for smoking) were 3.9 per Gy (95% confidence interval [CI]: 2.6– 

5.8) in males, and 19 per Gy (95% CI: 9.5–39) in females (attained age 60 years), 4.50 per Gy (95% CI: 

3.15–6.10) in males, and 0.11 per Sv (95% CI: 0.08–0.17) or 0.21 per Sv (95% CI: 0.15–0.35), 

depending on the smoking-radiation interaction model that was assumed (these estimates per Sv 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 11 

2. RELEVANCE TO PUBLIC HEALTH 

correspond to 2.2 or 4.3 per Gy, respectively, assuming a radiation weighting factor of 20 for -radiation). 

The ERR per Gy in Mayak workers declined strongly with attained age. In a recent cohort mortality 

study of the Mayak workers, significant plutonium dose-response relationships (p<0.001) were found for 

deaths due to lung or liver cancer, and for deaths in which bone cancer was considered a contributing 

cause. At attained age of 60 years, ERRs for lung cancer were 7.1 per Gy (95% CI: 4.9–10) in males and 

15 per Gy (95% CI: 7.6–29) in females. Averaged-attained age ERRs for liver cancer were 2.6 per Gy 

(95% CI: 0.7–6.9) for males and 29 per Gy (95% CI: 9.8–95) for females, and averaged-attained age 

ERRs for bone cancer were 0.76 per Gy (95% CI: <0–5.2) for males and 3.4 per Gy (95% CI: 0.4–20) 

for females. Elevated risks for bone cancer were observed only for workers with plutonium doses 

exceeding 10 Gy. For lung and bone cancer, the ERR declined with attained age, and for lung cancer, the 

ERR declined with age at first plutonium exposure. 

Decreased survival was noted in beagle dogs exposed to plutonium aerosols (238PuO2, 239PuO2, or 

239Pu(NO3)4) at levels resulting in initial lung burdens in the range of ≥1 kBq/kg body weight. Early 

deaths were attributed to radiation pneumonitis and decreased survival late in life was typically associated 

with tumor development. 

Cancer. Possible associations between exposure to plutonium and cancer mortality and morbidity have 

been examined in studies of workers at the U.S. plutonium production and/or processing facilities 

(Hanford, Los Alamos, Rocky Flats), as well as facilities in Russia (Mayak) and the United Kingdom 

(e.g., Sellafield). Compared to studies of U.K. and U.S. facilities, the Mayak cohorts had relatively high 

uptakes of plutonium (i.e., mean body burdens as high as 9.2 kBq, with much higher individual uptakes 

[up to 470 kBq] in relatively large numbers of these workers). Collectively, the Mayak studies provide 

evidence for an association between cancer mortality (lung, liver, bone) and uptake of plutonium. Studies 

of U.K. and U.S. facilities have examined cohorts of workers who had substantially lower estimated 

plutonium uptakes and corresponding internal radiation doses than the Mayak cohorts (e.g., Sellafield: 

≤1 kBq in 97% of the assessed workers; Los Alamos: mean body burden 0.970 kBq, range 0.05– 

3.18 kBq). Although a significantly higher incidence of cancer mortality in certain groups of plutonium 

workers has been found in some studies, higher cancer incidence and/or risks for tissues that received the 

highest plutonium radiation doses (i.e., lung, liver, bone) have not been found, making causal connections 

of these outcomes to plutonium exposure more uncertain. The Sellafield study is by far the strongest of 

these studies and did not find associations between plutonium exposure and cancers to tissues receiving 

the highest radiation doses from plutonium. 
PLUTONIUM 12 

2. RELEVANCE TO PUBLIC HEALTH 

Plutonium dose-response relationships for lung cancer mortality and morbidity have been corroborated in 

four Mayak studies. Estimated excess relative risk in these four studies (adjusted for smoking) were as 

follows: (1) 3.9 per Gy (95% CI: 2.6–5.8) in males and 19 per Gy (95% CI: 9.5–39) in females; 

(2) 7.1 per Gy (95% CI: 4.9–10) in males and 15 per Gy (95% CI: 7.6–29) in females at attained age of 

60 years; (3) 4.50 per Gy (95% CI: 3.15–6.10) in males; and (4) 0.11 per Sv (95% CI: 0.08–0.17) or 

0.21 per Sv (95% CI: 0.15–0.35), depending on the smoking-radiation interaction model that was 

assumed (these estimates per Sv correspond to 2.2 or 4.3 per Gy, respectively, assuming a radiation 

weighting factor of 20 for "-radiation). 

The risks of mortality and morbidity from bone and liver cancers have also been studied in Mayak 

workers. Increasing estimated plutonium body burden was associated with increasing liver cancer 

mortality, with higher risk in females compared to males. Relative risk for liver cancer for a cohort of 

males and females was estimated to be 17 (95% CI: 8.0–26) in association with plutonium uptakes 

>7.4 kBq; however, when stratified by gender, the relative risk estimates for females was 66 (95% CI: 

16–45) and higher than for males, 9.2 (95% CI: 3.3–23). Risk of bone cancer mortality in this same 

cohort (n=11,000) was estimated to be 7.9 (95% CI: 1.6–32) in association with plutonium uptakes 

>7.4 kBq (males and females combined). Risks of leukemia mortality, in the same cohort, were not 

associated with internal plutonium exposure. In a case control study of Mayak workers, the odds ratio for 

liver cancer was 11.3 (95% CI: 3.6–35.2) for subjects who received doses >2.0–5.0 Gy (relative to 0– 

2.0 Gy) and the odds ratios for hemangiosarcomas were 41.7 (95% CI: 4.6–333) for the dose group >2.0– 

5.0 Gy, and 62.5 (95% CI: 7.4–500) for the dose group >5.0–16.9 Gy; doses were estimated based on 

periodic urine sampling. A study reported averaged-attained age ERRs for liver cancer of 2.6 per Gy 

(95% CI: 0.7–6.9) for males and 29 per Gy (95% CI: 9.8–95) for females, and averaged-attained age 

ERRs for bone cancer of 0.76 per Gy (95% CI: <0–5.2) for males and 3.4 per Gy (95% CI: 0.4–20) for 

females. Elevated risks for bone cancer were observed only for workers with plutonium doses exceeding 

10 Gy. For lung and bone cancer, the ERR declined with attained age, and for lung cancer, the ERR 

declined with age at first plutonium exposure. 

Consistent with findings from human epidemiological studies, results of animal studies show that tissue 

location of plutonium-induced cancer is compound-dependent. A significant amount of plutonium from 

relatively soluble 239Pu(NO3)4 and 238PuO2 (more soluble than 239PuO2 due to higher specific activity of 

238Pu compared to 239Pu) is distributed to bone and liver. In contrast, relatively insoluble 239PuO2 is 

primarily retained in lung and associated lymph nodes, with approximately 10, 1, 0.2, and 0.002% 

relocating to liver, skeleton, spleen, and kidney, respectively. Bone tumors (predominantly 
PLUTONIUM 13 

2. RELEVANCE TO PUBLIC HEALTH 

osteosarcomas) were the primary cause of cancer deaths in dogs exposed once to 238PuO2 aerosols; lung 

tumor incidences were also relatively high in these dogs, and liver tumors appeared to be a contributing 

cause of death in a few 238PuO2-exposed dogs. The pattern of tumor development in dogs exposed to 

239Pu(NO3)4 was similar to that of dogs exposed to 238PuO2, with tumors observed in lung, bone, and liver 

(principally of bile- duct epithelium). Bone tumors were the main cause of death in the exposure groups 

with mean initial lung burdens of 1 and 5.9 kBq/kg. In contrast to the high incidences of bone tumors in 

the dogs exposed to 238PuO2 or 239Pu(NO3)4 aerosols, cancer deaths in dogs exposed to aerosols of the 

relatively insoluble 239PuO2 were predominantly associated with lung tumors consisting mainly of 

papillary adenocarcinomas based on a lifespan composite study. Tumor incidences at other sites in the 

239PuO2-exposed dogs were not statistically significantly different from those of controls. Earlier and 

shorter studies reported bronchiolo-alveolar carcinoma as the most frequently identified cancer type. 

Respiratory Effects. Possible associations between exposure to plutonium and respiratory tract 

disease have been examined in studies of workers at U.S. plutonium production and/or processing 

facilities (Hanford, Los Alamos, Rocky Flats), as well as facilities in Russia (Mayak) and the United 

Kingdom (e.g., Sellafield). Collectively, these studies have not found significant associations between 

mortality rates from respiratory tract disease, other than cancer, and exposures to plutonium among 

workers at these facilities. Possible associations between exposure to plutonium and pulmonary fibrosis 

were examined in a cohort of workers (n=326) at Rocky Flats. The study assessed lung interstitial 

abnormalities from the most recent available x-rays in relation to estimated lung equivalent dose from 

plutonium. Estimated lung equivalent doses ranged from 0 to 28 Sv (approximately 73% <1 Sv). The 

odds ratio (adjusted for age, smoking status, and evidence from pleural abnormalities from possible 

asbestos exposure) was significant for the dose group 10 Sv (5.3, 95% CI: 1.2–23.4). A report of one 

study was based on scoring radiographs for the severity of chest abnormalities considered consistent with 

fibrosis, and did not include information regarding a possible association between these lung 

abnormalities and clinical symptoms of disease. 

Radiation pneumonitis has been observed following inhalation exposure of dogs, nonhuman primates 

(monkeys and baboons), and rodents to plutonium (primarily insoluble) compounds, and was identified as 

primary, major contributing, or incidental cause of death in some dogs and nonhuman primates that 

inhaled 238PuO2, 239PuO2, or 239Pu(NO3). Results of lifetime studies in dogs indicate that radiation 

pneumonitis in the 239PuO2-exposed dogs occurred at lower ILBs and had a shorter time to onset 

compared to 238PuO2- or 239Pu(NO3)4-exposed dogs. This observation is consistent with the toxicokinetic 

differences observed for inhaled plutonium compounds, showing that inhaled 239PuO2 is cleared from the 
 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 14 

2. RELEVANCE TO PUBLIC HEALTH 

lung more slowly than 238PuO2 and 239Pu(NO3)4. The radiation pneumonitis/pulmonary fibrosis 

progressively impaired lung function, including alveolar-capillary gas exchange, resulting in increases in 

respiratory rate, minute volume, arterial CO2 pressure, and lung stiffness, along with decreases in tidal 

volume and arterial O2 pressure. Increases in radiation dose and dose rate corresponded to reduced times 

to the onset of symptoms and increased severity of effects. Radiation pneumonitis tended to be observed 

at lower ILBs in the 0.75 and 1.5 μm AMAD groups than in the 3.0 μm AMAD group. 

Hematological Effects. Possible associations between exposure to plutonium and mortality from 

hematopoietic diseases have been examined in studies of workers at plutonium production and/or 

processing facilities in the United States (Rocky Flats), United Kingdom (Sellafield). Collectively, these 

studies have not found significant associations between mortality rates from diseases of blood or bloodforming organs and exposures to plutonium among workers at these facilities. 

Compound- and dose-dependent decreased numbers of selected white blood cells were observed in dogs 

exposed to plutonium aerosols. Primary hematological effects following pulmonary deposition of 238PuO2 

and 239Pu(NO3)4 were lymphopenia and neutropenia, whereas lymphopenia was both the first biological 

effect to be observed and the primary hematological effect of inhaled 239PuO2. Persistent hematological 

effects occurred in 238PuO2- and 239PuO2-exposed dogs with initial lung burdens as low as 0.28 kBq/kg 

initial lung burdens that elicited hematological effects in 239Pu(NO3)4-exposed dogs appeared to be 

somewhat higher (mean initial lung burdens ≥5.91 kBq/kg. For 239PuO2-exposed dogs, the time of onset 

for significant lymphopenia was inversely related to dose (112 days, 180 days, 1 year, or up to 5 years for 

ILBs of 29, 14, 6.4, and 3.7 kBq/kg lung, respectively). Decreased lifespan was observed, although some 

of these dogs exhibited a return to normal lymphocyte counts after 5 years. No changes in red blood cell 

counts were observed through year 7 other than a compensatory increase in animals with pneumonitis or 

pulmonary fibrosis. Plutonium accumulated in the lymph nodes of the 239PuO2-exposed dogs, resulting in 

lymphoid atrophy and fibrosis, especially in the trachiobronchial region. The lymphopenia was 

considered to be the result of lymphocytes being irradiated as they passed through pulmonary lymph 

nodes. 

Hepatic Effects. Possible associations between exposure to plutonium and mortality from liver 

disease (e.g., liver cancer) have been examined in studies of workers at U.S. plutonium production and/or 

processing facilities (Hanford, Los Alamos, Rocky Flats), as well as facilities in Russia (Mayak) and the 

United Kingdom (e.g., Sellafield). Collectively, these studies have not found significant associations 
 

 

 

 

 

 

 

 

 

PLUTONIUM 15 

2. RELEVANCE TO PUBLIC HEALTH 

between mortality rates for liver disease, other than cancer, and exposures to plutonium among workers at 

these facilities. 

Elevated serum liver enzymes (indicative of adverse liver effects),were the most consistent indicators of 

non-neoplastic liver effects in dogs exposed to aerosols of 238PuO2 and 239Pu(NO3)4 at levels resulting in 

mean initial lung burdens ≥0.36 and ≥0.19 kBq/kg, respectively. No consistent changes in serum liver 

enzymes were seen in 239PuO2-exposed dogs. Although elevated liver enzymes may serve as indicators of 

hepatotoxicity, clinical signs of liver dysfunction (i.e., ascites, icterus clotting disorders) were not 

observed in the 238PuO2-exposed dogs. 

Musculoskeletal Effects. Possible associations between exposure to plutonium and mortality from 

bone disease (e.g., bone cancer) and other musculoskeletal diseases have been examined in studies of 

workers at U.S. plutonium production and/or processing facilities (Hanford, Los Alamos, Rocky Flats), as 

well as facilities in Russia (Mayak) and the United Kingdom (e.g., Sellafield). Collectively, these studies 

have not found significant associations between mortality rates for bone or musculoskeletal disease, other 

than cancer, and exposures to plutonium among workers at these facilities. Radiation osteodystrophy, 

observed in dogs with high intakes of plutonium, would be expected in humans following intake of large 

amounts of plutonium. 

Radiation osteodystrophy, characterized by peritrabecular fibrosis, osteosclerosis, and osteoporosis, was 

observed on necropsy in dogs exposed to 238PuO2. The incidence and severity was dose-related and was 

seen at mean initial lung burdens as low as 1.17 kBq/kg; necrotic osteoblasts and empty lacunae near 

endosteal surfaces were observed at relatively high initial lung burdens. Although osteodystrophy in 

238PuO2 exposed dogs was often associated with bone tumors, it also occurred in the absence of bone 

tumors. Radiation osteodystrophy has also been reported in dogs that inhaled 239Pu(NO3)4. 

Immunological Effects. Possible associations between exposure to plutonium and mortality from 

immunological or lymphoreticular diseases have been examined in studies of workers at plutonium 

production and/or processing facilities in the United States (Rocky Flats) and the United Kingdom 

(Sellafield). Collectively, these studies have not found statistically significant associations between 

mortality rates from diseases of the immunological or lymphoreticular systems and exposures to 

plutonium among workers at these facilities. 
 

 

 

 

 

 

 

 

 

PLUTONIUM 16 

2. RELEVANCE TO PUBLIC HEALTH 

Histopathologic lesions of lymph nodes, particularly tracheobronchial lymph nodes, have been observed 

following exposure of dogs to aerosols of 238PuO2, 239PuO2, or 239Pu(NO3)4. Fibrosis and loss of lungassociated and mediastinal lymph nodes were observed in dogs exposed to 238PuO2 at levels resulting in 

mean initial lung burdens ≥10 kBq/kg. Severity of non-neoplastic lesions was dose-related, progressing 

from lymphoid atrophy of medullary cords to significant lymph node atrophy with hypocellular scar 

tissue replacing lymphoid tissue. Similar dose-related atrophy and fibrosis of lung-associated, 

mediastinal, sternal, and hepatic lymph nodes were observed in dogs exposed to 239PuO2. Sclerotic lymph 

nodes were observed in the groups of 239Pu(NO3)4-exposed dogs with mean initial lung burdens 

≥5.91 kBq/kg, but lymph node lesions in these dogs were considered less severe than those observed in 

238PuOs- or 239PuO2-exposed dogs. 

Results of studies on immunological function indicate that inhalation exposure to 239PuO2 impairs T-cell 

response to antigens, as indicated by decreased response to antigen. A study detected accelerated aging of 

the T-cell response to mitogenic stimulation in dogs that had been exposed to 239PuO2 10 years earlier. 

Other reports of 239PuO2-induced effects from plutonium exposure include decreases in pulmonary 

alveolar macrophages in mice and depressed antibody-forming cells in hamsters. 

Cardiovascular Effects. Possible associations between exposure to plutonium and cardiovascular 

disease have been examined in studies of workers at production and/or processing facilities in the United 

Kingdom (Sellafield). One study compared mortality rates between plutonium workers and other 

radiation workers within a cohort of Sellafield workers and found the mortality rate ratios were 

significantly elevated for cerebrovascular disease (1.27, p<0.05) in a cohort of Sellafield workers. The 

cumulative internal uptakes of plutonium in the cohort were estimated to range from 0 to 12 kBq, with 

approximately 75% of the cohort having cumulative uptakes ≤250 Bq. Another study compared mortality 

rates between plutonium workers and other radiation workers within a cohort of Sellafield workers and 

found that morality rate ratios for plutonium workers were significantly elevated for deaths from 

circulatory disease (2.18, p<0.05) and ischemic heart disease (4.46, p<0.01). 

No significant changes in cardiovascular function were seen in dogs exposed to 239PuO2 at initial lung 

burdens up to and including those resulting in radiation pneumonitis; observed right ventricular 

hypertrophy was most likely a compensatory response to decreased respiratory function. 

Gastrointestinal Effects. Gastrointestinal effects were observed in rats following oral administration 

of 238Pu/kg (as plutonium citrate) by gavage. Effects included mild hypertrophy of the crypts of the small 
 

 

 

 

 

 

PLUTONIUM 17 

2. RELEVANCE TO PUBLIC HEALTH 

intestine in neonatal rats that received an oral dose of 5,300 kBq 238Pu/kg; total obliteration of epithelial 

cells and crypts, combined with intestinal hemorrhaging, were noted in rats that received 17,400 kBq 

238Pu/kg. Increased neutrophils were noted on the surface epithelium and superficial cellular layers of the 

large intestine in adult rats given 155 μCi 238PuO2/kg (5,740 kBq/kg). This effect was noted at 3 (but 

not 6) days posttreatment. 

2.3 MINIMAL RISK LEVELS (MRLs) 

Inhalation MRLs 

No acute-, intermediate-, or chronic-duration inhalation MRLs were derived for plutonium due to the lack 

of suitable human or animal data regarding health effects following inhalation exposure to plutonium. 

The strongest evidence for plutonium exposure-response and radiation dose-response relationships in 

humans is for cancers of the lung, liver, and bone. Although non-neoplastic lesions have been observed 

in animals exposed to 238PuO2, 239PuO2, and 239Pu(NO3)4, these lesions occurred in association with acute 

exposures that also resulted in fatal cancers. 

Oral MRLs 

No acute-, intermediate-, or chronic-duration oral MRLs were derived for plutonium due to the lack of 

suitable human or animal data regarding health effects following oral exposure to plutonium. No data are 

available on exposure- and radiation dose-response relationships in humans for oral exposures to 

plutonium. Animal studies of health effects of oral exposures to plutonium have not examined major 

health outcomes that would be expected to occur from absorbed plutonium (e.g., effects on skeleton, liver, 

and lymphopoietic systems). 
 

PLUTONIUM 18 

2. RELEVANCE TO PUBLIC HEALTH 

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PLUTONIUM 19 

3. HEALTH EFFECTS 

3.1 INTRODUCTION 

The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and 

other interested individuals and groups with an overall perspective on the toxicology of plutonium. It 

contains descriptions and evaluations of toxicological studies and epidemiological investigations and 

provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health. 

A glossary and list of acronyms, abbreviations, and symbols can be found at the end of this profile. 

Plutonium (Pu) is a radioactive element and a member of the actinides in the periodic table. Although 

trace amounts of plutonium exist naturally in the environment, the plutonium in the environment today 

has been (and continues to be) formed primarily from anthropogenic activity related to nuclear fission. 

Environmental plutonium levels are generally low and not of significant health concern. Anthropogenic 

isotopes with masses ranging from 228–247 have been produced and recorded on the chart of the 

nuclides; however, 238Pu and 239Pu, in their oxide and nitrate forms, are the plutonium isotopes most 

widely used in health effects studies. They are also the dominant isotopes that contribute to 

environmental and occupational exposure. Plutonium nitrates are associated with dissolving uraniumplutonium metal matrices after plutonium is produced in a nuclear reactor or by an accelerator. 

Plutonium oxides form on the surface of plutonium metal and are released through the machining of 

plutonium metal parts or the incomplete fissioning of plutonium during weapons detonation. 

Most plutonium isotopes emit a high energy (generally >5 MeV) alpha particle and low energy (<20 keV) 

gamma and x-rays as they transform into uranium. The others (241Pu and 243Pu) undergo beta minus 

decay and transform into isotopes of americium. The radiation dose from plutonium can be designated as 

either external (if the material is outside the body) or internal (if it is inside the body). The total radiation 

dose is the sum of external and internal radiation doses. The external dose from most plutonium isotopes 

is low because the x- and gamma-rays are of very low branching intensity and energy and the high energy 

alpha particles travel only very short distances and can only affect the outermost (epidermal) layers of 

intact skin even when in direct dermal contact. External beta emissions from isotopes such as 241Pu can 

travel slightly farther and may even penetrate the outer dermal layers, but are generally not of significant 

health concern unless a beta-emitting plutonium isotope comes into direct contact with the skin. Extreme 

skin contamination from plutonium-produced alpha and beta radiation, which could potentially occur in 

accidents or the workplace, might induce dermal and subdermal effects such as erythema, ulceration, or 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 20 

3. HEALTH EFFECTS 

even tissue necrosis. Internally deposited plutonium, however, possesses the potential to produce 

significant health effects via transfer of energy from alpha particles to nearby cellular molecules. Once 

plutonium is internalized, the distribution, retention, and excretion kinetics, paired with the plutonium 

decay and energy deposition parameters, determine how the radiation dose increases over time. 

In radiation biology, the term absorbed dose refers to the amount of energy deposited by radiation per unit 

mass of material (e.g., tissue), and is expressed in units of rad or gray (Gy) (see Appendix D for a detailed 

description of principles of ionizing radiation). One Gy is equivalent to 100 rad. Because alpha radiation 

is more biologically damaging internally than other types of radiation (i.e., x-rays, gamma rays, beta 

particles), a given absorbed dose (rad or Gy) is multiplied by a radiation weighting factor of 20 for alpha 

radiation or 1 for x-rays, gamma rays, and beta particles to obtain a quantity that expresses, on a common 

scale for all ionizing radiation, the biological damage (dose equivalent in units of rem or Sievert [Sv]) to a 

particular tissue. One Sv is equivalent to 100 rem. The committed dose equivalent is typically the 

radiation dose to a particular organ or tissue that is received from an intake of radioactive material by an 

individual during the 50-year period following the intake. The internal dose from plutonium is estimated 

using the quantity of material entering the body (via inhalation, ingestion, or dermal absorption), the 

biokinetic parameters for plutonium (distribution, retention, and excretion), the energies and intensities of 

the various radiations emitted, and the parameters describing the profile of absorbed energy within the 

body. For example, for a person who inhales a given activity of 239Pu (measured in becquerel [Bq] or 

curies [Ci]), a certain portion is retained and the body will absorb all of the alpha and beta energy emitted 

and some of the gamma energy in a pattern reflecting the temporal and spatial (tissue) distribution of the 

239Pu (which might be a function of age), the isotope decay rate, the production and decay rates of the 

progeny radionuclides, and radiation energy absorption factors. Each tissue, therefore, receives a tissuespecific radiation dose. The effective dose reflects the integration of dose over the time interval of 

interest and a tissue weighting factor scheme based on the relative sensitivities of the tissues and organs. 

Radiation-induced adverse health effects are related to the extent of molecular damage resulting from 

both direct ionization of atoms within range of the emitted radiation energy and interaction of radiationproduced free radicals with nearby molecules. Tissue damage occurs when the molecular damage is 

sufficiently extensive and insufficiently repaired in a timely manner. 

Uptake-to-dose conversion factors (dose coefficients) are typically expressed in terms of committed dose 

equivalent per unit intake of activity (Sv/Bq). Age-specific dose coefficients for isotope-specific 

inhalation and/or ingestion are available in U.S. EPA Federal Guidance Report Number 11 (EPA 1988b); 

U.S. EPA Federal Guidance Report Number 13 (EPA 1999) and supplemental CD (EPA 2002); 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 21 

3. HEALTH EFFECTS 

International Commission on Radiological Protection (ICRP) publications 56 (ICRP 1990), 71 (ICRP 

1996a), and 72 (ICRP 1996b); and the ICRP CD-ROM system (ICRP 2001). 

3.2 DISCUSSION OF HEALTH EFFECTS OF PLUTONIUM BY ROUTE OF EXPOSURE 

To help public health professionals and others address the needs of persons living or working near 

hazardous waste sites, the information in this section is organized first by route of exposure (inhalation, 

oral, and dermal) and then by health effect (death, systemic, immunological, neurological, reproductive, 

developmental, genotoxic, and carcinogenic effects). These data are discussed in terms of three exposure 

periods: acute (14 days or less), intermediate (15–364 days), and chronic (365 days or more). 

Levels of significant exposure for each route and duration are presented in tables and illustrated in 

figures. The points in the figures showing no-observed-adverse-effect levels (NOAELs) or lowestobserved-adverse-effect levels (LOAELs) reflect the actual doses (levels of exposure) used in the studies. 

LOAELs have been classified into "less serious" or "serious" effects. "Serious" effects are those that 

evoke failure in a biological system and can lead to morbidity or mortality (e.g., acute respiratory distress 

or death). "Less serious" effects are those that are not expected to cause significant dysfunction or death, 

or those whose significance to the organism is not entirely clear. ATSDR acknowledges that a 

considerable amount of judgment may be required in establishing whether an end point should be 

classified as a NOAEL, "less serious" LOAEL, or "serious" LOAEL, and that in some cases, there will be 

insufficient data to decide whether the effect is indicative of significant dysfunction. However, the 

Agency has established guidelines and policies that are used to classify these end points. ATSDR 

believes that there is sufficient merit in this approach to warrant an attempt at distinguishing between 

"less serious" and "serious" effects. The distinction between "less serious" effects and "serious" effects is 

considered to be important because it helps the users of the profiles to identify levels of exposure at which 

major health effects start to appear. LOAELs or NOAELs should also help in determining whether or not 

the effects vary with dose and/or duration, and place into perspective the possible significance of these 

effects to human health. 

The significance of the exposure levels shown in the Levels of Significant Exposure (LSE) tables and 

figures may differ depending on the user's perspective. Public health officials and others concerned with 

appropriate actions to take at hazardous waste sites may want information on levels of exposure 

associated with more subtle effects in humans or animals (LOAELs) or exposure levels below which no 
 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 22 

3. HEALTH EFFECTS 

adverse effects (NOAELs) have been observed. Estimates of levels posing minimal risk to humans 

(Minimal Risk Levels or MRLs) may be of interest to health professionals and citizens alike. 

A User's Guide has been provided at the end of this profile (see Appendix B). This guide should aid in 

the interpretation of the tables and figures for Levels of Significant Exposure and the MRLs. 

3.2.1 Inhalation Exposure 

Possible associations between exposure to plutonium and adverse health outcomes have been examined in 

studies of workers at the U.S. plutonium production and/or processing facilities (Hanford, Los Alamos, 

Rocky Flats), as well as facilities in Russia (e.g., Mayak) and the United Kingdom (e.g., Sellafield). 

Strengths and weaknesses of each study must be considered in interpreting the overall weight of evidence 

for plutonium-associated health outcomes in these populations. Studies that have individual subject 

plutonium dose or exposure measurements and that present exposure- or dose-response analyses are much 

stronger than those that simply compare risks for a group of exposed subjects with those for a group of 

unexposed subjects. A common study design has been to construct plutonium worker cohorts based 

solely on whether the individuals had been monitored for plutonium. However, this strategy may result in 

inclusion of workers who have been monitored but never experienced an internal plutonium deposition. 

The magnitude of the doses received in the study population is also an important design factor. In 

general, studies of populations that experienced relatively small plutonium radiation doses have limited 

statistical power for detecting plutonium effects; this includes all of the U.S. and U.K. worker studies. 

Failure to find significant associations between plutonium exposure and/or radiation dose in low-dose 

studies does not mean that such associations do not exist. In addition to statistical power, biological 

plausibility of findings must be considered. Effects observed in organs that receive relatively large 

plutonium radiation doses (e.g., lung, liver, bone) are more credible than effects observed in organs that 

are likely to have received relatively small plutonium radiation doses and may have been caused by other 

uncontrolled factors in the study (e.g., other forms of radiation, chemical exposures). Similarly, 

associations to plutonium exposure are more uncertain when observed effects are limited to tissues that 

receive relatively small doses of plutonium (i.e., in the absence of effects in tissues that received much 

higher plutonium radiation doses). Elevated risk in plutonium-exposed workers does not necessarily 

imply causal association to plutonium. Demonstration of a consistent increase in risk in association with 

increasing plutonium radiation dose is far stronger evidence of a causal relationship than a simple 

elevation of risk in an exposed group compared to an unexposed referent group. Common to the 

interpretation of any epidemiological studies of workers are factors such as the “healthy worker effect" 
 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 23 

3. HEALTH EFFECTS 

(e.g., relatively low mortality or morbidity rates in workers because of loss of unhealthy workers from the 

working population), false positive findings attributable to assessments of multiple outcomes in a single 

study, and adequate treatment of confounding and co-variables that may affect the measured outcome 

independently or in association with plutonium radiation dose. 

Numerous animal studies are available regarding adverse health effects following inhalation exposure to 

plutonium compounds; studies were conducted in nonhuman primates, dogs, and rodents. The discussion 

of animal studies in this profile has primarily focused on the wealth of information that has developed on 

the toxicology of plutonium in beagle dogs exposed by inhalation. The series of lifetime dog studies, 

conducted by the Inhalation Toxicology Research Institute (ITRI) and Battelle Pacific Northwest 

Laboratory (PNL) as a multi-laboratory effort during the 1950s through the 1990s, provide the most 

complete evaluations of the adverse health effects associated with inhaled plutonium compounds. Dogs 

were selected as the experimental model for these studies based on their relatively long life span (12– 

15 years) and physiologic and anatomical features common to dogs and humans (particularly regarding 

hematopoietic, pulmonary, and skeletal systems) (DOE 1989). Although conducted by two different 

laboratories, the ITRI and PNL studies used similar experimental protocols and evaluated the same 

comprehensive toxicological end points, providing an extensive database on the toxicity of inhaled 

plutonium. Therefore, information provided in the following sections primarily relies on data from the 

lifetime exposure studies in the ITRI and PNL dogs; results of inhalation studies conducted in rodents and 

nonhuman primates are briefly reviewed and included as supportive data. 

The most widely studied plutonium compound, 239PuO2, is only moderately soluble, which results in longterm retention in the lung following inhalation exposure. Other plutonium compounds assessed in 

lifetime dog studies include 238PuO2 (more rapidly cleared from the lung than 239PuO2 due to much higher 

specific activity, which results in fragmentation) and 239Pu(NO3)4 (more chemically soluble than 239PuO2). 

Studies conducted by PNL investigated the effects of single inhalation exposures of adult dogs to 238PuO2, 

239PuO2, or 239Pu(NO3)4. The lifetime exposure studies conducted by ITRI evaluated the effects of single 

exposures of adult dogs to 238PuO2 and 239PuO2 of varying particle sizes, single exposures of juvenile and 

elderly dogs to 239PuO2, and repeated exposures of adult dogs to 239PuO2 (Table 3-1). An overview of the 

complete series of lifetime exposure studies conducted by both PNL and ITRI was published by DOE 

(1989). A substantial amount of health effects data for the Pu-exposed dogs is available. In addition, 

comprehensive reports were published in the late 1990s for 238PuO2-induced health effects in the ITRI 

(Muggenburg et al. 1996) and PNL (Park et al. 1997) dogs. A comprehensive report has recently been 

finalized for 239PuO2-exposed dogs from the ITRI facility (Muggenburg et al. 2008). At present, available 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 24 

3. HEALTH EFFECTS 

Table 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 

Exposure and conversion information Study references 

238PuO2: 

ITRI evaluated single inhalation exposure of young adult male and female 

dogs (12–15 months of age) at two AMAD particle sizes, 1.6 and 2.9 μm. 

Test material was prepared at high calcining temperatures (700 C). 

Exposed dogs were assigned to one of six groups, which resulted in 

median ILBs (range) of 0 (0), 0.36 (0.10–0.69), 1.05 (0.77–1.55), 

2.84 (1.85–4.06), 5.99 (4.42–8.42), 11.2 (8.59–15.2), and 23.7 (15.3–45.4) 

kBq/kg body weight for dogs inhaling 1.6 μm AMAD particles, and 0 (0), 

0.47 (0.15–0.77), 1.35 (0.84–1.70), 3.00 (2.39–3.79), 7.02 (4.07–9.37), 

12.6 (10.4–15.6), and 25.4 (19.7–43.1) kBq/kg/body weight for dogs 

inhaling 2.9 μm AMAD particles. Because effects did not appear to depend 

on particle size, the study authors combined the results from the separate 

studies. 

PNL evaluated single inhalation exposure of young adult male and female 

dogs (12–20 months of age). Test material prepared at high calcining 

temperatures (750 C). Mean ILBs of 0, 0.13, 0.68, 3.1, 13, 52, and 

210 kBq were reported for controls and 6 experimental groups (Park et al. 

1997), and were converted to mean ILBs of 0, 0.01, 0.061, 0.28, 1.17, 4.68, 

and 18.9 kBq/kg body weight by dividing the reported ILBs by the reported 

median body weight of 11.1 kg at aerosol exposure. 

239PuO2: 

ITRI evaluated single inhalation exposure of young adult male and female 

dogs (12–15 months of age) at three different AMAD particle sizes, 0.75, 

1.5, and 3.0 μm. Test material was prepared at high calcining 

temperatures (700 C). Because effects did not appear to depend on 

particle size, the study authors combined the results. Median ILBs (range) 

of 0 (0), 0.19 (0.026–0.35), 0.63 (0.37–0.96), 1.6 (1.0–2.4), 3.7 (2.6–4.8), 

6.3 (5.2–9.3), 14 (10–20), and 30 (21–74) kBq/kg body weight were 

reported for controls and six experimental groups. 

PNL evaluated single inhalation exposure of young adult male and female 

dogs (12–20 months of age) at an AMAD particle size of 2.3 μm. The test 

material was prepared at high calcining temperatures (750 C). Mean ILBs 

of 0, 0.12, 0.69, 2.7, 11, 41, and 213 kBq were reported for controls and 

six experimental groups, and were converted to mean ILBs of 0, 0.01, 

0.064, 0.25, 1.0, 3.83, 19.9 kBq/kg body weight by dividing the reported 

ILBs by the reported mean body weight of 10.7 kg at the time of aerosol 

exposure. 

ITRI evaluated single and repeated exposure of young adult male and female 

dogs (12–15 months of age) at an AMAD particle size of 0.75 μm. 

Repeated exposures were once every 6 months for a total of 20 exposures. 

A mean ILB of 3.9 kBq/kg was reported for dogs exposed once; the mean 

total alveolar deposition was 5.3 kBq/kg body weight in the repeatedlyexposed dogs. 

DOE 1989; Gillett et 

al. 1988; Hahn et al. 

1991a; Muggenburg 

et al. 1996 

DOE 1978a, 1988a, 

1989; Park et al. 

1995, 1997; Weller et 

al. 1995a, 1996 

Diel et al. 1992; DOE 

1989; Hahn et al. 

1999; Muggenburg et 

al. 1988, 1999 

DOE 1988a, 1989; 

Weller et al. 1995b 

Diel et al. 1992; DOE 

1989 
 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 25 

3. HEALTH EFFECTS 

Table 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 

Exposure and conversion information Study references 

ITRI evaluated single exposure of juvenile male and female dogs (3 months 

of age) at an AMAD particle size of 1.5 μm. The dogs were placed into one 

of eight groups based on intended ILB, resulting in mean ILBs of 0, 0.018, 

0.11, 0.37, 1.1, 2.3, 3.7, 7.0, or 19 kBq/kg body weight. 

ITRI evaluated single exposure of aged male and female dogs (7–10 years of 

age) at an AMAD of 3.0 μm. The dogs were placed into one of five groups 

based on intended ILB. The reported mean ILBs of 0, 0.033, 0.091, 0.18, 

and 0.37 μCi/kg body weight were converted to 0, 1.22, 3.37, 6.6, and 

13.7 kBq/kg, respectively (1 μCi = 37 kBq). 

ITRI evaluated single inhalation exposures of beagle dogs (n=108 exposed 

and 18 controls for each sex) using three separate particle sizes (0.75, 1.5, 

and 3.0 μm AMAD with individual particle activities from 0.048 to 7.4 mBq), 

and four to eight graded exposure levels for each particle size (with median 

ILBs of 0.16, 0.63, 1.6, 3.7, 6.4, 14, and 29 kBq/kg lung). ILB was 

measured after allowing time for mucociliary clearance using 169Yb 

incorporated into the 239Pu particles as a tracer. Animals were followed until 

death. Information was collected on retention, distribution, respiratory 

function, and pathology. Data by time after exposure and particle size 

include percent activity retention, activity distribution and retention in five 

types of lymph nodes, lymphocyte counts, surviving fraction, lung dose, 

lung tumor probability, occurrence of radiation pneumonitis and its impact 

on respiratory function, malignant and benign tumors by organ system and 

type, causes of death, and competition between pneumonitis and lung 

cancer, Particle size was converted to activity, with 0.75 and 3.0 μm 

AMAD particles containing 0.048 and 7.4 mBq of 239Pu, respectively. 

239Pu(NO3)4: 

PNL evaluated single exposure of young adult male and female dogs (17– 

22 months of age) at an AMAD particle size of 0.81 μm. Mean ILBs of 0, 0, 

2±2; 8±4; 56±17; 295±67; 1,709±639; and 5,445±1,841 nCi were reported 

for unexposed controls, vehicle controls, and exposed groups 1–6, 

respectively, and were converted to mean ILBs of 0, 0, 0.0069, 0.030, 

0.207, 1.02, 5.91, and 18.83 kBq/kg body weight by converting nCi to kBq 

(1 nCi = 0.037 kBq), which were then divided by a mean body weight of 

10.7 kg (the reported mean body weight for the 239PuO2-exposed PNL 

dogs, which was assumed to represent the 239Pu(NO3)4-exposed PNL dogs 

as well since body weight data for these dogs were not located in available 

study reports). 

DOE 1989, 1994b 

DOE 1988d, 1989 

Muggenburg et al. 

2008 

Dagle et al. 1996; 

DOE 1986b;1988b, 

1989, 1994a; Park et 

al. 1995 

μCi = microCurie; AMAD = activity median aerodynamic diameter; ILB = initial lung burden; ITRI = Inhalation 

Toxicology Research Institute; kBq = kiloBequerel; PNL = Pacific Northwest Laboratory 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 26 

3. HEALTH EFFECTS 

239Pu(NO3)4 data from the dog studies consist of interim and annual reports and more recent publications 

that focus on selected end points of toxicity. The presentation of health effects in the dog studies from 

ITRI and PNL in this Toxicological Profile for Plutonium focuses primarily on results of the available 

comprehensive reports and secondarily on results of interim data. 

Inhalation exposures in the dog studies were quantified using radiological measurements to estimate 

initial plutonium burdens (activity or activity-per-body weight or activity-per-organ weight), rather than 

aerosol concentrations of plutonium. In the ITRI and PNL studies, exposure groups were defined as 

ranges or group means based on initial plutonium burdens. However, over the 30-year time span of 

publications, initial plutonium burdens were quantified using several different units (e.g., μCi, μCi/kg 

lung weight, kBq, kBq/kg body weight, total kBq deposited in the lung); thus, data obtained from a single 

study may have been reported in several different publications over a span of time during which changes 

may have been made in conventions for reporting initial lung burdens. The convention of kBq/kg body 

weight has been selected to express initial lung burden for the ITRI and PNL dog studies summarized in 

this toxicological profile for plutonium. Table 3-1 summarizes reported initial lung burden data from 

each of these studies, as well as any additional data used for conversions to the convention of kBq/kg 

body weight. Selected interim and final reports and all publicly-available comprehensive reports were 

consulted for relevant exposure and health effects data. It should be noted that for a particular study, 

various reports may vary slightly in estimated initial lung burdens. In this toxicological profile for 

plutonium, the most recent publications typically served as the definitive source of initial lung burden 

data. 

As discussed in Section 3.5, Mechanisms of Toxicity, plutonium-induced health effects are considered to 

be the result of energy deposited by alpha particle emissions in tissues that retain plutonium for extended 

periods (i.e., lung, bone, liver following inhalation exposure). Similar health effects would be expected 

from any alpha-emitting source that would result in similar cumulative tissue-specific radiation dose and 

dose rate. 

3.2.1.1 Death 

Epidemiological Studies in Humans. Possible associations between exposure to plutonium and mortality 

have been examined in studies of workers at the U.S. plutonium production and/or processing facilities 

(Hanford, Los Alamos, Rocky Flats), as wells as facilities in Russia (Mayak) and the United Kingdom 

(e.g., Sellafield). The most recent findings from these studies are summarized in Table 3-2. Collectively, 
 

 

 

 

 

 

 

 

 


 


 


 

PLUTONIUM 27 

3. HEALTH EFFECTS 

Table 3-2. Summary of Human Epidemiology Studies of Health Effects of 

Plutonium
 

Reference, study location,
 

period, and study description Dose measurementa Findings and interpretation
 

United States: 

Reference: Brown et al. 2004 

Location: Denver (Rocky Flats), 

Colorado 

Period: 1951–1989 

Design: retrospective case control 

Subjects: workers at Rocky Flats 

Plant; cases (n=180, 7 females); 

controls (n=720, 24 females) who 

also worked at the plant and were 

matched with cases for age, birth 

year, and gender 

Outcome measures: lung cancer 

mortality 

Analysis: incidence OR for 

cumulative internal lung dose, 

cumulative penetrating dose, period 

of first hire, and employment years 

(logistic regression models, adjusted 

for birth year and smoking) 

Reference: Gilbert et al. 1989b 

Location: Hanford, Washington 

Period: 1944–1981 

Design: retrospective cohort 

Subjects: workers at the Hanford 

plant (n=31,500, 12,600 females) 

who were hired during the period 

1944–1978. 

Outcome measures: cancer mortality 

Analysis: trend test for mortality 

ratios stratified by external radiation 

dose or internal Pu exposure 

(adjusted for age, calendar year, 

sex, and number of years 

monitored) 

Internal lung 

dose (mSv) Percent 

0 54 

0–100 18 

>100–400 13 

>400–644 5 

>644–900 5 

>940 5 

98% internal lung dose from 

plutonium or inbred 241Am 

Internal Pu 

exposure 

(kBq) Percent 

<0.074 28.7 

0.074–1.47 30 

>1.48 1.3 

In full cohort, OR for lung cancer mortality 

significant at dose strata 400–644 mSv, but 

was not significantly elevated at higher doses; 

there was no significant trend with dose. When 

restricted to subjects employed for 15– 

25 years, OR was significant at dose strata 

>644 mSv with significant dose trend; 

however, there was no evidence of a positive 

trend for those employed <10 years or 

≥25 years. 

Internal 

lung 

dose 

(mSv) 

OR (95% CI) full 

cohort 

OR (95% CI) 

employed 15– 

25 years 

0 1.0 (reference) 1.0 (reference) 

0–100 1.42 (0.87–2.33) 1.14 (0.46–2.86) 

>100–400 1.60 (0.83–3.10) 2.11 (0.86–5.20) 

>400–644 2.71 (1.20–6.09) 2.74 (0.92–8.19) 

>644–900 2.30 (0.96–5.53) 3.20 (1.15–8.94) 

>940 1.48 (0.56–3.89) 5.04 (1.55– 

16.40) 

No evidence for statistically significant excess 

cancer mortality or trend in cancer mortality 

with external radiation or Pu internal deposition 

(i.e., all cancers, digestive tract, lung, 

lymphatic and hematopoietic, prostatic). 
 

 

 

 

 


 


 


 

PLUTONIUM 28 

3. HEALTH EFFECTS 

Table 3-2. Summary of Human Epidemiology Studies of Health Effects of 

Plutonium
 

Reference, study location,
 

period, and study description Dose measurementa Findings and interpretation
 

Reference: Newman et al. 2005 

Location: Denver, Colorado 

Period: 1951–1998 

Design: retrospective cohort 

Subjects: male workers at Rocky 

Flats plant (n=326) hired between 

1951 and 1958 with lifetime doses 

>0.1 Sv; unexposed controls 

(n=194, 12 females) 

Outcome measures: lung opacity 

profusion score (based on most 

recent x-ray) for assessment of 

pulmonary fibrosis 

Analysis: multivariate logistic 

regression to test association 

between plutonium radiation dose 

categories and disease prevalence 

(covariates: age at x-ray, smoking 

status, evidence of pleural 

abnormalities [surrogate for 

asbestos exposure]) 

Reference: Voelz et al. 1997 

Location: Los Alamos, New Mexico 

Period: 1943–1990 

Design: retrospective cohort 

Subjects: adult male workers at Los 

Alamos National Laboratory 

exposed to plutonium in 1944–1945 

(n=26); controls (n=876) workers not 

exposed to plutonium 

Outcome measures: mortality 

Analysis: incidence rates of exposed 

group compared to controls 

(adjusted for age and year of death) 

Reference: Wiggs et al. 1994 

Location: Los Alamos, New Mexico 

Period: 1944–1990 

Design: retrospective cohort 

Subjects: male workers at Los 

Alamos National Laboratory 

(n=15,727 employed 1943–1973). 

Plutonium worker cohort consisted 

of 3,775 workers ever monitored for 

plutonium exposure 

Outcome measures: mortality 

Analysis: incidence rates for workers 

with plutonium whole-body 

deposition ≥74 Bq compared to 

<74 Bq (adjusted for age and year of 

death) 

Plutonium lung radiation dose 

in exposed group: 

Dose (Sv) n (percent) 

0–28 326 

0 194 (37%) 

>0–1 187 (36%) 

1–<5 101 (19%) 

5–<10 22 (4%) 

≥10 16 (3%) 

Pu body burden (Bq) 

mean 970 

median 565 

range 50–3,180 

Pu body dose (mSv) 

mean 2.08 

median 1.25 

range 0.1–7.2 

Pu body 

burden (Bq) n 

<74 3,472 

≥74 303 

Significant elevated risk for abnormal lung 

profusion score in lung dose strata ≥10 Sv: 

Lung dose (Sv) OR (95% CI) 

>0–<1 1.5 (0.6–3.8) 

1–<5 0.9 (0.3–2.6) 

5–<10 1.7 (0.5–6.6) 

≥10 5.3 (1.2–23.4) 

SMR and MRR not significantly elevated in 

plutonium workers (compared to controls): 

SMR MRR 

Category Deaths (95% CI) (95% CI) 

All deaths 7 0.43 (0.17– 0.77 (0.36– 

0.88) 1.6) 

All 3 0.75 (0.15– 1.5 (0.46– 

cancers 2.18) 4.9) 

Lung 1 0.68 (0.01– 3.31 (0.44– 

cancer 3.79) 25) 

Prostate 1 3.42 (0.04– No data 

cancer 19.04) 

Bone 1 96.4 (1.26– No data 

cancer 536.0) 

MRR not significantly associated with 

plutonium body burden (<74 Bq compared to 

≥74 Bq): 

Category MRR (95% CI) 

All deaths 0.89 (0.69–1.14) 

All cancers 1.07 (0.67–1.69) 

Respiratory tract cancer 1.77 (0.79–3.96) 

Lung cancers 1.78 (0.79–3.99) 

Bone cancer not reported (n=0) 

Lympho/hematopoietic 0.34 (0.05–2.24) 

cancer 
 

 

 

 

 

 

 

 

 


 


 


 

PLUTONIUM 29 

3. HEALTH EFFECTS 

Table 3-2. Summary of Human Epidemiology Studies of Health Effects of 

Plutonium
 

Reference, study location,
 

period, and study description Dose measurementa Findings and interpretation
 

Reference: Wing et al. 2004 

Location: Hanford, Washington 

Period: 1944–1994 

Design: retrospective cohort 

Subjects: workers at the Hanford 

plant (n=26,389, 8,145 females) who 

were hired during the period 1944– 

1978. Plutonium worker cohort 

consisted of workers in routine 

plutonium-associated jobs (n=3,065) 

or non-routine jobs (n=8,266). 

Outcome measures: cancer mortality 

Analysis: multivariate regression to 

test association between length of 

employment in jobs with plutonium 

exposure potential and mortality rate 

(covariates: age, race, gender, birth 

date, socioeconomic status, 

employment status) 

Russia: 

Reference: Gilbert et al. 2004 

Period: 1955–2000 

Design: retrospective cohort 

Subjects: workers at Mayak 

Production Association (n=21,790, 

5,332 female) employed during the 

period 1948–1972 

Outcome measures: lung cancer 

mortality 

Analysis: risk per unit of plutonium 

radiation dose (Poisson regression 

models, adjusted for age, gender, 

year of death, age at hire) 

Not reported 

Pu lung dose 

(Gy) n 

<DL 1,560 (25%) 

>0–0.2 3,688 (60%) 

>0.2–1.0 688 (11%) 

>1.0–3.0 163 (2.6%) 

>3.0–5.0 39 (0.6%) 

>5.0 55 (0.9%) 

mean: 0.24 Gy (lung) 

mean: 1.84 kBq (body) 

Workers in the plutonium-associated jobs 

category had lower death rates from all 

cancers, cancers of the lung, and “plutoniumcancers” (lung, liver, bone, and connective 

tissue) than other Hanford workers. Trends for 

increased mortality and duration of routine 

plutonium-associated jobs were as follows: 

Percent increase (± SE) in 

mortality per year in 

plutonium jobs (LRT for trend 

at 1 df; higher value means 

stronger association with job 

duration) 

Age <50 years Age ≥50 years 

Non-external 0.1±0.9 (0.01) 2.0±1.1 (3.37) 

deaths 

All cancers -1.5±1.7 (0.79) 2.6±2.0 (1.60) 

Pu cancers 0.6±0.05 (0.05) 4.9±3.3 (2.17) 

(lung, liver, 

skeletal, 

lymphatic) 

Lung cancers -1.0±2.7 (0.14) 7.1±3.4 (4.06) 

Cancer mortality risk was linearly related to 

plutonium radiation dose. Excess relative risk 

per Gy declined strongly with attained age 

(Gilbert et al. 2004). Increased ERR for lung 

cancer mortality in association with increasing 

lung dose (per Gy attained at age 60 years): 

Lung dose RR males RR females 

(Gy) (95% CI) (95% CI) 

>0–0.2 1.4 (1.0–1.8) 0.91 (<0.91– 

3.1) 

>0.2–1.0 2.4 (1.5–3.6) 16 (6.1–37) 

>1.0–3.0 10 (6.3–15) 

>3.0–5.0 19 (9.5–35) 

>1.0–5.0 15 (3.0–38) 

>5.0 33 (14–67) 250 (110–660) 

ERR per Gy 4.7 (3.3–6.7) 19 (9.5–39) 

lung dose 

ERR per Sv 0.23 (0.16– 0.93 (0.46– 

lung dose 0.33) 1.9) 

ERR per Gy 3.9 (2.6–5.8) 19 (7.7–51) 

lung dose 

(for subjects 

with 

smoking 

data, 

adjusted for 

smoking) 
 

 

 

 

 

 

 


 


 


 


 


 


 


 


 


 


 

PLUTONIUM 30 

3. HEALTH EFFECTS 

Table 3-2. Summary of Human Epidemiology Studies of Health Effects of 

Plutonium
 

Reference, study location,
 

period, and study description Dose measurementa Findings and interpretation
 

Reference: Gilbert et al. 2000 

Period: 1948–1996 

Design: retrospective cohort 

Subjects: workers at Mayak 

Production Association (n=11,000) 

hired during the period 1948–1958 

Outcome measures: liver cancer 

mortality 

Analysis: relative risk for plutonium 

body burden (general linear 

regression model adjusted for age, 

gender, year of death, external 

radiation) 

Reference: Jacob et al. 2005 

Period: 1948–1998 

Design: retrospective cohort 

Subjects: male workers at Mayak 

Production Association (n=5,058) 

employed during the period 1948– 

1972 

Outcome measures: lung cancer 

mortality 

Analysis: excess relative risk per 

plutonium dose unit (Sv) 

(mechanistic multistage regression 

model, adjusted for age and 

multiplicative or sub-multiplicative 

interaction with smoking) 

Reference: Koshurnikova et al. 2000 

Period: 1948–1996 

Design: retrospective cohort 

Subjects: workers at Mayak 

Production Association (n=11,000) 

hired during the period 1948–1958 

Outcome measures: bone cancer 

mortality 

Analysis: relative risk for plutonium 

body burden (general linear 

regression model adjusted for age, 

gender, year of death, external 

radiation) 

Pu body burden (kBq) 

Males 3.78 

Females 6.05 

Pu liver dose (Gy) 

Males 0.47
 

Females 0.88
 

n=2,207 (monitored)
 

Pu lung dose (Sv)
 

mean (range)
 

All plants 3.0 (0–24)
 

Pu production 8.7 (0–81)
 

Radiochemical 2.5 (0–15) 

Reactor 0.04 (0–0.40) 

Pu body burden (kBq) 

Males 3.78 

Females 6.05 

Pu bone surface dose (Gv) 

Males 2.99 

Females 5.56 

n=2,207 (monitored) 

Bone surface dose from 

Gilbert et al. (2000) 

Significantly increased RR within highest 

plutonium body burden stratum: 

Pu body 

burden 

(kBq) 

RR males 

(95% CI) 

RR females 

(95% CI) 

0–1.48 

1.4–7.40 

>7.4 

1.0 (reference) 

0.9 (0.1–3.2) 

9.2 (3.3–23) 

1.0 (reference) 

7.1 (0.9–59) 

66 (16–452) 

All workers 

>7.4 17 (8.0, 26) 

Significant ERR for lung cancer mortality in 

association with plutonium dose (per Sv), 

adjusted for smoking: 

Smoking interaction ERR per Sv (95% CI) 

Multiplicative 0.21 (0.15–0.35) 

Sub-multiplicative 0.11 (0.08–0.17) 

Significantly increased RR for bone cancer 

mortality within highest plutonium body burden 

stratum: 

Pu body burden (kBq) RR (95% CI) 

0–1.48 1.0 (reference) 

1.48–7.40 0.9 (0.05–5.5) 

>7.4 7.9 (1.6–32) 
 

 

 

 

 

 

 

 


 


 


 


 


 


 


 


 


 


 


 

PLUTONIUM 31 

3. HEALTH EFFECTS 

Table 3-2. Summary of Human Epidemiology Studies of Health Effects of 

Plutonium
 

Reference, study location,
 

period, and study description Dose measurementa Findings and interpretation
 

Reference: Kreisheimer et al. 2003 

Period: 1948–1999 

Design: retrospective cohort 

Subjects: male workers at Mayak 

Production Association (n=4,212) 

hired during the period 1948–1958 

Outcome measures: lung cancer 

mortality 

Analysis: excess relative risk per 

plutonium dose unit (Gy, Sv) 

(general linear regression models, 

adjusted for age and multiplicative 

interaction with smoking) 

Reference: Shilnikova et al. 2003 

Period: 1949–1997 

Design: retrospective cohort 

Subjects: workers at Mayak 

Production Association (n=21,557, 

24.2% female) employed during the 

period 1948–1972 

Outcome measures: cancer mortality 

Analysis: regression models, 

(adjusted for age, gender, year of 

death, age at hire) 

Reference: Tokarskaya et al. 2006 

Period: 1972–1999 

Design: retrospective case-control 

Subjects: workers at Mayak 

Production Association (n=44 

cases); controls (n=111) workers not 

exposed to plutonium matched for 

year of birth, gender, year of starting 

work, work assignment 

Outcome measures: liver cancer 

morbidity 

Analysis: OR for plutonium liver 

dose (Gy) (logistic regression model, 

adjusted for alcohol consumption, 

-radiation dose) 

Pu lung dose (Gy) 

Pu production 0.450 

Radiochemical 0.140 

Reactor Not reported 

Pu body burden 

2.9–18.5 kBq 

Cumulative lung Pu dose: 

0.28–1.92 Gy 

(hired 1948–1954) 

Pu liver dose 

Quartile (Gy) 

1st 0 

2nd 0–0.07 

3rd >0.07–0.54 

4th >0.54–16.9 

Significant ERR for lung cancer mortality: 

ERR unit ERR (95% CI) 

ERR per Gy 

ERR per Sv (assuming 

-radiation quality 

factor=20) 

4.50 (3.15–6.10) 

0.23 (0.16–0.31) 

Increased risk of plutonium cancers (i.e., lung,
 

liver or skeletal) in association with increased
 

internal exposure (p<0.001). Increased risk of
 

leukemia in association in increasing external
 

gamma radiation dose (p=0.04), but not for
 

internal exposure to plutonium.
 

Significant ORs for liver cancers:
 

Pu liver dose (Gy) OR (95% CI)
 

All liver cancers 

0–2.0 1.0 (reference) 

>2.0–16.9 11.3 (3.6–35.2) 

Hemiangiosarcomas 

0–2.0 1.0 (reference) 

>2.0–5.0 41.7 (4.6–333) 

>5.0–16.9 62.5 (7.4–500) 
 

 

 

 

 

 


 


 


 


 


 


 


 


 


 


 

PLUTONIUM 32 

3. HEALTH EFFECTS 

Table 3-2. Summary of Human Epidemiology Studies of Health Effects of 

Plutonium
 

Reference, study location,
 

period, and study description Dose measurementa Findings and interpretation
 

United Kingdom: 

Reference: Carpenter et al. 1998 

Period: Before 1976–1988 

Design: retrospective cohort 

Subjects: workers at U.K. nuclear 

facilities during the period before 

1976–1980 (n=40,761, 

3,366 females). Plutonium worker 

cohort consisted of 12,498 workers 

ever monitored for plutonium 

exposure 

Outcome measures: cancer mortality 

Analysis: mortality incidence rates in 

workers monitored for plutonium 

exposure compared to workers not 

monitored (adjusted for age, gender, 

year of death, social class) 

Reference: McGeoghegan et al. 

2003 

Period: 1947–1998 

Design: retrospective cohort 

Subjects: female workers ever 

employed at Sellafield plant 

(n=6,376). Plutonium worker cohort 

consisted of 5,203 workers ever 

monitored for plutonium exposure 

Outcome measures: mortality and 

cancer morbidity 

Analysis: mortality and morbidity 

incidence rates in plutonium workers 

compared to other radiation and 

non-radiation workers 

Not reported 

Pu internal lung radiation 

dose: 

Dose (mSv) 

Mean 3.45 

Median 1.59 

Maximum 178 

5th% 0.36 

95th% 8.89 

MRR for workers monitored for plutonium were 

not significant (monitored compared to not 

monitored): 

Category MRR (95% CI) 

All cancers 1.01 (0.90–1.13) 

Lung and bronchus 

cancer 1.18 (0.97–1.42) 

Pleura cancer 1.97 (0.71–5.49) 

Liver and gall bladder 

cancer 2.00 (0.59–6.38) 

Bone cancer 1.01 (0.12–7.35) 

Trends for all cancers were statistically 

significant (p<0.05), while those for lung and 

bronchus cancer were not: 

Years since MRR lung and 

first MRR bronchus 

monitored all cancers* cancer 

<10 0.79 0.95 

10–19 0.95 1.26 

≥20 1.20 1.26 

Number of 

years 

monitored 

MRR 

all cancers* 

MRR lung and 

bronchus 

cancer 

<10 0.85 1.09 

10–19 0.92 0.99 

≥20 1.15 1.45 

Significant (p<0.05) MRR for plutonium 

workers compared to other radiation workers 

(CIs not reported) with no significant trends 

with organ-specific plutonium radiation doses: 

MRR (*p<0.01; 

Category **p<0.05)
 

Mortality
 

All deaths 2.20*
 

All cancers 3.30*
 

Breast cancer 3.77**
 

Circulatory disease 2.18**
 

Ischemic heart 5.46*
 

disease 

Respiratory tract 4.05 

disease 

Digestive system 0.65 

disease 

Morbidity 

Breast cancer 2.61** 
 

 

 

 

 


 


 


 

PLUTONIUM 33 

3. HEALTH EFFECTS 

Table 3-2. Summary of Human Epidemiology Studies of Health Effects of 

Plutonium
 

Reference, study location,
 

period, and study description Dose measurementa Findings and interpretation
 

Reference: Omar et al. 1999 

Period: 1947–1992 

Design: retrospective cohort 

Subjects: workers at Sellafield plant 

(n=14,319, 2,689 females) who were 

employed at any time during the 

period 1947–1975; plutonium worker 

cohort consisted of 5,203 workers 

ever monitored for plutonium 

exposure 

Outcome measures: mortality and 

cancer morbidity 

Analysis: mortality and morbidity 

incidence (1971–1986) in plutonium 

workers compared to other radiation 

and non-radiation workers 

Cumulative Pu exposure: 

Exposure (Bq) Percent 

0–250 75 

>250–500 13 

>500–750 7 

>750–1,000 2 

>1,000 3 

Pu internal radiation dose 

(mean) : 

Tissue Dose (Sv) 

Bone surfaces 3,282 

Lungs 45–896 

Liver 421 

Digestive tract 8 

Whole body 219–355 

Significant (*p<0.01; **p<0.05) MRR for 

plutonium workers compared to other radiation 

workers (CIs not reported). Significant 

negative trend for deaths from all cancers with 

internal plutonium plus external radiation 

doses (trend tests for internal plutonium doses, 

alone, were not reported). No other significant 

dose trends. 

Category MRR 

All cancers 1.05 

Breast cancer 7.66* 

Not cancer 0.98 

Cerebrovascular disease 1.27** 

Respiratory tract disease 0.88 

Digestive system disease 0.60** 

a

1 kBq=0.027 Ci; 1Gy=100 rad; 1 Sv=100 rem 

CI = confidence interval; df = degrees of freedom; DL = detection limit; ERR = excess relative risk; LRT = likelihood 

ratio test; MRR = mortality and/or morbidity rate ratio; OR = odds ratio; RR = relative risk; SE = standard error 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 34 

3. HEALTH EFFECTS 

these studies provide evidence for an association between cancer mortality (bone, liver, lung) and 

exposure to plutonium. Plutonium dose-response relationships for lung cancer mortality and morbidity 

have been corroborated in four Mayak studies (Gilbert et al. 2004; Jacob et al. 2005; Kreisheimer et al. 

2003; Sokolnikov et al. 2008). Estimated excess relative risk in these four studies (adjusted for smoking) 

were as follows: (1) 3.9 per Gy (95% CI: 2.6–5.8) in males and 19 per Gy (95% CI: 9.5–39) in females 

(Gilbert et al. 2004); (2) 7.1 per Gy (95% CI: 4.9–10) in males and 15 per Gy (95% CI: 7.6–29) in 

females at attained age of 60 years (Sokolnikov et al. 2008); (3) 4.50 per Gy (95% CI: 3.15–6.10) in 

males (Kreisheimer et al. 2003); and (4) 0.11 per Sv (95% CI: 0.08–0.17) or 0.21 per Sv (95% CI: 0.15– 

0.35) (Jacob et al. 2005), depending on the smoking-radiation interaction model that was assumed (these 

estimates per Sv correspond to 2.2 or 4.3 per Gy, respectively, assuming a radiation weighting factor of 

20 for -radiation). The excess relative risk per Gy in Mayak workers declined strongly with attained age 

(Gilbert et al. 2004). 

The risks of mortality and morbidity from bone and liver cancers have also been studied in Mayak 

workers (Gilbert et al. 2000; Koshurnikova et al. 2000; Shilnikova et al. 2003; Sokolnikov et al. 2008; 

Tokarskaya et al. 2006). Increasing estimated plutonium body burden was associated with increasing 

liver cancer mortality, with higher risk in females compared to males. Relative risk for liver cancer for a 

cohort of males and females was estimated to be 17 (95% CI: 8.0–26) in association with plutonium 

uptakes >7.4 kBq; however, when stratified by gender, the relative risk estimate for females was 66 (95% 

CI: 16–45), while for males, it was lower at 9.2 (95% CI: 3.3–23; Gilbert et al. 2000). Risk of bone 

cancer mortality in this same cohort (n=11,000) was estimated to be 7.9 (95% CI: 1.6–32) in association 

with plutonium uptakes >7.4 kBq (males and females combined; Koshurnikova et al. 2000). Risks of 

leukemia mortality in the same cohort were not associated with internal plutonium exposure (Shilnikova 

et al. 2003). In a case control study of Mayak workers, the odds ratio for liver cancer was 11.3 (95% CI: 

3.6–35.2) for subjects who received doses >2.0–5.0 Gy (relative to 0–2.0 Gy), and the odds ratios for 

hemangiosarcomas were 41.7 per Gy (95% CI: 4.6–333) for the dose group >2.0–5.0 Gy and 62.5 per 

Gy (95% CI: 7.4–500) for the dose group >5.0–16.9 Gy. Doses were estimated based on periodic urine 

sampling (Tokarskaya et al. 2006). Sokolnikov et al. (2008) reported averaged-attained age ERRs for 

liver cancer of 2.6 per Gy (95% CI: 0.7–6.9) for males and 29 per Gy (95% CI: 9.8–95) for females, and 

averaged-attained age ERRs for bone cancer of 0.76 per Gy (95% CI: <0–5.2) for males and 3.4 per Gy 

(95% CI: 0.4–20) for females. Elevated risks for bone cancer were observed only for workers with 

plutonium doses exceeding 10 Gy. For lung and bone cancer, the ERR declined with attained age, and for 

lung cancer, the ERR declined with age at first plutonium exposure. 
 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 35 

3. HEALTH EFFECTS 

Epidemiological studies of cancer mortality and morbidity are described in detail in the discussion of 

cancer from inhaled plutonium (Section 3.2.1.7). 

Studies in Animals. 

Exposure of Dogs to 238PuO2. Decreased survival of dogs following inhalation of 238PuO2 was observed 

in the ITRI and PNL studies (Muggenburg et al. 1996; Park et al. 1997). In both studies, postexposure 

survival decreased with increasing initial 238Pu lung burden. In the ITRI study, survival appeared to 

decrease in dogs exposed to 238PuOs aerosols at a median initial lung burden as low as 0.36 kBq/kg body 

weight, although it was most apparent at median initial lung burdens ≥1.05 kBq/kg (Muggenburg et al. 

1996). At a mean initial lung burden of 23.7 kBq/kg, mean postexposure survival was only 1,316 days 

(range: 536–1,517 days), whereas mean survival of vehicle-exposed controls was 4,580 days (range: 

3,694-5,694 days). In the 238PuO2-exposed dogs at PNL, mean initial lung burdens ranged from 0.01 to 

18.9 kBq/kg body weight and survival was decreased at all levels, but statistically significantly decreased 

only at mean initial lung burdens ≥1.17 kBq/kg (Park et al. 1997). Radiation pneumonitis, lung tumors, 

bone tumors, and liver tumors were competing causes of death in the 238PuO2-exposed dogs of both ITRI 

and PNL (Muggenburg et al. 1996; Park et al. 1997). 

Exposures of Dogs to 239PuO2. Premature death was also observed in dogs exposed to aerosols of 

239PuO2. In the ITRI studies, a dose-related decrease in mean survival time was observed, with survival 

time inversely related to initial lung burden (Hahn et al. 1999; Muggenburg et al. 1999, 2008). Decreased 

postexposure survival was evident at a median initial lung burden as low as 0.63 kBq/kg. Survival ranged 

from 152 to 5,941 days in dogs with initial lung burdens between 1 and 10 kBq/kg. At the highest 

median initial lung burden (29 kBq/kg), postexposure survival times were as short as 105–1,525 days 

compared to 1,893–6,308 days in aerosol vehicle-exposed controls. In the PNL dogs, survival times were 

decreased at mean initial lung burdens ≥1 kBq/kg body weight (DOE 1988a; Weller et al. 1995b). 

Radiation pneumonitis/interstitial fibrosis and lung tumors were the primary cause of premature death in 

ITRI and PNL dogs highly exposed to 239PuO2 aerosols. The first two effects are shown together since 

the inflammation from radiation pneumonitis is constant due to long-term plutonium retention, and longterm inflammation always resulted in interstitial fibrosis. 

Exposures of Dogs to 239Pu(NO3)4. Decreased survival was observed in PNL dogs exposed to aerosols of 

239Pu(NO3)4 resulting in initial lung burdens ≥1.02 kBq/kg body weight (DOE 1986b, 1988b; Park et al. 

1995). In the highest exposure group (mean initial lung burden 18.83 kBq/kg), death due to radiation 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 36 

3. HEALTH EFFECTS 

pneumonitis was noted as early as 14 months postexposure (DOE 1988b). Radiation pneumonitis was the 

primary cause of early deaths. Lung tumors and bone tumors were the primary causes of death among 

dogs that either did not develop radiation pneumonitis or survived the condition (Park et al. 1995). 

Exposure of Other Laboratory Animal Species. Decreased survival has been observed in rats exposed to 

239PuO2 (Lundgren et al. 1995; Métivier et al. 1986; Oghiso and Yamada 2003a; Oghiso et al. 1994b, 

1998; Sanders and Lundgren 1995; Sanders et al. 1976, 1988a, 1988b, 1993b), mice (Lundgren et al. 

1987), hamsters (Lundgren et al. 1983; Sanders 1977), and baboons (Metivier et al. 1974, 1978b). In 

these animal species, death was usually caused by radiation pneumonitis accompanied by edema, fibrosis, 

and other signs of respiratory damage. Three Cynomolgus monkeys died at 155, 188, and 718 days, 

respectively, after aerosol exposure to 239Pu(NO3)4 at levels projected to produce an initial total lung 

burden of 40 kBq (1.1 μCi); each was diagnosed with radiation pneumonitis (Brooks et al. 1992). 

The highest NOAEL values and all reliable LOAEL values for deaths in each species and duration 

category are recorded in Table 3-3. 

