U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

PUBLIC COMMENT PERIOD ENDS: 

JULY 29, 2011

TOXICOLOGICAL PROFILE FOR

URANIUM

Public Health Service

Agency for Toxic Substances and Disease Registry

May 2011

DRAFT

Additional Resources
URANIUM 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. 

This information is distributed solely for the purpose of pre dissemination public comment under 

applicable information quality guidelines. It has not been formally disseminated by the Agency for Toxic 

Substances and Disease Registry. It does not represent and should not be construed to represent any 

agency determination or policy. 

***DRAFT FOR PUBLIC COMMENT*** 

 

URANIUM iii 

UPDATE STATEMENT 

A Toxicological Profile for Uranium was released in 1999. This present 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
 

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URANIUM iv 

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v 

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 information 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 of the profiles is on health and toxicologic information; 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 information concerning levels 

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

to determine 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 and EPA. 

Each profile includes the following: 

(A) The examination, summary, and interpretation of available toxicologic information 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 of whether adequate information on the health effects of each substance is 

available or in the process of development to determine levels of exposure that present a 

significant risk to human health of acute, subacute, and chronic health effects; and 

(C) Where appropriate, identification of toxicologic testing needed to identify the types or levels 

of exposure 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 of the public. We plan 

to revise these documents in response to public comments and as additional data become available. 

Therefore, we encourage comments that will make the toxicological profile series of the greatest use. 

Comments should be sent to: 

Agency for Toxic Substances and Disease Registry 

Division of Toxicology and Environmental Medicine 

Applied Toxicology Branch 

Regular Mailing Address: Physical Mailing Address: 

 1600 Clifton Road, N.E. 4770 Buford Highway 

Mail Stop F-62 Building 106, 8th floor, MS F-62

 Atlanta, Georgia 30333 Chamblee, Georgia 30341 

 Electronic Comments may be submitted via: www.regulations.gov. 

 Follow the on-line instructions for submitting comments identified by Docket ID No. CDC-2011-0005.
 
VI 

The toxicological profiles are developed under the Comprehensive Environmental Response, 

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

I 04(i)(I) directs the Administrator of ATSDR to " ... effectuate and implement the health related 

authorities" ofthe statute. This includes the preparation of toxicological 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 detennined by A TSDR and the EPA. Section 

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

for each substance on the list. In addition, ATSDR 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 ofliterature, research, and studies on the health effects oftoxic substances" under CERCLA 

Section 104(i)(I)(B), 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. 

This profile reflects ATSDR' s assessment of all relevant toxicologic testing and information that 

has been peer-reviewed. Staffs of the 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 is being made available for public review. Final responsibility for the 

contents and views expressed in this toxicological profile resides with A TSDR. 

Christop 1 . Portier, Ph.D. 
 
 

Assistant Administrator 
 
 

Agency for Toxic Substances and 
 
 

Disease Registry 
 
 
 


 

URANIUM 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 3.7 Children’s Susceptibility 

Section 6.6 Exposures of Children
 

Other Sections of Interest: 

Section 3.8 Biomarkers of Exposure and Effect 

Section 3.11 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. 

***DRAFT FOR PUBLIC COMMENT*** 
URANIUM 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/. 

***DRAFT FOR PUBLIC COMMENT*** 
URANIUM 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. 

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URANIUM x 

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URANIUM xi 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHOR(S): 

Sam Keith, M.S., CHP 

Obaid Faroon, D.V.M, Ph.D. 

Nickolette Roney, M.P.H.
 

Franco Scinicariello, M.D., M.P.H. 

Sharon Wilbur, M.A. 

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

Lisa Ingerman, Ph.D., DABT 

Fernando Llados, Ph.D.
 

Daneil Plewak, B.S.
 

David Wohlers, Ph.D. 

Gary Diamond, Ph.D.
 

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. 

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URANIUM xii 

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URANIUM	 xiii 

PEER REVIEW 

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

1.	 Rudolfs K. Zalups, Ph.D., Mercer University School of Medicine, Macon, Georgia; 

2.	 Walter W. Piegorsch, Ph.D., University of Arizona, Tucson, Arizona; 

3. Fletcher F. Hahn, DVM, Ph.D., DACVP, Lovelace Respiratory Research Institute, Albuquerque, 

New Mexico. 

These experts collectively have knowledge of uranium and uranium compound’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. 

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URANIUM xiv
 
 

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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 URANIUM?.................................................................................................................. 2
 

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

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

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

1.5 HOW CAN URANIUM AFFECT MY HEALTH? ....................................................................... 5
 

1.6 HOW CAN URANIUM AFFECT CHILDREN? .......................................................................... 6
 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO URANIUM? ...................... 7
 

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

TO URANIUM?............................................................................................................................. 7
 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? ................................................................................................... 8
 

1.10 WHERE CAN I GET MORE INFORMATION? .......................................................................... 9
 

2. RELEVANCE TO PUBLIC HEALTH ................................................................................................. 11
 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO URANIUM IN THE 

UNITED STATES ....................................................................................................................... 11
 

2.2 SUMMARY OF HEALTH EFFECTS ......................................................................................... 13
 

2.3 MINIMAL RISK LEVELS (MRLs) ............................................................................................ 18
 

3. HEALTH EFFECTS.............................................................................................................................. 37
 

3.1 INTRODUCTION........................................................................................................................ 37
 

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE ..................................... 39
 

3.2.1 Inhalation Exposure .............................................................................................................. 40
 

3.2.1.1 Death.............................................................................................................................. 41
 

3.2.1.2 Systemic Effects ............................................................................................................. 44
 

3.2.1.3 Immunological and Lymphoreticular Effects ................................................................ 98
 

3.2.1.4 Neurological Effects ...................................................................................................... 99
 

3.2.1.5 Reproductive Effects.................................................................................................... 101
 

3.2.1.6 Developmental Effects ................................................................................................. 101
 

3.2.1.7 Cancer .......................................................................................................................... 103
 

3.2.2 Oral Exposure...................................................................................................................... 107
 

3.2.2.1 Death............................................................................................................................ 108
 

3.2.2.2 Systemic Effects ........................................................................................................... 109
 

3.2.2.3 Immunological and Lymphoreticular Effects .............................................................. 146
 

3.2.2.4 Neurological Effects .................................................................................................... 147
 

3.2.2.5 Reproductive Effects.................................................................................................... 150
 

3.2.2.6 Developmental Effects ................................................................................................. 153
 

3.2.2.7 Cancer .......................................................................................................................... 155
 

URANIUM xv 

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3.2.3 Dermal Exposure................................................................................................................. 157
 

3.2.3.1 Death............................................................................................................................ 157
 

3.2.3.2 Systemic Effects ........................................................................................................... 158
 

3.2.3.3 Immunological and Lymphoreticular Effects .............................................................. 169
 

3.2.3.4 Neurological Effects .................................................................................................... 169
 

3.2.3.5 Reproductive Effects.................................................................................................... 169
 

3.2.3.6 Developmental Effects ................................................................................................. 169
 

3.2.3.7 Cancer .......................................................................................................................... 169
 

3.2.4 Other Routes of Exposure ................................................................................................... 170
 

3.3 GENOTOXICITY ...................................................................................................................... 178
 

3.4 TOXICOKINETICS................................................................................................................... 185
 

3.4.1 Absorption........................................................................................................................... 186
 

3.4.1.1 Inhalation Exposure ..................................................................................................... 186
 

3.4.1.2 Oral Exposure .............................................................................................................. 188
 

3.4.1.3 Dermal Exposure ......................................................................................................... 189
 

3.4.2 Distribution ......................................................................................................................... 190
 

3.4.2.1 Inhalation Exposure ..................................................................................................... 190
 

3.4.2.2 Oral Exposure .............................................................................................................. 193
 

3.4.2.3 Dermal Exposure ......................................................................................................... 196
 

3.4.2.4 Other Routes of Exposure............................................................................................ 197
 

3.4.3 Metabolism.......................................................................................................................... 197
 

3.4.4 Elimination and Excretion ................................................................................................... 198
 

3.4.4.1 Inhalation Exposure ..................................................................................................... 198
 

3.4.4.2 Oral Exposure .............................................................................................................. 201
 

3.4.4.3 Dermal Exposure ......................................................................................................... 202
 

3.4.4.4 Other Routes of Exposure............................................................................................ 202
 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models ........... 202
 

3.5 MECHANISMS OF ACTION ................................................................................................... 224
 

3.5.1 Pharmacokinetic Mechanisms ............................................................................................. 224
 

3.5.2 Mechanisms of Toxicity...................................................................................................... 225
 

3.5.3 Animal-to-Human Extrapolations ....................................................................................... 228
 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS........................... 228
 

3.7 CHILDREN’S SUSCEPTIBILITY ............................................................................................ 230
 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT ..................................................................... 233
 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Uranium ........................................ 234
 

3.8.2 Biomarkers Used to Characterize Effects Caused by Uranium ........................................... 235
 

3.9 INTERACTIONS WITH OTHER CHEMICALS ..................................................................... 236
 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE ................................................ 236
 

3.11 METHODS FOR REDUCING TOXIC EFFECTS .................................................................... 237
 

3.11.1 Reducing Peak Absorption Following Exposure ............................................................. 237
 

3.11.2 Reducing Body Burden ................................................................................................... 238
 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects .......................................... 239
 

3.12 ADEQUACY OF THE DATABASE ........................................................................................ 239
 

3.12.1 Existing Information on Health Effects of Uranium ....................................................... 240
 

3.12.2 Identification of Data Needs ............................................................................................ 242
 

3.12.3 Ongoing Studies .............................................................................................................. 252
 

4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION ............................................. 253
 

4.1 CHEMICAL IDENTITY............................................................................................................ 253
 

4.2 PHYSICAL, CHEMICAL, AND RADIOLOGICAL PROPERTIES ....................................... 253
 

URANIUM xvi 

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5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL.......................................................... 263
 

5.1 PRODUCTION .......................................................................................................................... 263
 

5.2 IMPORT/EXPORT .................................................................................................................... 270
 

5.3 USE ............................................................................................................................................ 270
 

5.4 DISPOSAL................................................................................................................................. 274
 

6. POTENTIAL FOR HUMAN EXPOSURE ......................................................................................... 277
 

6.1 OVERVIEW............................................................................................................................... 277
 

6.2 RELEASES TO THE ENVIRONMENT................................................................................... 281
 

6.2.1 Air ....................................................................................................................................... 282
 

6.2.2 Water................................................................................................................................... 287
 

6.2.3 Soil ...................................................................................................................................... 289
 

6.3 ENVIRONMENTAL FATE ...................................................................................................... 291
 

6.3.1 Transport and Partitioning................................................................................................... 291
 

6.3.2 Transformation and Degradation ........................................................................................ 296
 

6.3.2.1 Air ................................................................................................................................ 296
 

6.3.2.2 Water............................................................................................................................ 297
 

6.3.2.3 Sediment and Soil ........................................................................................................ 297
 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT .................................. 298
 

6.4.1 Air ....................................................................................................................................... 298
 

6.4.2 Water................................................................................................................................... 299
 

6.4.3 Sediment and Soil ............................................................................................................... 309
 

6.4.4 Other Environmental Media................................................................................................ 311
 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE ........................................ 311
 

6.6 EXPOSURES OF CHILDREN .................................................................................................. 320
 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES .............................................. 322
 

6.8 ADEQUACY OF THE DATABASE ........................................................................................ 323
 

6.8.1 Identification of Data Needs ............................................................................................... 325
 

6.8.2 Ongoing Studies .................................................................................................................. 328
 

7. ANALYTICAL METHODS ............................................................................................................... 329
 

7.1 BIOLOGICAL MATERIALS.................................................................................................... 329
 

7.1.1 Internal Uranium Measurements ......................................................................................... 332
 

7.1.2 External Measurements ....................................................................................................... 333
 

7.2 ENVIRONMENTAL SAMPLES .............................................................................................. 334
 

7.2.1 Field Measurements of Uranium ....................................................................................... 335
 

7.2.2 Collection of Environmental Samples ............................................................................... 336
 

7.2.3 Laboratory Analysis of Environmental Samples ............................................................... 337
 

7.3 ADEQUACY OF THE DATABASE ........................................................................................ 344
 

7.3.1 Identification of Data Needs ............................................................................................... 344
 

7.3.2 Ongoing Studies .................................................................................................................. 347
 

8. REGULATIONS, ADVISORIES, AND GUIDELINES ..................................................................... 349
 

9. REFERENCES .................................................................................................................................... 365
 

10. GLOSSARY ...................................................................................................................................... 431
 

URANIUM xvii 

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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 

URANIUM xviii 

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LIST OF FIGURES 

3-1. Levels of Significant Exposure to Uranium – Inhalation ................................................................... 73 

3-2. Levels of Significant Exposure to Uranium – Oral .......................................................................... 128 

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

Hypothetical Chemical Substance .................................................................................................... 204
 

3-4. Respiratory Tract Compartments in Which Particles May be Deposited ......................................... 207
 

3-5. Environmental Pathways for Potential Human Health Effects from Uranium ................................. 209
 

3-6. The Human Respiratory Tract Model: Absorption into Blood ........................................................ 214
 

3-7. Structure of the Human Alimentary Tract Model (HATM) ............................................................. 216
 

3-8. Biokinetic Model for Uranium after Uptake to Blood ......................................................................217
 

3-9. Multicompartmental Model for Uranium after Uptake to Blood...................................................... 220
 

3-10. Multicompartmental Model............................................................................................................ 221
 

3-11. Existing Information on Health Effects of Uranium ......................................................................241
 

5-1. Uranium Ore Processing ................................................................................................................... 266
 

6-1. Frequency of NPL Sites with Uranium Contamination .................................................................... 278
 

6-2. Major DOE Offices, Facilities, and Laboratories ............................................................................. 285
 

6-3. Environmental Pathways for Potential Human Health Effects from Uranium ................................. 292
 

6-4. Average Uranium Concentrations in Drinking Water for States Where Concentration Exceeds 

1 pCi/L.............................................................................................................................................. 304
 

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LIST OF TABLES 

2-1. Enriched, Natural, and Depleted Uranium Mass Equivalents for Radiological Effects ..................... 20
 

2-2. Renal Effects Following Intermediate-Duration Inhalation Exposure to Insoluble Uranium 

Compounds......................................................................................................................................... 24
 

2-3. Renal Effects Following Intermediate-Duration Inhalation Exposure to Soluble and Poorly
 

Soluble Uranium Compounds ............................................................................................................. 26
 

3-1. Levels of Significant Exposure to Uranium – Inhalation ................................................................... 45 

3-2. Levels of Significant Exposure to Uranium – Oral .......................................................................... 110 

3-3. Levels of Significant Exposure to Uranium – Dermal ..................................................................... 159
 

3-4. Summary of Significant Observations in Studies of a Cohort of Gulf War Veterans Exposed 

to Depleted Uranium ......................................................................................................................... 171
 

3-5. Genotoxicity of Uranium In Vivo ..................................................................................................... 181
 

3-6. Genotoxicity of Uranium In Vitro .................................................................................................... 183
 

3-7. Reference Respiratory Values for a General Caucasian Population at Different Levels of 

Activity ............................................................................................................................................. 208
 

3-8. Reference Values of Parameters for the Compartment Model to Represent Time-dependent 

Particle Transport from the Human Respiratory Tract ..................................................................... 210
 

3-9. Sensitivity and Calculated Transfer Coefficients (d-1)...................................................................... 223
 

4-1. Chemical Identity of Uranium Metal ................................................................................................ 254
 

4-2. Physical and Chemical Properties of Selected Uranium Compounds .............................................. 255
 

4-3. Percent Occurrence and Radioactive Properties of Naturally Occurring Isotopes of Uranium ........ 258
 

4-4. 238U Decay Series Showing Sources and Decay Products ................................................................ 259
 

5-1. Uranium Ores ................................................................................................................................... 264
 

5-2. Uranium Production in the United States by Uranium Mills and Other Sources ............................. 268
 

5-3. Uranium Mining Production, 1985–2009 ......................................................................................... 269
 

5-4. Import of Uranium and Compounds (in kg) into the United States (1990–1998) ............................ 271
 

5-5. Export of Uranium and Compounds (in kg) (1990–1998) ............................................................... 272
 

URANIUM xxi 

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URANIUM xxii 

5-6. Foreign Purchases and Foreign Sales of Uranium (kg U3O8 Equivalent) by U.S. Suppliers and 

Owners and Operators of U.S. Civilian Nuclear Power Reactors, 1994–2009 ................................. 273
 

6-1. Normalized Uranium Effluent Discharges from Uranium Mining, Milling, Conversion, 

Enrichment, and Fuel Fabrication ..................................................................................................... 283
 

6-2. Uranium in Airborne Particles (Composites) ................................................................................... 300
 

6-3. Uranium in Drinking Water (Composites) ....................................................................................... 305
 

6-4. Uranium Analyses of Select Precipitation Composite Samples March–May 1996 .......................... 306
 

6-5. Uranium in Rocks and Soils ............................................................................................................. 310
 

6-6. Concentrations of Uranium in Some Foods...................................................................................... 312
 

6-7. Geometric Mean and Selected Percentile of Urinary Concentrations of Uranium (μg/g 

Creatinine) for the U.S. Population from the National Health and Nutrition Examination 

Survey (NHANES) ........................................................................................................................... 315
 

6-8. Geometric Mean and Selected Percentile of Urinary Concentrations of Uranium (μg/L) for the 

U.S. Population from the National Health and Nutrition Examination Survey (NHANES) ............ 317
 

6-9. Urinary Levels of Uranium in Individuals Exposed through Military Use of Depleted Uranium ... 324
 

7-1. Analytical Methods for Determining Uranium in Biological Samples ............................................ 330
 

7-2. Analytical Methods for Determining Uranium in Environmental Samples ..................................... 338
 

7-3. Additional Analytical Methods for Determining Uranium in Environmental Samples ................... 345
 

8-1. Regulations and Guidelines Applicable to Uranium ........................................................................350
 

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URANIUM 1 

1. PUBLIC HEALTH STATEMENT 

This public health statement tells you about uranium, 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. Uranium has been found in at least 67 of the 1,699 current or former NPL 

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

exists that the number of sites at which uranium is found may 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 either from a large area, such as an industrial plant, or from a container, 

such as a drum or bottle, it enters the environment. Such a release does not always lead to exposure. You 

can be 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 uranium is radioactive, you can also 

be exposed to its radiation if you are near it. 

If you are exposed to uranium, 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. 