All reliable LOAEL values for death in dogs and nonhuman primates exposed to aerosols of plutonium 

are recorded in Table 3-3 and plotted in Figure 3-1. 

3.2.1.2 Systemic Effects 

No studies were located regarding dermal/ocular effects in humans or animals after inhalation exposure to 

plutonium. 

Respiratory Effects. 

Epidemiological Studies in Humans. Possible associations between exposure to plutonium and 

respiratory tract disease have been examined in studies of workers at U.S. plutonium production and/or 

processing facilities (Hanford, Los Alamos, Rocky Flats), as well as facilities in Russia (Mayak) and the 

United Kingdom (e.g., Sellafield). The most recent findings from these studies are summarized in 

Table 3-2. Study outcomes for mortality from lung or respiratory tract disease (e.g., cancer and other 

causes) are described in Section 3.2.1.1 (Brown et al. 2004; Carpenter et al. 1998; Gilbert et al. 1989b, 

2004; Jacob et al. 2005; Kreisheimer et al. 2003; McGeoghegan et al. 2003; Omar et al. 1999; Wiggs et 

al. 1994; Wing et al. 2004). Collectively, these studies have not found statistically significant 
121

8

125

11.7

115

1

117

5.91

113

1.6

104

0.77

129

1.60.63

Table 3-3 Levels of Significant Exposure to Plutonium - Inhalation 

Exposure/ LOAEL 

Duration/ 

a 

Key to 

Figure 

Species 

(Strain) 

Frequency 

(Route) 

ACUTE EXPOSURE Death 

1 Monkey 

(Cynomolgus) 

once 

System 

NOAEL 

(kBq/kg) 

Less Serious 

(kBq/kg) 

Serious 

(kBq/kg) 

8 M (fatal radiation 

pneumonitis) 

2 Monkey 

(Rhesus) 

once 11.7 M (fatal radiation 

pneumonitis) 

3 4 

Dog (Beagle) Dog (Beagle) 

once once 

1 

5.91 

(decreased survival) 

(fatal radiation 

pneumonitis) 

5 Dog 

(Beagle) 

once 1.6 (fatal radiation 

pneumonitis) 

6 Dog 

(Beagle) 

once 0.77 (markedly decreased 

survival) 

7 Dog 

(Beagle) 

Once 1.6 (fatal radiation 

pneumonitis) 

0.63 (decreased survival) 

Reference Chemical Form 

Brooks et al. 1992 239Pu(NO3)4 LaBauve et al. 1980 239PuO2 DOE 1988a 239PuO2 DOE 1988b 239Pu(NO3)4 Hahn et al. 1999 239PuO2 Muggenburg et al. 1996 238PuO2 Muggenburg et al. 2008 239PuO2 
118

1.02

108

1

122

1.9

4.8

19

120

1.02

5.91

Table 3-3 Levels of Significant Exposure to Plutonium - Inhalation (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (kBq/kg) Less Serious (kBq/kg) 

LOAEL 

Serious 

(kBq/kg) 

Reference Chemical Form 

8 Dog 

(Beagle) 

once 1.02 (decreased survival at 9 

years; 55% compared to 90% in controls) 

Park et al. 1995 239Pu(NO3)4 

9 Dog 

(Beagle) 

once 10-30 min 1 (significantly decreased survival) Park et al. 1997 238PuO2 

Systemic 

10 Monkey 

(Cynomolgus) 

once Resp 1.9 M 4.8 M (pulmonary lesions 

consisting of interstitial fibrosis and alveolar epithelial proliferation) 

Brooks et al. 1992 239Pu(NO3)4 

Hemato 19 M 

11 Dog 

(Beagle) 

once Hemato 1.02 5.91 (significantly decreased 

lymphocyte, neutrophil, total leukocyte counts) 

DOE 1988b 239Pu(NO3)4 
106

8.3

15

130

0.63

1.6

1.6

3.7

119

0.0069

0.028

Table 3-3 Levels of Significant Exposure to Plutonium - Inhalation (continued) 

a 

Key to 

Figure 

12 13 14 

Species 

(Strain) 

Dog (Beagle) Dog (Beagle) Dog (Beagle) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

once Once once 

System 

Resp 

Hemato Hepatic Resp 

Hemato 

Hepatic 

NOAEL 

(kBq/kg) 

0.63 

1.6 

0.0069 

LOAEL 

Less Serious Serious 

(kBq/kg) (kBq/kg) 

8.3 (fatal radiation 

pneumonitis) 

1 (decreased lymphocyte

count)

5 (increased serum liver

enzymes: ALP, ALT)

1.6 (fatal radiation 

pneumonitis) 

3.7 (significantly decreased

lymphocyte count)

0.028 (significantly increased 

severity of adenomatous hyperplasia) 

Reference Chemical Form 

Muggenburg et al. 1996 238PuO2 Muggenburg et al. 2008 239PuO2 Park et al. 1995 239Pu(NO3)4 
110

0.280.28

0.28

10.28

116

0.075

1.18

127

0.25

126

0.19

105

0.40.3

131

0.63

Table 3-3 Levels of Significant Exposure to Plutonium - Inhalation (continued) 

a 

Key to 

Figure 

15 16 

Cancer 

17 18 19 20 

Species 

(Strain) 

Dog (Beagle) Dog (Beagle) Dog (Beagle) Dog Dog (Beagle) Dog (Beagle) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (kBq/kg) Less Serious (kBq/kg) 

LOAEL 

Serious 

(kBq/kg) 

Reference Chemical Form 

once 10-30 min Resp 0.28 (chronic radiation pneumonitis) Park et al. 1997 238PuO2 

Hemato Musc/skel 0.28 

0.28 

1 

(lymphopenia) 

(radiation 

osteodystrophy) 

Hepatic 0.28 (increased serum liver 

ALT and ALP) 

once Hemato 0.075 1.18 (intermittent 

lymphopenia) 

Weller et al. 1995b 239PuO2 

once 0.25 (CEL: lung tumors) DOE 1988a 

239PuO2 

once 0.19 (CEL: bone tumors) DOE 1994a 

239Pu(NO3)4 

once 0.4 (CEL: bone tumors) 

0.3 (CEL: lung, liver tumors) 

Muggenburg et al. 1996 238PuO2 

Once 0.63 (CEL: lung tumors) Muggenburg et al. 2008 

239PuO2 
109

10.061

Table 3-3 Levels of Significant Exposure to Plutonium - Inhalation (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (kBq/kg) Less Serious (kBq/kg) 

LOAEL 

Serious 

(kBq/kg) 

Reference Chemical Form 

21 Dog 

(Beagle) 

once 10-30 min 1 (CEL: bone tumors) 

0.061 (CEL: lung tumors) 

Park et al. 1997 238PuO2 

a The number corresponds to entries in Figure 3-1. ALP = alkaline phosphatase; ALT = alanine aminotransferase; BW = body weight; CEL = cancer effect level; Hemato = hematological; ILB = initial lung burden; kBq

lung burden in kilobecquerel/kilogram body weight; LOAEL = lowest-observed-adverse-effect level; M = male; min = minute(s); NOAEL = no-observed-adverse-efferespiratory 
Figure 3-1 Levels of Significant Exposure to Plutonium - Inhalation 

Acute (≤14 days) 

Systemic 

kBq/kg BW Death 

Respiratory 

Hematological 

Musculoskeletal 

Hepatic 

Cancer * 

100 

10k 

2k 10 

1k 12d 

4d 11d 

10k 12d 

13d 

10k 5d 7d 13d 13d 

16d 1 3d 8d 9d 11d 12d 15d 21d
	 6d

7d 13d 20d 

19d 

15d 15d 15d 15d 19d 17d 

18d 

0.1 

16d 

21d 

14d 

0.01 

14d 

*Doses represent the lowest dose tested per study that produced a tumorigenic 

response and do not imply the existence of a threshold for the cancer endpoint. 

0.001 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans Minimal Risk Level

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans for effects

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans other than

q-Cow a-Sheep g-Guinea Pig Cancer 

PLUTONIUM

3. HEALTH EFFECTS

42
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 43 

3. HEALTH EFFECTS 

associations between mortality rates from noncancer respiratory tract diseases and exposure to plutonium 

among workers at these facilities. 

Possible associations between exposure to plutonium and pulmonary fibrosis was examined in a cohort of 

workers (n=326) at Rocky Flats (Newman et al. 2005). The study assessed lung interstitial abnormalities 

from the most recent available x-rays in relation to estimated lung equivalent doses from plutonium. 

Estimated lung equivalent doses ranged from 0 to 28 Sv (approximately 73% <1 Sv). The odds ratio 

(OR) (adjusted for age, smoking status, and evidence from pleural abnormalities from possible asbestos 

exposure) was significant for the dose group with lung equivalent doses ≥10 Sv (OR 5.3, 95% CI: 1.2– 

23.4). The report of Newman et al. (2005) was based on scoring radiographs for the severity of chest 

abnormalities consistent with fibrosis, and did not include information regarding a possible association 

between these lung abnormalities and clinical symptoms of disease. 

Studies in Animals. Radiation pneumonitis has been observed following plutonium (primarily insoluble) 

aerosol exposure of dogs, nonhuman primates (monkeys and baboons), and rodents. As discussed in 

Section 3.2.1.1, radiation pneumonitis was identified as primary, major contributing, or incidental cause 

of death in some dogs and nonhuman primates that inhaled 238PuO2, 239PuO2, or 239Pu(NO3)4 aerosols. 

Muggenburg et al. (2008) studied the effect of plutonium ILB and radiation dose on radiation 

pneumonitis in beagles as part of a plutonium lifespan composite study. The relationship between 

pneumonitis induction and the cause of death was reported to be a function of the plutonium ILB, the 

resulting cumulative radiation dose, and the particle size to some extent. Increased ILB and plutonium 

dose rate were associated with the fraction of animals with radiation pneumonitis as primary, major 

contributing, or incidental cause of death. A trend was observed for the induction of radiation 

pneumonitis at lower ILBs in the 0.75 and 1.5 μm AMAD groups than in the 3 μm AMAD group. At 

radiation doses sufficient to produce radiation pneumonitis, the resulting inflammation was a chronic 

symptom due to long-term retention of 239PuO2 in the lung. As a result, 239PuO2-induced radiation 

pneumonitis was always associated with pulmonary fibrosis. The radiation pneumonitis/pulmonary 

fibrosis progressively impaired lung function, including alveolar-capillary gas exchange, resulting in 

increases in respiratory rate, minute volume, arterial CO2 pressure, and lung stiffness, along with 

decreases in tidal volume and arterial O2 pressure. Symptoms in order of decreasing frequency were 

tachypnea, increased breath sounds, body weight loss, anorexia, dyspnea, cyanosis, bradycardia, and 

discharge from the nose, eyes, or mouth. Increasing radiation dose and dose rate corresponded to 
 

 

 

 

 

 

 

 

PLUTONIUM 44 

3. HEALTH EFFECTS 

progressively shorter times to onset of symptoms and increased severity of effects (Muggenburg et al. 

2008). 

Results of inhalation toxicity studies in dogs show that the clinical course of radiation pneumonitis is 

similar following exposure to 238PuO2 or 239PuO2. The typical initial presenting symptom of radiation 

pneumonitis is tachypnea (increased number of breaths per minute) with radiological evidence of 

pulmonary interstitial infiltrate. Histopathological findings include interstitial pneumonia with alveolar 

epithelial hyperplasia, vasculitis, inflammatory cells infiltration, and pulmonary fibrosis (Muggenburg et 

al. 1996, 1999, 2008; Park et al. 1997). Results of the ITRI and PNL studies indicate that radiation 

pneumonitis in the 239PuO2-exposed dogs occurred at lower initial lung burdens and had a shorter time to 

onset of symptoms (Muggenburg et al. 2008) compared to that observed in 238PuO2- or 239Pu(NO3)4-

exposed dogs. This observation is consistent with toxicokinetic differences observed for inhaled 

plutonium compounds, showing that inhaled 239PuO2 is cleared from the lung more slowly than 238PuO2 

and 239Pu(NO3)4 (see Section 3.4, Toxicokinetics). 

Exposure of Dogs to 238PuO2. In the ITRI 238PuO2 dog studies, the first symptom of radiation 

pneumonitis (tachypnea) was observed at approximately 600 days after initial exposure (Muggenburg et 

al. 1996). Pulmonary function tests performed periodically over several years on a subgroup of dogs with 

radiation pneumonitis (mean initial lung burden 28 kBq/kg) showed progressive changes in lung function 

including decreased dynamic lung compliance, decreased CO diffusing capacity, increased alveolararterial pO2, pulmonary edema (a near terminal event), and decreased arterial pO2 (terminal event). 

Pulmonary interstitial or septal fibrosis was observed at necropsy in all dogs with radiation pneumonitis; 

severity was dose-related. Radiation pneumonitis was the primary cause of death in eight dogs with 

initial lung burdens of 8.3–45 kBq/kg (Muggenburg et al. 1996). Similar observations were reported in 

the PNL studies on 238PuO2, with chronic radiation pneumonitis observed in dogs with initial lung 

burdens ≥0.28 kBq/kg (Park et al. 1997). 

Exposure of Dogs to 239PuO2. Chronic radiation pneumonitis also was observed in the ITRI and PNL 

dogs exposed to 239PuO2 aerosols. In the ITRI studies, tachypnea was first observed in cases of nonfatal 

radiation pneumonitis approximately 1 year after exposure (Muggenburg et al. 1988). Morphological 

changes to the lung included alveolar epithelial hyperplasia and interstitial fibrosis (Muggenburg et al. 

2008). Radiation pneumonitis was observed in dogs dying from 0.3 to 11.7 years after inhaling 239PuO2, 

with the time to death inversely related to initial lung burden (Hahn et al. 1999; Muggenburg et al. 1999, 

2008). The lowest initial lung burden causing fatal radiation pneumonitis was 1.0 kBq/kg (Muggenburg 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 45 

3. HEALTH EFFECTS 

et al. 1999, 2008). The time to death from radiation pneumonitis was not different in ITRI dogs 

administered a single exposure (initial lung burden of 3.9 kBq/kg) or repeated exposures (7–10 semiannual exposures for a mean total lung burden of 5.3 kBq/kg) (Diel et al. 1992). Death due to radiation 

pneumonitis was observed in 239PuO2-exposed PNL dogs at mean initial lung burdens ≥1 kBq/kg (DOE 

1988a; Weller et al. 1995b). Histopathologic changes to lungs included interstitial and subpleural 

fibrosis, alveolar hyperplasia, and squamous metaplasia. Radiation pneumonitis and lung cancer were 

competing causes of death in dogs that inhaled 239PuO2. The frequencies of both radiation pneumonitis 

and lung cancer were the same in dogs receiving an average ILB of 3.7 kBq/kg from 239PuO2. At higher 

doses, radiation pneumonitis occurred more frequently to the point that dogs died without signs of cancer 

at an average ILB of 29 kBq/kg. At lower doses, cancer occurred more frequently and radiation 

pneumonitis was not observed at average ILBs ≤0.63 kBq/kg (Muggenburg et al. 2008). In the ITRI 

dogs, radiation pneumonitis occurred at similar initial lung burdens whether the dogs were exposed as 

juveniles, young adults, or elderly adults (DOE 1988d, 1989, 1994b; Hahn et al. 1999; Muggenburg et al. 

1999). Radiation pneumonitis-induced death occurred earlier in the dogs exposed as elderly adults than in 

the dogs exposed as young adults (DOE 1988d). 

Exposure of Dogs to 239Pu(NO3)4. Radiation pneumonitis was the primary cause of death in all five dogs 

that died early following exposure to 239Pu(NO3)4 aerosols at levels resulting in a mean initial lung burden 

of 18.83 kBq/kg; death was noted as early as 14-months postexposure (DOE 1988b; Park et al. 1995). 

Data on the time to onset and clinical progression of disease or histopathologic findings were not 

reported. 

Exposure of Other Laboratory Animal Species. Baboons that inhaled 239PuO2 displayed a pattern of 

respiratory disease similar to that observed in dogs. Radiation pneumonitis-induced mortality was 

observed in one baboon within 400 days following exposure to 239PuO2 that resulted in an estimated initial 

lung burden of 28.5 kBq/kg body weight (Metivier et al. 1974, 1978b). Higher initial lung burdens 

resulted in earlier death from radiation pneumonitis accompanied by pulmonary edema. Radiation 

pneumonitis and pulmonary fibrosis were also reported in Rhesus monkeys at initial lung burdens of 

14.8 or 26.64 kBq/kg (LaBauve et al. 1980). Dose-related increased severity of radiation pneumonitis 

and pulmonary interstitial fibrosis were observed in Cynomolgus monkeys exposed to 239Pu(NO3)4 at 

levels resulting in initial total lung burdens ≥4.8 kBq/kg (based on reported initial lung burdens and mean 

body weight) (Brooks et al. 1992). Monkeys with the highest initial lung burdens exhibited extensive 

alveolar septal fibrosis and zonal pleural fibrosis accompanied by lymphocytic infiltrates and epithelial 

hyperplasia of alveolar lining cells. Radiation pneumonitis and pulmonary fibrosis have also been 
 

 

 

 

 

 

 

 

 

PLUTONIUM 46 

3. HEALTH EFFECTS 

observed in rats, mice, and hamsters that inhaled 239PuO2 (DOE 1986d; Lundgren et al. 1983, 1987, 1995; 

Oghiso et al. 1994b; Sanders 1977; Sanders and Mahaffey 1979). 

The highest NOAEL values and all reliable LOAEL values for respiratory effects in dogs and nonhuman 

primates exposed to aerosols of plutonium are recorded in Table 3-3 and plotted in Figure 3-1. 

Cardiovascular Effects. 

Epidemiological Studies in Humans. Possible associations between exposure to plutonium and 

cardiovascular disease have been examined in studies of workers at production and/or processing 

facilities in the United Kingdom (Sellafield) (McGeoghegan et al. 2003; Omar et al. 1999). These studies 

are summarized in Table 3-2 and study outcomes for mortality from cardiovascular disease are described 

in Section 3.2.1.1. Omar et al. (1999) compared mortality rates between plutonium workers and other 

radiation workers within a cohort of Sellafield workers and found that the mortality rate ratios were 

significantly elevated for cerebrovascular disease (1.27, p<0.05) in a cohort of Sellafield workers. The 

cumulative internal uptakes of plutonium in the cohort were estimated to range from 0 to 12 kBq, with 

approximately 75% of the cohort having cumulative uptakes ≤250 Bq. McGeoghegan et al. (2003) 

compared mortality rates between plutonium workers and other radiation workers within a cohort of 

Sellafield workers and found that morality rate ratios for plutonium workers were significantly elevated 

for deaths from circulatory disease (2.18, p<0.05) and ischemic heart disease (4.46, p<0.01). 

Studies in Animals. No significant changes in cardiovascular function were seen in the ITRI dogs 

exposed to 239PuO2 at initial lung burdens up to and including those resulting in radiation pneumonitis; 

observed right ventricular hypertrophy was most likely a compensatory response to decreased respiratory 

function (Diel et al. 1992; Muggenburg et al. 1999). 

Gastrointestinal Effects. Possible associations between exposure to plutonium and mortality from 

diseases of the gastrointestinal tract have been examined in studies of workers at plutonium production 

and/or processing facilities in the United Kingdom (Sellafield) (McGeoghegan et al. 2003; Omar et al. 

1999). These studies are summarized in Table 3-2 and study outcomes for mortality are described in 

Section 3.2.1.1. Collectively, these studies have not found statistically significant associations between 

mortality rates from diseases of the digestive tract and exposure to plutonium among workers at these 

facilities. 
 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 47 

3. HEALTH EFFECTS 

No reports were located regarding gastrointestinal effects in animals exposed to plutonium aerosols. 

Hematological Effects. Possible associations between exposure to plutonium and mortality from 

hematopoietic diseases have been examined in studies of workers at plutonium production and/or 

processing facilities in the United States (Rocky Flats) (Wiggs et al. 1994) and the United Kingdom 

(Sellafield) (McGeoghegan et al. 2003; Omar et al. 1999). These studies are summarized in Table 3-2 

and study outcomes for mortality are described in Section 3.2.1.1. Collectively, these studies have not 

found statistically significant associations between mortality rates from diseases of blood or bloodforming organs and exposure to plutonium among workers at these facilities. 

Studies in Animals. Inhalation exposure of dogs to plutonium compounds produced adverse 

hematological effects, specifically decreased numbers of lymphocytes, neutrophils, and leukocytes. 

Primary hematological effects of inhaled 238PuO2 and 239Pu(NO3)4 were lymphopenia and neutropenia. In 

contrast, lymphopenia was the only hematological effect of inhaled 239PuO2. The lymphopenia was 

considered the result of lymphocytes being irradiated as they passed through plutonium-containing 

pulmonary lymph nodes. Effects were not observed on other blood cell types, perhaps the result of the 

small fraction of 239PuO2 that translocated to bone or bone marrow (Muggenburg et al. 2008). No fatal 

cancers of the hematopoietic system were reported in studies of dogs or monkeys exposed to plutonium. 

Effects of plutonium compounds on functions of circulating immunological cells are discussed in 

Section 3.2.1.2, Immunological and Lymphoreticular Effects. 

Exposure of Dogs to 238PuO2. Lymphopenia and neutropenia were observed in dogs exposed to 238PuO2. 

In the ITRI dogs, dose-dependent decreases in lymphocyte and neutrophil counts occurred during the first 

year following exposure at initial lung burdens equal to 1 kBq/kg (Muggenburg et al. 1996). Similar 

results were observed in the PNL dogs, although decreased lymphocyte counts were observed at a lower 

initial lung burden (≥0.28 kBq/kg) than decreased neutrophil counts (≥4.68 kBq/kg) (Park et al. 1997). 

Exposure of Dogs to 239PuO2. Lymphopenia was both the first biological effect to be observed and the 

primary hematological effect observed in dogs exposed to 239PuO2, although leukopenia, and transient 

neutropenia have also been reported. Chronic lymphopenia developed during the first year of exposure in 

the ITRI dogs with initial lung burdens ≥3.7 kBq/kg (Muggenburg et al. 1999, 2008). In the PNL dogs, 

transient lymphopenia occurred at initial lung burdens ≥0.064 kBq/kg and transient and persistent 

lymphopenia was noted at initial lung burdens ≥0.25 kBq/kg (Weller et al. 1995b). The time of 

occurrence for significant lymphopenia was inversely related to dose (112 days, 180 days, 1 year, or up to 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 48 

3. HEALTH EFFECTS 

5 years for respective average initial lung burdens of 29, 14, 6.4, and 3.7 kBq/kg). Although the 

lymphocyte counts returned to normal after 5 years for some of these animals, all experienced a 

shortening of life. No changes in red blood cell counts were observed through year 7 other than a 

compensatory increase in animals with pneumonitis or pulmonary fibrosis. In addition to lymphopenia, 

plutonium accumulated in the pulmonary lymph nodes of the 239PuO2-exposed dogs. This resulted 

initially in corticomedullary lymphoid atrophy and fibrosis in the hilar areas, especially in the 

trachiobronchial region, and progressed to relatively complete atrophy and focal scarring (Muggenburg et 

al. 2008). Repeated inhalation exposure to 239PuO2 produced lymphopenia in dogs with total lung burden 

of 5.3 kBq/kg (Diel et al. 1992). 

Other hematological effects observed in dogs exposed to 239PuO2 aerosols include transient neutropenia, 

leukopenia, and erythrocytosis. Transient neutropenia developed 4 months after exposure to 239PuO2 in 

the ITRI dogs with initial lung burdens ≥8.4 kBq/kg, although the duration of the effect was not reported 

(Weller et al. 1995b). A reduction in total leukocytes was also observed in the PNL dogs at the “higher” 

(not otherwise specified) initial lung burden levels (Park et al. 1997). Erythrocytosis, secondary to 

decreased diffusing capacity of the lungs due to radiation pneumonitis, was reported in the 239PuO2-

exposed ITRI dogs (Muggenburg et al. 1999, 2008). Erythrocyte counts in were not affected in the 

239PuO2-exposed PNL dogs (DOE 1988a). 

Exposure of Dogs to 239Pu(NO3). In PNL dogs exposed to inhaled 239Pu(NO3)4, hematological effects 

were the first exposure-related effect observed. Lymphopenia, leukopenia, and neutropenia occurred 

4 weeks after exposures resulting in initial lung burdens ≥5.91 kBq/kg (DOE 1988b). Leukopenia was 

characterized by decreased numbers of neutrophils, lymphocytes, monocytes, and eosinophils. 

Exposure of Other Laboratory Animal Species. Lymphopenia was noted in Rhesus monkeys exposed to 

239PuO2 aerosols, but initial lung burdens resulting in this effect were not specified (LaBauve et al. 1980). 

Total leukocyte count (in the absence of lymphopenia and neutropenia) was decreased in Cynomolgus 

monkeys exposed to 239Pu(NO3)4, but the initial lung burdens at which the effect was noted were not 

specified (Brooks et al. 1992). 

The highest NOAEL values and all reliable LOAEL values for hematological effects in each species and 

duration category are recorded in Table 3-3. 
 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 49 

3. HEALTH EFFECTS 

The highest NOAEL values and all reliable LOAEL values for hematological effects in dogs and 

nonhuman primates exposed to aerosols of plutonium are recorded in Table 3-3 and plotted in Figure 3-1. 

Musculoskeletal Effects. 

Epidemiological Studies in Humans. Possible associations between exposure to plutonium and mortality 

from bone disease (e.g., bone cancer) and other musculoskeletal diseases have been examined in studies 

of workers at U.S. plutonium production and/or processing facilities (Hanford, Los Alamos, Rocky Flats), 

as well as facilities in Russia (Mayak) and the United Kingdom (e.g., Sellafield). The most recent 

findings from these studies are summarized in Table 3-2. Study outcomes for mortality (e.g., bone 

cancer) are described in Section 3.2.1.1 (Carpenter et al. 1998; Koshurnikova et al. 2000; McGeoghegan 

et al. 2003; Omar et al. 1999; Wiggs et al. 1994; Wing et al. 2004). Collectively, these studies have not 

found statistically significant associations between mortality rates for noncancer bone or musculoskeletal 

disease and exposure to plutonium among workers at these facilities (McGeoghegan et al. 2003; Omar et 

al. 1999; Wiggs et al. 1994). 

Studies in Animals. Radiation osteodystrophy, characterized by peritrabecular fibrosis, osteosclerosis, 

and osteoporosis, was observed on necropsy in ITRI and PNL dogs exposed to 238PuO2 aerosols (Hahn et 

al. 1991a; Muggenburg et al. 1996; Park et al. 1997). Although osteodystrophy in the 238PuO2-exposed 

ITRI dogs was often associated with bone tumors, it also occurred in the absence of bone tumors (Hahn et 

al. 1991a; Muggenburg et al. 1996). In the 238PuO2-exposed PNL dogs, radiation osteodystrophy was 

observed at initial lung burdens ≥1.17 kBq/kg (Park et al. 1997). The incidence and severity of 

osteodystrophy was dose-related and necrotic osteoblasts and empty lacunae near endosteal surfaces were 

observed at high (not otherwise specified) initial lung burdens (Park et al. 1997). Radiation 

osteodystrophy has also been reported in dogs exposed to 239Pu(NO3)4 aerosols (DOE 1986b, 1989). 

Information on plutonium-induced bone tumors is reviewed in Section 3.2.1.7, Cancer. 

The highest NOAEL values and all reliable LOAEL values for musculoskeletal effects in each species 

and duration category are recorded in Table 3-3. 

The highest NOAEL values and all reliable LOAEL values for musculoskeletal effects in dogs and 

nonhuman primates exposed to aerosols of plutonium are recorded in Table 3-3 and plotted in Figure 3-1. 
 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 50 

3. HEALTH EFFECTS 

Hepatic Effects. 

Epidemiological Studies in Humans. Possible associations between exposure to plutonium and mortality 

from liver disease (e.g., liver cancer) have been examined in studies of workers at U.S. plutonium 

production and/or processing facilities (Hanford, Los Alamos, Rocky Flats), as well as facilities in Russia 

(Mayak) and the United Kingdom (e.g., Sellafield). The most recent findings from these studies are 

summarized in Table 3-2. Study outcomes for mortality (e.g., liver cancer) are described in 

Section 3.2.1.1 (Carpenter et al. 1998; Gilbert et al. 1989b, 2000; McGeoghegan et al. 2003; Omar et al. 

1999; Wiggs et al. 1994; Wing et al. 2004). Collectively, these studies have not found statistically 

significant associations between mortality rates for noncancer liver disease and exposure to plutonium 

among workers at these facilities (McGeoghegan et al. 2003; Omar et al. 1999; Wiggs et al. 1994). 

Studies of liver cancer morbidity among Sellafield and Mayak workers are described in Table 3-2 and in 

greater detail in Section 3.2.1.7 (McGeoghegan et al. 2003; Omar et al. 1999; Tokarskaya et al. 2006). 

Studies in Animals. Adverse effects on the liver have been observed in dogs exposed to aerosols of 

plutonium. Elevated serum liver enzymes and non-neoplastic liver lesions were noted in dogs exposed to 

238PuO2 and 239Pu(NO3)4, and non-neoplastic liver lesions have been observed in dogs exposed to 239PuO2. 

In addition, bile duct hyperplasia was observed in dogs treated with 238PuO2 and 239Pu(NO3)4. Although 

elevated liver enzymes and non-neoplastic liver lesions indicate are indicative of plutonium-induced 

hepatotoxicity, clinical signs of liver dysfunction (i.e., ascites, icterus, clotting disorders) have not been 

observed (Park et al. 1997; Weller et al. 1995b). Information on plutonium-induced liver tumors is 

reviewed in Section 3.2.1.2, Cancer. 

Exposure of Dogs to 238PuO2. Elevated serum alkaline phosphatase (ALP) and alanine aminotransferase 

(ALT) was observed in 238PuO2-exposed ITRI and PNL dogs over the entire range of initial lung burdens 

(≥0.36 kBq/kg) (Muggenburg et al. 1996; Park et al. 1997; Weller et al. 1995b). The increased enzyme 

activity exhibited a biphasic (early and late effects) response that was dependent on time and exposure 

level (Park et al. 1997; Weller et al. 1995a). The time to occurrence was inversely related to initial lung 

burden, with elevations observed by 6–8 years postexposure in dogs with initial lung burden of 1 kBq/kg 

and in 4–6 years postexposure in dogs with higher initial lung burdens ( ≥5 kBq/kg) (Muggenburg et al. 

1996). The most common non-neoplastic liver lesion was nodular hyperplasia (or adenomatous 

hyperplasia), followed by vacuolar degeneration (Muggenburg et al. 1996). Periportal fibrosis and biliary 

fibrosis were also observed in 238PuO2-exposed dogs (Gillett et al. 1988). 
 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 51 

3. HEALTH EFFECTS 

Exposure of Dogs to 239PuO2. Centrilobular congestion and vacuolization were observed in dogs that 

inhaled 239PuO2 (initial lung burden ≥1 kBq/kg), although no consistent changes in serum liver enzymes 

were seen (DOE 1988a). 

Exposure of Dogs to 239Pu(NO3)4. Serum liver enzymes ALP and glutamic pyruvic transaminase (GPT) 

were significantly elevated In PNL dogs that inhaled 239Pu(NO3)4, at levels resulting in initial lung 

burdens ≥0.19 kBq/kg (DOE 1988b, 1994a; Park et al. 1995). Bile duct hyperplasia was reported in 

controls and plutonium-exposed dogs and did not appear to exhibit dose-related increased incidence or 

severity (Dagle et al. 1996). However, the severity of observed nodular hyperplasia was significantly 

higher in dogs with mean initial lung burdens ranging from 0.028 to 1.02 kBq/kg (Dagle et al. 1996). 

Exposure of Other Laboratory Animal Species. Degenerative liver lesions (hepatic degeneration, 

necrosis, fibrosis, and amyloidosis) were reported in Syrian hamsters exposed to 239PuO2 (once or 

repeatedly every other month for a total of seven doses over 12 months) at a target 239Pu lung burden of 

1.8 kBq/hamster; it was noted that the lesions observed in these hamsters were typical of those usually 

seen in aged Syrian hamsters (Lundgren et al. 1983). 

The highest NOAEL values and all reliable LOAEL values for hepatic effects in each species and 

duration category are recorded in Table 3-3. 

The highest NOAEL values and all reliable LOAEL values for hepatic effects in dogs and nonhuman 

primates exposed to aerosols of plutonium are recorded in Table 3-3 and plotted in Figure 3-1. 

Renal Effects. Possible associations between exposure to plutonium and mortality from diseases of 

the kidney and genitourinary tract have been examined in studies of workers at plutonium production 

and/or processing facilities in the United States (Rocky Flats) (Wiggs et al. 1994) and the United 

Kingdom (Sellafield) (McGeoghegan et al. 2003; Omar et al. 1999). These studies are summarized in 

Table 3-2 and study outcomes for mortality are described in Section 3.2.1.1. Collectively, these studies 

have not found significant associations between mortality rates from kidney or genitourinary tract disease 

and exposure to plutonium among workers at these facilities. 
 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 52 

3. HEALTH EFFECTS 

Endocrine Effects. 

Epidemiological Studies in Humans. Possible associations between exposure to plutonium and mortality 

from endocrine disorders have been examined in studies of workers at plutonium production and/or 

processing facilities in the United Kingdom (Sellafield) (McGeoghegan et al. 2003; Omar et al. 1999). 

These studies are summarized in Table 3-2 and study outcomes for mortality are described in 

Section 3.2.1.1. Collectively, these studies have not found significant associations between mortality 

rates from endocrine disorders and exposures to plutonium among workers at these facilities. 

Studies in Animals. Hypoadrenocorticism was reported in 238PuO2-exposed PNL dogs (n=6) with 

individual initial lung burdens in the range of 1–25 kBq/kg body weight and was considered the cause of 

death in 3 of the 6 dogs (Park et al. 1997). The time to detection of hypoadrenocorticism ranged from 

1,263 to 4,616 days after exposure; physical symptoms included depression, weakness, dehydration, 

bradycardia, and anorexia. Laboratory findings in affected animals (hemoconcentration, altered serum 

Na:K ratio, hypochloremia, hypoglycemia, metabolic acidosis, and hypercalcemia) were consistent with 

adrenal cortical insufficiency. Cardiovascular changes (bradycardia and other cardiac arrhythmias) were 

consistent with hypoadrenocorticism-induced hypokalemia. Histopathological findings included bilateral 

adrenal cortex atrophy with capsular thickening and fibrosis, and mononuclear cell infiltration. Results of 

ACTH response tests indicated that hypoadrenocorticism resulted from adrenal cortical insufficiency 

rather than from altered pituitary function. Based on the presence of anti-adrenal antibodies in serum, 

hypoadrenocorticism may have resulted from an autoimmune disorder caused by radiation damage to the 

lymphatic system (Park et al. 1997). 

3.2.1.3 Immunological and Lymphoreticular Effects 

Epidemiological Studies in Humans. Possible associations between exposure to plutonium and mortality 

from immunological or lymphoreticular diseases have been examined in studies of workers at plutonium 

production and/or processing facilities in the United States (Rocky Flats) (Wiggs et al. 1994) and the 

United Kingdom (Sellafield) (McGeoghegan et al. 2003; Omar et al. 1999). These studies are 

summarized in Table 3-2 and study outcomes for mortality are described in Section 3.2.1.1. Collectively, 

these studies have not found statistically significant associations between mortality rates from diseases of 

the immunological or lymphoreticular systems and exposures to plutonium among workers at these 

facilities. 
 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 53 

3. HEALTH EFFECTS 

Studies in Animals. As discussed in detail in Section 3.4, Toxicokinetics, inhaled plutonium compounds 

are translocated to tracheobronchial lymph nodes, resulting in a high tissue concentration of plutonium 

and sclerotic atrophy of lymph nodes. Exposure of lymphocytes in plutonium-laden tracheobronchial 

lymph nodes is considered the probable cause of lymphopenia in the plutonium-exposed dogs (Ragan et 

al. 1976). Effects of inhaled plutonium on the number lymphocytes circulating in blood are reviewed in 

Section 3.2.1.2, Hematological Effects. 

Histopathologic lesions of lymph nodes, particularly tracheobronchial lymph nodes, have been observed 

following exposure to 238PuO2, 239PuO2, or 239Pu(NO3)4. Fibrosis and loss of lung-associated and 

mediastinal lymph nodes were observed in the 238PuO2-exposed ITRI dogs with the highest initial lung 

burdens, although specific levels resulting in this effect were not specified (Muggenburg et al. 1996). 

Severity of non-neoplastic lesions in 238PuO2-exposed PNL dogs was related to dose, progressing from 

lymphoid atrophy of medullary cords at an initial lung burden of 0.061 kBq/kg to significant lymph node 

atrophy with hypocellular scar tissue replacing lymphoid tissue at higher (not otherwise specified) initial 

lung burdens (Park et al. 1997). Similar dose-related atrophy and fibrosis of lung-associated, mediastinal, 

sternal, and hepatic lymph nodes were observed in dogs exposed to 239PuO2 (DOE 1988a; Muggenburg et 

al. 1999, 2008). Sclerotic lymph nodes were observed in the groups of 239Pu(NO3)4-exposed PNL dogs 

with mean initial lung burdens ≥5.9 kBq/kg, but lymph node lesions in these dogs were considered less 

severe than those observed in 238PuOs- or 239PuO2-exposed dogs (DOE 1986b, 1989). 

Results of studies on immunological function indicate that inhalation exposure to 239PuO2 impairs T-cell 

response to antigens, as indicated by decreased response to antigen (DOE 1978a). Davila et al. (1992) 

detected accelerated aging of the T-cell response to mitogenic stimulation in dogs that had been exposed 

to 239PuO2 10 years earlier at levels resulting in mean initial lung burdens ≥6.5 kBq (0.61 kBq/kg, 

assuming a body weight of 10.7 kg at time of 239PuO2 aerosol exposure). Other reports of 239PuO2-

induced effects from plutonium exposure include decreases in pulmonary alveolar macrophages in mice 

(Moores et al. 1986) and depressed antibody-forming cells in hamsters (Bice et al. 1979). 

The highest NOAEL values and all reliable LOAEL values for immunological and lymphoreticular 

effects in each species and duration category are recorded in Table 3-3. 
 

 

 

 

 

 

PLUTONIUM 54 

3. HEALTH EFFECTS 

3.2.1.4 Neurological Effects 

Possible associations between exposure to plutonium and mortality from brain or neurological diseases 

have been examined in studies of workers at plutonium production and/or processing facilities in the 

United States (Rocky Flats) (Wiggs et al. 1994) and the United Kingdom (Sellafield) (McGeoghegan et 

al. 2003; Omar et al. 1999). These studies are summarized in Table 3-2 and study outcomes for mortality 

are described in Section 3.2.1.1. Collectively, these studies have not found statistically significant 

associations between mortality rates from diseases of the central or peripheral nervous systems and 

exposures to plutonium among workers at these facilities. 

3.2.1.5 Reproductive Effects 

Possible associations between exposure to plutonium and mortality from diseases of the genitourinary 

tract and diseases of pregnancy have been examined in studies of workers at plutonium production and/or 

processing facilities in the United States (Rocky Flats) (Wiggs et al. 1994) and the United Kingdom 

(Sellafield) (McGeoghegan et al. 2003; Omar et al. 1999). These studies are summarized in Table 3-2 

and study outcomes for mortality are described in Section 3.2.1.1. Collectively, these studies have not 

found statistically significant associations between mortality rates from genitourinary tract disease or 

diseases of pregnancy and exposures to plutonium among workers at these facilities. 

No studies were located regarding reproductive effects in animals following inhalation exposure to 

plutonium compounds. 

3.2.1.6 Developmental Effects 

No studies were located regarding developmental effects in humans or animals following inhalation 

exposure to plutonium compounds. 

3.2.1.7 Cancer 

Epidemiological Studies in Humans. Possible associations between exposure to plutonium and cancer 

mortality and morbidity have been examined in studies of workers at the U.S. plutonium production 

and/or processing facilities (Hanford, Los Alamos, Rocky Flats), as well as facilities in Russia (Mayak) 

and the United Kingdom (e.g., Sellafield). The most recent findings from these studies are summarized in 

Table 3-2. Compared to studies of U.K. and U.S. facilities, the Mayak cohorts had relatively high 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 55 

3. HEALTH EFFECTS 

exposures to plutonium (i.e., mean body burdens ranging from 0.09 to 9.2 kBq, with individual exposures 

as high as 470 kBq (Krahenbuhl et al. 2005). Collectively, the Mayak studies provide evidence for an 

association between cancer mortality and exposure to plutonium. Plutonium dose-response relationships 

for lung cancer mortality have been corroborated in three Mayak studies (Gilbert et al. 2004; Jacob et al. 

2005; Kreisheimer et al. 2003). Studies of U.K. and U.S. facilities have examined cohorts of workers 

who had substantially lower estimated plutonium exposures and corresponding internal radiation doses 

than the Mayak cohorts (e.g., Sellafield: body burdens ≤1 kBq in 97% of the assessed workers [Omar et 

al. 1999]; Los Alamos: mean body burden 0.970 kBq, range: 0.05–3.18 kBq [Voelz et al. 1997]). 

Although a significantly higher incidence of cancer mortality in certain groups of plutonium workers has 

been found in some studies, higher cancer incidence and/or risks for tissues that received the highest 

plutonium radiation doses (i.e., lung, liver, bone) have not been found, making causal connections of 

these outcomes to plutonium exposure more uncertain (Brown et al. 2004; Carpenter et al. 1998; Gilbert 

et al. 1989b; McGeoghegan et al. 2003; Omar et al. 1999; Wing et al. 2004). 

Mayak Production Association Workers. Studies of mortality of plutonium workers at Russian facilities 

are summarized in Table 3-2 (Gilbert et al. 2000, 2004; Jacob et al. 2005; Koshurnikova et al. 2000; 

Kreisheimer et al. 2003; Sokolnikov et al. 2008). The total Mayak cohort includes approximately 

22,000 workers; plutonium monitoring data exist on approximately 28% of subjects (Gilbert et al. 2004). 

However, reliability of the monitoring data varies across subjects, which introduces uncertainty into 

stratification of the cohort by estimated plutonium body burden or internal radiation absorbed dose (i.e., 

Gy) or effective dose equivalents (i.e., Sv). These data yielded estimates of mean plutonium body 

burdens in the full cohort that ranged from 0.9 to 9.2 kBq (Krahenbuhl et al. 2005). The mean body 

burden, based on data considered to be the most reliable, was 9.2 kBq (range: 0–469 kBq, n=805). In an 

earlier analysis of the Mayak monitoring data, Gilbert et al. (2004) and Shilnikova et al. (2003) estimated 

body burdens and lung radiation doses for various categories of employment (e.g., dates, jobs, work 

conditions, monitoring and autopsy data) and exposure. The estimated job category mean body burdens 

ranged from 0.45 to 17.8 kBq, and the corresponding internal absorbed doses to the lung ranged from 

0.016 to 2.91 Gy. The corresponding effective dose equivalents are 0.32 and 58 Sv (assuming a radiation 

weighting factor of 20 for -radiation). The mean body burden for the monitored fraction of the cohort 

(n=6,193) was 1.84 kBq, and the corresponding internal lung absorbed dose was 0.24 Gy (Gilbert et al. 

2004). Sokolnikov et al. (2008) applied recently improved individual dose estimates to 5,572 of the 

Mayak workers with confirmed plutonium exposure and estimated that the mean plutonium dose to the 

lung was 0.19 Gy (0.14 Gy for males and 0.29 Gy for females). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 56 

3. HEALTH EFFECTS 

Collectively, the Mayak studies provide evidence for increased risk of cancer mortality (bone, liver, lung) 

in association with increased internal plutonium-derived radiation dose and/or body burden, with 

approximately 4-fold higher risks in females compared to males. Four studies estimated lung cancer 

mortality risk among Mayak workers and yielded similar estimates of excess relative risk per Gy of 

internal lung dose. Gilbert et al. (2004) estimated the excess lung cancer mortality risk (per Gy attained at 

age 60 years) for essentially the entire cohort of Mayak workers (n=21,790) to be approximately 4.7 per 

Gy (95% CI: 3.3–6.7) in males, and 19 per Gy (95% CI: 9.5–39) in females. Adjustment for smoking, 

based on risk estimates in subgroups for which smoking data were available, decreased these estimates 

only slightly: males, 3.9 per Gy (95% CI: 2.6–5.8); and females, 19 (95% CI: 7.7–51). Cancer mortality 

risk was linearly related to plutonium radiation dose. Excess relative risk per Gy declined strongly with 

attained age (Gilbert et al. 2004). Kreisheimer et al. (2003) examined lung cancer mortality risk for a 

subset of male Mayak workers (n=4,212) and estimated smoking-adjusted excess relative risk to be 

4.50 per Gy (95% CI: 3.15–6.10). Jacob et al. (2005) used a mechanistic (i.e., multi-stage physiological) 

model to estimate smoking-adjusted lung cancer mortality risk in a similar cohort (n=5,058) and found 

the excess relative risk to be 0.11 per Sv (95% CI: 0.08–0.17); the corresponding estimate in units of 

absorbed radiation dose would be 2.2 per Gy (assuming a radiation weighting factor of 20 for 

-radiation). An alternative model that treated smoking as a multiplicative risk factor (rather than 

additive), yielded an estimated excess relative risk of 0.21 per Sv (95% CI: 0.15–0.35), which 

corresponds to approximately 4.3 per Gy, very close to the estimates from Gilbert et al. (2004) and 

Kreisheimer et al. (2003). Sokolnikov et al. (2008) estimated ERRs of 7.1 per Gy (95% CI: 4.9–10) in 

males and 15 per Gy (95% CI: 7.6–29) in females at attained age of 60 years among 5,572 of the Mayak 

workers with confirmed plutonium exposure. A significant dose-response was noted and lung cancer risk 

was reasonably described by a linear function. The ERR declined with attained age and age at first 

plutonium exposure. 

Risks of mortality and morbidity from bone and liver cancers have also been studied in Mayak workers 

(Gilbert et al. 2000; Koshurnikova et al. 2000; Shilnikova et al. 2003; Sokolnikov et al. 2008; Tokarskaya 

et al. 2006). Increasing estimated plutonium body burden was associated with increasing cancer 

mortality, with higher risk in females compared to males. Gilbert et al. (2000) examined liver cancer 

mortality in a cohort of Mayak workers (n=11,000). Mean plutonium body burdens for the cohort were 

estimated to have been 3.78 kBq in males and 6.05 kBq in females. The corresponding absorbed 

radiation doses to liver were 0.47 Gy in males and 0.88 Gy in females. A model in which liver cancer 

risk was treated as a quadratic function of plutonium body burden achieved better fit to the data than a 

linear model. Relative risk for liver cancer for the entire cohort was estimated to be 17 (95% CI: 8.0–26) 
 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 57 

3. HEALTH EFFECTS 

in association with plutonium body burdens >7.4 kBq; however, when stratified by gender, the relative 

risk estimate for females was 66 (95% CI: 16–45) and higher than for males (9.2; 95% CI: 3.3–23). 

Risk of bone cancer mortality in this same cohort (n=11,000) was estimated to be 7.9 (95% CI: 1.6–32) 

in association with plutonium body burdens >7.4 kBq for males and females combined (Koshurnikova et 

al. 2000). Risks of leukemia mortality, in the same cohort, were not associated with internal plutonium 

exposure (Shilnikova et al. 2003). Liver cancer risk was examined in a case-control study of Mayak 

workers (Tokarskaya et al. 2006). The case group consisted of histologically-confirmed cases of 

malignant liver tumors (n=44) diagnosed during the period 1972–1999. These were matched to members 

of a control group (n=111) for years of birth, gender, years of hire, and job assignments. Estimated 

absorbed radiation doses to the liver from plutonium ranged from 0 to 16.9 Gy (the 4th quartile range was 

0.54–16.9 Gy). When stratified by absorbed radiation dose to the liver, the odds ratio for liver cancer was 

11.3 (95% CI: 3.6–35.2) for subjects who experienced >2.0–5.0 Gy (relative to 0–2.0 Gy). Odds ratios 

for hemangiosarcomas were 41.7 (95% CI: 4.6–333) for the dose group >2.0–5.0 Gy, and 62.5 (95% CI: 

7.4–500) for the dose group >5.0–16.9 Gy. Sokolnikov et al. (2008) reported averaged-attained age 

ERRs for liver cancer of 2.6 per Gy (95% CI: 0.7–6.9) for males and 29 per Gy (95% CI: 9.8–95) for 

females, and averaged-attained age ERRs for bone cancer of 0.76 per Gy (95% CI: <0–5.2) for males and 

3.4 per Gy (95% CI: 0.4–20) for females. Elevated risks for bone cancer were observed only for workers 

with plutonium doses exceeding 10 Gy. For lung and bone cancer, the ERR declined with attained age, 

and for lung cancer, the ERR declined with age at first plutonium exposure. 

U.K. Atomic Energy Authority and Atomic Weapons Establishment Workers. Studies of mortality of 

plutonium workers at U.K. facilities are summarized in Table 3-2 (Carpenter et al. 1998; McGeoghegan et 

al. 2003; Omar et al. 1999). Although several studies have examined mortality rates in workers at the 

Sellafield nuclear facility (Douglas et al. 1994; McGeoghegan et al. 2003; Omar et al. 1999; Smith and 

Douglas 1986), the McGeoghegan et al. (2003) and Omar et al. (1999) studies attempted to estimate risks 

in association with plutonium exposures, as opposed to radiation exposures, in general. Omar et al. 

(1999) identified a cohort of plutonium workers as a subset (n=5,203) of workers who had been 

monitored at any time for exposure to plutonium (e.g., urinalysis). An analysis of monitoring data on 

these subjects provided estimates of internal uptakes of plutonium (Omar et al. 1999). Cumulative 

internal uptakes were estimated to range from 0 to 12 kBq, with approximately 75% of the cohort having 

cumulative uptakes ≤250 Bq. Cumulative radiation dose equivalents for plutonium were estimated to be 

approximately 3,280 Sv for bone surfaces, 44.5–896 Sv for lung, and 421 Sv for liver; however, analyses 

of dose trends were of the combined dose equivalents from plutonium and external radiation. In a 

comparison of mortality rates for plutonium workers compared to other radiation workers (i.e., those 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 58 

3. HEALTH EFFECTS 

never monitored for plutonium exposure), mortality rate ratios were not significant for deaths from cancer 

(1.05, all causes of cancer) or all causes other than cancer (0.98). Mortality rate ratios significantly 

decreased in association with increasing effective dose equivalents for plutonium and external radiation 

combined (trends for plutonium doses were not reported). However, when stratified by specific causes of 

death, mortality rate ratios were not significantly elevated (p≥0.05) for the tissues that received the 

highest plutonium radiation doses (lung, 1.12; liver, 0.85; bone, 0.00), nor were there significant positive 

trends with radiation dose (external plus internal plutonium dose). The mortality rate ratio was 

significantly elevated for breast cancer (7.66, p<0.01) and cerebrovascular disease (1.27, p<0.05). 

McGeoghegan et al. (2003) examined cancer mortality in a cohort of female Sellafield workers (n=6,376), 

from which a subset (n=837) of women who had been monitored for plutonium exposure was identified 

as plutonium workers. This cohort overlapped considerably with that studied by Omar et al. 1999). 

Effective dose equivalents to the lung from plutonium were estimated to have ranged up to 178 mSv 

(mean: 3.45 mSv, 5th–95th percentile range: 0.36–8.89 mSv). Comparisons of mortality rates between 

plutonium workers and other radiation workers yielded significantly elevated mortality rate ratios for all 

deaths (2.20, p<0.01), all cancers (3.30, p<0.01), breast cancer (3.77, p<0.05), circulatory disease (2.18, 

p<0.05), and ischemic heart disease (4.46, p<0.01). Mortality rate ratios were not elevated for cancers in 

tissues that received the highest plutonium radiation doses (lung, 2.36; bone; 0.00; digestive organs 

including liver, 3.90). Excess relative risks (per Sv) were estimated for external radiation, but not for 

plutonium, and were not statistically significant. Collectively, the Omar et al. (1999) and McGeoghegan 

et al. (2003) studies did not find elevated mortality rate ratios for the tissues that received the highest 

plutonium radiation doses among plutonium workers compared to other radiation workers (lung, liver, 

bone), and did not find significant positive trends in cancer mortality or incidence in these tissues with 

plutonium radiation dose. Although both studies found elevated mortality rate ratios in other selected 

organ categories (e.g., breast cancer), the associations between these outcomes and plutonium exposure 

are more uncertain, given the negative findings for lung, liver, or bone, and that other tissues, such as 

breast, received a much smaller radiation dose. The findings for all cancers and breast cancer may also 

have been influenced by the relatively low standardized mortality ratios (<100) for these end points in the 

other radiation workers (the comparison cohort to the plutonium workers), indicative of a “healthy worker 

effect”, that was not evident in the plutonium worker cohort. 

Carpenter et al. (1998) examined cancer mortality in workers at U.K. nuclear facilities (n=40,761) from 

which a subset (n=12,498), who had been monitored for plutonium exposure, was identified as plutonium 

workers. Plutonium exposures (i.e., Bq) or doses (i.e., Gy, Sv) were not included in this analysis; 

however, the number of years since first monitored or the total number of years monitored were 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 59 

3. HEALTH EFFECTS 

considered as surrogates for duration of plutonium exposures. Mortality rates for plutonium workers 

were not significantly elevated when compared to workers who were never monitored for radiation 

exposure (to any nuclide). However, when stratified by number of years since monitored or by number of 

years monitored, significant trends were found for increasing mortality rate ratios (monitored compared to 

never monitored) for all cancers (p<0.05) in association with increasing years of monitoring. 

U.S. Nuclear Facilities (Hanford, Los Alamos, Rocky Flats). Lung cancer mortality in plutonium 

workers employed at the Rocky Flats nuclear weapons plant has been examined in a case-control study 

(Brown et al. 2004). Lung cancer cases (n=180) were employed at the Rocky Flats facility for at least 

6 months during the period 1952–1989, when plutonium pits were fabricated at the facility. The control 

group (n=720) consisted of Rocky Flats workers who were matched with cases for age, birth, year, and 

gender. Internal lung radiation doses in the cohort derived primarily from exposures to 239Pu, 240Pu, 241Pu, 

241Am, and 238U; however, 98% of the internal effective dose equivalents in cases (96% in controls) were 

estimated to have come from Pu and 241Am (inbred from 241Pu). Estimated effective dose equivalents for 

internal -radiation (cases plus controls) ranged from 0 (54%) to >940 mSv (5%). In the full cohort, the 

odds ratio for lung cancer mortality was significant for the internal lung dose strata 400–644 mSv, but 

was not significantly elevated at higher doses; there was no significant trend with dose (2.71, 95% CI: 

1.20–6.09); the odds ratios were <1 for most dose categories for persons employed for <15 or >25 years. 

When the analysis was restricted to workers employed at the facility for 15–25 years, a significant trend 

was evident for increasing odds ratio in association with increasing internal lung effective dose 

equivalents; however, there was no evidence of a positive trend for those employed for <10 or ≥25 years. 

Some of the highest exposures to plutonium at Los Alamos occurred during the period 1944–1945 (i.e., 

Manhattan Project) when occupational safety procedures for handling of plutonium were not as complex 

or well-regulated as more recent procedures (Hempelmann et al. 1973). A small cohort of adult males 

(n=26) who worked at the Los Alamos facility at that time have been followed and assessed for health 

effects (Hempelmann et al. 1973; Voelz and Lawrence 1991; Voelz et al. 1997). Based on urine 

monitoring (up to 1994) and/or postmortem tissue analyses, plutonium body burdens ranged from 50 to 

3,180 Bq (median: 565 Bq), and effective dose equivalents ranged from 0.2 to 7.2 Sv (median: 1.25 Sv; 

Voelz et al. 1997). Mortality in the group was compared to that in a group of workers (n=876) employed 

at Los Alamos during the same period who had no history or evidence of exposure to plutonium (Voelz et 

al. 1997). At the time of the study (1994), seven deaths had occurred; three from cancer (bone, lung, 

prostrate), two from diseases of the circulatory system, one from respiratory disease, and one from 

external causes. The single bone cancer death greatly exceeded expected numbers (0.01 deaths; 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 60 

3. HEALTH EFFECTS 

standardized mortality ratio [SMR]=96; 95% CI: 1.26–536). Similarly the lower 95% confidence limit 

on the mortality rate ratio for bone cancer was >1. Standard mortality ratios and mortality rate ratios for 

other deaths were not statistically significant. 

A larger cohort study was examined for cancer mortality in Los Alamos workers (n=15,527 males) 

employed at the facility during the period 1943–1973 (Wiggs et al. 1994). From this larger cohort, a 

subset (n=3,775) had been monitored for plutonium exposure and, on that basis, were identified as 

plutonium workers in the study. Mortality incidence rates for plutonium workers who were estimated to 

have internal plutonium depositions ≥74 Bq (n=303) were compared to workers with depositions <74 Bq 

(n=3,472). Cancer mortality rate ratios were not statistically significant (e.g., all cancers, cancers of the 

respiratory tract or lung, bone, or lymphopoietic and hematopoietic systems). 

Workers at the Hanford plutonium production and processing facility have been examined for possible 

associations between cancer mortality and exposure to ionizing radiation (Gilbert et al. 1989b; Wing and 

Richardson 2005; Wing et al. 2004). Gilbert et al. (1989b) examined mortality in association with 

external radiation exposure and internal plutonium among workers at the Hanford plant. From the total 

cohort of workers (n=31,500), a subset of workers who had confirmed plutonium depositions (n=457) 

were identified. The cohort was stratified into exposure categories based internal depositions relative the 

maximum permissible body burden (MPBB) at that time (1,480 Bq): no evidence of deposition, 

deposition <5% of MPBB (<74 Bq), or deposition ≥5% of MPBB. Approximately 30% of the confirmed 

depositions were between 5 and 99% of the MPBB (74–1,465 Bq) and 1.3% were ≥100% of the MPBB. 

The study found no evidence for statistically significant excess cancer mortality or trends in cancer 

mortality with external radiation or Pu internal deposition (i.e., for all cancers, or cancers of the digestive 

tract, lung, lymphatic and hematopoietic tissues, or prostate). Wing et al. (2004) examined mortality in 

association with duration of engagement in plutonium-associated jobs as a surrogate for plutonium 

exposure or dose estimates. From the total cohort of workers (n=26,389), subsets of workers who had 

activities in routine plutonium-associated jobs (n=3,065) or nonroutine jobs (n=8,266) were identified (of 

these, only 377 had confirmed systemic plutonium deposition). Workers in the plutonium-associated jobs 

category had lower death rates from all cancers, cancers of the lung, and “plutonium-cancers” (lung, liver, 

bone, and connective tissue) than other Hanford workers. However, a significant trend for increased 

mortality from nonexternal causes of death with increasing duration at routine plutonium-associated jobs 

was observed (1.1% increase in mortality per year, standard error [SE]=0.06). When stratified by age, the 

trend was stronger among workers ≥50 years of age (2.0±1.1% per year), compared to ages <50 years 

(0.1±0.9% per year). The strongest trend was for lung cancer (7.1±3.4% per year). 
 

 

 

 

 

 

 

 

 

 

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Studies in Animals. Consistent with findings from human epidemiological studies, results of animal 

studies show that tissue location of plutonium-induced cancer is compound dependent. Compoundrelated differences in cancer location reflect differences in distribution of plutonium following inhalation; 

a significant amount of plutonium from the relatively soluble 238PuO2 and 239Pu(NO3)4 compounds is 

distributed to bone and liver. In contrast, the relatively insoluble 239PuO2 is primarily retained within the 

lungs and associated lymph nodes (DOE 1987f, 1988a), with approximately 10, <1, 0.2, and 0.002% 

relocating to liver, skeleton, spleen, and kidney, respectively (Muggenburg et al. 2008) (see Section 3.4, 

Toxicokinetics). Experiments in the ITRI and PNL dogs provide the most extensive database on 

radiation-induced cancer following inhalation exposure to plutonium. Information on plutonium-induced 

cancer as a primary cause of death is reviewed in Section 3.2.1.1. 

In addition, Muggenburg et al. (2008) provided evidence against the “hot particle” theory, which 

hypothesized that larger particles with higher activity and less uniform distribution might be more likely 

to cause cancer than smaller, more uniformly dispersed particles. The authors exposed dogs to three 

uniform sizes of plutonium particles (0.75, 1.5, and 3.0 μm AMAD, representing activities spanning more 

than 2 orders of magnitude from 0.048 to 7.7 mBq) and conducted a composite lifespan study. They 

found that smaller and more uniformly distributed particles have the same or greater potential to produce 

neoplasms than less uniformly distributed larger particles. 

Exposure of Dogs to 238PuO2. Bone tumors (predominantly osteosarcomas) were the primary cause of 

cancer deaths in dogs exposed once to 238PuO2 aerosols; lung tumor incidences were also relatively high 

in these dogs and liver tumors appeared to be a contributing cause of death in a few 238PuO2-exposed dogs 

(Muggenburg et al. 1996; Park et al. 1997). In the ITRI study (Muggenburg et al. 1996), initial 238Pu lung 

burdens ranged from 0.15 to 43.1 kBq/kg. Incidences of bone, lung, and liver tumors as the cause of 

death were 93/144, 36/144, and 2/144 dogs, respectively. The tumors appeared beginning at about 

3 years postexposure; liver tumors appeared later than bone and lung tumors. In the PNL study (Park et 

al. 1997), mean initial 238Pu lung burdens ranged from 0.01 to 18.9 kBq/kg. Incidences of bone, lung, and 

liver tumors were 34/116 (29%), 31/116 (27%), and 8/116 (7%), respectively. More deaths were due to 

bone tumors than lung tumors, although the average cumulative alpha radiation dose to the lung was 

higher than that to the skeleton. Bone tumors occurred more frequently in the axial skeleton than in the 

appendicular skeleton (Park et al. 1997). One of 20 control dogs was euthanized due to lung tumors and 

1 control dog had a nonfatal liver tumor. Most lung tumors in the 238PuO2-exposed ITRI and PNL dogs 

were located in peripheral lung, rather than central airways, and the majority were classified as 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 62 

3. HEALTH EFFECTS 

bronchoalveolar carcinomas and papillary adenocarcinomas (Muggenburg et al. 1996; Park et al. 1997). 

No single histopathological type of liver tumor was identified as the most frequent. Bile duct tumors 

were also observed in the 238PuO2-exposed ITRI and PNL dogs (Muggenburg et al. 1996; Park et al. 

1997). 

Exposure of Dogs to 239PuO2. In contrast to the high incidences of bone tumors in the dogs exposed to 

238PuO2 or 239Pu(NO3)4 aerosols, cancer deaths in dogs exposed to aerosols of the relatively insoluble 

239PuO2 were predominantly associated with lung tumors, as reported in a 20-year lifespan composite 

study (Muggenburg et al. 2008). The study included 18 control dogs and 108 239PuO2-exposed dogs per 

sex, including seven dose groups with average ILBs of 0.16, 0.63, 1.6, 3.7, 6.4, 14, and 29 kBq/kg lung. 

A total of 125 of the 239PuO2-exposed dogs developed primary lung tumors and died between days 1,086 

and 6,123 after receiving radiation lung doses between 1.7 and 80 Gy. The lowest absorbed dose for 

radiation pneumonitis in the dogs was in excess of 10-fold higher than that reported for humans by 

Newman et al. (2005). 

Most of the lung cancers were papillary adenocarcinomas (n=70) followed by bronchiolo-alveolar 

carcinomas (n=40) and adenosquamous carcinomas (n=22). The frequency of lung cancer occurrence 

exceeded that of radiation pneumonitis at the lower doses, but radiation pneumonitis dominated at doses 

above an ILB of 3.7 mBq/kg; there was insufficient time for cancer development at ILBs >14 kBq/kg 

(Muggenburg et al. 2008). Earlier and shorter studies reported bronchiolo-alveolar carcinoma as the most 

frequently identified cancer type. (DOE 1987f, 1988a, 1990a; Hahn et al. 1999; Weller et al. 1995b). At 

exposure levels used in those studies, surviving dogs were at high risk for lung tumors. In the dog study 

performed at PNL (DOE 1988a, 1990a; Weller et al. 1995b), death due at least in part to lung tumors was 

noted in 52/116 plutonium-exposed dogs versus 4/20 control dogs. 

Among the various studies, few dogs died from tumors of the bone, liver, or kidney where the respective 

radiation doses to those organ systems were approximately 2, 4, or 5 orders of magnitude lower than that 

to the lungs. Although up to 10 and 1% of the plutonium deposited in the lung relocated to liver and 

skeleton, respectively, tumor incidences in liver and skeleton of plutonium-exposed were not significantly 

different from those of controls (Muggenburg et al. 2008). Although bone tumors were reported as a 

primary cause of death in three PNL dogs from the two lowest exposure groups (mean ILBs of 0.01 or 

0.064 kBq/kg (DOE 1988a), they were not observed in dogs with higher ILBs and may not have been 

239PuO2-induced. Death due to radiation pneumonitis in dogs with higher ILBs would be expected to 

preclude late-developing lung tumors or tumors in organs where significantly lower radiation doses would 
 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 63 

3. HEALTH EFFECTS 

make them relatively unlikely to occur. Time-to-death in dogs with primary lung tumors ranged from 

1,086 days for a bronchioloalveolar carcinoma at 1.7 Gy to 6,123 days for a squamous cell carcinoma at 

80 Gy. Neither bone nor liver tumors were reported in the 239PuO2-exposed ITRI dogs (Hahn et al. 1999; 

Muggenburg et al. 2008). 

Exposure of Dogs to 239Pu(NO3)4. The pattern of tumor development in PNL dogs exposed to 

239Pu(NO3)4 was similar to that of dogs exposed to 238PuO2, with tumors observed in lung, bone, and liver 

(principally of bile-duct epithelium) (Dagle et al. 1996; DOE 1988b, 1994a). Bone tumors were the main 

cause of death in the exposure groups with mean initial lung burdens of 1.02 and 5.91 kBq/kg, exposure 

levels at which incidences of dogs with bone tumors were 10/20 and17/20, respectively (DOE 1994a). 

Three of 20 dogs in the next lower exposure group (initial lung burden of 0.19 kBq/kg) also exhibited 

bone tumors. No bone tumors were observed in the lowest exposure groups (mean initial lung burdens of 

0.028 or 0.0069 kBq/kg) or control dogs. Bone tumors were found in axial and appendicular skeleton and 

primarily consisted of osteogenic sarcomas arising from endosteal surfaces (DOE 1994a). In an interim 

report (DOE 1988b), lung tumors were a main cause of early death in 2/20, 6/20, and 11/20 dogs in the 

groups with mean initial lung burdens of 0.19, 1.02, and 5.91 kBq/kg, respectively. Final lung tumor 

incidences were not located in available reports of 239Pu(NO3)4-exposed PNL dogs. Incidences of liver 

tumors were 1/20, 0/20, 3/20, 3/20, 3/20, 5/20, and 0/20 in unexposed controls, vehicle controls, and lowto-high exposure groups (mean initial body burdens of 0.0069, 0.030, 0.19, 1.02, and 5.91 kBq/kg), 

respectively (DOE 1994a). At the highest exposure level, early deaths from other causes may have 

precluded the development of liver tumors. 

Exposure of Other Laboratory Animal Species. Lung tumors have been associated with exposure to 

239PuO2 aerosols in rats (Dudoignon et al. 2001, 2003; Herbert et al. 1993; Lundgren et al. 1995; Oghiso 

and Yamada 2003a; Oghiso et al. 1994b, 1998; Sanders and Lundgren 1995; Sanders and Mahaffey 1979; 

Sanders et al. 1988a, 1988b, 1993b), mice (Lundgren et al. 1987), and primates (Hahn et al. 1984; 

Metivier et al. 1974). Two of 32 baboons developed lung tumors following exposure to 239PuO2 aerosols 

at levels resulting in initial 239Pu lung burdens ranging from 10.6 to 267 kBq/kg lung (Metivier et al. 

1974). Lung tumors have also been reported in rats exposed to 238PuO2 aerosols (Sanders et al. 1977). 

Hamsters appear to be resistant to lung tumor induction following inhalation of plutonium. No 

statistically significant increases in tumor incidence occurred in lifetime studies of Syrian hamsters 

exposed once or repeatedly (seven exposures during 12 months) to 238PuO2 or 239PuO2 aerosols at levels 

resulting in initial or reestablished 238Pu or 239Pu lung burdens ranging from 52 to 130 kBq/kg (Sanders 
 

 

 

 

 

 

 

 

 

 

PLUTONIUM 64 

3. HEALTH EFFECTS 

1977). Hamsters were also resistant to radiation-induced lung cancer following exposure to other alphaemitting radionuclides, such as radon and radon daughters (Agency for Toxic Substances and Disease 

Registry/EPA 1990). 

All cancer effect levels (CELs) for dogs and nonhuman primates exposed to aerosols of plutonium 

compounds are recorded in Table 3-3 and plotted in Figure 3-1. 

3.2.2 Oral Exposure 

3.2.2.1 Death 

No studies were located regarding death or lifespan shortening in humans after oral exposure to 

plutonium. 

In neonatal rats, given a single 1.2x104 kBq 238Pu /kg dose (as plutonium citrate) by gavage, 

45% mortality was observed by 2 weeks postexposure; no deaths were reported following dosing at 

3.7 kBq/kg (Fritsch et al. 1987). 

3.2.2.2 Systemic Effects 

No studies were located regarding respiratory, cardiovascular, hematological, musculoskeletal, hepatic, 

renal, or dermal/ocular effects in humans or animals after oral exposure to plutonium. 

Gastrointestinal Effects. No studies were located regarding gastrointestinal effects in humans after 

oral exposure to plutonium. 

Gastrointestinal effects were observed in neonatal rats following oral administration of 238Pu/kg (as 

plutonium citrate) by gavage (Fritsch et al. 1987). Mild hypertrophy of the crypts of the small intestine, 

which form the secretions of the small intestine, was observed in the rats receiving a 5,300 kBq 238Pu/kg 

dose. Total disappearance of epithelial cells and crypts, combined with intestinal hemorrhaging, was 

observed in rats that received 17,400 kBq 238Pu /kg (Fritsch et al. 1987). Increased neutrophils were 

noted on the surface epithelium and superficial cellular layers of the large intestine in adult rats given 

155 μCi 238PuO2/kg (5,740 kBq/kg) (Sullivan et al. 1960). This effect was noted at 3 (but not 6) days 

postexposure. 
 

 

 

 

 

 

 

 

PLUTONIUM 65 

3. HEALTH EFFECTS 

No studies were located regarding the following health effects in humans or animals after oral exposure to 

plutonium: 

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 

No studies were located regarding death or the shortening of lifespan in humans or animals after dermal 

exposure to plutonium. 

3.2.3.2 Systemic Effects 

No studies were located regarding respiratory, cardiovascular, gastrointestinal, hematological, 

musculoskeletal, hepatic, renal, or dermal/ocular effects in humans or animals after dermal exposure to 

plutonium. 

No studies were located regarding the following health effects in humans or animals following dermal 

exposure to plutonium: 

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 

Numerous health effects studies are available for plutonium-injected animals. Results of the injection 

studies support the findings from the inhalation studies. For example, bone and liver tumors were 

observed in dogs exposed to aerosols of 238PuO2 or 239Pu(NO3)4 that resulted in toxicologically significant 
 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 66 

3. HEALTH EFFECTS 

systemic distribution of plutonium (see Section 3.2.1). Similarly, bone and liver tumors were associated 

with intravenous injection of 239Pu (as plutonium citrate) in dogs (Lloyd et al. 1993, 1995a, 1999a, 1999b; 

Taylor et al. 1991). Detected plutonium levels in testes and ovaries of mice intravenously injected with 

239Pu (as the citrate) provide suggestive evidence that internalized plutonium could result in the irradiation 

of germ cells (Green et al. 1976, 1977). However, Brooks et al. (1979) noted the lack of significantly 

increased frequency of chromosomal aberrations in spermatogonia of rodents following intravenous 

injection of 239Pu (as the citrate) at levels high enough to induce marked life shortening and increased 

cancer incidence. Collectively, these results indicate that irradiation from internalized plutonium is not of 

particular reproductive toxicity concern. 

Because adequate information is available regarding health effects in animals following inhalation 

exposure to aerosols of plutonium compounds that resulted in toxicologically significant levels of 

internalized plutonium, the results of the injection studies are not presented in detail in this toxicological 

profile for plutonium. 

3.3 GENOTOXICITY 

Abundant information is available regarding the genotoxicity of ionizing radiation (refer to the 

Toxicological Profile for Ionizing Radiation for a detailed discussion of the genotoxic effects of various 

forms of ionizing radiation). The genotoxicity of alpha radiation from plutonium sources has been 

investigated in various groups of plutonium workers, as well as in vivo animal studies and a variety of 

in vitro test systems. Tables 3-4 and 3-5 present the results of in vivo and in vitro genotoxicity studies, 

respectively. 

Although epidemiological studies do not provide conclusive evidence that plutonium produces genetic 

damage in humans, results of some studies provide suggestive evidence of dose-related increases in 

chromosomal aberrations in plutonium workers with measurable internalized plutonium. For example, 

Livingston et al. (2006) examined relationships between external radiation dose, internal radiation dose, 

and frequencies of chromosomal aberrations and micronuclei in peripheral blood lymphocytes of a group 

of 30 retired plutonium workers with dosimetrically-estimated internal and external radiation doses 

>0.5 Sv, another 17 workers with predominantly external radiation doses <0.1 Sv, and 21 control subjects 

with no history of occupational radiation exposure. Frequency of chromosomal aberrations was 

positively correlated with the bone marrow dose (alpha radiation from internalized plutonium; 168 mSv 
 

 

 

 

 

 

 

 

 

 

 

	 


 


 

	 

	 

	 

	 

	 

	 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 

	 

PLUTONIUM 67 

3. HEALTH EFFECTS 

Table 3-4. Genotoxicity of Plutonium In Vivo 

Species (test system) End point	 Results Reference 

Mammalian systems: 

Human (peripheral Chromosomal aberrations + Schofield 1980
 

blood lymphocytes)
 

Human (peripheral Chromosomal aberrations (+)	 Brandom et al. 1990; Hande et al. 

blood lymphocytes)	 2003, 2005; IAEA 1979; Livingston et 

al. 2006; Mitchell et al. 2004; 

Okladnikova et al. 2005; Tawn et al. 

1985; Whitehouse et al. 1998 

Human (whole blood) Chromosomal aberrations –	 Hempelmann et al. 1973; Voelz et al. 

1979 

Monkey (peripheral Chromosomal aberrations + Brooks et al. 1992; LaBauve et al. 

blood lymphocytes) 1980 

Mouse (testes) Chromosomal aberrations +	 Beechey et al. 1975; Generoso et al. 

1985; Pomerantseva et al. 1989 

Mouse (testes) Chromosomal aberrations –	 Brooks et al. 1979; Searle et al. 1976 

Mouse (bone marrow) Chromosomal aberrations +	 Svoboda et al. 1987 

Chinese hamster Chromosomal aberrations – Brooks et al. 1979
 

(testes)
 

Chinese hamster Chromosomal aberrations + IAEA 1976b, 1976e
 

(liver cells)
 

Chinese hamster Chromosomal aberrations + DOE 1976
 

(blood cells)
 

Syrian hamster (lung Chromosomal aberrations + Stroud 1977
 

cells)
 

Mouse (pulmonary Micronuclei + Talbot et al. 1986, 1989
 

alveolar
 

macrophages)
 

Mouse (male germ Dominant lethal + IAEA 1976k; Lüning et al. 1976;
 

cells) Pomerantseva et al. 1989
 

Mouse (male germ Dominant lethal – Searle et al. 1976
 

cells)
 

Mouse (ovaries) Dominant lethal (+)	 Searle et al. 1982 

– = negative result; + = positive result; (+) = positive or marginal result 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


 


 


 


 


 

	 

	 

	 

	 

	 

	 

	 

	 

	 

	 

	 

	 

	 

	 

	 

	 

	 

	 

	 

	 

PLUTONIUM 68 

3. HEALTH EFFECTS 

Table 3-5. Genotoxicity of Plutonium In Vitro 

Result 

With Without 

Species (test system) End point activation activation Reference 

Mammalian cells: 

Human (peripheral blood Chromosomal No data + Purrott et al. 1980 

lymphocytes) aberrations 

Human (lymphoblastic cell Chromosomal No data + DOE 1980h 

line) aberrations 

Mouse (10T1/2, 3T3 cells) Chromosomal No data + Nagasawa et al. 1990a 

aberrations 

Mouse (bone marrow) Chromosomal No data + Kadhim et al. 1992 

aberrations 

Chinese hamster (M3-1 cells) Chromosomal No data + Welleweerd et al. 1984 

aberrations 

Chinese hamster (V79 cells) Chromosomal No data + Griffin et al. 1994 

aberrations 

Chinese hamster (ovary K-1 Chromosomal No data + Nagasawa et al. 1990b 

cells) aberrations 

Human (peripheral blood Sister chromatid No data + Aghamohammadi et al. 

lymphocytes) exchanges 1988 

Mouse (10T1/2, 3T3 cells) Sister chromatid No data + Nagasawa et al. 1990a 

exchanges 

Chinese hamster (ovary cells) Sister chromatid No data + Nagasawa and Little 

exchanges 1992; Nagasawa et al. 

1990b 

Human (peripheral blood Micronuclei No data + Bilbao et al. 1989 

lymphocytes) 

Human (embryonic skin Gene mutation No data + Chen et al. 1984 

fibroblasts) 

Chinese hamster (ovary cell Gene mutation No data + Barnhart and Cox 1979; 

line) DOE 1980h 

Chinese hamster (V79-4 cells) Gene mutation No data + Thacker et al. 1982 

Chinese hamster (V79-4 cells) DNA double-strand No data + Jenner et al. 1993 

breaks 

Chinese hamster (V79-379A DNA double-strand No data + Fox and McNally 1990 

lung fibroblasts) breaks 

Chinese hamster DNA damage No data + Prise et al. 1987 

(V79-379A cells) 

Mouse-rat (hybrid cell line) Reduction in radio- No data + Robertson and Raju 1980 

resistance 

Prokaryotic organisms: 

Salmonella typhimurium Gene mutation No data – DOE 1980h 

(TA100, TA98, TA1535, 

TA1537, TA1538, TA2420, 

TA2421) 

C = negative result; + = positive result 
 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 69 

3. HEALTH EFFECTS 

median dose to the bone marrow), but not with the external radiation dose. Frequency of micronuclei did 

not differ significantly among the three study groups. 

Significantly increased frequencies of symmetrical and asymmetrical chromosomal aberrations were 

reported among workers at the Sellafield (United Kingdom) plutonium facility with internalized 

plutonium in excess of 20% of the maximum permissible body burden (Tawn et al. 1985). Frequencies of 

symmetrical aberrations were significantly higher at retesting 10 years later, although no significant 

external radiation exposure had occurred during the 10-year interim (Whitehouse et al. 1998). This 

finding is consistent with the hypothesis that internally-deposited plutonium irradiates hemopoietic 

precursor cells (Whitehouse et al. 1998). 

Internal plutonium dose-related increased frequencies in chromosomal aberrations have also been 

reported in peripheral blood lymphocytes of plutonium workers with estimated plutonium body burdens 

as high as 15.5 kBq from exposure at the Mayak plutonium facilities in Russia (Hande et al. 2003, 2005; 

Mitchell et al. 2004; Okladnikova et al. 2005). The increased frequencies of chromosomal aberrations in 

the Mayak workers persisted many years following the cessation of exposure (Hande et al. 2003, 2005; 

Mitchell et al. 2004). 

Significantly increased frequencies of chromosomal aberrations were observed among Rocky Flats 

(Colorado) plutonium workers with internal plutonium burdens >740 Bq (Brandom et al. 1990; IAEA 

1979). Conversely, among Manhattan Project plutonium workers followed for up to 32 years, no 

apparent correlation was found between the frequency of chromosomal aberrations and plutonium body 

burdens in the range of 0.185–15.4 kBq (Hempelmann et al. 1973; Voelz et al. 1979). 

Open wounds represent a significant route through which plutonium workers might be exposed to 

plutonium alpha particles. Chromosomal aberrations were observed in lymphocytes among eight 

plutonium workers in the United Kingdom occupationally exposed to plutonium with the primary routes 

of exposure through wounds, punctures, or abrasions (estimated plutonium body burdens from 0.78 to 

1.5 kBq). In exposed individuals, the number of dicentric aberrations averaged 5 per 500 cells, while the 

natural population background frequency of this aberration is 1 per 4,000 cells (Schofield 1980; Schofield 

et al. 1974). 

Results of in vivo genotoxicity studies in laboratory animals consistently reveal alpha radiation-induced 

dose-related increases in the frequency of chromosomal aberrations following internalization of 
 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 70 

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plutonium. Chromosomal aberrations were observed in monkeys and hamsters following inhalation 

exposure to plutonium. Increases in chromosomal aberrations in blood lymphocytes were seen in 

immature Rhesus monkeys exposed to 239PuO2 at concentrations resulting in initial lung burdens of 1.9– 

19 kBq 239Pu/kg body weight (LaBauve et al. 1980) and Cynomolgus monkeys exposed to 239Pu(NO3)4 at 

a concentration resulting in a projected initial lung burden of 40 kBq (Brooks et al. 1992), but not at lower 

levels. Dose-related increases in the frequency of chromosomal aberrations were observed in Chinese 

hamster blood cells 30 days after exposure of the animals at aerosol concentrations resulting in deposition 

of 370–9600 kBq 239Pu/g of lung tissue (DOE 1976). Increases in chromosomal aberrations in bone 

marrow cells were observed in mice following intravenous injection of 239Pu (as the citrate) at 13 kBq 

239Pu/kg body weight (Svoboda et al. 1987). The highest incidence of these mutations was observed in 

the early days postinjection. Increased frequency of chromosomal aberrations was observed in liver 

tissue of Chinese hamsters intravenously given 239Pu or 238Pu (as the citrate or the dioxide) to achieve 

levels ranging from 0.026 to 0.74 kBq 239Pu or 238Pu/g of liver tissue (DOE 1976) or 74 kBq 239Pu/kg 

body weight (IAEA 1976b). The frequency of aberrations was much higher in hamsters exposed by 

intravenous injection to 239Pu or 238Pu (as the citrate) than in hamsters exposed to 239PuO2 or 238PuO2 

(IAEA 1976a, 1976b). Stroud (1977) reported significantly increased frequency of chromosomal 

aberrations in lung cells of Syrian hamsters following inhalation exposure to 238PuO2-ZrO2 particles at a 

level resulting in initial 238Pu lung burden of approximately 5.2 kBq. 

The induction of micronuclei in pulmonary alveolar macrophages (PAM) was noted in mice exposed to 

238PuO2 or 239Pu O2 aerosols under exposure conditions that resulted in mean initial lung deposits of 

approximately 550 and 580 Bq, respectively (approximately 22 and 24 Bq/kg body weight, respectively) 

(Talbot et al. 1989). Micronuclei in PAM of control mice averaged <0.1%, whereas peak incidences of 

micronuclei in the 238PuO2- and 239PuO2-exposed mice reached 3 and 5%, respectively, at 21 days 

postexposure. 

Increased frequency of chromosomal aberrations have been observed in spermatogonia of rodents 

following parenteral administration of plutonium compounds at activity levels much higher than those 

known to cause marked life shortening and increased cancer incidence. Markedly increased frequencies 

of chromosomal aberrations were observed in spermatogonia of mice receiving a single intraperitoneal 

injection of 238Pu(NO3)4 at 238Pu activity levels ≥231 kBq/kg body weight (Pomerantseva et al. 1989). 

Increased frequency of reciprocal translocations in spermatogonia was observed in male mice 6–18 weeks 

after intravenous injection of 239Pu (as the citrate) at 370 kBq 239Pu/kg body weight (Beechey et al. 1975). 

An increase in the frequency of heritable translocations was also observed in spermatogonia of male mice 
 

 

 

 

 

 

 

 

 

 

PLUTONIUM 71 

3. HEALTH EFFECTS 

intravenously injected with 239Pu (as the citrate) at 370 kBq 239Pu/kg body weight (Generoso et al. 1985). 

The frequency of translocations increased as a function of time and dose. However, induction of 

reciprocal translocations was not significant in male mice intravenously injected with 150 kBq 239Pu/kg 

body weight (Searle et al. 1976). No statistically significant increases in the incidence of chromosomal 

aberrations per spermatogonia cell were observed in mice or hamsters following intravenous 

administration of 239Pu (as the citrate) at activity levels (ranging from 22 to 74 kBq 239Pu/kg body weight) 

high enough to induce marked life shortening and increased cancer incidence (Brooks et al. 1979). 

Dominant lethality has been observed in plutonium-exposed mice. Fetal intrauterine death occurred in 

female mice mated with male mice that had received 239Pu (as the citrate) at levels ranging from 3.7 or 

18.5 kBq 4 weeks prior to mating (IAEA 1976k; Lüning et al. 1976). The effects of the dominant lethal 

mutations were also observed when untreated females were mated with male mice from the F1 generation. 

Exposure of male mice to higher doses of 239Pu resulted in sterility 12 weeks postexposure (IAEA 1976k; 

Lüning et al. 1976). Pomerantseva et al. (1989) reported the induction of dominant lethal mutations in 

male mice that had been administered single intraperitoneal injection of 239Pu(NO3)4 at levels 

≥0.925 kBq/g body weight 2–22 weeks prior to mating; males receiving 1.85 kBq/g body weight became 

sterile 9 weeks postinjection. Exposure of female mice to plutonium also resulted in dominant lethal 

mutations (Searle et al. 1982). Intravenous injection of female mice with 239Pu (as the citrate) at 740 kBq 

239Pu/kg body weight resulted in marked oocyte killing and subsequently reduced number of mice which 

became pregnant, compared with the controls. Both pre- and postimplantation dominant lethals were 

induced when mating occurred at long periods (12 weeks) after intravenous exposure to plutonium. 

Consistently positive genotoxicity results have been reported in various test systems exposed to the alpha 

radiation from plutonium compounds in vitro (see Table 3-5). Chromosomal aberrations were reported in 

human peripheral blood lymphocytes and lymphoblasts (DOE 1980h; Purrott et al. 1980); bone marrow 

and 10T1/2, 3T3 cells from mice (Kadhim et al. 1992; Nagasawa et al. 1990a); and M3-1, V79, and ovary 

K-1 cells from Chinese hamsters (Griffin et al. 1994; Nagasawa et al. 1990b; Welleweerd et al. 1984). 

Sister chromatid exchanges were noted in plutonium-exposed human peripheral blood lymphocytes 

(Aghamohammadi et al. 1988), mouse 10T1/2, 3T3 cells (Nagasawa et al. 1990a), and Chinese hamster 

ovary cells (Nagasawa and Little 1992; Nagasawa et al. 1990b). Bilbao et al. (1989) reported plutoniuminduced micronuclei in human peripheral blood lymphocytes. Other positive genotoxicity results include 

gene mutation in human and hamster cell lines (Barnhart and Cox 1979; Chen et al. 1984; DOE 1980h; 

Thacker et al. 1982), DNA double-strand breaks in Chinese hamster V79-4 and V79-379A cells (Fox and 

McNally 1990; Jenner et al. 1993), DNA damage in Chinese hamster V79379A cells (Prise et al. 1987), 
 

 

 

 

 

 

 

 

 

 

 

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and reduction in radio-resistance in mouse-rat (hybrid) cell line (Robertson and Raju 1980). Results were 

negative for plutonium-induced gene mutation in several strains of Salmonella typhimurium (DOE 

1980h). 

3.4 TOXICOKINETICS 

Studies of the toxicokinetics of plutonium have focused on two general classes of compounds: highly 

insoluble compounds (e.g., PuO2) and soluble compounds (e.g., Pu[NO3]4, plutonium citrate complexes). 

However, factors other than solubility affect the behavior of plutonium in biological systems. These 

include: (1) hydrolysis reactions at physiological pH that yield highly insoluble polymers from soluble 

Pu(IV); (2) particle size, which affects deposition characteristics in the respiratory tract and absorption 

rates from the lung and gastrointestinal tract; (3) firing temperature at which the PuO2 was formed, which 

may affect particle surface characteristics and susceptibility to physical transformation reactions that 

increase mobility and absorption; and (4) isotope specific activity, which can affect the intensity of 

radiation of the particles and rates of radiolytic fragmentation of particles in tissues. These various 

factors give rise to toxicokinetics of the various plutonium compounds that are not easily distinguished 

solely on the basis of water solubility. The toxicokinetics of inhaled 238PuO2 is distinctly different from 

that of inhaled 239PuO2 having a similar particle size range (>1 μm). Inhaled 238PuO2 that deposits in the 

lung is much more rapidly absorbed and distributed to liver and skeleton (predominantly) compared to 

239PuO2. As a result, deposition of similar initial lung burdens of the two isotopes will result in long-term 

(e.g., chronic) radiation doses to liver and skeleton (i.e., bone and marrow) that are higher, and lung doses 

that are lower, following exposures to 238PuO2 compared to 239PuO2. The consequences of these different 

radiation doses are distinct patterns of health effects that have been observed in controlled lifetime studies 

in animals, with more prominent lung effects following exposures to 239PuO2.and more prominent effects 

on bone, marrow, and liver following exposures to 238PuO2 (see Section 3.2.1). The kinetics, distribution, 

and health outcomes of inhaled 239Pu(NO3)4 are similar to those of 238PuO2. 

3.4.1 Absorption 

3.4.1.1 Inhalation Exposure 

Evidence for absorption of inhaled plutonium in humans derives from several types of measurements: 

(1) measurements of fecal and urinary excretion of plutonium following occupational inhalation 

exposures (Carbaugh and La Bone 2003; DOE 1985k, 1991c; James et al. 2003; Kathren and McInroy 

1991; Kurihara et al. 2002; McInroy et al. 1991; Voelz et al. 1979; Woodhouse and Shaw 1998); 
 

 

 

 

 

 

 

 

 

 

 

 

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(2) postmortem plutonium levels in tissues of workers exposed to airborne plutonium (Filipy and Kathren 

1996; Filipy et al. 1994; Hahn et al. 2003, 2004; Kathren and McInroy 1991; Khokhryakov et al. 2005; 

McInroy et al. 1989, 1991; Romanov et al. 2003; Voelz et al. 1997); (3) in vivo chest radiation 

measurements (241Am) following occupational exposures to airborne 241Pu (Carbaugh and La Bone 2003; 

DOE 1991c); and (4) experimental studies in which in vivo blood, urine, and organ x-ray emission were 

measured in subjects who inhaled 237Pu nitrate (Etherington et al. 2003; Hodgson et al. 2003). 

Inhaled plutonium particles that deposit in the respiratory tract are subject to three general distribution 

processes: (1) bronchial and tracheal mucociliary transport to the gastrointestinal tract; (2) transport to 

thoracic lymph nodes (e.g., lung, tracheobronchial, mediastinal); or (3) absorption by blood and/or lymph 

and transfer to other tissues (e.g., bone, liver). The above processes apply to all forms of deposited 

plutonium, although the relative contributions of each pathway and rates associated with each pathway 

vary with the physical characteristics (e.g., particle size), chemical form (degree of water solubility), and 

radiological characteristics (e.g., specific activity). The various processes that contribute to the 

elimination of plutonium from the respiratory tract give rise to multi-phasic lung retention kinetics. In 

most studies of lung retention, at least two kinetic components are evident. The faster phase is thought to 

be contributed by relatively rapid mechanical clearance mechanisms (e.g., mucociliary transport) and 

absorption to blood of soluble or relatively rapidly dissolved insoluble material deposited in the lung. 

The slower phase is contributed by the transformation and dissolution and/or mechanical clearance (e.g., 

phagocytic) of highly insoluble particles. 

Etherington et al. (2003) measured plutonium kinetics in two adult subjects who inhaled an aerosol of 

237+244Pu(NO3)4 (activity median aerodynamic diameter [AMAD]=1.1 μm; geometric standard deviation 

[GSD]=1.2). Lung, liver, and urine plutonium levels were estimated from K x-ray emission from the 

decay of 237Pu; blood plutonium levels were measured by mass spectrometry of 244Pu. Initial lung 

burdens were estimated to be 8 kBq 237Pu and 35 ng 244Pu. Lung retention half-times, estimated from 

observations made up to 120 days following the exposure, were 1.6–3.0 days (20%) for the fast phase, 

and 280–430 days (80%) for the slow phase. Longer-term observations of lung retention kinetics are 

available from studies of accidental inhalation exposures to plutonium oxide containing 241Pu (Carbaugh 

and La Bone 2003; DOE 1991c). In these studies, lung plutonium burdens were inferred from 

measurements of external radiation emitted by 241Am, a gamma-emitting daughter of 241Pu. Estimated 

lung retention half-times for 10 subjects ranged from 14 to 80 years. 
 

 

 

 

 

 

 

 

 

 

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The relatively long retention kinetics of inhaled plutonium particles in the lung is thought to reflect, in 

part, rates of physical transformation and dissolution of the particles. Various estimates have been made 

for these rates, based on modeling of data on urinary excretion and tissue burdens of plutonium following 

inhalation exposures (James et al. 2003; Khokhryakov et al. 2005). Based on an analysis of data from 

535 autopsies of plutonium workers, particle dissolution half-times were estimated to range from 

approximately 5–6 years, for exposures to highly insoluble plutonium oxides, to 1–2 years for exposures 

to more soluble forms (e.g., plutonium nitrate; Khokhryakov et al. 2005). James et al. (2003) estimated 

the lung dissolution half-time to be approximately 7 years in a subject who inhaled PuO2 ceramic 

particles. 

Absorption of inhaled PuO2 has been studied in various nonhuman primate species (Brooks et al. 1992; 

LaBauve et al. 1980; Lataillade et al. 1995; Metivier et al. 1974, 1978b; Stanley et al. 1982). Observed 

lung retention kinetics were biphasic. The slow-phase retention half-time in baboons exposed to 238PuO2 

(count median aerodynamic diameter [CMAD]=2.1 μm±1.3 standard deviation [SD]) was estimated to be 

approximately 400 days (range: 200–600 days), based on measurements made during the first 30– 

170 days after exposure (Metivier et al. 1974); however with longer observation periods (>200– 

300 days), the half-time was estimated to be approximately 1,000 days (Metivier et al. 1978b). Lataillade 

et al. (1995) estimated the lung retention half-time in baboons that inhaled an aerosol of an industrial 

PuO2 (AMAD=1.9 μm1.7 SD) consisting primarily of 239Pu and 240Pu (≈94 w%, 0.2 w% 238Pu); the 

estimated half-time was approximately 66 days, for an observation period of 180 days. Slow-phase lung 

retention half-times measured in Cynomolgus monkeys exposed to an aerosol of 239PuO2 

(AMAD=1.6 μm; GSD=1.6) ranged from 300 to 1,800 days (LaBauve et al. 1980). In Rhesus monkeys 

exposed to 239PuO2 from industrial ball milling processes (AMAD=1.5 μg±1.6 SE), the slow-phase lung 

retention half-time was estimated to be approximately 300 days (Stanley et al. 1982). Lung plutonium 

burdens have also been measured at various times in Cynomolgus monkeys exposed to aerosols of 

239Pu(NO3)4 (AMAD=06 μm; GSD=2.1); based on these data, the slow-phase retention half-time was 

approximately 200–300 days (Brooks et al. 1992). 

Numerous studies have examined the lung deposition and kinetics of absorption of inhaled plutonium in 

dogs (Bair et al. 1962b; Dagle et al. 1996; Guilmette et al. 1984, 1987; Mewhinney and Diel 1983; 

Muggenburg et al. 1996; Park et al. 1997). Inhaled aerosols of 238PuO2 were more rapidly cleared from 

the lung than aerosols of 239PuO2 of similar particle size distributions (Guilmette et al. 1984; Park et al. 

1997). This difference has been attributed to radiolytic fragmentation of particles in the lung, resulting in 

more enhanced particle dissolution and absorption from the lung (Mewhinney and Diel 1983). Lung 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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retention half-times following exposure of young adult beagles to aerosols of 239PuO2 

(AMAD=1.6 μm1.2 SD) were 86 days (32%) and 1,386 days (Guilmette et al. 1984). In comparison, 

lung retention half-times following exposure of young adult beagles to aerosols of 238PuO2 

(AMAD=1.8 μm1.9 SD) were 174 days (84%) and 908 days (Park et al. 1997). The corresponding 

times to achieve 50% of initial lung burdens are approximately 500 days for exposure to 239PuO2 and 

250 days for exposure to 238PuO2 (Park et al. 1997). Mewhinney and Diel (1983) analyzed data on lung 

retention in beagles exposed to 238PuO2 of various particle sizes (AMAD 0.7, 1.7, 2.7 μm) in order to 

estimate fragmentation rates of the deposited particles. Estimated fragmentation rates appeared to 

increase with time after exposure and particle size. Corresponding fragmentation half-times at 100 days 

postexposure were 100–250 days and, at 500 days postexposure were 50–120 days. Particle size (AMAD 

0.7–2.7 μm) had little effect on long-term lung retention (Mewhinney and Diel 1983). In beagles, shortterm (i.e., <1 month) lung retention of inhaled 239PuO2 was influenced by aerosol particle size 

distribution, with faster clearance from the lung as particle size decreased (Bair et al. 1962b). Long-term 

lung retention in beagles is also influenced by particle size. In beagles that were exposed to 239PuO2, the 

slow phase lung retention half-times were 700 days (90%, AMAD=0.9 μm1.4 SD), 1,400 days (68%, 

AMAD=1.6 μm1.2 SD), and 1,800 days (78%, AMAD=2.8 μm1.2 SD) (Guilmette et al. 1984). The 

method used to produce PuO2 also appears to affect the absorption of inhaled PuO2. Oxides produced at 

high temperature (i.e., high-fired, e.g., 1,000 °C) had longer lung retention than oxides produced at low 

temperature (i.e., low-fired, e.g., 350 °C) (Bair et al. 1973). 

Inhaled aerosols of 238Pu(NO3)4 are also more rapidly cleared from the lung than aerosols of 239Pu(NO3)4 

(Dagle et al. 1983, 1996). In beagles, this difference was most pronounced in the first 30 days 

postexposure, during which approximately 80% of the initial lung burden from 238Pu(NO3)4 was cleared 

compared to approximately 40% from 239Pu(NO3)4. Retention half-times were similar (≈130–150 days) 

for the two isotopes, for observations extending from 30 days to 1 year. 

3.4.1.2 Oral Exposure 

Absorption of plutonium accumulated in shellfish (mollusks) has been studied in humans. Adult subjects 

ingested winkles (six males, two females) or cockles (five males, one female) containing 239,240Pu that 

were collected from marine waters near the British Nuclear Fuels facility at Sellafield, Cumbria (Hunt 

1998; Hunt et al. 1986, 1990). The range of the ingested activity of 239+240Pu was 6–16 Bq. Serial 

24-hour urine samples were collected from each subject for up to 7 days after they ingested the mollusks. 

The fraction of the activity absorbed was estimated as the ratio of the observed cumulative urinary 
 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 76 

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excretion of 239+240Pu to that of the excretion predicted to occur if absorption had been complete. The 

latter was predicted using kinetic models of excretion of absorbed plutonium (Durbin 1972; Talbot et al. 

1987, 1993). The reported mean absorption fraction was 1.7x10-4 (range: 0.2x10-4–4.9x10-4) for subjects 

who ingested winkles. The estimated mean absorption fraction for subjects who ingested cockles was 

3.4x10-4 (range up to 7x10-4) based on the kinetic model of Durbin (1972), which predicts approximately 

1.1% of the body burden eliminated in 7 days, or 1.9x10-4 (range up to 3.9x10-4), based on the kinetic 

model of Talbot et al. (1987, 1993), which predicts approximately 2% of the body burden eliminated in 

7 days. 

Gastrointestinal absorption was also measured in three adult male volunteers following ingestion of a 

plutonium citrate solution along with food (Popplewell et al. 1994). Based on comparisons between 

measured urinary plutonium excretion for 8 or 9 days postingestion and similar assessments following 

intravenous injection of plutonium citrate 6 months later, calculated fractional absorption of ingested 

plutonium ranged from 2x10-4 to 9x10-4 . 

The gastrointestinal absorption fraction has also been estimated in human populations, based on analyses 

of inhalation and ingestion intakes, biological monitoring of plutonium excretion in urine or 

measurements of body burdens at autopsy. These estimates rely on model-based assumptions regarding 

the deposition of inhaled plutonium and the absorption fraction for plutonium deposited in the respiratory 

tract. Sun and Meinhold (1997) conducted an analysis of data on 34 residents of Rongelap Island who 

were exposed to plutonium fallout during and following the nuclear bomb detonations in the Marshall 

Islands. Based on measurements of urinary plutonium excretion and assumptions regarding the 

deposition and absorption of inhaled plutonium, the gastrointestinal absorption fraction (for diet and soil, 

combined) was estimated to be approximately 4.2x10-4 (range: 1.7x10-4–7.1x10-4). Mussalo-Rauhamaa 

et al. (1984) conducted an analysis of plutonium body burdens in Finnish Lapps and, along with estimates 

of inhalation and dietary intake of plutonium (primarily from consumption of reindeer), and assumptions 

regarding elimination rate of plutonium, estimated the gastrointestinal absorption fraction to range from 

approximately 8x10-4 to 9x10-4 . 

The gastrointestinal absorption of plutonium has been studied in nonhuman primates, dogs, and a variety 

of rodent species. Most of these studies have estimated absorbed plutonium as the sum of the plutonium 

burden in major tissue depots (e.g., liver and skeleton), plus the plutonium excreted in urine. Double 

isotope techniques have also been used to estimate the gastrointestinal absorption of plutonium in 

nonhuman primates (USNRC 1992). In this study, 239Pu(VI) bicarbonate was administered orally and 
 

 

 

 

 

 

 

 

 

 

 

 

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236Pu(VI) bicarbonate (or 238Pu) was administered intravenously to baboons and the gastrointestinal 

absorption fraction was estimated from the retention ratios for the two isotope ratios in tissues and 

cumulative excretion ratio in urine. Absorption was estimated to be 0.22% of the oral dose in fasted 

baboons and 0.011% in fed baboons. Gastrointestinal absorption of plutonium was measured in adult 

marmosets that received single gavage doses of either 239Pu citrate or 239Pu citrate added to powdered 

potato, and was based on levels of activity measured in tissues (mainly liver and skeleton) following 

sacrifice (Ham et al. 1994). Absorption was approximately 0.24% of the dose when administered as 

plutonium citrate and 0.14% of the dose when administered in potato powder. 

In addition to the above studies conducted in nonhuman primates, gastrointestinal absorption of 

plutonium, in various isotopic and chemical forms, has been measured in pigs, dogs, and various rodent 

species. Results from these studies support the following general conclusions regarding factors that affect 

absorption: (1) in general, absorption of plutonium citrate tends to be greater than nitrate, which is 

greater than plutonium oxide (PuO2) (Sullivan 1980a); (2) most estimates of absorption of plutonium 

citrate and nitrate in adult animals are <0.1% of the dose; (3) fasting tends to increase absorption 

(Bhattacharyya et al. 1986; USNRC 1992); (4) absorption is 10–1,000 times greater in neonates compared 

to adults, depending on the animal species and chemical form of plutonium (Sullivan 1980a, 1980b; 

Sullivan and Gorham 1983; Sullivan et al. 1985); (5) iron deficiency increases absorption in juvenile rats 

and administration of ferric iron (Fe3+) to iron-deficient rats decreases absorption (Sullivan and Ruemmler 

1988); and (6) absorption of plutonium in surface dusts (e.g., bomb test sites) in guinea pigs was <0.001% 

of the dose (Harrison et al. 1994). 

3.4.1.3 Dermal Exposure 

Occupational accidents have resulted in dermal exposures and/or penetration of plutonium into skin 

wounds and subsequent systemic absorption of plutonium (McInroy et al. 1989; Woodhouse and Shaw 

1998). In one case, postmortem measurements of 239Pu levels in tissues, measured 17 years following the 

incident, showed that liver contained approximately 41% of the body burden and skeleton contained 49% 

of the body burden (McInroy et al. 1989). Woodhouse and Shaw (1998) reported urinary excretion of 

plutonium during 20–30-year periods following various wound-related exposures to PuO2 (oxalate), 

Pu(NO3)4, or plutonium metal. Systemic absorption of 239Pu was estimated to have been approximately 

0.001%. Plutonium absorption through the intact human palmar skin was estimated to have been 

0.0002%/hour when applied as the nitrate (10 μg Pu) in a 0.4 N nitric acid solution for 8 hours (Langham 
 

 

 

 

 

 

 

 

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1959) and approximately 0.001%/hour following contamination of finger skin with Pu(NO3)4 in 9% HCl 

(Lister et al. 1963). 

Studies conducted in rodents have shown that dermal absorption of plutonium is accelerated when 

plutonium is applied to the skin in an acid medium and increases with severity of acid burns (ICRP 1986). 

Plutonium has been found to migrate down hair follicles (AEC 1955) and into sweat and sebaceous 

glands (AEC 1970b). 

3.4.2 Distribution 

3.4.2.1 Inhalation Exposure 

Information on the general pattern of distribution of absorbed plutonium in humans is available from 

direct measurements of plutonium in human autopsy tissues. Such measurements generally reflect the 

long-term distribution pattern, in some cases being heavily influenced by discrete exposure events that 

occurred years before death. Although some uncertainty exists regarding the relative contributions of 

inhalation and oral exposures to the tissue distributions observed in the autopsy studies (in particular, 

those of general populations), the finding of substantial amounts of plutonium in thoracic lymph nodes is 

considered to be indicative of inhalation exposures to insoluble plutonium compounds. 

Much more detailed information on the extra-respiratory distribution of inhaled plutonium derives from 

numerous studies that have been conducted in animals, including nonhuman primates, dogs, and various 

rodent species. The dog studies are of particular relevance to our understanding of the toxicology of 

inhaled plutonium. Beginning in the early 1950s, the U.S. government initiated several life-span studies 

of the toxicology of inhaled plutonium in beagles (DOE 1989). The results of these studies form part of 

the basis for our understanding of the toxicity and carcinogenicity of inhaled plutonium (see Section 3.2). 

Organ Distribution of Absorbed Plutonium in Humans. Information on tissue distribution of plutonium 

in humans has come from the analysis of plutonium levels in postmortem tissue samples. Postmortem 

studies have included workers exposed occupationally (Filipy and Ford 1997; Filipy and Kathren 1996; 

Filipy et al. 1994; James et al. 2003; McInroy et al. 1989, 1991; Suslova et al. 2002), as well as studies of 

the populations from the general public (Bunzl and Kracke 1983; Ibrahim et al. 2002; Kawamura and 

Tanaka 1983; Mussalo et al. 1981; Mussalo-Rauhamma et al. 1984; Nelson et al. 1993; Popplewell et al. 

1985; Singh and Wrenn 1983; Yamamoto et al. 2008a). Collectively, these studies have shown that 

approximately 95% of the systemic (i.e., absorbed) plutonium burden is found in skeleton (≈45%), liver 
 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 79 

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(≈45%), and skeletal muscle (≈5%). A substantial fraction of the total body burden (e.g., 20–70%) has 

also been found in the respiratory tract (including associated lymph nodes) in workers who experienced 

inhalation exposures (James et al. 2003; McInroy et al. 1989). Autopsy studies of subjects from the 

general public have found respiratory tract plutonium burdens ranging from approximately 3 to 6% of the 

combined burdens of respiratory tract, liver and skeleton (Ibrahim et al. 2002; Kawamura and Tanaka 

1983; Singh and Wrenn 1983). Yamamoto et al. (2008a) also evaluated the activity ratios of 240Pu/239Pu 

in autopsy samples from individuals surrounding the Semipalatinsk Nuclear Test Site in the former Soviet 

Union. They determined that both isotopes were present at highest concentrations in liver followed by 

lungs and kidney, and that the isotopic ratios ranged from 0.088 to 0.207, which were consistent with 

values obtained elsewhere from exposure to atomic weapons fallout. 

The highest concentrations of absorbed plutonium are usually found in liver, bone, and spleen (Filipy and 

Ford 1997; Filipy et al. 1994; McInroy et al. 1991; Yamamoto et al. 2008a). However, concentrations of 

plutonium in the respiratory tract and associated lymph nodes can exceed that of other tissues when 

exposures occur from inhalation (McInroy et al. 1991; Singh and Wrenn 1983). Skeletal:liver 

concentration ratios measured in tissues from deceased plutonium workers ranged from approximately 

0.05 to 1 (Filipy and Kathren 1996). Tissue:liver concentration ratios in a deceased plutonium worker 

were as follows: tracheobronchial lymph node [TBLN], 100; lung, 2.6; pituitary, 1.1; skeleton, 0.23; 

spleen, 0.22; and other soft tissues <0.2 (McInroy et al. 1991). An analysis of tissue plutonium levels in a 

group of deceased plutonium workers (n=69–137) found the following soft tissue:liver concentration 

ratios: skeleton (0.2) and spleen (0.05–0.08); ratios for other tissues were <0.05 (Filipy and Ford 1997; 

Filipy et al. 1994). 

The above estimates reflect measurements made at autopsy and not initial distributions of absorbed 

plutonium or redistribution of plutonium over time. Although processes involved in the distribution, 

initial deposition, and redistribution of absorbed plutonium are not clearly defined, available human and 

animal data collectively provide some insight. Inhaled plutonium that has entered the blood appears to be 

largely bound to transferrin and becomes associated with iron-binding proteins such as ferritin and 

lipofuscin upon entering hepatocytes (Stevens et al. 1968; Stover 1968a; Suslova et al. 2002; Taylor et al. 

1991). Based on regression analysis of autopsy data from Mayak workers, approximately 50 and 38% of 

the plutonium entering the blood from the lung initially deposited in the liver and skeleton, respectively 

(Suslova et al. 2002). Liver retention decreased linearly from 50% at the beginning of exposure to 42% at 

25 years postexposure, during which time skeletal deposition increased from 38 to 50%. This 

redistribution of approximately 8% of the total systemic content from liver to skeleton during the 25-year 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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postexposure period represents a translocation rate of approximately 0.32% per year. Redistribution of 

plutonium from other soft tissue is expected to contribute to increased skeletal content over time as well. 

Considerable effort and progress has been made in developing models that simulate the distribution and 

elimination kinetics of absorbed plutonium. These models are described in greater detail in Section 3.4.5. 

Organ Distribution of Absorbed Plutonium in Animals. Numerous studies conducted in various animal 

models, including nonhuman primates, rodents, and dogs, provide additional evidence for distribution of 

absorbed plutonium to thoracic lymph nodes, liver, and skeleton, following inhalation exposures to 

plutonium aerosols (Bair et al. 1962b, 1966; Buldakov et al. 1972; Dagle et al. 1986; Guilmette et al. 

1984; Lataillade et al. 1995; Mewhinney and Diel 1983; Morin et al. 1972; Muggenburg et al. 2008; 

Nenot et al. 1972; Park et al. 1972; Sanders 1973; Sanders and Mahaffey 1979; Sanders et al. 1977). 

These observations are consistent with the larger body of observations of the distribution of plutonium 

following parenteral administration of plutonium compounds (Bair et al. 1973; DOE 1989; Vaughan et al. 

1973). 

Studies conducted in animals have also shown that particle size and physical and chemical form of 

inhaled plutonium influence both the kinetics and patterns of tissue distribution of plutonium. 

Muggenburg et al. (2008) showed that, for monodisperse particles of 0.75, 1.5, or 3.0 μm AMAD, the 

smallest particles were most rapidly removed from the lungs during the first few hundred days. 

Thereafter, removal of the larger particles was more rapid than that of the smaller particles; this trend 

persisted past 6,000 days. The rate of particle distribution from the lung was greatest to the skeleton 

followed by liver and spleen. Activity (as percent ILB) in the skeleton increased to 1% at 6,000 days. 

Activity in the liver reached 10% at 1,500 days and slowly decreased thereafter. Activity in the spleen 

reached 0.2% at 1500 days and likewise slowly decreased afterward. Activity in the kidney initially 

reached 0.002% and then slowly decreased. In general, exposures to more insoluble forms of Pu (e.g., 

PuO2) result in distribution (percent of ILB) of plutonium from the lungs to thoracic lymph nodes 

comparable to that of the liver and greater compared to that of more soluble Pu(IV) complexes (e.g., 

citrate, nitrate) (Bair et al. 1966, 1973; DOE 1988b, 1989; Morin et al. 1972; Muggenburg et al. 2008; 

Park et al. 1972). The highest concentrations of plutonium in lymph nodes were observed initially in 

thoracic lymph nodes. Levels in selected lymph nodes increased to 10% ILB after 500 days (thoracic 

lymph nodes), 10% ILB at 6,000 days (mediastinal lymph nodes), 1% ILB at 2,000 days (hepatic lymph 

nodes), 0.1% ILB at 6,000 days (sternal lymph nodes), and 0.01% ILB at 300 days (retropharyngeal 

lymph nodes) (Muggenburg et al. 2008). Whereas plutonium concentrations in the thoracic lymph nodes 

of 239PuO2-exposed dogs remain high during lifetime observation, Mewhinney and Diel (1983) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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demonstrated that the concentrations in the thoracic lymph nodes of 238PuO2-exposed dogs rapidly 

increased to peak levels (approximately 10% of the initial lung burden) within the first year postexposure, 

then declined to <5% of the initial lung burden during the next 3 years. This difference in retention of 

plutonium by the thoracic lymph nodes is thought to result from radiation fragmentation and subsequent 

dissolution of the resulting smaller 238Pu particles, lymphatic transport to systemic circulation, and 

subsequent deposition principally in liver and skeleton (Mewhinney and Diel 1983). The method used to 

produce PuO2 also appears to affect the distribution of inhaled plutonium oxide. Distribution to thoracic 

lymph nodes, bone, and liver was greater when exposure was to chemically prepared oxides or to airoxidized or low-fired plutonium compared to the high-fired forms (Bair et al. 1973; Sanders and 

Mahaffey 1979). 

Distribution of PuO2 from the respiratory tract and associated lymph nodes is affected by the size of the 

particles initially deposited in the lung. Larger particle sizes (e.g., 2–4 μm MMD) deposited in the 

alveolar region of the lung undergo less extensive mucociliary transport to the gastrointestinal tract and 

more extensive transfer into bronchial lymph nodes (Bair et al. 1962b, 1973; Guilmette et al. 1984). On 

the other hand, transfer to extra-respiratory tissues is augmented with decreasing particle size (e.g., <2 μm 

mass median diameter [MMD]) (Bair et al. 1973; DOE 1989). Plutonium deposited in lung from 

exposure to 238PuO2 or 239Pu(NO3)4 is rapidly and more extensively distributed to extra-respiratory tissues 

than is 239PuO2 (Dagle et al. 1983, 1996; Guilmette et al. 1984; Park et al. 1997). For example, 

1,000 days after beagles were exposed to aerosols of similarly sized particles of 238PuO2 or 239PuO2, liver 

and skeletal burdens (fraction of initial lung burden) were approximately 100 times higher in dogs 

exposed to 238PuO2, and lung burdens were approximately 3–5 times higher in dogs exposed to 239PuO2 

(Guilmette et al. 1984; Park et al. 1997). The isotope effect is thought to result from the relatively high 

specific activity of 238 Pu, which contributes to radiolytic fragmentation of Pu-containing particles in lung 

and lymph nodes, augmenting transport and distribution to lymph and blood (Bair et al. 1973; Diel and 

Mewhinney 1983). The distribution kinetics of inhaled 239Pu(NO3)4 more closely resemble those of 

238PuO2 than 239PuO2 (Dagle et al. 1983, 1996; Park et al. 1995). 

Distribution of inhaled 239PuO2 to bone is influenced by age. In immature dogs, a 5-fold increase in 

distribution to the bone was seen compared to that in young adult dogs (DOE 1986c). These observations 

are consistent with similar observations made following parenteral administration of Pu(IV) (Bruenger et 

al. 1991a) and reflect higher bone turn-over in juveniles (see Distribution within Bone). 
 

 

 

 

 

 

 

 

 

 

 

 

 

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Maternal-fetal Transfer of Plutonium. Absorbed maternal plutonium can be transferred to the placenta 

and fetus (Lund and Tkatchev 1996; Prosser et al. 1994; Russell et al. 2003). Analyses of plutonium 

concentration in the placenta from a live birth that occurred 12 years following a work-related accidental 

inhalation exposure to plutonium found concentration ratios for placenta:maternal (estimated maternal 

body burden per kg body weight) of 0.16–0.27 (Russell et al. 2003). Analyses of plutonium in a sample 

of aborted fetuses from the general public found fetal:maternal concentration ratios to be <0.2 (Prosser et 

al. 1994). Studies in which animals received parenteral injections of plutonium (in most cases, as 

plutonium citrate) confirm that absorbed plutonium can be transferred to the fetus (Green et al. 1979; 

Kubota et al. 1993; Morgan et al. 1992; Paquet et al. 1998; Russell et al. 2003; Weiss and Walburg 1978). 

This distribution pathway would be expected after inhalation exposure. In baboons, fetal:maternal whole 

body concentration varied with the period of gestation at which the parenteral injection of plutonium 

occurred and were highest when plutonium was administered during early gestation: day 22, 

fetal:maternal=4; day 38, fetal:maternal=0.13; and day 106, fetal:maternal=0.04 (Russell et al. 2003, 

attributed to Andrew et al. 1977). A similar pattern has been observed in other animal species, and is 

thought to reflect distribution and dilution of plutonium initially transferred to the fetal-placental unit, as 

fetal growth progresses. A larger fraction of an administered maternal dose of plutonium is transferred to 

fetal-placental tissues during late pregnancy. In baboons that received a single intravenous injection of 

plutonium citrate during the 5th month of pregnancy, approximately 3–4% of the activity was transferred 

to the fetus within 7 days postadministration (Paquet et al. 1998). The fetal:maternal whole-body 

concentration ratio was approximately 1.3 and the tissue distribution in the fetus was similar to that 

observed in adult animals, with the skeleton and liver accounting for most of the plutonium activity in the 

fetal body. Fetal-placental burden was approximately 1% of the administered plutonium dose in guinea 

pigs, mice, and rats that received an injection of plutonium citrate during late pregnancy (Kubota et al. 

1993; Morgan et al. 1991). Maternal-fetal transfer of plutonium, administered as an intravenous injection 

of plutonium citrate on day 16 of pregnancy was dose-dependent in mice, and ranged from approximately 

5% of the dose following administration of 0.1 μCi/kg (3.7 kBq/kg) to approximately 1% following 

administration of 27 μCi/kg (100 kBq/kg; Weiss and Walburg 1978). The highest concentrations of 

plutonium in the fetal-placental unit are found in the yolk sac; however, as organogenesis progresses, 

plutonium is also found in other tissues, with the largest fraction of the fetal burden in liver and bone 

(Green et al. 1979; Kubota et al. 1993; Morgan et al. 1991; Paquet et al. 1998). 
 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 83 

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3.4.2.2 Oral Exposure 

Studies of the distribution of plutonium in humans exposed to plutonium solely through the ingestion 

pathway have not been reported. Studies conducted in nonhuman primates, dogs, and various rodent 

species have shown that plutonium absorbed from the gastrointestinal tract is distributed predominantly 

(≈90%) to liver and skeleton. A study conducted in fasted adult baboons (n=4) found that, 46 days after a 

single gavage dose of 239Pu(VI) carbonate, approximately 90% of total body burden was in the skeleton 

and liver, and that the skeletal:liver plutonium ratio (total burden) was approximately 1.2 (range: 0.7–1.7; 

USNRC 1992). Skeletal:liver ratios ranging from 1 to 4 have been observed in dogs, following oral 

exposures to plutonium bicarbonate and nitrate (Sullivan 1980a; Sullivan and Gorham 1983; Toohey et al. 

1984), and values ranging from 1 to 8 have been observed in rats and mice (Sullivan et al. 1985). 

3.4.2.3 Dermal Exposure 

Occupational accidents have resulted in dermal exposures and/or penetration of plutonium into skin 

wounds and subsequent systemic absorption of plutonium (McInroy et al. 1989; Woodhouse and Shaw 

1998). In one case involving a plutonium-contaminated finger wound, postmortem measurements of 

239Pu levels in tissues, measured 17 years following the incident, showed that 41 and 49% of the body 

burden were contained in the liver and skeleton, respectively; another 6.6% was associated with muscle 

tissue (McInroy et al. 1989). In a similar case of a plutonium-contaminated left finger wound (Popplewell 

and Ham 1989), postmortem measurements taken 18 years postaccident revealed a total estimated 

plutonium body burden of 2.4 kBq. The left arm axillary lymph nodes accounted for approximately 76% 

of the total body burden; other sites of deposition included skeleton (13%), left hand (5.5%), liver (4.5%), 

and left arm flesh (1%). 

3.4.2.4 Other Routes of Exposure 

Plutonium tissue distributions (postmortem) have been measured following intravenous injection of 

Pu(IV) citrate into subjects suffering from chronic disorders (Langham et al. 1980). Various analyses and 

summaries of these data have been published (AEC 1971; Durbin 1972; Kathren 2004; Leggett 1985). 

Postmortem tissue plutonium measurements for seven subjects have been reported; data for five of the 

subjects were obtained 1 year following exposure, data for the other two subjects were obtained 7 or 

21 years after exposure. Approximately 66% of the injected dose was found in skeleton (most of which 

appeared to be associated with bone marrow) and 20–40% in liver (Langham et al. 1980). 
 

 

 

 

 

 

 

 

 

 

PLUTONIUM 84 

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Postmortem plutonium tissue distributions were also measured in healthy subjects receiving a single 

intravenous injection of 237Pu(IV) citrate (Newton et al. 1998; Warner et al. 1994). As much as 73% of 

the injected 237Pu dose was found in the liver at 7–230 days postinjection; approximately half of the liver 

237Pu concentration was achieved within the first 2 days postinjection (Newton et al. 1998). Early 

gonadal uptake of 237Pu in four healthy males was in excess of 0.05%; mean retention between 30 and 

86 days postinjection was approximately 0.015% (Warner et al. 1994). 

Distribution of plutonium following intravenous injection of plutonium has been studied in nonhuman 

primates, dogs, and rodents (e.g., Bair et al. 1973; Bruenger et al. 1991a; Durbin et al. 1972, 1997; 

Guilmette et al. 1978; Polig 1989; Polig et al. 2000; USNRC 1992). 

3.4.3 Metabolism 

Plutonium metabolism in physiological systems consists, primarily, of hydrolytic reactions and formation 

of complexes with protein and nonprotein ligands. Plutonium can exist in oxidation states III–VI in 

solution; however, under most (if not all) physiological conditions, the predominant state is Pu(IV) 

(Gorden et al. 2003). At neutral pH, Pu(IV) ion rapidly undergoes hydrolysis to monomeric and insoluble 

polymeric plutonium hydroxides (e.g., nPu[OH]4) (Taylor 1973). Pu(IV) forms complexes with a variety 

of physiological proteins, including albumin, globulins (e.g., transferrin), ferritin, and various low 

molecular weight proteins (Gorden et al. 2003; Lehmann et al. 1983; Stevens et al. 1968; Stover et al. 

1968a; Taylor 1973). The dissociation constant of Pu(IV)-transferrin complex has not been measured; 

however, the complex appears to be less stable than Fe(III)-transferrin complex (Kd≈10-22 M) (Aisen and 

Listowsky 1980; Turner and Taylor 1968). As a result, binding of Fe(III) to transferrin can influence the 

degree of binding of Pu(IV). Excess iron results in reduced binding of plutonium to transferrin (Turner 

and Taylor 1968). Plutonium also forms complexes with nonprotein ligands, polycarboxylates (e.g., 

citrate, lactate). The stability constants for the mono- and di-citrate complexes are approximately 

1015 and 1030 M, respectively (Taylor 1973). 

3.4.4 Elimination and Excretion 

Kinetics of elimination of absorbed plutonium reflect relatively long retention times of plutonium in liver 

(half-time >9 years) and skeleton (half-time >20 years; ICRP 1994a, 1996a, 2001) (Leggett 1985), the 

dominant sites of accumulation of absorbed plutonium. Analyses of data on excretion and tissue burdens 

of plutonium in humans have contributed to the development of mechanistic models of plutonium kinetics 

(see Section 3.4.5). These models predict observed multi-phasic elimination kinetics, reflecting the 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 85 

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variation in kinetics and relative sizes of the major tissue depots for plutonium, with the half-time for the 

dominant kinetic process estimated to be 50–100 years (ICRP 1972, 1979, 1994a; Khokhryakov et al. 

2002; Leggett 1985). This general pattern of multi-phasic elimination with a dominant slow phase would 

be expected to apply to absorbed plutonium regardless of the route of exposure. However, with inhalation 

exposure, additional processes influence the elimination kinetics, including physical transformation and 

dissolution of particles deposited in the lung, which can provide a source of replenishment of plutonium 

to blood and other tissues (see Section 3.4.1.1). 

3.4.4.1 Inhalation Exposure 

Following inhalation exposure to PuO2, plutonium is excreted in feces and urine (DOE 1991c; 

Khokhryakov et al. 2004; Kurihara et al. 2002; Voelz et al. 1979). Excretion in feces peaks within 2– 

5 days following exposure, reflecting bronchial and tracheal mucociliary transport of deposited plutonium 

particles to the gastrointestinal tract (Kurihara et al. 2002); however, it persists for years after cessation of 

exposure (DOE 1991c; Khokhryakov et al. 2004; Voelz et al. 1979). In observations made on retired 

plutonium workers (n=19, ≥40 years following retirement), the median value for fecal:urine excretion 

ratio was 0.57 (GSD: 1.12; mean=0.83±0.73 SD) (Khokhryakov et al. 2004). Observations made at 

earlier times yielded higher ratios, indicating a gradual decline in the ratio with time. Group mean 

fecal:urine ratios in 345 workers (2–30 years postexposure) ranged from approximately 0.7 to 1.4 and 

were similar for oxides and nitrates (Khokhryakov et al. 2004). Voelz et al. (1979) determined a median 

fecal:urine ratio of 0.30 for 12 former workers in the United States. 

Kinetics of urinary excretion of inhaled plutonium reflect the kinetics of dissolution and absorption of 

plutonium particles deposited in the lung (half-times 1–20 years) and the relatively long retention times of 

plutonium in liver (half-time >9 years) and skeleton (half-time >20 years) (ICRP 1994a, 1996a). 

Following inhalation exposure to 238PuO2 ceramic particles, plutonium was not detected in urine until 

123 days after exposure and peak excretion rates occurred approximately 1,000 days following exposure 

(James et al. 2003). The delay in observed urinary excretion is thought to reflect, in part, the relatively 

slow dissolution kinetics of the particles (half-time ≈7 years) (James et al. 2003). Over longer periods of 

time following exposure, urinary excretion of plutonium exhibits multi-phasic kinetics, with declining 

rates over time (Kathren and McInroy 1991; Suslova et al. 2006; Woodhouse and Shaw 1998). Repeated 

measurements of urinary plutonium excretion in 6 workers who experienced inhalation exposures to 

aerosols of plutonium nitrate showed that excretion rate declined with a mean half-time of 12 years 

(95% CI: 10–16 years), when measured at times 1,000–9,000 days postexposure (Woodhouse and Shaw 
 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 86 

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1998). Suslova et al. (2006) measured urinary plutonium excretion and terminal body burdens in 

187 healthy plutonium workers. When expressed as a fraction of terminal body burden (measured at 

autopsy), the mean excretion rate was 1.5x10-5 d-1 (GSD=1.78); this corresponds to a urinary elimination 

half-time of approximately 127 years. The excretion rates were higher in workers who died of 

malignancies, cardiovascular or respiratory tract disease (2.1x10-5 d-1, half-time: 90 years), or liver 

disease (2.6x10-5 d-1, half-time: 73 years). Excretion rates among workers exposed primarily to more 

soluble forms of plutonium (e.g., plutonium nitrate; 1.4x10-5 d-1, half-time: 136 years) were 

approximately twice those of workers exposed primarily to plutonium metal and oxides (0.7x10-5 d-1 , 

half-time: 271 years). Kathren and McInroy (1991) analyzed data on urinary excretion of plutonium and 

postmortem tissue levels in five plutonium workers (four of whom were exposed to plutonium by the 

inhalation route) and concluded that body burdens were consistent with biphasic urinary elimination 

kinetics with approximate half-times of 40 and 100 years. Etherington et al. (2003) measured urinary and 

blood plutonium kinetics in two adult subjects who inhaled an aerosol of 237+244Pu(NO3)4 

(AMAD=1.1 μm; GSD=1.2). Urinary clearance (expressed as a fraction of blood plutonium burden 

excreted per day) ranged from 0.03 to 0.1 d-1 during the first 30 days following exposure (corresponding 

half-times are 7–23 days). Medical follow-up studies have been conducted on persons exposed to 

plutonium during work related to the Manhattan Project (Voelz and Lawrence 1991; Voelz et al. 1979, 

1985, 1997). Leggett (1985) reported an analysis of a subset of 12 subjects (Voelz et al. 1979), 30 years 

following the conclusion of the exposure period, and estimated urinary and fecal clearance (fraction of 

blood burden) to be 0.06 and 0.024 d-1, respectively (corresponding half-times are approximately 12 and 

29 days). 

Studies conducted with nonhuman primates have confirmed that the relatively slow excretion and 

elimination kinetics of inhaled plutonium arise from long retention times in lung, liver, and skeleton 

(Brooks et al. 1992; LaBauve et al. 1980; Lataillade et al. 1995; Metivier et al. 1978b; Stanley et al. 

1982). Studies conducted in dogs (i.e., beagles) have shown that lung retention is a greater contributor to 

slow elimination of 239PuO2 than it is for 238PuO2, 238Pu(NO3)4, or 239Pu(NO3)4, which are more rapidly 

absorbed and distributed to the liver and skeleton. In beagles, during the first few days following 

inhalation exposure to PuO2 or Pu(NO3)4, fecal excretion is the dominant excretory pathway, reflecting 

mucociliary clearance of deposited plutonium to the gastrointestinal tract where the absorbed fraction is 

relatively low (e.g., <1%). Following this period of relatively rapid clearance of plutonium from the 

respiratory tract, fecal excretion declines and urinary excretion makes a larger contribution to elimination 

of the body burden, equaling or exceeding fecal excretion (Bair et al. 1973; Mewhinney and Diel 1983). 

However, both fecal and urinary excretion rates (percent of body burden/day) decline over time and vary 
 

 

 

 

 

 

 

 

 

PLUTONIUM 87 

3. HEALTH EFFECTS 

with different chemical and physical forms and isotopes of plutonium. Bair et al. (1973) compared 

urinary excretion kinetics during the first 100 days following exposures of beagles to 239PuO2 (MMD 1– 

5 μm), 239PuO2 (MMD 0.1 μm), 238PuO2 (MMD 0.1 μm), or 239Pu(NO3)4 (MMD 0.12 μm). Urinary 

excretion of plutonium (per cent of body burden, 50–100 days postexposure) following exposure to 

239PuO2 (MMD 1–5 μm) was slower (≈5–10x10-5% body burden/day) than following exposure to 239PuO2 

(MMD 0.1 μm; ≈1x10-3% body burden/day), 238PuO2 (≈2–3x10-3% body burden/day) or 239Pu(NO3)4 (≈1– 

2x10-2% body burden/day). 

3.4.4.2 Oral Exposure 

Enhanced urinary excretion of 239+240Pu was observed in humans during 7 days following ingestion of 

mollusks containing 239+240Pu (Hunt 1998; Hunt et al. 1986, 1990). Excretion of plutonium in urine was 

also observed in the first 24 hours following an oral dose of 236Pu(VI) bicarbonate (or 239Pu(VI) 

bicarbonate) administered to baboons (USNRC 1992). Priest et al. (1999) observed urinary excretion of 

plutonium in a human who ingested plutonium-contaminated sediments. Studies conducted in dogs and 

various rodent species have shown that following ingestion, absorbed plutonium is excreted in urine 

(Sullivan 1980a; Sullivan et al. 1985). 

3.4.4.3 Dermal Exposure 

Occupational accidents have resulted in dermal exposures and/or penetration of plutonium into skin 

wounds and subsequent systemic absorption of plutonium (McInroy et al. 1989; Woodhouse and Shaw 

1998). In one case, postmortem measurements of 239Pu levels in tissues, measured 17 years following the 

incident, showed that liver contained approximately 41% of the body burden and skeleton contained 49% 

of the body burden (McInroy et al. 1989). Woodhouse and Shaw (1998) reported urinary excretion of 

plutonium during 20–30-year periods following various wound-related exposures to PuO2 (oxalate), 

Pu(NO3)4, or plutonium metal. Slow-phase urinary excretion half-times for six subjects ranged from 17 to 

34 years. 

3.4.4.4 Other Routes of Exposure 

Plutonium excretion and tissue distributions (postmortem) have been measured following intravenous 

injection of Pu(IV) citrate (Langham et al. 1980; Talbot et al. 1997). Various analyses and summaries of 

the data from Langham et al. (1980) have been published (AEC 1971; Durbin 1972; Kathren 2004; 

Leggett 1985). Postmortem tissue plutonium measurements for seven subjects have been reported; data 
 

 

 

 

 

 

 

 

 

PLUTONIUM 88 

3. HEALTH EFFECTS 

for five of the subjects were obtained 1 year following exposure and data for the other two subjects were 

obtained 7 or 21 years after exposure. Whole-body retention half-times ranged from 84 to 175 years 

(mean: 118 years). Retention of plutonium in blood exhibited multi-phasic kinetics, with the fastest 

phase (52% of clearance) having a half-time of approximately 20 minutes, and the slowest phase (0.4% of 

clearance) having a half-time of approximately 80 days. The corresponding time to half of the initial 

blood burden was approximately 1 hour. Fecal excretion was the dominant pathway for excretion during 

the first 30 days following exposure, after which urinary excretion exceeded fecal excretion (Leggett 

1985). Urinary and fecal excretion rates (fraction of blood burden excreted/day) were approximately 

0.08 and 0.07 during the period 19–24 days postexposure; corresponding half-times are approximately 8– 

9 days (Leggett 1985). 

Urinary excretion of plutonium has also been monitored in healthy volunteers following intravenous 

injection of 237Pu (as the citrate) with a short half-life (45.66 days) compared to 24,100 years for 239Pu. 

Mean 24-hour urinary excretion of 237Pu ranged from 0.8 to 1.4% following intravenous injection of 

Pu(IV) citrate into 10 healthy subjects (4 males, 6 females); retention was generally greater in women 

than men (Talbot et al. 1997). Results of a similar study of two healthy male volunteers indicated 2.0– 

2.4% urinary excretion during 21 days postinjection (Talbot et al. 1993). 

Excretion of plutonium following intravenous injection of plutonium has been studied in nonhuman 

primates, dogs, and rodents (e.g., Bair et al. 1973; Bruenger et al. 1991a; Durbin et al. 1972, 1997; 

Guilmette et al. 1978; Polig 1989; Polig et al. 2000; USNRC 1992). 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models 

Physiologically based pharmacokinetic (PBPK) models use mathematical descriptions of the uptake and 

disposition of chemical substances to quantitatively describe the relationships among critical biological 

processes (Krishnan et al. 1994). PBPK models are also called biologically based tissue dosimetry 

models. PBPK models are increasingly used in risk assessments, primarily to predict the concentration of 

potentially toxic moieties of a chemical that will be delivered to any given target tissue following various 

combinations of route, dose level, and test species (Clewell and Andersen 1985). Physiologically based 

pharmacodynamic (PBPD) models use mathematical descriptions of the dose-response function to 

quantitatively describe the relationship between target tissue dose and toxic end points. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 89 

3. HEALTH EFFECTS 

PBPK/PD models refine our understanding of complex quantitative dose behaviors by helping to 

delineate and characterize the relationships between: (1) the external/exposure concentration and target 

tissue dose of the toxic moiety; and (2) the target tissue dose and observed responses (Andersen and 

Krishnan 1994; Andersen et al. 1987). These models are biologically and mechanistically based and can 

be used to extrapolate the pharmacokinetic behavior of chemical substances from high to low dose, from 

route to route, between species, and between subpopulations within a species. The biological basis of 

PBPK models results in more meaningful extrapolations than those generated with the more conventional 

use of uncertainty factors. 

The PBPK model for a chemical substance is developed in four interconnected steps: (1) model 

representation; (2) model parameterization; (3) model simulation; and (4) model validation (Krishnan and 

Andersen 1994). In the early 1990s, validated PBPK models were developed for a number of 

toxicologically important chemical substances, both volatile and nonvolatile (Krishnan and Andersen 

1994; Leung 1993). PBPK models for a particular substance require estimates of the chemical substancespecific physicochemical parameters, and species-specific physiological and biological parameters. The 

numerical estimates of these model parameters are incorporated within a set of differential and algebraic 

equations that describe the pharmacokinetic processes. Solving these differential and algebraic equations 

provides the predictions of tissue dose. Computers then provide process simulations based on these 

solutions. 

The structure and mathematical expressions used in PBPK models significantly simplify the true 

complexities of biological systems. If the uptake and disposition of the chemical substance(s) are 

adequately described, however, this simplification is desirable because data are often unavailable for 

many biological processes. A simplified scheme reduces the magnitude of cumulative uncertainty. The 

adequacy of the model is, therefore, of great importance, and model validation is essential to the use of 

PBPK models in risk assessment. 

PBPK models improve the pharmacokinetic extrapolations used in risk assessments that identify the 

maximal (i.e., the safe) levels for human exposure to chemical substances (Andersen and Krishnan 1994). 

PBPK models provide a scientifically sound means to predict the target tissue dose of chemicals in 

humans who are exposed to environmental levels (for example, levels that might occur at hazardous waste 

sites) based on the results of studies where doses were higher or were administered in different species. 

Figure 3-2 shows a conceptualized representation of a PBPK model. Figures 3-3–3-8 show models for 

radionuclides in general or specifically for plutonium. 
 


 


 

PLUTONIUM 90 

3. HEALTH EFFECTS 

Figure 3-2. Conceptual Representation of a Physiologically Based
 

Pharmacokinetic (PBPK) Model for a 

Hypothetical Chemical Substance
 

Lungs 

Liv er 

F at 

S lo w ly 

perfus ed 

tis s ues 

R ic h ly 

perfus ed 

tis s ues 

K idney 

S k in 

V 

E 

N 

O 

U 

S 

B 

L 

O 

O 

D 

A 

R 

T 

E 

R 

I 

A 

L 

B 

L 

O 

O 

D 

V m a x 

K m 

Inges tion 

Inhaled c hem ic al E x ha led c hem ic al 

GI 

T ra c t 

F ec es 

U rin e

 C h e m ic a ls 

contacting skin 

Note: This is a conceptual representation of a physiologically based pharmacokinetic (PBPK) model for a 

hypothetical chemical substance. The chemical substance is shown to be absorbed via the skin, by inhalation, or by 

ingestion, metabolized in the liver, and excreted in the urine or by exhalation. 

Source: adapted from Krishnan and Andersen 1994 
 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 91 

3. HEALTH EFFECTS 

For radionuclides, the PBPK model is replaced with a set of sophisticated physiologically based 

biokinetic (PBBK) models for inhalation, ingestion, and submersion. These were developed to 

accomplish virtually the same end as the PBPK models above, while integrating additional parameters 

(for radioactive decay, particle and photon transport, and compound-specific factors). Goals are to 

facilitate interpreting chest monitoring and bioassay data, assessing risk, and calculating radiation doses 

to a variety of tissues throughout the body. The standard for these models has been set by the ICRP and 

their models receive international support and acceptance. ICRP periodically considers newer science in 

a type of weight of evidence approach toward improving the state of knowledge and reducing 

uncertainties associated with applying the model to any given radionuclide. ICRP publications also allow 

for the use of situation- and individual-specific data to reduce the overall uncertainty in the results. Even 

though there may be conflicting data for some parameters, such as absorption factors, one can use 

conservative values and still reach conclusions on whether the dose is below recommended limits. One of 

the strengths of the ICRP model is that it permits the use of experimentally determined material-specific 

absorption parameter values rather than requiring the use of those provided for default types. If the 

material of interest does not have absorption parameter values that correspond to those in the model (e.g., 

Type F, M, or S), the difference can have a profound effect on the assessment of intake and dose from 

bioassay measurements. This has been discussed in National Radiological Protection Board (NRPB) 

published reports on uranium (NRPB 2002). 

The ICRP (1994b, 1996a) developed a Human Respiratory Tract Model for Radiological Protection, 

which contains respiratory tract deposition and clearance compartmental models for inhalation exposure 

that may be applied to particulate aerosols of plutonium compounds. The ICRP (1986, 1990) has a 

biokinetic model for human oral exposure that applies to plutonium. The National Council on Radiation 

Protection and Measurements (NCRP) has also developed a respiratory tract model for inhaled 

radionuclides (NCRP 1997). At this time, the NCRP recommends the use of the ICRP model for 

calculating exposures for radiation workers and the general public. Readers interested in this topic are 

referred to NCRP Report No. 125; Deposition, Retention and Dosimetry of Inhaled Radioactive 

Substances (NCRP 1997). In the appendix to the report, NCRP provides the animal testing clearance data 

and equations fitting the data that supported the development of the human model for plutonium. 