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URANIUM 2 

1. PUBLIC HEALTH STATEMENT 

1.1 WHAT IS URANIUM? 

Description Uranium is a naturally occurring radioactive 

element. Natural uranium is a mixture of three 

isotopes: 234U, 235U, and 238U. The most 

common isotope is 238U; it makes up about 99% 

of natural uranium. 

All three isotopes behave the same chemically, 

but they have different radioactive properties. 

The half-lives of uranium isotopes (the amount 

of time needed for half of the isotope to give off 

its radiation and change into a different 

element) is very long (4.5 billion years for 238U). 

The industrial process called enrichment is 

used to separate the uranium isotopes and 

increase the concentration of 235U; uranium with 

higher concentrations of 235U than occurs in 

nature is called enriched uranium. The process 

also results in uranium with lower 

concentrations of 235U than found in nature, 

which is called depleted uranium. 

Uses The main civilian uses of enriched uranium are 

fuel for nuclear power plants; depleted uranium 

is used as a counterbalance on helicopters 

rotors and airplane control surfaces. 

Depleted uranium is used by the armed forces 

to increase the density of munitions to help 

them penetrate enemy armored vehicles and is 

also used as armor in some parts of military 

tanks. 

For more information about the properties and uses of uranium, see Chapters 4, 5, and 6. 

1.2 WHAT HAPPENS TO URANIUM WHEN IT ENTERS THE ENVIRONMENT? 

Releases to the environment Uranium is naturally present in nearly all rocks 

and soils. It can be released into the 

environment through wind and water erosion 

and volcanic eruptions. Uranium can be found 

in drinking water from wells drilled in uraniumrich rock formations. 

Industries involved in mining, milling, and 

processing of uranium can also release it into 

the environment. 

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URANIUM 3 

1. PUBLIC HEALTH STATEMENT 

Fate

 • Air 

 • Soil

 • Water 

In the air, uranium exists as dust. Very small 

dust-like particles of uranium in the air fall out of 

the air onto water, plants, and land. Rain 

increases the amount of uranium in air that will 

settle to the ground. 

Uranium deposited on land can be 

reincorporated into soil, washed into surface 

water, or adsorbed onto plant roots. 

Uranium in surface water can be transported 

large distances. Some of the uranium in water 

will adsorb to sediment and other particles in 

the water. 

For more information about what happens to uranium in the environment, see Chapter 5. 

1.3 HOW MIGHT I BE EXPOSED TO URANIUM? 

Food—primary sources of exposure Food and drinking water are the primary 

sources of uranium intake for the general 

public. 

Root crops such as potatoes, parsnips, turnips, 

and sweet potatoes contribute the highest 

amounts of uranium to the diet. The 

concentrations in these foods are directly 

related to the concentrations of uranium in the 

soil where the foods are grown. 

Water In most areas of the United States, low levels of 

uranium are found in the drinking water. Higher 

levels may be found in areas with high levels of 

naturally occurring uranium in rocks and soil. 

Air Very low levels of uranium are found in the air. 

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URANIUM 4 

1. PUBLIC HEALTH STATEMENT 

Occupational exposure People who work with materials and products 

that contain uranium may be exposed at work. 

This includes workers involved in the mining, 

milling, processing, and/or production of 

uranium products. People who work with 

phosphate fertilizers may also be exposed to 

higher levels of uranium. 

People who live near uranium mining, 

processing, and manufacturing facilities may be 

exposed to higher levels of uranium that have 

been released into the environment. 

People who fire uranium weapons, clean these 

weapons after use, or work on equipment that 

has been bombarded with these weapons can 

be exposed to uranium. 

For more information about how you may be exposed to uranium, see Chapter 6. 

1.4 HOW CAN URANIUM ENTER AND LEAVE MY BODY? 

Enter your body

 • Inhalation 

 • Ingestion 

• Dermal contact 

About 0.76–5% of the uranium you breathe will 

enter the bloodstream through the respiratory 

tract. 

About 0.1–6% of the uranium you ingest will 

enter the bloodstream through the 

gastrointestinal tract. Uranium compounds that 

dissolve in water enter the bloodstream more 

easily than uranium compounds poorly soluble 

in water. Unabsorbed uranium is excreted in 

the feces. 

Uranium can be absorbed through the skin; 

water-soluble uranium compounds are the most 

easily absorbed. 

Leave the body Uranium is deposited throughout the body; the 

highest levels are found in bone, liver, and 

kidney. About half of the uranium in bone 

leaves in 11 days. It takes 2–6 days for half of 

the uranium in the kidney to leave. 

Most of the uranium in the body leaves your 

body in the urine. Most ingested uranium is not 

absorbed into the body and leaves the body in 

the feces. 

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URANIUM 5 

1. PUBLIC HEALTH STATEMENT 

For more information about how uranium can leave your body, see Chapter 3. 

1.5 HOW CAN URANIUM AFFECT MY HEALTH? 

This section looks at studies concerning potential health effects in animal and human studies. 

Humans The main target for inhaled uranium in humans 

is the kidneys. Workers who inhaled uranium 

hexafluoride have experienced respiratory 

irritation and accumulation of fluid in the lungs. 

However, these effects were attributed to the 

irritant hydrofluoric acid rather than the uranium. 

Oral exposure to large amounts of uranium can 

damage the kidneys. 

Evaluations of Gulf War veterans having 

depleted uranium shrapnel fragments did not 

show consistent changes in renal and liver 

function, blood cell levels, sex hormone levels, 

sperm parameters, or bone function, changes in 

neurocognitive function, or damage to genes or 

chromosomes. 

Animals The kidney is the most sensitive target for 

uranium toxicity following inhalation, oral, or 

dermal exposure. If inhaled, uranium can also 

damage the respiratory tract. 

Oral exposure studies in animals have shown 

that water-soluble uranium compounds will 

result in kidney effects at lower doses than 

following exposure to insoluble uranium 

compounds. 

Prolonged oral administration of uranium to rats 

has induced neurobehavioral changes as well 

as changes in the levels of certain chemicals in 

the brain. 

Uranium affected fertility in male rats and mice. 

Treating male rats or mice with uranium for a 

few weeks before mating with untreated females 

resulted in a reduced number of babies being 

born. 

Application of soluble uranium compounds to 

the skin of animals has produced skin irritation 

and mild skin damage. 

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URANIUM 6 

1. PUBLIC HEALTH STATEMENT 

Cancer There is no conclusive evidence that uranium 

produces cancer in humans. Neither the 

International Agency for Research on Cancer 

(IARC) nor the EPA has a cancer classification 

for uranium. 

For more information about how uranium can affect your health, see Chapters 2 and 3. 

1.6 HOW CAN URANIUM AFFECT CHILDREN? 

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

conception to maturity at 18 years of age. Potential effects on children resulting from exposures of the 

parents are also considered. 

Effects in children The health effects seen in children from 

exposure to toxic levels of uranium are 

expected to be similar to the effects seen in 

adults. 

Birth defects and other effects We do not know whether uranium can cause 

birth defects in people. There are some studies 

that suggest that exposure to depleted uranium 

increased the frequency of birth defects, but the 

studies are inadequate to establish firm 

conclusions. 

Studies in animals exposed to high levels of 

uranium during pregnancy, which caused 

toxicity in the mothers, have resulted in early 

deaths and birth defects in the young. It is not 

clear if this can happen in the absence of effects 

on the mother. 

In some studies, exposure of rats during 

pregnancy altered the results of tests of brain 

function in the offspring. Other similar studies 

observed changes in the ovaries of the female 

offspring. 

One study reported that giving a high amount of 

uranium to newborn rats altered the formation of 

teeth. 

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URANIUM	 7 

1. PUBLIC HEALTH STATEMENT 

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

Food Exposure to the levels of uranium that are 

naturally present in food and water are not high 

enough to be considered harmful. 

Avoid consuming root vegetables grown in soils 

with high levels of uranium. At least consider 

washing fruits and vegetables grown in that soil 

and discard the outside portion of root 

vegetables. 

Water Consider drinking bottled water if you suspect 

that your drinking water might have elevated 

levels of uranium. 

Soil If you live near a hazardous waste site where 

high levels of uranium are not controlled, 

prevent your children from eating dirt and make 

sure that they wash their hands frequently, 

especially before eating. 

If your doctor finds that you have been exposed to significant amounts of uranium, ask whether your 

children might also be exposed. Your doctor might need to ask you state health department to investigate. 

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

URANIUM? 

Detecting exposure Uranium can be measured in blood, urine, hair, 

and body tissues. Normally, urinary sampling 

is the preferred method for assessing uranium 

exposure. 

Measuring exposure Because most uranium leaves the body within 

a few days, higher than normal amounts in your 

urine shows that you have been exposed to 

larger than normal amounts within the last 

week or so. 

Some highly sensitive instruments can 

measure radioactivity in the body or on your 

skin for a long time after you take in a large 

amount uranium or some other radioactive 

material. 

See Chapters 3 and 7 for more information. 

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URANIUM 8 

1. PUBLIC HEALTH STATEMENT 

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. The EPA, the Occupational Safety and Health Administration (OSHA), and the 

Food and Drug Administration (FDA) are some federal agencies that develop regulations for toxic 

substances. Recommendations provide valuable guidelines to protect public health, but cannot be 

enforced by law. The Agency for Toxic Substances and Disease Registry (ATSDR) and the National 

Institute for Occupational Safety and Health (NIOSH) are two federal organizations that develop 

recommendations for toxic substances. 

Regulations and recommendations can be expressed as “not-to-exceed” levels. These are levels of a toxic 

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

on levels that affect animals; they are then adjusted to levels that will help protect humans. Sometimes 

these not-to-exceed levels differ among federal organizations because they used different exposure times 

(an 8-hour workday or a 24-hour day), 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. 

Some regulations and recommendations for uranium include the following: 

Drinking water The EPA has established a maximum 

contaminant level of 0.03 μg/L and set a 

maximum contaminant level goal of no uranium 

in drinking water. 

Workplace air OSHA set a legal limit of 0.05 mg U/m3

 for 

soluble uranium and 0.25 mg U/m3

 for insoluble 

uranium averaged over an 8-hour work day. 

NIOSH recommends an exposure limit of 

0.05 mg U/m3

 for soluble uranium and 0.2 mg 

U/m3

 for insoluble uranium averaged for up to a 

10-hour work day. 

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URANIUM 9 

1. PUBLIC HEALTH STATEMENT 

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 

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/
 

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URANIUM 10 

1. PUBLIC HEALTH STATEMENT 

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URANIUM 11 

2. RELEVANCE TO PUBLIC HEALTH
 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO URANIUM IN THE UNITED 

STATES 

Uranium is an alpha-emitting, radioactive, heavy metal that occurs naturally in the earth’s crust at an 

average concentration of about 2 ppm (approximately 1 pCi/g). Uranium exists in several isotopic forms. 

The most toxicologically important forms are anthropogenic 232U and 233U and naturally occurring 234U, 

235U, and 238U. Uranium isotopes decay by alpha emission. 238U decays through 16 radioactive progeny, 

including 234U, to reach stable lead-206 (206Pb), while 235U decays through 13 radioactive progeny to reach 

stable 207Pb. Uranium is present in nearly all rocks and soils; some parts of the United States, particularly 

the West, has higher-than-average uranium levels due to natural geological formations. Anthropogenic 

sources of uranium include uranium mining and milling, uranium conversion and enrichment, uranium 

fuel fabrication, nuclear weapons production, production of phosphate fertilizers from phosphate rocks 

containing uranium, and the improper disposal of uranium mine tailings. 

Naturally occurring uranium is an isotopic mixture containing a large percentage of 238U and very small 

percentages of 234U and 235U, by mass. The industrial process of enrichment is used to increase the 

percentage of 235U and decrease the percentage of 238U in natural uranium; enrichment also increases the 

percentage of 234U. This results in a continuum of additional isotope mixtures in which the percentage of 

235U is either larger (enriched uranium) or smaller (depleted uranium) than that of natural uranium. 

Natural uranium consists of 99.284% 238U, 0.711% 235U, and 0.005% 234U by weight (49% 238U, 2% 235U, 

and 49% 234U by radioactivity) and has a very low specific activity (0.68 μCi/g). Uranium enrichment for 

commercial nuclear energy produces uranium that contains about 3% 235U; this is called 3% enriched 

uranium. Uranium enrichment for other purposes, including nuclear weapons production, can produce 

uranium containing as much as 97.3% 235U and having a higher specific activity (~50 μCi/g). Depleted 

uranium is the byproduct of the enrichment process. Depleted uranium has even less specific activity 

(0.33 μCi/g) than natural uranium. 

The general population is exposed to uranium via ingestion of food and drinking water and inhalation of 

air, with food being the primary contributor to body burden. The daily intake of uranium from food 

sources ranges from 0.6 to 1.0 pCi/day (0.9–1.5 μg/day). Uranium from soil is not taken up by plants, but 

rather is adsorbed onto the roots. Thus, the highest levels of uranium are found in root vegetables, 

primarily unwashed potatoes. Populations living near uranium mills or mines or other areas with elevated 

uranium in soil may be exposed to higher levels of uranium from locally grown vegetables. Uranium 

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URANIUM 12 

2. RELEVANCE TO PUBLIC HEALTH 

levels in drinking water vary widely, with a mean population-weighted average of 0.8 pCi/L. Compared 

to the ingestion route, the intake of uranium via inhalation is small; intakes range from 0.0007 to 

0.007 pCi/day (0.001–0.01 μg/day). 

Uranium is present in the body at very low or trace concentrations and is not known to be an essential 

element. Human intakes are constant through very small amounts of natural uranium in food and water, 

and even smaller amounts in air. The following anthropogenic activities increase the potential for human 

exposure to uranium: mining, milling, and handling uranium; processing uranium ore end products 

(uranium dioxide, uranium hexafluoride); producing nuclear energy and nuclear weapons; producing 

phosphate fertilizers from phosphate rocks that contain much higher-than-average levels of uranium; and 

improperly disposing of wastes. Occupational exposure to airborne uranium ore dust occurs in uranium 

mines and mills and in processing plants. Typically, uranium represents only 0.2–5% by weight of the 

ore; however, levels as high as 22% have been reported in Athabasca basin region of Canada. 

Uranium is poorly absorbed following inhalation, oral, or dermal exposure and the amount absorbed is 

heavily dependent on the solubility of the compound. The site of deposition of inhaled particles in the 

respiratory tract also influences absorption. Larger particles deposited in the nasal cavity or 

tracheobronchial region are rapidly transported via the mucociliary escalator to the pharynx and are 

eventually swallowed. Smaller particles are deposited deeper in the respiratory tract. The more soluble 

compounds are more likely to be absorbed into the blood at the alveolar level within days. The less 

soluble compounds are more likely to remain in the lung tissue and associated lymph nodes either for 

weeks (uranium trioxide, uranium tetrafluoride) or years (uranium dioxide, triuranium octaoxide), 

resulting in significant pulmonary retention in inhalation-exposure toxicity and a greater dose of alpha 

radiation. Absorption efficiencies of 18–40 and 23% have been reported in animals exposed to uranium 

hexafluoride or uranium trioxide aerosols. Following oral exposure, <0.1–6% of the uranium is absorbed, 

depending on the solubility of the uranium compound. Following dermal application of uranyl nitrate, 

0.4% of the dose was absorbed through the skin of hairless rats. Damage to the skin resulted in 

substantially higher absorption efficiencies. Transdermally absorbed uranium and uranium released from 

embedded fragments is expected to behave identically to uranium compounds absorbed through the lungs 

and the gastrointestinal tract. Regardless of solubility, a portion of uranium quickly reaches the systemic 

circulation. Uranium is usually found in compounds that can break down and recomplex to form other 

compounds. In body fluids, tetravalent uranium is likely to oxidize to the hexavalent form, followed by 

formation of the uranyl ion. Uranium generally complexes with citrate, bicarbonates, or protein in 

plasma. Approximately 67% of uranium in the blood is filtered in the kidneys and leaves the body in 

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URANIUM 13 

2. RELEVANCE TO PUBLIC HEALTH 

urine within 24 hours; the remainder distributes to tissues, primarily the bone, liver, and kidney. The 

retention half times for uranium in bone and the kidney are 11 and 2–6 days, respectively. The main site 

of long-term retention for inhaled insoluble compounds that are deposited in the deep respiratory tract 

tend to accumulate in the lungs and pulmonary lymph nodes. 

2.2 SUMMARY OF HEALTH EFFECTS 

This profile discusses the chemical and radiological health effects of the three groupings of uranium 

isotope mixtures (natural uranium, enriched uranium, and depleted uranium) and the various compounds 

in which uranium is usually found. The health effects of daughter radioactive elements (radium and 

radon) are addressed in other toxicological profiles (consult the ATSDR toxicological profiles for radium 

and radon for more information regarding these radioactive elements). The chemical action of all 

isotopes and isotopic mixtures of uranium are identical, regardless of the specific activity, because 

chemical action depends only on chemical properties. Thus, the chemical toxicities of natural, depleted, 

and enriched uranium are identical. Current evidence from animal studies suggests that the toxicity of 

uranium is mainly due to its chemical damage to kidney tubular cells, leading to nephritis. Other 

sensitive targets of toxicity include the respiratory tract (inhalation only), neurological system, 

reproductive system, and the developing organism. 

There are limited data on the renal toxicity of uranium following inhalation exposure in humans. A 

number of studies found no alterations in mortality due to renal disease in uranium workers. An autopsy 

study of long-time workers exposed to low levels of uranium did not find evidence of renal injury years 

after exposure termination. However, a study of uranium mill workers exposed to uranium found 

evidence of renal dysfunction (β-2-microglobinuria, aminoaciduria); the severity and incidence of the 

effects appeared to be related to exposure duration. Several epidemiology studies have found associations 

between parameters of renal dysfunction (e.g., urine levels of albumin, β2-microglobulin, glucose, and 

protein HC) and elevated uranium levels in drinking water. These studies did not find overt signs of 

toxicity and in many cases, the biomarkers of renal dysfunction were within the normal range. Although 

most of the epidemiology studies provided information on uranium levels in the drinking water, there was 

often a large range of exposure levels; thus, the human oral exposure studies do not provide reliable doseresponse data. Studies of Gulf War veterans with embedded shrapnel containing depleted uranium found 

alterations in biomarkers of renal function (e.g., urinary retinol binding protein and β2-microglobulin 

levels); however, the alterations were not statistically significant, as compared to non exposed veterans. 

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URANIUM 14 

2. RELEVANCE TO PUBLIC HEALTH 

Renal effects have been observed in a number of animal species exposed to various uranium compounds. 