Models of the pharmacokinetics of plutonium have been developed for humans (ICRP 1972, 1986, 1994a; 

Khokhryakov et al. 1994, 2000, 2005; Leggett 1985; Leggett et al. 2005), dogs (Mewhinney and Diel 

1983; Polig et al. 2000), rats (Durbin et al. 1972), and mice (Durbin et al. 1997). Models of plutonium 
 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 92 

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pharmacokinetics in humans that are currently being used for predicting internal exposures and radiation 

doses are described below. 

Human Respiratory Tract Model for Radiological Protection (ICRP 1994b) 

Deposition. The ICRP (1994b) has developed a deposition model for behavior of aerosols and vapors 

in the respiratory tract. It was developed to estimate the fractions of radioactivity in breathing air that are 

deposited in each anatomical region of the respiratory tract. ICRP (1994b) provides inhalation dose 

coefficients that can be used to estimate radiation doses to organs and tissues throughout the body based 

on a unit intake of radioactive material. The model applies to three levels of particle solubility, a wide 

range of particle sizes (approximately 0.0005–100 μm in diameter), and parameter values that can be 

adjusted for various segments of the population (e.g., sex, age, and level of physical exertion). This 

model also allows one to evaluate the bounds of uncertainty in deposition estimates. Uncertainties arise 

from natural biological variability among individuals and the need to interpret some experimental 

evidence that remains inconclusive. It is applicable to particulate aerosols containing plutonium, but was 

developed for a wide variety of radionuclides and their chemical forms. 

The ICRP deposition model estimates the fraction of inhaled material initially retained in each 

compartment (see Figure 3-3). The model was developed with five compartments: (1) the anterior nasal 

passages (ET1); (2) all other extrathoracic airways (ET2) (posterior nasal passages, the naso- and 

oropharynx, and the larynx); (3) the bronchi (BB); (4) the bronchioles (bb); and (5) the alveolar 

interstitium (AI). Particles deposited in each of the regions may be removed and redistributed either 

upward into the respiratory tree or to the lymphatic system and blood by different particle removal 

mechanisms. 

For extrathoracic deposition of particles, the model uses measured airway diameters and experimental 

data, where deposition is related to particle size and airflow parameters, and scales deposition for women 

and children from adult male data. Similar to the extrathoracic region, experimental data served as the 

basis for lung (bronchi, bronchioles, and alveoli) aerosol transport and deposition. A theoretical model of 

gas transport and particle deposition was used to interpret data and to predict deposition for compartments 

and subpopulations other than adult males. Table 3-6 provides reference respiratory values for the 

general Caucasian population during various intensities of physical exertion. 
 

Figure 3-3. Compartment Model to Represent Particle Deposition and 

Time-Dependent Particle Transport in the Respiratory Tract*
 

SequesteredinTissueSurface Transport

Anterior
 

Nasal 1
 ET EnvironmentExtrathoracic1

14 16

Naso-oro­- 0.001ET 100

2 GI Tract

pharynx

15

LN

Larynx 

ETET 11

nx SEQ

1312

0.0310

0.01

BBSEQBB2BB1Bronchi

987

0.032

0.01bbSEQ bb2bb1BronchiolesLNTH

65 4

0.00010.0010.02

0.00002

Al3Al2Al1 Alveolar

1032 1 Interstitium

Thoracic

 

PLUTONIUM 93 

3. HEALTH EFFECTS 

*Compartment numbers shown in lower right corners are used to define clearance pathways. The clearance rates, 

half-lives, and fractions by compartment, as well as the compartment abbreviations are presented in Table 3-6. 

Source: ICRP 1994b 
 

 

 

 

 

 

 

 

 

 

 

 


 


 

PLUTONIUM 94 

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Table 3-6. Reference Respiratory Values for a General Caucasian Population at
 

Different Levels of Activity
 

Breathing 10 Years 15 Years Adult 

parameters: 3 Months 1 Year 5 Years Male Female Both Male Female Male Female 

Resting (sleeping); maximal workload 8% 

Breathing parameters: 

VT(L) 0.04 0.07 0.17 — — 0.3 0.500 0.417 0.625 0.444 

B(m3hour-1) 0.09 0.15 0.24 — — 0.31 0.42 0.35 0.45 0.32 

fR(minute-1) 38 34 23 — — 17 14 14 12 12 

Sitting awake; maximal workload 12% 

Breathing parameters: 

VT(L) NA 0.1 0.21 — — 0.33 0.533 0.417 0.750 0.464 

B(m3hour-1) NA 0.22 0.32 — — 0.38 0.48 0.40 0.54 0.39 

fR(minute-1) NA 36 25 — — 19 15 16 12 14 

Light exercise; maximal workload 32% 

Breathing parameters: 

VT(L) 0.07 0.13 0.24 — — 0.58 1.0 0.903 1.25 0.992 

B(m3hour-1) 0.19 0.35 0.57 — — 1.12 1.38 1.30 1.5 1.25 

fR(minute-1) 48 46 39 — — 32 23 24 20 21 

Heavy exercise; maximal workload 64% 

Breathing parameters: 

VT(L) NA NA NA 0.841 0.667 — 1.352 1.127 1.923 1.364 

B(m3hour-1) NA NA NA 2.22 1.84 — 2.92 2.57 3.0 2.7 

fR(minute-1) NA NA NA 44 46 — 36 38 26 33 

B = ventilation rate; fR = respiration frequency; NA = not applicable; VT = tidal volume 

Source: See Annex B (ICRP 1994b) for data from which these reference values were derived. 
 

 

 

 

 

 

 

 

 

 

	 

	 

	 

PLUTONIUM 95 

3. HEALTH EFFECTS 

Deposition of inhaled gases and vapors is modeled as a partitioning process that depends on the 

physiological parameters noted above as well as the solubility and reactivity of a compound in the 

respiratory tract (see Figure 3-4). The ICRP (1994b) model defines three categories of solubility and 

reactivity: SR-0, SR-1, and SR-2: 

•	 Type SR-0 compounds include insoluble and nonreactive gases (e.g., inert gases such as H2, He). 

These compounds do not significantly interact with the respiratory tract tissues, and essentially all 

compound inhaled is exhaled. Radiation doses from inhalation exposure of SR-0 compounds are 

assumed to result from the irradiation of the respiratory tract from the air spaces. 

•	 Type SR-1 compounds include soluble or reactive gases and vapors which are expected to be 

taken up by the respiratory tract tissues and may deposit in any or all of the regions of the 

respiratory tract, depending on the dynamics of the airways and properties of the surface mucous 

and airway tissues, as well as the solubility and reactivity of the compound. 

•	 Type SR-2 compounds include soluble and reactive gases and vapors which are completely 

retained in the extrathoracic regions of the respiratory tract. SR-2 compounds include sulfur 

dioxide (SO2) and hydrogen fluoride (HF). 

Respiratory Tract Clearance. This portion of the model identifies the principal clearance pathways 

within the respiratory tract. The model was developed to predict the retention of various radioactive 

materials. The compartmental model represents particle deposition and time-dependent particle transport 

in the respiratory tract (see Figure 3-3) with reference values presented in Table 3-7 (A,B). This table 

provides clearance rates, expressed as a fraction per day and also as half-time (Part A), and deposition 

fractions (Part B) for each compartment for insoluble particles. ICRP (1994b) also developed modifying 

factors for some of the parameters, such as age, smoking, and disease status. Parameters of the clearance 

model are based on human evidence for the most part, although particle retention in airway walls is based 

on experimental data from animal experiments. 

The clearance of particles from the respiratory tract is a dynamic process. The rate of clearance generally 

changes with time from each region and by each route. Following deposition of large numbers of 

particles (acute exposure), transport rates change as particles are cleared from the various regions. 

Physical and chemical properties of deposited material determine the rate of dissolution and, as particles 

dissolve, absorption rates tend to change over time. By creating a model with compartments of different 

clearance rates within each region (e.g., BB1, BB2, BBseq), the ICRP model overcomes problems 

associated with time-dependent functions. Each compartment clears to other compartments by constant 

rates for each pathway. 
 

Figure 3-4. Reaction of Gases or Vapors at Various Levels of the
 

Gas-Blood Interface
 

Airway Uptake Gas or Vapor Convection 

Lumen Diffusion 

Airway Reaction Gas/Vapor Fluid Product 

Reaction Bound Tissue Gas/Vapor Product Material 

Sb 

Reaction Blood Gas/Vapor Product Blood 

Source: ICRP 1994b 

PLUTONIUM 96 

3. HEALTH EFFECTS 
 


 


 


 


 

PLUTONIUM 97 

3. HEALTH EFFECTS 

Table 3-7. Reference Values of Parameters for the Compartment Model to
 

Represent Time-dependent Particle Transport from the
 

Human Respiratory Tract
 

Part A
 

Clearance rates for insoluble particles 

Pathway From To Rate (d-1) Half-lifea 

m1,4 AI1 bb1 0.02 35 days 

m2,4 AI2 bb1 0.001 700 days 

m3,4 AI3 bb1 1x10-4 7,000 days 

m3,10 AI3 LNTH 2x10-5 No data 

m4,7 bb1 BB1 2 8 hours 

m5,7 bb2 BB1 0.03 23 days 

m6,10 bbseq LNTH 0.01 70 days 

m7,11 BB1 ET2 10 100 minutes 

m8,11 BB2 ET2 0.03 23 days 

m9,10 BBseq LNTH 0.01 70 days 

m11,15 ET2 GI tract 100 10 minutes 

m12,13 ETseq LNET 0.001 700 days 

m14,16 ET1 Environment 1 17 hours 
 

 

 

 

 

 

 

 

 

 

 

 


 


 


 


 

	 

	 

	 

	 


 


 


 


 


 

PLUTONIUM 98 

3. HEALTH EFFECTS 

Table 3-7. Reference Values of Parameters for the Compartment Model to
 

Represent Time-dependent Particle Transport from the Human
 

Respiratory Tract
 

Part B
 

Partition of deposit in each region between compartmentsb 

Fraction of deposit in region 

Region or deposition site Compartment assigned to compartmentc 

ET2 ET2 0.9995 

ETseq 0.0005 

BB BB1 0.993-fs 

BB2 fs 

BBseq 0.007 

bb bb1 0.993-fs 

bb2 fs 

bbseq 0.007 

AI	 AI1 0.3 

AI2 0.6 

AI3 0.1 

a

The half-lives are approximate since the reference values are specified for the particle transport rates and are rounded in units of
 

days-1 . A half-life is not given for the transport rate from Al3 to LNTH, since this rate was chosen to direct the required amount of
 

material to the lymph nodes. The clearance half-life of compartment Al3 is determined by the sum of the clearance rates.
 b

See paragraph 181, Chapter 5 (ICRP 1994b) for default values used for relating fs to dae.
 c

It is assumed that fs is size-dependent. For modeling purposes, fs is taken to be:
 

f s = 0. 5 for d ae ≤ 2 . 5 ρ / χ μm and 

f = 0. 5 e 

0 . 63 (dae ρ / χ −2. 5 )

s for d ae > 2 . 5 ρ / χ μm 

where 

fs = fraction subject to slow clearance 

dae = aerodynamic particle diameter/(μm) 

ρ = particle density (g/cm3

) 

χ = particle shape factor 

AI = alveolar-interstitial region; BB = bronchial region; bb = bronchiolar region; BBseq = compartment representing prolonged 

retention in airway walls of small fraction of particles deposited in the bronchial region; bbseq = compartment representing prolonged 

retention in airway walls of small fraction of particles deposited in the bronchiolar region; ET = extrathoracic region; ETseq = 

compartment representing prolonged retention in airway tissue of small fraction of particles deposited in the nasal passages; GI = 

gastrointestinal; LNET = lymphatics and lymph nodes that drain the extrathoracic region; LNTH = lymphatics and lymph nodes that 

drain the thoracic region 

Source: ICRP 1994b 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 99 

3. HEALTH EFFECTS 

Particle transport from all regions is toward both the lymph nodes and the pharynx, and a majority of 

deposited particles end up being swallowed. In the front part of the nasal passages (ET1), nose blowing, 

sneezing, and wiping remove most of the deposited particles. Particles remain here for about a day. For 

particles with AMADs of a few micrometers or greater, the ET1 compartment is probably the largest 

deposition site. A majority of particles deposited at the back of the nasal passages and in the larynx (ET2) 

are removed quickly by the fluids that cover the airways. In this region, particle clearance is completed 

within 15 minutes. 

Ciliary action removes deposited particles from both the bronchi and bronchioles. Though it is generally 

thought that mucociliary action rapidly transports most particles deposited here toward the pharynx, a 

fraction of these particles is cleared more slowly. Evidence for this is found in human studies. For 

humans, retention of particles deposited in the lungs (BB and bb) is apparently biphasic. The “slow” 

action of the cilia may remove as much as half of the bronchi- and bronchiole-deposited particles. In 

human bronchi and bronchiole regions, mucus moves more slowly when it is closer to the alveoli. For the 

faster compartment, it has been estimated that it takes about 2 days for particles to travel from the bronchioles to the bronchi and 10 days from the bronchi to the pharynx. The second (slower) compartment is 

assumed to have approximately equal fractions deposited between BB2 and bb2, with both fractions 

having clearance half-times estimated at 20 days. Particle size is a primary determinant of the fraction 

deposited in this slow thoracic compartment. A small fraction of particles deposited in the BB and bb 

regions is retained in the airway wall for even longer periods (BBseq and bbseq). 

If particles reach and become deposited in the alveoli, they tend to stay imbedded in the fluid on the 

alveolar surface or move into the lymph nodes. Coughing is the one mechanism by which particles are 

physically resuspended and removed from the AI region. For modeling purposes, the AI region is divided 

into three subcompartments to represent different clearance rates, all of which are slow. 

In the alveolar-interstitial region, human lung clearance has been measured. The ICRP model uses 2 halftimes to represent clearance: about 30% of the particles have a 30-day half-time, and the remaining 70% 

are assigned a half-time of several hundred days. Over time, AI particle transport falls, and some 

compounds have been found in lungs 10–50 years after exposure. 

Absorption into Blood. The ICRP model assumes that absorption into blood occurs at equivalent 

rates in all parts of the respiratory tract, except in the anterior nasal passages (ET1), where no absorption 

occurs. It is essentially a 2-stage process, as shown in Figure 3-5. First, there is a dissociation 
 

 

PLUTONIUM 100 

3. HEALTH EFFECTS 

Figure 3-5. The Human Respiratory Tract Model: Absorption into Blood 

Particulate Material 

Dissolution 

Dissociated Material 

Bound Material 

Uptake 

Blood 

Source: ICRP 1994b 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

	 

	 

	 

	 

	 

PLUTONIUM	 101 

3. HEALTH EFFECTS 

(dissolution) of particles; then the dissolved molecules or ions diffuse across capillary walls and are taken 

up by the blood. Immediately following dissolution, rapid absorption is observed. For some elements, 

rapid absorption does not occur because of binding to respiratory-tract components. In the absence of 

specific data for specific compounds, the model uses the following default absorption rate values for those 

specific compounds that are classified as Types F (fast), M (medium), S (slow), and V (instantaneous): 

•	 For Type F, there is rapid 100% absorption within 10 minutes of the material deposited in the BB, 

bb, and AI regions, and 50% of material deposited in ET2. Thus, for nose breathing, there is rapid 

absorption of approximately 25% of the deposit in ET; for mouth breathing, the value is 50%. 

•	 For Type M, about 70% of the deposit in AI reaches the blood eventually. There is rapid 

absorption of about 10% of the deposit in BB and bb, and 5% of material deposited in ET2. Thus, 

there is rapid absorption of approximately 2.5% of the deposit in ET for nose breathing, and 

5% for mouth breathing. 

•	 For Type S, 0.1% is absorbed within 10 minutes and 99.9% is absorbed within 7,000 days, so 

there is little absorption from ET, BB, or bb, and about 10% of the deposit in AI reaches the 

blood eventually. 

•	 For Type V, complete absorption (100%) is considered to occur instantaneously. 

ICRP (1996a) classifies insoluble plutonium oxides as Type S and recommends assigning all other 

plutonium aerosols to Type M in the absence of specific information supporting an alternative 

classification. 

ICRP (1994a) Plutonium Biokinetics Model 

Description of the Model. ICRP (1990, 1994a) developed a compartmental model of the kinetics of 

ingested plutonium in humans that is applicable to infants, children, adolescents, and adults. The model 

is a modification and expansion of a similar model for plutonium (DOE/EPA 1984), described by Leggett 

(1985). The fraction of ingested plutonium that is absorbed (uptake to blood) is assumed to vary by 

chemical form and age (Table 3-8). Absorbed plutonium enters the blood plasma where it distributes to 

the skeleton, liver, and other tissues (Figure 3-6). Excretion pathways included in the model are plasma 

to urine and feces, including transfers to gastrointestinal tract from blood and liver. Transfer rate 

coefficients between compartments are age-specific and, depending on the specific coefficient, values can 

change at ages 3 months, 1, 5, 10, and 15 years, and adult (>15 years) (Table 3-8). 
 

 

PLUTONIUM 102 

3. HEALTH EFFECTS 

Table 3-8. Parameters of ICRP (1994a) Model 

of Plutonium Biokinetics in Humansa 

Age 

Parameterb 3 months 1 year 5 years 10 years 15 years Adult 

Soft tissue (ST0) to 6.93x10-1 6.93x10-1 6.93x10-1 6.93x10-1 6.93x10-1 6.930x10-1 

blood 

Soft tissue (ST1) to 4.75x10-4 4.75x10-4 4.75x10-4 4.75x10-4 4.75x10-4 4.75x10-4 

blood 

Soft tissue (ST2) to 1.9x10-5 1.9x10-5 1.9x10-5 1.9x10-5 1.9x10-5 1.9x10-5 

blood 

Cortical/trabecular 7.6x10-3 7.6x10-3 7.6x10-3 7.6x10-3 7.6x10-3 7.6x10-3 

bone marrow to blood 

Other kidney tissue to 1.39x10-3 1.39x10-3 1.39x10-3 1.39x10-3 1.39x10-3 1.39x10-3 

blood 

Liver (2) to blood 2.11x10-4 2.11x10-4 2.11x10-4 2.11x10-4 2.11x10-4 2.11x10-4 

Gonads to blood 1.9x10-4 1.9x10-4 1.9x10-4 1.9x10-4 1.9x10-4 1.9x10-4 

Blood to soft tissue 2.773x10-1 2.773x10-1 2.773x10-1 2.773x10-1 2.773x10-1 2.773x10-1 

(ST0) 

Blood to soft tissue 8.06x10-2 8.06x10-2 8.06x10-2 8.06x10-2 8.06x10-2 8.06x10-2 

(ST1) 

Blood to soft tissue 1.29x10-2 1.29x10-2 1.29x10-2 1.29x10-2 1.29x10-2 1.29x10-2 

(ST2) 

Blood to trabecular 2.264x10-1 2.264x10-1 1.941x10-1 1.941x10-1 1.941x10-1 1.941 x10-1 

surface 

Blood to cortical 2.264x10-1 2.264x10-1 1.941x10-1 1.941x10-1 1.941x10-1 1.294x10-1 

surface 

Trabecular surface to 8.22x10-3 2.88x10-3 1.81x10-3 1.32x10-3 9.59x10-4 2.47x10-4 

volume 

Cortical surface to 8.22x10-3 2.88x10-3 1.53x10-3 9.04x10-4 5.21x10-4 4.11x10-5 

volume 

Trabecular surface to 8.22x10-3 2.88x10-3 1.81x10-3 1.32x10-3 9.59x10-4 4.93x10-4 

marrow 

Trabecular volume to 8.22x10-3 2.88x10-3 1.81x10-3 1.32x10-3 9.59x10-4 4.93x10-4 

marrow 

Cortical surface to 8.22x10-3 2.88x10-3 1.53x10-3 9.04x10-4 5.21x10-4 8.21x10-5 

marrow 

Cortical volume to 8.22x10-3 2.88x10-3 1.53x10-3 9.04x10-4 5.21x10-4 8.21x10-5 

marrow 

Blood to other kidney 3.23x10-3 3.23x10-3 3.23x10-3 3.23x10-3 3.23x10-3 3.23x10-3 

tissue 

Blood to liver (1) 6.47x10-2 6.47x10-2 1.294x10-1 1.294x10-1 1.294x10-1 1.941x10-1 

Liver (1) to liver (2) 1.77x10-3 1.77x10-3 1.77x10-3 1.77x10-3 1.77x10-3 1.77x10-3 

Blood to testes 1.3x10-5 1.9x10-5 2.2x10-5 2.6x10-5 2.1x10-4 2.3x10-4 
 

 

 

 


 


 


 


 

PLUTONIUM 103 

3. HEALTH EFFECTS 

Table 3-8. Parameters of ICRP (1994a) Model 

of Plutonium Biokinetics in Humansa 

Age 

Parameterb 3 months 1 year 5 years 10 years 15 years Adult 

Blood to ovaries 8.0x10-6 1.0x10-5 2.6x10-5 4.5x10-5 7.8x10-5 7.1x10-5 

Liver (1) to small 1.33x10-4 1.33x10-4 1.33x10-4 1.33x10-4 1.33x10-4 1.330x10-4 

intestine 

Blood to upper large 1.29x10-2 1.29x10-2 1.29x10-2 1.29x10-2 1.29x10-2 1.290x10-2 

intestine contents 

Blood to kidney 6.47x10-3 6.47x10-3 6.47x10-3 6.47x10-3 6.47x10-3 6.470x10-3 

(urinary path) 

Blood to urinary 1.29x10-2 1.29x10-2 1.29x10-2 1.29x10-2 1.29x10-2 1.290x10-2 

bladder contents 

Soft tissue (ST1) to 4.75x10-4 4.75x10-4 4.75x10-4 4.75x10-4 4.75x10-4 4.750x10-4 

urinary bladder 

contents 

Kidneys (urinary path) 1.386x10-2 1.386x10-2 1.386x10-2 1.386x10-2 1.386x10-2 1.386x10-2 

to bladder 

Gastrointestinal tract 5.0x10-3 5.0x10-4 5.0x10-4 5.0x10-4 5.0x10-4 5.0x10-4 

to bloodc 

a

See Figure 3-6 for schematic representation of model. b

Units are in days-1, except for gastrointestinal tract to blood, which is unitless.
 c

Values shown for the absorption fraction are for general public exposures (e.g., diet). Recommended values for
 

occupational exposures are as follows: oxides (excluding poly-disperse oxides), 1x10-5; nitrates, 1x10-4; other
 

compounds or unknown mixtures, 1x10-4 .
 
 

PLUTONIUM 104 

3. HEALTH EFFECTS 

Figure 3-6. Schematic Representation of the ICRP (1994a)
 

Model of Plutonium Biokinetics in Humans*
 
 

Other Soft Tissues 

Rapid turnover Intermediate Slow turnover 

(ST0) turnover (ST1) (ST2) 

Kidneys 

Other kidney Liver 2 Urine Urinary tissue 

bladder 

contents Liver 1 Urinary path 

Blood 

Skeleton 

Gastrointestinal 

tract contents 

Cortical Cortical Cortical 

volume surface marrow 

Feces 

Trabecular Trabecular Trabecular 

volume surface marrow 

Gonads 

*See Table 3-8 for parameter values. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 105 

3. HEALTH EFFECTS 

Bone is divided into trabecular and cortical components, with each further divided into bone surface, bone 

volume, and bone cavity (marrow compartment). Initial deposition of plutonium is assumed to occur 

from blood directly to bone surfaces, where it can be transferred to bone marrow or to bone volume. 

Elimination of plutonium in bone surface and bone volume is assumed to occur through bone marrow to 

blood. Transfers of plutonium within the cortical or trabecular bone compartments are modeled based on 

assumptions about rates of bone formation and resorption, which are assumed to be vary with age (ICRP 

1990; Leggett 1985). Movement of plutonium to the marrow compartment is determined by the bone 

resorption rate, whereas movement from the bone surface to the bone volume is assumed to occur by 

burial of surface deposits with new bone and is determined by the bone formation rate. During growth, 

bone formation and resorption are assumed to occur at different sites within bone; therefore, the rate of 

removal of plutonium from the bone surface is approximated by the sum of the bone resorption rate 

(represented in the model by the movement of plutonium to the marrow compartment) and the rate of 

bone formation, which results in burial of surface deposits (represented by movement of plutonium from 

the bone surface to bone volume). In adults, the possibility of resorption and formation of bone occurring 

at the same site is assumed; therefore, only a portion (50%) of the bone formation rate results in burial of 

surface deposits and movement of plutonium from the bone surface to the bone volume. Rates of uptake 

of plutonium into bone surface are assumed to be relatively fast (half-life=3–6 days, adults) compared to 

rates for distribution within bone and exit from bone (half-life=103

–104 days, adults; 102–103 days, 

children); this results in relatively rapid uptake and long retention of plutonium in bone. Rates of 

distribution within bone are assumed to be higher in children (by a factor of approximately 10), reflecting 

more rapid bone turn-over in children. Rates of uptake of plutonium into liver are assumed to be 

relatively fast (half-life=3–11 days) compared to elimination from liver (t1/2=103 days), which results in 

relatively rapid uptake and long retention of plutonium in liver. Predicted kinetics of skeletal and liver 

plutonium burdens in adults and children, following a single dose of plutonium to blood (e.g., intravenous 

dose) are shown in Figure 3-7. 

Validation of the Model. ICRP 1994a has been evaluated with data on plutonium excretion and 

postmortem tissue levels in plutonium workers (e.g., Carbaugh and La Bone 2003; Filipy and Kathren 

1996; Fritsch 2007; Hodgson et al. 2003; James et al. 2003; Singh et al. 2003). Uncertainty analysis of 

model predictions has been reported (Suzuki et al. 2002). 

Risk Assessment. The model has been used to establish the radiation dose (Sv) per unit of ingested 

or inhaled plutonium (Bq) for intake ages 3 months to 70 years (ICRP 1994a, 2001). The dose integration 
PLUTONIUM 106

3. HEALTH EFFECTS

Figure 3-7. ICRP (1994a) Model Simulation of Elimination of an Absorbed 

Plutonium Dose (e.g., Intravenous) from the Body in Infants, 

Children, and Adults

80

70

60

50

Adult (20 yr) 40

30 Age 10 yr

20

Infant (3 mo)

10

0

0 10 20 30 40 50

Time after Exposure (yr)

50

40

30

Adult (20 yr)

20

Age 10 yr

10 Infant (3 mo) 

0

0 10 20 30 40 50

Time after Exposure (yr)

Liver Burden (% of Initial) Skeletal Burden (% of Initial)
 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 107 

3. HEALTH EFFECTS 

period is 50 years for acute intake as an adult (age 25 years) and from intake to age 70 years for acute 

intake at ages ≤15 years. 

Target Tissues. The model is designed to calculate radiation dose coefficients (Sv/Bq) corresponding 

to specific inhalation or ingestion exposures to plutonium isotopes. Dose coefficients have been 

estimated for all major organs, including the bone surfaces, bone marrow, and liver, and other tissues 

(ICRP 1994a, 1996a). 

Species Extrapolation. The model is based on both human and animal data. However, it is intended 

for applications to human dosimetry. Applications to other species would require consideration of 

species-specific adjustments in model parameters. 

Interroute Extrapolation. The ICRP model is designed to simulate kinetics of ingested plutonium, 

injected plutonium, and if combined with a respiratory tract model (e.g., ICRP Human Respiratory Tract 

Model for Radiological Protection, ICRP 1994b), inhalation exposures to plutonium. The model can be 

applied to any other route of exposure for which the transfer rate to blood is available. 

Luciani and Polig (2000) Plutonium Biokinetics Model 

Description of the Model. Luciani and Polig (2000) developed a modification of the ICRP (1994a) 

model that provided a more physiological parameterization of urinary excretion pathways and 

modifications to the bone model. Modifications to the structure of the model were: (1) deletion of the 

transfer pathway from soft tissue ST1 to urinary bladder; (2) deletion of transfer pathways from cortical 

and trabecular bone surfaces to bone volume; and (3) addition of a transfer pathway from blood to bone 

volume (Figure 3-8). Specific changes made to rate coefficients are presented in Table 3-9. 

Validation of the Model. The Luciani and Polig (2000) model was calibrated with data on long-term 

kinetics of plutonium in blood, urine, and feces following intravenous injection of Pu(IV) citrate into 

subjects suffering from chronic disorders (Langham et al. 1950, 1980; Moss and Gautier 1983; Rundo et 

al. 1976), and urinary excretion of plutonium in workers exposed to plutonium at the Mayak plant 

(Khokhryakov et al. 1994). Predicted urinary excretion of plutonium was compared to observations made 

on nine workers (USTUR 1993; Voelz et al. 1979, 1985). The Luciani and Polig (2000) model showed 

improved agreement between predictions and observations compared to the ICRP (1994a) model (Luciani 
 

Figure 3-8. Schematic Representation of the Luciani and Polig (2000)
 

Model of Plutonium Biokinetics in Humans
 
 

Other soft tissues 

Rapid turnover Intermediate Slow turnover 

(ST0) turnover (ST1) (ST2) 

Kidneys 

Other kidney Liver 2 Urinary Urine tissue 

bladder 

contents Liver 1 Urinary path 

Blood 

Skeleton 

Gastrointestinal 

tract contents 

Cortical Cortical Cortical 

volume surface marrow 

Feces 

Trabecular Trabecular Trabecular 

volume surface marrow 

Gonads 

PLUTONIUM 108 

3. HEALTH EFFECTS 
 

 

 

 


 


 


 


 


 

PLUTONIUM 109 

3. HEALTH EFFECTS 

Table 3-9. Comparison of Parameters of ICRP (1994a) Model and Luciani and 

Polig (2000) Model of Plutonium Biokinetics in Humansa
 

Adult parameter values 

Parameterb ICRP (1994a) Luciani and Polig (2000) 

Soft tissue (ST0) to blood 6.93x10-1 1.39x10-1 d 

Soft tissue (ST1) to blood 4.75x10-4 9.50x10-4 d 

Soft tissue (ST2) to blood 1.9x10-5 1.9x10-5 

Cortical/trabecular bone marrow to blood 7.6x10-3 7.6x10-3 

Other kidney tissue to blood 1.39x10-3 1.39x10-3 

Liver (2) to blood 2.11x10-4 4.00x10-4 d 

Gonads to blood 1.9x10-4 1.9x10-4 

Blood to soft tissue (ST0) 2.773x10-1 2.773x10-1 

Blood to soft tissue (ST1) 8.06x10-2 8.06x10-2 

Blood to soft tissue (ST2) 1.29x10-2 1.29x10-2 

Blood to trabecular surface 1.941x10-1 2.26x10-1 d 

Blood to cortical surface 1.294x10-1 9.52x10-2 d 

Trabecular surface to volume 2.47x10-4 Deleted 

Cortical surface to volume 4.11x10-5 Deleted 

Trabecular surface to marrow 4.93x10-4 1.59x10-3 d 

Trabecular volume to marrow 4.93x10-4 1.59x10-4 d 

Cortical surface to marrow 8.21x10-5 1.56x10-4 d 

Cortical volume to marrow 8.21x10-5 8.22x10-5 d 

Blood to other kidney tissue 3.23x10-3 3.23x10-3 

Blood to liver (1) 1.941x10-1 1.20x10-1 d 

Liver (1) to liver (2) 1.77x10-3 1.00x10-2 d 

Blood to testes 2.3x10-4 2.3x10-4 

Blood to ovaries 7.1x10-5 7.1x10-5 

Liver (1) to small intestine 1.33x10-4 4.00x10-4 d 

Blood to upper large intestine contents 1.29x10-2 8.0x10-3 d 

Blood to kidney (urinary path) 6.47x10-3 9.93x10-3 d 

Blood to urinary bladder contents 1.29x10-2 9.46x10-3 d 

Soft tissue (ST1) to urinary bladder contents 4.75x10-4 Deleted 

Kidneys (urinary path) to bladder 1.386x10-2 1.02x10-2 d 

Gastrointestinal tract to bloodc 5.0x10-4 5.0x10-4 

a

See Figure 3-8 for schematic representation of model. b

Units are in days-1, except for gastrointestinal tract to blood, which is unitless.
 c

Values shown for the absorption fraction are for general public exposures (e.g., diet). Recommended values for 

occupational exposures are as follows: oxides (excluding poly-disperse oxides), 1x10-5; nitrates, 1x10-4; and other
 

compounds or unknown mixtures, 1x10-4 .
 d

Modified in Luciani and Polig (2000).
 
 

 

 

 

 

 

 

 

 

PLUTONIUM 110 

3. HEALTH EFFECTS 

and Polig 2000). Sensitivity and uncertainty analyses of model predictions have been reported (Luciani et 

al. 2001, 2003). 

Risk Assessment. The model could be used to establish the radiation dose (Sv) per unit of ingested 

or inhaled plutonium (Bq) in adults if linked to radioactive decay and radiation dose models. 

Target Tissues. The model is designed to calculate radiation dose coefficients (Sv/Bq) corresponding 

to specific inhalation or ingestion exposures to plutonium isotopes. 

Species Extrapolation. The model is intended for applications to human dosimetry. Applications to 

other species would require consideration of species-specific adjustments in model parameters. 

Interroute Extrapolation. The Luciani and Polig (2000) model is designed to simulate kinetics of 

absorbed plutonium, and includes gastrointestinal tract compartments for simulating absorption from 

ingestion. If combined with a respiratory tract model (e.g., ICRP 1994b), the model can be used to 

simulate inhalation exposures to plutonium. The model has been applied to injection exposures (Luciani 

and Polig 2000) and can be applied to any other route of exposure for which the transfer rate to blood is 

available. 

First Branch of the First Institute of Biophysics (FIB-1) Biokinetic Plutonium Model 

Description of the Model. Khokhryakov et al. (1994, 2000, 2002) developed a biokinetics model for 

predicting the accumulation of plutonium in the lungs (and corresponding radiation doses) of workers at 

the Mayak Production Association (Russian Federation), based on exposure information and 

biomonitoring of urinary plutonium. The model included a lung clearance model, which delivered 

plutonium into a multi-compartment elimination (urinary and fecal) model (Figure 3-9). In the lung 

clearance model shown in Figure 3-9, inhaled plutonium was distributed to three lung clearance 

pathways: rapid clearance, slow clearance (to systemic compartments and lymph nodes), or fixed 

(permanently retained in the lung). Plutonium compounds were assigned specific distributions to the 

three pathways according to estimates of “biological transportability” (S) as determined by dialysis 

through a semi-permeable membrane (Khokhryakov et al. 1998). Compounds in the low transportability 

class (S=0.3%; e.g., PuO2) were assigned larger distribution fractions to fixed and slow clearance 

pathways, compared to higher transportability classes (e.g., S=3%, Pu[NO3]4). For PuO2, lung retention 
 

 

PLUTONIUM 111 

3. HEALTH EFFECTS 

Figure 3-9. Schematic Representation of the First Institute of Biophysics (FIB) 

Model of Plutonium Biokinetics in Humans* 

V(T) 

Systemic 1 Systemic 6 

Systemic 2 Systemic 7 

Systemic 3 Systemic 8 

Systemic 4 Systemic 9 

Systemic 5 Systemic 

10 

Urine Feces 

Fixed lung 

(Qf) 

Slow clearing 

lung (Qs) Lymph nodes 

(Qn) 

Kf 

Kn 

Δ 

λ 

1-Kn 

λ 

β 

x1 

x2 

x3 

x6 

x4 

x5 

x7 

x8 

x9 

x10 

*See Table 3-10 for explanation of symbols and parameter values. 

Source: Khokhryakov et al. 2002 
 

 

 

 

 

 

 

 

 

 

PLUTONIUM 112 

3. HEALTH EFFECTS 

half-times are assumed to be approximately 4.4 days (fast) and 2,000 days (slow; corresponding halftimes for Pu(NO3)4 are 31 and 1,500 days, respectively. 

Plutonium absorbed from the lung enters a systemic compartment composed of 10 sub-compartments 

from which plutonium is transferred to urine (5) or feces (5). The sub-compartments represent kinetically 

similar pools of plutonium in the body, rather than specific tissues (i.e., the model was intended to 

simulate lung retention and excretion, not plutonium burdens in other tissues), and are assigned unique 

excretion rate constants. Summing the outflow from all five compartments provides the estimated total 

excreted plutonium per day. Distribution fractions and transfer rates, and half-times for the various 

compartments are presented in Table 3-10. A recent configuration of the model (Khokhryakov et al. 

2005) replaced the FIB-1 lung clearance model with the ICRP Human Respiratory Tract Model for 

Radiological Protection (ICRP 1994b). 

Validation of the Model. The FIB-1 model has been evaluated with data on plutonium excretion and 

postmortem lung and total body burdens in 543 Mayak workers (Khokhryakov et al. 2002). An 

adaptation of the FIB-1 model, with the lung clearance model replaced by the ICRP Human Respiratory 

Tract Model for Radiological Protection (ICRP 1994b), has also been evaluated against the same data 

(Khokhryakov et al. 2005; Suslova et al. 2003). An uncertainty analysis of model predictions has been 

reported (Krahenbuhl et al. 2005). 

Risk Assessment. The model has been used to establish the lung radiation dose (Sv) per unit of 

plutonium intake (Bq) in plutonium production workers (Khokhryakov et al. 2002, 2005). 

Target Tissues. The model is designed to calculate radiation dose coefficients (Sv/Bq) to the lung 

corresponding to specific inhalation exposures to plutonium isotopes or from urine plutonium 

biomonitoring data (Khokhryakov et al. 2002, 2005). 

Species Extrapolation. The model is based on both human and animal data. However, it is intended 

for applications to human dosimetry. Applications to other species would require consideration of 

species-specific adjustments in modal parameters. 

Interroute Extrapolation. The FIB-1 model was constructed to simulate kinetics of inhaled 

plutonium. The systemic portion of the model is an empirical model (compartmental with no assignments 

of compartments to physiological entities) for which parameter values were derived from data on 
 

 

 

PLUTONIUM 113 

3. HEALTH EFFECTS 

Table 3-10. Parameters of the First Branch of the First Institute of Biophysics 

(FIB-1) Biokinetic Plutonium Modela 

Parameter Symbol Unit S=0.3% S=1.0% S=3.0% 

Fraction of inhaled V(T) percent Particle size-dependent 

deposited in lung 

Fraction to fast lung  percent 26.5±46.5 71.7±9.1 90.1±3.5 

clearance 

Fraction to fixed lung Kf percent 15.4±4.2 4.3±0.7 1.8±0.2 

compartment 

Fraction to slow lung  percent 58.0±46.4 24.0±9.1 8.1±3.5 

clearance compartment 

Fraction to lymph nodes Kn percent 26.0±4.2 21.0±1.6 11.0±0.9 

Clearance rate from slow  year -1 0.134±0.103 0.133±0.045 0.170±0.063 

lung compartment 

Urine Feces 

ai xi ai xi 

Systemic compartment 1 a1, x1 day-1 4.1x10-3 5.634x10-1 6.0x10-3 3.465x10-1 

Systemic compartment 2 a2, x2 day-1 1.2x10-3 1.26x10-1 1.6x10-3 1.05x10-1 

Systemic compartment 3 a3, x3 day-1 1.3x10-4 1.65x10-2 1.2x10-4 1.24x10-2 

Systemic compartment 4 a4, x4 day-1 3.0x10-5 2.31x10-3 2.0x10-5 1.8x10-3 

Systemic compartment 5 a5, x5 day-1 1.3x10-5 2.0x10-5 5.2x10-6 2.0x10-5 

a

See Figure 3-9 for schematic representation of model. 

Source: Khokhryakov et al. 2002 
 

 

 

 

 

 

 

 

 

 

PLUTONIUM 114 

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plutonium excretion and postmortem lung and total body burdens in Mayak workers. The model cannot 

be directly extrapolated to predicting the kinetics of systemic plutonium following exposures by other 

routes (e.g., dermal, oral). 

Leggett et al. (2005) Plutonium Biokinetics Model 

Description of the Model. Leggett et al. (2005) developed a modification of the ICRP (1994a) 

model. A schematic diagram of the model and list of parameter values are presented in Figure 3-10 and 

Table 3-11, respectively. The major important features introduced into the Leggett et al. (2005) model 

are the simulations of blood and urinary excretion from blood, liver, and bone. The blood compartment in 

the Leggett et al. (2005) model is divided into two sub-compartments (blood 1, blood 2). Absorbed 

plutonium enters blood 1, from where it distributes to other tissues and is excreted into urine. Plutonium 

in tissues returns to blood 2 (recycled plutonium), from where it distributes to blood 1, the rapid soft 

tissue compartment (ST0), and is excreted in urine. The two blood compartments, with both contributing 

to urinary bladder contents, provides a simulation of a relatively fast pathway for urinary excretion of 

recycled plutonium (blood 2 to urine, t1/2≈5 hours) and a slower excretion pathway for initially-absorbed 

plutonium (blood 1 to urine, t1/2≈45 days). The liver is divided into three compartments (liver 0, 1, and 

2). Liver 0 receives plutonium from blood 1 from where it can be secreted into the gastrointestinal tract 

(e.g., bile), or transferred to liver 1 and liver 2. The latter sub-compartments simulate faster and slower 

transfers of plutonium from liver to blood 2 (liver 1 to blood, t1/2≈460 days; liver 2 to blood, 

t1/2≈5,500 days). This configuration (i.e., fast and slower liver compartments) results in a gradual shift in 

the systemic plutonium distribution from liver to skeleton, with the liver burden being greater than 

skeletal burden, initially after absorption, and the liver contribution diminishing, relative to skeletal, over 

time. As in the ICRP (1994a) model, the skeleton is divided into trabecular and cortical components, 

with each further divided into surface bone, bone volume, and bone cavity (marrow) compartments. In 

the ICRP (1994a) model, initial deposition of plutonium is assumed to occur from blood directly to bone 

surfaces, where it can be transferred to bone marrow or to bone volume (i.e., burial). In the Leggett et al. 

(2005) model, plutonium in blood 1 is directly transferred to both bone surface and volume 

compartments. This configuration simulates faster and slower components of burial of plutonium in bone 

volume. The fast component is represented by direct transfer from blood 1 to bone volume (t1/2≈50 days 

and 150 days for trabecular and cortical volume, respectively) and the slower component is represented 

by transfer from bone surface to volume (t1/2≈ 15 and 93 years for trabecular and cortical, respectively). 
 

PLUTONIUM 115 

3. HEALTH EFFECTS 

Figure 3-10. Schematic Representation of the Leggett et al. (2005) Model of
 

Plutonium Biokinetics in Humans*
 

Other Soft Tissues 

Intermediate Rapid Slow turnover 

turnover (ST1) turnover (ST0) (ST2) 

Kidneys 

Other kidney Liver 2 

Urine Urinary tissue 

bladder Liver 1 

contents 

Renal tubule Liver 0 

Blood 2 

Skeleton Gastrointestinal 

tract contents 

Cortical Cortical Cortical 

volume surface marrow Feces 

Gonads Trabecular Trabecular Trabecular 

volume surface marrow 

Blood 1 

*See Table 3-11 for parameter values. 
 

 
 

PLUTONIUM 116 

3. HEALTH EFFECTS 

Table 3-11. Parameters of Leggett et al. (2005) Model of Plutonium Biokinetics in 

Humansa
 

Parameterb Adult value 

Blood (1) to liver (0) 4.6200x10-1 

Blood (1) to cortical surface 8.7780x10-2 

Blood (1) to cortical volume 4.6200x10-3 

Blood (1) to trabecular surface 1.2474x10-1 

Blood (1) to trabecular volume 1.3860x10-2 

Blood (1) to urinary bladder contents 1.5400x10-2 

Blood (1) to renal tubules 7.7000x10-3 

Blood (1) to other kidney 3.8500x10-4 

Blood (1) to upper large intestine contents 1.1550x10-2 

Blood (1) to testes 2.6950x10-4 

Blood (1) to ovary 8.4700x10-5 

Blood (1) to soft tissue (1) 1.8511x10-2 

Blood (1) to soft tissue (2) 2.3100x10-2 

Soft tissue (0) to blood (1) 9.9000x10-2 

Blood (2) to urinary bladder contents 3.5000x100 

Blood (2) to blood (1) 6.7550x101 

Blood (2) to soft tissue (0) 2.8950x101 

Renal tubules to urinary bladder contents 1.7329x10-2 

Other kidney to blood (2) 1.2660x10-4 

Soft tissue (1) to blood (2) 1.3860x10-3 

Soft tissue (2) to blood (2) 1.2660x10-4 

Liver (0) to small intestine contents 9.2420x10-4 

Liver (0) to liver (1) 4.5286x10-2 

Liver (1) to blood (2) 1.5200x10-3 

Liver (1) to liver (2) 3.8000x10-4 

Liver (2) to blood (2) 1.2660x10-4 

Tests to blood (2) 3.8000x10-4 

Ovaries to blood (2) 3.8000x10-4 

Cortical surface to cortical marrow 8.2100x10-5 

Cortical surface to cortical volume 2.0500x10-5 

Cortical volume to cortical marrow 8.2100x10-5 

Trabecular surface to trabecular marrow 4.9300x10-4 

Trabecular surface to trabecular volume 1.2300x10-4 

Trabecular volume to trabecular marrow 4.9300x10-4 
 

 
 

PLUTONIUM 117 

3. HEALTH EFFECTS 

Table 3-11. Parameters of Leggett et al. (2005) Model of Plutonium Biokinetics in 

Humansa
 

Parameterb Adult value 

Cortical marrow to blood (2) 7.6000x10-3 

Trabecular marrow to blood (2) 7.6000x10-3 

a

See Figure 3-10 for schematic representation of model. b

Units are d-1 . 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 118 

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Validation of the Model. The Leggett et al. (2005) model has been evaluated with data on plutonium 

excretion and postmortem tissue levels in plutonium workers at the Mayak production plant (e.g., 

Khokhryakov et al. 1994, 2000) and data from plutonium injection studies (Langham et al. 1950, 1980; 

Talbot et al. 1997). The model provides predictions of blood, liver, and fecal plutonium kinetics that 

more closely simulate observations made in injection studies compared to predictions from the ICRP 

(1994a) model (Leggett et al. 2005). The model also predicts urinary plutonium based on observed 

urinary excretion kinetics in Mayak production plant workers (Leggett et al. 2005). 

Risk Assessment. The Leggett et al. (2005) model was developed to update and replace the ICRP 

(1994a) model that is currently being used to establish radiation doses (Sv) per unit of ingested or inhaled 

plutonium (Bq) (ICRP 1994a, 2001) 

Target Tissues. The model was developed for calculating whole-body and tissue-specific radiation 

dose coefficients (Sv/Bq) corresponding to absorbed activities of plutonium isotopes. Target tissues 

represented in the model are shown in Figure 3-10. 

Species Extrapolation. The model is intended for applications to human dosimetry. Applications to 

other species would require consideration of species-specific adjustments in modal parameters. 

Interroute Extrapolation. The Leggett et al. (2005) model is designed to simulate kinetics of 

absorbed plutonium and, if combined with a gastrointestinal absorption or respiratory tract model (e.g., 

ICRP 1979, 1994a), could be used to simulate systemic kinetics of ingestion or inhalation exposures. The 

model can be applied to any other route of exposure for which the transfer rate to blood is available. 

3.5 MECHANISMS OF ACTION 

3.5.1 Pharmacokinetic Mechanisms 

Absorption. Several mechanisms appear to contribute to the absorption of inhaled plutonium: 

(1) physical transformation of plutonium particles deposited (or formed from hydrolysis reactions) in the 

lung, including fragmentation of particles, accelerated by alpha-radiation; (2) dissolution of particles; and 

(3) phagocytosis of particles by macrophages (Bair et al. 1973; Mewhinney and Diel 1983). The relative 

contributions of these mechanisms appear to depend on several factors, including: (1) particle size of the 

inhaled aerosol; (2) water solubility of the inhaled plutonium (e.g., PuO2, Pu[NO3]4); (3) isotope specific 
 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 119 

3. HEALTH EFFECTS 

activity (e.g., 238Pu, 239Pu), which determines intensity of alpha-radiation of the particles; and (4) in the 

case of PuO2, surface characteristics of the particles, affected by temperatures at which the PuO2 was 

produced. 

Mechanisms of absorption of plutonium from the gastrointestinal tract have not been elucidated. Studies 

conducted in animals have shown that gastrointestinal absorption of plutonium is increased in irondeficiency, and is decreased in iron-deficient animals by the co-administration of Fe3+, suggesting that 

mechanisms involved in iron absorption may contribute to plutonium absorption (Sullivan and Ruemmler 

1988; Sullivan et al. 1986). Gastrointestinal absorption of plutonium compounds appears to be higher for 

more water-soluble compounds of plutonium; absorption of plutonium citrate tends to be greater than 

nitrate, which is greater than plutonium oxide (PuO2) (Sullivan 1980a). This suggests that dissolution of 

plutonium in the gastrointestinal tract may contribute to absorption (possibly, in addition to endocytosis 

of particles). Gastrointestinal absorption is higher in neonatal animals compared to mature animals, 

which may reflect a more permeable gastrointestinal tract in neonates or physiological adjustments in 

neonates related to nutrient (e.g., iron) absorption that affect plutonium uptake (Sullivan 1980a, 1980b; 

Sullivan and Gorham 1983; Sullivan et al. 1985). Fasting tends to increase absorption, which suggests 

the possibility of binding interactions with food components in the gastrointestinal tract and/or 

competition for absorption with other nutrients (Bhattacharyya et al. 1986; USNRC 1992). 

Results from these studies support the following general conclusions regarding factors that affect 

absorption: (1) in general, absorption of plutonium citrate tends to be greater than nitrate, which is 

greater than plutonium oxide (PuO2) (Sullivan 1980a); (2) most estimates of absorption of plutonium 

citrate and nitrate in adult animals are <0.1% of the dose; (3) fasting tends to increase absorption 

(USNRC 1992); (4) absorption is 10–1,000 times greater in neonates compared to adults, depending on 

the animal species and chemical form of plutonium (Sullivan 1980a, 1980b; Sullivan and Gorham 1983; 

Sullivan et al. 1985); (5) iron deficiency increases absorption in juvenile rats and administration of ferric 

iron (Fe3+) to iron-deficient rats decreases absorption (Sullivan and Ruemmler 1988); and (6) absorption 

of plutonium in surface dusts (e.g., bomb test sites) in guinea pigs was <0.001% of the dose (Harrison et 

al. 1994). 

Distribution. 

Distribution in Blood. Dissolved plutonium distributes in blood predominantly as Pu(IV) complexes 

with plasma proteins (Lehmann et al. 1983; Stevens et al. 1968; Stover et al. 1968a; Taylor 1973). 
 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 120 

3. HEALTH EFFECTS 

Although Pu(IV) forms complexes with a variety of plasma proteins, including albumin, -globulins, and 

low molecular weight proteins, the dominant complex is with transferrin. The dissociation constant of 

Pu(IV)-transferrin complex has not been measured; however, the complex appears to be less stable than 

Fe(III)-transferrin complex (Kd≈10-22 M) (Aisen and Listowsky 1980). As a result, binding of Fe(III) to 

transferrin can influence the degree of binding of Pu(IV). Plutonium also forms complexes with 

nonprotein ligands, polycarboxylates (e.g., citrate, lactate). The stability constants for the mono- and 

di-citrate complexes are approximately 1015 and 1030 M, respectively (Taylor 1973). 

Distribution within Soft Tissues. Plutonium, because it is strongly bound to proteins in blood, does not 

escape easily from the vasculature. However, at sites within the body where blood sinusoids are present 

(e.g., in the liver, red bone marrow), protein-plutonium complexes in plasma can leave the vasculature 

and distribute to sites within tissues. Plutonium can exist within tissues as an ion bound to binding sites 

on proteins, including those associated with iron metabolism (e.g., transferrin, haemosiderin, and ferritin) 

or as insoluble particulates. Particulates may derive from inhalation of particles of plutonium (e.g., PuO2) 

or may form by aggregation of polymeric hydrolysis products of more soluble Pu(IV) compounds (e.g., 

plutonium citrate and plutonium nitrate) (Taylor 1973). In the lung, plutonium accumulates within 

alveolar macrophages and Type I alveolar epithelial cells (both of which phagocytize plutonium 

particles), and in lung-associated lymph nodes (Bair et al. 1973). Aggregation of macrophages can result 

in localized regions of high activity that can become encapsulated in fibrotic material, inhibiting the 

dissolution of the plutonium and the further migration of the macrophages from the lung. Plutonium is 

also found associated with hemosiderin (in bone marrow macrophages) and with ferritin in liver and other 

tissues (e.g., spleen, bone marrow) where ferritin is expressed (Gorden et al. 2003; Taylor 1973). The 

sequestration of plutonium into ferritin may contribute to the relatively long retention time of plutonium 

in liver. Following intravenous administration of 239Pu-citrate or 239Pu(NO3)4 to rats, plutonium was 

found in hepatocytes and sinusoidal cells. Distribution of plutonium within liver was relatively 

homogeneous following injection of 239Pu-citrate compared to a heterogeneous pattern of aggregation in 

liver following injection of 239Pu(NO3)4 (Fouillit et al. 2004). A similar pattern has been observed in dogs 

(Gearhart et al. 1980). These observations suggest distinct mechanisms of transfer of the two compounds 

into and/or within liver. The temporal changes in the distribution pattern of plutonium in liver and lung 

also occur. In liver, this may derive from regeneration of injured tissue. In the lung, plutonium deposits 

become focalized, over time, within macrophages. Within the lungs, after intakes of insoluble plutonium 

particles the number of contaminated macrophages decreases and the remaining macrophages become 

loaded with even larger amounts of plutonium. These often come together to form local hotspots that 
 

 

 

 

 

 

 

 

 

PLUTONIUM 121 

3. HEALTH EFFECTS 

sometimes form a fibroid capsule around them, which inhibits both the dissolution of the plutonium and 

the further migration of the macrophages. 

Distribution within Bone. Plutonium in bone initially distributes to bone surfaces adjacent to blood 

sinusoids in bone marrow and can subsequently be redistributed within bone volume during bone growth 

and remodeling. Redistribution of plutonium from bone to bone marrow can also occur, at least in part, 

from macrophage phagocytosis of plutonium released from bone during bone resorption. Various studies 

of bone uptake of injected plutonium suggest the following general pattern of deposition of plutonium on 

bone surfaces (DOE 1989; Leggett 1985; Priest 1990; Rosenthal et al. 1972a, 1972b; Vaughan et al. 

1973): (1) monomeric complexes of plutonium (e.g., monomeric plutonium citrate) deposit preferentially 

at bone surfaces, with relatively little initial distribution to marrow; whereas, highly polymeric plutonium 

deposits preferentially in marrow; (2) initial deposition is greater on trabecular compared to cortical bone 

surfaces; (3) initial deposition occurs preferentially on endosteal surfaces compared to periosteal surfaces; 

(4) deposition is greater on surfaces where active resorption is occurring compared to surfaces undergoing 

mineralization; and (5) deposition is greater on surfaces of the axial skeleton (i.e., skull, hyoid bone, 

sternum, ribs, and vertebrae) then on the appendicular skeleton (i.e., limbs). Mechanisms of plutonium 

deposition at bone surfaces are not completely understood. Plutonium (IV) can form complexes with 

bone glycoproteins, collagen, and bone mineral (Vaughan et al. 1973). 

The deposition pattern in bone is age-dependent. A comparison of bone distribution of plutonium in 

juvenile (3 months) beagles, compared to young adult (17–20 months) and mature (60 months) beagles 

that received a single injection of plutonium citrate showed the following patterns (Bruenger et al. 1991a): 

(1) deposition (per cent of dose) was higher in juveniles; (2) a larger fraction of the skeletal deposition 

occurred in limb bones of juveniles; and (3) plutonium in bone volume (as opposed to bone surface) was 

more pronounced in juveniles. These observations are consistent with the concept that plutonium 

preferentially deposits in regions adjacent to red marrow, which has a wider distribution in juveniles than 

in adults, and is more prominent in trabecular bone than in cortical bone, and in bones of the axial 

skeleton. High bone turn-over in juveniles contributes to more rapid distribution of plutonium from bone 

surface to bone volume as a result of burial of surface deposits, uncovering buried deposits, and recycling 

of the plutonium between marrow, bone, and blood (Bruenger et al. 1991a; Leggett 1985; Priest 1990; 

Vaughan et al. 1973). 

Metabolism. Plutonium metabolism in physiological systems consists, primarily, of hydrolytic 

reactions and formation of complexes with protein and nonprotein ligands. 
 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 122 

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Excretion. Absorbed plutonium is excreted in urine and feces. Following inhalation exposure to 

plutonium aerosols, plutonium particulates are transported from the respiratory tract to the gastrointestinal 

tract. Because the fractional absorption of plutonium in the gastrointestinal tract is approximately 1x10-3– 

1x10-4, nearly all of this transported plutonium is excreted in feces. This mechanism explains the fecal 

excretion that has been observed in humans and animals during the first few days following exposure. 

Mechanisms for fecal excretion that persists for months to years following exposure are not as well 

understood. Plutonium injected intravenously is excreted in feces in humans (Langham 1959; Talbot et 

al. 1993, 1997), nonhuman primates (USNRC 1985), dogs (Bair et al. 1974; Ballou et al. 1972; Guilmette 

and Muggenburg 1993; Stover et al. 1959), and rodents (Carritt et al. 1947). Direct evidence for biliary 

secretion of injected plutonium comes from studies conducted in rats (Ballou et al. 1972; Bhattacharyya et 

al. 1978). 

Mechanisms of urinary excretion have not been elucidated and may involve excretion of plutonium from 

plasma, or secretion of plutonium into urine from renal tissue. In plasma, plutonium exists predominantly 

bound to proteins; <5% appears to be in the form of low-molecular weight complexes. The dominant 

protein complex is with transferrin (molecular weight=88 kDa), which can account for 90% of plasma 

plutonium following intravenous administration of either Pu-citrate complex or Pu(NO3)4 (Lehmann et al. 

1983; Stevens et al. 1968; Stover et al. 1968a; Taylor 1973). Renal clearance (plasma-to-urine) of 

transferrin in humans is approximately 1-3x10-4 L/day (Pesce and First 1979); this corresponds to a 

plasma half-time of approximately 20–40 years (assuming a plasma volume in the adult human of 3 L). 

Therefore, excretion of circulating Pu-transferrin complex is unlikely to account for blood-to-urine 

clearances reported in adults (e.g., corresponding half-times 7–30 days) (Etherington et al. 2003; Leggett 

1985). Other possible mechanisms that contribute to urinary excretion are blood-to-urine clearance of 

low molecular weight plutonium complexes, or secretion of plutonium from tissue into urine. 

3.5.2 Mechanisms of Toxicity 

Toxicity of plutonium derives from the biological effects of radiation emitted during the radiological 

decay of plutonium isotopes. The isotopes 238Pu and 239Pu decay by emitting a high-energy alpha particle. 

A very small amount of the energy in the form of gamma rays is also released during the decay of 

plutonium isotopes. However, gamma radiation from 238Pu and 239Pu decay is of such small magnitude 

and energy that the dominant mechanisms of toxicity are associated with alpha radiation. Molecular 

damage results from the direct ionization of atoms that are encountered by alpha (and gamma) radiation 
 

 

 

 

 

 

 

 

PLUTONIUM 123 

3. HEALTH EFFECTS 

and by interactions of resulting free radicals (e.g., H•, OH•) with nearby macromolecules (e.g., lipids, 

nucleic acids, proteins). Tissue damage results when the molecular damage is sufficiently extensive 

and/or repair of the damage is not sufficiently rapid. 

Alpha radiation emitted by plutonium isotopes cannot penetrate the outer layers of the skin. However, 

once plutonium is internalized, the extremely short-range alpha radiation produces a very localized 

radiation dose. As a result, toxicity of plutonium coincides with the distribution of plutonium in the body. 

As discussed in Section 3.4, Toxicokinetics, the distribution of plutonium depends on many factors, 

including route of exposure, chemical form and physical characteristics of the plutonium compound (and 

its complexes), and isotope specific activity (i.e., Bq/g). The patterns of toxicity observed in dogs 

exposed to various compounds of plutonium reflect, primarily, the distribution of plutonium that follows 

exposure to each compound. Lung cancers and other effects of 239PuO2 on the lung (e.g., pneumonitis) 

were the dominant effects observed in dogs following inhalation of 239PuO2, which is cleared relatively 

slowly from the lung (and from thoracic lymph nodes). As a result, following inhalation exposures to 

239PuO2, the highest radiation doses (i.e., effective dose equivalents) occur in the lung. In contrast, 

inhaled 238PuO2 is more rapidly cleared from the lung and, once absorbed, distributes primarily to skeletal 

tissues (bone surfaces and marrow) and liver, resulting in relatively high radiation doses to bone and liver, 

as well as to lung. This is consistent with observations of bone, liver, and lung toxicity in dogs following 

inhalation exposures to 238PuO2. 

3.5.3 Animal-to-Human Extrapolations 

Mechanisms of toxicity and toxicokinetics of plutonium, described in Sections 3.5.1 and 3.5.2, are 

directly applicable to humans. Numerous studies of the distribution of plutonium in humans (i.e., autopsy 

studies of individuals occupationally exposed to plutonium) have shown that the general pattern of 

distribution of plutonium in humans is consistent with that observed in various animal models, with the 

highest portion of the body burden in lung (following inhalation exposures), skeletal tissues, and liver. 

Epidemiologic studies of health outcomes among workers in industries that produce and/or process 

plutonium have provided evidence for increased risk of lung, liver, and bone cancers in association with 

exposures to plutonium. These observations are consistent with the pattern of health effects observed in 

animals. 
 

 

 

 

 

 

 

 

 

 

 

 

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3. HEALTH EFFECTS 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS 

Recently, attention has focused on the potential hazardous effects of certain chemicals on the endocrine 

system because of the ability of these chemicals to mimic or block endogenous hormones. Chemicals 

with this type of activity are most commonly referred to as endocrine disruptors. However, appropriate 

terminology to describe such effects remains controversial. The terminology endocrine disruptors, 

initially used by Thomas and Colborn (1992), was also used in 1996 when Congress mandated the EPA to 

develop a screening program for “...certain substances [which] may have an effect produced by a 

naturally occurring estrogen, or other such endocrine effect[s]...”. To meet this mandate, EPA convened a 

panel called the Endocrine Disruptors Screening and Testing Advisory Committee (EDSTAC), and in 

1998, the EDSTAC completed its deliberations and made recommendations to EPA concerning endocrine 

disruptors. In 1999, the National Academy of Sciences released a report that referred to these same types 

of chemicals as hormonally active agents. The terminology endocrine modulators has also been used to 

convey the fact that effects caused by such chemicals may not necessarily be adverse. Many scientists 

agree that chemicals with the ability to disrupt or modulate the endocrine system are a potential threat to 

the health of humans, aquatic animals, and wildlife. However, others think that endocrine-active 

chemicals do not pose a significant health risk, particularly in view of the fact that hormone mimics exist 

in the natural environment. Examples of natural hormone mimics are the isoflavinoid phytoestrogens 

(Adlercreutz 1995; Livingston 1978; Mayr et al. 1992). These chemicals are derived from plants and are 

similar in structure and action to endogenous estrogen. Although the public health significance and 

descriptive terminology of substances capable of affecting the endocrine system remains controversial, 

scientists agree that these chemicals may affect the synthesis, secretion, transport, binding, action, or 

elimination of natural hormones in the body responsible for maintaining homeostasis, reproduction, 

development, and/or behavior (EPA 1997). Stated differently, such compounds may cause toxicities that 

are mediated through the neuroendocrine axis. As a result, these chemicals may play a role in altering, 

for example, metabolic, sexual, immune, and neurobehavioral function. Such chemicals are also thought 

to be involved in inducing breast, testicular, and prostate cancers, as well as endometriosis (Berger 1994; 

Giwercman et al. 1993; Hoel et al. 1992). 

No studies were located regarding endocrine disruption in humans or animals after exposure to 

plutonium. No in vitro studies were located regarding endocrine disruption of plutonium. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

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3.7 CHILDREN’S SUSCEPTIBILITY 

This section discusses potential health effects from exposures during the period from conception to 

maturity at 18 years of age in humans, when all biological systems will have fully developed. Potential 

effects on offspring resulting from exposures of parental germ cells are considered, as well as any indirect 

effects on the fetus and neonate resulting from maternal exposure during gestation and lactation. 

Relevant animal and in vitro models are also discussed. 

Children are not small adults. They differ from adults in their exposures and may differ in their 

susceptibility to hazardous chemicals. Children’s unique physiology and behavior can influence the 

extent of their exposure. Exposures of children are discussed in Section 6.6, Exposures of Children. 

Children sometimes differ from adults in their susceptibility to hazardous chemicals, but whether there is 

a difference depends on the chemical (Guzelian et al. 1992; NRC 1993). Children may be more or less 

susceptible than adults to health effects, and the relationship may change with developmental age 

(Guzelian et al. 1992; NRC 1993). Vulnerability often depends on developmental stage. There are 

critical periods of structural and functional development during both prenatal and postnatal life, and a 

particular structure or function will be most sensitive to disruption during its critical period(s). Damage 

may not be evident until a later stage of development. There are often differences in pharmacokinetics 

and metabolism between children and adults. For example, absorption may be different in neonates 

because of the immaturity of their gastrointestinal tract and their larger skin surface area in proportion to 

body weight (Morselli et al. 1980; NRC 1993); the gastrointestinal absorption of lead is greatest in infants 

and young children (Ziegler et al. 1978). Distribution of xenobiotics may be different; for example, 

infants have a larger proportion of their bodies as extracellular water, and their brains and livers are 

proportionately larger (Altman and Dittmer 1974; Fomon 1966; Fomon et al. 1982; Owen and Brozek 

1966; Widdowson and Dickerson 1964). The infant also has an immature blood-brain barrier (Adinolfi 

1985; Johanson 1980) and probably an immature blood-testis barrier (Setchell and Waites 1975). Many 

xenobiotic metabolizing enzymes have distinctive developmental patterns. At various stages of growth 

and development, levels of particular enzymes may be higher or lower than those of adults, and 

sometimes unique enzymes may exist at particular developmental stages (Komori et al. 1990; Leeder and 

Kearns 1997; NRC 1993; Vieira et al. 1996). Whether differences in xenobiotic metabolism make the 

child more or less susceptible also depends on whether the relevant enzymes are involved in activation of 

the parent compound to its toxic form or in detoxification. There may also be differences in excretion, 

particularly in newborns who all have a low glomerular filtration rate and have not developed efficient 
 

 

 

 

 

 

 

 

 

 

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tubular secretion and resorption capacities (Altman and Dittmer 1974; NRC 1993; West et al. 1948). 

Children and adults may differ in their capacity to repair damage from chemical insults. Children also 

have a longer remaining lifetime in which to express damage from chemicals; this potential is particularly 

relevant to cancer. 

Certain characteristics of the developing human may increase exposure or susceptibility, whereas others 

may decrease susceptibility to the same chemical. For example, although infants breathe more air per 

kilogram of body weight than adults breathe, this difference might be somewhat counterbalanced by their 

alveoli being less developed, which results in a disproportionately smaller surface area for alveolar 

absorption (NRC 1993). 

Numerous epidemiological studies of ionizing radiation exposures have found higher cancer risks 

associated with exposures of infants and children infancy and childhood, compared to adults (Agency for 

Toxic Substances and Disease Registry 1999). Although there is no direct evidence for increased 

susceptibility of children to toxicity from plutonium, several kinds of observations made in animals 

suggest that immature animals may be more vulnerable to plutonium as a result of higher deposition of 

absorbed plutonium on bone surfaces and higher turn-over of bone. Studies conducted in immature 

beagles (inhalation exposures to 239PuO2 at age 2.6–3.6 months) showed that, in comparison to similar 

exposures of adult beagles, a larger fraction of the initially deposited lung burden was transferred to the 

skeleton (DOE 1988d, 1989). This observation is consistent with the results from injection studies. A 

comparison of bone distribution of plutonium in juvenile beagles (3 months of age), compared to young 

adult (17–20-month-old) and mature (60-month-old) beagles that received a single injection of plutonium 

citrate showed that skeletal deposition (percent of dose) was higher in juveniles, occurred more 

extensively in growing limb bones, and within bone, a larger portion of the bone burden was associated 

within bone volume (Bruenger et al. 1991a). As discussed in Section 3.5, Mechanisms of Toxicity, these 

observations are consistent with the concept that plutonium preferentially deposits in regions adjacent to 

red marrow, which has a wider distribution in juveniles than in adults, and is more prominent in 

trabecular bone than in cortical bone, and in bones of the axial skeleton. High bone turn-over in juveniles 

may also contribute to more rapid distribution of plutonium from bone surface to bone volume as a result 

of burial of surface deposits, uncovering buried deposits, and recycling of the plutonium between marrow, 

bone, and blood (Bruenger et al. 1991a; Leggett 1985; Vaughan et al. 1973). These observations suggest 

the possibility that children may have a higher susceptibility to bone marrow toxicity and related 

outcomes (e.g., leukemia) and skeletal toxicity of plutonium than adults, although this has not been 

verified either experimentally, or in epidemiological studies. One observation that may be pertinent is 
 

 

 

 

 

 

 

 

 

 

 

 

 


 


 


 


 


 


 


 


 

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that dogs, examined 5 years after an inhalation exposure to 239PuO2 at age 2.6–3.6 months, showed a
 

lower incidence of radiation pneumonitis than dogs exposed as adults. This would be consistent with a
 

greater transfer of plutonium from the lung to the skeleton. Lung tissue growth in the younger dogs may
 

have resulted in some lung tissue with little or no plutonium.
 

Gastrointestinal absorption of ingested plutonium is higher in neonatal animals compared to mature
 

animals, which may reflect a more permeable gastrointestinal tract in neonates or physiological
 

adjustments in neonates related to nutrient (e.g., iron) absorption that affect plutonium uptake. 

Absorption has been shown to be 10–1,000 times greater in neonates compared to adults, depending on 

animal species and chemical form of plutonium (Sullivan 1980a, 1980b; Sullivan and Gorham 1983;
 

Sullivan et al. 1985). Iron deficiency increases absorption in juvenile rats (Sullivan and Ruemmler 1988). 

However, available animal data have not demonstrated that increased plutonium uptake by neonatal and 

juveniles results in increased susceptibility to the toxic effects of internalized plutonium.
 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT 

Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility (NAS/NRC 

1989). 