The observed effects have primarily involved damage to the proximal tubules and have been observed 

following inhalation, oral, dermal exposures; and from embedded fragments. The preponderance of the 

data on the renal toxicity of uranium come from a collection of experiments conducted in late 1940s and 

early 1950s. The results of these studies demonstrate compound- and species-related differences in 

toxicity. Soluble uranium compounds (e.g., uranyl nitrate, uranyl fluoride, uranium hexafluoride, and 

uranium tetrachloride) are more toxic than insoluble uranium compounds (e.g., uranium dioxide, uranium 

peroxide, uranium trioxide, and triuranium oxtaoxide). Renal effects have been observed in animals 

exposed to aerosols of soluble uranium compounds at concentrations of ≥0.13 mg U/m3 for intermediate 

durations. However, no renal effects were observed in animals exposed to 1.0 mg U/m3 as insoluble 

compounds; the lowest-observed-adverse-effect level (LOAEL) was 8.2 mg U/m3

. These data suggest 

that soluble compounds are at least 5 times more toxic than insoluble compounds. The difference in 

toxicity is likely due to the more efficient absorption of soluble uranium compounds. Of the animals 

tested in intermediate-duration inhalation studies, dogs and rabbits are the most sensitive followed by rats, 

mice, and guinea pigs. The severity of renal lesions increases with increasing exposure concentrations; 

very slight renal tubular damage is observed at low concentrations and marked degeneration and necrosis 

are observed at higher concentrations. Little differences have been found between the adverse effect 

levels following 30 days of exposure and 1 year of exposure, suggesting that in animals, the toxicity is not 

strongly influenced by the duration of exposure. The oral and dermal databases are more limited than the 

inhalation database. Acute- and intermediate-duration oral studies in laboratory animals (rats, mice, 

rabbits, and dogs) provide strong support for identifying the kidney as a sensitive target of uranium 

toxicity. Acute exposure to lethal doses of uranyl nitrate or uranyl acetate resulted in renal dysfunction in 

rats and mice as evidenced by increases in urine volume, plasma urea, blood urea nitrogen (BUN), and 

urinary total protein. Minimal histological alterations in the glomerulus, proximal tubules, and/or 

interstitium have been observed in rats and rabbits exposed to intermediate-duration doses of soluble 

uranium compounds as low as 0.05 mg U/kg/day; the severity of the renal lesions increased with dose. 

Additionally, a rabbit study demonstrated that renal lesions persisted up to 91 days following termination 

of a 91-day oral exposure. Due to the poor absorption of ingested insoluble uranium compounds, there 

are significant differences in the renal toxicity of various uranium compounds. No renal effects were 

observed in rats exposed to doses as high as 11,000–12,000 mg U/kg/day as uranium dioxide, uranium 

trioxide, uranyl octaoxide, or uranium tetrafluoride for 30 days. In contrast, adverse renal effects were 

observed at doses of 140–270 mg U/kg/day as uranyl nitrate, uranium peroxide, or uranyl fluoride and 

doses of 440–790 mg U/kg/day as uranium tetrachloride or uranium acetate. As with other routes of 

exposure, proteinuria, renal failure, and renal lesions were observed in laboratory animals following acute 

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URANIUM 15 

2. RELEVANCE TO PUBLIC HEALTH 

dermal exposure to uranyl nitrate and in rats with depleted uranium fragments embedded in the 

gastrocnemius muscle. 

General damage to pulmonary structures, usually noncancerous alveolar epithelium damage of type II 

cells, can occur upon inhalation of insoluble reactive chemicals such as some uranium compounds 

(uranium tetrafluoride, uranium dioxide, uranium trioxide, triuranium octaoxide). In acute exposures, 

pulmonary damage may be limited to interstitial inflammation of the alveolar epithelium leading 

eventually to emphysema or pulmonary fibrosis. In studies of the pulmonary effects of airborne uranium 

dust in uranium miners, the respiratory diseases reported were aggravated by the insoluble aerosol 

particles (mine dust) to which these miners were exposed because most of the noncancerous respiratory 

diseases reported in these studies were consistent with toxicity of inhalable dust particles other than 

uranium, such as silica. Respiratory effects reported in workers acutely exposed to uranium hexafluoride 

were caused by hydrogen fluoride, a potent lung irritant and a spontaneous byproduct of the reaction 

between uranium hexafluoride and water, such as in mucous membranes. Similar to human studies, signs 

of respiratory irritation (rhinitis and lung edema, hemorrhage, and emphysema) have been observed in 

animals exposed to uranium hexafluoride, uranyl fluoride, and uranium tetrafluoride. It is likely that 

these effects were due to co-exposure to hydrogen fluoride. Inhalation exposure to insoluble uranium 

compounds also results in pulmonary damage. Very slight pulmonary lesions were observed in rats and 

dogs exposed to uranium trioxide for 4 weeks; mild to severe renal tubular necrosis was also observed at 

this concentration. In contrast, chronic exposure to uranium dioxide for at least 3.5 years resulted in lung 

fibrosis in monkey and dogs; renal effects were not observed in either species. 

In general, studies of uranium workers have not provided evidence of adverse neurological effects, 

although tests to detect subtle neurological alterations were not conducted. Although poorer performance 

on neurological tests were observed in Gulf War veterans exposed to depleted uranium from embedded 

shrapnel, the effects were not consistently observed, and were found to be strongly influenced by two 

subjects with extremely high uranium levels and severely complex co-morbid conditions. Frank 

neurological effects have been observed in animals exposed to lethal inhalation concentrations or oral 

doses of several uranium compounds. It is not known if these effects were directly related to uranium 

exposure. The effect of uranium compounds on neurobehavior and on neurotransmitter levels in various 

areas of the brain has been investigated in several studies. Uranium increased motor activity in male rats 

exposed to 28 mg U/kg/day and female mice exposed to 6 mg U/kg/day in acute-duration drinking water 

studies. Uranium also decreased spatial working memory in rats dosed with 2.5–2.7 mg U/kg/day as 

enriched uranium for 9 months. However, these effects were not observed in rats similarly exposed to 

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URANIUM 16 

2. RELEVANCE TO PUBLIC HEALTH 

depleted uranium. It should be mentioned that a study in rats implanted with up to 20 depleted uranium 

pellets (approximately 760 mg depleted uranium) for 150 days reported no significant alterations in tests 

of spontaneous motor activity. Investigators have tried to identify biochemical and morphological 

substrates that, when altered, could explain the behavioral alterations. Increased motor activity showed a 

weak correlation with increased lipid oxidation in the brain of rats in a 2-week study. Uranium also 

altered the levels of neurotransmitters and their metabolites in brain areas from mice and rats. Of various 

brain areas examined, the hippocampus from rats exposed to uranium in the drinking water for 90 days 

had the most uranium, suggesting that this area may play an important role in the neurobehavioral 

alterations caused by exposure to uranium; alterations in the levels of oxidative stress indicators were also 

observed in other regions of the brain with lower uranium concentrations. Implantation of depleted 

uranium pellets in rats resulted in measurable uranium in the brain at 6–18 months after implantation and 

was accompanied by electrophysiological changes in hippocampal slices from the treated animals at 6 and 

12 months, but not at 18 months. The mechanism(s) by which uranium induces neurological alterations is 

not known, but as is the case with other metals, it could be interfering with calcium by mimicking or 

blocking its actions. A recent study in rats also suggested that uranium may affect genes involved in 

cholinergic transmission. These investigators reported that exposure to uranium seemed to induce 

transcriptional alterations in the hippocampus aimed at preserving acetylcholine levels, whereas in the 

cortex, exposure led mainly to translational alterations that increased acetylcholinesterase mRNA levels 

after 9 months of exposure. Although there was an increase in the genes expressing cortical 

acetylcholinesterase, there was a decrease in acetylcholinesterase activity in the cortex. 

Limited data are available regarding reproductive effects of uranium in humans. Studies of uranium 

miners, millers, and processors found that male uranium miners had more first-born female children than 

expected, suggesting that uranium=s alpha radiation damaged the y-chromosomes of the miners. 

However, the workers were also exposed to 222Rn, chlorine, hydrofluoric acid, lead sulfate, nickel, nitric 

acid and nitrogen oxides, silicon dioxide, and sulfuric acid. Longitudinal assessments of relatively small 

numbers of males who were exposed to depleted uranium in the Gulf War via retained metal shrapnel 

fragments have not provided evidence of adverse reproductive effects. Uranium reduced fertility, likely 

due to reductions in spermatozoa counts, was observed in male mice exposed to ≥5.6 mg U/kg/day in 

drinking water and mated with untreated females. However, fertility was not significantly affected in 

another study in mice in which males and females were treated by gavage with up to 14 mg U/kg/day. 

These apparently discrepant results may be due to the different mode of dosing between the two studies 

(i.e., gavage vs. drinking water), which may have resulted in different rates of absorption. Uranium also 

reduced fertility in male rats dosed with 11.2 mg/kg/day and mated with untreated females; the NOAEL 

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URANIUM 17 

2. RELEVANCE TO PUBLIC HEALTH 

was 5.6 mg U/kg/day. Effects on female reproductive health have also been observed in mice orally 

exposed to uranium. Alterations in ovarian folliculogenesis were observed at ≥1.25 mg U/kg/day. 

Another study reported slight alterations in ovarian folliculogenesis in mice at very low doses 

(≥0.00039 mg U/kg/day in the drinking water). A reduced number of small primary follicles were 

observed on postnatal day 5; however, all other follicle populations including primordial, 

secondary/growing, healthy, and atretic were unchanged. It would be helpful to try to replicate these 

results because effects were reported at considerably lower doses than the adverse effect levels in other 

studies, effects were only observed in one type of follicle population, and the doses were below the 

detection limit and normal drinking water background levels. Uranium also showed estrogenic properties 

in mice at very low doses. Exposure of ovariectomized mice to depleted uranyl nitrate at 0.005 mg 

U/kg/day for 10 days or 0.009 mg U/kg/day for 30 days significantly increased uterine weight; an 

increase in the presence of cornified vaginal cells, indicative of an estrogenic effect was also observed at 

0.005 and 0.009 mg U/kg/day. However, these effects were not observed at higher doses (0.09 or 0.9 mg 

U/kg/day for 30 days). Again, it would be helpful to try to replicate these results observed at such low 

doses particularly since the study only found effects at the lower doses tested, but not at the higher doses. 

Enriched uranium, but not depleted uranium, increased serum testosterone and the expression of genes 

involved in steroidogenesis in male rats in a 9-month drinking water study. In addition, enriched uranium 

significantly increased the expression of transcription factors involved in the regulation of steroidogenic 

genes. These results suggested that the observed effects were mainly due to the radiation emitted by 

enriched uranium. 

Developmental effects have been observed in the offspring of mice; these effects have often been 

observed at maternally toxic doses. Elevated uranium levels were measured in the offspring of rats 

exposed to uranyl acetate prior to mating and during gestation and lactation, suggesting transplacental 

and/or lactational transfer of uranium. The observed effects included lethality, reductions in growth, 

increase in visceral and skeletal abnormalities, and reproductive effects. Lethality effects consisted of 

reductions in viability on postnatal day 21 in offspring of mice dosed with 28 mg U/kg/day on gestation 

day 13 to postnatal day 21, decreases neonatal viability in the offspring of mice exposed to 5.6 mg 

U/kg/day prior to mating and throughout gestation and lactation, and increases in late resorptions and 

decreases in the number of live fetuses in the offspring of mice exposed to 14 mg U/kg/day prior to 

mating and during gestation. Reductions in fetal body weight were observed in the offspring of mice 

dosed with ≥2.8 mg U/kg/day on gestation days 6–15. This study also reported significant increases in 

the total number of external malformations at ≥2.8 mg U/kg/day and the total number of skeletal defects 

at ≥14 mg U/kg/day. Maternal toxicity may have played a role in this study since maternal weight gain 

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URANIUM 18 

2. RELEVANCE TO PUBLIC HEALTH 

during exposure was reduced by at least 43%. Alterations in ovarian folliculogenesis, similar to those 

described in the discussion of reproductive toxicity have been observed in the female pups of mice 

exposed to uranium prior to mating and/or during gestation; as discussed in the previous paragraph on 

reproduction toxicity, the doses tested in the study were much lower than effect levels reported in other 

studies, were below the detection limit, and are lower than normal background levels. In rats, doses of 

22.5 or 45 mg U/kg/day administered from before mating until gestation day 14 were not fetotoxic; 

however, continued dosing during lactation resulted in a significant reduction in pups weight on postnatal 

day 21. Uranium did not affect developmental landmarks or neuromotor maturation in the pups, but the 

high dose altered learning and memory. Pups from rats exposed to a smaller dose of approximately 

4.3 mg enriched U/kg/day during gestation showed delayed hyperactivity when tested at 5 and 9 months 

of age. Uranium was also shown to interfere with tooth eruption and development in young rats. 

Since uranium is weakly radioactive, it has been assumed to be potentially carcinogenic at occupational 

levels by NIOSH. The International Agency for Research on Cancer (IARC) has no classification for 

uranium. Although significant increases in the occurrence of respiratory tract cancer (predominantly lung 

cancer) have been found in numerous studies of uranium miners, radon progeny in the mines, and not the 

uranium, were clearly identified as the carcinogenic agents. (For further information on cancer risks from 

radon, refer to the ATSDR Toxicological Profile for Radon.) Studies of workers at uranium milling or 

nuclear facilities and residents living near uranium mining and milling facilities have not found 

significant increases in cancer mortality associated with uranium exposure. Most studies of animals 

exposed to soluble or insoluble uranium compounds for at least 1 year via inhalation or oral exposure did 

not report increases in the incidence of malignant tumors. However, increases in pulmonary neoplasms 

were observed in dogs exposed to uranium dioxide for 1–5 years and rats exposed to uranium ore 

(containing 44% uranium) for 65 weeks. The investigators for the uranium dioxide study suggested that 

the increased incidence of lung tumors may have been the result of radiation exposure. 

2.3 MINIMAL RISK LEVELS (MRLs) 

Estimates of exposure levels posing minimal risk to humans (MRLs) have been made for uranium. An 

MRL is defined as an estimate of daily human exposure to a substance that is likely to be without an 

appreciable risk of adverse effects (noncarcinogenic) over a specified duration of exposure. 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 within a given route of exposure. MRLs are based on 

noncancerous health effects only and do not consider carcinogenic effects. MRLs can be derived for 

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URANIUM 19 

2. RELEVANCE TO PUBLIC HEALTH 

acute, intermediate, and chronic duration exposures for inhalation and oral routes. Appropriate 

methodology does not exist to develop MRLs for dermal exposure. 

Although methods have been established to derive MRLs (Barnes and Dourson 1988; EPA 1990d), 

uncertainties are associated with these techniques. Furthermore, ATSDR acknowledges additional 

uncertainties inherent in the application of the procedures to derive less than lifetime MRLs. As an 

example, acute inhalation MRLs may not be protective for health effects that are delayed in development 

or are acquired following repeated acute insults, such as hypersensitivity reactions, asthma, or chronic 

bronchitis. As these kinds of health effects data become available and methods to assess levels of 

significant human exposure improve, these MRLs will be revised. 

Minimal Risk Levels (MRLs) have been derived for the effects from inhalation and oral exposure to 

uranium, and those values are identified in this section and their bases are detailed in Appendix A. MRLs 

for radiological exposure were not calculated because: 

	 no data are available for use in calculating radiological MRLs for any duration because no 

radiological effects were identified in any of the available studies that used natural uranium as a 

test material; 

	 the MRLs for chemical effects would adequately protect against the possible radiotoxicity of 

natural and depleted uranium because radiological effects are not expected to occur, based on the 

low specific activities of these isotopic mixtures and the current toxicity data in humans and 

animals; 

	 the studies that reported potential radiological effects (severe pulmonary fibrosis, friable blood 

vessels) used highly enriched uranium in a single inhalation exposure (Filippova et al. 1978; 

Morris et al. 1989); and 

	 United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) has 

considered that limits for natural (and depleted) uranium in food and drinking water (should be 

based on the chemical toxicity rather than on a hypothetical radiological toxicity, which has not 

been observed in either humans or animals (UNSCEAR 1993; Wrenn et al. 1985). 

Lack of radiological effects in studies that used natural uranium is due to the low specific activities of 

natural and depleted uranium, which are 0.67 and 0.3 μCi/g, respectively. In comparison, the calculated 

specific activity for 97.5% enriched uranium is approximately 50 μCi/g. 

Table 2-1 shows the mass equivalents for natural and depleted uranium for radiation levels that caused 

potential radiological effects in rats exposed once for 100 minutes to airborne 92.8% enriched uranium 

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URANIUM 20 

2. RELEVANCE TO PUBLIC HEALTH 

Table 2-1. Enriched, Natural, and Depleted Uranium Mass Equivalents for
 

Radiological Effects
 

Highly enriched 

uranium Natural Depleted 

Intake duration Effect 

radioactivity 

concentrationa 

uranium mass 

equivalentb 

uranium mass 

equivalentc 

Threshold 

limit valued 

Acute Severe alveolar 

fibrosis 

5 μCi/m3 

(≈0.111 g/m3

) 

7.2 g/m3 15.3 g/m3 0.0002 g/m3 

Intermediate No datae No data No data No data Not applicable 

Chronic No data No data No data No data Not applicable 

a

Value calculated from a highly 235U-enriched uranium dioxide exposure of 111 mg/m3 (97.8 mg uranium/m3) and a 

specific activity of 1.91 kBq/g (51.6 μCi/g) (Morris et al. 1990).

b

Value based on a highly 235U-enriched dioxide radioactivity concentration of 5 μCi/m3 and a specific activity of
 

0.7 μCi/g for natural uranium.
	 c

Value based on a highly 235U-enriched dioxide radioactivity concentration of 5 μCi/m3 and a specific activity of
 

0.33 μCi/g for depleted uranium.
	 d

This is a time-weighted average concentration for short-term (8-hour) inhalation exposure to insoluble natural
 

uranium compounds in the workplace for which no adverse effects (chemical or radiological) are expected (NIOSH
 

1994).
 e

Because the observations in the Morris et al. (1989) studies were made through 720 days, the conclusions may be 

applicable to intermediate and chronic durations.
 

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2. RELEVANCE TO PUBLIC HEALTH 

with an estimated specific activity of 51.6 μCi/g (Morris et al. 1989). These mass equivalent values for 

natural and depleted uranium for the minimal concentration of radioactivity that is expected to induce 

potential radiological effects are well above levels that would be expected to be inhaled or ingested. In 

addition, the mass equivalents for natural and depleted uranium for potential radiological effects are 

3,600 and 76,500 times higher, respectively, than the occupational exposure limits (short-term exposure) 

recommended by NIOSH (1997). Therefore, MRLs for uranium based on studies that used enriched 

uranium are inappropriate. 