A biomarker of exposure is a xenobiotic substance or its metabolite(s) or the product of an interaction 

between a xenobiotic agent and some target molecule(s) or cell(s) that is measured within a compartment 

of an organism (NAS/NRC 1989). The preferred biomarkers of exposure are generally the substance 

itself, substance-specific metabolites in readily obtainable body fluid(s), or excreta. However, several 

factors can confound the use and interpretation of biomarkers of exposure. The body burden of a 

substance may be the result of exposures from more than one source. The substance being measured may 

be a metabolite of another xenobiotic substance (e.g., high urinary levels of phenol can result from 

exposure to several different aromatic compounds). Depending on the properties of the substance (e.g., 

biologic half-life) and environmental conditions (e.g., duration and route of exposure), the substance and 

all of its metabolites may have left the body by the time samples can be taken. It may be difficult to 

identify individuals exposed to hazardous substances that are commonly found in body tissues and fluids 

(e.g., essential mineral nutrients such as copper, zinc, and selenium). Biomarkers of exposure to 

plutonium are discussed in Section 3.9.1. 
 

 

 

 

 

 

 

 

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Biomarkers of effect are defined as any measurable biochemical, physiologic, or other alteration within an 

organism that, depending on magnitude, can be recognized as an established or potential health 

impairment or disease (NAS/NRC 1989). This definition encompasses biochemical or cellular signals of 

tissue dysfunction (e.g., increased liver enzyme activity or pathologic changes in female genital epithelial 

cells), as well as physiologic signs of dysfunction such as increased blood pressure or decreased lung 

capacity. Note that these markers are not often substance specific. They also may not be directly 

adverse, but can indicate potential health impairment (e.g., DNA adducts). Biomarkers of effects caused 

by plutonium are discussed in Section 3.9.2. 

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism's ability 

to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic or 

other characteristic or a preexisting disease that results in an increase in absorbed dose, a decrease in the 

biologically effective dose, or a target tissue response. If biomarkers of susceptibility exist, they are 

discussed in Section 3.11, Populations That Are Unusually Susceptible. 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Plutonium 

Plutonium is a radioactive element. Plutonium within the body can be inferred from radioassays of urine, 

feces, or tissue samples by gross alpha analysis, alpha spectroscopy, gamma-ray spectroscopy, mass 

spectrometry, and liquid scintillation techniques (Alvarez and Navarro 1996; Dacheux and Aupiais 1997; 

DOE 1990b, 1997; Guilmette 1986). 

3.8.2 Biomarkers Used to Characterize Effects Caused by Plutonium 

Limited information is available regarding biomarkers of effect of plutonium exposure and observed 

effects are not specific to radiation from plutonium or any other radionuclide. The presence of 

chromosome aberrations has been reported in humans and laboratory animals following the 

internalization of plutonium (see Section 3.3 for a discussion of plutonium-induced genotoxic effects). 

Relatively early adverse health effects in animals following the internalization of inhaled plutonium 

include radiation pneumonitis and lymphopenia; late-occurring effects may include bone, lung, and liver 

tumors (see Section 3.2.1 for detailed discussion of plutonium-induced health effects following inhalation 

exposure). 
 

 

 

 

 

 

 

 

 

 

 

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3.9 INTERACTIONS WITH OTHER CHEMICALS 

The toxicokinetics of plutonium appear to be influenced by exposure to cigarette smoke. Cigarette 

smoke, when administered to mice following inhalation exposure to 239PuO2, appeared to inhibit the 

clearance of plutonium (Talbot et al. 1987). At 49 days postexposure, animals exposed to plutonium and 

cigarette smoke retained approximately 20% more plutonium than those animals exposed to plutonium 

alone. In another study, rats were given single pernasal exposures to 239PuO2 with or without chronic 

exposure to cigarette smoke (Finch et al. 1998). Rats receiving both plutonium and cigarette smoke 

exposure exhibited retarded 239Pu clearance from the lung. The above toxicokinetic interactions may 

contribute to interactions relevant to the estimation of lung cancer risks associated with plutonium 

exposures in human populations. Both additive and multiplicative interaction models have been used to 

model interactions between smoking and lung cancer risk in studies of plutonium workers (Jacob et al. 

2005; Kreisheimer et al. (2003). 

Increased lung retention of 239Pu (as the hydroxide colloid containing a relatively high concentration of 

gadolinium) and decreased fecal excretion of plutonium were noted in rats administered 239Pu (as the 

hydroxide colloid) containing a relatively high concentration of gadolinium compared to rats receiving 

239Pu in the absence of gadolinium (Sato et al. 2001). 

Exposure to inhaled 239PuO2 followed by intratracheal instillation of benzo(a)pyrene resulted in a higher 

incidence of lung tumors and a decrease in median survival time compared to animals exposed to 239PuO2 

alone (Métivier et al. 1984). As the dose of benzo(a)pyrene increased, survival time decreased. Exposure 

of rats to a single intra-abdominal injection of a mixture of 239PuO2 and benzo(a)pyrene resulted in an 

additive effect in the induction of abdominal sarcomas, compared to animals given benzo(a)pyrene or 

plutonium only (AEC 1973b). 

A decrease in median survival time was observed in rats injected intravenously with 239Pu, immediately 

followed by exposure to x-rays (Ballou et al. 1962), as compared to those animals exposed to plutonium 

alone. As exposure to x-rays increased, survival time decreased. However, when exposure to x-ray was 

delayed (as much as 14 days) following exposure of the rats to 239Pu, the number of deaths occurring 

before 40 days was reduced. 

Exposure of rats to 239PuO2 and asbestos by intraperitoneal injection resulted in a higher incidence of 

abdominal tumors compared to animals exposed to 239PuO2 alone (AEC 1973b). However, this additive 
 

 

 

 

 

 

 

 

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effect of asbestos and plutonium was not observed in the induction of pulmonary sarcomas when asbestos 

was administered to rats in combination with 239PuO2 via intratracheal instillation (Sanders 1975b). In the 

same study, asbestos did not influence the translocation of plutonium in rats. However, asbestos 

increased the pulmonary retention of plutonium compared to plutonium-only exposure (Sanders 1975b). 

An increased incidence of metaplasia was observed in rats experiencing a single inhalation exposure to 

239PuO2 followed by administration of 1 or 10 mg vitamin C/mL of drinking water for 1 year 

postexposure, compared to rats exposed to plutonium only (Sanders and Mahaffey 1983). However, the 

incidence of squamous cell carcinomas in animals exposed to plutonium and vitamin C decreased with 

increasing dose of vitamin C. The authors stated that vitamin C may interfere with the progression of 

squamous cell metaplasia to squamous cell carcinoma. 

Studies in laboratory animals have also demonstrated the influence of metals on the toxicokinetics of 

plutonium. Pretreatment of rats with subcutaneous injection of cadmium or copper followed by 

intravenous injection of 238Pu or 239Pu resulted in changes in the distribution patterns of plutonium, but not 

in total retention of either isotope. Plutonium retention of both isotopes, following pretreatment with 

either metal, was increased in the spleen and the kidneys, as compared to animals treated with plutonium 

only (Volf 1980). Liver retention of plutonium appeared to be increased by copper pretreatment and 

decreased by cadmium pretreatment; these differences may reflect different properties of the respective 

metal-binding proteins or different mechanisms of action (Volf 1980). 

Inhalation exposure of rats to beryllium oxide, followed by 239PuO2, resulted in increased retention of 

plutonium in the lungs and subsequently-increased translocation of plutonium to thoracic lymph nodes 

(Sanders et al. 1978). Although lung retention of plutonium was increased and beryllium and plutonium 

are both considered to be lung carcinogens, combined exposures of rats to beryllium and 239Pu did not 

significantly increase the incidence of lung tumors, compared to plutonium-only exposure (Sanders et al. 

1978). 

Administration of alcohol prior to exposure to plutonium appears to have an effect on the toxicokinetics 

of plutonium. Rats were treated orally with 12.5 or 25% ethanol (in 25% sucrose) for 1 or 6 weeks, 

followed by an intravenous injection of polymeric 239Pu and sacrifice 1 or 41 days postexposure (DOE 

1978e). In animals given ethanol for 6 weeks, retention of plutonium in the liver was increased at 1 day 

postexposure, but returned to normal 41 days postexposure, compared to plutonium-only exposure. At 

1-day postexposure, lung retention of plutonium was increased in animals given ethanol for 1 week, while 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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lung retention of plutonium was decreased in animals given ethanol for 6 weeks. These differences were 

still apparent at 41 days postinjection (DOE 1978e). 

Animal studies have been conducted to study the relative hazards of "diffuse" versus "localized" 

irradiation of the lung (Anderson et al. 1979; Muggenburg et al. 2008) in an effort to determine if there is 

a "hot particle" or "hot spot" effect. The theory hypothesized that larger particles with higher activity and 

less uniform distribution might be more likely to cause cancer than smaller, more uniformly dispersed 

particles. In perhaps the most direct and relevant study of this theory using plutonium, Muggenburg et al. 

(2008) provide direct evidence against the “hot particle” theory. The authors exposed beagle dogs by 

inhalation to three uniform sizes of 239PuO2 particles (0.75, 1.5, and 3.0 μm AMAD, representing particle 

activities spanning more than 2 orders of magnitude from 0.048 to 7.7 mBq) as part of a composite 

lifespan study. They found that smaller and more uniformly distributed particles have the same or greater 

potential to produce neoplasms than less uniformly distributed particles. In the Anderson et al. (1979) 

studies, hamsters were exposed by instillation of 238PuO2 or 239PuO2 contained in zirconium dioxide 

spheres. Both installation and the use of the 238Pu isotope represent confounders to assessing the “hot 

particle” theory. Instillation is a less relevant route than inhalation since it more coarsely distributes 

material in a less defined manner to a smaller portion of the lung. Also, the specific activity of the 238Pu 

particles is several hundred times greater that of its 239Pu counterpart, and the intense radiation that it 

emits causes particles to fragment. Following "localized" exposure, the incidence of lung tumors was 

significantly increased (3/102) only at the highest exposure level (3.5x106 pCi [1.3x105 Bq] 238Pu/kg body 

weight). However, following "diffuse" exposure, a significant increase in the incidence of lung tumors 

was observed at exposures of 8.4x105 pCi (3.1x104 Bq) 238Pu/kg body weight and 9.4x105 pCi 

(3.5x104 Bq) 239Pu/kg body weight. The authors concluded that for a given lung burden of plutonium, the 

most hazardous distribution was "diffuse." 

Animal studies have shown the effects of chelation therapy on the removal of previously incorporated 

actinide elements, such as plutonium. Single intravenous injection of polymeric 239Pu (plus 237Pu as a 

tracer) into young adult beagle dogs, followed by weekly exposure to diethylenetriamine-pentaacetate 

(DTPA) as calcium salt (Ca-DTPA) or daily exposure of DTPA as zinc salt (Zn-DTPA), resulted in 14.6 or 

10.4% 237Pu excretion, respectively, vs. 7.1% plutonium excretion at 24 hours postexposure in those 

animals exposed to plutonium alone (Lloyd et al. 1978c). After 28 days, cumulative excretion (corrected 

for radioactive decay) reached 38.2% for Ca-DTPA, 49.4% for Zn-DTPA, and 12.1% for those animals 

treated with plutonium alone. The study indicated that daily exposure of beagle dogs to Zn-DTPA is more 

effective in increasing the excretion of incorporated plutonium than weekly exposure to Ca-DTPA. As 
 

 

 

 

 

 

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speculated by the authors, the enhanced plutonium excretion may have occurred as a result of calcium 

replacement in Ca-DTPA or zinc replacement in Zn-DTPA by plutonium at the cellular level. 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to plutonium than will most 

persons exposed to the same level of plutonium in the environment. Reasons may include genetic 

makeup, age, health and nutritional status, and exposure to other toxic substances (e.g., cigarette smoke). 

These parameters result in reduced detoxification or excretion of plutonium or compromised function of 

organs affected by plutonium. Populations who are at greater risk due to their unusually high exposure to 

plutonium are discussed in Section 6.7, Populations with Potentially High Exposures. 

Studies designed to assess unusual susceptibility of human populations to the effects of plutonium 

exposure were not located. Epidemiological studies typically involve healthy workers occupationally 

exposed to low levels of plutonium; these studies have not identified unusually susceptible populations. 

However, present knowledge regarding the behavior of plutonium in humans and animals provides some 

insight into populations that might exhibit increased susceptibility to the effects of plutonium exposure. 

Children may be particularly susceptible to the adverse effects of plutonium. Cells are replicating much 

more rapidly in growing children than in adults. Rapidly regenerating cells are more radiosensitive than 

slowly regenerating cells (see Appendix D). Therefore, children may be more susceptible to the radiation 

effects of plutonium than adults. 

Persons with chronic obstructive lung diseases may be more susceptible to the toxic effects of inhaled 

plutonium. Based on results from studies in rats with pulmonary emphysema, plutonium deposition 

would be decreased in a person with pulmonary emphysema, but retention would be increased (Lundgren 

et al. 1981). Therefore, a greater radiation dose would be delivered to the lungs of a person with 

emphysema or other chronic obstructive lung diseases. 

Persons who are anemic due to an iron deficiency may be more susceptible to the toxic effects of 

plutonium. Studies by DOE (1977a) demonstrated that gastrointestinal absorption of plutonium was 

4-fold higher in iron-deficient mice than in mice with normal iron levels. Therefore, persons who are iron 

deficient may absorb more plutonium (Sullivan and Ruemmler 1988). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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3.11 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to plutonium. However, because some of the treatments discussed may be experimental and 

unproven, this section should not be used as a guide for treatment of exposures to plutonium. When 

specific exposures have occurred, poison control centers and medical toxicologists should be consulted 

for medical advice. The following texts provide specific information about treatment following exposures 

to plutonium: 

Ellenhorn MJ, Schonwald S, Ordog G, et al., eds. 1997. Radiation poisoning. Ellenhorn's medical 

toxicology. Diagnosis and treatment of human poisoning. Baltimore, MD: Williams & Wilkins, 1682-

1723. 

REAC/TS. 2010a. Package insert-instructions for use: Pantetate calcium trisodium injection. Radiation 

Emergency Assistance Center/Training Site. Oak Ridge Institute for Science and Education. U.S. 

Department of Energy. http://orise.orau.gov/files/reacts/Calcium-DTPA-package-insert.pdf. May 22, 

2010. 

REAC/TS. 2010b. Package insert-instructions for use: Pantetate zinc trisodium injection. Radiation 

Emergency Assistance Center/Training Site. Oak Ridge Institute for Science and Education. U.S. 

Department of Energy. http://orise.orau.gov/files/reacts/Zinc-DTPA-package-insert.pdf. May 22, 2010. 

Viccellio P, Bania T, Brent J, et al., eds. 1998. Ionizing radiation. Emergency toxicology. 2nd ed. 

Philadelphia, PA: Lippincott-Raven Publishers, 991-996. 

Wang RY, Chiang WK. 1998. Radiation poisoning. In: Haddad LM, Shannon MW, Winchester JF, 

eds. Clinical management of poisoning and drug overdose. 3rd ed. Philadelphia, PA: W.B. Sanders 

Company, 413-425. 

Compounds used to reduce absorption and body burden are used for heavy metals in general. However, 

treatment procedures have been adapted and used for the management of plutonium exposures in the 

workplace. Treatments using chelators are well accepted. REAC/TS has tested and possesses the 

investigational new drug license for the use of calcium and zinc diethylaminetriaminepentaacetic acid 

(Ca-DTPA and ZN-DTPA) in the United States. These substances were tested on adults and their safety 

and effectiveness was established for the adult population. This was extrapolated to the pediatric 

population based on comparability of pathophysiologic mechanisms (REAC/TS 2010a, 2010b). 

Pulmonary lavage is a unique treatment for reducing the lung burden from inhaled insoluble plutonium 

compounds. It has been used only occasionally and is useful only in cases involving relatively high lung 

burdens of insoluble plutonium compounds. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

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3.11.1 Reducing Peak Absorption Following Exposure 

Topical applications of DTPA solution have been used to remove plutonium from skin and wounds after 

accidental dermal exposure (Khokhryakov et al. 2003). In extracellular fluid, the chelating agent, DTPA 

(a polycarboxylate compound), forms stable water-soluble complexes, which can be excreted in the urine 

(Durbin 1973; Taylor 1973). Both Ca-DTPA and Zn-DTPA complexes are used to decrease the risk of 

calcium and zinc depletion. Based on animal experiments, it appears that administered DTPA aerosols 

would form stable complexes with soluble forms of inhaled plutonium in the lung, thus reducing the 

amount of plutonium available for systemic deposition following absorption (Gervelas et al. 2007; 

Ménétrier et al. 2005; Sérandour et al. 2007; Stradling et al. 2000b). Bronchopulmonary lavage has been 

recommended in cases where inhalation of insoluble plutonium compounds such as 239PuO2 may result in 

doses to the lung in excess of 5 mSv within a few weeks (CEC/DOE 1992; Wood et al. 2000). 

Postexposure treatments that are effective in reducing toxic effects of radionuclides such as plutonium 

typically concentrate on decorporation (removal of plutonium from the body following absorption) and 

are discussed in Section 3.11.2. 

3.11.2 Reducing Body Burden 

Numerous animal studies have been performed to assess the effectiveness of various methods for 

decorporation of absorbed plutonium and other radionuclides. Recent summaries of results from animal 

studies and published guidance for decorporation of radionuclides such as plutonium include CEC/DOE 

(1992); Gorden et al. (2003); Ménétrier et al. (2005); Stradling et al. (2000a, 2000b); and Wood et al. 

(2000). 

DTPA has been used as a chelating agent to accelerate the urinary excretion of plutonium in humans who 

were accidentally exposed to plutonium. In one case of accidental exposure to plutonium nitrate, 

absorption into the blood from a skin wound reached 4.3% of the amount deposited on the skin; as a 

result of prompt and repeated intravenous injections of DTPA, most of the absorbed plutonium was 

excreted in the urine (Khokhryakov et al. 2003). Recent recommendations suggest using the Ca-DTPA 

complex for initial treatment and the Zn-DTPA complex for subsequent administrations (Ménétrier et al. 

2005), although Zn-DTPA has not been universally authorized for use. Prolonged use of Ca-DTPA 

results in the depletion of essential metals (particularly zinc), whereas gram quantities of Zn-DTPA can 

be administered indefinitely without such depletion. With the exception of the liver, DTPA appears to 

form complexes primarily with plutonium in soft tissues other than the liver, which exchanges more 
 

 

 

 

 

 

 

 

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rapidly with plutonium in plasma than in bone. Therefore, DTPA may be less effective in reducing bone 

plutonium levels (Durbin 1973). 

Several recent investigations have focused on methods to enhance DPTA-based decorporation of 

plutonium in laboratory animals. Encapsulation of DTPA in conventional and stealth liposomes resulted 

in increased accumulation of DTPA in liver, bone, and spleen of rats administered a single intravenous 

dose of 238Pu (as the citrate) and, presumably, increased decorporation of plutonium from these tissues 

and increased urinary excretion (Phan et al. 2004, 2006b). Previous reports had demonstrated that DTPA 

liposomes were more efficient than free DTPA at reducing plutonium deposited in bone and liver of mice 

(Rahman et al. 1973; Rosenthal et al. 1975). Pulmonary administration of a dry powder formulation of 

DTPA to rats that had been exposed (nose only) to aerosols of relatively insoluble 239PuO2 resulted in a 

3-fold increase in plutonium urinary excretion in the absence of enhanced dissolution of 239PuO2 in the 

lungs (Gervelas et al. 2007; Sérandour et al. 2007). Lifetime oral administration (via drinking water) of 

ZnDTPA to rats that had received single intravenous injection of 239Pu (as the citrate) reduced the 

incidence of osteosarcomas (Volf et al. 1999). 

Other agents have been recently tested for efficacy in decorporation of internalized plutonium. Oral or 

intravenous administration of octadentate spermine-based siderophore analogues, 3,4,3-LIHOPO and 

4,4,4-LIHOPO, appears to be much more effective than DTPA for decorporation of internalized 

plutonium in laboratory animals (Durbin et al. 2003; Ramounet-Le Gall et al. 2003). Orally-administered 

amphipathic triethylenetetraminepentaacetic acids (TT) appear to be useful in removal of plutonium and 

other actinide elements from the body, particularly when longer-term decorporation is indicated (Miller et 

al. 2006). 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects 

No information was located regarding reduction of the toxic effects of plutonium through interfering with 

mechanisms of action. 

3.12 ADEQUACY OF THE DATABASE 

Section 104(I)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of plutonium is available. Where adequate information is not 

available, ATSDR, in conjunction with the National Toxicology Program (NTP), is required to assure the 
 

 

 

 

 

 

 

 

 

 

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initiation of a program of research designed to determine the health effects (and techniques for developing 

methods to determine such health effects) of plutonium. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

3.12.1 Existing Information on Health Effects of Plutonium 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

plutonium are summarized in Figure 3-11 for radioactive plutonium. The purpose of this figure is to 

illustrate the existing information concerning the health effects of plutonium. Each dot in the figure 

indicates that one or more studies provide information associated with that particular effect. The dot does 

not necessarily imply anything about the quality of the study or studies, nor should missing information in 

this figure be interpreted as a “data need”. A data need, as defined in ATSDR’s Decision Guide for 

Identifying Substance-Specific Data Needs Related to Toxicological Profiles (Agency for Toxic 

Substances and Disease Registry 1989), is substance-specific information necessary to conduct 

comprehensive public health assessments. Generally, ATSDR defines a data gap more broadly as any 

substance-specific information missing from the scientific literature. 

Figure 3-11 graphically describes whether a particular health effect end point has been studied for a 

specific route and duration of exposure. Information on health effects in humans is very limited largely 

because exposed populations are small. Epidemiological studies of people who have been occupationally 

exposed by inhalation to plutonium have evaluated end points such as mortality, cancer, and systemic 

effects following chronic-duration exposure. No information on health effects in humans after acute- or 

intermediate-duration exposure to plutonium was located. Information on health effects from animal 

studies is more extensive than that which has been reported in epidemiological studies. These studies in 

animals provide information on health effects following both acute- and intermediate-duration inhalation 

exposure and limited information on acute oral exposure. 
 

PLUTONIUM 137 

3. HEALTH EFFECTS 

Figure 3-11. Existing Information on Health Effects of Plutonium 

Systemic 

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Existing Studies 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 138 

3. HEALTH EFFECTS 

3.12.2 Identification of Data Needs 

Acute-Duration Exposure. The possibility of brief exposure of humans to plutonium exists at 

hazardous waste sites or at accidental spill sites. However, no data are available for humans exposed 

acutely via inhalation or oral routes. Information on the toxicity of plutonium in laboratory animals 

following single high-dose inhalation exposure is extensive and indicates that the lung is the main target 

organ for inhaled plutonium. Laboratory animals exposed by this route have developed pneumonitis, 

fibrosis, metaplasia, and cancer. Acute exposure of laboratory animals to lower doses of plutonium 

would be useful to identify possible inhalation toxicity in humans. Limited information on adverse 

effects in laboratory animals following acute oral exposure indicates that the gastrointestinal tract is the 

main target organ. However, kinetic studies indicate that plutonium absorbed from the gastrointestinal 

tract is distributed to the skeleton and other tissues; therefore, other organs may also be affected. Because 

there are no data on humans, and animal data are insufficient, additional information is needed on adverse 

effects following acute exposure by the oral route. No data are available on adverse effects following 

acute dermal exposure in humans or animals. Limited information from kinetics studies in humans and 

animals indicates that there is little absorption of plutonium through intact skin. However, plutonium 

deposited in wounds is absorbed and distributes to numerous organs, including regional lymph nodes and 

the liver. Since industrial accidents resulting in plutonium-contaminated wounds are known to occur, 

additional information on adverse effects following this type of exposure would be helpful. One 

outstanding problem with all of the existing acute exposure tests in laboratory animals is that the doses 

tested are extremely high. Further single-dose studies for all exposure routes using a number of lower 

exposure concentrations would be useful in determining any dose-response relationship for adverse health 

effects. 

Intermediate-Duration Exposure. All of the major studies of cancer and other health end points in 

animals have involved lifetime follow up of animals acutely exposed to plutonium aerosols. The 

relatively long retention time of plutonium in the body produces a chronic radiation dosing of tissues that 

retain plutonium. These studies have provided the bases for absorbed radiation dose-response 

relationships for inhaled plutonium compounds (e.g., 238PuO2, 238PuO2, and 238Pu[NO3]4). Toxicokinetic 

studies, and models derived from these studies, allow predictions of the tissue distribution of plutonium 

that would be expected with repeated exposures. These can be used to predict dose-response relationships 

for repeated dosing scenarios. The feasibility of conducting studies of intermediate- or chronic-duration 

exposures to plutonium compounds should be weighed against current uncertainties in predicting the 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 139 

3. HEALTH EFFECTS 

outcomes from existing knowledge. Furthermore, repeated exposure does not alter risk; the total dose of 

alpha radiation is important, not the temporal pattern of exposure. 

Few studies of the health effects of plutonium administered to animals by the oral route have been 

reported. A single study in rats found profound effects on the gastrointestinal epithelium, consistent with 

radiation-induced injury. Given the relatively small fractional absorption of ingested plutonium (<0.1% 

of administered dose), it is very likely that repeated (or single) oral dosing studies that produce systemic 

toxicity will produce lethal effects on the gastrointestinal tract. Thus, the feasibility of conducting studies 

of intermediate- or chronic-duration oral exposures to plutonium compounds should be weighed against 

current uncertainties in predicting the outcomes from existing knowledge. 

Chronic-Duration Exposure and Cancer. Epidemiological studies of occupational cohorts with 

long-term exposure to plutonium include those established from employees at U.S. plutonium production 

and/or processing facilities (Hanford, Los Alamos, Rocky Flats), as well as facilities in Russia (Mayak) 

and the United Kingdom (e.g., Sellafield). Studies of Mayak cohorts provide evidence for an association 

between cancer mortality and exposure to plutonium. Plutonium dose-response relationships for lung 

cancer mortality have been corroborated in four Mayak studies (Gilbert et al. 2004; Jacob et al. 2005; 

Kreisheimer et al. 2003; Sokolnikov et al. 2008). Studies of U.K. and U.S. facilities have examined 

cohorts of workers who had substantially lower estimated plutonium exposures and corresponding 

internal radiation doses than the Mayak cohorts. Collectively, findings from these studies are not as 

consistent as the Mayak studies; although significantly higher incidence of cancer mortality in certain 

groups of plutonium workers has been found in some studies, higher cancer incidence and/or risks for 

tissues that received the highest plutonium radiation doses (i.e., lung, liver, bone) have not been found, 

making causal connections of these outcomes to plutonium exposure more uncertain (Brown et al. 2004; 

Carpenter et al. 1998; Gilbert et al. 1989b; McGeoghegan et al. 2003; Omar et al. 1999; Wing et al. 

2004). Uncertainties in exposures received by each of these populations are a major contributor to the 

overall uncertainty in estimates of radiation doses and dose-response relationships. For the Mayak cohort, 

an extensive collaborative effort between U.S. and Russian scientists has led to many improvements in 

both external and internal doses. The improved doses (Leggett et al. 2005) have not been used in 

published analyses, but are likely to be used future analyses (Leggett et al. 2005; Vasilenko et al. 2007). 

Continued follow up of these cohorts, using improved exposure estimates, would extend our 

understanding of dose-response relationships. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 140 

3. HEALTH EFFECTS 

All of the major studies of cancer and other health effects in animals have involved lifetime follow up of 

animals acutely exposed to plutonium aerosols. The relatively long retention time of plutonium in the 

body produces a chronic radiation dosing of tissues that retain plutonium. These studies have provided 

the bases for absorbed radiation dose-response relationships for inhaled plutonium compounds (e.g., 

238PuO2, 239PuO2, and 239Pu[NO3]4). Toxicokinetic studies, and models derived from these studies, allow 

predictions of the tissue distribution of plutonium that would be expected with repeated exposures. These 

can be used to predict dose-response relationships for repeated dosing scenarios. The feasibility of 

conducting studies of chronic-duration exposures to plutonium compounds should be weighed against 

current uncertainties in predicting the outcomes from existing knowledge. 

Few studies of the health effects of plutonium administered to animals by the oral route have been 

reported. A single study in rats found profound effects on the gastrointestinal epithelium, consistent with 

radiation-induced injury. Given the relatively small fractional absorption of ingested plutonium (<0.1% 

of administered dose), it is very likely that repeated (or single) oral dosing studies that produce systemic 

toxicity will produce lethal effects on the gastrointestinal tract. Thus, the feasibility of conducting studies 

of chronic-duration oral exposure to plutonium compounds should be weighed against current 

uncertainties in predicting the outcomes from existing knowledge. 

Genotoxicity. Although epidemiological studies do not provide conclusive evidence that plutonium 

produces genetic damage in humans, results of some studies provide suggestive evidence of dose-related 

increases in chromosomal aberrations in plutonium workers with measurable internalized plutonium. 

In vitro tests using human lymphocytes irradiated with plutonium demonstrated increases in sister 

chromatid exchange. Laboratory animals have exhibited increases in chromosomal aberrations in blood 

lymphocytes following exposure to plutonium by inhalation. Other effects in plutonium-exposed animals 

include dominant lethality and reciprocal chromosomal translocation. In vitro tests using mammalian 

cells confirm the in vivo results. The evidence is clear that plutonium is genotoxic. However, more 

extensive study of occupationally exposed individuals would be useful, and would hopefully clarify the 

equivocal reports of previous studies. Results of in vitro assessment of the potential for plutoniuminduced hprt mutations would also be useful. 

Reproductive Toxicity. No data are available regarding the reproductive toxicity of plutonium after 

inhalation, oral, or dermal exposure in either humans or animals. In laboratory animals given a single 

injection of a high dose of plutonium, significantly increased incidences of fetal death were reported and 

attributed to dominant lethality. Kinetic studies following single injection of plutonium indicate that 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 141 

3. HEALTH EFFECTS 

plutonium is distributed to the testes or ovaries of laboratory animals (Green et al. 1976, 1977) and is 

retained there for an indefinite period of time (>575 days) (Green et al. 1977; Taylor 1977). However, 

Brooks et al. (1979) noted the lack of significantly increased frequency of chromosomal aberrations in 

spermatogonia of rodents following intravenous injection of 239Pu (as the citrate) at levels high enough to 

induce marked life shortening and increased cancer incidence. Therefore, studies designed to assess the 

reproductive toxicity of internalized plutonium do not appear necessary at this time. 

Developmental Toxicity. No data are available regarding the developmental toxicity of plutonium 

after inhalation, oral, or dermal exposure in either humans or animals. However, results of kinetics 

studies in which animals were given a single injection of plutonium demonstrated that plutonium crosses 

the placenta and is retained in the fetus (DOE 1978c; Green et al. 1977). These results indicate a potential 

for adverse health effects in fetuses exposed to plutonium via their mothers; animal studies could be 

designed to investigate the developmental toxicity of internalized plutonium. 

Immunotoxicity. No data are available regarding the immunotoxicity of plutonium after inhalation, 

oral, or dermal exposure in humans. In dogs exposed to plutonium via inhalation for a single day, 

damage to lymph nodes was observed in conjunction with radiation pneumonitis (Gillett et al. 1988). 

Once plutonium particles have been deposited in the lung, macrophages play a role in the clearing 

process. In this clearing process, macrophages phagocytize plutonium particles and ultimately deposit 

them in the lymph nodes. This mechanism may lead to secondary damage to the lymph nodes and thus to 

the immune system. In dogs given a single subcutaneous injection of plutonium, damage to lymph nodes 

draining the injection site, as well as lymphopenia, were observed (Dagle et al. 1984). The studies in 

dogs, together with knowledge of the clearing process in the lung, indicate that studies designed to 

evaluate the direct toxic effects of plutonium on the immune system would be useful. 

Neurotoxicity. No studies have been performed to determine the neurotoxicity of plutonium. 

However, cells and tissues of the nervous system may be less radiosensitive than faster regenerating cells 

of the gastrointestinal tract or pulmonary epithelium. Consequently, neuronal impairment would not be 

expected. For this reason, assessment of plutonium neurotoxicity is not considered necessary at this time. 

Epidemiological and Human Dosimetry Studies. Epidemiological studies of occupational 

cohorts with long-term exposure to plutonium include those established from employees at U.S. 

plutonium production and/or processing facilities (Hanford, Los Alamos, Rocky Flats), as well as 

facilities in Russia (Mayak) and the United Kingdom (e.g., Sellafield). Studies of Mayak cohorts provide 
 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 142 

3. HEALTH EFFECTS 

evidence for an association between cancer mortality and exposure to plutonium. Plutonium doseresponse relationships for lung cancer mortality have been corroborated in four Mayak studies (Gilbert et 

al. 2004; Jacob et al. 2005; Kreisheimer et al. 2003; Sokolnikov et al. 2008). Studies of U.K. and U.S. 

facilities have examined cohorts of workers who had substantially lower estimated plutonium exposures 

and corresponding internal radiation doses than the Mayak cohorts. Collectively, findings from these 

studies are not as consistent as the Mayak studies, although significantly higher incidence of cancer 

mortality in certain groups of plutonium workers has been found in some studies, higher cancer incidence 

and/or risks for tissues that received the highest plutonium radiation doses (i.e., lung, liver, bone) have not 

been found, making causal connections of these outcomes to plutonium exposure more uncertain (Brown 

et al. 2004; Carpenter et al. 1998; McGeoghegan et al. 2003; Omar et al. 1999; Wing et al. 2004). 

Uncertainties in exposures received by each of these populations are a major contributor to the overall 

uncertainty in estimates of radiation doses and dose-response relationships. For the Mayak cohort, an 

extensive collaborative effort between U.S. and Russian scientists has led to many improvements in both 

external and internal doses. The improved doses (Leggett et al. 2005) have not been used in published 

analyses, but are likely to be used future analyses (Leggett et al. 2005; Vasilenko et al. 2007). Continued 

follow up of these cohorts, using improved exposure estimates, would extend our understanding of doseresponse relationships. Examination of these cohorts for end points other than cancer may extend our 

understanding of dose-response relationships for effects that have been consistently observed in animals 

(e.g., lymphopenia and neutropenia and potential secondary consequences of these effects on the immune 

system). Continued epidemiological studies should receive high priority. 

Biomarkers of Exposure and Effect. 

Exposure. Biomarkers of exposure to plutonium are well established. Plutonium-specific radioactivity 

from internalized plutonium can be detected by external radiation detection devices. Plutonium can also 

be detected in the blood, urine, feces, and tissue samples from individuals who have internalized 

plutonium deposits. Estimates of the extent of exposure can be made using PBBK models. Additional 

studies designed to assess biomarkers of exposure to plutonium are not necessary. 

Effect. Biomarkers of effect resulting from plutonium-released radiation are not specific to plutonium. 

Radiological effects in animals exposed to plutonium have been well documented. Additional studies of 

biomarkers of effect for plutonium are not necessary. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 143 

3. HEALTH EFFECTS 

Absorption, Distribution, Metabolism, and Excretion. For laboratory animals, detailed 

quantitative information is available regarding the absorption, distribution, and excretion of plutonium 

compounds following acute exposure by inhalation or injection. There is no information on the 

toxicokinetics of plutonium following chronic exposure to low levels, and studies in this area would be 

more applicable to human exposure situations than single exposure studies. Information concerning the 

toxicokinetics of plutonium in adult animals following oral exposure is available. However, previous 

animal studies have indicated that very little plutonium is absorbed following oral exposure. Therefore, 

studies of kinetics following oral exposure are not needed at this time. Additional studies of age-related 

differences in the toxicokinetics of plutonium would be useful. Little is known regarding the absorption, 

distribution, and excretion of plutonium compounds following dermal exposure. However, it appears that 

the skin is an effective barrier against most plutonium compounds. 

Comparative Toxicokinetics. Numerous studies of the distribution of plutonium in humans (i.e., 

autopsy studies of individuals occupationally exposed to plutonium) have shown that the general pattern 

of distribution of plutonium in humans is consistent with that observed in various animal models, with the 

highest portion of the body burden in lung (following inhalation exposures), skeletal tissues, and liver. 

Epidemiologic studies of health outcomes among workers in industries that produce and/or process 

plutonium have provided evidence for increased risk of lung, liver, and bone cancers in association with 

exposures to plutonium. These observations are consistent with the pattern of health effects observed in 

animals, particularly dogs. Additional comparative toxicokinetics studies do not appear necessary at this 

time. 

Methods for Reducing Toxic Effects. Current strategies for reducing toxic effects of plutonium 

are to hasten the elimination of plutonium from the body by administering complexing/chelating agents. 

A major challenge in applying this strategy is that Pu(IV) in the body forms insoluble precipitates within 

tissues which are unavailable for interaction with dissolved substances. Most agents that have been tested 

perform relatively poorly at mobilizing plutonium from bone, which harbors a large fraction of the body 

burden. Continued research to develop more effective agents that have low toxicity would potentially 

lead to more successful therapies for reducing toxic effects of plutonium. This research should receive 

high priority. 

Children’s Susceptibility. Data needs relating to both prenatal and childhood exposures, and 

developmental effects expressed either prenatally or during childhood, are discussed in detail in the 

Developmental Toxicity subsection above. 
 

 

 

 

 

 

 

 

 

 

PLUTONIUM 144 

3. HEALTH EFFECTS 

Studies conducted in animals have shown that exposures to plutonium that occur in young animals result 

in greater distribution of plutonium to skeletal tissues and that neonates absorb a substantially larger 

fraction of an ingested dose of plutonium than adults. These observations suggest that infants and 

children may have a higher, or altered, susceptibility to plutonium toxicity. Studies on toxicokinetics and 

health effects for exposures that occur during postnatal development would improve our understanding of 

potential vulnerabilities of children to plutonium. 

In adults, approximately 50% of the plutonium body burden resides in bone. The potential effects of 

increased mobilization of bone mineral during pregnancy, to support the development of the fetal 

skeleton, on maternal-fetal transfer of plutonium has not been examined. Studies of plutonium levels in 

offspring of mothers who carry a bone burden of plutonium would improve our understanding of potential 

pre- and postnatal exposures the might emanate from maternal-fetal transfer. 

Child health data needs relating to exposure are discussed in Section 6.8.1, Identification of Data Needs: 

Exposures of Children. 

3.12.3 Ongoing Studies 

Dr. Charles Watson, from Washington State University, and several active or retired Pacific Northwest 

National Laboratory scientists are finishing a comprehensive report on the biological effects of inhaled 

239PuO2 in beagle dogs; the completed report will be submitted to Radiation Research. 

The following ongoing studies were identified in the Federal Research In Progress database (FEDRIP 

2007). 

Dr. Richard Day, from the University of Pittsburgh, Pittsburgh, Pennsylvania, is continuing longitudinal 

follow-up health effects assessment of radiation exposures in a cohort of workers from the Mayak 

facilities in Russia. Dr. Martha Linet, from the Division of Cancer Epidemiology and Genetics, National 

Cancer Institute, is studying populations exposed to occupational radiation, which includes a cohort of 

26,000 Mayak nuclear facility workers (in the former Soviet Union) exposed to particularly high doses of 

external radiation and alpha radiation from internalized plutonium. Dr. Ray Lloyd, from the University of 

Utah, Salt Lake City, Utah, is testing recently-developed plutonium biokinetic models to human data from 

Russian nuclear workers to extend current biokinetic, dosimetric, and risk models to the human. 
 

 

PLUTONIUM 145 

4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION 

4.1 CHEMICAL IDENTITY 

Information regarding the chemical identity of plutonium and selected plutonium compounds is located in 

Table 4-1. 

4.2 PHYSICAL, CHEMICAL, AND RADIOLOGICAL PROPERTIES 

Information regarding the physical and chemical properties of plutonium and selected plutonium 

compounds is located in Table 4-2. Information regarding the radiological properties of selected 

plutonium isotopes is located in Table 4-3. The decay schemes for 239Pu and 241Pu are summarized in 

Figures 4-1 and 4-2, respectively. 

Plutonium is a member of the actinide series and is a human-made element (atomic number 94). 

Actinides are the 15 elements starting with actinium, atomic number 89, and extending to lawrencium, 

atomic number 103. All of the isotopes of the actinide elements are radioactive. Plutonium was the first 

human-made element to be synthesized in weighable amounts. 238Pu was discovered in 1940 by Seaborg 

and co-workers; it was synthesized by the bombardment of uranium with deuterons (2

H). Isotopes with 

mass numbers 228–247 have been identified for plutonium; all are radioactive. The most important 

isotope is 239Pu, which has a half-life that is sufficiently long (24,100 years) to permit its preparation in 

large amounts, making it possible to perform chemical studies. Metallic plutonium exists in six allotropic 

modifications under ordinary pressure; a seventh phase exists under high pressure. Five oxidation states, 

Pu(III), Pu(IV), Pu(V), Pu(VI), and Pu(VII), are known to exist in compounds and solution (Clark et al. 

2006). Plutonium(III) and plutonium(IV) are considered to be the reduced forms of plutonium, while 

plutonium(V) and plutonium(VI) are the oxidized forms (DOE 1987a). While the atomic mass of 

plutonium depends on the isotope, 244 is frequently listed as the mass of plutonium on periodic tables. 

244Pu is the isotope with the longest half-life. 
 

 

PLUTONIUM 146 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Plutonium and Selected Plutonium Compounds 

Characteristic Informationa 

Chemical name Plutonium Plutonium(IV) dioxide Plutonium nitride 

Synonym(s) No data Plutonium dioxide No data 

Registered trade name(s) No data No data No data 

Chemical formula Pu PuO2 PuN 

Identification numbers: 

CAS registry 7440-07-5b 12059-95-9 12033-54-4 

NIOSH RTECS No data No data No data 

EPA hazardous waste No data No data No data 

OHM/TADS No data No data No data 

DOT/UN/NA/IMDG shipping No data No data No data 

EINECS 231-117-7 235-037-3 No data 

HSDB 6465 No data No data 

NCI No data No data No data 
 

 

 

 

PLUTONIUM 147 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Plutonium and Selected Plutonium Compounds 

Characteristic Informationa 

Chemical name Plutonium nitrate Plutonium(VI) 

fluoride 

Plutonium(IV) 

Oxalatec 

Plutonium(IV) 

fluoride 

Synonym(s) Nitric acid, Plutonium No data Plutonium 

plutonium(4+) hexafluoride tetrafluoride 

salt 

Registered trade name(s) No data No data No data No data 

Chemical formula Pu(NO3)4 PuF6 Pu(C4O8)2 PuF4 

Identification numbers: 

CAS registry 13823-27-3 13693-06-6 14448-76-1c 

13278-81-4d 

13709-56-3 

NIOSH RTECS No data No data No data No data 

EPA hazardous waste No data No data No data No data 

OHM/TADS No data No data No data No data 

DOT/UN/NA/IMDG shipping No data No data No data No data 

EINECS 238-979-3e No data No data No data 

HSDB No data No data No data No data 

NCI No data No data No data No data 

a

All information obtained from ChemIDplus 2009, Lide 2008, and HSDB 2009 except where noted b

This is the generic CAS Registry Number for plutonium (unspecified form). Each isotope has an individual CAS 

Registry Number (Table 4-3) c

ChemBioFinder 2009 d

Clark et al. 2006 

e

This EINCES number refers to plutonium nitrate (CAS Registry No. 14913-29-2) with a chemical formula of 

Pu(NO3)x. (ChemIDplus 2009) 

CAS = Chemical Abstracts Service; DOT/UN/NA/IMDG = Department of Transportation/United Nations/North 

America/International Maritime Dangerous Goods Code; EINECS = European Inventory of Existing Chemical 

Substances EPA = Environmental Protection Agency; HSDB = Hazardous Substances Data Bank; NCI = National 

Cancer Institute; NIOSH = National Institute for Occupational Safety and Health; OHM/TADS = Oil and Hazardous 

Materials/Technical Assistance Data System; RTECS = Registry of Toxic Effects of Chemical Substances 
 

 

 

 

 

 


 


 

PLUTONIUM 148 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Plutonium and Selected
 

Plutonium Compounds
 

Property Informationa 

Chemical name Plutonium Plutonium dioxide Plutonium nitride 

Molecular weightb 244 276 258 

Physical description Silver, white metal 

Six allotropic 

modifications 

under ordinary 

pressurec 

Yellow-brown cubic 

crystals 

Gray cubic crystals 

Melting point 

Boiling point 

Density 

Odor 

640 °C 

3,228 °C 

19.7 g/cm3 

No data 

2,390 °C 

No data 

11.5 g/cm3 

No data 

2,550 °C 

No data 

14.4 g/cm3 

No data 

Odor threshold: 

Water No data No data No data 

Air No data No data No data 

Solubility: 

Water No data No data No data 

Organic solvents No data No data No data 

Other 

Partition coefficients: 

Soluble in 

hydrochloric acid; 

insoluble in nitric 

acid, concentrated 

hydrogen sulfide 

No data No data 

Log Kow 

Log Koc 

No data 

No data 

No data 

No data 

No data 

No data 

Vapor pressure No data No data No data 

Henry's law constant 

Autoignition temperature 

No data 

No data 

No data 

No data 

No data 

No data 

Flashpoint 

Flammability limits 

No data 

No data 

No data 

No data 

No data 

No data 

Conversion factors No data No data No data 

Explosive limits No data No data No data 
 

 

 

	 


 


 

	 

	 


 


 


 


 


 


 

PLUTONIUM	 149 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Plutonium and Selected
 

Plutonium Compounds
 

Property	 Informationa 

Chemical name Plutonium nitrate Plutonium Plutonium Plutonium 

hexafluoride oxalate tetrafluoride 

Molecular weightb No data 358 No data 320 

Physical description No data	 Red-brown Green-yellow Red-brown 

orthorhombic solidd monoclinic 

crystals crystals 

Melting point No data 51.6 °C No data 1,037 °C 

Boiling point No data No data No data No data 

Density No data 5.08 g/cm3 No data 7.1 g/cm3 

Odor No data No data No data No data 

Odor threshold: 

Water No data No data No data No data
 

Air No data No data No data No data
 

Solubility: 

Water No data No data No data No data 

Organic solvents No data No data No data No data 

Other No data No data No data No data 

Partition coefficients: No data 

Log Kow No data No data No data No data 

Log Koc No data No data No data No data 

Vapor pressure No data No data No data No data 

Henry's law constant No data No data No data No data 

Autoignition temperature No data No data No data No data 

Flashpoint No data No data No data No data 

Flammability limits No data No data No data No data 

Conversion factors No data No data No data No data 

Explosive limits No data No data No data No data 

a

All information obtained from HSDB 2009 and Lide 2008, except where noted

b

Molecular weights will be dependent on the isotope of plutonium
 c

α-phase, simple monoclinic; β-phase, body-centered monoclinic; γ-phase, face-centered orthorhombic; δ phase,
 

face-centered cubic; δ’’ phase, body-centered tetragonal; εε phase, body-centered cubic (Clark et al. 2006)
 d

Pu(C2O4)2•6H2O (CAS No. 26588-74-9) (Clark et al. 2006)
 
 

 

 

 

 

 

 

 

 

PLUTONIUM 150 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-3. Radiological Properties of Plutonium Isotopes 

Isotope 

CAS Registry 

No. Half-life 

Decay mode(s)/ 

Energy (MeV) 

Decay 

product(s) 

Specific activity 

(Ci/g) 

236Pu 15411-92-4 2.87 years 

1.5x109 years 

α/5.867 MeV 

SF/1.9x10-7 MeV 

232U 540 

237Pu 15411-93-5 45.7 days EC/0.220(99.9%) 

α/ 5.747 (0.003%) 

233U 12,100a 

238Pu 13981-16-3 87.7 years 

4.75x1010 years 

α/5.593 

SF/ 1.8x10-7 

234U 17 

239Pu 15117-48-3b 

19257-39-7c 

2.410x104 years 

8x1015 years 

α/5.244 

SF/3x10-10 

235U 0.063 

240Pu 14119-33-6 6.56x103 years 

1.14x1011 years 

α/5.255 

SF/5.7x10-6 

236U 0.23 

241Pu 14119-32-5 14.3 years 

<6x1016 years 

β-/0.0208 (99+%) 

α/5.139 (0.002%) 

SF/>2.4x10-14 

241Am 

237U 

100 

242Pu 13982-10-0 3.75x105 years 

6.77x1010 years 

α/4.983 

SF/5.5x10-4 

238U 0.0040 

243Pu 15706-37-3 4.956 hours β-

/0.582 243Am 2.6x106c 

244Pu 14119-34-7 8.00x107 years 

6.6x1010 years 

α/4.665 (99.9%) 

SF/0.12 

240U 1.8x10-5 

a

Calculated values 

b

Another CAS Registry number listed for 239Pu is 97918-67-7 c

CAS Registry Number for 239Pu4+ ion 

α = alpha particle emission; β-= negative beta emission; SF = spontaneous fission 

Sources: Baum et al. 2002; ChemIDplus 2009; Clark et al. 2006; DOE 2005a; Lide 2008 
Figure 4-1. 238Pu Decay Series 

238

Pu Pu 87.7 years 

Np 

234

U 

U 2.46x105 

years 

Pa 

230

Th 

Th 7.54x104 

years 

Ac 

226Ra Ra 1599 years 

Fr 

222Rn Rn 3.8325 days 

218

At At 1.5 sec 

214 218 Po Po 210Po Po 164 3.10 minutes 138.38 days μseconds 

214Bi 210Bi Bi 19.9 minutes 5.01 days 

214Pb 210Pb 206Pb Pb 27 minutes 22.3 years Stable 

210Tl 206Tl Tl 1.3 minutes 4.20 minutes 

 

alpha (α) decay beta (β-

) decay 

Sources: Baum et al. 2002; Lide 2005 

PLUTONIUM 151 

4. CHEMICAL AND PHYSICAL INFORMATION 
Figure 4-2. 239Pu Decay Series 

Am 

239Pu 

Pu 2.410x104  

years 

Np 

235U 

U 7.04x108 

years 

231Pa 

Pa 3.28x104  

years 

227 231 Th Th Th 18.68 1.063 days days 

227Ac Ac 21.772 years 

223Ra Ra 11.435 days 

Fr 

219Rn 

Rn 3.96 

seconds 

At 

215Po 

Po 0.001781 

seconds 

211Bi 

Bi 2.14 

minutes 

211Pb 207Pb Pb 36.1 minutes stable 

207Tl Tl 4.77 minutes 

 

alpha (α) decay beta (β-

) decay 

PLUTONIUM 152 

4. CHEMICAL AND PHYSICAL INFORMATION 

Sources: Baum et al. 2002; Lide 2005 
 

 

 

 

 

 

PLUTONIUM 153 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

5.1 PRODUCTION 

No information is available in the TRI database on facilities that manufacture or process plutonium 

because this chemical is not required to be reported under Section 313 of the Emergency Planning and 

Community Right-to-Know Act (Title III of the Superfund Amendments and Reauthorization Act of 

1986) (EPA 1998). 

Plutonium was the first human-made element to be synthesized in weighable amounts. 238Pu was 

discovered in 1940 by Seaborg and co-workers; it was synthesized by the bombardment of uranium with 

deutrons (2

H). Isotopes with mass numbers 228–247 have been identified; all are radioactive (Clark et al. 

2006). Trace amounts of plutonium are found worldwide, mostly due to fall-out from atmospheric 

nuclear testing, which ended in 1980 and released several isotopes of plutonium, including 238Pu, 239Pu, 

240Pu, and 241Pu (Clark et al. 2006; DOE 2005a; Eisenbud and Gesell 1997). Plutonium is not considered 

a naturally occurring element; however, trace amounts of 239Pu are found in naturally occurring uranium 

ores, but the amounts are in such small amounts that extraction is not practical (Clark et al. 2006; EPA 

2006b; Lide 2008). Small amounts of 244Pu exist in nature from remnants of primordial stellar 

nucleosynthesis (Clark et al. 2006). Small amounts of plutonium were produced in natural reactors, such 

as the Oklo natural reactor in Gabon, which existed about 2 billion years ago (DOE 2005a). The most 

common form of plutonium found in the environment is 239Pu, followed by 240Pu (DOE 1999a). 

Large quantities of plutonium were first produced during the 1940’s as part of the Manhattan Project in 

order to produce the atomic bomb. Production continued throughout the years of the Cold War (DOE 

2005a). The United States built and operated 14 plutonium-production reactors at the Hanford and 

Savannah River Sites starting in 1944 and ending in 1988 with the shutdown of the last reactor. A total of 

approximately 100 metric tons of plutonium was produced during this time (DOE 1996b). Currently, 

238,239, 240,241,242Pu are commercially available from Oak Ridge National Laboratory for laboratory research 

(DOE 2007a). 

Plutonium is a byproduct of nuclear energy generation. Most plutonium isotopes are produced in 

uranium-fueled reactors through neutron capture by 238U (Clark et al. 2006; Koch 2005). Approximately 

1,855 metric tons of plutonium were estimated to exist worldwide at the end of 2003. Most of the 

plutonium (1,370 metric tons) was found in irradiated fuel from nuclear power plants. A plutonium 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 154 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

production rate of 70–75 metric tons/year was estimated for reactors worldwide at the end of 2003 

(Albright and Kramer 2004; Clark et al. 2006). 

Plutonium from spent nuclear fuel is recovered by the PUREX (Plutonium, Uranium, Reduction, 

Extraction) liquid-liquid extraction process (Clark et al. 2006; Koch 2005). This process is the main 

method to separate plutonium and uranium from used reactor fuel and neutron-irradiated actinide material 

(Clark et al. 2006). The basis of the PUREX process involves the selective extraction of U(VI) and 

Pu(IV) from a nitric acid solution of dissolved irradiated fuel into an aliphatic hydrocarbon solvent that 

contains tri(n-butyl)phosphate. Most of the fission products are left in the acid solution (Clark et al. 

2006). Other processes (e.g., the bismuth phosphate process at the Hanford site) have been used to 

separate and purify plutonium from irradiated fuels; however, many of these are now of only historical 

interest (Clark et al. 2006). 

Modern plutonium metal production involves recovery and recycling of residues and scrap (Clark et al. 

2006). Plutonium metal is produced by pyrochemical processes in either centrifugal or stationary bombs. 

The major pyrochemical processes used by large facilities are bomb reduction of plutonium tetrafluoride, 

direct oxide reduction (DOR), molten salt extraction (MSE), anode casting, electrorefining (ER), and 

pyroredox. In DOR, plutonium dioxide is reduced with calcium metal to produce plutonium metal and 

calcium oxide. The MSE process reduces the amount of 241Am, which is a decay product of 241Pu, in 

plutonium metal. It also separates the more reactive elements (e.g., rare earth (lanthanide), alkali, and 

alkaline-earth metals) from the plutonium metal. In the ER process, liquid plutonium oxidizes from the 

anode ingot, which is cast from the plutonium metal derived from the MSE process, into a molten-salt 

electrolyte. The Pu(III) ions are transported through the salt to the cathode where they are reduced to the 

metal. The pyroredox process recovers plutonium metal from impure scrap material and from spent 

anode heels from the ER process (Clark et al. 2006). 

5.2 IMPORT/EXPORT 

There is no information on the import or export of plutonium. The import and export of plutonium in the 

United States is governed by the U.S. Nuclear Regulatory Commission (USNRC 2009b). 

5.3 USE 

239Pu was first used in fission weapons beginning in 1945 (DOE 2005a). In a reactor of a nuclear power 

plant, the fissioning of 235U produce two or three neutrons, which can be absorbed by 238U to produce 
 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 155 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

239Pu. The 239Pu formed can also absorb neutrons and undergo fission, which provides about one-third of 

the total energy produced in a typical commercial nuclear power plant (DOE 2005a). 238Pu is used as a 

heat source in nuclear batteries to produce electricity in devices such as unmanned spacecraft, and 

interplanetary probes (DOE 2005a; Koch 2005). Plutonium is a carefully regulated material under 

government control. Small quantities are used in research laboratories (Clark et al. 2006) and quantities 

of plutonium oxides are used in MOX (mixed oxide plutonium and uranium) fuels as an alternative to low 

enriched uranium fuel used in light water nuclear power reactors (Makhijani 1997). 236Pu and 242Pu are 

used as tracers in plutonium determinations in environmental and biological samples (Brouns 1980; DOE 

1997; Kressin et al. 1975). 

5.4 DISPOSAL 

Plutonium isotopes are classified as hazardous substances under Section 102(a) of the Comprehensive 

Environmental Response, Compensation, and Liability Act of 1980 (CERCLA), commonly known as 

Superfund. Under CERCLA, spills or discharges into the environment of plutonium isotopes of more 

than 0.01 Ci (370 MBq) (238Pu, 239Pu, 240Pu, 242Pu, and 244Pu), 1 Ci (3.7x104 MBq) (241Pu), or 1,000 Ci 

(3.7x107 MBq) (237Pu and 243Pu) must be reported immediately to the National Response Center (EPA 

2007c). The final reportable quantities for all radionuclides apply to chemical compounds containing the 

radionuclides and elemental forms regardless of the diameter of pieces of solid material (EPA 2007c). 

During 1944–1988, most nuclear fuel rods and targets irradiated in the reactors at the 14 plutoniumproduction reactors at the Hanford and Savannah River Sites were reprocessed to extract the plutonium. 

When the Department of Energy stopped reprocessing spent-fuel elements in April 1992, approximately 

2,700 metric tons of spent fuel were accumulated in 30 storage ponds. About 99% of this spent fuel is 

stored at the Hanford Site in Washington, the Savannah River Site in South Carolina, the Idaho National 

Engineering Laboratory, and West Valley in New York. Approximately 30,000 metric tons of spent fuel 

from commercial nuclear power plants are stored at more than 100 nuclear reactor sites around the United 

States (DOE 1996b). Most spent nuclear fuel is stored in specially designed pools at individual reactor 

sites around the country in 33 states (USNRC 2009a, 2009c). 

The disposal of radioactive waste is regulated by the rules of the USNRC and EPA. Spent fuel, which 

contains approximately 0.88% 239,240,241,242Pu combined, is considered high-level waste (HLW) (Murray 

2005; Murray and Fentiman 2006). Currently, the preferred method for HLW disposal is deep 

underground burial in a mined cavity; however, no facilities in the United States have been authorized for 
 

 

 

 

 

 

 

 

 

PLUTONIUM 156 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

the disposal of HLW. An alternative to burial of spent fuel is to store it for future use as fuel for nuclear 

reactors. The uranium and plutonium could be extracted from spent fuel to be used as fuel in nuclear 

power plants. 

Transuranic wastes (TRUs) contain significant amounts of plutonium or other transuranic elements. As 

of 2006, the Waste Isolation Pilot Plant (WIPP) near Carlsbad, New Mexico was the only operating 

geological disposal facility in the world; TRU has been disposed of in the WIPP since 1999 (Murray and 

Fentiman 2006). 

In 2002, Yucca Mountain was approved by the Congress and the President as the site for the nation’s first 

permanent spent nuclear fuel and high-level radioactive waste geologic repository (DOE 2007b). Most of 

the waste that may be disposed at Yucca Mountain will be spent nuclear fuel and high-level radioactive 

waste. About 90% of this waste is from commercial nuclear power plants and the rest comes from 

defense programs. Currently, this waste is stored at facilities in 43 states. By Department of Energy 

(DOE) projections, the earliest the proposed repository at Yucca Mountain could open and begin 

accepting waste is 2017; however, various steps must first be met before this can occur (EPA 2009). 

Spent fuels must be stored in water pools or in dry storage casks at nuclear plant sites until a repository is 

completed (Murray 2005). 
 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 157 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.1 OVERVIEW 

Plutonium has been identified in at least 16 of the 1,689 hazardous waste sites that have been proposed 

for inclusion on the EPA National Priorities List (NPL) (HazDat 2007). However, the number of sites 

evaluated for plutonium is not known. The frequency of these sites can be seen in Figure 6-1. Of these 

sites, all are located within the United States. 

Trace amounts of plutonium are found worldwide, mostly due to fallout from atmospheric nuclear testing, 

which ended in 1980, and released several isotopes of plutonium, including 238Pu, 239Pu, 240Pu, and 241Pu 

(Clark et al. 2006; DOE 2005a; Eisenbud and Gesell 1997). Plutonium is not naturally occurring; 

however, trace amounts of 239Pu are found in naturally occurring uranium ores, but the amounts are in 

such small amounts that extraction is not practical (Clark et al. 2006; Lide 2005). Small amounts of 244Pu 

exist in nature from remnants of primordial stellar nucleosynthesis (Clark et al. 2006). Small amounts of 

plutonium were produced in natural reactors, such as the Oklo natural reactor in the African nation of 

Gabon, which existed about 2 billion years ago (DOE 2005a). The most common form of plutonium 

found in the environment is 239Pu, followed by 240Pu (DOE 1999a). 

Large quantities of plutonium were first produced during the 1940s as part of the Manhattan Project in 

order to produce the atomic bomb. Production continued throughout the years of the Cold War (DOE 

2005a). The United States built and operated 14 plutonium-production reactors at the Hanford, 

Washington and Savannah River, South Carolina sites starting in 1944 and ending in 1988 with the 

shutdown of the last reactor. A total of approximately 100 metric tons of plutonium was produced during 

this time (DOE 1996b). 

The principal plutonium isotopes used in military and nonmilitary applications are 238Pu and 239Pu. These 

two isotopes are used because of their ease of production and their relatively long half-lives. 238Pu is used 

as a heat source in nuclear batteries to produce electricity in devices such as unmanned spacecraft, and 

interplanetary probes (DOE 2005a; Koch 2005). 239Pu and 240Pu are produced in nuclear power plants as 

a product of nuclear fission as well as in production facilities for use in nuclear weapons. 

Possible sources of plutonium to the environment include: past atmospheric weapons testing, accidents 

involving weapons transport, accidents involving failed space launches of satellites, operating nuclear 

reactors and radioisotope generators, fuel processing and reprocessing activities, and fuel transport 
PLUTONIUM 158 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-1. Frequency of NPL Sites with Plutonium and Selected Isotopes 

Contamination 
 

 

 

 

 

 

 

 

 

 

PLUTONIUM 159 

6. POTENTIAL FOR HUMAN EXPOSURE 

(NEA/OECD 1981). Plutonium is a byproduct of nuclear energy generation. It is produced in uraniumfueled reactors through neutron capture by uranium-238 (238U) (Clark et al. 2006; Koch 2005). 

Approximately 1,855 metric tons of plutonium were estimated to exist worldwide at the end of 2003, with 

1,370 metric tons found within used fuel from nuclear power plants. A plutonium production rate of 70– 

75 metric tons/year was estimated for reactors worldwide at the end of 2003 (Albright and Kramer 2004; 

Clark et al. 2006). 

The main sources of plutonium in the environment are releases from research facilities, past atmospheric 

nuclear weapons testing, waste disposal, nuclear weapons production facilities, and accidents (DOE 

1999a). Atmospheric testing of nuclear weapons, which ended in 1980, is the source of most of the 

plutonium in the environment worldwide, which released approximately 10,000 kg of plutonium (DOE 

2005a). Nuclear reactor accidents (e.g., the Chernobyl reactor in 1986) and other accidents involving 

non-U.S. nuclear-powered submarines or nuclear weapons have also released plutonium into the 

environment. The total amount of plutonium released during these accidents is small on a global scale as 

compared to the amount of plutonium released during atmospheric nuclear weapons testing. Plutonium 

released to the atmosphere reaches the earth's surface through wet and dry deposition to the soil and 

surface water. Once in these media, plutonium can sorb to soil and sediment particles or bioaccumulate 

in terrestrial and aquatic food chains. 

6.2 RELEASES TO THE ENVIRONMENT 

Concentrations of plutonium are generally expressed in terms of activity, either in the curie (Ci) or the SI 

unit, the becquerel (Bq), where 1 Ci=3.7x1010 Bq=0.037 TBq or 1 Bq=2.7x10-11 Ci=27 pCi. Activities 

may be converted into mass units using the specific activities for each plutonium isotope. Specific 

activities for various plutonium isotopes are provided in Table 4-3. Throughout this chapter, the units 

used to express concentration or intake of plutonium are generally the same units reported by the authors, 

which are followed by converted units in parenthesis. However, in some cases, the units originally 

reported by the authors may be converted (e.g., from Bq to mBq or from nCi to pCi) for ease of 

comparison of concentrations within a section. Common metric prefixes are provided in Table 6-1. 

Possible sources of plutonium to the environment include: atmospheric weapons testing, accidents 

involving weapons transport, operating nuclear reactors and radioisotope generators, fuel processing and 

reprocessing activities, and fuel transport (NEA/OECD 1981). However, plutonium or plutonium 
PLUTONIUM 160 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Common Metric Prefixes 

Factor Prefix Symbol Factor Prefix Symbol 

10-18 atto a 102 hecto h 

10-15 femto f 103 kilo k 

10-12 pico p 106 mega M 

10-9 nano n 109 giga G 

10-6 micro μ 1012 tera T 

10-3 milli m 1015 peta P 

10-2 1018 centi c exa E 
 

 

 

 

 

 

 

PLUTONIUM 161 

6. POTENTIAL FOR HUMAN EXPOSURE 

compounds are listed on the Superfund Amendments and Reauthorization Act (SARA) Section 313 toxic 

chemical list and, therefore, are not included in the Toxics Release Inventory (TRI). 

6.2.1 Air 

The main sources of plutonium in the environment are releases from research facilities, nuclear weapons 

testing, waste disposal, nuclear weapons production facilities, and accidents (DOE 1999a). Areas 

contaminated with plutonium, such as the Nevada Test Site or other national facilities, could release 

plutonium if the contaminated soils are re-suspended during windy or fire conditions (e.g., Cerro Grande 

fire in New Mexico), surface cleanup, construction, vehicular travel, or other disturbances to the 

contaminated soil (DOE 2005b). 

Atmospheric testing of nuclear weapons, which ended in 1980, is the source of most of the plutonium in 

the environment worldwide, which released approximately 10,000 kg of plutonium (DOE 2005a). 

Approximately 320 kCi (1.2x104 TBq) of 239,240Pu and 9 kCi (300 TBq) of 238Pu have been released to the 

atmosphere by nuclear tests and distributed worldwide (Eisenbud and Gesell 1997). Concentrations of 

transuranics introduced into the environment through underground test venting, accidents involving U.S. 

nuclear weapons, and releases during weapon production operations have been negligible in comparison 

with those released during atmospheric testing of nuclear explosives in the 1960s (DOE 1980g). 

In April, 1964, a Transit Navigational Satellite was launched in California with a payload that included a 

Satellite for a Nuclear Auxiliary Power Generator (SNAP-9A) containing 17 kCi (630 TBq) of 238Pu. The 

rocket system failed and the satellite reentered the atmosphere in the Southern Hemisphere and burned 

over the Indian Ocean at an altitude of about 50 km (Harley 1980). The destruction of the SNAP-9A 

resulted in the largest single release of 238Pu to the atmosphere, primarily in the form of very small oxide 

particles (Harley 1980). An estimated 37 TBq (1 kCi) of 239,240Pu was released during the Chernobyl 

accident, April 26, 1986 (Clark et al. 2006). The only area around Chernobyl after the April 1986 

accident with plutonium levels exceeding 4 kBq/m2 was located within the 30-km zone. 239,240Pu 

deposition densities ranged from 0.07 to 0.7 kBq/m2

 in the Gomel-Mogilev-Bryansk area, 200 km northnortheast of the reactor, and from 0.07 to 0.3 kBq m2 in the Kaluga-Tula-Orel area, 500 km northeast of 

the reactor. At Korosten, located about 115 km southwest of the Chernobyl power plant, the 239,240Pu 

deposition density due to the Chernobyl accident was about 0.06 kBq/m2

, 4–8 times lower than the 

239,240Pu deposition density from global fallout (UNSCEAR 2000b). Garger et al. (2006) reported that the 
 

 

 

 

 

 

 

 

 

PLUTONIUM 162 

6. POTENTIAL FOR HUMAN EXPOSURE 

total flow of activity through the gaps of the shelter of the Chernobyl reactor measured during 1996–1999 

was 8.64x109 Bq/year (0.234 Ci/year); 0.4% of this was due to 239,240Pu. 

Research facilities and plants have also released plutonium to the atmosphere. For example, the 

Department of Energy (DOE) Mound Plant in Miamisburg, Ohio, released about 30 Ci (1x1012 Bq) to the 

atmosphere from the beginning of its operation through 1976 (NEA/OECD 1981). The vast majority of 

these releases occurred in the 1960s. By 1972, total 238Pu air releases were about 0.1% of the quantity 

released in 1967, and they have been much lower than that in the years since 1972 (Agency for Toxic 

Substances and Disease Registry 1998). A commercially operated reprocessing plant in West Valley, 

New York, has reportedly released 5x10-3 Ci (2x10-8 Bq) of plutonium to the atmosphere over the course 

of 6 years (NEA/OECD 1981). The Savannah River Site, which produced plutonium and tritium as well 

as other nuclear materials, released 1.4x1011 Bq (3.8 Ci) of plutonium to air during the period of 1954– 

1989 (Carlton et al. 1996). An estimated total air emissions from the Nevada Test Site (NTS) of 0.29 Ci 

(1.1x1010 Bq) 239,240Pu was reported for calendar year 2004 (DOE 2005b). Air samplers in two areas of 

the NTS showed that 239,240Pu is routinely detected due to blowing contaminated soil; however, 

concentrations are only slightly above minimum detectable concentrations. Air sampling in the past has 

shown that 238Pu is not detected in air at the NTS (DOE 2005b). 

Small amounts of various long-lived radionuclides, including 238Pu, 239,240Pu, and 241Pu, are still released 

to the environment through state and federally permitted release points at the Hanford Site. Generally, the 

radionuclide emissions in these releases are near concentrations that are indistinguishable from 

background radionuclide concentrations that occur naturally or are from fallout (DOE 2005c). From 1994 

to 2004, releases of 239,240Pu to air from the Hanford Site ranged from 6x10-4 Ci (2x107 Bq) in 1998 to 

1x10-4 Ci (4x106

 Bq) during 2002–2004. During 2004, releases of 238Pu to air ranged from 1.1x10-8 to 

2.7x10-6 Ci (407–1.0x105 Bq) in three areas at the Hanford Site. Releases of 241Pu to air were 

1.5x10-4 and 5.3x10-4 Ci (5.6x106

 and 2.0x107 Bq) at two areas, and not detected at two other areas. 

Releases of 239,240Pu, which included gross alpha data, ranged from 1.4x10-7 to 6.7x10-5 Ci (5.2x103

– 

2.5x106

 Bq) at five areas at the Hanford Site during 2004 (DOE 2005c). 