Chemically, natural and depleted uranium are identical. Therefore, the MRLs calculated for chemical 

effects, based on studies that tested natural uranium, are applicable to the chemical actions of depleted 

uranium because the nature and extent of chemical toxicity are determined only by chemical properties. 

The health effects associated with exposure to natural and depleted uranium appear to be solely chemical 

in nature and not radiological; exposure to enriched uranium may also include a radiological component, 

but the data are limited. The toxicity of a variety of uranium compounds has been investigated in a 

number of animal species; the results of these studies support the findings of the available human studies. 

Regardless of the exposure duration or route, the animal data provide strong evidence that kidney damage 

is the principal toxic effect of uranium and that the toxicity varies according to solubility of the uranium 

compound. Other sensitive end points include the respiratory tract following chronic exposure to 

insoluble uranium compounds and developmental toxicity following acute oral exposure to soluble 

uranium compounds. The more soluble uranium compounds (uranium hexafluoride, uranium 

tetrachloride, uranyl fluoride, uranyl nitrate) have the highest renal toxicity, followed by the less soluble 

compounds (ammonium diuranate, sodium diuranate, uranium tetrafluoride) and the insoluble uranium 

compounds (uranium dioxide, uranium trioxide, uranium peroxide, triuranium octaoxide). The difference 

in toxicity is due to the easier absorption of soluble compounds from the lung or gastrointestinal tract into 

the blood and distribution to other tissues (Tannenbaum et al. 1951). 

ATSDR has determined that the toxicity database for uranium justifies the derivation of separate MRLs 

for soluble and insoluble forms of uranium for certain durations and routes of exposure. This is based on 

toxicokinetic evidence that absorption of uranium (and concentration in target tissue) is significantly 

greater during exposure to the more water-soluble compounds. Where the database is not extensive 

enough to allow separate MRLs, the MRL for the soluble form should be protective for health effects due 

to all forms of uranium. 

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URANIUM 22 

2. RELEVANCE TO PUBLIC HEALTH 

Inhalation MRLs. 

Acute-Duration Inhalation MRL 

There are limited data on the toxicity of uranium compounds in humans and animals following acuteduration inhalation exposure. Several case reports of individuals briefly exposed to uranium hexafluoride 

(Kathren and Moore 1986; USNRC 1986) or uranium tetrafluoride (Lu and Zhao 1990) are available. 

The observed effects included eye irritation and respiratory irritation, chemical burns, renal toxicity, and 

gastrointestinal irritation; however, some of these effects may have been caused by the rapid release of 

hydrogen fluoride when uranium hexafluoride reacted with water in the air and mucous membranes. 

Respiratory and renal effects have been observed in acutely exposed laboratory animals. Severe alveolar 

septal fibrosis was observed in rats exposed to 5,051 mg U/m3 as enriched uranium dioxide for 

100 minutes (Morris et al. 1990) and gasping and nasal irritation were observed in mice exposed to 

637 mg Um/m3

 as uranium hexafluoride for 10 minutes (Spiegl 1949). The renal effects included 

proteinuria and glucosuria in rats exposed to 426 mg U/m3

 for 10 minutes or 1,430 mg U/m3 for 2 minutes 

as uranium hexafluoride (Leach et al. 1984) or in guinea pigs exposed to 23,040 mg U/m3

 as uranium 

hexafluoride for 2 minutes (Leach et al. 1984). 

The available data were not considered adequate for derivation of an acute-duration inhalation MRL for 

uranium; the human studies did not reliably report exposure levels and the animal studies involved very 

short (<2 hours) exposure durations. Using one of the short exposure animal studies to derive an MRL 

may not be protective for continuous exposure for 2 weeks; longer-term animal studies with serial 

sacrifices (Stokinger et al. 1953) reported renal lesions following 3 days of exposure to soluble uranium 

compounds. These data are poorly reported and involved very small number of animals and are not 

suitable for MRL derivation. 

Intermediate-Duration Inhalation MRL 

	 An MRL of 0.002 mg U/m3

 has been derived for intermediate-duration inhalation exposure (15– 

364 days) to insoluble compounds of uranium. 

Intermediate-duration inhalation studies in animals have examined the toxicity of various insoluble 

uranium compounds including uranium dioxide, uranium peroxide, uranium trioxide, and triuranium 

octaoxide in several animal species. The results of these studies suggest that the kidney and the 

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URANIUM 23 

2. RELEVANCE TO PUBLIC HEALTH 

respiratory tract are sensitive targets of uranium toxicity, with the kidney being the most sensitive target. 

A summary of the adverse effect levels for renal effects identified in reliable intermediate duration studies 

is presented in Table 2-2. Renal effects were observed at ≥8.2 mg U/m3

; the severity of the lesions was 

concentration-related. Very slight tubular lesions were observed in dogs exposed to 8.2 mg U/m3

, and 

mild to severe necrosis was observed in rats, rabbits, and dogs exposed to 16 mg U/m3

. Although there 

are limited data to make species comparisons, data for uranium dioxide suggest that rabbits are more 

sensitive than rats, mice, or guinea pigs; the data do not allow for a comparison between rabbits and dogs. 

In addition to the renal effects observed in rats, rabbits, and dogs exposed to uranium trioxide, very slight 

pulmonary lesions were observed in dogs and rats exposed to 16 mg U/m3 and severe effects were 

observed in rabbits dying early after exposure to 16 mg U/m3 (Rothstein 1949c). 

The lowest LOAEL for renal or pulmonary effects following intermediate-duration exposure to an 

insoluble uranium compound was 8.2 mg U/m3 identified in dogs exposed to uranium dioxide for 5 weeks 

(Rothstein 1949b). In this study, groups of 6–19 dogs of unspecified strain and gender were exposed to 

1.3, 9.3, or 10.4 mg/m3 uranium dioxide (1.1, 8.2, or 9.2 mg U/m3

) 6 days/week for 5 weeks, presumably 

for 6 hours/day. The following parameters were used to assess toxicity: mortality, body weight changes, 

standard hematology, clinical chemistry, urinalysis, and histopathology. No dogs died from exposure to 

uranium dioxide dust. Additionally, no alterations in body weight gain or hematology, serum clinical 

chemistry, or urinalysis parameters were noted. Histopathological alterations were limited to the kidneys; 

“very slight” renal tubular degeneration was observed in two of six dogs at 8.2 mg U/m3

. No alterations 

were observed in two dogs examined from the 9.2 mg U/m3 group. The results of this study are supported 

by the findings of slight to mild tubular degeneration in dogs exposed to 10 mg U/m3 as uranium dioxide 

for 1 year; no effects were observed at 1 mg U/m3 (Stokinger et al. 1953). 

Benchmark dose (BMD) modeling was not used to estimate the point of departure due to the limited 

reporting of incidence data. The no-observed-adverse-effect level (NOAEL) of 1.1 mg U/m3 was used to 

derive the MRL. This value was adjusted for intermittent exposure (6 hours/24 hours, 6 days/7 days) 

resulting in a NOAELADJ of 0.24 mg U/m3

. Because regional deposited dose ratios (RDDRs) are not 

available for dogs, dosimetric adjustments could not be made; thus, the NOAELADJ was used as the point 

of departure. The NOAELADJ was divided by an uncertainty factor of 100 (10 for extrapolation from 

animals to humans and 10 for human variability), resulting in an intermediate-duration inhalation MRL of 

0.002 mg U/m3 for insoluble uranium compounds. 

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URANIUM 24 

2. RELEVANCE TO PUBLIC HEALTH 

Table 2-2. Renal Effects Following Intermediate-Duration Inhalation Exposure to 

Insoluble Uranium Compounds
 

NOAEL LOAEL 

Species Duration (mg U/m3

) (mg U/m3) Effect Reference 

Uranium dioxide 

Rat 5 weeks 19.4 Rothstein 1949b 

Mouse 5 weeks 19.4 Rothstein 1949b 

Rabbit 5 weeks 19.4 Marked tubular necrosis Rothstein 1949b 

Rabbit 7 months 10 Stokinger et al. 1953 

Guinea pig 5 weeks 19.4 Rothstein 1949b 

Guinea pig 7 months 10 Stokinger et al. 1953 

Dog 5 weeks 1.1 8.2 Very slight tubular injury Rothstein 1949b 

Uranium peroxide 

Rabbit 23 days 15.4 Moderate necrosis Dygert 1949d 

Uranium trioxide 

Rat 4 weeks 16 Mild to severe necrosis Rothstein 1949c 

Rabbit 4 weeks 16 Mild to severe necrosis Rothstein 1949c 

Dog 4 weeks 16 Mild to severe necrosis Rothstein 1949c 

Triuranium octaoxide 

Rat 26 days 14 Dygert 1949c 

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URANIUM 25 

2. RELEVANCE TO PUBLIC HEALTH 

•	 An MRL of 0.0001 mg U/m3 has been derived for intermediate-duration inhalation exposure (15– 

364 days) to soluble compounds of uranium.

Intermediate-duration inhalation studies in animals have identified the kidney and lung as the most 

sensitive targets of toxicity following inhalation exposure to soluble or poorly soluble uranium 

compounds. The renal toxicity of various uranium compounds in several animal species is summarized in 

Table 2-3. These data demonstrate that the soluble uranium compounds are more toxic than the poorly 

soluble compounds, dogs, rabbits, and possibly rats are the most sensitive species tested, and guinea pigs 

are the least sensitive. 

In addition to the renal effects, pulmonary toxicity has been observed in animals particularly after 

exposure to uranium hexafluoride. Exposure to 2 mg U/m3 for 30 days resulted in severe pulmonary 

edema in rabbits and slight pneumonia in dogs (Spiegl 1949). At higher concentrations (13.3 mg U/m3

), 

lung edema, hemorrhage, and emphysema were observed in rats, rabbits, and guinea pigs (Spiegl 1949). 

Since uranium hexafluoride is readily hydrolyzed to uranyl fluoride and hydrogen fluoride and hydrogen 

fluoride is a strong respiratory irritant resulting in pulmonary edema, it is likely that the observed 

respiratory effects are due to the hydrogen fluoride exposure. Respiratory effects have also been observed 

in rabbits and rats exposed to 6.8 mg U/m3 as ammonium diuranate (Dygert 1949b). In rabbits, 

ammonium diuranate exposure (6.8 mg U/m3

) resulted in extensive respiratory tract irritation, evidence 

by nasal bleeding and pulmonary edema, hemorrhage, and necrosis. Respiratory irritation (nasal bleeding 

and interstitial bronchiopneumonia) was also observed in rats exposed to 6.8 mg U/m3

. It is possible that 

these effects were secondary to the release of the ammonium ion, rather than uranium toxicity. 

Respiratory effects have not been consistently observed following exposure to other uranium compounds. 

As presented in Table 2-3, dogs are the most sensitive species to the renal toxicity of uranium 

compounds. The lowest LOAEL values identified in dogs are 0.13 mg U/m3 as uranyl nitrate for 

proteinuria (Roberts 1949) and 0.15 mg U/m3 as uranyl fluoride for tubular damage (Rothstein 1949a). In 

the Roberts (1949) study, an increase in urinary protein excretion was observed between days 9 and 12 

and then returned to normal; very mild histological changes, which the investigator noted were not of 

sufficient severity to be of concern, were observed in the renal cortex in two dogs exposed for 10 days. 

Since the two LOAEL values are almost identical, the Rothstein (1949a) study was selected as the basis 

of the MRL because it included histological examination of dogs exposed for an intermediate duration 

(the one dog examined at the end of the Roberts study had severe chronic nephritis, which precluded 

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2. RELEVANCE TO PUBLIC HEALTH 

Table 2-3. Renal Effects Following Intermediate-Duration Inhalation Exposure to 

Soluble and Poorly Soluble Uranium Compounds
 

NOAEL LOAEL 

Species Duration (mg U/m3

) (mg U/m3) Effect Reference 

Uranium hexafluoride 

Rat 30 days 0.05 0.2 Mild tubular damage Spiegl 1949 

Mouse 30 days 2 13.3 Severe degeneration, Spiegl 1949 

necrosis 

Rabbit 9 months 0.2 Very mild tubular injury Stokinger et al. 1953 

Guinea pig 30 days 13.3 Severe degeneration, Spiegl 1949 

necrosis 

Guinea pig 9 months 0.05 Stokinger et al. 1953 

Dog 30 days 0.05 0.2 Mild tubular regeneration Spiegl 1949 

Uranyl fluoride 

Rat 5 weeks 0.5 2.2 Minimal degeneration Rothstein 1949a 

Guinea pig 5 weeks 2.2 9.2 Severe degeneration Rothstein 1949a 

Dog 5 weeks 0.15 Very slight degeneration Rothstein 1949a 

Uranyl nitrate 

Rat 30 days 0.13 Slight degeneration Roberts 1949 

Rabbit 6.5 months 0.25 Mild tubular atrophy Stokinger et al. 1953 

Guinea pig 6.5 months 2 Stokinger et al. 1953 

Dog 30 days 0.13 Proteinuria Roberts 1949 

Uranium tetrachloride 

Rabbit 7.5 months 0.2 Stokinger et al. 1953 

Guinea pig 7.5 months 0.2 Stokinger et al. 1953 

Sodium diuranate 

Rat 5 weeks 15 Moderate degeneration, Rothermel 1949 

necrosis 

Rabbit 5 weeks 15 Degeneration, necrosis Rothermel 1949 

Ammonium diuranate 

Rat 30 days 6.8 Minimal necrosis Dygert 1949b 

Rabbit 30 days 6.8 Severe necrosis Dygert 1949b 

Uranium tetrafluoride 

Rat 30 days 4 18 Slight azotemia Dygert 1949a 

Rabbit 9 months 3 Stokinger et al. 1953 

Guinea pig 30 days 4 18 Moderate-severe Dygert 1949a 

necrosis 

Guinea pig 9 months 3 Stokinger et al. 1953 

Dog 30 days 0.5 3 Very slight degeneration Dygert 1949a 

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URANIUM 27 

2. RELEVANCE TO PUBLIC HEALTH 

observing any possible uranium-induced renal effects). Although the lowest LOAEL value in rats (0.13 

mg U/m3

) was similar to the lowest LOAEL values in dogs, the intermediate and chronic databases for 

soluble uranium compounds provide strong evidence that dogs are more sensitive than rats. In the 

Rothstein (1949a) study, groups of 2–6 dogs (strain and gender not specified) were exposed to 0.19, 2.8, 

or 12.2 mg/m3 of uranyl fluoride dust (0.15, 2.2, or 9.2 mg U/m3

) for 6 hours/day, 6 days/week for 

5 weeks. Clinical signs of toxicity, mortality, body weight changes, hematology, and blood and urine 

chemistries were monitored. At the termination of the study, the animals were sacrificed, selected organs 

were histopathologically examined, and uranium levels were determined. Anorexia, rhinitis, and 

polydipsia were observed in the two dogs exposed to 9.2 mg U/m3

; prior to death, vomiting blood, severe 

muscle weakness, and exhibited lassitude were observed. No deaths or clinical signs were observed at 

0.15 or 2.2 mg U/m3

. Severe weight loss was also observed at 9.2 mg U/m3; no alterations in body weight 

gain were observed at 0.15 or 2.2 mg U/m3

. At 9.2 mg U/m3, both dogs had increased blood nonprotein 

nitrogen (NPN) levels with the maximum value over 200 mg%. At 2.2 mg U/m3

, blood NPN and urinary 

amino acid levels were normal while one of three dogs had increased urinary protein levels. At 9.2 mg 

U/m3

, severe renal damage was seen in dogs. Moderate renal damage (no additional information 

provided) was observed at 2.2 mg U/m3 and very slight damage was observed in about 50% of the dogs at 

0.15 mg U/m3

. 

A NOAEL/LOAEL approach was used to identify the point of departure for the MRL; BMD modeling 

was not used because incidence data were not available for all groups. The LOAEL of 0.15 mg U/m3 for 

minimal renal lesions was used to derive the MRL. This value was adjusted for intermittent exposure 

(6 hours/24 hours, 6 days/7 days) resulting in a LOAELADJ of 0.032 mg U/m3

. Because RDDRs are not 

available for dogs, dosimetric adjustments could not be made; thus, the LOAELADJ was used as the point 

of departure. The LOAELADJ was divided by an uncertainty factor of 300 (3 for the use of a minimal 

LOAEL, 10 for extrapolation from animals to humans, and 10 for human variability), resulting in an 

intermediate-duration inhalation MRL of 0.0001 mg U/m3 for soluble uranium compounds. 

Chronic-Duration Inhalation MRL 

•	 An MRL of 0.0008 mg U/m3 has been derived for chronic-duration inhalation exposure (365 days 

or more) to insoluble compounds of uranium.

There are limited data available to assess the toxicity of chronic exposure to insoluble uranium 

compounds. Slight to mild renal tubular degeneration was observed in dogs exposed to 10 mg U/m3 as 

uranium dioxide for 1 year (Stokinger et al. 1953); no alterations were observed at 1 mg U/m3

. Although 

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2. RELEVANCE TO PUBLIC HEALTH 

several tissues were examined histologically, significant alterations were only noted for the kidneys. 

Stokinger et al. (1953) also exposed rats to 1 or 10 mg U/m3 as uranium dioxide, but no uranium-related 

alterations were observed. In a second chronic-duration study, no adverse effects were observed in rats or 

dogs exposed to 5.1 mg U/m3 as uranium dioxide for 1–5 years (Leach et al. 1970). However, fibrosis in 

the tracheobronchial lymph nodes and fibrosis and metaplasia in the lungs were observed in dogs during a 

6.5-year postexposure period (Leach et al. 1973). In monkeys, exposure to 5.1 mg U/m3 resulted in lung 

fibrosis beginning after 3.6 years of exposure (Leach et al. 1970); the severity of the fibrosis increased 

with exposure duration. Fibrosis was also present in the lungs and tracheobronchial lymph nodes in 

monkeys sacrificed during the 6.5-year postexposure period (Leach et al. 1973). The investigators noted 

that the fibrosis may have been a radiotoxic effect based on the magnitude of the radiation dose, the 

absence of renal effects, and the similarity of the lesions to those observed following exposure to 

plutonium dioxide; the alpha-radiation tissue doses were >500 rads (5 Gy) for the lungs and 7,000 rads 

(70 Gy) for the lymph nodes. However, it is unclear whether the damage was chemically or 

radiologically induced (or both); similar degenerative effects in the lungs have also been observed 

following prolonged exposure to diverse inorganic dusts. An elevation of blood NPN level was also 

observed in the monkeys during the postexposure period, but no histological alterations were observed in 

the kidneys (Leach et al. 1973). 