Plutonium has been identified in 9 air sample collected from 1,689 current or former NPL hazardous 

waste sites where it was detected in some environmental media (HazDat 2007). 
 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 163 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.2.2 Water 

Fallout from atmospheric weapons testing, accidents involving nuclear weapons, planned as well as 

accidental reactor effluent releases, and disposal of radioactive wastes are all means by which plutonium 

can be introduced into water systems (Harley 1980; NEA/OECD 1981). In a typical 1,000 megawatt 

electric (MWe) light water reactor in a nuclear power plant, about 200 kg of plutonium [equivalent to 

1.3x104 Ci (4.8x1014 Bq), one curie of 239Pu=16 g] are generated per year of operation (DOE 1980g; 

NEA/OECD 1981). Contaminated cooling water containing plutonium from nuclear production facilities 

may have been discharged into oceans or rivers. If release occurs from waste containers, buried 

radioactive wastes may migrate or seep into groundwater (NEA/OECD 1981). As an example of plant 

emissions, the Mound Plant in Miamisburg, Ohio, discharged a total of about 0.5 Ci (2x1010 Bq) 238Pu 

into a river near the site from the beginning of its operation through 1976 (NEA/OECD 1981). The 

Savannah River Site, South Carolina, which produced plutonium and tritium as well as other nuclear 

materials from 1954 to 1988, released 2.3x1010 Bq (0.62 Ci) of plutonium to site streams and ponds 

during the period of 1954–1989 (Carlton et al. 1996). From 1954 to 1988, the plutonium and uranium 

extraction (PUREX) process was used in the F-area of the Savannah River Site to recover 239Pu, as well as 

other radionuclides, from irradiated 238U. During this time, the total reported release of 239Pu to the 

seepage basin at the F-area was 2.09x1011 Bq (5.65 Ci) (Dai et al. 2002). 

Liquid effluent containing various radionuclides is discharged from some of the facilities at the Hanford 

Site. During 2004, 5.5x10-6 Ci (2.0x105 Bq) of 239,240Pu were released to the Columbia River from the 

100 areas at the Hanford Site (DOE 2005c). 

In January, 1968, while attempting to make an emergency landing, a U.S. military aircraft with four 

nuclear weapons on board crashed in Thule, Greenland. The impact resulted in detonation of the high 

explosives in all four nuclear weapons aboard. The oxidized plutonium was dispersed by both the 

explosion and the fire involving the fuel in the jet (Harley 1980). Amounts of plutonium released to the 

air in this accident have been estimated at 24 Ci (8.9x1011 Bq) of insoluble plutonium (NEA/OECD 

1981). The maximum concentration of plutonium in ocean sediments was found 1 km from the point of 

impact. The sediment-bound plutonium was found to migrate both downward in the sediment column 

and horizontally from the point of impact. The concentrations decreased with distance from the point of 

impact. 
 

 

 

 

 

 

 

 

 

 

PLUTONIUM 164 

6. POTENTIAL FOR HUMAN EXPOSURE 

Sediments can act as both a repository for and a source of waterborne plutonium. Atmospheric fallout 

reaching surface water can settle in the sediments. The plutonium in the ocean sediments at Bikini Atoll, 

for example, was found to be resuspended and released to the bottom waters (DOE 1980b). In a 

freshwater waste pond at the Hanford reactor, plutonium was found to be bound to the sediments and was 

not available for uptake by plants or animals in the pond (DOE 1980f). The difference between the 

observations in the two ecosystems may be due to the dynamic nature of the ocean water near Bikini Atoll 

versus the relatively static nature of a waste water pond. 

On May 4, 2000, a prescribed burn grew out of control in Cerro Grande, New Mexico near the Los 

Alamos National Laboratory (LANL), which burned about 7,400 acres of forest on the LANL site (DOE 

2004). The burned landscapes resulted in increased storm runoff and transport of various contaminants, 

which included plutonium and other radionuclides by runoff and erosion in the canyons traversing LANL. 

Compared with amounts measured in the 5 years before the fire, the yearly average amount of 

radioactivity carried by storm runoff flows beyond LANL downstream boundary in the two to three years 

following the fire increased about 55 times for 239,240Pu. The increases were due mostly to erosion of 

LANL contaminated sediments. Annually, the estimated postfire transport of 239,240Pu downstream ranged 

from 2 millicuries (mCi) in the first year after the fire to 28 mCi in year 1 and a total of about 64 mCi of 

239,240Pu was transported downstream in storm runoff through the 4-year period from 2000 through 2003 

(DOE 2004). 

Plutonium has been identified in 6 groundwater and 7 surface water samples collected from 1,689 NPL 

hazardous waste sites, where it was detected in some environmental media (HazDat 2007). 

6.2.3 Soil 

Plutonium has been detected in extremely small amounts as a naturally occurring constituent of some 

minerals and ores. Uranium and thorium ores in Canadian pitchblende, Belgium Congo pitchblende, 

Colorado pitchblende, Brazilian monazite, and North Carolina monazite have been found to contain 244Pu 

at a weight ratio of up to 9.1x10-12 kg plutonium/kg ore (Leonard 1980). 

Soils may become contaminated from fallout associated with nuclear weapons tests, such as those 

conducted at the Trinity Site in southern New Mexico, the Pacific Proving Ground at the Enewetak Atoll, 

and the Nevada Test Site or with accidental, nonnuclear detonation of nuclear weapons, such as occurred 

at Palomares, Spain. Research facilities, such as the Los Alamos National Laboratory, Los Alamos, New 
 

 

 

 

 

 

 

PLUTONIUM 165 

6. POTENTIAL FOR HUMAN EXPOSURE 

Mexico, may release treated radioactive wastes under controlled conditions. Production facilities, such as 

the Hanford and Savannah River Plants, and experimental reactor stations, for example, the Idaho 

National Engineering Laboratory, Idaho Falls, Idaho, also released treated plutonium-bearing radioactive 

wastes under controlled conditions to soils (Hanson 1975). 

Atmospheric weapons testing fallout has been a global source of transuranics, including plutonium, in 

soils (Agency for Toxic Substances and Disease Registry 1999; Harley 1980; NEA/OECD 1981). The 

Centers for Disease Control and Prevention (CDC) has estimated that the total deposition of plutonium 

from weapons tests at the Nevada Test Site was 1.8x104

 Ci (6.7x1014 Bq) (CDC 2005). 

During 2004, only facilities in the 200 Areas of the Hanford Site discharged radioactive liquid effluents to 

the ground at a State-Approved Land Disposal Site. Releases of 238Pu and 239,240Pu were 6.9x10-6 and 

7.5x10-6 Ci (2.5x105

 and 2.8x105 Bq), respectively (DOE 2005c). 

Several of the major nuclear facilities in the United States use plutonium and some of these have released 

plutonium to the environment. These releases have taken place at remote sites and generally have not 

been measurable outside the plant property. Approximately 2 Ci (7x1010 Bq) of plutonium have been 

disposed in the Los Alamos National Laboratory canyon waste disposal sites (Harley 1980). The 

Savannah River Plant, Aiken, South Carolina, has released a total of 5 Ci (2x1011 Bq) of plutonium to 

local soil (Harley 1980). Leakage of stored waste released between 10–100 Ci (3.7x1011–3.7x1012 Bq) of 

plutonium to the soil over a period of several years at the Rocky Flats facility, Golden, Colorado (DOE 

1980g). A break in a waste transfer line caused the release of about 300 Ci (1x1013 Bq) of 238Pu at the 

Mound Plant, Miamisburg, Ohio, in 1969 (DOE 1980g). 

A fire on May 11, 1969, occurred at the plutonium processing facility at Rocky Flats, which caused 

concerns about possible contamination of the surrounding areas (Agency for Toxic Substances and 

Disease Registry 2005). Studies showed that while trace amounts of plutonium were present in soil, the 

distribution was not consistent with the wind direction at the time of the fire. It was determined that the 

major source of plutonium contamination was leakage from drums of machine oil containing plutonium 

that were being stored in an outdoor area (Eisenbud and Gesell 1997). 

Another source of soil contamination at Rocky Flats was the leakage of plutonium-contaminated oil. 

Plutonium was present as the dioxide when it was released. The dioxide was then adsorbed to the soil. 

Fugitive dust emissions caused plutonium-contaminated soil to be distributed away from the spill. Most 
 

 

 

 

 

 

 

 

 

 

PLUTONIUM 166 

6. POTENTIAL FOR HUMAN EXPOSURE 

of the plutonium remained on the surface, although some was released and migrated downward through 

the soil column (Little and Whicker 1978). 

A U.S. military aircraft carrying four nuclear bombs collided with a tanker aircraft during refueling in 

Palomares, Spain, in January, 1966. The bombs broke free of the airplane and the high explosive in two 

of the weapons detonated when the bombs hit the ground. Initial surveys showed plutonium 

concentrations of 3x10-5 Ci/m2

 (1x106 Bq/m2), in the form of a finely powdered dioxide, were spread over 

2 hectares (20,000 m2

) (Harley 1980). A large amount of the contaminated soil was brought back to the 

Savannah River facility in the United States for decontamination and the soil with low-level 

contamination was plowed to a depth of 30 cm (Harley 1980). 

Plutonium has been identified in 6 soil and 9 sediment samples collected from 1,689 NPL hazardous 

waste sites, where it was detected in some environmental media (HazDat 2007). 

6.3 ENVIRONMENTAL FATE 

6.3.1 Transport and Partitioning 

Plutonium enters the environment primarily through releases to the atmosphere or direct discharge to 

ponds, streams, or oceans. Emissions to the atmosphere will result in plutonium fallout. In the case of 

weapons testing, approximately one-fifth of the plutonium released falls on the test site (Harley 1980). 

The rest is carried in the atmosphere, adsorbed to particulate matter and is transported back to earth via 

dry or wet deposition. Once plutonium is deposited either on the land or surface water, sorption to soils 

or sediments is the primary environmental fate of plutonium. A small fraction of plutonium reaching the 

soil will become solubilized either through chemical or biological processes, depending upon its chemical 

form. In soluble form, plutonium can either migrate in groundwater or surface water or be available for 

uptake into plants; colloidal forms of plutonium are not as available for uptake as soluble forms. 

Atmospheric releases of plutonium occurred as a result of former atmospheric nuclear weapons testing or 

routine or nonroutine nuclear reactor operations and fuel reprocessing. The rate at which plutonium is 

removed from the atmosphere depends on the chemical and physical properties of the particles, as well as 

the meteorological conditions. The larger the particles, the faster fallout will occur. The particle size 

expected to be released from either of the above mentioned sources ranges from 0.3 to 1.1 μm. At the 

highest altitudes, aerosols in the atmosphere descend by gravity; at lower levels, they are transported with 

the general air movement (UNSCEAR 2000a). In the lower stratosphere, the mean residence time of 
 

 

 

 

 

 

 

 

 

 

PLUTONIUM 167 

6. POTENTIAL FOR HUMAN EXPOSURE 

aerosols range from 3–12 and 8–24 months in the polar and equatorial regions, respectively. Removal 

half-times from the upper atmosphere to the next lower region range from 6 to 9 months and removal 

half-times from the high atmosphere were found to be 24 months (UNSCEAR 2000a). The global fallout 

rate of 238Pu, predominantly from the SNAP-9 accident, as determined by Harley (1980), was 

0.002 pCi/m2

/day (7.4x10-5 Bq/m2/day) based on plutonium levels measured in surface soils. The global 

deposition rate of 239,240Pu was equal to 0.03 pCi/m2

/day (1x103 Bq/m2/day) (Corey et al. 1982). 

Plutonium deposited on soil surfaces may be resuspended in the atmosphere especially in areas that have 

low soil moisture levels, such as the Nevada Test Site. In drier areas, the levels of ambient airborne dust 

are expected to be higher than in areas with normal rainfall (Harley 1980). The highest concentrations of 

plutonium are likely to be found in the fine silt-clay particle size range. Particles of this size tend to be 

transported the farthest distance by wind and water (WHO 1983). 

The transport and partitioning of plutonium in soils depends on the form of the compound. The solubility 

of plutonium depends on the properties of the soil, the presence of organic and inorganic complexing 

agents, the form of plutonium that enters the soil environment, and the presence of soil microorganisms 

(Bell and Bates 1988; DOE 1980c; Kabata-Pendias and Pendias 1984; WHO 1983). Plutonium fallout 

from the atmosphere, for example, tends to be deposited primarily as the insoluble dioxide (DOE 1987b; 

Harley 1980). The majority of plutonium remains within the top few centimeters of the soil surface as the 

dioxide form (WHO 1983). Microorganisms can change the oxidation state of plutonium, thereby either 

increasing or decreasing its solubility. 

The types of organic and inorganic materials disposed of in waste streams can also affect the mobility of 

plutonium. For example, in some waste streams, such as the Hanford location, the chelating agent 

ethylenediaminetetraacetate (EDTA) was used during the production and processing of plutonium and 

was widely present in the mixed wastes at the site (Smith and Amonette 2006). EDTA forms complexes 

with plutonium, which will increase its mobility in soils and also possesses the ability to adsorb onto soil 

itself, thus reducing the number of available surface sites at which plutonium can adsorb to. 

Plutonium will migrate in soils as the hydrolyzed ion or as a complex, formed with organic or inorganic 

acids. Mewhinney et al. (1987) found that particles subjected to wetting and drying, such as those found 

on the soil surface, released more plutonium than soils continually immersed in a solvent, such as that 

found in lakes. This phenomenon is attributed to the formation of a soluble dioxide layer on the particle's 

surface during the drying phase. Soil organisms have also been found to enhance the solubility of 
 

 

 

 

 

 

 

 

PLUTONIUM 168 

6. POTENTIAL FOR HUMAN EXPOSURE 

plutonium (DOE 1987b). Once plutonium enters the soluble phase, it then becomes available for uptake 

by plants. The plutonium(IV) oxidation state is found in plants due to the ability of the environment to 

hydrolyze it (DOE 1987c; Garland et al. 1981). Cataldo et al. (1987) postulate that reduction of the 

higher oxidation states, such as plutonium(VI), occurs prior to absorption/transport across the root 

membrane. 

In aqueous solution, plutonium typically exists in one of four common oxidation states and the 

environmental fate of plutonium in surface waters is dependent upon both the oxidation state and the 

nature of the suspended solids and sediments contained in the water column. Under reducing conditions, 

plutonium(III) and plutonium(IV) are the most stable oxidation states, with plutonium(III) dominating at 

pH values <8.5 and plutonium(IV) dominating at pH values >8.5 (Smith and Amonette 2006). Under 

oxidizing conditions, plutonium(IV), plutonium(V), and plutonium (VI) oxidation states tend to form at 

pH values >4. The plutonium(V) and plutonium(VI) oxidation states typically form more soluble 

complexes and possess greater mobility than the plutonium(III) and plutonium(IV) complexes. Humic 

materials (naturally occurring organic acids) were found to reduce plutonium(V) to plutonium(IV) in 

seawater. This was followed by adsorption of plutonium(IV) onto iron dioxides and deposition into the 

sediments (DOE 1987h). 

The partitioning of plutonium from surface water to sediments in freshwater and marine environments 

depends on the equilibrium between plutonium(IV) and plutonium(V), and the interaction between 

plutonium(IV) in solution and plutonium sorbed onto sediment particle surfaces (NCRP 1984). Sorption 

onto marine clays was found to be largely irreversible (Higgo and Rees 1986). Higgo and Rees (1986) 

also found that the initial sorption of plutonium onto clays was effective in removing most of the 

plutonium species that would be able to sorb onto the clay. When sorption to carbonate marine sediments 

was investigated, it was found that some desorption from the surface would also occur. This behavior 

was due to the presence of plutonium carbonate complexes on the sediment surfaces which were sorbed 

less strongly than plutonium dioxide complexes (Higgo and Rees 1986). In fact, the formation of 

plutonium complexes with organic carbon causes plutonium to remain in solution as a complex (NCRP 

1984). Plutonium can become adsorbed onto colloids, small (micrometer) particles that are often found in 

groundwater. Adsorption to colloidal particles can enhance the mobility of plutonium in groundwater 

(DOE 1999a). 
 

 

 

 

 

 

 

PLUTONIUM 169 

6. POTENTIAL FOR HUMAN EXPOSURE 

Carroll et al. (1999) reported distribution coefficients (Kd) ranging from 3x104 to 8x104 for plutonium in 

bottom sediments from the Kara Sea. The International Atomic Energy Agency (IAEA)-recommended 

Kd value for sediments is 1x105 for plutonium (Carroll et al. 1999; IAEA 2004). 

Plutonium can be taken up from various environmental media into plants and animals. The primary 

factor that governs whether plutonium in soil can be taken up by plants roots is the presence of soluble 

forms of plutonium in adjacent subsurface soils. The highest concentrations of plutonium in plants are 

generally found in the roots where plutonium is present as a surface-absorbed plutonium complex, a 

stabilized complex, or a soluble plutonium complex (Garland et al. 1981). Concentration ratios 

(concentration of plutonium per gram of dry plant tissue divided by concentration in the soil) of 1x10-6– 

2.5x10-4 were calculated based on radioisotope experiments in soybean plants grown in controlled 

environments. The stems and leaves were found to possess lower overall concentrations of plutonium 

than the roots, but higher concentrations of soluble plutonium (Cataldo et al. 1987). 

In studies on orange trees, Pinder et al. (1987) found that 238Pu was deposited on the leaf or soil surface, 

remained there, and that no measurable quantities were transferred to the fruits. Grain crops grown near 

the Savannah River Plant, Aiken, South Carolina, were found to contain higher concentrations of 

plutonium the closer to the facility they were grown. During harvesting, plutonium from soils or straw 

was resuspended and mixed with the crop. Plutonium in vegetable crops grown at Oak Ridge National 

Laboratory, Oak Ridge, Tennessee, contained higher plutonium concentrations in the foliage biomass 

than in the fruit. Peeling of potatoes and beets removed 99% of the residual plutonium (DOE 1980d). 

The Mayak Production Association (PA), which processed weapons-grade plutonium from 1949 to 1952, 

discharged radioactive wastes into the Techa River, which belongs to the Kara Sea basin of the Arctic 

Ocean. Akleyev et al. (2000) reported plutonium accumulation coefficients ranged widely from 2x10-4 to 

0.8 for vegetation samples the area of the Techa River. The authors noted that plutonium accumulation is 

highly species-dependent. 

Plutonium uptake by grazing herbivores was predominantly located within the animal's pelt and 

gastrointestinal tract (DOE 1980i). Rodents studied near the Los Alamos and Trinity sites in New 

Mexico support this claim. DOE (1980i) found no evidence of bioconcentration through the food chain 

from soil to plants to rodents. They concluded that soil was the source of plutonium in rodents. In 

contrast, a study by Sullivan et al. (1980) showed that rodents absorbed more 238Pu when it was 

incorporated into alfalfa (by growing it in soil containing plutonium) than when it was administered in the 
 

 

 

 

 

 

 

 

 

PLUTONIUM 170 

6. POTENTIAL FOR HUMAN EXPOSURE 

inorganic form (Sullivan et al. 1980). This study suggests that plutonium bound to organic compounds 

may have increased availability. 

Plutonium was found to bioaccumulate in aquatic organisms, primarily at the lower end of the food chain. 

The bioconcentration factors (i.e., the amount of the chemical found in the organism divided by the 

concentration in the surrounding water over the same time period) were 1,000 for mollusks and algae, 

100 for crustacea, and 10 for fish (WHO 1983). Plutonium is concentrated in the bones of fish rather than 

in muscle tissues, as seen by whole fish to muscle tissue ratios of 40:1 (NCRP 1984). Swift (1992) 

reported that whole-body concentration factors for juvenile lobsters did not exceed 250 over an exposure 

period of 49 days in seawater containing 237Pu. 237Pu was found to accumulate mostly in the gills and 

exoskeleton. 

6.3.2 Transformation and Degradation 

Plutonium isotopes are transformed by radioactive decay to either uranium or americium based on the 

isotope, but as an element, plutonium cannot degrade. The most common isotopes of plutonium are 238Pu, 

239Pu, 240Pu, and 241Pu with respective half-lives of 87.7, 2.410x104

, 6.56x103, and 14.4 years (Lide 2005). 

The half-lives for 239Pu and 240Pu are very long, and only a small amount of transformation would occur 

over a human lifetime. 241Pu has a much shorter half-life and would undergo transformation over a 

human lifetime. 241Pu decays into 241Am, which has a half-life of 432.7 years and is also an alpha particle 

emitter (Baum et al. 2002). Information on the radioactive transformation of various plutonium isotopes 

can be found in Table 4-3. 

6.3.2.1 Air 

Plutonium does not undergo transformation processes in the air beyond those related to radioactive decay. 

Radioactive decay in air is not significant for those plutonium isotopes with long half-lives compared 

with residence times in the atmosphere. For plutonium injected into the atmosphere from a weapon 

detonation, the residence half-time of particulate debris in the troposphere of approximately 30 days 

(Bennett 1979; Nero 1979). 

6.3.2.2 Water 

The solution chemistry of plutonium is complex due to the ease with which it can undergo oxidationreduction reactions and its extreme oxophilicity (tendency to bind oxygen) of plutonium cations (Clark et 
 

 

 

 

 

 

 

 

 

 

PLUTONIUM 171 

6. POTENTIAL FOR HUMAN EXPOSURE 

al. 2006). Oxidation states (III)–(VII) can be prepared and stabilized in solution under appropriate 

conditions. The lower oxidation states (III and IV) are more stable under acid conditions; the higher 

oxidation states (VI and VII) are more stable under alkaline conditions. Pu(IV) is the most stable and 

most studied oxidation state, followed by (III) and (VI). Pu(V) and Pu(VI) cations are strong Lewis acids 

and hydrolyze in solution to form trans dioxo cations, PuO2

+

 and PuO2

2+, which are commonly referred to 

as plutonyl ions. The reduction potentials that couple the four most common oxidation states of 

plutonium (III, IV, V, VI) in acidic solution are very close in magnitude and are close to 1 volt vs. the 

standard hydrogen electrode. In addition the kinetics oxidation-reduction reactions between these 

oxidation states are such that multiple oxidation states of plutonium can exist in aqueous solution under 

appropriate conditions (Clark et al. 2006; EPA 2006b). 

The important chemical transformation process in surface water is the oxidation or reduction of 

plutonium. In waters with low suspended solids, plutonium is generally found in oxidized forms, 

dissolved in the water. In waters with high suspended solids, plutonium is generally reduced and sorbed 

onto either suspended solids or sediments (DOE 1987a, 1987h; Higgo and Rees 1986). 

Plutonium behaves differently than many other inorganic elements in that it can exist simultaneously in 

four oxidation states over a range of pH values. Under acidic conditions, the nature of the complexing 

ligands present in solution will influence the oxidation state of plutonium. The presence of fulvic acid (a 

naturally occurring organic acid) facilitates the reduction of plutonium(IV) to plutonium(III), especially 

below pH 3.1. The reduction of the higher oxidation states appears to be even less dependent on pH, 

especially below pH 6 (IAEA 1976d). 

6.3.2.3 Sediment and Soil 

Plutonium found in soils may undergo the same oxidation/reduction reactions described for surface 

waters in places where soil contacts water. In addition to oxidation/reduction reactions, plutonium can 

react with other ions in soil to form complexes. These complexes may then be absorbed by roots and 

move within plants; however, the relative uptake by plants is low. In plants, the complex can be degraded 

but the elemental plutonium will remain. 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

Reliable evaluation of the potential for human exposure to plutonium depends in part on the reliability of 

supporting analytical data from environmental samples and biological specimens. Concentrations of 
 

 

 

 

 

 

 

 

 

 

PLUTONIUM 172 

6. POTENTIAL FOR HUMAN EXPOSURE 

plutonium in unpolluted atmospheres and in pristine surface waters are often so low as to be near the 

limits of current analytical methods. In reviewing data on plutonium levels monitored or estimated in the 

environment, it should also be noted that the amount of chemical identified analytically is not necessarily 

equivalent to the amount that is bioavailable. The analytical methods available for monitoring plutonium 

in a variety of environmental media are detailed in Chapter 7. 

Monitoring studies typically report combined 239,240Pu concentrations because 239Pu and 240Pu are not 

readily distinguishable by alpha spectroscopy (Eisenbud and Gesell 1997). 

6.4.1 Air 

Atmosphere nuclear weapons testing, which ended in 1980, is the major source of plutonium 

contamination. Since this time, essentially all fallout 239Pu has been removed from the atmosphere, 

allowing for measurement of baseline measurement of plutonium in air. 

Air concentrations of 239Pu at the Pacific Northwest National Laboratory near Richland, Washington 

averaged 1.3x10-7 Bq/m3

 (3.5x10-6 pCi/m3). During 2004, a network of 85 continuously operating air 

samplers were used to monitor radioactive material in air near the Hanford Site (DOE 2005c). In 2004, 

238Pu was detected in 4 of 40 site-wide composite air samples, with average and maximum concentrations 

of 5x10-7 and 1.3x10-5 pCi/m3

 (2x10-8 and 4.8x10-7 Bq/m3), respectively. From 1999 to 2003, 238Pu was 

detected in 10 site-wide air samples, with a maximum concentration of 5.3x10-6 pCi/m3

 (2.0x10-7 Bq/m3). 

Only 7 of the 40 site-wide air samples had detectable amounts of 239,240Pu in 2004 with an average 

concentration of 1.5x10-6 pCi/m3

 (5.6x10-8 Bq/m3). One of the 28 perimeter samples had a detectable 

amount of 239,240Pu at a concentration of 2.5x10-6 pCi/m3

 (9.3x10-8 Bq/m3). In 2004, none of the nearby or 

distant communities site air samples contained detectable amounts of 238Pu or 239,240Pu. From 1999 to 

2003, 238Pu was found in one air sample each from perimeter site and nearby communities sites; 239,240Pu 

was detected in seven, four, and one of the perimeter, nearby, and distant communities air samples, 

respectively (DOE 2005c). 

Concentrations measured at the Argonne National Laboratory-East near Chicago, Illinois ranged from 

6x10-8 to 1.4x10-7 Bq/m3

 (1.6x10-6–3.8x10-6 pCi/m3) (DOE 1999a). 

239,240Pu concentrations in airborne particulate matter collected during 2005 from five locations at the site 

boundary of the Rocky Flats Environmental Technology Site (RFETS), Colorado, a former nuclear 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 173 

6. POTENTIAL FOR HUMAN EXPOSURE 

weapons plant, were all <1x10-5 pCi/m3 (<4x10-7 Bq/m3) (DOE 2005d, 2005e, 2005f, 2006a). 239,240Pu 

concentrations in airborne particulate matter collected during the first and second quarters of 2005 at 

RFETS from an industrial area were 8.3x10-5 and 1.2x10-4 pCi/m3

 (3.1 x10-6 and 4.4 x10-6 Bq/m3), 

respectively. 

Aerosol particulate samples were collected at three sites (On Site, Near Field, and Cactus Field) near the 

Waste Isolation Pilot Plant (WIPP), a deep underground nuclear waste-storage facility near Carlsbad, 

New Mexico (Arimoto et al. 2005). The On Site sampling location was 0.1 km downwind of the WIPP 

exhaust shaft. The Near Field station was 1 km downwind of WIPP. The Cactus Field station was 19 km 

upwind of the WIPP, and served as a reference background site. Concentrations of 241Pu were below the 

minimum detection limit (1.2x10-6 Bq/m3

 [3.2x10-5 pCi/m3]) for all 204 samples collected. 238Pu was 

detected above the minimum detection limit (3.9x10-9 Bq/m3

 [1.1x10-7 pCi/m3]) in 6 of the 204 samples. 

239,240Pu was detected above the minimum detection limit (2.6x10-9 Bq/m3

 [7x10-8 pCi/m3]) in 203 of the 

204 samples. Mean concentrations of 239,240Pu in the 10 μm particulate matter fraction were 1.1x10-8 and 

8.1x10-9 Bq/m3

 (3.0x10-7 and 2.2x10-7 pCi/m3) at the Cactus Flats and Near Field stations, respectively. 

Mean concentrations of 239,240Pu in the total suspended particulate were 1.8x10-8, 1.3x10-8, and 1.4x10-8 

Bq/m3

 (4.9x10-7, 3.5x10-7, and 3.8x10-7 pCi/m3) at the Cactus Flats, Near Field, and On Site stations, 

respectively (Arimoto et al. 2005). 

Lehto et al. (2006) determined radionuclide concentrations from air sampler filters collected in the town 

of Kurchatov and the city of Astana in Kazakhstan. Kurchatov is near the former Semipalatinsk nuclear 

test site, which is highly contaminated from nuclear explosions carried out from 1949 to 1989. Astana is 

about 500 km west of Kurchatov. Median concentration of 1x10-7 and 3.4x10-8 Bq/m3

 (2.7x10-6 and 

9.2x10-7 pCi/m3

) for 239,240Pu and 238Pu, respectively, were reported in weekly air samples (25,000 m3 

volume) collected during 2000–2001 in Kuchatov. Median concentrations of 2.9x10-8 and 9x10-9 Bq/m3 

(7.8x10-7 and 2.4x10-7 pCi/m3

) for 239,240Pu and 238Pu, respectively, were reported in air samples collected 

during a 3-month period in 2001 in Astana; 238Pu activity was below the detection limit in half of the 

filters (Lehto et al. 2006). 

Hölgye (2008) reported 239,240Pu and 238Pu concentrations in air collected from 1997 to 2006 in Prague, 

Czechoslovakia of 0.53–5.06 and <0.16–1.10 nBq/m3

(1.4x10-8–1.7x10-7 and <4.3x10-9–3.0x10-8 pCi/m3), 

respectively. 239,240Pu concentrations in Prague post-Chernobyl air samples taken in April 29–May 5, 

1986 were 10–28Bq/m3

 (2.7x10-4–7.6x10-4 pCi/m3). 
 

 

 

 

 

PLUTONIUM 174 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.4.2 Water 

Hirose and Aoyama (2003) used the HAM database, a comprehensive data set of various anthropogenic 

radionuclides, to calculate background levels of 239,240Pu concentrations surface waters of the Pacific 

Ocean. In this study, the authors divided the Pacific Ocean basin into 12 “boxes”, which take into 

account the analyses of latitudinal and longitudinal distributions of anthropogenic radionuclides. Based 

on their analysis, 239,240Pu concentrations ranged from 6x10-7 to 2.7x10-6 Bq/L (2x10-5–7.3x10-5 pCi/L) 

within the 12 “boxes”. 

Seawater samples collected in 1999 in various regions of the southern Baltic Sea were analyzed for 

plutonium (Struminska and Skwarzec 2004). The highest concentrations of plutonium were generally 

found in the dissolved fractions of seawater, and ranged from 1.5x10-6 to 1.45x10-4 Bq/L (4.1x10-5– 

3.92x10-3 pCi/L) for 238Pu in samples from Gdansk Bay seaport and 239,240Pu in samples from Pomeranian 

Bay, respectively. The lowest plutonium concentrations were found in the colloidal fractions. 238Pu and 

239,240Pu concentrations in the colloidal fractions were generally ≤1x10-6 Bq/L (2.7x10-5 pCi/L) 

(Struminska and Skwarzec 2004). Hirose and Aoyama (2002) reported that the 239,240Pu particulate 

concentrations in surface waters of the western North Pacific Ocean ranged from 3x10-8 to 3x10-7 Bq/L 

(8x10-7–8x10-6 pCi/L) during 1987–1997. Ahier and Tracy (1995) reported 239,240Pu water concentrations 

in Lake Michigan, Huron, Erie, and Ontario of 4.4x10-7, 4.8x10-7, 1.8x10-7, and 1.7x10-7 Bq/L (1.1x10-5 , 

1.3x10-5, 4.8x10-6, and 4.6x10-6 pCi/L), respectively. 

Hirose et al. (2007) reported 239,240Pu concentrations in surface waters collected during 2003–2004 from 

the South Pacific Ocean mid-latitude region (32.5°S) ranging from 0.5 to 4.1 mBq/m3

 (0.01–1.1 pCi/m3). 

Yamada and Zheng (2008) reported 239,240Pu surface water concentrations in samples taken in the vicinity 

of the nuclear fuel reprocessing plant at Rokkasho, Japan of 7.6 and 7.8 mBq/m3 (0.20 and 0.21 pCi/m3

) 

on sampling dates September, 1991 and June 1993, respectively. 239,240Pu concentrations in surface water 

collected at sites along the Japan Sea coast sampled in June, 2003 were 4.9 and 5.9 mBq/m3

 (0.13 and 

0.16 pCi/m3

) at Sado Island and at Ajigasawa, respectively. Yamada et al. (2007) reported 239,240Pu 

concentrations of 13.4, 20.7, 37.2, 26.8, 39.6, 20.6, and 19.2 mBq/m3

 (0.362, 0.559, 1.01, 0.724, 1.07, 

0.557, and 0.519 pCi/m3

) at depths of 0, 150, 250, 600, 900, 1,200, and 1,490 m, respectively, in samples 

from Sagami Bay, Japan, western Northwest Pacific Ocean collected on March 23, 1992. 

During 2004, water samples from the Columbia River were collected at Priest Rapids Dam, the most 

upstream dam from the Hanford Site, and from Richland, Washington, on the Hanford Site. Average 
 

 

 

 

 

 

 

PLUTONIUM 175 

6. POTENTIAL FOR HUMAN EXPOSURE 

239,240Pu concentrations in water samples collected at the Priest Rapids Dam were 9.5x10-6 and 

2.7x10-5 pCi/L (3.5x10-7 and 1x10-6 Bq/L) in the particulate and dissolved fractions, respectively, in 

samples collected in 2004, and were 3.2x10-5 and 2.4x10-5 pCi/L (1.2x10-6 and 8.9x10-7 Bq/L) in the 

particulate and dissolved fractions, respectively, collected in 1999–2003 (DOE 2005c, 2005g). Average 

239,240Pu concentrations in river water samples collected at Richland, Washington were 1.5x10-5 and 

3.0x10-5 pCi/L (5.6x10-8 and 1.1x10-6 Bq/L) in the particulate and dissolved fractions, respectively, in 

samples collected in 2004, and were 2.5x10-5 and 3.0x10-5 pCi (9.3x10-7 and 1.1x10-6 Bq/L)in the 

particulate and dissolved fractions, respectively, collected in 1999–2003 (DOE 2005c, 2005g). Dai et al. 

(2005) reported 239Pu concentrations ranging from <3x10-4 to 9.71x10-2 pCi/kg (<1x10-5–3.6x10-3 Bq/kg) 

in unfiltered water collected from the Hanford Site 100K-Area groundwater monitoring wells. 

The Mayak nuclear fuel reprocessing plant in Russia PA, discharged radioactive wastes into the Techa 

River, which belongs to the Kara Sea basin of the Arctic Ocean. 239,240Pu concentrations in water samples 

from the Techa River showed a decrease from approximately 3x103

 Bq/L down to 2 Bq/L, over a distance 

of 150 km starting from Dam 11, which is 30 km from the site of radioactive waste disposal (Akleyev et 

al. 2000). Børretzen et al. (2005) reported concentrations of 0.31 and 0.088 mBq/kg (8.4x10-3 and 

2.4x10-3 pCi/kg) for 239Pu and 240Pu, respectively, in water samples collected on June 26, 1994 from 

Reservoir 11 at Mayak, which received radioactive wastes,. Levels in samples from the Asanov Swamp, 

downstream from the Mayak PA, were 0.12 and 0.13 mBq/kg (3.2x10-3 and 3.5x10-3 pCi/kg) for 239Pu and 

240Pu, respectively. 

Skipperud et al. (2009) reported average 239,240Pu concentrations of 40.6, 29.0, and 6.4 Bq/m3

 (1,100, 780, 

and 170 pCi/m3

), respectively, in water samples collected in 1996 from the Ob Estuary, Yenisey Estuary 

(both of which have weapons-grade plutonium sources in their catchment areas), and Kara Sea, Russia. 

Surface water samples upstream and downstream from the Savannah River Site are analyzed quarterly or 

on a bi-annual basis for 238Pu and 239Pu (Agency for Toxic Substances and Disease Registry 2007). From 

1993 to 2004, there were no detectable levels of 238Pu or 239Pu upstream or downstream from the facility 

(Agency for Toxic Substances and Disease Registry 2007). 

Groundwater samples were collected in May 1998 from four of the F-area wells at the Savannah River 

Site (Dai et al. 2002). Well 1 is upgradient from the F-area seepage basins, and wells 2–4 define a 

transect along the contamination plume. 239Pu concentrations were lowest in well 1, at approximately 

1x106

 and 1x105 atoms/kg (approximately 2x10-5 and 2x10-6 pCi/kg [7x10-7 and 7x10-8 Bq/kg]) in 

unfiltered and filtered fractions, respectively. 239Pu concentrations were highest in well 2, which is 
 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 176 

6. POTENTIAL FOR HUMAN EXPOSURE 

closest to the seepage basins, and were approximately 1x108 and 1.5x108 atoms/kg (approximately 

2x10-3 and 3.7x10-3 pCi/kg [7.4x10-5 and 1.4x10-4 Bq/kg]) in the unfiltered and filtered fractions, 

respectively (Dai et al. 2002). 

238Pu concentrations ranging from <0.01 to 0.078 pCi/L (<3.7x10-4–2.9x10-3 Bq/L) and from <0.01 to 

0.059 pCi/L (<3.7x10-4–2.2x10-3 Bq/L) were reported in unfiltered and filtered (0.05 μm filtrate) 

groundwater, respectively, sampled near the disposal well at the Idaho Chemical Processing Plant, Idaho 

National Engineering Laboratory (Cleveland and Rees 1982). Mururoa and Fangataufa Atolls were used 

from 1975 to 1996 for underground testing of nuclear weapons (Mulsow et al. 1999). Of the nine sites at 

Mururoa sampled for underground water, only the site at Ceto, had a measurable concentration of 239,240Pu 

at 2x10-5 Bq/L (5x10-4 pCi/L). The remaining eight sites at Mururoa and the two sites at Fangataufa had 

238Pu 239,240Pu concentrations ranging from <5x10-5 to <4x10-6 Bq/L (<1x10-3–<1x10-4 pCi/L). 

concentrations at both of these sites ranged from <2x10-6 to <5x10-5 Bq/L (5x10-5–<1x10-3 pCi/L) 

(Mulsow et al. 1999). 

Gordeev et al. (2007) reported 239,240Pu concentrations in groundwater samples obtained in 2005 from the 

Sary-Uzen nuclear excavation explosion site of the Semipalatinsk test area, Russia, ranging from 4x10-3 

to 6.0x10-2 Bq/L (0.1–1.6 pCi/L). Concentrations of 239,240Pu in water samples from the Tobol-Irtysh area 

of the Techa-Iset-Tobol-Irtysh-Ob river system, through which Mayak PA radioactive wastes are 

transported, were studied using samples collected from September 11 to 28, 2004 (Nikitin et al. 2007). 

239,240Pu concentrations ranged from 4.1 mBq/m3

 (0.11 pCi/m3) at the left-bank confluence of the IsetTobol Rivers to 7.5 mBq/m3

 (0.20 pCi/m3) at the left bank confluence of the Tobol-Irtysh Rivers; a value 

of 13.0 mBq/m3

 (0.35 pCi/m3) was reported at midstream samples of the Ob River (Nikitin et al. 2007). 

6.4.3 Sediment and Soil 

Average plutonium concentrations in surface soil from fallout range from about 0.01 to 0.1 pCi/g (4x10-4– 

4x10-3 Bq/g) (DOE 2005a). Essentially all of the plutonium found in the surface of the Earth’s crust is a 

product of human activity occurring over the past 60 years (Ketterer and Szechenyi 2008). 

The Rocky Flats Plant in Colorado processed weapons-grade plutonium from 1952 to 1989 (Ibrahim et al. 

1997). Contamination from plutonium production is composed mostly of 239,240Pu and a small amount 

(~3%) of 238Pu. Other releases of plutonium to this site, now called the RFETS, include global fallout, 

low-level releases during normal plant operations, accidental releases during fires between 1957 and 
 

 

 

 

 

 

PLUTONIUM 177 

6. POTENTIAL FOR HUMAN EXPOSURE 

1969, and leakage of drums of plutonium contaminated cutting oil to soil onsite. Resuspension of 

contaminated soils during remediation activities resulted in most of the releases of plutonium at the 

RFETS. Soil samples collected at the RFETS during 1992–1994 were reported to range from 1.1 Bq/kg 

(30 pCi/kg) offsite to 57 Bq/kg (1,500 pCi/kg) onsite. Isotopic ratios of 240Pu:239Pu increased from 

0.055 onsite to 0.123 at 19 km east of the RFETS boundary. An isotopic ratio of 0.06 is associated with 

contamination from activities at the RFETS, whereas the world mean isotopic ratio due to fallout was 

estimated at 0.176 (Ibrahim et al. 1997). ATSDR examined surface-soil contamination from an 

industrial portion of RFETS known as the “903 Pad Area”, because multiple site reports indicate that 

off-site surface-soil contamination largely originated from this location (Agency for Toxic 

Substances and Disease Registry 2005). Surface soils in the 903 Pad Area were originally 

contaminated when industrial oils containing trace amounts of plutonium leaked from steel drums 

stored at the site between 1958 and 1968. Although DOE contractors remediated many of the highest 

priority waste sites to levels meant to be protective of workers and rural residents near the site, soil 

sampling activities in this area found 239,240Pu levels as high as 457,000 pCi/kg (16,909 Bq/kg), 

which is nearly 10 times greater than the action level of 50,000 pCi/kg (Agency for Toxic Substances 

and Disease Registry 2005). The highest off-site concentration of 239,240Pu observed during a 

remedial investigation was 6,500 pCi/kg (240 Bq/kg). A separate sampling study conducted in the 

1990s at 42 locations adjacent to RFETS measured 239,240Pu concentrations in soil ranging from 0.22 to 

14.80 Bq/kg (5.9–400 pCi/kg) (Litaor 1999). 

In 1960 at the McGuire Air Force Base in New Jersey, a missile caught fire at the Boeing Michigan 

Aeronautical Research Center and the warhead partially burned and melted, releasing weapons-grade 

plutonium (WGP) to the local environment (Lee and Clark 2005). The WGP at this site consisted of 

mostly 239,240Pu, with a small amount of 241Pu and a negligible amount of 241Am (Amercium-241) at the 

time of its manufacture. Soil samples (0–2 inches) were collected from this site in June 2000 and 

analyzed for various plutonium isotopes. Concentrations were 0.42–6.34 Bq/g (11–171 pCi/g) for 

239,240Pu, 0.010–0.110 Bq/g (0.3–3.0 pCi/g) for 238Pu, and 0.33–8.17 Bq/g (8.9–220 pCi/g) for 241Pu in soil 

samples with various particle size fractions. The soil fraction with the smallest particle size (75–147 μm) 

contained the highest concentrations of plutonium, which were about 4 orders of magnitude higher than 

fallout levels. Based on the activity ratios of 241Pu/239,240Pu and 241Am/239,240Pu in the samples, the origin 

of the plutonium isotopes was identified as WGP (Lee and Clark 2005). 
 

 

 

 

 

 

PLUTONIUM 178 

6. POTENTIAL FOR HUMAN EXPOSURE 

Soil samples were collected in 2004 on and around the Hanford Site (DOE 2005c). Average 239,240Pu 

concentrations in surface soil collected on the 100-N Area, near facilities and operations in the 200 and 

600 areas, and near facilities and operations in the 300 and 400 Areas were 0.004, 0.35, and 0.03 pCi/g 

(1x10-4, 1.3x10-2, and 1x10-3 Bq/g) dry weight, respectively. With the exception of the concentration 

from the 200 and 600 Areas, the soil concentrations in 2004 were similar to levels determined from 1999 

to 2003. Average 239,240Pu concentrations in surface soil collected near Hanford Site facilities and 

operations in the 200 and 600 Areas from 1999 to 2003 were reported as 0.08, 0.29, 0.10, 0.12, and 

0.09 pCi/g (3x10-3, 1.1x10-2, 4x10-3, 4x10-3, and 3x10-3 Bq/g) dry weight, respectively. An average 

239,240Pu concentration of 0.0033 pCi/g (1.2x10-4 Bq/g) dry weight was reported in surface soil collected 

from a distant community in 2004 (DOE 2005c). Radionuclides, including 239,240Pu, were detected in 

river sediment adjacent to and downstream from the Hanford Site during 2004. Maximum 239,240Pu 

concentrations in Columbia River sediment collected from four sites near the Hanford Site ranged from 

7.8x10-4 to 0.011 pCi/g (2.9x10-5–4.1x10-4 Bq/g) dry weight (DOE 2005c, 2005g). Median 239,240Pu 

concentrations from two of these sites, where more than one sample was collected, were 0.0084 and 

0.0078 pCi/g (3.1x10-4 and 2.9x10-4 Bq/g) dry weight. Median 239,240Pu concentrations in sediment 

collected from 1999 to 2003 from six sites in the Columbia River near the Hanford Site ranged from 

0.0016 to 0.0098 pCi/g (5.9x10-5–3.6x10-4 Bq/g) (DOE 2005c). 

Concentrations of 239,240Pu ranged from 0.006 to 0.80 pCi/g (2x10-4–3x10-2 Bq/g) dry weight in soil 

collected from communities surrounding the Nevada Test Site in southern Nevada and southern Utah 

during the summer 1996 and spring 1997. The activity ratios of radiocesium to plutonium in the soil 

samples suggest that the Nevada Test Site had a significant contribution to plutonium levels in this area as 

compared to global fallout (Cizdziel et al. 1998). 

A study on radionuclide levels in west Cumbrian soils contaminated by low-level discharges from 

Sellafield reported 238Pu levels detected at a range of 200–18,000 pCi/kg (8–670 Bq/kg) and 239,240Pu 

levels detected at a range of 800–83,000 pCi/kg (30–3,100 Bq/kg) (Livens and Baxter 1988). Core 

samples of surface soil at the Maxey Flats facility, Kentucky, where radioactive wastes were buried, were 

reported to contain a mean concentration of 1.9x105

 pCi/kg (7,000 Bq/kg) of 238Pu and 2.2x104 pCi/kg 

(810 Bq/kg) of 239,240Pu (NEA/OECD 1981). 

Maximum 239,240Pu concentrations of 488 and 27,900 Bq/kg (1.31x104

 and 7.54x105 pCi/kg) have been 

reported in composite (0–20 cm) and surface (0–5 cm) soil samples, respectively, collected in the vicinity 

of ground zero of the first thermonuclear explosions at the Semipalatinsk Test Site (STS) (Carlsen et al. 
 

 

 

 

 

 

 

PLUTONIUM 179 

6. POTENTIAL FOR HUMAN EXPOSURE 

2001). Maximum 239,240Pu concentrations of 192 and 8,850 Bq/kg (5.19x103 and 2.39x105 pCi/kg) have 

been reported in composite (0–20 cm) and surface (0–5 cm) soil samples, respectively, collected at a 

crater created by an underground nuclear explosions in 1965 along the Shagan River at the STS. 

Maximum 239,240Pu concentration of 2.8 and 3.98 Bq/kg (76 and 108 pCi/kg) have been reported in 

composite (0–20 cm) and surface (0–5 cm) soil samples, respectively, from villages near the STS. The 

activities in soil from the villages are typical of levels associated with global fallout (Carlsen et al. 2001). 

Michel et al. (2002) reported mean concentrations 101 and 4.5 Bq/m2

 (2.8x103 and 120 pCi/m2), for 

239,240Pu and 238Pu, respectively, for soil cores collected at seven sites adjacent to the catchment of 

Blelham Tarn, a small lake in Cumbria, United Kingdom. Sediment cores were collected from 

14 locations in the lake during March 1997 and mean concentrations of 239,240Pu and 238Pu were 183 and 

4.5 Bq/m2

 (4.95x103 and 120 pCi/m2), respectively. Isotopic ratios indicated that the source of these 

plutonium isotopes was fallout from atmospheric weapons testing (Michel et al. 2002). 239,240Pu 

concentrations in 96 surface soil samples (0–5 cm) collected from 32 areas in Iran ranged from 0.080 to 

0.360 Bq/kg (2.2–9.7 pCi/kg) (Aliabadi et al. 2005). Luksiene et al. (2006) reported 239,240Pu 

concentrations in beach and forest surface soils (0–5 cm) collected in 1996–2001 from the Baltic coastline 

in Lithuania ranging from 0.06 to 0.80 and from 0.09 to 0.4 Bq/kg (1.6–22 and 2.4–11 pCi/kg), 

respectively. Ivanova et al. (1995) reported concentration ranging from 0.05 to 2.73 Bq/kg (1– 

73.8 pCi/kg) for 238Pu and from 0.37 to 5.04 Bq/kg (10–136 pCi/kg) for 239,240Pu in surface soils (0–2 cm) 

collected in the Bryansk, Orel, and Tula regions of Russia in 1992. 

239,240Pu concentrations in surface (0–5 cm) soil samples collected in 1996 in the Gomel region of Belarus, 

near the Chernobyl nuclear plant, were reported as 3.7 and 0.8 Bq/kg (100 and 20 pCi/kg) dry weight 

from Chiepietovitach and Pecki, respectively (Michel et al. 1999). Concentrations of 239,240Pu in soil 

samples from the 5–10 and 10–15 cm depths at Pecki were 0.52 and 0.45 Bq/kg (14 and 12 pCi/kg) dry 

weight, respectively. Soil concentrations of 238Pu were 2.2 and 0.39 Bq/kg (59 and 11 pCi/kg) dry weight 

from Chiepietovitach and Pecki, respectively. 238Pu concentrations in soil samples from the 5–10 and 10– 

15 cm depths at Pecki were 0.04 and 0.06 Bq/kg (1 and 2 pCi/kg) dry weight, respectively (Michel et al. 

1999). 

The Mayak PA, which processed weapons-grade plutonium from 1949 to 1952, discharged radioactive 

wastes into the Techa River. Contamination densities of 239,240Pu in floodplain soil on the Techa River 

showed a decrease from approximately 2 to 4x10-2 kBq/m2

 (50–1 nCi/m2) over a distance of 200 km 

starting from Dam 11, which is 30 km from the site of radioactive waste disposal. 239,240Pu concentrations 
 

 

 

 

 

 

 

 

PLUTONIUM 180 

6. POTENTIAL FOR HUMAN EXPOSURE 

in bottom soil along the river course decreased from approximately 5x10-2 to 2x10-2 Bq/kg (1.4– 

0.5 nCi/m2

) over the same distance (Akleyev et al. 2000). Børretzen et al. (2005) reported concentrations 

of 1.81x106

–2.0x106 and 1.22x105–1.35x105 mBq/kg (48.9–54.1 and 3.30–3.65 nCi/kg) dry weight for 

239Pu and 240Pu, respectively in surface soil samples from the Asanov Swamp at Mayak PA, collected on 

June 26, 1994. 

In 1966, two nuclear weapons were accidentally detonated during a collision of two aircraft in the area of 

the village of Palomares, Spain. 239,240Pu inventories in surface soil ranging from 8 to 57,900 Bq/m2

 (0.2– 

1,560 nCi/m2

) were reported in samples collected in the vicinity of the village of Palomares in October 

2001 (Jimenez-Ramos et al. 2006). Concentrations in soil samples from Tabernas, 200 km away from 

Palomares, were reported as 0.36 Bq/kg (9.7 pCi/kg) for 239,240Pu Bq/kg dry weight and <0.48 Bq/kg 

(<13 pCi/kg) dry weight for 238Pu (Rubio Montero and Sanchez 2001). 

Concentrations of 239,240Pu in peat bog samples from the area of the Tomsk-Seversk nuclear facility 

(Siberia, Russia) were reported as 0.5, 0.6, and 10.5 Bq/kg (13, 16, and 284 pCi/kg) at depths of surface5, 11–13, and 20 cm, respectively; reported concentrations for 238Pu were 0.06, 0.01, and 0.34 Bq/kg (1.6, 

0.3, and 9.2 pCi/kg), respectively. Concentrations of 239,240Pu in forest soil samples from this area were 

reported as 0.052, 0.055, and 0.054 Bq/kg (1.4, 1.5, and 1.5 pCi/kg) at depths of surface, 3-6, and 32– 

40 cm, respectively, while concentrations in samples from an area river bank were 0.050, 0.049, and 

0.050 Bq/kg (1.5, 1.4, and 1.5 pCi/kg) at depths of 0–3, 9–12, and 18–21 cm, respectively (GauthierLafaye et al. 2008). 

Yamamoto et al. (2008b) reported 239,240Pu concentrations ranging from 0.16 to 51.87 Bq/kg (4.3– 

1,401 pCi/kg) in 26 soil samples collected in October 2005 from Dolon located 60 km northeast of the 

Semipalatinsk Nuclear Test Site in Kazakhstan, an area contaminated mainly by the first USSR nuclear 

test on August 29, 1949. 

Yoshida et al. (2007) reported a 239,240Pu soil (0–5 cm) concentration of 59.9 Bq/kg (1,620 pCi/kg) dry 

weight at 300 m west from the Nishiyama reservoir Nagasaki Japan. This concentration decreased with 

increasing distance for the Nishiyama reservoir. The 239,240Pu concentration in the surface soil at farther 

sampling point was 1.82Bq/kg (49.2 pCi/kg) dry weight, a level within the range with global fallout 

plutonium concentrations in surface soil of Japanese forests (0.15–4.31 Bq/kg (3.8–116 pCi/kg, dry 

weight) (Yoshida et al. 2007). 
 

 

 

 

 

 

PLUTONIUM 181 

6. POTENTIAL FOR HUMAN EXPOSURE 

Concentrations of 239,240Pu in soils from counties throughout Hungary ranged from 0.020 to 0.61 Bq/kg 

(0.54–17 pCi/kg) and concentrations of 241Pu in these same samples were reported to range from 0.043 to 

1.70 Bq/kg (1.2–46 pCi/kg) (Varga and Tarján 2008). Isotopic ratio analysis indicated that the plutonium 

levels in Hungary arise from global fallout related to atmospheric testing of nuclear weapons. 

239,240Pu concentrations in sediment cores collected from Lake Michigan in 1972–1974 ranged from 

0.003 to 0.401 pCi/g (1x10-4–1.48x10-2 Bq/g) dry weight. It was estimated in this report that radioactivity 

in the sediments was confined to the upper 6 cm of the sediments, and in many of the core samples, no 

radioactivity was detected below a depth of 3 cm (IAEA 1976g). 

Rapiejko et al. (2001) reported 239,240Pu median concentrations of 2.2 (59) (0.00–0.06 cm depth near 

sewage treatment plant), 1.3 (35) (0.06–0.15 cm depth), 1.1 (30) (0.15–0.24 cm depth), and 2.1 (57) 

(0.24–0.37 cm depth) Bq/kg (pCi/kg) in sediment samples collected in April 1999 from the Peconic 

River, downstream from the Brookhaven National Laboratory (BNL). Concentrations of 238Pu in these 

same samples were 0.09, <0.07, <0.07, and <0.09 Bq/kg (2, <2, <2, and <2 pCi/kg), respectively. The 

median concentrations of 239,240Pu in sediments from Donahues Pond and Forge Pond, further down 

stream from BNL, were 4.0 and 1.6 Bq/kg (108 and 43 pCi/kg), respectively; 238Pu was not detected in 

these samples. Concentration ranges for 239,240Pu in control samples from the Connetquot River were 1.7– 

3.7 Bq/kg (46–100 pCi/kg) at 0.0–0.06 cm depth and 0.13–0.48 Bq/kg (4–13 pCi/kg) at 0.06–0.15 cm 

depth; 238Pu concentrations were reported as 0.15–0.26 Bq/kg (4–7 pCi/kg) at 0.0–0.06 cm depth and 

<0.07–0.074 Bq/kg (<2–2 pCi/kg) at 0.06–0.15 cm depth (Rapiejko et al. 2001). 

Skipperud et al. (2009) reported average 239,240Pu concentrations of 0.40, 0.24, and 0.55 Bq/kg (10, 6.5, 

and 15 pCi/kg), respectively, in sediments collected in 1996 from the Ob Estuary and Yenisey Estuary 

(both of which have weapons-grade plutonium sources in their catchment areas), and Kara Sea, Russia. 

Surface sediment samples (0–1 cm) from the Rhone River collected in March 2001 at the input into the 

Gulf of Lions (Northwestern Mediterranean Sea) were reported to contain concentrations of 239,240Pu and 

238Pu of 0.329–549 Bq/kg (8.89–41.86 pCi/kg) and 0.025–0.143 Bq/kg (0.68–3.86 pCi/kg), respectively 

(Lansard et al. 2007). Concentrations of 239,240Pu in sediment cores collected in November 2001 ranged 

from 0.256 to 5.974 Bq/kg (6.92–161.5 pCi/kg) at 5–10 cm and 280–290 cm depth, respectively. 

Concentrations of 238Pu in sediment cores collected in November 2001 ranged from 0.035 to 1.254 Bq/kg 

(0.95–33.89 pCi/kg) at 5–10 cm and 280–290 cm depth, respectively. Sources of plutonium isotopes in 

the Rhone River valley have been identified as weathering of the catchment basin contaminated by 
 

 

 

 

 

 

 

 

 

 

PLUTONIUM 182 

6. POTENTIAL FOR HUMAN EXPOSURE 

atmospheric fallout and liquid effluents released from the Marcoule reprocessing plant (located upstream 

120 km from the river mouth) since 1961 (Lansard et al. 2007). 

Liao et al. (2008) reported 239Pu concentrations in sediment from Lake Poyang, East China of 0.066, 

240 0.395, and 0.062 mBq/g (1.8, 11, and 1.7 pCi/kg) at 0–1, 5–6, and 10–11 cm depth, respectively. Pu

concentrations of 0.046, 0.270, and 0.042 mBq/g (1.2, 7.3, and 1.1 pCi/kg) were reported at these same 

depths, respectively. The 240Pu/239Pu ratio (0.187) in sediment samples from Lake Poyang indicated that 

plutonium pollution was from global fallout. 

6.4.4 Other Environmental Media 

238,239,240Pu was identified in imported food collected 2 weeks after the Chernobyl accident in an 

FDA/USDA-sponsored survey; however, concentrations were not provided. Generally, contamination 

levels for the radionuclides surveyed were below FDA’s levels of concern (Cunningham et al. 1989). The 

FDA developed guidance levels for radionuclide activity concentration, called derived intervention levels 

(DILs), which help determine whether domestic food in interstate commerce or food offered for import 

into the United States present a safety concern (FDA 2005). The DIL for 238Pu + 239Pu + 241Am is 

2 Bq/Kg (FDA 2005). Various radionuclides were measured in 1996 on samples of mixed diet from 

regions throughout the United Kingdom (MAFF 1997b). Concentrations of all artificial radionuclides 

were reported to be low and of little significance. Concentrations of 238Pu were generally <0.00030 Bq/kg 

(0.008 pCi/kg) and concentrations of 239,240Pu ranged from 0.00011 to 0.00040 Bq/kg (3x10-3–0.01 

pCi/kg) (MAFF 1997b). Samples of milk, crops, bread, and meat collected from the United Kingdom in 

1996 were analyzed for various natural and artificial radionuclides; concentrations of plutonium (238Pu 

and 239,240Pu) were generally <0.0002 Bq/L (<0.005 pCi/L) for milk and <0.0002 Bq/kg (<0.005 pCi/kg) 

for crops, bread, and meat (MAFF 1997b). 

Seventy-two beverage brands available to the public in the United Kingdom were surveyed for natural 

and anthropogenic radionuclides. Beverages included in this survey were fruit juices, fruit juice drinks, 

fruit squashes, carbonated drinks, baby juices, flavored spring and mineral waters, ciders, wines, beers, 

and others beverages, such as powdered chocolate and malt drinks. Levels of all anthropogenic 

radionuclides surveyed, including 238Pu and 239,240Pu, were below the limits of detection (MAFF 1997a). 

Sanchez et al. (1999) studied doses of artificial radionuclides, including 239,240Pu, in the diet of individuals 

living in Cumbria, United Kingdom. This investigation included three duplicate diet studies conducted in 

1986, 1995, and 1996. In general, mean 239,240Pu concentrations in diet samples from these surveys were 
 

 

 

 

 

PLUTONIUM 183 

6. POTENTIAL FOR HUMAN EXPOSURE 

reported to range from <1x10-4 (the detection limit) to <2.8x10-3 Bq/kg (<2.7x10-3–<7.6x10-2 pCi/kg) 

fresh weight in both the control group from west Cumbria 1986 and the study group from Sellafield in 

1995. The highest 239,240Pu concentrations of 1.7x104

 and 1.2x104 Bq/kg (0.46 and 0.32 pCi/kg) fresh 

weight were found in 1986 diet surveys, which contained crab (Sellafield) and cockles (west Cumbria) 

(Sanchez et al. 1999). Cooper et al. (1992) analyzed food and total diet samples for various radioactive 

isotopes that were collected from selected communities in areas of the former Union of the Soviet 

Socialist Republic (U.S.S.R.) that were contaminated with fallout from the accident at Chernobyl. 

Concentrations of 239,240Pu in total diet samples ranged from 1.5x10-3 to 7.0x10-3 Bq/kg (4.1x10-3– 

2x10-2 pCi/kg) dry weight (Cooper et al. 1992). 

Twenty Emmental cheese samples were collected from 6 European regions (Allgäu, Germany; Bretagne, 

France; Savoie, France; Switzerland; Finland; and Vorarlberg, Austria,) and analyzed for various 

radionuclides. 238Pu and 239,240Pu concentrations were determined in one sample from each location, 

except Finland, and were found to be less than the detection limit (0.3 Bq/kg [8 pCi/kg]; Froidevaux et al. 

2004). 

Samples of bottom-feeding fish, white sucker (Catostomus commersoni), channel catfish (Ictalurus 

punctatus), and carp (Cyprinus carpio) were collected along the Rio Grande upstream and downstream of 

the Los Alamos National Laboratory (LANL) in September 1997 and analyzed for various radionuclides 

(Fresquez et al. 1999b). Mean concentration of 239,240Pu in samples collected downstream of LANL 

ranged from 4.8x10-5 to 47.5x10-5 pCi/g (1.8x10-6 to 1.76x10-5 Bq/g) in muscle and bone, and from 

27.5x10-5 to 135.0x10-5 pCi/g (1.02x10-5 to 5.00x10-5 Bq/g) in viscera. In samples collected upstream of 

LANL, 239,240Pu concentrations ranged from 5.5x10-5 to 33.1x10-5 pCi/g (2.0x10-6 to 1.22x10-5 Bq/g) in 

muscle and bone, and a mean concentration of 85.1x10-5 pCi/g (3.15x10-5 Bq/g) was determined in 

viscera. For most of the radionuclides, concentrations in fish collected downstream of LANL were not 

significantly higher than those in fish collected upstream of LANL (Fresquez et al. 1999b). 

Børretzen et al. (2005) reported 239Pu concentrations of 1,010, 12, 95, and 119 mBq/kg (27.30, 0.32, 2.6, 

and 3.22 pCi/kg) wet weight and 240Pu concentrations reported of 1,150, 4, 6, and 44 Bq/kg (31.1, 0.11, 

0.16, and 1.2 pCi/kg) wet weight in mussels, pike bone, pike filet, and roach, respectively, collected on 

June 26, 1994 from a reservoir adjacent to the Asanov Swamp, downstream from the Mayak PA. 

Oikawa and Yamamoto (2007) reported 239Pu and 240Pu concentrations livers of Surume squid caught 

during the fishery season from September–December 2002 in the coastal seawaters off Japan. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 184 

6. POTENTIAL FOR HUMAN EXPOSURE 

Concentrations of 239Pu and 240Pu of 1.5–28 mBq/kg (0.041–0.76 pCi/kg) and 1.1–24 mBq/kg (0.030– 

0.65 pCi/kg), respectively; these concentrations were several thousand times higher than levels found in 

seawater. 

Various metals and radionuclides, including 238Pu and 239,240Pu, were measured in birds and eggs from 

Amchitka and Kiska Islands in the Bering Sea/Northern Pacific Ocean. 238Pu was not detected over the 

minimum detectable activity (MDA) in any samples. 239,240Pu was only detected above the MDA at 

0.31 Bq/kg (8.4 pCi/kg) wet weight in a guillemot composite (Burger and Gochfeld 2007). 

Concentrations of 239,240Pu ranged from 12 to 680 pCi/kg (0.44 –25 Bq/kg) dry weight in attic dust 

collected from communities surrounding the Nevada Test Site in southern Nevada and southern Utah 

during the summer 1996 and spring 1997. The activity ratios of radiocesium to plutonium in the dust 

samples suggest that the Nevada Test Site had a significant contribution to plutonium levels in this area as 

compared to global fallout (Cizdziel et al. 1998). 

Plutonium concentrations in vegetation were monitored during 2004 on the Hanford Site. 239,240Pu was 

not detected in vegetation samples collected on the Hanford Site in the 100-N Area and the 300 and 

400 Areas (DOE 2005c). An average 239,240Pu concentration of 0.003 pCi/g (1x10-4 Bq/g) dry weight, was 

reported in vegetation samples collected from the 200 and 600 Areas. A 239,240Pu concentration of 

0.00033 pCi/g (1.2x10-5 Bq/g) dry weight was reported in vegetation from distant communities. Average 

239,240Pu concentrations in vegetation samples collected in 1999–2002 in the 100-N Area and the 300 and 

400 Areas ranged from 0.0004 to 0.024 and from 0.003 to 0.005 pCi/g (1.5x10-5–8.9x10-4 and 1x10-4– 

2x10-4 Bq/g) dry weight and was not detected in the 2003 samples. Average 239,240Pu concentrations in 

vegetation samples collected during 1999–2003 ranged from 0.003 to 0.033 pCi/g (1x10-4–1.2x10-3 Bq/g) 

dry weight (DOE 2005c). In 2004, mean 239,240Pu concentrations of 0.0020, 0.0050, 0.0017, and 

0.00022 pCi/g (7x10-5, 2x10-4, 6.3x10-5, and 8.1x10-6 Bq/g) dry weight were reported in vegetation 

samples collected site-wide at the Hanford Site, at the perimeter, at the shoreline of the Hanford Reach of 

the Columbia River, and at a distant site, respectively. 238Pu was only detected in one of five samples 

collected on-site at a concentration of 6.0x10-6 pCi/g (2x10-7 Bq/g) dry weight. The results reported for 

the 2004 samples were similar to those reported in 1993, 1994, 1998, and 2001 (DOE 2005c). 

Akleyev et al. (2000) reported that plutonium concentrations in grass samples from the Asanov Swamps 

and dams on the Techa River were estimated to be 7–80 Bq/kg (200–2,200 pCi/kg). Average values for 

plutonium concentrations in vegetation from the flood plain section from Dam 11 to the village of 
 

 

 

 

 

 

 

 

PLUTONIUM 185 

6. POTENTIAL FOR HUMAN EXPOSURE 

Muslyumovo were reported as 7 Bq/kg (200 pCi/kg), and 1.1 Bq/kg (30 pCi/kg) in the section from 

Muslyumovo to Zarechnoye. These sites are in the area of the Mayak PA (Akleyev et al. 2000). 

Børretzen et al. (2005) reported concentrations of 163 and 207 mBq/kg (4.41 and 5.59 pCi/kg) for 239Pu 

and 23 and 24 mBq/kg (0.62 and 0.65 pCi/kg) for 240Pu in two dried grass samples from the Asanov 

Swamp collected on June 26, 1994. 239Pu and 240Pu concentrations of 1,700 and 362 mBq/kg (46 and 

9.78 pCi/kg) dry weight and 190 and 36 mBq/kg (5.1 and 0.97 pCi/kg) dry weight were also reported in 

two samples of water plants, respectively (Børretzen et al. 2005) 

Plutonium concentrations in moss samples from counties in Hungary were reported as 1.06 and 

0.007 Bq/kg (28.7 and 0.2 pCi/kg) for 239,240Pu and 2.39 and 0.011 Bq/kg (64.6 and 0.30 pCi/kg) for 241Pu 

in Komarom and Heves, respectively (Varga and Tarján 2008). 239,240Pu concentrations in ashed fodder 

(Pest), hay (Bacs-Kiskun), and sedge (Tolna) were reported as 1.91, 0.004, and 0.038 Bq/kg (51.6, 0.1, 

and 1.03 pCi/kg), respectively. 241Pu concentrations in these same samples were reported as 131, 0.22, 

and 0.69 Bq/kg (3540, 6.0, and 19 pCi/kg), respectively (Varga and Tarján 2008). 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

The estimated 50-year dose commitment from plutonium for people in the north temperate zone due to 

atmospheric nuclear weapons tests conducted before 1973 is 0.2 mrad (0.002 mGy) to the bone lining 

cells (Eisenbud 1987). The average annual dose equivalent from all background radiation to an individual 

residing in the United States is estimated to be 360 mrem (3.6 mSv) (NCRP 1987). 

Sanchez et al. (1999) reported that 239,240Pu contributed the lowest dose of radionuclides studied in a 

survey of the diets of individuals living in Cumbria, United Kingdom; the average dose was <0.04 μSv 

(0.004 mrem). Concentrations of 239,240Pu in total diet samples collected from areas of the former 

U.S.S.R. that were contaminated by fallout from Chernobyl ranged from 1.5x10-7 to 7x10-7 Bq/g 

(4.1x10-6–2x10-5 pCi/g) dry weight; a worst-case calculated dose of 0.2 μSv (0.02 mrem) was reported for 

239,240Pu (Cooper et al. 1992). Pietrzak-Flis and Orzechowska (1993) studied the content of 239,240Pu in 

daily diet samples collected from a hospital in Bialystok, Poland from March 1987 to May 1992. The 

estimated annual intake of plutonium was 0.774 Bq/year (20.9 pCi/year) in the first year after the accident 

at Chernobyl; after the sixth year, the daily intake was 0.088 Bq/year (2.4 pCi/year) (Pietrzak-Flis and 

Orzechowska 1993). Daily ingestion of 239,240Pu in food in Japan between 1978 and 1980 due to 

atmospheric fallout was estimated to be 4.5x10-3 pCi/day (1.7x10-4 Bq/day) (Hisamatsu et al. 1987). 
 

 

 

 

 

 

PLUTONIUM 186 

6. POTENTIAL FOR HUMAN EXPOSURE 

Filipy et al. (2003) reported plutonium concentrations in bone samples collect at autopsy from eight 

individuals for the United States Transuranium and Uranium Registries (USTUR). The USTUR 

documents levels and distribution of uranium and transuranium isotopes in human tissues for 

occupationally exposed workers who donate their bodies to science (USTUR 2003). Plutonium levels 

were measured in various bone samples: clavicle; patella; ribs (5–10); sternum; and vertebrae (T5–L3). 