Rhesus monkeys (5 males, 20 females) were exposed to 5.8 mg/m3 uranium dioxide (5.1 mg U/m3

) 

5.4 hours/day, 5 days/week for 5 years; the mass median particle diameter was 1.03 μm with a geometric 

standard deviation of 2.40. Another group of one male and five female monkeys served as controls. 

Groups of 1–2 monkeys were killed after 1 day, 4 days, 15 days, 1 month, 2 months, 3 months, 5 months, 

1 year, 1.5 years, 1.8 years, 1.9 years, 3.6 years, 4.1 years, or 4.7 years; two monkeys were killed at 

5 years. Six monkeys were observed for 6.5 years after exposure termination; two were killed after 

12 months, one after 6 years, and three after 6.5 years; the results of the recovery period examinations 

were reported in Leach et al. (1973). The following parameters were used to assess toxicity: general 

health, body weight, peripheral hematology, blood NPN levels, and histopathology of major tissues and 

organs. No uranium dioxide-related deaths were observed. No alterations in body weight, hematological 

parameters, or blood NPN levels were found. Histological alterations were limited to the lungs and 

tracheobronchial lymph nodes. After 2–3 months of exposure, granular black pigment accumulations 

were found in the lungs and tracheobronchial lymph nodes. After 3.6 years of exposure, slight fibrosis 

was observed in the lungs and hyaline fibrosis was observed in the tracheobronchial lymph nodes; the 

severity of the fibrosis increased with exposure duration and was not observed in the controls. Fibrosis 

was still present in the lungs and tracheobronchial lymph nodes 6.5 years postexposure. 

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URANIUM 29 

2. RELEVANCE TO PUBLIC HEALTH 

The LOAEL of 5.1 mg U/m3 was selected as the point of departure for the MRL; BMD modeling was not 

used due to the small number of animals sacrificed at each time period. The LOAEL was adjusted for 

intermittent exposure (5.4 hours/24 hours, 5 days/7 days) resulting in a LOAELADJ of 0.82 mg U/m3

. 

Because RDDRs are not available for monkeys, dosimetric adjustments could not be made; thus, the 

LOAELADJ was used as the point of departure. The LOAELADJ was divided by an uncertainty factor of 

1,000 (10 for the use of a LOAEL, 10 for extrapolation from animals to humans, and 10 for human 

variability), resulting in a chronic-duration inhalation MRL of 0.0008 mg U/m3 for insoluble uranium 

compounds. A full uncertainty factor of 10 was used for extrapolation from monkeys to humans because 

no data were available to make dosimetric adjustments (pharmacokinetic component of uncertainty 

factor) and there are inadequate human data to assess potential differences in sensitivity between monkeys 

and humans (pharmacodynamic component of uncertainty factor). A wide range of sensitivity has been 

found in animal species, but it is not known where humans would fall in the range of sensitivity. 

•	 An MRL of 0.00004 mg U/m3 has been derived for chronic-duration inhalation exposure
 

(365 days or more) to soluble compounds of uranium.
 

There are limited human data on the chronic toxicity of soluble uranium. Thun et al. (1985) examined 

uranium mill workers exposed to yellowcake (26–86% ammonium diuranate), which was considered 

biologically soluble, for at least 1 year. Significant increases in urinary excretion of β2-microglobulin and 

amino acids were observed in the uranium workers suggesting impaired renal tubular function. Clearance 

of β-2-microglobulin relative to that of creatinine was significantly associated with the length of time that 

the uranium workers had spent in the yellowcake area. Although urinary uranium levels were reported, 

atmospheric concentrations were not reported. 

Stokinger et al. (1953) examined the chronic toxicity of uranium hexafluoride, uranium tetrachloride, and 

uranyl nitrate in dogs and rats following a 1-year exposure. Slight to mild renal tubular atrophy was 

observed in dogs and rats exposed to 0.2 mg U/m3 as uranium hexafluoride or uranium tetrachloride; no 

effects were observed at 0.05 mg U/m3

. Exposure to uranyl nitrate resulted in mild to moderate tubular 

atrophy in dogs exposed to 0.25 mg U/m3 (NOAEL of 0.15 mg U/m3

) and mild to marked tubular atrophy 

in rats exposed to 2 mg U/m3 (NOAEL of 0.25 mg U/m3

). 

The chronic-duration inhalation MRL for soluble uranium compounds was based on a 1-year dog study 

involving exposure to uranium tetrachloride (Stokinger et al. 1953). In this study, dogs of both sexes 

(11–12 males, 9–10 females) were exposed to uranium tetrachloride in inhalation chambers for 

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2. RELEVANCE TO PUBLIC HEALTH 

33 hours/week for 1 year at concentrations of 0.05, and 0.20 mg U/m3. The animals were monitored for 

body weight alterations, clinical signs of toxicity, and biochemical alterations in the blood and urine. At 

the termination of the study, the animals were sacrificed and selected organs were histopathologically 

examined. All dogs survived the 1-year exposure period. No alterations in body weight gain, 

hematological parameters, or blood NPN levels were observed. Urinary protein levels were elevated, as 

compared to controls; however, pre-exposure levels were also elevated, precluding evaluating the clinical 

significance of the effect. Alterations in bromsulfalein retention test, indicating impaired liver function, 

were observed in the four dogs tested (0.2 mg U/m3 group); no alterations in blood clotting times were 

observed. In the absence of histological evidence of liver damage, the change was not considered 

clinically significant. Renal tubular atrophy was observed in 2/16 dogs exposed to 0.05 mg U/m3 (not 

statistically significant using Fisher Exact test). Slight tubular atrophy in the inner cortex was observed in 

7/14 dogs exposed to 0.2 mg U/m3

. 

Data for the incidence of renal tubular atrophy were analyzed using all available dichotomous models in 

the EPA Benchmark Dose Software (BMDS, version 2.1.2) using the extra risk option; details of the 

BMD modeling are presented in Appendix A. The benchmark concentrations (BMCs) ranged from 

0.032 to 0.082 mg U/m3 and the 95% lower confidence limits on the BMCs (BMCLs) ranged from 

0.019 to 0.054 mg U/m3

. A BMCL10 of 0.019 mg U/m3 was selected as a point of departure. The 

BMCL10 was adjusted for intermittent exposure (33 hours/168 hours) resulting in a BMCLADJ of 

0.0037 mg U/m3

. Because RDDRs are not available for dogs, dosimetric adjustments could not be made; 

thus, the BMCLADJ was used as the point of departure. The BMCLADJ was divided by an uncertainty 

factor of 100 (10 for extrapolation from animals to humans and 10 for human variability), resulting in a 

chronic-duration inhalation MRL of 0.00004 mg U/m3 for soluble uranium compounds. 

Oral MRLs. 

Acute-Duration Oral MRL 

•	 An MRL of 0.002 mg U/kg/day has been derived for acute-duration oral exposure (≤15 days) to 

soluble compounds of uranium.

There are limited human data on the oral toxicity of uranium. Signs of gastrointestinal irritation (nausea, 

vomiting, diarrhea) were observed in a subject ingesting 14.3 mg U/kg as uranyl nitrate in drinking water 

(Butterworth 1955); other potential targets of toxicity were not examined. Acute oral exposure studies in 

rats and mice have examined the lethality, systemic toxicity, neurotoxicity, and developmental toxicity of 

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2. RELEVANCE TO PUBLIC HEALTH 

uranium. Information on the systemic toxicity is limited to two single-exposure toxicity study in rats 

(Domingo et al. 1987) and mice (Martinez et al. 2003) administered lethal doses and a repeated exposure 

study in mice (Ozmen and Yurekli 1998). In the 2 weeks following administration of a single gavage 

dose of 118 mg U/kg as uranyl acetate to rats, significant increases in urine volume (in the absence of 

changes in water consumption), plasma creatinine and urea, and urinary total protein and creatinine were 

observed; hyperemia and microhemorrhagic foci were also observed in the liver and kidneys at the end of 

the 2-week observation period (Domingo et al. 1987). In mice, administration of 166 mg U/kg as uranyl 

nitrate resulted in increases in blood urea and creatinine levels and proximal tubular necrosis (Martinez et 

al. 2003). Similarly, significant increases in BUN and creatinine levels were observed in mice exposed to 

508 mg U/kg/day as uranyl acetate in the diet for 5 days (Ozmen and Yurekli 1998); the study did not 

include a histological examination of the kidney or other tissues. Neurological effects consisted of 

increased motor activity (Briner and Murray 2005) and increased open field activity (Briner 2009) in mice 

administered 28 or 6 mg U/kg/day, respectively, as depleted uranyl acetate in drinking water for 2 weeks; 

exposure to 28 mg U/kg/day also resulted in a 53% decrease in body weight gain. Gestational exposure 

to ≥2.8 mg U/kg/day as uranyl acetate resulted in significant decreases in fetal body weights and increases 

in the occurrence hematomas in the fetuses of mice exposed on gestation days 6–15 (Domingo et al. 

1989c); increases in the incidence of cleft palate were observed at ≥5.6 mg U/kg/day. Decreases in 

maternal body weight gain were observed at ≥2.8 mg U/kg/day. Exposure of neonatal rats (1 or 7 days of 

age) to 42.7 mg U/kg/day as uranyl nitrate administered via gavage in water, resulted in significant 

reductions in bone formation, increases in bone resorption, and diminished tooth development (Pujadas 

Bigi et al. 2003). 

The available data provide evidence that the gastrointestinal tract, kidney, and developing organisms are 

target of uranium toxicity following acute oral exposure. Longer duration oral studies and inhalation 

studies identify the kidney as the most sensitive target of toxicity. The Domingo et al. (1989c) 

developmental toxicity study identified the lowest LOAEL (2.8 mg U/kg/day) and was selected as the 

basis of acute-duration oral MRL. In this study, groups of 20 pregnant Swiss mice were administered via 

gavage 0, 5, 10, 25, or 50 mg/kg/day uranyl acetate dihydrate (0, 2.8, 5.6, 14, or 28 mg U/kg/day) on 

gestation days 6–15. Body weights, food consumption, and general appearance were monitored daily. At 

termination, maternal liver and kidney weights were measured and uterine contents (number of 

implantation sites, resorptions, dead fetuses, and live fetuses) were evaluated. Live fetuses were 

evaluated for body weight, body length, sex, gross morphological abnormalities, visceral malformations, 

visceral anomalies, and skeletal defects. Significant decreases in maternal body weight were observed in 

all uranium groups; during the exposure period, the dams in the 2.6, 5.6, 14, and 28 mg U/kg/day groups 

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URANIUM 32 

2. RELEVANCE TO PUBLIC HEALTH 

weighed 33, 53, 75, and 88% less than controls, respectively. Significant decreases in food intake were 

also observed in the dams exposed to 5.6 mg U/kg/day and higher. A significant decrease in the number 

of live fetuses was observed at 5.6 mg U/kg/day, but was not observed at the two higher dose levels. No 

significant alterations in the number of early or late resorptions, number of dead fetuses, or sex ratio were 

observed. Significant decreases in fetal body weight were observed at ≥2.8 mg U/kg/day and decreases in 

fetal length were observed at ≥5.6 mg U/kg/day. Significant increases in the incidences of external 

defects were observed at 2.8 mg U/kg/day. The external alterations included cleft palate (significant at 

≥5.6 mg U/kg/day) and hematomas (significant at 2.8 and 28 mg U/kg/day). The total number of skeletal 

defects was significantly increased at 14 and 28 mg U/kg/day; skeletal defects included bipartite 

sternebrae (significant at 2.8, 14, and 28 mg U/kg/day), some metatarsal of hindlimb poorly ossified 

(significant at 14 and 28 mg U/kg/day), delayed ossification of skull (significant at 14 and 28 mg 

U/kg/day), and caudal reduced ossification (significant at 14 and 28 mg U/kg/day). 

The results of the Domingo et al. (1989c) study suggest maternal body weight gain and fetal body weight 

and external and skeletal alterations as sensitive end points of uranium toxicity. It is possible that the 

developmental effects were secondary to the maternal toxicity; however, some of these effects may also 

be primary effects of uranium on the developing fetus. Thus, maternal and fetal end points were 

considered as the basis of possible points of departure for the acute-duration MRL. Data for the number 

of litters with total external alterations, cleft palate, total skeletal defects, and bipartite sternebrae were 

analyzed using all available dichotomous models in the EPA BMDS (version 2.1.2) using the extra risk 

option; details of the BMD modeling are presented in Appendix A. The fetal body weight data and 

maternal body weight gain data were fit to all available continuous models in EPA’s BMDS 

(version 2.1.2); however, none of the models provided an adequate fit to either data set. 

The BMDL values for the four fetal alterations ranged from 0.08 to 0.42 mg U/kg/day and the average of 

these values (0.2 mg U/kg/day) was selected as the point of departure. This point of departure is 

approximately 10-fold lower than the LOAEL for maternal and fetal body weight effects and is likely to 

be protective of these effects. The 0.2 mg U/kg/day point of departure was divided by an uncertainty 

factor of 100 (10 for extrapolation from animals to humans and 10 for human variability) resulting in an 

acute-duration oral MRL of 0.002 mg U/kg/day. 

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2. RELEVANCE TO PUBLIC HEALTH 

Intermediate-Duration Oral MRL 

•	 An MRL of 0.0002 mg U/kg/day has been derived for intermediate-duration oral exposure (15– 

364 days) to soluble compounds of uranium.

No studies have been identified that examined the toxicity of uranium in humans following an 

intermediate-duration oral exposure. A number of studies have examined the intermediate-duration oral 

toxicity of uranium in laboratory animals. Most of these studies involved exposure to soluble uranium 

compounds such as uranyl nitrate and uranyl acetate; there are limited data on poorly soluble or insoluble 

uranium compounds. The available data suggest that the kidney is the most sensitive target of uranium 

toxicity; at higher dose levels, neurological, reproductive, and developmental effects have been reported. 

At lower concentrations, histological alterations have been observed in the proximal tubules, glomerulus, 

and/or renal interstitium in rats and mice exposed to uranyl nitrate in drinking water (Gilman et al. 1998a, 

1998b, 1998c; McDonald-Taylor et al. 1992, 1997). At higher concentrations (40.38 mg U/kg/day), 

evidence of renal dysfunction (e.g., dlycosuria, proteinuria) have also been observed (Gilman et al. 

1998c). The Gilman et al. (1998a, 1998b) studies identified LOAELs of 0.06 and 0.05 mg U/kg/day for 

renal effects in rats and rabbits, respectively; neither study identified NOAEL values. 

The LOAELs for neurological, reproductive, and developmental effects are similar and are about 50-fold 

higher than the LOAEL for renal effects. Neurological effects such as sleep and behavior alterations and 

decreased spatial memory were observed in rats exposed to 2.5–2.7 mg U/kg/day as enriched uranyl 

nitrate (Houpert et al. 2005, 2007b). However, no neurological effects were observed in rats similarly 

exposed to the same dose of depleted uranyl nitrate (Houpert et al. 2005). The investigators suggest that 

the observed effects may have been related to radiological activity. The reproductive effects consisted of 

decreases in male fertility in rats and mice following exposure to ≥5.6 mg U/kg/day as uranyl acetate 

(Linares et al. 2005; Llobet et al. 1991) and alterations in ovarian folliculogenesis in mice at ≥1.25 mg 

U/kg/day as uranyl nitrate (Arnault et al. 2008; Feugier et al. 2008; Kundt et al. 2009). A recent study by 

Raymond-Whish et al. (2007) also reported alterations in ovarian folliculogenesis in mice, but the effects 

were at an extremely low dose (0.00039 mg U/kg/day). Additional data are needed to support whether 

reproductive effects occur at this dose level and to evaluate the toxicological significance of the observed 

effect (reduced number of small primary follicles, but no effect on primordial, secondary/growing, 

healthy, or atretic follicle populations). Developmental effects have been observed in rats and mice; most 

effects occurred at maternally toxic doses. The observed effects included neurobehavioral effects in the 

offspring of rats exposed premating and during gestation and lactation to 4.3 mg U/kg/day as enriched 

uranyl nitrate (Houpert et al. 2007a), decreases in pup body weight at ≥2.8 mg U/kg/day as uranyl acetate 

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URANIUM 34 

2. RELEVANCE TO PUBLIC HEALTH 

(Paternain et al. 1989; Sánchez et al. 2006), decreases in litter size, live fetuses, or viability at ≥14 mg 

U/kg/day as uranyl acetate (Domingo et al. 1989b; Paternain et al. 1989), and altered ovarian 

folliculogenesis in 3-month-old pups of dams exposed to 1.25 mg U/kg/day as uranyl nitrate (Arnault et 

al. 2008). 

The LOAELs of 0.05 and 0.06 mg U/kg/day for kidney effects in rats and rabbits (Gilman et al. 1998a, 

1998b) were considered as possible points of departure for an intermediate-duration oral MRL for soluble 

uranium compounds. Although the rabbit study identified the slightly lower LOAEL, the rat LOAEL was 

selected as the point of departure for the MRL due to possible subclinical infection in the rabbits. Gilman 

et al. (1998b, 1998c) conducted two 91-day studies in rabbits. The kidney uranium levels for the two 

studies were not comparable; rabbits in the first study (Gilman et al. 1998b) had higher kidney uranium 

levels than in the second study (Gilman et al. 1998c) even though the dose was lower in the first study 

(28.70 mg U/kg/day dose and 4.98 μg U/g kidney level in the Gilman et al. 1998b study compared to 

40.98 mg U/kg/day dose and 3.48 μg U/g kidney level in the Gilman et al. 1998c study). In the Gilman et 

al. (1998b) study, the male rabbits were not SPF derived and four animals developed Pasteurella 

multocida infections during the study; Gilman et al. (1998c) suggested that even though the affected 

rabbits were removed from the study, it is possible that other animals had a subclinical infection and that 

this may have increased sensitivity. Thus, the rat study was selected as the basis of the MRL; the rats 

used in the Gilman et al. (1998a) study were SPF derived. The Raymond-Whish et al. (2007) study was 

not selected as the point of departure because there are no other data to support this extremely low value 

and the toxicological significance of this slight change in one follicle population is not known. 