238Pu concentrations ranged from 0.146 (clavicle) to 82.7 (sternum) Bq/kg (3.95–2,240 pCi/kg) dry 

weight. 239Pu concentrations ranged from 0.441 (patella) to 398.0 (vertebrae) Bq/kg (11.9– 

10,800 pCi/kg) dry weight. 241Pu concentrations ranged from 0.850 (sternum) to 25.2 (sternum) Bq/kg 

(23–681 pCi/kg) dry weight (Filipy et al. 2003). Ivanova et al. (1995) measured plutonium 

concentrations in lungs, tracheobronchial lymph nodes (TLN), liver, and bone in 59 individuals who lived 

in the areas of the Bryansk region of Russia that was contaminated by the Chernobyl accident. Average 

concentrations of 238,239,240Pu in lung, TLN, liver, and bone tissue were 0.060, 0.530, 0.070, and 

0.070 Bq/kg (1.6, 14, 1.9, and 1.9 pCi/kg) dry weight, respectively (Ivanova et al. 1995). 

Total plutonium deposition in five Manhattan Project workers exposed to plutonium in 1944–1945 ranged 

from 98 to 3,300 Bq (2,600–89,000 pCi) according to autopsy data (Voelz et al. 1997). Mean 

concentrations of 239,240Pu in human tissues from autopsy specimens in Japan ranged from 2.5x10-4 pCi/g 

(9.3x10-6 Bq/g) (cerebrum) to 1.5x10-3 pCi/g (5.6x10-5 Bq/g) (gonads) wet weight (Takizawa 1982). 

Wrenn and Cohen (1977) reported 239Pu levels in tissues derived from 12 autopsy cases in New York City 

from 1973 to 1976. Average levels for lung, liver, vertebrae, and gonads were 2.4x10-4, 7x10-4, 1.7x10-4 , 

and 4x10-4 pCi/g (8.9x10-6, 3x10-5, 6.3x10-6, and 1x10-5 Bq/g), respectively. Tissue samples from autopsy 

cases of nonoccupationally exposed individuals from Great Britain showed median 239,240Pu 

concentrations for ribs, vertebrae, femur, liver, and lungs of 1.6x10-4, 1.2x10-4, 9.5x10-5, 7x10-4, and 

4.9x10-5 pCi/g (5.9x10-6, 4.4x10-6, 3.5x10-6, 2.6x10-5, and 1.8x10-6 Bq/g), respectively. Comparable 

samples taken from autopsy cases from a region in Great Britain located near a plutonium processing 

plant had median concentrations of 2.2x10-4, 1.9x10-4, 1.5x10-4, 1.4x10-4, and 1.8x10-4 pCi/g (8.1x10-6 , 

7.0x10-6, 5.5x10-6, 5.2x10-6, and 6.7x10-6 Bq/g) for ribs, vertebrae, femur, liver, and lungs, respectively 

(Popplewell et al. 1988). 

Ibrahim et al. (1999) studied the excretion of 239Pu in urine of residents living near the Rocky Flats 

Environmental Technology Site (RFETS). The Rocky Flats group consisted of two groups of individuals 

living near RFETS, who were not occupationally exposed to plutonium. Urine was collected from the 

first group during 1992–1993 and samples were collected from the second group in 1995. Background 
 

 

 

 

 

 

 

 

 

 

PLUTONIUM 187 

6. POTENTIAL FOR HUMAN EXPOSURE 

samples were also collected during two periods from individuals living in Colorado least 16 km from the 

RFETS. Mean 239Pu excretion rates of 1.1x10-6 and 8.5x10-7 Bq/day (3.0x10-5 and 2.3x10-5 piCi/day) 

were reported for the entire Rocky Flats group and the background group, respectively. Analysis 

indicated that these data were not statistically significantly different. Measured levels of 239Pu in urine 

from the Rocky Flats group were within the range reported for background levels (Ibrahim et al. 1999). 

Bolotov et al. (2003) reported 239Pu concentrations in human hair ranging from 0.90 to 3.0 Bq/kg (20– 

80 pCi/kg) in samples from the area of the heavily damaged Semipalatinsk nuclear bomb test site region 

in Russia. 239Pu concentrations in human gall stones collected from three individuals from Minsk, 

Belarus were 0.28–0.53 Bq/kg (7.5–14 pCi/kg); gall stones from another individual in Krakow, Poland 

contained <0.05 Bq/kg (<1 pCi/kg) 239Pu (Bolotov et al. 2003). 

Yamamoto et al. (2008a) reported plutonium concentrations human tissue samples, including bone 

(vertebra), lungs, liver, and kidneys, collected during 2000–2002 at autopsy from nine residents who died 

in some settlements and in Semipalatinsk City around the Semipalatinsk Nuclear Test Site. 239,240Pu 

239 concentrations in four bone (vertebra) samples ranged from 0.049 to 0.13 mBq/g ashed weight. Pu

concentrations in six kidney samples ranged from 0.023 to 0.25 mBq/g ashed weight; 240Pu was not 

detected in these kidney samples. In the nine liver samples 239Pu and 240Pu concentrations were 0.39– 

4.83 and 0.2–2.74 mBq/g ashed weight, respectively. In the nine lung samples 239Pu and 240Pu 

concentrations ranged from 0.044 to 1.56 and from not detected to 1.83 mBq/g ashed weight, 

respectively. In addition, bone samples, mainly vertebral bone, were collected from 23 deceased residents 

of this area. 239,240Pu activity in these bone samples ranged from 0.020 to 0.107 mBq/g ashed weight, with 

a mean of 0.46 mBq/g ash weight. Yamamoto et al. (2008a) reported that the 239,240Pu levels in bone, 

lung, and liver samples in this study did not seem to be largely different from ranges found for human 

tissue samples for residents from other countries that were due solely to global fallout during the 1970s– 

1980s. Human tissue autopsy samples were obtained for the period of 1975–2003 from nonoccupationally exposed residents of Ozyorsk, Russia in the vicinity of the Mayak nuclear facility. Since 

the early 1950s, the plutonium body burden in the Ozyorsk population was shown to grow at a nearly 

constant rate and total accumulation amounted to 5.8 Bq at 35 years after the construction of the plant in 

the city (Suslova et al. 2007). 
 

 

 

 

 

 

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6. POTENTIAL FOR HUMAN EXPOSURE 

6.6 EXPOSURES OF CHILDREN 

This section focuses on exposures from conception to maturity at 18 years in humans. Differences from 

adults in susceptibility to hazardous substances are discussed in Section 3.7, Children’s Susceptibility. 

Children are not small adults. A child’s exposure may differ from an adult’s exposure in many ways. 

Children drink more fluids, eat more food, breathe more air per kilogram of body weight, and have a 

larger skin surface in proportion to their body volume. A child’s diet often differs from that of adults. 

The developing human’s source of nutrition changes with age: from placental nourishment to breast milk 

or formula to the diet of older children who eat more of certain types of foods than adults. A child’s 

behavior and lifestyle also influence exposure. Children crawl on the floor, put things in their mouths, 

sometimes eat inappropriate things (such as dirt or paint chips), and spend more time outdoors. Children 

also are closer to the ground, and they do not use the judgment of adults to avoid hazards (NRC 1993). 

Children would be exposed to plutonium from fallout by similar routes are adults, such as ingestion of 

food and water and breathing ambient air. However, levels would generally be low for children not living 

near areas with known plutonium contamination (e.g., areas where nuclear accidents or former plutonium 

processing plants). Limited data on exposures of children to plutonium were located. 

Compared to adults, the potential for plutonium exposure is greater for children who consume foods (e.g., 

milk, grains) produced in areas with elevated concentrations of plutonium in the soil and for children with 

elevated concentrations of plutonium in their drinking water. Children are more likely to be exposed to 

plutonium in dairy products produced in contaminated areas. 

O’Donnell et al. (1997) reported an average 239,240Pu concentration in permanent teeth collected from 

children within the United Kingdom and Republic of Ireland of 5 mBq/kg (0.1 pCi/kg) ash weight. 

239,240Pu concentrations decreased with increasing distance from Sellafield; at 0–50, 50–150, and 

>150 miles from Sellafield, average 239,240Pu concentrations were 7.1, 5.0, and 3.0 mBq/kg (0.20, 0.10, 

and 0.08 pCi/kg) ash weight, respectively. These levels are not considered to present a radiological 

hazard (O’Donnell et al. 1997). Urine collected during a 24-hour period from 17 school-aged children in 

North London contained 3.5 μBq/day of 239Pu (Priest et al. 1999). 
 

 

 

 

 

 

 

 

PLUTONIUM 189 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

Total plutonium deposition in five Manhattan Project workers exposed to plutonium in 1944–1945 ranged 

from 98 to 3,300 Bq (2,600–89,000 pCi) according to autopsy data (Voelz et al. 1997). 

Individuals living near facilities which utilize plutonium in their operations may have higher exposure 

potential due to regular releases through stack-emissions or waste water. In addition, atmospheric fallout 

to the soil can result in secondary releases due to dust generation while farming or due to uptake by crops 

and subsequent ingestion of contaminated crops (Corey et al. 1982). 

Individuals living in Palomares, Spain, were exposed to plutonium after the dispersal of the plutonium in 

two bombs released during the midair collision of two airplanes (Iranzo et al. 1987). Exposure via 

inhalation due to the resuspension of contaminated soil was studied for 15 years following the release. 

Those individuals living near cultivated lands with the highest contamination received a cumulative total 

of 52.3 mrem (5.2x10-1 mSv) from 1966 to 1980 while those in the urban area of Palomares, farther away 

from the source, received 5.4 mrem (5.4x10-2 mSv) (Iranzo et al. 1987). 

Kathren et al. (1987) determined levels of 239Pu at autopsy in bones of an individual known to have had 

occupational exposure to plutonium. Values ranged from 1.9x10-4 to 1.14x10-2 pCi/g ash (7.0x10-6– 

5.0x10-5 Bq/g ash), with the highest value detected in the scapula. 

Kawamura (1987) estimated the 239,240Pu inhalation intake of visitors to Kiev after the Chernobyl accident 

to be 0.8 pCi/day (0.03 Bq/day) during peak fallout exposure. 

6.8 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of plutonium is available. Where adequate information is not 

available, ATSDR, in conjunction with NTP, is required to assure the initiation of a program of research 

designed to determine the health effects (and techniques for developing methods to determine such health 

effects) of plutonium. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 
 

 

 

 

 

 

 

 

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6. POTENTIAL FOR HUMAN EXPOSURE 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

6.8.1 Identification of Data Needs 

Physical and Chemical Properties. Table 4-2 summarizes many of the relevant physical and 

chemical properties of plutonium and selected plutonium compounds. Table 4-3 summarizes the 

radiological properties of selected plutonium isotopes. There are adequate data for the physical, 

chemical, and radiological properties of plutonium and plutonium compounds. No data needs are 

identified. 

Production, Import/Export, Use, Release, and Disposal. According to the Emergency 

Planning and Community Right-to-Know Act of 1986, 42 U.S.C. Section 11023, industries are required 

to submit substance release and off-site transfer information to the EPA. The TRI, which contains this 

information for 2004, became available in May of 2006. This database is updated yearly and should 

provide a list of industrial production facilities and emissions. 

The potential for human exposure to plutonium is great due to its ubiquitous presence in the environment, 

resulting from releases from production facilities and from weapons testing, and its radiological half-life. 

However, the level of exposure to plutonium will generally be small. The production and use of 

plutonium 238–243 are well documented. There is little information regarding the production of 237Pu. 

The amounts of these plutonium isotopes produced for various applications have been documented; 

however, the most current information is from 1974. More recent data are needed in order to compare 

past and present production and to project future production. The majority of information on the 

production and use of plutonium is classified in the nation's defense program. Information on past major 

releases of plutonium from weapons testing and from the explosion of a navigational satellite is available. 

However, current information on releases from production facilities is unavailable and is needed in order 

to monitor populations that might be exposed. The disposal of plutonium prior to 1970 is documented, 

but again, more recent information regarding amounts being held for mandated disposal in the proposed 

high-level disposal facility is needed. Rules and regulations for the disposal of plutonium have been 

established and these are reported in Chapter 8. 
 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 191 

6. POTENTIAL FOR HUMAN EXPOSURE 

Environmental Fate. The major transport processes involved in the environmental fate of plutonium, 

as it relates to potential human exposure, have been fairly well defined. These processes include transport 

in the atmosphere when adsorbed to particulate matter and dry or wet deposition on land and water. 

Information on environmental compartments, such as flux rates, and the mechanisms and rates of several 

processes involved in the biogeochemical cycling of plutonium are still undefined. The data available 

regarding uptake of plutonium by plants are limited. There is some information regarding the conversion 

of the oxidized forms of plutonium to reduced forms followed by uptake into plants. Information 

regarding the influence of inorganic complexes on transport and regarding the media-specific effects of 

pH on the oxidation states of plutonium would be useful in order to more fully understand transport 

processes. The persistence of plutonium isotopes is well documented. Transformation of plutonium is 

through radioactive decay or chemical oxidation/reduction reactions. These processes have been well 

characterized. 

Bioavailability from Environmental Media. Plutonium is known to be absorbed following 

inhalation exposure. Bioavailability following oral and dermal exposure is very low; however, plutonium 

can be absorbed from contaminated wounds. Bioassay data are available on absorption from 

contaminated air and water. 

Food Chain Bioaccumulation. Plutonium has been shown to bioconcentrate in aquatic organisms at 

the lower end of the food chain (WHO 1983). However, data do not indicate that plutonium is 

bioconcentrated in plants, higher aquatic organisms, or animals. In addition, there is no indication that 

plutonium is biomagnified in terrestrial or aquatic food chains. No additional information on 

bioaccumulation appears to be necessary at this time. 

Exposure Levels in Environmental Media. Reliable monitoring data for the levels of plutonium 

in contaminated media at hazardous waste sites are needed so that the information obtained on levels of 

plutonium in the environment can be used in combination with the known body burden of plutonium to 

assess the potential risk of adverse health effects in populations living in the vicinity of hazardous waste 

sites. 

A number of studies have been performed throughout the years on the fallout associated with the testing 

of nuclear weapons. Information is available on levels in air, water, soil, plant materials, and foodstuffs 

(Ahier and Tracy 1995; Arimoto et al. 2005; Dai et al. 2002; DOE 1999a, 2005a, 2005c, 2005d, 2005e, 

2005f, 2006a; Hirose and Aoyama 2003; Ibrahim et al. 1997; Lee and Clark 2005; Lehto et al. 2006; 
 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 192 

6. POTENTIAL FOR HUMAN EXPOSURE 

Litaor 1999; Mulsow et al. 1999; Struminska and Skwarzec 2004). In particular, information is very 

limited on levels in media associated with areas surrounding waste sites. Such information is needed in 

order to quantify the potential exposure via these sources. Limited data are available on estimates of 

human intake via specific media (e.g., food) (Cooper et al. 1992; Pietrzak-Flis and Orzechowska 1993; 

Sanchez et al. 1999). This information would be important in determining the impact of exposure through 

each of these media. In general, plutonium levels found in environmental media that resulted from fallout 

are low and exposure would also be expected to be low. Plutonium exposure would likely only be 

relevant to individuals living near areas with known plutonium contamination (e.g., nuclear accident sites 

or waste sites). 

Exposure Levels in Humans. Plutonium concentrations have been reported in various tissues and 

biological fluids, including urine, and in lung, liver, and bone tissues obtained from autopsy (Filipy et al. 

2003; Ibrahim et al. 1999; Ivanova et al. 1995; Popplewell et al. 1988; Takizawa 1982; Voelz et al. 1997; 

Wrenn and Cohen 1977). Occupationally exposed populations are likely routinely biomonitored through 

urinalysis. However, such data are not made available and are needed to quantify exposure to these 

individuals. In addition, no information is available on biomonitoring of individuals around NPL sites 

where plutonium has been found or of the general public. 

This information is necessary for assessing the need to conduct health studies on these populations. 

Exposures of Children. Children would be exposed to plutonium from fallout by similar routes are 

adults, such as ingestion of food and water and breathing ambient air. However, levels would generally 

be low for children not living near areas with known plutonium contamination (e.g., areas where nuclear 

accidents or former plutonium processing plants). Limited data on exposures of children to plutonium 

were located. O’Donnell et al. (1997) reported 239,240Pu levels in permanent teeth collected from children 

in the United Kingdom and Republic of Ireland. Priest et al. (1999) reported 239Pu content in urine in 

North London school children. 

There do not appear to be any childhood-specific means to decrease exposure to plutonium. However, as 

levels of plutonium in food and ambient air are generally low, exposure to plutonium would also be 

expected to be low. 

No data were located on plutonium concentrations in breast milk or infant formulas. Additional studies 

on daily intake of plutonium in children and infants would be useful to estimate the exposure of this 
 

 

 

 

 

PLUTONIUM 193 

6. POTENTIAL FOR HUMAN EXPOSURE 

population to plutonium, particularly in areas contaminated with plutonium where exposure may be of 

greater concern. 

Child health data needs relating to susceptibility are discussed in Section 3.12.2, Identification of Data 

Needs: Children’s Susceptibility. 

Exposure Registries. No exposure registries for plutonium were located. This substance is not 

currently one of the compounds for which a sub-registry has been established in the National Exposure 

Registry. The substance will be considered in the future when chemical selection is made for subregistries to be established. The information that is amassed in the National Exposure Registry facilitates 

the epidemiological research needed to assess adverse health outcomes that may be related to exposure to 

this substance. 

USTUR established a database to document levels and distribution of uranium and transuranium isotopes 

in human tissues for occupationally exposed workers who donate their bodies to science (USTUR 2003). 

The Department of Energy (DOE) has developed the Comprehensive Epidemiologic Data Resource 

(CEDR) Program to provide public access to health and exposure data concerning DOE installations. In 

addition, studies relating to populations residing near DOE installations, as well as other studies of 

radiation exposures and health effects, such as atomic bomb survivors, are included in CEDR (CEDR 

2007). 

6.8.2 Ongoing Studies 

No ongoing studies pertaining to the environmental fate of plutonium or plutonium compounds were 

identified in a search of the Federal Research in Progress database (FEDRIP 2007). 
PLUTONIUM 194
 
 

6. POTENTIAL FOR HUMAN EXPOSURE 

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PLUTONIUM 195 

7. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting, 

measuring, and/or monitoring plutonium, its metabolites, and other biomarkers of exposure and effect to 

plutonium. The intent is not to provide an exhaustive list of analytical methods. Rather, the intention is 

to identify well-established methods that are used as the standard methods of analysis. Many of the 

analytical methods used for environmental samples are the methods approved by federal agencies and 

organizations such as EPA and the National Institute for Occupational Safety and Health (NIOSH). Other 

methods presented in this chapter are those that are approved by groups such as the Association of 

Official Analytical Chemists (AOAC) and the American Public Health Association (APHA). 

Additionally, analytical methods are included that modify previously used methods to obtain lower 

detection limits and/or to improve accuracy and precision. 

The accurate and reliable determination of plutonium in biological and environmental samples is 

important because of the potential impact of this element on public health. Analytical methods used to 

measure plutonium in biological and environmental media are highly refined compared to other 

transuranics. Alpha spectrometry is the most widely used method for the determination of plutonium. 

However, this method typically cannot resolve the 239Pu and 240Pu peaks due to their similar energies 

(5.15 and 5.16 MeV). An independent mass spectrometric analysis is required in order to determine the 

individual concentrations of 239Pu and 240Pu (Muramatsu et al. 2001a; Wolf 2006). Mitchell et al. (1997) 

have described a deconvolution technique based on commercial software to resolve the 239,240Pu peaks in 

alpha spectroscopy. Other methods such as thermal ionization mass spectrometry (TIMS) and accelerator 

mass spectrometry (AMS) have been used for the determination of plutonium. Inductively coupled 

plasma-mass spectrometry (ICP-MS) has advantages of ease of operation and rapid analysis. In addition, 

ICP-MS can provide information about the 239Pu/240Pu ratio in a sample, which can, in turn, provide 

important information about the source of plutonium contamination (Muramatsu et al. 2001a; Varga et al. 

2007; Wolf 2006). Interferences that may be observed with ICP-MS are caused by polyatomic ions in the 

plasma, such as 238UH+ and 238UH2

+

, which can interfere with 239Pu and 240Pu, respectively, in samples 

with high concentrations of uranium (Epov et al. 2005; Figg et al. 2000). 

General environmental survey instruments (e.g., alpha particle meters) are available, but they are not 

specific for plutonium. The predominant analytical method for measuring plutonium present at or near 

background concentrations in both biological and environmental media requires radiochemical separation 
 

 

 

 

 

 

 

 

 

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7. ANALYTICAL METHODS 

and purification in conjunction with a quantitative measurement technique (e.g., alpha spectrometry, 

liquid scintillation, or mass spectrometry). 

7.1 BIOLOGICAL MATERIALS 

Methods for the determination of plutonium in biological materials are summarized in Table 7-1. The 

procedures that have been developed for the determination of small quantities of plutonium in biological 

samples, as well as in environmental samples, include the following steps: 

•	 Release of plutonium from the sample's matrix into solution and the addition of plutonium 

tracers; 

•	 Concentration by precipitation with a nonisotopic carrier (e.g., lanthanum or neodymium) or by 

solvent extraction; 

•	 Purification by precipitation, liquid extraction, or ion exchange chromatography; and 

•	 Determination of the plutonium content of the sample by alpha spectroscopy or other techniques. 

Two common methods for releasing plutonium from the sample's matrix into solution are acid extraction 

and acid dissolution. Samples are wet- or dry-ashed prior to solubilization. Leaching the sample with a 

mixture of acids (e.g., nitric acid and hydrochloric acid) has the advantage of easily handling large sample 

volumes, but with the potential disadvantage of leaving plutonium compounds in the residue. The acid 

dissolution procedure includes the addition of excess hydrofluoric acid (HF) to the above mixture of acids 

and results in dissolution of much, if not all, of the sample matrix. Refractory plutonium compounds 

(e.g., PuO2) are more likely to be dissolved upon addition of HF. However, dissolution of interfering 

elements, such as iron, phosphorous, and other rare earths (e.g., alpha-particle emitters) is also increased 

in acid dissolution. 

A third example of a dissolution method is fusion, which is used primarily for decomposition of 

geological and solid environmental media and is suitable for large samples (several grams) (Wolf 2006). 

Fusion decomposition is performed by heating a sample with a flux reagent at atmospheric pressure in a 

graphite, zirconium, or platinum crucible. Common fluxes include hydroxides, peroxides, carbonates, 

bisulfates, hydrosulfates, pyrosulfates, tetraborates, and metaborates. Fusion with sodium hydroxide and 

sodium peroxide (NaOH-Na2O2) is an effective method for decomposition of silica-containing matrices. 

A disadvantage of fusion decomposition is that use of a large amount of flux material results in a solution 
 

 

 

 

 

 

 

PLUTONIUM 197 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Plutonium in Biological Materials 

Sample matrix Preparation method 

Analytical 

method 

Sample 

detection limit 

Percent 

recovery Reference 

Tissue Wet ashed with HNO3/H2O2, 

separation by anion 

exchange, 

ICP-MS 1 fg/mL No data Yamamoto 

et al. 2008a 

Urine Samples were spiked with a 

known amount of plutonium 

and digested with nitric 

acid/hydrogen peroxide 

Non-digested (raw) samples 

were also analyzed 

ICP-MS 0.18 pg/L 

(digested 

samples after 

preconcentration) 

1.9 pg/L (raw 

samples) 

70–100% 

(raw 

samples) 

Epov et al. 

2005 

Tissue Wet ashed with 

HNO3/H2SO4; collected on 

Fe(OH)2; separation by ion 

exchange and 

electrodeposition or 

microprecipitation 

α spectrometry 0.0007 Bq 

(400 minutes) 

No data DOE 1997 

Pu-04-RC 

Tissue Wet ashed with HNO3/HF; 

separation by solvent 

extraction; electrodeposition 

onto platinum disc 

solid state α 

spectrometry 

0.65 Bq 

(400 minutes) 

No data DOE 1997 

Pu-05-RC 

Urine Wet ashing with 

H2O2/HNO3/HCl/HF/H2SO4; 

separation by anion 

exchange chromatography; 

electrodeposition onto 

platinum disc 

solid state α 

spectrometry 

0.60 Bq 

(400 minutes) 

No data DOE 1997 

Pu-06-RC 

Urine Wet ashed with 

HNO3/H2O2/HCl; purified by 

ion exchange 

chromatography 

α spectrometry No data No data DOE 1997 

Pu-07-RC; 

Pu-11-RC 

Tissue Ashed at 400 oC; dissolved 

in HNO3/HCl; filtered; 

decomposed with HF; 

purified by ion exchange 

chromatography 

α spectrometry No data No data DOE 1997 

Pu-08-RC; 

Pu-11-RC 

Tissue Digested with HNO3/H2SO4; 

coprecipitation of plutonium 

with Fe(OH)3; purified by ion 

exchange chromatography 

α spectrometry No data No data DOE 1997 

Pu-09-RC; 

Pu-11-RC 

Tissue Ashing; electrodeposition α spectrometry 

No data No data USTUR 

Method 600 

Biological soft 

tissues 

Wet ash; filter; extract; 

electrodeposition on 

platinum disk 

α spectrometry No data No data Singh and 

Wrenn 1988 

Urine Evaporate; wet ash; filter; 

extract; electrodeposit on 

platinum disk 

α spectrometry No data No data Singh and 

Wrenn 1988 
 

 

 

 

PLUTONIUM 198 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Plutonium in Biological Materials 

Sample matrix Preparation method 

Analytical 

method 

Sample 

detection limit 

Percent 

recovery Reference 

Fecal matter Wet ash; filter; extract; 

electrodeposition on 

platinum disk 

α spectrometry No data No data Singh and 

Wrenn 1988 

Bones Dry ash; reduce valence 

state; extract; electrodeposition on platinum disk 

α spectrometry No data No data Singh and 

Wrenn 1988 

Milk Dry ashed; dissolution in 

HCl; extraction with 

triisooctylamine; 

coprecipitate with lanthanum 

fluoride; filtration 

α spectrometry No data No data EPA 1984 

(Method 

00-09) 

Plant Dissolve starch; filter; wet 

ash; extract; electrodeposition on platinum disk 

α spectrometry 0.0027 pCi 

(0.1x10-4 Bq) 

No data Bunzl and 

Kracke 1987 

ICP-MS = inductively coupled plasma-mass spectrometry 
 

 

 

 

 

 

 

 

 

PLUTONIUM 199 

7. ANALYTICAL METHODS 

with a high content of total dissolved solids, requiring chemical separation of the analyte from the 

dissolved flux material (Wolf 2006). 

Plutonium solutions that contain: (1) other alpha-particle emitters (e.g., americium and neptunium); or 

(2) large amounts of fission products (e.g., cesium), or interfering amounts of other substances such as 

iron, calcium, uranium, and phosphorous need to undergo additional chemical separation procedures. 

Non-radioactive carriers, such as lanthanum fluoride (LaF3), neodymium fluoride (NdF3), and zirconium 

phenylphosphate (ZrC6H6PO4), are used to selectively precipitate the lanthanides. Solvent extraction and 

ion exchange separation methods are preferred methods because of better separations. In addition, they 

do not involve the addition of nonvolatile substances resulting in an easier preparation of the coprecipitation source used for alpha-particle counting. 

These extraction techniques can be made very efficient and selective by adjusting the oxidation state of 

the plutonium and other sample constituents. Common extraction methods specific for plutonium use 

2-thenoyltrifluoroacetone (TTA), tetrapropylammonium trinitrate in isopropylacetone or triisooctylamine, 

cupferron in chloroform, tributylphosphate, and tri-octylphosphine dioxide. Anion exchange methods 

with either nitric or hydrochloric acid solutions are commonly used. Cation exchange column methods 

are less frequently used (Brouns 1980). 

Prior to measurement, the separated and purified plutonium is typically deposited as a very thin layer on a 

highly polished metal plancet. Two techniques that are commonly used are: (1) electrodeposition; and 

(2) co-precipitation with a carrier. In electrodeposition, the plutonium is electrodeposited on a polished 

stainless steel, or platinum disk. In the co-precipitation technique, actinides can be co-precipitated from a 

large volume of solution using anions such as fluorides, hydroxides, and phosphate. Actinides in the trior tetravalent state can be removed from solution by the addition of lanthanide fluoride carriers, such as 

NdF3 or LaF3, which are used to co-precipitate the separated and purified plutonium from solution. Iron 

hydroxide can also be used to co-precipitate actinides from a carbonate-free solution. The precipitate is 

then prepared for counting by either filtration or by evaporation of a slurry of the precipitate onto a 

stainless steel disk (Hindman 1983; Mitchell 1960; Sill and Williams 1981; Talvitie 1972; Wolf 2006). 

The U.S. Department of Energy Environmental Measurement Laboratory Procedures Manual and the U.S. 

Transuranium and Uranium Registries Radio Analysis Procedures Manual provide techniques for the 

determination of plutonium in biological samples using alpha spectroscopy (DOE 1997; USTUR 2001). 
 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 200 

7. ANALYTICAL METHODS 

The other two alpha-particle emitting plutonium isotopes, 236Pu and 242Pu, are normally not found in 

environmentally significant quantities, and are not common constituents of nuclear fuels or waste waters. 

Therefore, they can be used as tracers to aid in the analysis of other isotopes. In this calibration 

procedure, a known quantity of a tracer is added to the sample being analyzed in order to determine the 

yield. This is the percentage of the total amount of plutonium in the sample that is actually measured in 

the electrodeposited amount after the separation, purification, and preparation of the source (Brouns 

1980). 

The most critical step in the analysis of biological samples is complete dissolution of the sample to assure 

solubilization of all plutonium compounds. Biological samples are generally dissolved by wet ashing or a 

combination of wet and dry ashing. High temperatures (700–1,000 °C) during ashing should be avoided 

in order to prevent the formation of an insoluble form of plutonium dioxide (Nielson and Beasley 1980; 

Sill 1975). Plutonium that has been distributed to urine, blood, or soft tissue as a result of metabolic 

processes is usually in a readily soluble form. Lung tissue, feces, and excised tissue from wound sites 

will likely contain insoluble forms of plutonium and will require treatment with HF and repeated ashings 

to effect solubilization. Tissues, feces, and vegetation require repeated treatment with a mixture of 

concentrated nitric acid (HNO3), perchloric acid (HClO4), and sulfuric acid (H2SO4) in order to oxidize 

the large amount of organic materials in these samples. If an insoluble residue remains after repeated 

ashings, then fusion of the residue with gram quantities of an inorganic flux (e.g., sodium carbonate, 

sodium pyrosulfate) can be used to effect solution. Known amounts of a plutonium isotope are 

commonly added subsequent to the dissolution step so that the percentage of plutonium recovered after 

separation and purification (i.e., the yield) may be determined. This added plutonium must be in the same 

chemical form as the plutonium in the sample or the yield estimates will not reflect the percentage of 

plutonium recovered from the dissolved sample (EPA 1976a; Nielson and Beasley 1980). 

Methods used for concentrating plutonium in a sample by a carrier are often specific to one oxidation 

state of the plutonium. For example, the classical bismuth phosphate-lanthanum fluoride method of 

concentrating plutonium from urine samples is specific to plutonium in the tri- and tetravalent states and 

will leave plutonium(VI) in solution. The fate of the various oxidation states of plutonium in humans is 

not well understood and analysis procedures must insure reduction or oxidation of plutonium into 

appropriate oxidation states. Liver and kidney samples may contain metals (e.g., iron) that may greatly 

reduce chemical yields during the final electrodeposition step (EPA 1976a). 
 

 

 

 

 

 

 

 

PLUTONIUM 201 

7. ANALYTICAL METHODS 

Sensitive methods for analysis of plutonium in urine are particularly important for estimating 

occupational plutonium body burdens. Routinely available instrumentation, such as the alpha 

spectrometer, can readily detect these low concentrations. More sensitive methods are commonly 

required for urine samples in order to assess chronic exposures to plutonium. These low detection limits 

were first achieved in the past by nuclear emulsion track counting. In this method, the electrodeposited 

sample is exposed to nuclear track film, subsequent to the isolation of plutonium. The alpha-particle 

emitting isotopes of plutonium will leave tracks on the film, which are counted to quantify the amount of 

plutonium. Nuclear emulsion track counting has been used in the past to measure plutonium 

concentrations in the urine of workers at a nuclear reactor plant (Nielson and Beasley 1980). A type of 

scintillation counting has been used to measure 239Pu and americium-241 (241Am) in animal tissues 

(NCRP 1985). 

Epov et al. (2005) reported a method where nondigested urine samples could be analyzed with a detection 

limit of 1.9 pg/L. The authors noted that in the case of an emergency, urine analysis without digestion 

could provide a rapid determination (about 1 hour) of plutonium levels in urine. However, sample 

digestion would be needed if more precise and sensitive analysis is required. Four hours are required to 

analyze urine samples with digestion (Epov et al. 2005). 

7.2 ENVIRONMENTAL SAMPLES 

Methods for the determination of plutonium in environmental samples are summarized in Table 7-2. The 

separation and extraction methods used to prepare biological samples for plutonium analysis are 

commonly used for environmental samples. Large volumes of air samples (e.g., 10,000 m3

) should be 

collected in order to obtain detectable amounts of plutonium in particulate in air (EPA 1976a). 

Field survey instruments for measuring photons of 241Am in surface soils and on airborne particulates are 

available (e.g., Field Instrument for Detecting Low Energy Radiation or FIDLER) with a minimum 

detection limit of approximately twice the magnitude of a background level of 239Pu (1x103

– 

2x103 pCi/m2

; 37–74 Bq/m2). The FIDLER uses a sodium iodide or calcium fluoride crystal and photonheight discrimination in order to detect the 17 keV x-rays emitted from the progeny of plutonium, or the 

60 keV gamma photons of 241Am. These instruments are useful for identifying areas of contamination, 

but cannot be used to accurately predict the concentration of plutonium in surface soils (EPA 1976a). 

This instrument has been used in aerial surveys of large area sources, such as the Nevada Test Site. 
 

 

 

 

 

 

 

 

PLUTONIUM 202 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Plutonium in Environmental
 

Samples
 

Sample 

matrix Preparation method 

Analytical 

method 

Sample 

detection limit Recovery Reference 

Air filter, 

soil, water, 

vegetation 

Fusion with KF and 

pyrosulfate; dissolution 

in HCl; coprecipitation 

on BaSO4; dissolution of 

α spectrometry No data 85–95% DOE 1999c 

CHEM-TP-A.20 

BaSO4 and 

reprecipitation with 

DPTA 

Water Separation of 

radionuclides by 

Eichrom resins 

α spectrometry 0.6 mBq 

(400 minutes) 

93% DOE 1997 

Se-03 

Soil Plutonium isotopes are 

leached from soil using 

HNO3/HCl 

α spectrometry 1 mBq 

(400 minutes) 

No data DOE 1997 

Pu-02-RC 

Air filter Digestion with HNO3 

followed by treatment 

with HF; decompose 

filters composed of 

organic polymer 

overnithe at 450 oC prior 

to digestion 

α spectrometry No data No data DOE 1997 

Pu-01-RC; 

Pu-11-RC; 

G-03 

Soil, 

sediment 

Plutonium isotopes are 

leached with HNO3/HCl; 

purification by ion 

exchange 

chromatography; 

microprecipitation 

α spectrometry 1 mBq 

(400 minutes) 

No data DOE 1997 

Pu-12-RC 

Water Heated in HNO3/HCl; 

evaporation and 

dissolution in HNO3; 

α spectrometry No data No data DOE 1997 

Pu-07-RC; 

Pu-11-RC; G-03 

purified by ion 

exchange; 

microprecipitation 

Vegetation Ashed at 400 oC; 

dissolved in HNO3/HCl; 

filtered; decomposed 

with HF; purified by ion 

exchange 

chromatography 

α spectrometry No data No data DOE 1997 

Pu-08-RC; 

Pu-11-RC 

Vegetation Digested with 

HNO3/H2SO4; 

coprecipitation of 

plutonium with Fe(OH)3; 

purified by ion exchange 

chromatography 

α spectrometry No data No data DOE 1997 

Pu-09-RC; 

Pu-11-RC 
 

 

 

 

PLUTONIUM 203 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Plutonium in Environmental
 

Samples
 

Sample Analytical Sample 

matrix Preparation method method detection limit Recovery Reference 

Food HNO3, closed-vessel ICP-MS 0.020 pg/g 100±20% Evans et al. 2003 

microwave digestion 

Air Dry ash; filter; extract; α spectrometry No data No data EPA 1984 

reduce valence; (EPA Method 

coprecipitate with 00-04) 

lanthanum fluoride 

Soil, coal, Ashed or evaporated; α spectrometry No data No data EPA 1984 (EPA 

fly ash, dissolved with HF, Method Pu-01) 

ores, HClO4, and HCl; 

vegetation, extraction with 

biotia, and triisooctylamine/pwater xylene; stripped with 

HNO3; wet ashed; coprecipitated with 

lanthanum fluoride; 

filtration 

Water, soil, Ashing; ion exchange α spectrometry 0.02 pCi/sample No data EPA 1979 

air, separation; 

vegetation, electrodeposition 

and animal 

tissue 

Water Filter; extract; α particle No data No data EPA 1980 

coprecipitate with counter (either (EPA method 

lanthanum fluoride proportional or 907.0) 

scintillation 

detectors) 

Drinking Acidify; oxidation with α particle No data 93% EPA 1982 (EPA 

water sodium nitrite; counter Method 911) 

precipitation; extraction 

with tri-isooctylamine; 

co-precipitated with 

lanthanum fluoride 

DPTA = diethylenetriamine-pentaacetic acid; ICP-MS = inductively coupled plasma-mass spectrometry 
 

 

 

 

 

 

 

PLUTONIUM 204 

7. ANALYTICAL METHODS 

Since soil-adsorbed plutonium contamination exists as discrete particles of various sizes, analysis of 

larger soil volumes (25–100 g) is recommended (EPA 1976a). Commonly, soil samples with high 

amounts of carbonate are difficult to analyze. More rapid, efficient, and economical procedures have 

been developed to sequentially analyze a number of radioactive actinides (Hindman 1986). 

The U.S. Department of Energy Environmental Measurement Laboratory provides techniques for the 

determination of plutonium in various biological and environmental samples using alpha spectroscopy. 

EPA methods are available for the determination of plutonium in air, soil, coal fly ash, ores, vegetation, 

biota, and water. APHA has standard methods for determination of gross alpha and beta radioactivity and 

gamma-emitting radionuclides in water, Methods 7110 and 7120, respectively; however, no methods that 

are specific to plutonium isotopes are reported (APHA 1998a, 1998b). No methods were reported by the 

AOAC for the determination of plutonium (AOAC 1990). 

Anderson et al. (2001) reported that the U.S. Food and Drug Administration determines 239Pu 

concentration using electroplating and alpha-spectroscopy, following sequential nitric acid/hydrofluoric 

acid and nitric acid/hydrofluoric acid/hydrochloric acid digestions of ashed food samples. A detection 

limit of 0.004 Bq/kg for 239Pu is reported for this method. 

Alpha spectrometry is the most common analytical method for measuring plutonium concentrations in 

environmental samples. Other measurement techniques available are liquid scintillation, mass 

spectrometry (MS), and gamma spectrometry. ICP-MS has been used increasingly for the determination 

of plutonium in environmental samples (Muramatsu et al. 2001a). Low concentrations of plutonium in 

environmental samples with high salt and organic matter content cause signal suppression and make it 

difficult to obtain an accurate plutonium determination. Preconcentration and matrix separation are 

typically required in these analyses (Epov et al. 2005; Figg et al. 2000). 

MS is used by some research laboratories to determine the concentration of each plutonium isotope, 

including the naturally-occurring 244Pu. MS determines the number of atoms of a given mass number 

and, therefore, can measure the concentration of all of the plutonium isotopes, not only the alpha-particle 

emitters as in alpha spectrometry. MS is several orders of magnitude more sensitive than alpha 

spectrometry in determining the quantities of plutonium isotopes with long half-lives, which also tend to 

be the heavier isotopes. 
 

 

 

 

 

 

 

 

 

 

PLUTONIUM 205 

7. ANALYTICAL METHODS 

Quantities of 241Pu, a beta-particle emitter, can be quantified from assumed isotopic abundance ratios; 

estimated in-growth of its progeny 241Am by gamma spectrometry; or MS (EPA 1976a). 241Am is 

produced from the beta decay of 241Pu and, therefore, can be used to indirectly measure the concentration 

of 241Pu (Metz and Waterbury 1962). Direct determination of 241Pu by measurement of its low energy 

beta-particle decay has been reported using liquid scintillation analysis (Martin 1986). 

7.3 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of plutonium is available. Where adequate information is not 

available, ATSDR, in conjunction with NTP, is required to assure the initiation of a program of research 

designed to determine the health effects (and techniques for developing methods to determine such health 

effects) of plutonium. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

7.3.1 Identification of Data Needs 

Analytical methods are available and are adequately sensitive to detect plutonium isotopes in biological 

materials (e.g., blood, urine, and bone) and in environmental samples (e.g., water, soil, air, and food). No 

data needs are identified at this time. 

Methods for Determining Biomarkers of Exposure and Effect. 

Exposure. There are methods available for measuring the isotopes of plutonium in biological samples. 

The measurement of plutonium in the urine is considered a biomarker of exposure to plutonium. Methods 

are available to detect plutonium in the urine. However, no information was available concerning the 

reliability of these methods for determining plutonium levels in the urine. Plutonium can be determined 

sensitively and selectively by alpha spectrometry and ICP-MS in urine and tissues (DOE 1997; Epov et 
 

 

 

 

 

PLUTONIUM 206 

7. ANALYTICAL METHODS 

al. 2005). Analytical methods with satisfactory sensitivity and precision are available to determine levels 

of plutonium in human tissues and body fluids. 

Effect. Existing methods are sensitive enough to measure background levels for plutonium in the 

population and levels at which biological effects occur. 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. Environmental media are analyzed to identify contaminated areas and to determine if 

contaminant levels constitute a concern for human health. The detection of plutonium in air, water, and 

soil is of concern due to the potential for human exposure. There are many steps involved in the analysis 

of plutonium in environmental media. Alpha spectrometry a satisfactory method available for the 

determination of plutonium in water, air, and solid waste samples (DOE 1997, 1999c). 

7.3.2 Ongoing Studies 

No ongoing studies pertaining to analytical methods for plutonium were identified in a search of the 

Federal Research in Progress database (FEDRIP 2007). 
 

 

 

 

 

 

 

PLUTONIUM 207 

8. REGULATIONS, ADVISORIES, AND GUIDELINES
 

International and national regulations and guidelines pertinent to human exposure to plutonium and to 

other radioactive substances are summarized in Table 8-1. Recommendations for radiation protection for 

people in the general population as a result of exposure to radiation in the environment are found in the 

International Commission on Radiological Protection (ICRP) Publication 60 (ICRP 1991). National 

guidelines for occupational radiation protection are found in the "Federal Radiation Protection Guidance 

for Occupational Exposure" (EPA 1987). The guidance presents general principles for the radiation 

protection of workers and specifies the numerical primary guides for limiting occupational exposure. 

These recommendations are consistent with the ICRP (ICRP 1991). 

The basic philosophy of radiation protection is the concept of ALARA (As Low As Reasonably 

Achievable). ALARA requires that social and economic factors to be taken into consideration, and 

that further reductions in dose are not indicated where the costs of reducing exposure become 

disproportionate to the benefit achieved. As a rule, all exposure should be kept as low as reasonably 

achievable and the regulations and guidelines are meant to give an upper limit to exposure. Based on the 

primary guidelines (EPA 1987), guides for Annual Limits on Intake (ALIs) and Derived Air 

Concentrations (DACs) have been calculated (USNRC 2007a). The ALI is defined as "the annual intake 

of a given radionuclide by Reference Man which would result in a committed effective dose equivalent of 

5 rems (stochastic) or 50 rems to an organ or tissue (non-stochastic)” (USNRC 2007a). The DAC is 

defined as "the concentration of a given radionuclide in air which, if breathed by the reference man for a 

working year of 2,000 hours under conditions of light work (inhalation rate of 1.2 m3

 of air/hour), results 

in the intake of one ALI" (USNRC 2009a). The ALIs and DACs refer to occupational situations, but may 

be converted to apply to exposure of persons in the general population by application of conversion 

factors (Table 8-1). 

No inhalation or oral MRLs were derived for plutonium or plutonium compounds. 

The EPA IRIS database has withdrawn its cancer classification for radionuclides, but the EPA Office of 

Air and Radiation believes that all radionuclides, including the plutonium isotopes, should be considered 

to be known carcinogens, and has assigned them to Group A. Carcinogenic toxicity values for plutonium 

isotopes are listed in EPA’s Radionuclide Table: Radionuclide Carcinogenicity – Slope Factors (Federal 

Guidance Report No. 13 Morbidity Risk Coefficients, in Units of Picocuries) (EPA 2001). Lifetime 

excess total cancer risk per unit intake is included for water ingestion, food ingestion, soil ingestion, 
 

 

 

 

 

 

 

 

 

PLUTONIUM 208 

8. REGULATIONS, ADVISORIES, AND GUIDELINES 

Table 8-1. Regulations, Advisories, and Guidelines Applicable to Plutonium and 

Plutonium Compounds
 

Agency Description Information Reference 

INTERNATIONAL 

Guidelines: 

IARC Carcinogenicity classification 

239Pu and its decay products (may 

contain 240Pu and other isotopes), as 

aerosols 

Group 1a 

IARC 2006 

ICRP Occupational—whole body exposure 5 rem/year ICRP 1977 

Individual—short-term, to critical 

populations 

0.5 rem/year 

Individual—chronic exposure 0.1 rem/year 

WHO Air quality guidelines No data WHO 2000 

Drinking water quality guidelines No data WHO 2004 

NATIONAL 

Regulations and 

Guidelines: 

a. Air 

ACGIH Dose limits for exposure to ionizing 

radiation 

ACGIH 2006 

Effective dose 

In any single year 50 mSv 

Averaged over 5 years 20 mSv per year 

Annual equivalent dose to 

Lens of the eye 150 mSv 

Skin 500 mSv 

Hands and feet 500 mSv 

Embryo-fetus exposures once the 

pregnancy is known 

Monthly equivalent dose 

Dose to the surface of women’s 

abdomen (lower trunk) 

0.5 mSv 

2 mSv for the remainder 

of the pregnancy 

Intake of radionuclide 1/20 of ALI 

EPA AEGL-1, -2, and -3 No data EPA 2007b 

Occupational—the committed effective 

dose equivalent (internal) and annual 

effective dose equivalent (external) 

combined 

5 rem/year EPA 1987 
 

 

 

 

 

 

 

 

 

PLUTONIUM	 209 

8. REGULATIONS, ADVISORIES, AND GUIDELINES 

Table 8-1. Regulations, Advisories, and Guidelines Applicable to Plutonium and 

Plutonium Compounds
 

Agency Description	 Information Reference 

NATIONAL (cont.) 

FRC	 Individual—whole body exposure 5 rem/year 

Individual—operational guide for 0.17 rem/year 

“suitable sample of population” when 

individual whole body doses are not 

known 

EPA	 National emission standards for 10 mrem/year
 

emissions of radionuclides other than 

radon from Department of Energy
 

facilities
 

NIOSH	 REL (10-hour TWA) No data 

OSHA	 Exposure limits of individuals to ionizing
 

radiation in restricted areas (rems per
 

calendar quarter)
 

Whole body: head and trunk; active 1.25 rems 

blood-forming organs; lens of eyes; 

or gonads 

Hands and forearms; feet and ankles 18.75 rems 

Skin of whole body	 7.5 rems 

USNRC Occupational values for oral ingestion 

ALI (μCi) of Class W
 

236Pu
 2x10+0 

237Pu 1x10+4 

238Pu 9x10-1 (bone surface) 

239Pu 8x10-1 (bone surface) 

240Pu 8x10-1 (bone surface) 

241Pu 4x10+1 (bone surface) 

242Pu 8x10-1 (bone surface) 

243Pu 2x10+4 

244Pu 8x10-1 (bone surface) 

Occupational values for inhalation ALI 

(μCi) of Class Wb 

236Pu 2x10-2 

237Pu 3x10+3 

238Pu 7x10-3 (bone surface) 

239Pu 6x10-3 (bone surface) 

240Pu 6x10-3 (bone surface) 

241Pu 3x10-1 (bone surface) 

242Pu 7x10-3 (bone surface) 

243Pu 4x10+4 

244Pu 7x10-3 (bone surface) 

FRC 1960 

EPA 2002 

40 CFR Part 61 

OSHA 2006 

29 CFR 1910.1096 

USNRC 2007a 

10 CFR 20, 

Appendix B 
 

 

 

 

 

 

PLUTONIUM 210 

8. REGULATIONS, ADVISORIES, AND GUIDELINES 

Table 8-1. Regulations, Advisories, and Guidelines Applicable to Plutonium and 

Plutonium Compounds
 

Agency Description Information Reference 

NATIONAL (cont.) 

Occupational values for inhalation ALI 

(μCi) of Class Yb 

236Pu 

237Pu 

238Pu 

239Pu 

240Pu 

241Pu 

242Pu 

243Pu 

244Pu 

USNRC Occupational values for inhalation DAC 

(μCi/mL) of Class Wb 

236Pu 

237Pu 

238Pu 

239Pu 

240Pu 

241Pu 

242Pu 

243Pu 

244Pu 

Occupational values for inhalation DAC 

(μCi/mL) of Class Yb 

236Pu 

237Pu 

238Pu 

239Pu 

240Pu 

241Pu 

242Pu 

243Pu 

244Pu 

b. Water 

Drinking water standards and health 

advisories for gross alpha particle 

activity 

10-4 Cancer risk 

National primary drinking water 

standards for alpha particles 

MCLG 

MCL 

Public health goal 

4x10-2
 

3x10+3
 

2x10-2
 

2x10-2 (bone surface)
 

2x10-2 (bone surface)
 

8x10-1 (bone surface)
 

2x10-2 (bone surface)
 

4x10+4
 

2x10-2 (bone surface)
 

8x10-12
 

1x10-6
 

3x10-12
 

3x10-12
 

3x10-12
 

1x10-10
 

3x10-12
 

2x10-5
 

3x10-12
 

2x10-11
 

1x10-6
 

8x10-12
 

7x10-12
 

7x10-12
 

3x10-10
 

7x10-12
 

2x10-5
 

7x10-12
 

15 pCi/L
 

Zero
 

15 pCi/L
 

Zero
 

USNRC 2007a 

10 CFR 20, 

Appendix B 

EPA 2006 

EPA 2003 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 211 

8. REGULATIONS, ADVISORIES, AND GUIDELINES 

Table 8-1. Regulations, Advisories, and Guidelines Applicable to Plutonium and 

Plutonium Compounds
 

Agency Description Information Reference 

NATIONAL (cont.) 

c. Food No data 

FDA Guidance level for radionuclide in 

domestic and imported food 

FDA 2004 

Derived intervention level 2 Bq/kg 

d. Other 

ACGIH Carcinogenicity classification No data ACGIH 2006 

EPA Carcinogenicity classification Group Ac EPA 2001 

EPA Superfund, emergency planning, and 

community right-to-know 

EPA 2007c 

40 CFR 302.4 

Designated CERCLA hazardous 

substance 

Reportable quantity (Ci) 

236Pu 

237Pu 

238Pu 

239Pu 

240Pu 

241Pu 

242Pu 

243Pu 

244Pu 

0.1 

1,000 

0.01 

0.01 

0.01 

1 

0.01 

1,000 

0.01 

NTP Carcinogenicity classification Known to be human 

carcinogens 

NTP 2005 

a

Group 1: carcinogenic to humans

b

The ALIs and DACs for inhalation are given for an aerosol with an activity median aerodynamic diameter (AMAD) of
 

1 μm and for three classes (D,W,Y) of radioactive material, which refer to their retention (approximately days, weeks,
 

or years) in the pulmonary region of the lung. This classification applies to a range of clearance half-times of less
 

than 10 days for D, for W from 10 to 100 days, and for Y greater than 100 days (USNRC 2007a).
 c

Group A: known human carcinogen
 

ACGIH = American Conference of Governmental Industrial Hygienists; AEGL = Acute Exposure Guideline Levels;
 

ALI = Annual Limit on Intake; CERCLA = Comprehensive Environmental Response, Compensation, and Liability Act;
 

CFR = Code of Federal Regulations; DAC = Derived Air Concentration; EPA = Environmental Protection Agency;
 

FDA = Food and Drug Administration; FRC = Federal Radiation Council; IARC = International Agency for Research
 

on Cancer; ICRP = International Commission on Radiological Protection; MCL = maximum contaminant level;
 

MCLG = maximum contaminant level goal; NIOSH = National Institute for Occupational Safety and Health;
 

NTP = National Toxicology Program; OSHA = Occupational Safety and Health Administration; REL = recommended 

exposure limit; RfC = inhalation reference concentration; RfD = oral reference dose; TWA = time-weighted average;
 

USNRC = U.S. Nuclear Regulatory Commission; WHO = World Health Organization
 
 

PLUTONIUM 212 

8. REGULATIONS, ADVISORIES, AND GUIDELINES 

inhalation, and external exposure. The risk values for selected plutonium isotopes are presented in 

Table 8-2. The EPA has not derived reference concentrations (RfCs) or reference doses (RfDs) for 

plutonium (IRIS 2009), but has derived a maximum contaminant level (MCL) of 15 pCi/L for total alphaemitters (including plutonium), less uranium and radon (EPA 2003). 
 

 

 

 

 

 

 

 

 

 

PLUTONIUM 213 

8. REGULATIONS, ADVISORIES, AND GUIDELINES 

Table 8-2. Radionuclide Carcinogenicity—Slope Factors for Plutonium (Federal
 

Guidance Report No. 13 Morbidity Risk Coefficients, in Units of Picocuries)a
 

Slope factor (morbidity risk coefficient) lifetime excess total cancer risk per unit 

intake or exposure 

Gastro- External 

intestinal Water Food Soil exposure 

absorption ingestion ingestion ingestion Inhalation (risk/year 

Isotopeb Fractionc (risk/pCi) (risk/pCi) (risk/pCi) (risk/pCi) per pCi/g) 

Pu-234 5.00x10-4 8.58x10-13 1.25x10-12 2.39x10-12 6.85x10-11 1.61x10-7
 

Pu-235 5.00x10-4 4.37x10-15 6.03x10-15 9.73x10-15 2.39x10-15 2.37x10-7
 

Pu-236 5.00x10-4 7.47x10-11 9.92x10-11 1.74x10-10 2.28x10-8 1.19x10-10
 

Pu-237 5.00x10-4 5.77x10-13 8.40x10-13 1.62x10-12 1.27x10-12 1.12x10-7
 

Pu-238 5.00x10-4 1.31x10-10 1.69x10-10 2.72x10-10 3.36x10-8 7.22x10-11
 

Pu-239 5.00x10-4 1.35x10-10 1.74x10-10 2.76x10-10 3.33x10-8 2.00x10-10
 

Pu-240 5.00x10-4 1.35x10-10 1.74x10-10 2.77x10-10 3.33x10-8 6.98x10-11
 

Pu-241 5.00x10-4 1.76x10-12 2.28x10-12 3.29x10-12 3.34x10-10 4.11x10-12
 

Pu-242 5.00x10-4 1.28x10-10 1.65x10-10 2.63x10-10 3.13x10-8 6.25x10-11
 

Pu-243 5.00x10-4 4.74x10-13 6.92x10-13 1.34x10-12 2.94x10-13 5.50x10-8
 

Pu-244 5.00x10-4 1.37x10-10 1.80x10-10 2.94x10-10 2.93x10-8 3.01x10-11
 

Pu-245 5.00x10-4 4.48x10-12 6.55x10-12 1.28x10-11 2.07x10-12 1.77x10-6
 

Pu-246 5.00x10-4 1.73x10-11 2.53x10-11 4.92x10-11 1.73x10-11 4.04x10-7
 

a

EPA classifies all radionuclides as Group A (known human) carcinogens. Radionuclide risk coefficients, or slope 

factors, are calculated by EPA's ORIA to assist HEAST users with risk-related evaluations and decision-making at 

various stages of the remediation process. Most values presented are taken from EPA (1999, 2000); risk 

estimates for the soil ingestion pathway are not addressed, but have been computed using similar methods. 

Ingestion and inhalation slope factors are central estimates in a linear model of the age-averaged, lifetime 

attributable radiation cancer incidence (fatal and nonfatal cancer) risk per unit of activity inhaled or ingested, 

expressed as risk/pCi. Slope factors can be converted into the SI units of becquerels (1 Bq=1 nuclear 

transformation per second) by dividing each inhalation, ingestion, or external exposure value by 0.037. Ci, the 

customary unit of activity is equal to 3.7x1,010 nuclear transformations per second (1 pCi=10–12 Ci). Inhalation 

values for particulates represent the indicated ICRP lung absorption type (medium, particulate). External exposure 

slope factors are central estimates of the lifetime attributable radiation cancer incidence risk for each year of 

exposure to external radiation from photon-emitting radionuclides uniformly distributed in a thick layer of soil 

(expressed as risk/year per pCi/g of soil).

b

For each radionuclide listed, slope factors correspond to the risks per unit intake or exposure for that radionuclide 

only. 

c

Gastrointestinal absorption fractions are the fractional amounts of each radionuclide absorbed across the 

gastrointestinal tract into the bloodstream. 

Bq = Becquerel; Ci = curie; EPA = Environmental Protection Agency; HEAST = Health Effects Assessment 

Summary Table; ICRP = International Commission on Radiological Protection; ORIA = Office of Radiation and 

Indoor Air; pCi = picocurie; SI = International System 

Source: EPA 2001 
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10. GLOSSARY
 

Absorbed dose—The amount of energy deposited by ionizing radiation in a unit mass of tissue. It is 

expressed in units of joule per kilogram (J/kg), and called “Gray” (Gy). 

Absorption—The taking up of liquids by solids, or of gases by solids or liquids. 

Acute Exposure—Exposure to a chemical for a duration of 14 days or less, as specified in the 

Toxicological Profiles. 

Adsorption—The adhesion in an extremely thin layer of molecules (as of gases, solutes, or liquids) to the 

surfaces of solid bodies or liquids with which they are in contact. 

Adsorption Coefficient (Koc)—The ratio of the amount of a chemical adsorbed per unit weight of 

organic carbon in the soil or sediment to the concentration of the chemical in solution at equilibrium. 

Adsorption Ratio (Kd)—The amount of a chemical adsorbed by sediment or soil (i.e., the solid phase) 

divided by the amount of chemical in the solution phase, which is in equilibrium with the solid phase, at a 

fixed solid/solution ratio. It is generally expressed in micrograms of chemical sorbed per gram of soil or 

sediment. 

Benchmark Dose (BMD)—Usually defined as the lower confidence limit on the dose that produces a 

specified magnitude of changes in a specified adverse response. For example, a BMD10 would be the 

dose at the 95% lower confidence limit on a 10% response, and the benchmark response (BMR) would be 

10%. The BMD is determined by modeling the dose response curve in the region of the dose response 

relationship where biologically observable data are feasible. 

Benchmark Dose Model—A statistical dose-response model applied to either experimental toxicological 

or epidemiological data to calculate a BMD. 

Bioconcentration Factor (BCF)—The quotient of the concentration of a chemical in aquatic organisms 

at a specific time or during a discrete time period of exposure divided by the concentration in the 

surrounding water at the same time or during the same period. 

Biomarkers—Broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility. 

Cancer Effect Level (CEL)—The lowest dose of chemical in a study, or group of studies, that produces 

significant increases in the incidence of cancer (or tumors) between the exposed population and its 

appropriate control. 

Carcinogen—A chemical capable of inducing cancer. 

Case-Control Study—A type of epidemiological study that examines the relationship between a 

particular outcome (disease or condition) and a variety of potential causative agents (such as toxic 

chemicals). In a case-controlled study, a group of people with a specified and well-defined outcome is 

identified and compared to a similar group of people without outcome. 

Case Report—Describes a single individual with a particular disease or exposure. These may suggest 

some potential topics for scientific research, but are not actual research studies. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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10. GLOSSARY 

Case Series—Describes the experience of a small number of individuals with the same disease or 

exposure. These may suggest potential topics for scientific research, but are not actual research studies. 

Ceiling Value—A concentration of a substance that should not be exceeded, even instantaneously. 

Chronic Exposure—Exposure to a chemical for 365 days or more, as specified in the Toxicological 

Profiles. 

Cohort Study—A type of epidemiological study of a specific group or groups of people who have had a 

common insult (e.g., exposure to an agent suspected of causing disease or a common disease) and are 

followed forward from exposure to outcome. At least one exposed group is compared to one unexposed 

group. 

Cross-sectional Study—A type of epidemiological study of a group or groups of people that examines 

the relationship between exposure and outcome to a chemical or to chemicals at one point in time. 

Data Needs—Substance-specific informational needs that if met would reduce the uncertainties of human 

health assessment. 

Developmental Toxicity—The occurrence of adverse effects on the developing organism that may result 

from exposure to a chemical prior to conception (either parent), during prenatal development, or 

postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any point 

in the life span of the organism. 

Dose Equivalent—A quantity used in radiation protection to place all radiation on a common scale for 

calculating tissue damage. Dose equivalent is the absorbed dose in grays multiplied by a radiation 

weighting factor. The radiation weighting factor accounts for differences in radiation effects caused by 

different types of ionizing radiation. Some radiation, including alpha particles, causes a greater amount of 

damage per unit of absorbed dose than other radiation. The sievert (Sv) is the unit used to measure dose 

equivalent. 

Dose-Response Relationship—The quantitative relationship between the amount of exposure to a 

toxicant and the incidence of the adverse effects. 

Effective Dose—A dosimetric quantity useful for comparing the overall health effects of irradiation of 

the whole body. It takes into account the absorbed doses received by various organs and tissues and 

weighs them according to present knowledge of the sensitivity of each organ to radiation. It also accounts 

for the type of radiation and the potential for each type to inflict biologic damage. The effective dose is 

used, for example, to compare the overall health detriments of different radionuclides in a given mix. The 

unit of effective dose is the sievert (Sv); 1 Sv = 1 J/kg. 

Embryotoxicity and Fetotoxicity—Any toxic effect on the concepts as a result of prenatal exposure to a 

chemical; the distinguishing feature between the two terms is the stage of development during which the 

insult occurs. The terms, as used here, include malformations and variations, altered growth, and in utero 

death. 

Environmental Protection Agency (EPA) Health Advisory—An estimate of acceptable drinking water 

levels for a chemical substance based on health effects information. A health advisory is not a legally 

enforceable federal standard, but serves as technical guidance to assist federal, state, and local officials. 
 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 257 

10. GLOSSARY 

Epidemiology—Refers to the investigation of factors that determine the frequency and distribution of 

disease or other health-related conditions within a defined human population during a specified period. 

Equivalent Dose—The absorbed dose in an organ or tissue multiplied by the relevant radiation weighting 

factor wR. 

Genotoxicity—A specific adverse effect on the genome of living cells that, upon the duplication of 

affected cells, can be expressed as a mutagenic, clastogenic, or carcinogenic event because of specific 

alteration of the molecular structure of the genome. 

Half-life—A measure of rate for the time required to eliminate one half of a quantity of a chemical from 

the body or environmental media. 

Immediately Dangerous to Life or Health (IDLH)—The maximum environmental concentration of a 

contaminant from which one could escape within 30 minutes without any escape-impairing symptoms or 

irreversible health effects. 

Immunologic Toxicity—The occurrence of adverse effects on the immune system that may result from 

exposure to environmental agents such as chemicals. 

Immunological Effects—Functional changes in the immune response. 

Incidence—The ratio of individuals in a population who develop a specified condition to the total 

number of individuals in that population who could have developed that condition in a specified time 

period. 

Intermediate Exposure—Exposure to a chemical for a duration of 15–364 days, as specified in the 

Toxicological Profiles. 

In Vitro—Isolated from the living organism and artificially maintained, as in a test tube. 

In Vivo—Occurring within the living organism. 

Lethal Concentration(LO) (LCLO)—The lowest concentration of a chemical in air that has been reported 

to have caused death in humans or animals. 

Lethal Concentration(50) (LC50)—A calculated concentration of a chemical in air to which exposure for 

a specific length of time is expected to cause death in 50% of a defined experimental animal population. 

Lethal Dose(LO) (LDLo)—The lowest dose of a chemical introduced by a route other than inhalation that 

has been reported to have caused death in humans or animals. 

Lethal Dose(50) (LD50)—The dose of a chemical that has been calculated to cause death in 50% of a 

defined experimental animal population. 

Lethal Time(50) (LT50)—A calculated period of time within which a specific concentration of a chemical 

is expected to cause death in 50% of a defined experimental animal population. 

Lowest-Observed-Adverse-Effect Level (LOAEL)—The lowest exposure level of chemical in a study, 

or group of studies, that produces statistically or biologically significant increases in frequency or severity 

of adverse effects between the exposed population and its appropriate control. 
 

 

 

 

 

 

 

PLUTONIUM 258 

10. GLOSSARY 

Lymphoreticular Effects—Represent morphological effects involving lymphatic tissues such as the 

lymph nodes, spleen, and thymus. 

Malformations—Permanent structural changes that may adversely affect survival, development, or 

function. 

Minimal Risk Level (MRL)—An estimate of daily human exposure to a hazardous substance that is 

likely to be without an appreciable risk of adverse noncancer health effects over a specified route and 

duration of exposure. 

Modifying Factor (MF)—A value (greater than zero) that is applied to the derivation of a Minimal Risk 

Level (MRL) to reflect additional concerns about the database that are not covered by the uncertainty 

factors. The default value for a MF is 1. 

Morbidity—State of being diseased; morbidity rate is the incidence or prevalence of disease in a specific 

population. 

Mortality—Death; mortality rate is a measure of the number of deaths in a population during a specified 

interval of time. 

Mutagen—A substance that causes mutations. A mutation is a change in the DNA sequence of a cell’s 

DNA. Mutations can lead to birth defects, miscarriages, or cancer. 

Necropsy—The gross examination of the organs and tissues of a dead body to determine the cause of 

death or pathological conditions. 

Neurotoxicity—The occurrence of adverse effects on the nervous system following exposure to a 

chemical. 

No-Observed-Adverse-Effect Level (NOAEL)—The dose of a chemical at which there were no 

statistically or biologically significant increases in frequency or severity of adverse effects seen between 

the exposed population and its appropriate control. Effects may be produced at this dose, but they are not 

considered to be adverse. 

Octanol-Water Partition Coefficient (Kow)—The equilibrium ratio of the concentrations of a chemical 

in n-octanol and water, in dilute solution. 

Odds Ratio (OR)—A means of measuring the association between an exposure (such as toxic substances 

and a disease or condition) that represents the best estimate of relative risk (risk as a ratio of the incidence 

among subjects exposed to a particular risk factor divided by the incidence among subjects who were not 

exposed to the risk factor). An OR of greater than 1 is considered to indicate greater risk of disease in the 

exposed group compared to the unexposed group. 

Organophosphate or Organophosphorus Compound—A phosphorus-containing organic compound 

and especially a pesticide that acts by inhibiting cholinesterase. 

Permissible Exposure Limit (PEL)—An Occupational Safety and Health Administration (OSHA) 

allowable exposure level in workplace air averaged over an 8-hour shift of a 40-hour workweek. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM 259 

10. GLOSSARY 

Pesticide—General classification of chemicals specifically developed and produced for use in the control 

of agricultural and public health pests. 

Pharmacokinetics—The dynamic behavior of a material in the body, used to predict the fate 

(disposition) of an exogenous substance in an organism. Utilizing computational techniques, it provides 

the means of studying the absorption, distribution, metabolism, and excretion of chemicals by the body. 

Pharmacokinetic Model—A set of equations that can be used to describe the time course of a parent 

chemical or metabolite in an animal system. There are two types of pharmacokinetic models: data-based 

and physiologically-based. A data-based model divides the animal system into a series of compartments, 

which, in general, do not represent real, identifiable anatomic regions of the body, whereas the 

physiologically-based model compartments represent real anatomic regions of the body. 

Physiologically Based Pharmacodynamic (PBPD) Model—A type of physiologically based doseresponse model that quantitatively describes the relationship between target tissue dose and toxic end 

points. These models advance the importance of physiologically based models in that they clearly 

describe the biological effect (response) produced by the system following exposure to an exogenous 

substance. 

Physiologically Based Pharmacokinetic (PBPK) Model—Comprised of a series of compartments 

representing organs or tissue groups with realistic weights and blood flows. These models require a 

variety of physiological information: tissue volumes, blood flow rates to tissues, cardiac output, alveolar 

ventilation rates, and possibly membrane permeabilities. The models also utilize biochemical 

information, such as air/blood partition coefficients, and metabolic parameters. PBPK models are also 

called biologically based tissue dosimetry models. 

Prevalence—The number of cases of a disease or condition in a population at one point in time. 

Prospective Study—A type of cohort study in which the pertinent observations are made on events 

occurring after the start of the study. A group is followed over time. 

q1*—The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the 

multistage procedure. The q1* can be used to calculate an estimate of carcinogenic potency, the 

incremental excess cancer risk per unit of exposure (usually μg/L for water, mg/kg/day for food, and 

μg/m3 for air). 

Recommended Exposure Limit (REL)—A National Institute for Occupational Safety and Health 

(NIOSH) time-weighted average (TWA) concentration for up to a 10-hour workday during a 40-hour 

workweek. 

Reference Concentration (RfC)—An estimate (with uncertainty spanning perhaps an order of 

magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) 

that is likely to be without an appreciable risk of deleterious noncancer health effects during a lifetime. 

The inhalation reference concentration is for continuous inhalation exposures and is appropriately 

expressed in units of mg/m3 or ppm. 

Reference Dose (RfD)—An estimate (with uncertainty spanning perhaps an order of magnitude) of the 

daily exposure of the human population to a potential hazard that is likely to be without risk of deleterious 

effects during a lifetime. The RfD is operationally derived from the no-observed-adverse-effect level 

(NOAEL, from animal and human studies) by a consistent application of uncertainty factors that reflect 

various types of data used to estimate RfDs and an additional modifying factor, which is based on a 
 

 

 

 

 

 

 

PLUTONIUM 260 

10. GLOSSARY 

professional judgment of the entire database on the chemical. The RfDs are not applicable to 

nonthreshold effects such as cancer. 