In the Gilman et al. (1998a) study, five groups of Sprague-Dawley rats (15/sex/dose, 60 g) were exposed 

to uranium as uranyl nitrate in drinking water (0, 0.96, 4.8, 24, 120, and 600 mg/L) for 91 days. Timeweighted average doses (as mg U/kg/day) calculated by the authors from fluid intake data were 

<0.0001 (control group), 0.06, 0.31, 1.52, 7.54, and 36.73 mg U/kg/day in males and <0.0001 (controls), 

0.09, 0.42, 2.01, 9.98, and 53.56 mg U/kg/day in females. Clinical signs were monitored daily and body 

weights were measured weekly; fluid intake and feed consumption were also measured, but the frequency 

was not reported. Hematological and serum clinical chemistry parameters, organ weights, and 

histopathology examination of major tissues and organs were assessed at termination. Hematological and 

biochemical parameters were not affected in a significant exposure-related manner. Statistically 

significant increases in renal lesions included cytoplasmic vacuolization, tubular dilation, and lymphoid 

cuffing in males at ≥0.06 mg U/kg/day; capsular sclerosis, tubular anisokaryosis, and interstitial reticulin 

sclerosis in females at ≥0.09 mg U/kg/day; nuclear vesiculation in males and females at ≥0.06/0.09 mg 

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URANIUM 35 

2. RELEVANCE TO PUBLIC HEALTH 

U/kg/day; and glomerular adhesions and cytoplasmic degeneration in males at ≥0.31 mg U/kg/day. 

Lesions were also observed in the liver at all doses including anisokaryosis, vesiculation, increased portal 

density, perivenous vacuolation, and homogeneity; the investigators considered these adaptive and likely 

reversible. Thyroid lesions were observed in both sexes (multifocal reduction of follicular size, increased 

epithelial height in males at 0.31 mg/kg/day and females at 2.01 mg/kg/day). A decreased amount and 

density of colloid in the thyroid was observed in males only. Sinus hyperplasia of the spleen was 

observed in males and females at 36.73/53.56 mg/kg/day. 

An attempt was made to fit the incidence data to BMD models; however, none of the models provided an 

adequate fit. Thus, a NOAEL/LOAEL approach was used to derive the MRL. The LOAEL value of 

0.06 mg U/kg/day for renal effects in rats (Gilman et al. 1998a) was divided by an uncertainty factor of 

300 (3 for the use of a minimal LOAEL, 10 for animals to human extrapolation, and 10 for human 

variability) resulting in an intermediate-duration oral MRL of 0.0002 mg U/kg/day for soluble uranium 

compounds. A partial uncertainty factor was used to extrapolate from a LOAEL because the histological 

alterations observed at 0.06 mg U/kg/day were considered minimally adverse. 

There are inadequate data to derive an MRL for insoluble uranium compounds (e.g., uranium 

tetrafluoride, uranium trioxide, uranium dioxide, uranium peroxide, triuranium octaoxide). The toxicity 

of insoluble uranium compounds were tested in a series of 30-day studies conducted by Maynard and 

Hodge (1949). No histological alterations were observed at the highest uranium dioxide, uranium 

trioxide, uranyl octaoxide, or uranium tetrafluoride doses (11,000–12,000 mg U/kg/day). By comparison, 

the study found renal lesions were observed following exposure to 200 mg U/kg/day as uranyl nitrate. 

These data suggest that the toxicity of soluble uranium compounds are at least an order of magnitude 

higher than for insoluble uranium compounds. 

Chronic-Duration Oral MRL 

Available data on the chronic oral toxicity of uranium comes from several ecological studies examining 

the possible association between elevated levels of uranium in drinking water and alterations in kidney 

function (Kurttio et al. 2002, 2006a; Limson Zamora et al. 1998, 2009; Mao et al. 1995; Seldén et al. 

2009). Associations between parameters of renal dysfunction (e.g., urine levels of albumin, β2-microglobulin, glucose, and protein HC) and elevated uranium levels in drinking water were observed in some 

of the studies (Kurttio et al. 2002; Limson Zamora et al. 1998, 2009; Mao et al. 1995; Seldén et al. 2009). 

These studies did not find overt signs of toxicity and in many cases, the biomarkers of renal dysfunction 

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2. RELEVANCE TO PUBLIC HEALTH 

were within the normal range. Although most of the epidemiology studies provided information on 

uranium levels in the drinking water, there was often a large range of exposure levels; thus, the human 

oral exposure studies do not provide reliable dose-response data. 

No studies in laboratory animals examining the chronic toxicity of ingested uranium were identified. Due 

to the limitations in the human studies and lack of animal data, the chronic oral database was considered 

inadequate for derivation of a chronic-duration oral MRL. 

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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 uranium. 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. 

The health effects associated with oral or dermal exposure to natural and depleted uranium appear to be 

solely chemical in nature and not radiological, while those from inhalation exposure may also include a 

slight radiological component, especially if the exposure is protracted. This profile is primarily concerned 

with the effects of exposure to natural and depleted uranium, but does include limited discussion 

regarding enriched uranium, which is considered to be more of a radiological than a chemical hazard. 

Also, whenever the term Aradiation@ is used, it applies to ionizing radiation and not to non-ionizing 

radiation. 

Although natural and depleted uranium are primarily chemical hazards, the next several paragraphs 

describe the radiological nature of the toxicologically-important uranium isotopes, because individual 

isotopes are addressed in some of the health effects studies. Uranium is a naturally occurring radioactive 

element and a member of the actinide series. Radioactive elements are those that undergo spontaneous 

transformation (decay), in which energy is released (emitted) either in the form of particles, such as alpha 

or beta particles, or electromagnetic radiation with energies sufficient to cause ionization, such as gamma 

rays. This transformation or decay results in the formation of different elements, some of which may 

themselves be radioactive, in which case they will also decay. The process continues until a stable 

(nonradioactive) state is reached (see Appendix D for more information). 

Uranium exists in several isotopic forms, all of which are radioactive. The most toxicologically important 

of the 22 currently recognized uranium isotopes are anthropogenic uranium-232 (232U) and uranium-233 

(

233U) and naturally occurring uranium-234 (234U), uranium-235 (235U), and uranium-238 (238U). When an 

atom of any of these five isotopes decays, it emits an alpha particle (the nucleus of a helium atom) and 

transforms into a radioactive isotope of another element. The process continues through a series of 

radionuclides until reaching a stable, non-radioactive isotope of lead. The radionuclides in these 

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URANIUM 38 

3. HEALTH EFFECTS 

transformation series (such as radium and radon), emit alpha, beta, and gamma radiations with energies 

and intensities that are unique to the individual radionuclide. 

Natural uranium consists of isotopic mixtures of 234U, 235U, and 238U. There are three kinds of mixtures 

(based on the percentage of the composition of the three isotopes): natural uranium, enriched uranium, 

and depleted uranium. Natural uranium in uranium ore is comprised of 99.274% 238U, 0.720% 235U, and 

0.005% 234U by mass. Combining these mass percentages with the unique half-life of each isotope 

converts mass into radioactivity units and shows that uranium ore contains 48.7% 234U, 2.27% 235U, and 

49.0% 238U by radioactivity, and has a very low specific activity of 0.68 μCi/g based on data compiled by 

the National Nuclear Data Center (NNDC 2011). Enriched and depleted uranium are the products of a 

process, which increases (or enriches) the percentages of 234U and 235U in one portion of a uranium 

sample and decreases (or depletes) their percentages in the remaining portion. Enriched uranium is 

quantified by its 235U percentage. Uranium enrichment for nuclear energy produces uranium that 

typically contains 3% 235U. Uranium enrichment for a number of other purposes, including nuclear 

weapons, can produce uranium that contains as much as 97.3% 235U and has a higher specific activity 

(~50 μCi/g). The residual uranium after the enrichment process is called “depleted uranium”, which 

possesses even less radioactivity (0.36 μCi/g) than natural uranium. The USNRC considers the specific 

activity of depleted uranium to be 0.36 μCi/g (10 CFR 20), but more aggressive enrichment processes can 

drive this value slightly lower (0.33 μCi/g). In this profile, both natural and depleted uranium are referred 

to as “uranium”, although depleted uranium is specified when this use benefits the text. The higher 

specific-activity mixtures and isotopes are described in the profile as “enriched uranium,” or as 232U, 233U, 

or 234U, as applicable, in the summary of the studies in which these mixtures and isotopes were used. 

Uranium is a heavy metal that forms compounds and complexes of different varieties and solubilities. 

The chemical action of all isotopes and isotopic mixtures of uranium is identical, regardless of the 

specific activity (i.e., enrichment), because chemical action depends only on chemical properties. Thus, 

the chemical toxicity of a given amount or weight of natural, depleted, and enriched uranium is identical. 

The toxicity of uranium varies according to its chemical form and route of exposure. On the basis of the 

toxicity of different uranium compounds in animals, it was concluded that the relatively more watersoluble compounds (uranyl nitrate, uranium hexafluoride, uranyl fluoride, uranium tetrachloride) were the 

most potent systemic toxicants. The poorly water-soluble compounds (uranium tetrafluoride, sodium 

diuranate, ammonium diuranate) were of moderate-to-low systemic toxicity, and the insoluble compounds 

(uranium trioxide, uranium dioxide, uranium peroxide, triuranium octaoxide) had a much lower potential 

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3. HEALTH EFFECTS 

to cause systemic toxicity but could cause pulmonary toxicity when exposure was by inhalation. The 

terms soluble, poorly soluble, and insoluble are often used in this profile without relisting the specific 

compounds. Generally, hexavalent uranium, which tends to form relatively soluble compounds, is more 

likely to be a systemic toxicant than tetravalent uranium, which forms relatively insoluble compounds. 

Ingested uranium is less toxic than inhaled uranium, which may be partly attributable to the relatively low 

gastrointestinal absorption of uranium compounds. 

The hazard from inhaled uranium aerosols, or any noxious agent, is determined by the likelihood that the 

agent will reach the site of its toxic action. Two main factors that influence the degree of hazard from 

toxic airborne particles are the site of deposition in the respiratory tract of the particles and the fate of the 

particles within the lungs. The deposition site within the lungs depends mainly on the particle size of the 

inhaled aerosol, while the subsequent fate of the particle depends mainly on the physical and chemical 

properties of the inhaled particles and the physiological status of the lungs. 

Because natural uranium produces very little radioactivity per mass of uranium, the renal and respiratory 

effects from exposure of humans and animals to uranium are usually attributed to the chemical properties 

of uranium. However, in exposures to more radioactive uranium isotopes (e.g., 232U and 233U, and 

naturally occurring 234U and 235U), it has been suggested that the chemical and radiological toxicity may 

be additive or may potentiate in some instances. In these instances, this dual mode of uranium toxicity 

may not be distinguishable by end point because of the overlap of etiology and manifested effects. The 

mechanism of this interaction is as yet unclear. 

3.2 DISCUSSION OF HEALTH EFFECTS 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 

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URANIUM 40 

3. HEALTH EFFECTS 

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 

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 the general public alike. 

Levels of exposure associated with carcinogenic effects (Cancer Effect Levels, CELs) of uranium are 

indicated in Table 3-1 and Figure 3-1. 

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 

The toxicity of uranium compounds to the lungs and distal organs varies when exposed by the inhalation 

route. In general, the more soluble compounds (uranyl fluoride,1 uranium tetrachloride, uranyl nitrate 

hexahydrate) are less toxic to the lungs but more toxic systemically by the inhalation route due to easier 

1

Uranium hexafluoride is hydrolyzed to uranyl fluoride and hydrogen fluoride. Hydrogen fluoride is highly toxic in 

acute exposures and causes pulmonary edema, which may be immediately life-threatening. 

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URANIUM 41 

3. HEALTH EFFECTS 

absorption from the lungs into the blood and transportation to distal organs (Tannenbaum et al. 1951). A 

study summary of the data for inhalation toxicity (lethality) studies in mice exposed to equivalent 

uranium concentrations of uranium tetrafluoride, uranyl fluoride, uranium tetrachloride, uranyl nitrate 

hexahydrate, or triuranium octaoxide concluded that the order of decreasing systemic toxicity for these 

compounds may be as follows: very toxic, uranyl fluoride; toxic, uranyl nitrate hexahydrate; and 

nontoxic (at the levels tested in companion studies), uranium tetrachloride, uranium tetrafluoride, and 

triuranium octaoxide (Stokinger et al. 1953; Tannenbaum et al. 1951). Although uranium tetrachloride is 

highly soluble in water, it is easily hydrolyzed and oxidized into less soluble uranyl chloride and insoluble 

uranium dioxide. For this reason, inhaled uranium tetrachloride tends not to behave as if it is a highly 

soluble uranium compound. Conversely, the more common insoluble salts and oxides (uranium 

tetrafluoride, uranium dioxide, uranium trioxide, triuranium octaoxide) are generally more toxic to the 

lungs through inhalation exposure because of the longer retention time in the lung tissue but they are less 

toxic to distal organs. 

3.2.1.1 Death 

The lethal effects of inhalation exposure to uranium have been investigated in humans in epidemiological 

studies and in animal studies under controlled conditions. Epidemiological studies indicate that routine 

exposure of humans (in the workplace and the environment at large) to airborne uranium is not associated 

with increased mortality. Brief accidental exposures to very high concentrations of uranium hexafluoride 

have caused fatalities in humans. Laboratory studies in animals indicate that inhalation exposure to 

certain uranium compounds can be fatal. These deaths are believed to result from renal failure caused by 

absorbed uranium. The low specific activity of uranium precludes the possibility of absorbing enough 

uranium to deliver a lethal dose of radiation. 

No definitive evidence has been found in epidemiologic studies that links human deaths to uranium 

exposure. Uranium miners have higher-than-expected rates of death from lung cancer; however, this 

finding is attributed to the radiological effects of radon and its decay products, which are progeny of 

uranium and, therefore, present in uranium mines. In addition, the role of tobacco smoking was not 

evaluated in some of the studies (Archer et al. 1973a; Gottlieb and Husen 1982; Lundin et al. 1969; Samet 

et al. 1984a, 1986). Epidemiologic studies of workers at uranium mill and metal processing plants (where 

there is little or no exposure to radon in excess of normal environmental levels) showed no significant 

increase in overall deaths attributable to exposure to uranium (Archer et al. 1973b; Boice et al. 2008; 

Checkoway et al. 1988; Cragle et al. 1988; Hadjimichael et al. 1983; NIOSH 1987; Pinkerton et al. 2004; 

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URANIUM 42 

3. HEALTH EFFECTS 

Polednak and Frome 1981; Scott et al. 1972; Waxweiler et al. 1983). Results of several mortality 

assessments of populations living near uranium mining and milling operations have not demonstrated 

significant associations between mortality and exposure to uranium (Boice et al. 2003, 2007a, 2007b, 

2010). 

Deaths occurred after accidental releases of uranium hexafluoride at uranium-processing facilities in 1944 

and 1986, but these deaths were not attributed to the uranium component of this compound (Kathren and 

Moore 1986; Moore and Kathren 1985; USNRC 1986). These releases resulted in the generation of 

concentrated aerosols of highly toxic hydrofluoric acid2

. In the 1944 incident, exposure time was 

estimated to be only 17 seconds; deaths occurred in 2 of 20 workers within an hour and were attributed to 

severe chemical burns of the lungs. In the 1986 incident, 1 of 23 workers died from massive pulmonary 

edema. Estimated airborne concentrations were 20 mg uranium hexafluoride/m3 for a 1-minute exposure 

and 120 mg uranium hexafluoride/m3 for a 60-minute exposure (15.2 and 91 mg U/m3

, respectively). For 

both accidents, the observed effects are suggestive that inhalation of hydrofluoric acid was responsible for 

death. 

A study of U.K. Gulf War veterans (>50,000 veterans) did not find a significant increase in the risk of 

dying in a 13-year follow-up period, as compared to >50,000 veterans not deployed to the gulf. Among 

the 7% of Gulf War veterans who reported exposure to depleted uranium, a non-statistically significant 

increase in the risk of dying was found (mortality rate ratio of 1.99, 95% confidence interval [CI] of 0.98– 

4.04). Of the nine veterans who died and reported exposure to depleted uranium, seven deaths were from 

cancer; cancer types were esophagus (3) and brain (4) (Macfarlane et al. 2005). 

Mortality can be induced in animals exposed to sufficiently high concentrations of pure uranium 

compounds. The acute-duration LC50 (lethal concentration, 50% death) for uranium hexafluoride has 

been calculated for Long-Evans rats and Hartley guinea pigs (Leach et al. 1984). The animals were 

exposed to uranium hexafluoride in a nose-only exposure apparatus for periods of up to 10 minutes and 

then observed for 14 days. Total mortality in rats was 34% (157/460): 25% of the deaths occurred during 

exposure or within 48 hours, 59% between days 3 and 7, and 17% between days 7 and 14. Guinea pigs 

were more sensitive than rats; total mortality was 46% (36/78), and 64% of deaths occurred within 

48 hours. In guinea pigs, the LC50 was estimated as 35,011 mg U/m3 for a 2-minute exposure limit. For a 

5-minute inhalation exposure, the LC50 in Long-Evans rats was estimated as 26,098 mg U/m3

; the LC50 

2

Uranium hexafluoride rapidly dissociates into hydrofluoric acid and uranyl fluoride on contact with moisture in the 

air. 

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URANIUM 43 

3. HEALTH EFFECTS 

for a 10-minute inhalation was estimated as 8,114 mg U/m3. The animals that died showed some damage 

to the respiratory tract, probably due to hydrofluoric acid, but this damage was not judged to be the cause 

of death, at least in the animals that died more than 2 days postexposure. Urinalysis and histopathological 

examination indicated that renal injury was the primary cause of death (Leach et al. 1984). In other acute 

lethality studies, rats, mice, and guinea pigs suffered 10, 20, and 13% mortality, respectively, following a 

10-minute inhalation of uranium hexafluoride corresponding to 637 mg U/m3 (Spiegl 1949). 

In intermediate-duration studies, rabbits and cats were generally the most sensitive species to uranium 

lethality. Deaths in these studies generally occurred beginning 2 weeks after exposure started and 

continued to the end of the experiment. Exposure to 2 mg U/m3 (as uranium hexafluoride) 6 hours/day 

for 30 days caused 5, 20, and 80% mortality in guinea pigs, dogs, and rabbits, respectively (Spiegl 1949). 

An exposure to 9.5 mg U/m3 (as uranyl nitrate hexahydrate) for 8 hours/day, 5 days/week for 30 days 

caused 10% mortality in rats and guinea pigs, and 75% mortality in dogs. Exposure to 2 mg U/m3 killed 

all four cats tested (Roberts 1949). Exposure to 9.2 mg U/m3 (as uranyl fluoride) 6 hours/day, 

5.5 days/week for 5 weeks caused 0, 100, 83, and 55% mortality in rats, mice, rabbits and guinea pigs, 

and deaths in two dogs and two cats tested at this concentration (Rothstein 1949a). The lowest exposure 

causing death with uranyl fluoride was 0.15 mg U/m3 in mice and rabbits and 2.2 mg U/m3 in guinea pigs. 

Exposure to 15.4 mg U/m3 (as uranium peroxide) 5 hours/day, 5 days/week for 23 days caused 10, 63, 40, 

80, and 100% mortality in rats, mice, guinea pigs, rabbits, and cats, respectively, while 9.2 mg U/m3 

killed all of the dogs tested (Dygert 1949d). Inhalation of air containing 15 mg U/m3 (as sodium 

diuranate) for 6 hours/day, 5.5 days/week for 5 weeks caused 13 and 28% mortality in guinea pigs and 

rabbits, respectively (Rothermel 1949). 

Insoluble uranium compounds were also lethal to animals by the inhalation route, but at higher 

concentrations than soluble compounds. Exposure to 15.8 mg U/m3 (as uranium trioxide) 6 hours/day, 

5.5 days/week for 4 weeks caused 10, 9, 17, and 67% mortality in rats, guinea pigs, dogs, and rabbits, 

respectively (Rothstein 1949c). Inhalation of air containing 19.4 mg U/m3 (as uranium dioxide) for 

6 hours/day, 5.5 days/week for 5 weeks, caused 60% mortality in rabbits but no mortality in rats, mice, 

guinea pigs, or dogs (Rothstein 1949b). Inhalation of air containing 18 mg U/m3 (as uranium 

tetrafluoride) for 5 hours/day for 30 days caused 15, 32, 33, and 100% mortality in guinea pigs, rats, 

rabbits, and cats, respectively, and death in a single dog tested at this concentration. Inhalation at 

4 mg U/m3 caused no deaths in a group of 18 dogs, and one death in a group of 30 rats (Dygert 1949a). A 

mortality of 4% was observed among rabbits given 3 mg U/m3 (Stokinger et al. 1953). Exposure to 

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URANIUM 44 

3. HEALTH EFFECTS 

6.8 mg U/m3 (as ammonium diuranate) 6 hours/day for 30 days caused 20 and 100% mortality in guinea 

pigs and rabbits, respectively (Dygert 1949b). 

In chronic-duration experiments, inhalation of 2 mg U/m3 as uranyl nitrate hexahydrate for 6 hours/day, 

5.5 days/week for 92–100 weeks resulted in 1% mortality in rats (Stokinger et al. 1953). This is not an 

unusual mortality rate for rats, so it is unlikely that these deaths can be attributed to uranium exposure. 

Dogs exposed to uranyl nitrate hexahydrate for 2 years suffered 4% mortality (Stokinger et al. 1953). Out 

of 25 exposed dogs, 1 dog died at 0.25 mg U/m3 and another died at 2 mg U/m3

. Death may or may not 

have been attributable to uranium, according to the study investigators. 

In several other inhalation-exposure animal studies, no deaths were observed when either soluble or 

insoluble uranium compounds were administered. In one of these animal studies, no mortality was 

observed in monkeys exposed by inhalation to uranium dioxide dust at a concentration of 5 mg U/m3 for 

5 years. The death of Beagle dogs similarly exposed could not be attributed to uranium by the 

investigators (Leach et al. 1970). 

The percent mortality values for each species and other LOAEL values for mortality from exposure to 

uranium by the inhalation route are presented in Table 3-1 and plotted in Figure 3-1. 

3.2.1.2 Systemic Effects 

No human studies were located regarding the cardiovascular, musculoskeletal, endocrine, metabolic, 

dermal, ocular, body weight, or other systemic effects of elemental uranium following acute-duration 

inhalation exposure. Nor were any human studies located regarding the respiratory, hematological, 

cardiovascular, gastrointestinal, musculoskeletal, hepatic, renal, endocrine, metabolic, dermal, ocular, 

body weight, or other systemic effects of uranium following intermediate-duration inhalation exposure. 

No studies were found regarding the cardiovascular, gastrointestinal, musculoskeletal, renal, endocrine, 

metabolic, dermal, ocular, body weight, or other systemic effects in humans following chronic-duration 

inhalation exposure. The existing human data on the respiratory and hepatic effects of uranium are 

limited to acute- and chronic-duration inhalation exposures, hematological effects are limited to chronicduration inhalation exposure, and gastrointestinal and renal effects are limited to acute-duration inhalation 

exposure. 

***DRAFT FOR PUBLIC COMMENT*** 
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation 

Exposure/ LOAEL

Duration/

a

Key to 

Figure

Species

(Strain)

Frequency

(Route)

ACUTE EXPOSURE 

Death

1 Rat

(Long- Evans) 

5 min 

System

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

Serious

(mg/m3)

18210 M (40% mortality by day 14 

postexposure)

2 Rat

(NS)

1 d 10 min 1544 (75% mortality 30 days postexposure)

3 Mouse

(NS)

1 d 10 min 637 (20% mortality 30 days post-exposure)

4 Gn Pig 

(Hartley)

2 min 23040 M (2/6 died 48 hrs 

postexposure)

5 Gn Pig 

(NS)

1 d 10 min 637 (13% mortality 30 days post-exposure)

Systemic

6 Rat

(Long- Evans) 

5 min Resp 9131 54503 M (severe nasal 

congestion, hemorrhage) 

7 Rat

(Long- Evans) 

10 min 

RenalRenal

392 M (glucosuria) 426 M (proteinuria, glucosuria, 

and polyuria) 

ReferenceChemical Form 

Leach et al. 1984 Uranium Hexafluoride Spiegl 1949 Uranium Hexafluoride Spiegl 1949 Uranium Hexafluoride Leach et al. 1984 Uranium Hexafluoride Spiegl 1949 Uranium Hexafluoride Leach et al. 1984 Uranium Hexafluoride Leach et al. 1984 Uranium Hexafluoride 
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

LOAEL

Serious

(mg/m3)

ReferenceChemical Form 

8 Rat

(Long- Evans) 

2 min Renal 920 M 1430 M (proteinuria) Leach et al. 1984 

Uranium Hexafluoride 

9 Rat

(Fischer- 344) 

once 100 min Resp 5051 M (severe alveolar fibrosis) Morris et al. 1990 

Uranium Dioxide 

10 Rat

(NS)

1 d 10 min Resp 637 (gasping in 100% of rats; severe irritation of nasal 

passages)

Spiegl 1949 Uranium Hexafluoride 

Renal 637 (severe degeneration of 

renal cortical tubules 5-8 days post-exposure) 

Ocular 637 (conjunctivitis) 

11 Mouse

(NS)

1 d 10 min Resp 637 (gasping in 100% of mice; severe irritation of 

nasal passages) 

Spiegl 1949 Uranium Hexafluoride 

Ocular 637 (conjunctivitis) 

12 Gn Pig 

(Hartley)

2 min Renal 23040 M (glucosuria and polyuria) Leach et al. 1984 

Uranium Hexafluoride 

13 Gn Pig 

(Hartley)

2 min Renal 23040 M (glucosuria and polyuria) Leach et al. 1984 

Uranium Hexafluoride 
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

a

Key to 

Figure

Species

(Strain) System

Exposure/

Duration/

Frequency

(Route)

NOAEL

(mg/m3)

LOAEL

Less Serious 

(mg/m3)

Serious

(mg/m3)

ReferenceChemical Form 

14 Resp Dog [Beagle] once 0.5-1 hr 

Renal

270 Morrow et al. 1982a 

Uranyl Fluoride 

250 (extensive degeneration 

in kidney cortex and tubules)

Immuno/ Lymphoret 

15 Rat

(Fischer- 344) 

once Morris et al. 1989 

Uranium Dioxide 

44 M (increased macrophage 

activity)

16 Rat

(Fischer- 344) 

once Morris et al. 1992 

Uranium Dioxide 

132 M (increased macrophage 

activity)

INTERMEDIATE EXPOSURE 

Death

17 Rat

(NS)

30 d 6 hr/d Dygert 1949a 

Uranium Tetrafluoride 

18 (32% mortality) 

18 Rat

(NS)

30 d 6 hr/d Spiegl 1949 

Uranium Hexafluoride 

13.3 (75% mortality) 

19 Mouse

(NS)

23 d 5 d/wk 5 hr/d 

Dygert 1949d Uranium Peroxide 

15.4 (63% mortality) 

20 Mouse

(NS)

30 d 6 hr/d Spiegl 1949 

Uranium Hexafluoride 

2 (92% mortality) 

21 Gn Pig 

(NS)

30 d 6 hr/d Dygert 1949a 

Uranium Tetrafluoride 

18 (15% mortality) 
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

LOAEL

Serious

(mg/m3)

ReferenceChemical Form 

2223

Gn Pig (NS)Gn Pig (NS)

30 d 6 hr/d 23 d 5 d/wk 5 hr/d 

6.8 (20% mortality) 

15.4 (40% mortality) 

Dygert 1949b 

Ammonium Diuranate 

Dygert 1949d Uranium Peroxide 

24 Gn Pig 

(NS)

5 wk 6 d/wk 6 hr/d 

9.2 (55% mortality) Rothstein 1949a 

Uranyl Fluoride 

25 Gn Pig 

(NS)

5 wk 5.5 d/wk 6 hr/d 

15 (13% mortality) Rothstein 1949d 

Sodium Uranate 

26272829

Gn Pig (NS)Dog(NS)Dog(NS)Dog(NS)

30 d 6 hr/d 30 d 6 hr/d 30 d Cont. 4 wk 6 d/wk 6 hr/d 

13.3 (45% mortality) 

18 (lethal dose) 

9.5 (75% mortality) 

15.8 (17% mortality) 

Spiegl 1949 Uranium Hexafluoride Dygert 1949a Uranium Tetrafluoride Roberts 1949 Uranyl Nitrate Rothstein 1949c Uranium Trioxide 

30 Dog

(NS)

5 wk 6 d/wk 6 hr/d 

9.2 (100% mortality) Rothstein 1949a 

Uranyl Fluoride 
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

LOAEL

Serious

(mg/m3)

ReferenceChemical Form 

31323334

Dog(NS)Rabbit(NS)Rabbit(NS)Rabbit(NS)

30 d 6 hr/d 30 d 6 hr/d 30 d 6 hr/d 23 d 5 hr/d 5 d/wk 

13.3 (40% mortality) 

18 (33% mortality) 

6.8 (100% mortality) 

15.4 (80% mortality) 

Spiegl 1949 Uranium Hexafluoride Dygert 1949a Uranium Tetrafluoride Dygert 1949b 

Ammonium Diuranate 

Dygert 1949d Uranium Peroxide 

35 Rabbit

(NS)

4 wk 6 d/wk 6 hr/d 

15.8 (67% mortality) Rothstein 1949c

 Uranium Trioxide 

3637

Rabbit(NS)Rabbit(NS)

5 wk 6 d/wk 5 wk 5.5 d/wk 6 hr/d 

19.4

15

(60% mortality) 

(28% mortality) 

Rothstein 1949b Uranium Dioxide Rothstein 1949d Sodium Uranate 

3839

Rabbit(NS)Cat(NS)

30 d 6 hr/d 30 d 6 hr/d 

2

18

(80% mortality) 

(100% mortality) 

Spiegl 1949 Uranium Hexafluoride Dygert 1949a Uranium Tetrafluoride 
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

a

Key to Species 

Figure (Strain) 

40 Cat 23 d 

(NS) 5 d/wk 5 hr/d 

41 Cat 30 d Cont. 

(NS)

Systemic

42 Rat 30 d 

(NS) 6 hr/d 

43 Rat 30 d 

(NS) 6 hr/d 

Exposure/

Duration/

Frequency

(Route)

LOAEL

System

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

Serious

(mg/m3)

ReferenceChemical Form 

15.4 (100% mortality) Dygert 1949d 

Uranium Peroxide 

2 (100% mortality) Roberts 1949 

Uranyl Nitrate 

Gastro 0.4 (ulceration of cecum) Dygert 1949a 

Uranium Tetrafluoride 

Hemato 18 Hepatic 0.4 (focal necrosis of liver) Renal 4 18 (slight azotemia) Bd Wt 4 18 (26% decrease body 

weight)

Resp 6.8 (intersitial Dygert 1949b 

bronchopneumonia in Ammonium Diuranate 

25% of animals; nasal irritation)

Hemato 6.8 (decreased RBC, 

hemoglobin)

Renal 6.8 (minimal necrosis of 

tubular epithelium followed by regeneration) 

Bd Wt 6.8 
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

LOAEL

Serious

(mg/m3)

ReferenceChemical Form 

44 Rat

(NS)

30 d Cont. Hemato 2.1 9.5 (decreased RBC, 

hemoglobin)

Roberts 1949 Uranyl Nitrate 

Renal 0.13 (slight renal tubular 

degeneration in 33% after 28 days exposure) 

Bd Wt 2.1 9.5 (5.6-12.6% decreased 

body weight) 

45 Rat

(NS)

4 wk 6 d/wk 6 hr/d 

Resp 16 (very slight degenerative 

changes in the lungs) 

Rothstein 1949c Uranium Trioxide 

Hemato 16 (increased percentage of 

myeloblasts and lymphoid cells of bone marrow)

HepaticRenal

16

16 (mild to severe tubular 

necrosis)

Bd Wt 16
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

a

Key to Species 

Figure (Strain) 

46 Rat

(NS)

47 Rat

(NS)

48 Rat

(NS)

Exposure/

Duration/

Frequency

(Route)

5 wk 6 d/wk 6 hr/d 5 wk 6 d/wk 5 wk 5.5 d/wk 6 hr/d 

System

HematoRenalBd Wt RespHematoRenalHematoRenal

LOAEL

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

Serious

(mg/m3)

ReferenceChemical Form 

9.20.5

2.2

2.29.2

(minimal renal tubular degeneration)(unspecified moderate weight loss) 

Rothstein 1949a Uranyl Fluoride 

19.419.419.4

Rothstein 1949b Uranium Dioxide 

15

15 (moderate renal 

degeneration and necrosis)

Rothstein 1949d Sodium Uranate 
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

LOAEL

Serious

(mg/m3)

ReferenceChemical Form 

49 Rat

(NS)

30 d 6 hr/d Resp 2 13.3 (lung edema, hemorrhage,

emphysema)

Spiegl 1949 Uranium Hexafluoride 

HematoRenal

13.30.05 0.2 (mild renal tubular 

damage)

OcularBd Wt 

22

13.3 (eye irritation) 

13.3 (6% weight loss) 

50 Mouse

(NS)

5 wk 6 d/wk Resp

HematoRenalBd Wt 

19.419.419.4

19.4

Rothstein 1949b Uranium Dioxide 
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

LOAEL

Serious

(mg/m3)

ReferenceChemical Form 

51 Mouse

(NS)

30 d 6 hr/d Resp 2 13.3 (lung edema, hemorrhage, and 

emphysema;inflammation of bronchi, alveoli, and alveolar interstitices)

Spiegl 1949 Uranium Hexafluoride 

Renal 2 13.3 (severe renal-tubular 

degeneration followed by regeneration, and necrosis, and the presence of casts in the tubules)

Ocular 2 13.3 (eye irritation) Bd Wt 2 13.3 (unspecified weight loss) 

52 Gn Pig 

(NS)

30 d 6 hr/d Hemato 18 Dygert 1949a 

Uranium Tetrafluoride 

Renal 4 18 (moderate to severe 

necrosis of corticomedullary tubular epithelium)

53 Gn Pig 

(NS)

30 d Cont. Bd Wt 2.1 9.5 (2.9-27.9% decreased 

body weight) 

Roberts 1949 Uranyl Nitrate 
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

Exposure/

Duration/

a

Key to Species Frequency

Figure (Strain) (Route)

54 Gn Pig 

(NS)

5 wk 6 d/wk 6 hr/d 

55 Gn Pig 

(NS)

5 wk 6 d/wk 

56 Gn Pig 

(NS)

30 d 6 hr/d 

System

RenalBd Wt RespHematoRenalBd Wt RespRenalBd Wt 

LOAEL

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

Serious

(mg/m3)

ReferenceChemical Form 

2.2 Rothstein 1949a 

Uranyl Fluoride 

9.2 (severe degeneration of 

renal tubular epithelium) 

2.2 (unspecified moderate 

weight loss) 

19.419.419.4

19.4

Rothstein 1949b Uranium Dioxide 

2 Spiegl 1949 

Uranium Hexafluoride 

13.3 (lung edema, 

hemorrhage, and emphysema, acute inflammation was seen in the bronchi, alveoli, and alveolar interstitices) 

2 13.3 (severe renal-tubular 

degeneration, necrosis, regeneration; casts in the tubules)

2 13.3 (13% decreased body 

weight)
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

LOAEL

Serious

(mg/m3)

ReferenceChemical Form 

57 Gn Pig 7.5 months 

33 hr/wk Renal

Bd Wt 

0.2

0.2

Stokinger et al. 1953 Uranium Tetrachloride 

58 Gn Pig 9 mo 

5.5 d/wk 6 hr/d 

RenalBd Wt 

0.05

0.05

Stokinger et al. 1953 Uranium Hexafluoride 

59 Gn Pig 

(NS)

7 mo 33 hrs/wk Renal

Bd Wt 

10

10

Stokinger et al. 1953 Uranium Dioxide 

60 Gn Pig 

(NS)

6.5 mo 33 hrs/wk Hemato

Renal

2 M 2 M 

Stokinger et al. 1953 Uranyl Nitrate 

61 Gn Pig 9 mo 

5.5 d/wk 6 hr/d 

HematoRenal

33

Stokinger et al. 1953 Uranium Tetrafluoride 

Bd Wt 3
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

LOAEL

Serious

(mg/m3)

ReferenceChemical Form 

62 Dog

(NS)

30 d 6 hr/d Gastro

Hemato

4

18

18 (vomited blood) Dygert 1949a 

Uranium Tetrafluoride 

Renal 0.5 3 (very slight degenerative 

changes in tubular epithelium)

OcularBd Wt 

44

18 (conjunctivitis)

18 (26% decreased body 

weight)

63 Dog

(NS)

23 d 5 d/wk 5 hr/d 

Hemato 15.4 Dygert 1949d 

Uranium Peroxide 

Bd Wt 15.4
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

Exposure/

Duration/

a

Key to Species Frequency

Figure (Strain) (Route)

64 Dog 30 d Cont. 

(NS)

65 Dog

(NS)

4 wk 6 d/wk 6 hr/d 

System

RespGastroHematoRenalBd Wt OtherRespHematoHepaticRenalBd Wt 

LOAEL

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

Serious

(mg/m3)

ReferenceChemical Form 

2.1 9.5 (rales; slight 

degeneration in lung epithelium)

Roberts 1949 Uranyl Nitrate 

2.1 9.5

0.13

(vomiting, anorexia) (slightly decreased 

fibrinogen)

0.13 (proteinuria, transient 

increase in bromosulfalein retention) 

2.1 9.5 (approximately 25% 

decreased body weight in 3/4 that died) 