Reportable Quantity (RQ)—The quantity of a hazardous substance that is considered reportable under 

the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). Reportable 

quantities are (1) 1 pound or greater or (2) for selected substances, an amount established by regulation 

either under CERCLA or under Section 311 of the Clean Water Act. Quantities are measured over a 

24-hour period. 

Reproductive Toxicity—The occurrence of adverse effects on the reproductive system that may result 

from exposure to a chemical. The toxicity may be directed to the reproductive organs and/or the related 

endocrine system. The manifestation of such toxicity may be noted as alterations in sexual behavior, 

fertility, pregnancy outcomes, or modifications in other functions that are dependent on the integrity of 

this system. 

Retrospective Study—A type of cohort study based on a group of persons known to have been exposed 

at some time in the past. Data are collected from routinely recorded events, up to the time the study is 

undertaken. Retrospective studies are limited to causal factors that can be ascertained from existing 

records and/or examining survivors of the cohort. 

Risk—The possibility or chance that some adverse effect will result from a given exposure to a chemical. 

Risk Factor—An aspect of personal behavior or lifestyle, an environmental exposure, or an inborn or 

inherited characteristic that is associated with an increased occurrence of disease or other health-related 

event or condition. 

Risk Ratio—The ratio of the risk among persons with specific risk factors compared to the risk among 

persons without risk factors. A risk ratio greater than 1 indicates greater risk of disease in the exposed 

group compared to the unexposed group. 

Short-Term Exposure Limit (STEL)—The American Conference of Governmental Industrial 

Hygienists (ACGIH) maximum concentration to which workers can be exposed for up to 15 minutes 

continually. No more than four excursions are allowed per day, and there must be at least 60 minutes 

between exposure periods. The daily Threshold Limit Value-Time Weighted Average (TLV-TWA) may 

not be exceeded. 

Standardized Mortality Ratio (SMR)—A ratio of the observed number of deaths and the expected 

number of deaths in a specific standard population. 

Target Organ Toxicity—This term covers a broad range of adverse effects on target organs or 

physiological systems (e.g., renal, cardiovascular) extending from those arising through a single limited 

exposure to those assumed over a lifetime of exposure to a chemical. 

Teratogen—A chemical that causes structural defects that affect the development of an organism. 

Threshold Limit Value (TLV)—An American Conference of Governmental Industrial Hygienists 

(ACGIH) concentration of a substance to which most workers can be exposed without adverse effect. 

The TLV may be expressed as a Time Weighted Average (TWA), as a Short-Term Exposure Limit 

(STEL), or as a ceiling limit (CL). 
 

 

 

 

PLUTONIUM 261 

10. GLOSSARY 

Time-Weighted Average (TWA)—An allowable exposure concentration averaged over a normal 8-hour 

workday or 40-hour workweek. 

Toxic Dose(50) (TD50)—A calculated dose of a chemical, introduced by a route other than inhalation, 

which is expected to cause a specific toxic effect in 50% of a defined experimental animal population. 

Toxicokinetic—The absorption, distribution, and elimination of toxic compounds in the living organism. 

Uncertainty Factor (UF)—A factor used in operationally deriving the Minimal Risk Level (MRL) or 

Reference Dose (RfD) or Reference Concentration (RfC) from experimental data. UFs are intended to 

account for (1) the variation in sensitivity among the members of the human population, (2) the 

uncertainty in extrapolating animal data to the case of human, (3) the uncertainty in extrapolating from 

data obtained in a study that is of less than lifetime exposure, and (4) the uncertainty in using lowestobserved-adverse-effect level (LOAEL) data rather than no-observed-adverse-effect level (NOAEL) data. 

A default for each individual UF is 10; if complete certainty in data exists, a value of 1 can be used; 

however, a reduced UF of 3 may be used on a case-by-case basis, 3 being the approximate logarithmic 

average of 10 and 1. 

Xenobiotic—Any chemical that is foreign to the biological system. 
PLUTONIUM 262
 

10. GLOSSARY 

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PLUTONIUM A-1 

APPENDIX A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS 

The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) [42 U.S.C. 

9601 et seq.], as amended by the Superfund Amendments and Reauthorization Act (SARA) [Pub. L. 99– 

499], requires that the Agency for Toxic Substances and Disease Registry (ATSDR) develop jointly with 

the U.S. Environmental Protection Agency (EPA), in order of priority, a list of hazardous substances most 

commonly found at facilities on the CERCLA National Priorities List (NPL); prepare toxicological 

profiles for each substance included on the priority list of hazardous substances; and assure the initiation 

of a research program to fill identified data needs associated with the substances. 

The toxicological profiles include an examination, summary, and interpretation of available toxicological 

information and epidemiologic evaluations of a hazardous substance. During the development of 

toxicological profiles, Minimal Risk Levels (MRLs) are derived when reliable and sufficient data exist to 

identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration for a 

given route of exposure. An MRL is an estimate of the daily human exposure to a hazardous substance 

that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration 

of exposure. MRLs are based on noncancer health effects only and are not based on a consideration of 

cancer effects. These substance-specific estimates, which are intended to serve as screening levels, are 

used by ATSDR health assessors to identify contaminants and potential health effects that may be of 

concern at hazardous waste sites. It is important to note that MRLs are not intended to define clean-up or 

action levels. 

MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty factor 

approach. They are below levels that might cause adverse health effects in the people most sensitive to 

such chemical-induced effects. MRLs are derived for acute (1–14 days), intermediate (15–364 days), and 

chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. Currently, 

MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified a method 

suitable for this route of exposure. MRLs are generally based on the most sensitive chemical-induced end 

point considered to be of relevance to humans. Serious health effects (such as irreparable damage to the 

liver or kidneys, or birth defects) are not used as a basis for establishing MRLs. Exposure to a level 

above the MRL does not mean that adverse health effects will occur. 

MRLs are intended only to serve as a screening tool to help public health professionals decide where to 

look more closely. They may also be viewed as a mechanism to identify those hazardous waste sites that 
 

 

 

 

 

 

 

PLUTONIUM A-2 

APPENDIX A 

are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of 

the lack of precise toxicological information on the people who might be most sensitive (e.g., infants, 

elderly, nutritionally or immunologically compromised) to the effects of hazardous substances. ATSDR 

uses a conservative (i.e., protective) approach to address this uncertainty consistent with the public health 

principle of prevention. Although human data are preferred, MRLs often must be based on animal studies 

because relevant human studies are lacking. In the absence of evidence to the contrary, ATSDR assumes 

that humans are more sensitive to the effects of hazardous substance than animals and that certain persons 

may be particularly sensitive. Thus, the resulting MRL may be as much as 100-fold below levels that 

have been shown to be nontoxic in laboratory animals. 

Proposed MRLs undergo a rigorous review process: Health Effects/MRL Workgroup reviews within the 

Division of Toxicology and Environmental Medicine, expert panel peer reviews, and agency-wide MRL 

Workgroup reviews, with participation from other federal agencies and comments from the public. They 

are subject to change as new information becomes available concomitant with updating the toxicological 

profiles. Thus, MRLs in the most recent toxicological profiles supersede previously published levels. 

For additional information regarding MRLs, please contact the Division of Toxicology and 

Environmental Medicine, Agency for Toxic Substances and Disease Registry, 1600 Clifton Road NE, 

Mailstop F-62, Atlanta, Georgia 30333. 

MRLs were not derived for plutonium, as discussed in Section 2.3. 
 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM	 B-1 

APPENDIX B. USER'S GUIDE 

Chapter 1 

Public Health Statement 

This chapter of the profile is a health effects summary written in non-technical language. Its intended 

audience is the general public, especially people living in the vicinity of a hazardous waste site or 

chemical release. If the Public Health Statement were removed from the rest of the document, it would 

still communicate to the lay public essential information about the chemical. 

The major headings in the Public Health Statement are useful to find specific topics of concern. The 

topics are written in a question and answer format. The answer to each question includes a sentence that 

will direct the reader to chapters in the profile that will provide more information on the given topic. 

Chapter 2 

Relevance to Public Health 

This chapter provides a health effects summary based on evaluations of existing toxicologic, 

epidemiologic, and toxicokinetic information. This summary is designed to present interpretive, weightof-evidence discussions for human health end points by addressing the following questions: 

1. What effects are known to occur in humans? 

2. What effects observed in animals are likely to be of concern to humans? 

3. What exposure conditions are likely to be of concern to humans, especially around hazardous 

waste sites? 

The chapter covers end points in the same order that they appear within the Discussion of Health Effects 

by Route of Exposure section, by route (inhalation, oral, and dermal) and within route by effect. Human 

data are presented first, then animal data. Both are organized by duration (acute, intermediate, chronic). 

In vitro data and data from parenteral routes (intramuscular, intravenous, subcutaneous, etc.) are also 

considered in this chapter. 

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using 

existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer 

potency or perform cancer risk assessments. Minimal Risk Levels (MRLs) for noncancer end points (if 

derived) and the end points from which they were derived are indicated and discussed. 

Limitations to existing scientific literature that prevent a satisfactory evaluation of the relevance to public 

health are identified in the Chapter 3 Data Needs section. 

Interpretation of Minimal Risk Levels 

Where sufficient toxicologic information is available, ATSDR has derived MRLs for inhalation and oral 

routes of entry at each duration of exposure (acute, intermediate, and chronic). These MRLs are not 

meant to support regulatory action, but to acquaint health professionals with exposure levels at which 

adverse health effects are not expected to occur in humans. 
 

 

 

 

 

 

 

 

 

 

PLUTONIUM B-2 

APPENDIX B 

MRLs should help physicians and public health officials determine the safety of a community living near 

a chemical emission, given the concentration of a contaminant in air or the estimated daily dose in water. 

MRLs are based largely on toxicological studies in animals and on reports of human occupational 

exposure. 

MRL users should be familiar with the toxicologic information on which the number is based. Chapter 2, 

"Relevance to Public Health," contains basic information known about the substance. Other sections such 

as Chapter 3 Section 3.9, "Interactions with Other Substances,” and Section 3.10, "Populations that are 

Unusually Susceptible" provide important supplemental information. 

MRL users should also understand the MRL derivation methodology. MRLs are derived using a 

modified version of the risk assessment methodology that the Environmental Protection Agency (EPA) 

provides (Barnes and Dourson 1988) to determine reference doses (RfDs) for lifetime exposure. 

To derive an MRL, ATSDR generally selects the most sensitive end point which, in its best judgement, 

represents the most sensitive human health effect for a given exposure route and duration. ATSDR 

cannot make this judgement or derive an MRL unless information (quantitative or qualitative) is available 

for all potential systemic, neurological, and developmental effects. If this information and reliable 

quantitative data on the chosen end point are available, ATSDR derives an MRL using the most sensitive 

species (when information from multiple species is available) with the highest no-observed-adverse-effect 

level (NOAEL) that does not exceed any adverse effect levels. When a NOAEL is not available, a 

lowest-observed-adverse-effect level (LOAEL) can be used to derive an MRL, and an uncertainty factor 

(UF) of 10 must be employed. Additional uncertainty factors of 10 must be used both for human 

variability to protect sensitive subpopulations (people who are most susceptible to the health effects 

caused by the substance) and for interspecies variability (extrapolation from animals to humans). In 

deriving an MRL, these individual uncertainty factors are multiplied together. The product is then 

divided into the inhalation concentration or oral dosage selected from the study. Uncertainty factors used 

in developing a substance-specific MRL are provided in the footnotes of the levels of significant exposure 

(LSE) tables. 

Chapter 3 

Health Effects 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables and figures are used to summarize health effects and illustrate graphically levels of exposure 

associated with those effects. These levels cover health effects observed at increasing dose 

concentrations and durations, differences in response by species, MRLs to humans for noncancer end 

points, and EPA's estimated range associated with an upper- bound individual lifetime cancer risk of 1 in 

10,000 to 1 in 10,000,000. Use the LSE tables and figures for a quick review of the health effects and to 

locate data for a specific exposure scenario. The LSE tables and figures should always be used in 

conjunction with the text. All entries in these tables and figures represent studies that provide reliable, 

quantitative estimates of NOAELs, LOAELs, or Cancer Effect Levels (CELs). 

The legends presented below demonstrate the application of these tables and figures. Representative 

examples of LSE Table 3-1 and Figure 3-1 are shown. The numbers in the left column of the legends 

correspond to the numbers in the example table and figure. 
 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM	 B-3 

APPENDIX B 

LEGEND 

See Sample LSE Table 3-1 (page B-6) 

(1)	 Route of Exposure. One of the first considerations when reviewing the toxicity of a substance 

using these tables and figures should be the relevant and appropriate route of exposure. Typically 

when sufficient data exist, three LSE tables and two LSE figures are presented in the document. 

The three LSE tables present data on the three principal routes of exposure, i.e., inhalation, oral, 

and dermal (LSE Tables 3-1, 3-2, and 3-3, respectively). LSE figures are limited to the inhalation 

(LSE Figure 3-1) and oral (LSE Figure 3-2) routes. Not all substances will have data on each 

route of exposure and will not, therefore, have all five of the tables and figures. 

(2)	 Exposure Period. Three exposure periods—acute (less than 15 days), intermediate (15– 

364 days), and chronic (365 days or more)—are presented within each relevant route of exposure. 

In this example, an inhalation study of intermediate exposure duration is reported. For quick 

reference to health effects occurring from a known length of exposure, locate the applicable 

exposure period within the LSE table and figure. 

(3)	 Health Effect. The major categories of health effects included in LSE tables and figures are 

death, systemic, immunological, neurological, developmental, reproductive, and cancer. 

NOAELs and LOAELs can be reported in the tables and figures for all effects but cancer. 

Systemic effects are further defined in the "System" column of the LSE table (see key number 

18). 

(4)	 Key to Figure. Each key number in the LSE table links study information to one or more data 

points using the same key number in the corresponding LSE figure. In this example, the study 

represented by key number 18 has been used to derive a NOAEL and a Less Serious LOAEL 

(also see the two "18r" data points in sample Figure 3-1). 

(5)	 Species. The test species, whether animal or human, are identified in this column. Chapter 2, 

"Relevance to Public Health," covers the relevance of animal data to human toxicity and 

Section 3.4, "Toxicokinetics," contains any available information on comparative toxicokinetics. 

Although NOAELs and LOAELs are species specific, the levels are extrapolated to equivalent 

human doses to derive an MRL. 

(6)	 Exposure Frequency/Duration. The duration of the study and the weekly and daily exposure 

regimens are provided in this column. This permits comparison of NOAELs and LOAELs from 

different studies. In this case (key number 18), rats were exposed to “Chemical x” via inhalation 

for 6 hours/day, 5 days/week, for 13 weeks. For a more complete review of the dosing regimen, 

refer to the appropriate sections of the text or the original reference paper (i.e., Nitschke et al. 

1981). 

(7)	 System. This column further defines the systemic effects. These systems include respiratory, 

cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, and 

dermal/ocular. "Other" refers to any systemic effect (e.g., a decrease in body weight) not covered 

in these systems. In the example of key number 18, one systemic effect (respiratory) was 

investigated. 

(8)	 NOAEL. A NOAEL is the highest exposure level at which no harmful effects were seen in the 

organ system studied. Key number 18 reports a NOAEL of 3 ppm for the respiratory system, 

which was used to derive an intermediate exposure, inhalation MRL of 0.005 ppm (see 

footnote "b"). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM	 B-4 

APPENDIX B 

(9)	 LOAEL. A LOAEL is the lowest dose used in the study that caused a harmful health effect. 

LOAELs have been classified into "Less Serious" and "Serious" effects. These distinctions help 

readers identify the levels of exposure at which adverse health effects first appear and the 

gradation of effects with increasing dose. A brief description of the specific end point used to 

quantify the adverse effect accompanies the LOAEL. The respiratory effect reported in key 

number 18 (hyperplasia) is a Less Serious LOAEL of 10 ppm. MRLs are not derived from 

Serious LOAELs. 

(10)	 Reference. The complete reference citation is given in Chapter 9 of the profile. 

(11)	 CEL. A CEL is the lowest exposure level associated with the onset of carcinogenesis in 

experimental or epidemiologic studies. CELs are always considered serious effects. The LSE 

tables and figures do not contain NOAELs for cancer, but the text may report doses not causing 

measurable cancer increases. 

(12)	 Footnotes. Explanations of abbreviations or reference notes for data in the LSE tables are found 

in the footnotes. Footnote "b" indicates that the NOAEL of 3 ppm in key number 18 was used to 

derive an MRL of 0.005 ppm. 

LEGEND 

See Sample Figure 3-1 (page B-7) 

LSE figures graphically illustrate the data presented in the corresponding LSE tables. Figures help the 

reader quickly compare health effects according to exposure concentrations for particular exposure 

periods. 

(13)	 Exposure Period. The same exposure periods appear as in the LSE table. In this example, health 

effects observed within the acute and intermediate exposure periods are illustrated. 

(14)	 Health Effect. These are the categories of health effects for which reliable quantitative data 

exists. The same health effects appear in the LSE table. 

(15)	 Levels of Exposure. Concentrations or doses for each health effect in the LSE tables are 

graphically displayed in the LSE figures. Exposure concentration or dose is measured on the log 

scale "y" axis. Inhalation exposure is reported in mg/m3

 or ppm and oral exposure is reported in 

mg/kg/day. 

(16)	 NOAEL. In this example, the open circle designated 18r identifies a NOAEL critical end point in 

the rat upon which an intermediate inhalation exposure MRL is based. The key number 18 

corresponds to the entry in the LSE table. The dashed descending arrow indicates the 

extrapolation from the exposure level of 3 ppm (see entry 18 in the table) to the MRL of 

0.005 ppm (see footnote "b" in the LSE table). 

(17)	 CEL. Key number 38m is one of three studies for which CELs were derived. The diamond 

symbol refers to a CEL for the test species-mouse. The number 38 corresponds to the entry in the 

LSE table. 
 

 

PLUTONIUM	 B-5 

APPENDIX B 

(18)	 Estimated Upper-Bound Human Cancer Risk Levels. This is the range associated with the upperbound for lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. These risk levels are derived 

from the EPA's Human Health Assessment Group's upper-bound estimates of the slope of the 

cancer dose response curve at low dose levels (q1*). 

(19)	 Key to LSE Figure. The Key explains the abbreviations and symbols used in the figure. 
SAMPLE

1 → Table 3-1. Levels of Significant Exposure to [Chemical x] – Inhalation 

LOAEL (effect) Exposure 

Key to frequency/ NOAEL Less serious Serious (ppm) figurea Species duration System (ppm) (ppm) Re

2 3 4 

→ INTERMEDIATE EXPOSURE 

5 6 7 8 9 10 

→ Systemic ↓ ↓ ↓ ↓ ↓ ↓

18 Rat 13 wk Resp 3b 10 (hyperplasia) 

→ 5 d/wk Nit

6 hr/d 

CHRONIC EXPOSURE 

Cancer 11 

↓

38 Rat 18 mo 20 (CEL, multiple Wo

5 d/wk organs) 7 hr/d 

39 Rat 89–104 wk 10 (CEL, lung tumors, NT

5 d/wk nasal tumors) 6 hr/d 

40 Mouse 79–103 wk 10 (CEL, lung tumors, NT

5 d/wk hemangiosarcomas) 6 hr/d 

12 → a The number corresponds to entries in Figure 3-1. b Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5x10-3 ppm; dose adjusted for intermittent ex

by an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability). 

PLUTONIUM B-8
 

APPENDIX B 

This page is intentionally blank. 
PLUTONIUM C-1 

APPENDIX C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS 

ACGIH American Conference of Governmental Industrial Hygienists 

ACOEM American College of Occupational and Environmental Medicine 

ADI acceptable daily intake 

ADME absorption, distribution, metabolism, and excretion 

AED atomic emission detection 

AFID alkali flame ionization detector 

AFOSH Air Force Office of Safety and Health 

ALI annual limits on intake 

ALT alanine aminotransferase 

AMAD activity median aerodynamic diameter 

AML acute myeloid leukemia 

AOAC Association of Official Analytical Chemists 

AOEC Association of Occupational and Environmental Clinics 

AP alkaline phosphatase 

APHA American Public Health Association 

AST aspartate aminotransferase 

atm atmosphere 

ATSDR Agency for Toxic Substances and Disease Registry 

AWQC Ambient Water Quality Criteria 

BAT best available technology 

BCF bioconcentration factor 

BEI Biological Exposure Index 

BMD/C benchmark dose or benchmark concentration 

BMDX dose that produces a X% change in response rate of an adverse effect 

BMDLX 95% lower confidence limit on the BMDX 

BMDS Benchmark Dose Software 

BMR benchmark response 

Bq Becquerel 

BSC Board of Scientific Counselors 

C centigrade 

CAA Clean Air Act 

CAG Cancer Assessment Group of the U.S. Environmental Protection Agency 

CAS Chemical Abstract Services 

CDC Centers for Disease Control and Prevention 

CEL cancer effect level 

CELDS Computer-Environmental Legislative Data System 

CERCLA Comprehensive Environmental Response, Compensation, and Liability Act 

CFR Code of Federal Regulations 

Ci curie 

CI confidence interval 

CL ceiling limit value 

CLP Contract Laboratory Program 

cm centimeter 

CMAD count median aerodynamic diameter 

CML chronic myeloid leukemia 

CPSC Consumer Products Safety Commission 

CWA Clean Water Act 

DAC derived air concentration 

DHEW Department of Health, Education, and Welfare 
 

 

PLUTONIUM C-2 

APPENDIX C 

DHHS Department of Health and Human Services 

DNA deoxyribonucleic acid 

DOD Department of Defense 

DOE Department of Energy 

DOL Department of Labor 

DOT Department of Transportation 

DOT/UN/ Department of Transportation/United Nations/ 

NA/IMDG North America/Intergovernmental Maritime Dangerous Goods Code 

DWEL drinking water exposure level 

ECD electron capture detection 

ECG/EKG electrocardiogram 

EEG electroencephalogram 

EEGL Emergency Exposure Guidance Level 

EPA Environmental Protection Agency 

F Fahrenheit 

F1 first-filial generation 

FAO Food and Agricultural Organization of the United Nations 

FDA Food and Drug Administration 

FEMA Federal Emergency Management Agency 

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act 

FPD flame photometric detection 

fpm feet per minute 

FR Federal Register 

FSH follicle stimulating hormone 

g gram 

GC gas chromatography 

gd gestational day 

GLC gas liquid chromatography 

GPC gel permeation chromatography 

GSD geometric standard deviation 

Gy gray 

HPLC high-performance liquid chromatography 

HRGC high resolution gas chromatography 

HSDB Hazardous Substance Data Bank 

IARC International Agency for Research on Cancer 

ICRP International Commission on Radiological Protection 

IDLH immediately dangerous to life and health 

ILO International Labor Organization 

IRIS Integrated Risk Information System 

ITRI Inhalation Toxicology Research Institute 

kBq kiloBequerel 

Kd adsorption ratio 

kg kilogram 

kkg metric ton 

Koc organic carbon partition coefficient 

Kow octanol-water partition coefficient 

L liter 

LC liquid chromatography 

LC50 lethal concentration, 50% kill 

LCLo lethal concentration, low 

LD50 lethal dose, 50% kill 
 

 

PLUTONIUM C-3 

APPENDIX C 

LDLo lethal dose, low 

LDH lactic dehydrogenase 

LH luteinizing hormone 

LOAEL lowest-observed-adverse-effect level 

LSE Levels of Significant Exposure 

LT50 lethal time, 50% kill 

m meter 

MA trans,trans-muconic acid 

MAL maximum allowable level 

mCi millicurie 

MCL maximum contaminant level 

MCLG maximum contaminant level goal 

MF modifying factor 

MFO mixed function oxidase 

mg milligram 

mL milliliter 

mm millimeter 

MMD mass median diameter 

mmHg millimeters of mercury 

mmol millimole 

mppcf millions of particles per cubic foot 

MRL Minimal Risk Level 

MS mass spectrometry 

NAAQS National Ambient Air Quality Standard 

NAS National Academy of Science 

NATICH National Air Toxics Information Clearinghouse 

NATO North Atlantic Treaty Organization 

NCE normochromatic erythrocytes 

NCEH National Center for Environmental Health 

NCI National Cancer Institute 

NCRP National Council on Radiation Protection 

ND not detected 

NFPA National Fire Protection Association 

ng nanogram 

NHANES National Health and Nutrition Examination Survey 

NIEHS National Institute of Environmental Health Sciences 

NIOSH National Institute for Occupational Safety and Health 

NIOSHTIC NIOSH's Computerized Information Retrieval System 

NLM National Library of Medicine 

nm nanometer 

nmol nanomole 

NOAEL no-observed-adverse-effect level 

NOES National Occupational Exposure Survey 

NOHS National Occupational Hazard Survey 

NPD nitrogen phosphorus detection 

NPDES National Pollutant Discharge Elimination System 

NPL National Priorities List 

NR not reported 

NRC National Research Council 

NS not specified 

NSPS New Source Performance Standards 
 

 

PLUTONIUM C-4 

APPENDIX C 

NTIS National Technical Information Service 

NTP National Toxicology Program 

ODW Office of Drinking Water, EPA 

OERR Office of Emergency and Remedial Response, EPA 

OHM/TADS Oil and Hazardous Materials/Technical Assistance Data System 

OPP Office of Pesticide Programs, EPA 

OPPT Office of Pollution Prevention and Toxics, EPA 

OPPTS Office of Prevention, Pesticides and Toxic Substances, EPA 

OR odds ratio 

OSHA Occupational Safety and Health Administration 

OSW Office of Solid Waste, EPA 

OTS Office of Toxic Substances 

OW Office of Water 

OWRS Office of Water Regulations and Standards, EPA 

PAH polycyclic aromatic hydrocarbon 

PBBK physiologically based biokinetic 

PBPD physiologically based pharmacodynamic 

PBPK physiologically based pharmacokinetic 

PCE polychromatic erythrocytes 

PEL permissible exposure limit 

pg picogram 

PHS Public Health Service 

PID photo ionization detector 

pmol picomole 

PMR proportionate mortality ratio 

PNL Pacific Northwest Laboratory 

ppb parts per billion 

ppm parts per million 

ppt parts per trillion 

PSNS pretreatment standards for new sources 

RBC red blood cell 

REL recommended exposure level/limit 

RfC reference concentration 

RfD reference dose 

RNA ribonucleic acid 

RQ reportable quantity 

RTECS Registry of Toxic Effects of Chemical Substances 

SARA Superfund Amendments and Reauthorization Act 

SCE sister chromatid exchange 

SD standard deviation 

SE standard error 

SGOT serum glutamic oxaloacetic transaminase 

SGPT serum glutamic pyruvic transaminase 

SIC standard industrial classification 

SIM selected ion monitoring 

SMCL secondary maximum contaminant level 

SMR standardized mortality ratio 

SNARL suggested no adverse response level 

SPEGL Short-Term Public Emergency Guidance Level 

STEL short term exposure limit 

STORET Storage and Retrieval 
PLUTONIUM C-5 

APPENDIX C 

Sv sievert 

TD50 toxic dose, 50% specific toxic effect 

TLV threshold limit value 

TOC total organic carbon 

TPQ threshold planning quantity 

TRI Toxics Release Inventory 

TSCA Toxic Substances Control Act 

TWA time-weighted average 

UF uncertainty factor 

U.S. United States 

USDA United States Department of Agriculture 

USGS United States Geological Survey 

USNRC United States Nuclear Regulatory Commission 

VOC volatile organic compound 

WBC white blood cell 

WHO World Health Organization 
 

PLUTONIUM C-6 

APPENDIX C 

> greater than 

≥ greater than or equal to 

= equal to 

< less than 

≤ less than or equal to 

% percent 

α alpha 

β beta 

γ gamma 

δ delta 

μm micrometer 

μg microgram q1

* cancer slope factor 

– negative 

+ positive 

(+) weakly positive result 

(–) weakly negative result 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM D-1 

APPENDIX D. OVERVIEW OF BASIC RADIATION PHYSICS, CHEMISTRY, 

AND BIOLOGY 

Understanding the basic concepts in radiation physics, chemistry, and biology is important to the 

evaluation and interpretation of radiation-induced adverse health effects and to the derivation of radiation 

protection principles. This appendix presents a brief overview of the areas of radiation physics, 

chemistry, and biology and is based to a large extent on the reviews of Mettler and Moseley (1985), 

Hobbs and McClellan (1986), Eichholz (1982), Hendee (1973), Cember (1996), and Early et al. (1979). 

D.1 RADIONUCLIDES AND RADIOACTIVITY 

The substances we call elements are composed of atoms. Atoms in turn are made up of neutrons, protons 

and electrons: neutrons and protons in the nucleus and electrons in a cloud of orbits around the nucleus. 

Nuclide is the general term referring to any nucleus along with its orbital electrons. The nuclide is 

characterized by the composition of its nucleus and hence by the number of protons and neutrons in the 

nucleus. All atoms of an element have the same number of protons (this is given by the atomic number) 

but may have different numbers of neutrons (this is reflected by the atomic mass numbers or atomic 

weight of the element). Atoms with different atomic mass but the same atomic numbers are referred to as 

isotopes of an element. 

The numerical combination of protons and neutrons in most nuclides is such that the nucleus is quantum 

mechanically stable and the atom is said to be stable, i.e., not radioactive; however, if there are too few or 

too many neutrons, the nucleus is unstable and the atom is said to be radioactive. Unstable nuclides 

undergo radioactive transformation, a process in which a neutron or proton converts into the other and a 

beta particle is emitted, or else an alpha particle is emitted. Each type of decay is typically accompanied 

by the emission of gamma rays. These unstable atoms are called radionuclides; their emissions are called 

ionizing radiation; and the whole property is called radioactivity. Transformation or decay results in the 

formation of new nuclides some of which may themselves be radionuclides, while others are stable 

nuclides. This series of transformations is called the decay chain of the radionuclide. The first 

radionuclide in the chain is called the parent; the subsequent products of the transformation are called 

progeny, daughters, or decay products. 

In general there are two classifications of radioactivity and radionuclides: natural and artificial (manmade). Naturally-occurring radioactive material (NORM) exists in nature and no additional energy is 

necessary to place them in an unstable state. Natural radioactivity is the property of some naturally 

occurring, usually heavy elements, that are heavier than lead. Radionuclides, such as radium and 

uranium, primarily emit alpha particles. Some lighter elements such as carbon-14 and tritium (hydrogen3) primarily emit beta particles as they transform to a more stable atom. Natural radioactive atoms 

heavier than lead cannot attain a stable nucleus heavier than lead. Everyone is exposed to background 

radiation from naturally-occurring radionuclides throughout life. This background radiation is the major 

source of radiation exposure to man and arises from several sources. The natural background exposures 

are frequently used as a standard of comparison for exposures to various artificial sources of ionizing 

radiation. 

Artificial radioactive atoms are produced either as a by-product of fission of uranium or plutonium atoms 

in a nuclear reactor or by bombarding stable atoms with particles, such as neutrons or protons, directed at 

the stable atoms with high velocity. These artificially produced radioactive elements usually decay by 

emission of particles, such as positive or negative beta particles and one or more high energy photons 

(gamma rays). Unstable (radioactive) atoms of any element can be produced. 
 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM D-2 

APPENDIX D 

Both naturally occurring and artificial radioisotopes find application in medicine, industrial products, and 

consumer products. Some specific radioisotopes, called fall-out, are still found in the environment as a 

result of nuclear weapons use or testing. 

D.2 RADIOACTIVE DECAY 

D.2.1 Principles of Radioactive Decay 

The stability of an atom is the result of the balance of the forces of the various components of the nucleus. 

An atom that is unstable (radionuclide) will release energy (decay) in various ways and transform to 

stable atoms or to other radioactive species called daughters, often with the release of ionizing radiation. 

If there are either too many or too few neutrons for a given number of protons, the resulting nucleus may 

undergo transformation. For some elements, a chain of daughter decay products may be produced until 

stable atoms are formed. Radionuclides can be characterized by the type and energy of the radiation 

emitted, the rate of decay, and the mode of decay. The mode of decay indicates how a parent compound 

undergoes transformation. Radiations considered here are primarily of nuclear origin, i.e., they arise from 

nuclear excitation, usually caused by the capture of charged or uncharged nucleons by a nucleus, or by the 

radioactive decay or transformation of an unstable nuclide. The type of radiation may be categorized as 

charged or uncharged particles, protons, and fission products) or electromagnetic radiation (gamma rays 

and x rays). Table D-1 summarizes the basic characteristics of the more common types of radiation 

encountered. 

D.2.2 Half-Life and Activity 

For any given radionuclide, the rate of decay is a first-order process that is constant, regardless of the 

radioactive atoms present and is characteristic for each radionuclide. The process of decay is a series of 

random events; temperature, pressure, or chemical combinations do not effect the rate of decay. While it 

may not be possible to predict exactly which atom is going to undergo transformation at any given time, it 

is possible to predict, on average, the fraction of the radioactive atoms that will transform during any 

interval of time. 

The activity is a measure of the quantity of radioactive material. For these radioactive materials it is 

customary to describe the activity as the number of disintegrations (transformations) per unit time. The 

unit of activity is the curie (Ci), which was originally related to the activity of one gram of radium, but is 

now defined as that quantity of radioactive material in which there are: 

1 curie (Ci) = 3.7x1010 disintegrations (transformations)/second (dps) or 2.22x1012 disintegrations 

(transformations)/minute (dpm). 

The SI unit of activity is the becquerel (Bq); 1 Bq = that quantity of radioactive material in which there is 

1 transformation/second. Since activity is proportional to the number of atoms of the radioactive 

material, the quantity of any radioactive material is usually expressed in curies, regardless of its purity or 

concentration. The transformation of radioactive nuclei is a random process, and the number of 

transformations is directly proportional to the number of radioactive atoms present. For any pure 

radioactive substance, the rate of decay is usually described by its radiological half-life, TR, i.e., the time 

it takes for a specified source material to decay to half its initial activity. The specific activity is an 

indirect measure of the rate of decay, and is defined as the activity per unit mass or per unit volume. The 

higher the specific activity of a radioisotope, the faster it is decaying. 
 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM D-3 

APPENDIX D 

The activity of a radionuclide at time t may be calculated by: 

-0.693t/Trad A = Aoe

where A is the activity in dps or curies or becquerels, Ao is the activity at time zero, t is the time at which 

measured, and Trad is the radiological half-life of the radionuclide (Trad and t must be in the same units of 

time). The time when the activity of a sample of radioactivity becomes one-half its original value is the 

radioactive half-life and is expressed in any suitable unit of time. 

Table D-1. Characteristics of Nuclear Radiations 

Typical Path lengthb 

Radiation Rest massa Charge energy range Air Solid Comments 

Alpha (α) 4.00 amu +2 4–10 MeV 5–10 cm 25–80 μm Identical to ionized 

He nucleus 

Negatron (β–

) 5.48x10-4 amu; –1 0–4 MeV 0–10 m 0–1 cm Identical to electron 

0.51 MeV 

Positron (β+

) 5.48x10-4 amu; +1 0-4 MeV 0–10 m 0–1 cm Identical to electron 

0.51 MeV except for sign of 

charge 

Neutron 1.0086 amu; 0 0–15 MeV b b Free half-life: 16 min 

939.55 MeV 

X ray (e.m. photon) – 0 5 keV–100 keV b b Photon from 

transition of an 

electron between 

atomic orbits 

Gamma () 

(e.m. photon) 

– 0 10 keV–3 MeV b b Photon from nuclear 

transformation 

a The rest mass (in amu) has an energy equivalent in MeV that is obtained using the equation E=mc2

, where 1 amu = 932 MeV. b Path lengths are not applicable to x- and gamma rays since their intensities decrease exponentially; path lengths in solid tissue 

are variable, depending on particle energy, electron density of material, and other factors. 

amu = atomic mass unit; e.m. = electromagnetic; MeV = MegaElectron Volts 

The specific activity is a measure of activity, and is defined as the activity per unit mass or per unit 

volume. This activity is usually expressed in curies per gram and may be calculated by 

curies/gram = 1.3x108 / (Trad) (atomic weight) or 

[3.577 x 105

 x mass(g)] / [Trad x atomic weight] 

where Trad is the radiological half-life in days. 

In the case of radioactive materials contained in living organisms, an additional consideration is made for 

the reduction in observed activity due to regular processes of elimination of the respective chemical or 

biochemical substance from the organism. This introduces a rate constant called the biological half-life 

(Tbiol) which is the time required for biological processes to eliminate one-half of the activity. This time 

is virtually the same for both stable and radioactive isotopes of any given element. 
 

 

 

 

 

 

 

 

 

 

PLUTONIUM D-4 

APPENDIX D 

Under such conditions the time required for a radioactive element to be halved as a result of the combined 

action of radioactive decay and biological elimination is the effective clearance half-time: 

Teff = (Tbiol x Trad) / (Tbiol + Trad). 

Table D-2 presents representative effective half-lives of particular interest. 

Table D-2. Half-Lives of Some Radionuclides in Adult Body Organs 

Half-lifea 

Radionuclide Critical organ Physical Biological Effective 

Uranium 238 Kidney 4,460,000,000 y 4 d 4 d 

Hydrogen 3b Whole body 12.3 y 10 d 10 d 

(Tritium) 

Iodine 131 Thyroid 8 d 80 d 7.3 d 

Strontium 90 Bone 28 y 50 y 18 y 

Plutonium 239 Bone surface 24,400 y 50 y 50 y 

Lung 24,400 y 500 d 500 d 

Cobalt 60 Whole body 5.3 y 99.5 d 95 d 

Iron 55 Spleen 2.7 y 600 d 388 d 

Iron 59 Spleen 45.1 d 600 d 42 d 

Manganese 54 Liver 303 d 25 d 23 d 

Cesium 137 Whole body 30 y 70 d 70 d 

a

d = days, y = years

b

Mixed in body water as tritiated water
 

D.2.3 Interaction of Radiation with Matter 

Both ionizing and nonionizing radiation will interact with materials; that is, radiation will lose kinetic 

energy to any solid, liquid or gas through which it passes by a variety of mechanisms. The transfer of 

energy to a medium by either electromagnetic or particulate radiation may be sufficient to cause 

formation of ions. This process is called ionization. Compared to other types of radiation that may be 

absorbed, such as ultraviolet radiation, ionizing radiation deposits a relatively large amount of energy into 

a small volume. 

The method by which incident radiation interacts with the medium to cause ionization may be direct or 

indirect. Electromagnetic radiations (x rays and gamma photons) are indirectly ionizing; that is, they give 

up their energy in various interactions with cellular molecules, and the energy is then utilized to produce a 

fast-moving charged particle such as an electron. It is the electron that then may react with a target 

molecule. This particle is called a “primary ionizing particle. Charged particles, in contrast, strike the 

tissue or medium and directly react with target molecules, such as oxygen or water. These particulate 

radiations are directly ionizing radiations. Examples of directly ionizing particles include alpha and beta 

particles. Indirectly ionizing radiations are always more penetrating than directly ionizing particulate 

radiations. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM D-5 

APPENDIX D 

Mass, charge, and velocity of a particle, as well as the electron density of the material with which it 

interacts, all affect the rate at which ionization occurs. The higher the charge of the particle and the lower 

the velocity, the greater the propensity to cause ionization. Heavy, highly charged particles, such as alpha 

particles, lose energy rapidly with distance and, therefore, do not penetrate deeply. The result of these 

interaction processes is a gradual slowing down of any incident particle until it is brought to rest or 

"stopped" at the end of its range. 

D.2.4 Characteristics of Emitted Radiation 

D.2.4.1 Alpha Emission. In alpha emission, an alpha particle consisting of two protons and two 

neutrons is emitted with a resulting decrease in the atomic mass number by four and reduction of the 

atomic number of two, thereby changing the parent to a different element. The alpha particle is identical 

to a helium nucleus consisting of two neutrons and two protons. It results from the radioactive decay of 

some heavy elements such as uranium, plutonium, radium, thorium, and radon. All alpha particles 

emitted by a given radioisotope have the same energy. Most of the alpha particles that are likely to be 

found have energies in the range of about 4 to 8 MeV, depending on the isotope from which they came. 

The alpha particle has an electrical charge of +2. Because of this double positive charge and their size, 

alpha particles have great ionizing power and, thus, lose their kinetic energy quickly. This results in very 

little penetrating power. In fact, an alpha particle cannot penetrate a sheet of paper. The range of an 

alpha particle (the distance the charged particle travels from the point of origin to its resting point) is 

about 4 cm in air, which decreases considerably to a few micrometers in tissue. These properties cause 

alpha emitters to be hazardous only if there is internal contamination (i.e., if the radionuclide is inside the 

body). 

D.2.4.2 Beta Emission. A beta particle () is a high-velocity electron ejected from a disintegrating 

nucleus. The particle may be either a negatively charged electron, termed a negatron (-) or a positively 

charged electron, termed a positron (+). Although the precise definition of "beta emission" refers to 

both - and +, common usage of the term generally applies only to the negative particle, as distinguished 

from the positron emission, which refers to the + particle. 

D.2.4.2.1 Beta Negative Emission. Beta particle (-) emission is another process by which a 

radionuclide, with a neutron excess achieves stability. Beta particle emission decreases the number of 

neutrons by one and increases the number of protons by one, while the atomic mass number remains 

unchanged.1 This transformation results in the formation of a different element. The energy spectrum of 

beta particle emission ranges from a certain maximum down to zero with the mean energy of the 

spectrum being about one-third of the maximum. The range in tissue is much less. Beta negative 

emitting radionuclides can cause injury to the skin and superficial body tissues, but mostly present an 

internal contamination hazard. 

D.2.4.2.2 Positron Emission. In cases in which there are too many protons in the nucleus, positron 

emission may occur. In this case a proton may be thought of as being converted into a neutron, and a 

positron (+) is emitted.1 This increases the number of neutrons by one, decreases the number of protons 

by one, and again leaves the atomic mass number unchanged. The gamma radiation resulting from the 

annihilation (see glossary) of the positron makes all positron emitting isotopes more of an external 

radiation hazard than pure  emitters of equal energy. 

D.2.4.2.3 Gamma Emission. Radioactive decay by alpha, beta, or positron emission, or electron 

capture often leaves some of the energy resulting from these changes in the nucleus. As a result, the 

1 Neutrinos also accompany negative beta particles and positron emissions 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM D-6 

APPENDIX D 

nucleus is raised to an excited level. None of these excited nuclei can remain in this high-energy state. 

Nuclei release this energy returning to ground state or to the lowest possible stable energy level. The 

energy released is in the form of gamma radiation (high energy photons) and has an energy equal to the 

change in the energy state of the nucleus. Gamma and x rays behave similarly but differ in their origin; 

gamma emissions originate in the nucleus while x rays originate in the orbital electron structure or from 

rapidly changing the velocity of an electron (e.g., as occurs when shielding high energy beta particles or 

stopping the electron beam in an x ray tube). 

D.3 ESTIMATION OF ENERGY DEPOSITION IN HUMAN TISSUES 

Two forms of potential radiation exposures can result: internal and external. The term exposure denotes 

physical interaction of the radiation emitted from the radioactive material with cells and tissues of the 

human body. An exposure can be "acute" or "chronic" depending on how long an individual or organ is 

exposed to the radiation. Internal exposures occur when radionuclides, which have entered the body (e.g., 

through the inhalation, ingestion, or dermal pathways), undergo radioactive decay resulting in the 

deposition of energy to internal organs. External exposures occur when radiation enters the body directly 

from sources located outside the body, such as radiation emitters from radionuclides on ground surfaces, 

dissolved in water, or dispersed in the air. In general, external exposures are from material emitting 

gamma radiation, which readily penetrate the skin and internal organs. Beta and alpha radiation from 

external sources are far less penetrating and deposit their energy primarily on the skin's outer layer. 

Consequently, their contribution to the absorbed dose of the total body dose, compared to that deposited 

by gamma rays, may be negligible. 

Characterizing the radiation dose to persons as a result of exposure to radiation is a complex issue. It is 

difficult to: (1) measure internally the amount of energy actually transferred to an organic material and to 

correlate any observed effects with this energy deposition; and (2) account for and predict secondary 

processes, such as collision effects or biologically triggered effects, that are an indirect consequence of 

the primary interaction event. 

D.3.1 Dose/Exposure Units 

D.3.1.1 Roentgen. The roentgen (R) is a unit of x or gamma-ray exposure and is a measured by the 

amount of ionization caused in air by gamma or x radiation. One roentgen produces 2.58x10-4 coulomb 

per kilogram of air. In the case of gamma radiation, over the commonly encountered range of photon 

energy, the energy deposition in tissue for a dose of 1 R is about 0.0096 joules (J) /kg of tissue. 

D.3.1.2 Absorbed Dose and Absorbed Dose Rate. The absorbed dose is defined as the energy 

imparted by the incident radiation to a unit mass of the tissue or organ. The unit of absorbed dose is the 

rad; 1 rad = 100 erg/gram = 0.01 J/kg in any medium. An exposure of 1 R results in a dose to soft tissue 

of approximately 0.01 J/kg. The SI unit is the gray which is equivalent to 100 rad or 1 J/kg. Internal and 

external exposures from radiation sources are not usually instantaneous but are distributed over extended 

periods of time. The resulting rate of change of the absorbed dose to a small volume of mass is referred 

to as the absorbed dose rate in units of rad/unit time. 

D.3.1.3 Working Levels and Working Level Months. Working level (WL) is a measure of the 

atmospheric concentration of radon and its short-lived progeny. One WL is defined as any combination 

of short-lived radon daughters (through polonium-214), per liter of air, that will result in the emission of 

1.3x105

 MeV of alpha energy. An activity concentration of 100 pCi radon-222/L of air, in equilibrium 

with its daughters, corresponds approximately to a potential alpha-energy concentration of 1 WL. The 

WL unit can also be used for thoron daughters. In this case, 1.3x105 MeV of alpha energy (1 WL) is 

released by the thoron daughters in equilibrium with 7.5 pCi thoron/L. The potential alpha energy 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM D-7 

APPENDIX D 

exposure of miners is commonly expressed in the unit Working Level Month (WLM). One WLM 

corresponds to exposure to a concentration of 1 WL for the reference period of 170 hours, or more 

generally 

WLM = concentration (WL) x exposure time (months) (one “month” = 170 working hours). 

D.3.2 Dosimetry Models 

Dosimetry models are used to estimate the dose from internally deposited to radioactive substances. The 

models for internal dosimetry consider the amount of radionuclides entering the body, the factors 

affecting their movement or transport through the body, distribution and retention of radionuclides in the 

body, and the energy deposited in organs and tissues from the radiation that is emitted during spontaneous 

decay processes. The dose pattern for radioactive materials in the body may be strongly influenced by the 

route of entry of the material. For industrial workers, inhalation of radioactive particles with pulmonary 

deposition and puncture wounds with subcutaneous deposition have been the most frequent. The general 

population has been exposed via ingestion and inhalation of low levels of naturally occurring 

radionuclides as well as radionuclides from nuclear weapons testing. 

The models for external dosimetry consider only the photon doses (and neutron doses, where applicable) 

to organs of individuals who are immersed in air or are exposed to a contaminated object. 

D.3.2.1 Ingestion. Ingestion of radioactive materials is most likely to occur from contaminated 

foodstuffs or water or eventual ingestion of inhaled compounds initially deposited in the lung. Ingestion 

of radioactive material may result in toxic effects as a result of either absorption of the radionuclide or 

irradiation of the gastrointestinal tract during passage through the tract, or a combination of both. The 

fraction of a radioactive material absorbed from the gastrointestinal tract is variable, depending on the 

specific element, the physical and chemical form of the material ingested, and the diet, as well as some 

other metabolic and physiological factors. The absorption of some elements is influenced by age, usually 

with higher absorption in the very young. 

D.3.2.2 Inhalation. The inhalation route of exposure has long been recognized as being a major 

portal of entry for both nonradioactive and radioactive materials. The deposition of particles within the 

lung is largely dependent upon the size of the particles being inhaled. After the particle is deposited, the 

retention will depend upon the physical and chemical properties of the dust and the physiological status of 

the lung. The retention of the particle in the lung depends on the location of deposition, in addition to the 

physical and chemical properties of the particles. The converse of pulmonary retention is pulmonary 

clearance. There are three distinct mechanisms of clearance which operate simultaneously. Ciliary 

clearance acts only in the upper respiratory tract. The second and third mechanisms act mainly in the 

deep respiratory tract. These are phagocytosis and absorption. Phagocytosis is the engulfing of foreign 

bodies by alveolar macrophages and their subsequent removal either up the ciliary "escalator" or by 

entrance into the lymphatic system. Some inhaled soluble particles are absorbed into the blood and 

translocated to other organs and tissues. 

D.3.3 Internal Emitters 

An internal emitter is a radionuclide that is inside the body. The absorbed dose from internally deposited 

radioisotopes depends on the energy absorbed per unit tissue by the irradiated tissue. For a radioisotope 

distributed uniformly throughout an infinitely large medium, the concentration of absorbed energy must 

be equal to the concentration of energy emitted by the isotope. An infinitely large medium may be 

approximated by a tissue mass whose dimensions exceed the range of the particle. All alpha and most 

beta radiation will be absorbed in the organ (or tissue) of reference. Gamma-emitting isotope emissions 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM D-8 

APPENDIX D 

are penetrating radiation, and a substantial fraction of gamma energy may be absorbed in tissue. The dose 

to an organ or tissue is a function of the effective retention half-time, the energy released in the tissue, the 

amount of radioactivity initially introduced, and the mass of the organ or tissue. 

D.4 BIOLOGICAL EFFECTS OF RADIATION 

When biological material is exposed to ionizing radiation, a chain of cellular events occurs as the ionizing 

particle passes through the biological material. A number of theories have been proposed to describe the 

interaction of radiation with biologically important molecules in cells and to explain the resulting damage 

to biological systems from those interactions. Many factors may modify the response of a living 

organism to a given dose of radiation. Factors related to the exposure include the dose rate, the energy of 

the radiation, and the temporal pattern of the exposure. Biological considerations include factors such as 

species, age, sex, and the portion of the body exposed. Several excellent reviews of the biological effects 

of radiation have been published, and the reader is referred to these for a more in-depth discussion 

(Brodsky 1996; Hobbs and McClellan 1986; ICRP 1984; Mettler and Moseley 1985; Rubin and Casarett 

1968). 

D.4.1 Radiation Effects at the Cellular Level 

According to Mettler and Moseley (1985), at acute doses up to 10 rad (100 mGy), single strand breaks in 

DNA may be produced. These single strand breaks may be repaired rapidly. With doses in the range of 

50–500 rad (0.5–5 Gy), irreparable double-stranded DNA breaks are likely, resulting in cellular 

reproductive death after one or more divisions of the irradiated parent cell. At large doses of radiation, 

usually greater than 500 rad (5 Gy), direct cell death before division (interphase death) may occur from 

the direct interaction of free-radicals with essentially cellular macromolecules. Morphological changes at 

the cellular level, the severity of which are dose-dependent, may also be observed. 

The sensitivity of various cell types varies. According to the Bergonie-Tribondeau law, the sensitivity of 

cell lines is directly proportional to their mitotic rate and inversely proportional to the degree of 

differentiation (Mettler and Moseley 1985). Rubin and Casarett (1968) devised a classification system 

that categorized cells according to type, function, and mitotic activity. The categories range from the 

most sensitive type, "vegetative intermitotic cells, " found in the stem cells of the bone marrow and the 

gastrointestinal tract, to the least sensitive cell type, "fixed postmitotic cells," found in striated muscles or 

long-lived neural tissues. 

Cellular changes may result in cell death, which if extensive, may produce irreversible damage to an 

organ or tissue or may result in the death of the individual. If the cell recovers, altered metabolism and 

function may still occur, which may be repaired or may result in the manifestation of clinical symptoms. 

These changes may also be expressed at a later time as tumors or cellular mutations, which may result in 

abnormal tissue. 

D.4.2 Radiation Effects at the Organ Level 

In most organs and tissues the injury and the underlying mechanism for that injury are complex and may 

involve a combination of events. The extent and severity of this tissue injury are dependent upon the 

radiosensitivity of the various cell types in that organ system. Rubin and Casarett (1968) describe and 

schematically display the events following radiation in several organ system types. These include: a 

rapid renewal system, such as the gastrointestinal mucosa; a slow renewal system, such as the pulmonary 

epithelium; and a nonrenewal system, such as neural or muscle tissue. In the rapid renewal system, organ 

injury results from the direct destruction of highly radiosensitive cells, such as the stem cells in the bone 

marrow. Injury may also result from constriction of the microcirculation and from edema and 
 

 

 

 

 

 

 

 

 

 

 

 

PLUTONIUM D-9 

APPENDIX D 

inflammation of the basement membrane, designated as the histohematic barrier (HHB), which may 

progress to fibrosis. In slow renewal and nonrenewal systems, the radiation may have little effect on the 

parenchymal cells, but ultimate parenchymal atrophy and death over several months result from HHB 

fibrosis and occlusion of the microcirculation. 

D.4.3 Low Level Radiation Effects 

Cancer is the major latent harmful effect produced by ionizing radiation and the one that most people 

exposed to radiation are concerned about. The ability of alpha, beta, and gamma radiation to produce 

cancer in virtually every tissue and organ in laboratory animals has been well-demonstrated. The 

development of cancer is not an immediate effect. Radiation-induced leukemia has the shortest latent 

period at 2 years, while other radiation induced cancers have latent periods >20 years. The mechanism by 

which cancer is induced in living cells is complex and is a topic of intense study. Exposure to ionizing 

radiation can produce cancer at any site within the body; however, some sites appear to be more common 

than others, such as the breast, lung, stomach, and thyroid. 

DNA is a major target molecule during exposure to ionizing radiation. Other macromolecules, such as 

lipids and proteins, are also at risk of damage when exposed to ionizing radiation. The genotoxicity of 

ionizing radiation is an area of intense study, as damage to the DNA is ultimately responsible for many of 

the adverse toxicological effects ascribed to ionizing radiation, including cancer. Damage to genetic 

material is basic to developmental or teratogenic effects, as well. However, for effects other than cancer, 

there is little evidence of human effects at low levels of exposure. 

D.5 UNITS IN RADIATION PROTECTION AND REGULATION 

D.5.1 Dose Equivalent (or equivalent dose) 

Dose equivalent (as measured in rem or Sievert) is a special radiation protection quantity that is used, for 

administrative and radiation safety purposes only, to express the absorbed dose in a manner which 

considers the difference in biological effectiveness of various kinds of ionizing radiation. The dose 

equivalent concept is applicable only to doses that are not great enough to produce biomedical effects. 

The NRC defines the dose equivalent, H, as the product of the absorbed dose, D, and the quality factor, Q, 

at the point of interest in biological tissue. This relationship is expressed as H = D x Q. The NCRP 

defines equivalent dose, H, as the product of the absorbed dose, D, and the radiation weighting factor, wr. 

This relationship is expressed as H = Dwr. 

The quality factor or radiation weighting factor is a dimensionless quantity that depends in part on the 

stopping power for charged particles, and it accounts for the differences in biological effectiveness found 

among the types of radiation. Originally relative biological effectiveness (RBE) was used rather than Q 

to define the quantity, rem, which was of use in risk assessment. The generally accepted values for 

quality factors and radiation weighting factors for various radiation types are provided in Table D-3. The 

dose equivalent rate is the time rate of change of the dose equivalent to organs and tissues and is 

expressed as rem/unit time or sievert/unit time. 
 

 

 

 

 

 

 

 

PLUTONIUM D-10
 

APPENDIX D
 

Table D-3. Quality Factors (Q) and Radiation Weighting Factors 

Radiation Weighting Factor (wr) 

Type of radiation Quality factor (Q) 

X, gamma, or beta radiation 1 1 

Alpha particles, multiple-charged 20 20 

particles, fission fragments and 

heavy particles of unknown charge 

Neutrons (100 keV to 2 MeV), 7.5-11 depending on 20 

protons, alpha particles, charged energy 

particles of unknown energy 

Neutrons of unknown energy 10 

Thermal neutrons 2 5 

High-energy protons 10 5 

Source:
 

USNRC. 2004. Standards for the protection against radiation, tables 1004(b).1 and 1004(b).2. 10 CFR 20.1004. U.S. 

Nuclear Regulatory Commission, Washington, D.C.
 

NCRP 1993
 

D.5.2 Relative Biological Effectiveness 

RBE is used to denote the experimentally determined ratio of the absorbed dose from one radiation type 

to the absorbed dose of a reference radiation required to produce an identical biologic effect under the 

same conditions. Gamma rays from cobalt-60 and 200–250 keV x-rays have been used as reference 

standards. The term RBE has been widely used in experimental radiobiology, and the term quality factor 

(or radiation weighting factor) used in calculations of dose equivalent for radiation safety purposes (ICRP 

1977; NCRP 1971; UNSCEAR 1982). RBE applies only to a specific biological end point, in a specific 

exposure, under specific conditions to a specific species. There are no generally accepted values of RBE. 

D.5.3 Effective Dose Equivalent (or effective dose) 

The absorbed dose is usually defined as the mean absorbed dose within an organ or tissue. This 

represents a simplification of the actual problem. Normally when an individual ingests or inhales a 

radionuclide or is exposed to external radiation that enters the body (gamma), the dose is not uniform 

throughout the whole body. The simplifying assumption is that the detriment will be the same whether 

the body is uniformly or non-uniformly irradiated. In an attempt to compare detriment from absorbed 

dose of a limited portion of the body with the detriment from total body dose, the ICRP (1977) derived a 

concept of effective dose equivalent. ICRP (1990) changes this term to effective dose, but it has not yet 

been adopted by the NRC or DOE. 

The effective dose equivalent, HE, is 

HE = ∑ Wt Ht 

where Ht is the dose equivalent (or equivalent dose) in the tissue t, Wt is the tissue weighting factor in that 

tissue, which represents the estimated proportion of the stochastic risk resulting from tissue, t, to the 
 

 

 

 

PLUTONIUM D-11 

APPENDIX D 

stochastic risk when the whole body is uniformly irradiated for occupational exposures under certain 

conditions (ICRP 1977). Tissue weighting factors for selected tissues are listed in Table D-4. 

The ICRU (1980), ICRP (1984), and NCRP (1985) now recommend that the rad, roentgen, curie, and rem 

be replaced by the SI units: gray (Gy), Coulomb per kilogram (C/kg), Becquerel (Bq), and sievert (Sv), 

respectively. The relationship between the customary units and the international system of units (SI) for 

radiological quantities is shown in Table D-5. 

Table D-4. Tissue Weighting Factors for Calculating Effective Dose
 

Equivalent and Effective Dose for Selected Tissues
 

Tissue Weighting factor 

Tissue NCRP115/ ICRP60 NRC/ICRP26 

Bladder 0.05 – 

Bone marrow 0.12 0.12 

Bone surface 0.01 0.03 

Breast 0.05 0.15 

Colon 0.12 – 

Esophagus 0.05 – 

Gonads 0.20 0.25 

Liver 0.05 – 

Lung 0.12 0.12 

Ovary – 

Skin 0.01 – 

Stomach 0.12 – 

Thyroid 0.05 0.03 

Remainder 0.05 0.30 

Total 1.00 1.00 

ICRP60 = International Commission on Radiological Protection, 1990 Recommendations of the ICRP 

NCRP115 = National Council on Radiation Protection and Measurements. 1993. Risk Estimates for Radiation Protection, 

Report 115. Bethesda, Maryland 

NRC = Nuclear Regulatory Commission, Title 10, Code of Federal Regulations, Part 20 
 

 

 

 

 

 

 

PLUTONIUM D-12
 

APPENDIX D
 

Table D-5. Comparison of Common and SI Units for Radiation Quantities 

Customary 

Quantity units Definition SI units Definition 

Activity (A) 

Absorbed dose (D) 

Absorbed dose rate 

(Ď) 

Dose equivalent 

(H) 

Dose equivalent 

rate () 

Effective dose 

Equivalent dose 

(H) 

Linear energy 

transfer (LET) 

curie (Ci) 3.7x1010 

transformations s-1 

becquerel (Bq) s

-1 

rad (rad) 10-2 Jkg-1 gray (Gy) Jkg-1 

rad per second 

(rad s-1) 

10-2 Jkg-1s

-1 gray per second 

(Gy s-1) 

Jkg-1 s

-1 

rem 10-2 Jkg-1 sievert (Sv) Jkg-1 

rem per second 

(rem s-1) 

10-2 Jkg-1s

-1 sievert per second 

(Sv s-1) 

Jkg-1 s

-1 

rem 10-2 Jkg-1 sievert (Sv) Jkg-1 

rem 10-2 Jkg-1 sievert (Sv) Jkg-1 

kiloelectron volts 1.602x10-10 Jm-1 kiloelectron volts 1.602x10-10 Jm-1 

per micrometer 

(keV μm-1) 

per micrometer 

(keV μm-1) 

Jkg-1 = Joules per kilogram; Jkg-1s

-1 = Joules per kilogram per second; Jm-1 = Joules per meter; s-1 = per second 
 

 

 

 

 

PLUTONIUM D-13 

APPENDIX D 

REFERENCES FOR APPENDIX D 

ATSDR. 1990a. Toxicological profile for thorium. U.S. Department of Health and Human Services. 

Public Health Service. Agency for Toxic Substances and Disease Registry. Atlanta, GA. 

ATSDR. 1990b. Toxicological profile for radium. U.S. Department of Health and Human Services. 

Public Health Service. Agency for Toxic Substances and Disease Registry. Atlanta, GA. 

ATSDR. 1990c. Toxicological profile for radon. U.S. Department of Health and Human Services. 

Public Health Service. Agency for Toxic Substances and Disease Registry. Atlanta, GA. 

ATSDR. 1999. Toxicological profile for uranium. U.S. Department of Health and Human Services. 

Public Health Service. Agency for Toxic Substances and Disease Registry. Atlanta, GA. 

BEIR III. 1980. The effects on populations of exposure to low levels of ionizing radiation. Committee 

on the Biological Effects of Ionizing Radiations, National Research Council. Washington, DC: National 

Academy Press. 

BEIR IV. 1988. Health risks of radon and other internally deposited alpha emitters. Committee on the 

Biological Effects of Ionizing Radiations, National Research Council. Washington, DC: National 

Academy Press. 

BEIR V. 1988. Health effects of exposure to low levels of ionizing radiation. Committee on the 

Biological Effects of Ionizing Radiations, National Research Council. Washington, DC: National 

Academy Press. 

Brodsky A. 1996. Review of radiation risks and uranium toxicity with application to decisions 

associated with decommissioning clean-up criteria. Hebron,Connecticut: RSA Publications. 

Cember H. 1996. Introduction to health physics. New York., NY: McGraw Hill. 

Early P, Razzak M, Sodee D. 1979. Nuclear medicine technology. 2nd ed. St. Louis: C.V. Mosby 

Company. 

Eichholz G. 1982. Environmental aspects of nuclear power. Ann Arbor, MI: Ann Arbor Science. 

Hendee W. 1973. Radioactive isotopes in biological research. New York, NY: John Wiley and Sons. 

Hobbs C, McClellan R. 1986. Radiation and radioactive materials. In: Doull J, et al., eds. Casarett and 

Doull's Toxicology. 3rd ed. New York, NY: Macmillan Publishing Co., Inc., 497-530. 

ICRP. 1977. International Commission on Radiological Protection. Recommendations of the 

International Commission on Radiological Protection. ICRP Publication 26. Vol 1. No. 3. Oxford: 

Pergamon Press. 

ICRP. 1979. International Commission on Radiological Protection. Limits for intakes of radionuclides 

by workers. ICRP Publication 20. Vol. 3. No. 1-4. Oxford: Pergamon Press. 

ICRP. 1979. Limits for Intakes of Radionuclides by Workers. Publication 30. International 

Commission on Radiological Protection. Pergamon Press. 
 

 

 

 

 

 

 

 

 

PLUTONIUM D-14 

APPENDIX D 

ICRP. 1984. International Commission on Radiological Protection. A compilation of the major concepts 

and quantities in use by ICRP. ICRP Publication 42. Oxford: Pergamon Press. 

ICRP. 1990. International Commission on Radiological Protection 1990 Recommendations of the ICRP 

ICRU. 1980. International Commission on Radiation Units and Measurements. ICRU Report No. 33. 

Washington, DC. 

James A. 1987. A reconsideration of cells at risk and other key factors in radon daughter dosimetry. In: 

Hopke P, ed. Radon and its decay products: Occurrence, properties and health effects. ACS Symposium 

Series 331. Washington, DC: American Chemical Society, 400-418. 

James A, Roy M. 1987. Dosimetric lung models. In: Gerber G, et al., ed. Age-related factors in 

radionuclide metabolism and dosimetry. Boston: Martinus Nijhoff Publishers, 95-108.
 

Kondo S. 1993. Health effects of low-level radiation. Kinki University Press, Osaka, Japan (available 

from Medical Physics Publishing, Madison, Wisconsin).
 

Kato H, Schull W. 1982. Studies of the mortality of A-bomb survivors. Report 7 Part 8, Cancer 

mortality among atomic bomb survivors, 1950-78. Radiat Res 90;395-432. 

Mettler F, Moseley R. 1985. Medical effects of ionizing radiation. New York: Grune and Stratton. 

NCRP. 1971. Basic radiation protection criteria. National Council on Radiation Protection and 

Measurements. Report No. 39. Washington, DC. 

NCRP. 1985. A handbook of radioactivity measurements procedures. 2nd ed. National Council on 

Radiation Protection and Measurements. Report No. 58. Bethesda, MD: 

NCRP. 1993. Risk estimates for radiation protection. National Council on Radiation Protection and 

Measurements. Report 115. Bethesda, Maryland 

Otake M, Schull W. 1984. Mental retardation in children exposed in utero to the atomic bombs: A 

reassessment. Technical Report RERF TR 1-83, Radiation Effects Research Foundation, Japan. 

Rubin P, Casarett G. 1968. Clinical radiation pathology. Philadelphia: W.B. Sanders Company, 33. 

UNSCEAR. 1977. United Nations Scientific Committee on the Effects of Atomic Radiation. Sources
 

and effects of ionizing radiation. New York: United Nations.
 

UNSCEAR. 1982. United Nations Scientific Committee on the Effects of Atomic Radiation. Ionizing
 

radiation: Sources and biological effects. New York: United Nations.
 

UNSCEAR. 1986. United Nations Scientific Committee on the Effects of Atomic Radiation. Genetic
 

and somatic effects of ionizing radiation. New York: United Nations.
 

UNSCEAR. 1988. United Nations Scientific Committee on the Effects of Atomic Radiation. Sources, 

effects and risks of ionization radiation. New York: United Nations. 
 

PLUTONIUM D-15 

APPENDIX D 

UNSCEAR. 1993. United Nations Scientific Committee on the Effects of Atomic Radiation. Sources 

and effects of ionizing radiation. New York: United Nations. 

USNRC. 1999. Standards for the protection against radiation, table 1004(b).1. 10 CFR 20.1004. U.S. 

Nuclear Regulatory Commission, Washington, D.C. 
PLUTONIUM D-16
 

APPENDIX D 

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PLUTONIUM E-1 

APPENDIX E. INDEX 

absorbed dose.......................................................................................................................... 20, 55, 62, 128
 

activity median aerodynamic diameter (see AMAD) ................................................................... 25, 73, 211
 

adenocarcinomas................................................................................................................................... 13, 62
 

adsorbed.................................................................................................................... 165, 166, 168, 191, 204
 

adsorption.................................................................................................................................................. 168 

alanine aminotransferase (see ALT) ........................................................................................................... 50 

ALI (see annual limits on intake).............................................................................. 207, 208, 209, 210, 211
 

ALT (see alanine aminotransferase)........................................................................................................... 50 

AMAD (activity median aerodynamic diameter) ................. 14, 24, 25, 43, 61, 73, 74, 75, 80, 86, 131, 211
 

ambient air ................................................................................................................................ 167, 188, 192
 

annual limits on intake (see ALI).............................................................................................................. 207 

bioaccumulation........................................................................................................................................ 191 

bioconcentration factor ............................................................................................................................. 170 

biokinetic .............................................................................................................................. 20, 91, 110, 144
 

biomarker .................................................................................................................. 127, 128, 142, 195, 205
 

blood cell count..................................................................................................................................... 14, 48
 

breast milk......................................................................................................................................... 188, 192
 

cancer........................4, 10, 11, 12, 13, 14, 15, 25, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 45, 49, 50, 54, 56, 

58, 59, 60, 61, 62, 64, 66, 70, 126, 129, 131, 136, 138, 139, 140, 141, 142, 207, 213 

carcinogen................................................................................................................................................. 211 

carcinogenic ........................................................................................................................................ 21, 211
 

carcinogenicity............................................................................................................................................ 78 

carcinoma ................................................................................................................................ 13, 62, 63, 130
 

carcinomas .......................................................................................................................................... 62, 130
 

cardiac arrhythmia ...................................................................................................................................... 52 

cardiovascular ..................................................................................................................... 16, 46, 64, 65, 86
 

cardiovascular effects............................................................................................................................ 16, 46
 

chromosomal aberrations................................................................................................ 66, 69, 70, 140, 141
 

clearance ............................................... 25, 73, 75, 86, 88, 91, 93, 95, 98, 99, 110, 112, 113, 122, 129, 211
 

DAC (see derived air concentration) ........................................................................................ 207, 210, 211
 

death........... 13, 21, 25, 28, 29, 30, 31, 32, 35, 36, 43, 44, 45, 52, 58, 59, 60, 61, 62, 63, 64, 65, 71, 78, 140
 

derived air concentration (see DAC) ........................................................................................................ 207 

elimination half-time................................................................................................................................... 86 

elimination rate ........................................................................................................................................... 76 

endocrine............................................................................................................................................. 52, 124
 

endocrine effects ......................................................................................................................................... 52 

erythema...................................................................................................................................................... 19 

fetus................................................................................................................................. 5, 82, 125, 141, 208
 

fractional absorption ........................................................................................................... 76, 122, 139, 140
 

gastrointestinal effects .............................................................................................................. 16, 46, 47, 64
 

general population................................................................................................................. 3, 5, 10, 78, 207
 

genotoxic............................................................................................................................... 21, 66, 128, 140
 

genotoxicity..................................................................................................................................... 66, 69, 71
 

geometric standard deviation (see GSD) .................................................................................................... 73 

groundwater ...................................................................................................... 163, 164, 166, 168, 175, 176 

GSD (see geometric standard deviation) .................................................................................. 73, 74, 85, 86
 

half-life...................................................................................................... 2, 88, 98, 105, 127, 145, 170, 190
 

hematological effects .......................................................................................................... 14, 47, 48, 49, 53
 

hematopoietic................................................................................................................ 14, 23, 27, 28, 47, 60
 
 

 

 

 

 

 

 

 

 

 

 

 

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
 

Kow .................................................................................................................................................... 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