2.1

16 (very slight pulmonary 

degenerative changes) 

Rothstein 1949c

 Uranium Trioxide 

1616

16 (mild to severe tubular 

necrosis)

16
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

LOAEL

Serious

(mg/m3)

ReferenceChemical Form 

66 Dog

(NS)

5 wk 6 d/wk 6 hr/d 

Gastro 2.2 9.2 (vomited blood) Rothstein 1949a 

Uranyl Fluoride 

HematoRenal

9.2

b

0.15 (very slight renal 

degeneration in approximately 50% of dogs)

Bd Wt 2.2 9.2 (unspecified severe 

weight loss) 

67 Dog

(NS)

5 wk 6 d/wk Resp 9.2 Rothstein 1949b 

Uranium Dioxide 

HematoRenal

9.2

c

1.1 8.2 (slight renal tubular 

degeneration in 2/6) 

Bd Wt 9.2

68 Dog

(NS)

30 d 6 hr/d Resp 0.2 2 (slight pneumonia) Spiegl 1949 

Uranium Hexafluoride 

Hemato 2Renal 0.05 0.2 (slight pneumonia) Ocular 2 13.3 (conjunctivitis)
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

LOAEL

Serious

(mg/m3)

ReferenceChemical Form 

69 Rabbit

(NS)

30 d 6 hr/d Hemato

Renal

18

0.4 (increased urinary 

catalase and phosphatase)

Dygert 1949a Uranium Tetrafluoride 

Bd Wt 3 18 (24% decreased body 

weight)

70 Rabbit

(NS)

30 d 6 hr/d Resp 6.8 (pulmonary edema, hemorrhage, and 

necrosis)

Dygert 1949b 

Ammonium Diuranate 

Hemato 6.8 (increased neutrophils, 

decreased lymphocytes) 

Renal 6.8 (severe necrosis of the 

tubular epithelium) 
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

LOAEL

Serious

(mg/m3)

ReferenceChemical Form 

71 Rabbit

(NS)

23 d 5 d/wk 5 hr/d 

Resp 15.4 (edematous alveoli, 

alveolar hemorrhage, hyperemia, and atelectasis)

Dygert 1949d Uranium Peroxide 

Hemato 15.4Hepatic 15.4Renal 15.4 (moderate

corticomedullary tubule necrosis with regeneration of tubular cells; azotemia) 

Bd Wt 15.4

72 Rabbit

(NS)

30 d Cont. Resp

Hemato

0.2

0.13 (increased plasma 

prothrombin and fibrinogen)

Roberts 1949 Uranyl Nitrate 

Renal 0.13 (increased urinary 

catalase)

Bd Wt 0.13 0.2 (unspecified decrease in 

body weight) 
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

Exposure/

Duration/

a

Key to Species Frequency

Figure (Strain) (Route)

73 Rabbit

(NS)

4 wk 6 d/wk 6 hr/d 

74 Rabbit

(NS)

5 wk 6 d/wk 

System

RespHematoHepaticRenalBd Wt RespHematoRenalBd Wt 

LOAEL

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

Serious

(mg/m3)

ReferenceChemical Form 

Rothstein 1949c Uranium Trioxide 

16 (hemorrhage and 

consolidation in lungs of animals that died) 

16

16 (moderate fatty livers in 

5/8 animals that died) 

16 (mild to severe necrosis 

of the tubular epithelium with degeneration and regeneration; increased NPN)

16

19.419.4

9.2

Rothstein 1949b Uranium Dioxide 

19.4 (severe tubular necrosis 

in dying animals) 

8.2 9.2 (unspecified decreased 

body weight) 
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

Exposure/

Duration/

a

Key to Species Frequency

Figure (Strain) (Route)

75 Rabbit

(NS)

5 wk 5.5 d/wk 6 hr/d 

76 Rabbit

(NS)

30 d 6 hr/d 

77 Rabbit

(NS)

6.5 mo 5.5 d/wk 6 hr/d 

LOAEL

System

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

Serious

(mg/m3)

ReferenceChemical Form 

Hepatic 15 (slight decrease in Rothstein 1949d 

lactate) Sodium Uranate 

Renal 15 (progressive

degeneration and necrosis followed by regeneration of tubular epithelium; increased NPN)

Bd Wt 15 

Resp 0.2 2 (severe pulmonary Spiegl 1949 

edema) Uranium Hexafluoride 

Hemato 13 Renal 0.2 (mild tubular 

degeneration)

Bd Wt 0.2 2 (12% decreased body 

weight)

Hemato 2 Stokinger et al. 1953 

Uranyl Nitrate 

Renal 0.25 mild tubular atrophy) Bd Wt 2 (weight loss) 
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

Exposure/

Duration/

a

Key to Species Frequency

Figure (Strain) (Route)

78 Rabbit 9 mo 

5.5 d/wk 6 hr/d 

79 Rabbit 9 mo 

5.5 d/wk 6 hr/d 

80 Rabbit

(NS)

7 mo 33 hrs/wk 

81 Rabbit 7.5 mo 

33 hr/wk 

System

RenalBd Wt HematoRenalBd Wt HematoRenalBd Wt RenalBd Wt 

LOAEL

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

Serious

(mg/m3)

ReferenceChemical Form 

0.2

0.2 (very mild tubular injury) Stokinger et al. 1953 

Uranium Hexafluoride 

33

3

Stokinger et al. 1953 Uranium Tetrafluoride 

1010

Stokinger et al. 1953 Uranium Dioxide 

10

0.2

0.2

Stokinger et al. 1953 Uranium Tetrachloride 
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

Exposure/

Duration/

a

Key to Species Frequency

Figure (Strain) (Route)

82 Cat 30 d 

(NS) 6 hr/d 

83 Cat 23 d 

(NS) 5 d/wk 5 hr/d 

84 Cat 4 wk 

(NS) 6 d/wk 6 hr/d 

LOAEL

System

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

Serious

(mg/m3)

ReferenceChemical Form 

Resp 18 (rhinitis) Dygert 1949a 

Uranium Tetrafluoride 

Gastro 18 (vomited blood) Hemato 18 Renal 18 (moderate to severe 

typical renal injury in 2/3 dying cats; azotemia) 

Ocular 18 (conjunctivitis)Bd Wt 18 (18% decreased body 

weight)

Hemato 15.4 Dygert 1949d 

Uranium Peroxide 

Renal 15.4 (azotemia) Bd Wt 15.4 Hemato 16 Rothstein 1949c

 Uranium Trioxide 

Renal 16 (diuresis; proteinuria; 

increased NPN) 

Bd Wt 16 
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

LOAEL

Serious

(mg/m3)

ReferenceChemical Form 

85 Cat

(NS)

5 wk 6 d/wk 6 hr/d 

Resp 2.2 9.2 (rhinitis) Rothstein 1949a 

Uranyl Fluoride 

Gastro 2.2 9.2 (vomited blood prior to 

death)

Renal 2.2 9.2 (severe degeneration of 

renal tubular epithelium) 

Immuno/ Lymphoret 

86 Rat

(NS)

30 d 6 hr/d 0.4 (edematous cecal lymph nodes; focal necrosis of 

spleen)

Dygert 1949a Uranium Tetrafluoride 

87 Rat

(NS)

30 d 6 hr/d 6.8 (rise in neutrophils, decreased lymphocytes, 

moderate fall in the white blood count, rise in the eosinophils)

Dygert 1949b 

Ammonium Diuranate 

88 Rat

(NS)

30 d Cont. 2.1 9.5 (decreased absolute 

number of lymphocytes and neutrophils) 

Roberts 1949 Uranyl Nitrate 

Neurological

89 Rat

(SpragueDawley)

3 wk 4 d/wk 0.5 hr (NS)

190 M (increased spontaneous 

activity; decreased spatial working memory) 

Monleau et al. 2005 Uranium Dioxide 
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

LOAEL

Serious

(mg/m3)

ReferenceChemical Form 

90 Dog

(NS)

30 d 6 hr/d 4 18 (weakness and unsteady gait) Dygert 1949a Uranium Tetrafluoride 

91 Cat

(NS)

30 d 6 hr/d 18 (weakness and unsteady gait) Dygert 1949a Uranium Tetrafluoride 

CHRONIC EXPOSURE 

Death

92 Dog

(Beagle)

5 yr 5 d/wk 5.4 hr/d 

Systemic

93 Monkey 5 yr 

5 d/wk 5.4 hr/d 

Resp

d

5.1 (minimal pulmonary 

hyaline fibrosis) 

5 (4.5% mortality) Leach et al. 1970, 1973 

Uranium Dioxide Leach et al. 1970, 1973 Uranium Dioxide 

HepaticRenalBd Wt 

5.15.1

5.1
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

LOAEL

Serious

(mg/m3)

ReferenceChemical Form 

94 Rat

(NS)

1 yr 33 hrs/wk Resp

Gastro

0.20.2

Stokinger et al. 1953 Uranium Tetrachloride 

HepaticRenal

0.2

0.05 0.2 (slight to mild tubular 

injury)

Endocr 0.2Bd Wt 0.2

95 Rat

(NS)

1 yr 33 hrs/wk Resp

Renal

2

0.25 2 (mild to marked renal 

tubular atrophy) 

Stokinger et al. 1953 Uranyl Nitrate 

Bd Wt 2
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

Exposure/

Duration/

a

Key to Species Frequency

Figure (Strain) (Route)

96 Rat

(NS)

1 yr 5.5 d/wk 6 hr/d 

97 Rat

(NS)

2 yr 5.5 d/wk 6 hr/d 

98 Rat

(NS)

1 yr 5.5 d/wk 6 hr/d 

System

RespCardioGastroHematoHepaticRenalEndocrDermalBd Wt HematoRenalBd Wt HematoRenalBd Wt 

LOAEL

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

Serious

(mg/m3)

ReferenceChemical Form 

0.2 Stokinger et al. 1953 

Uranium Hexafluoride 

0.2

0.20.20.2

0.05 0.2 (very mild renal tubular 

lesions)

0.20.2

0.2

2 Stokinger et al. 1953 

Uranyl Nitrate 

2

2 (mild tubular atrophy) 

3 Stokinger et al. 1953 

Uranium Tetrafluoride 

3

3
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

LOAEL

Serious

(mg/m3)

ReferenceChemical Form 

99 Rat 1 yr 

33 hrs/wk Hemato

Renal

1010

Stokinger et al. 1953 Uranium Dioxide 

Bd Wt 10

100 Dog

(Beagle)

1-5 yr 5 d/wk 5.4 hr/d 

Resp 5.1 Leach et al. 1970, 1973 

Uranium Dioxide 

HematoRenalBd Wt 

5.15.1

5.1

101 Dog

(NS)

1 yr 33 hrs/wk Hemato

HepaticRenalBd Wt 

0.20.2

e

0.05

0.2

0.2 (slight tubular atrophy) 

Stokinger et al. 1953 Uranium Tetrachloride 

102 Dog

(NS)

1 yr 5.5 d/wk 6 hr/d 

Hemato 2 Stokinger et al. 1953 

Uranyl Nitrate 

HepaticRenal

2

0.15 0.25 (mild to moderate tubular 

atrophy)

Bd Wt 2 
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

Exposure/

Duration/

a

Key to Species Frequency

Figure (Strain) (Route)

103 Dog 1 yr 

33 hrs/wk 

104 Dog 1 yr 

5.5 d/wk 6 hr/d 

105 Dog 1 yr 

5.5 d/wk (NS) 6 hr/d 

106 Dog 2 yr 

5.5 d/wk (NS) 6 hr/d 

System

HematoRenalBd Wt HematoRenalBd Wt RespHematoRenalBd Wt HematoRenal

LOAEL

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

Serious

(mg/m3)

ReferenceChemical Form 

10

1 10 (slight to mild tubular 

degeneration)

Stokinger et al. 1953 Uranium Dioxide 

10

3 Stokinger et al. 1953 

Uranium Tetrafluoride 

0.5

3

3 (tubular damage) 

0.2 Stokinger et al. 1953 

Uranium Hexafluoride 

0.2

0.05

0.2

0.2 (mild tubular injury) 

2 Stokinger et al. 1953 

Uranyl Nitrate 

2 (moderate tubular 

atrophy)
***DRAFT FOR PUBLIC COMMENT***

Table 3-1 Levels of Significant Exposure to Uranium - Inhalation (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/m3)

Less Serious 

(mg/m3)

LOAEL

Serious

(mg/m3)

ReferenceChemical Form 

Immuno/ Lymphoret 

107 Dog

(Beagle)

5 yr 5 d/wk 5.4 hr/d 

5.1 (minimal lymph node 

fibrosis)

Leach et al. 1970, 1973 Uranium Dioxide 

Cancer

108 Rat

(SpragueDawley)

65 wk 5 d/wk 4.2 hr/d 

8.4 M (CEL: malignant lung 

tumors)

Mitchel et al. 1999 Uranium dust 

109 Dog

(NS)

1-5 yr 5 d/wk 5.4 hr/d 

5.1 (CEL: lung cancer) Leach et al. 1973 

Uranium Dioxide 

a The number corresponds to entries in Figure 3-1. b Used to derive an intermediate-duration inhalation minimal risk level (MRL) of 0.0001 mg U/m3 for soluble uranium compounds based on a LOAELADJ of 0.032 muncertainty factor of 300 (3 for use of a minimal LOAEL, 10 for extrapolation from animals to humans, and 10 for human variability). c Used to derive an intermediate-duration inhalation minimal risk level (MRL) of 0.002 mg U/m3 for insoluble uranium compounds based on a NOAELADJ of 0.24 muncertainty factor of 100 (10 for extrapolation from animals to humans and 10 for human variability). d Used to derive a chronic-duration inhalation minimal risk level (MRL) of 0.0008 mg U/m3 for insoluble uranium compounds based on a LOAELADJ of 0.82 mg/m3 uncertainty factor of 1000 (10 for use of LOAEL, 10 for extrapolation from animals to humans and 10 for human variability). e Used to derive a chronic-duration inhalation minimal risk level (MRL) of 0.00004 mg U/m3 for soluble uranium compounds based on a BMCLADJ of 0.0037 mg/muncertainty factor of 100 (10 for extrapolation from animals to humans and 10 for human variability). Bd Wt = body weight; Cardio = cardiovascular; CEL = cancer effect level; d = day(s); Endocr = endocrine; Gastro = gastrointestinal; Gn Pig = guinea pig; Hemato = = hour(s); LOAEL = lowest-observed-adverse-effect level; M = male; min = minute(s); NOAEL = no-observed-adverse-effect level; NS = not specified; occup = occurespiratory; wk = week(s); yr = year(s) 
Death 

I

100000 

mg/m3 

6r 

4g 12g 13g 

1r 

10000 6r 

9r 

2r 8r 

1000 8r 

5g 3m 11m 10r 10r 11m 10r 

7r 6r 

14d 14d 

16r 

100 

15r 

10 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

Respiratory 

Renal 

Ocular 

mmuno/Lymphor 

URANIUM

***DRAFT FOR PUBLIC COMMENT***

3. HEALTH EFFECTS

Figure 3-1 Levels of Significant Exposure to Uranium - Inhalation 

Acute (≤14 days) 

Systemic 

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

73
Death 

mg/m3 

1000 

100 

39c 27d 21g 17r 32h 36h 82c 55g 50m 40c 29d 23g 25g 19m 34h 35h 37h 65d 45r 31d 26g 18r 56g 51m

10 28d 30d 24g 85c 64d 67d 

22g 33h 43r 

41c 20m 38h 85c 64d 68d 56g 51m 

1 

68d 

0.1 

0.01 

0.001 

0.0001 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

Respiratory 

URANIUM

***DRAFT FOR PUBLIC COMMENT***

3. HEALTH EFFECTS

Figure 3-1 Levels of Significant Exposure to Uranium - Inhalation (Continued)

Intermediate (15-364 days) 

Systemic 

74
mg/m3 Respiratory 

1000 

100 

47r 74h 82c 62d 82c 62d 52g 55g 50m 42r 47r 69h

71h 73h 83c 84c 63d 65d 45r 48r 49r 49r

10 64d 44r 85c 66d 66d 67d 46r 

70h 43r 70h 

62d 

61g 85c 64d 66d 44r 

1 

42r 

72h 

49r 76h 68d 60g 

76h 

64d 0.1 

0.01 

0.001 

0.0001 

c-Cat 

d-Dog

r-Rat 

 -Humans 

k-Monkey

m-Mouse 

f-Ferret 

j-Pigeon

e-Gerbil 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

 LD50/LC50

Minimal Risk Level

 for effects

Gastrointestinal 

Hematological 

URANIUM

***DRAFT FOR PUBLIC COMMENT***

3. HEALTH EFFECTS

Figure 3-1 Levels of Significant Exposure to Uranium - Inhalation (Continued)

Intermediate (15-364 days) 

Systemic 

p-Pig

q-Cow

h-Rabbit 

a-Sheep 

s-Hamster 

g-Guinea Pig 

NOAEL - Animals NOAEL - Humans other than

 Cancer 

75
mg/m3 Hem

Hep

Ren

1000 

100 

74h 55g 50m 47r 82c 52g 42r 71h 73h 65d 45r 71h 73h 75h 83c 84c 65d 45r 71h 73h 76h 56g 51m 48r

10 80h 85c 54g 59g 74h 67d 43r 70h 

52g 42r 79h 62d 61g 85c 54g 46r 

1 

77h 56g 60g 51m 

67d 

62d 46r 42r 69h 

68d 57g 49r 

66d 72h 64d 44r 72h 0.1 

68d 58g 49r 

0.01 

0.001 

0.0001 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

atological 

atic 

al 

URANIUM

***DRAFT FOR PUBLIC COMMENT***

3. HEALTH EFFECTS

Figure 3-1 Levels of Significant Exposure to Uranium - Inhalation (Continued)

Intermediate (15-364 days) 

Systemic 

76
Renal 

Ocular 

Body Weight 

mg/m3 

1000 

100 

74h 82c 62d 55g 50m 82c 62d 42r

75h 83c 84c 63d 65d 45r 68d 51m 49r 56g 51m

10 80h 64d 66d 67d 53g 59g 44r

43r 

62d 62d 42r

79h 61g

68d 51m 49r 64d 66d 53g 54g 56g 51m 44r

1 

77h 76h 78h 81h 57g 

0.1 

58g 

0.01 

0.001 

0.0001 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

URANIUM

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Figure 3-1 Levels of Significant Exposure to Uranium - Inhalation (Continued)

Intermediate (15-364 days) 

Systemic 

77
Body Weight 

Other Immuno/Lymph

Neurological 

1000 

mg/m3 

89r 

100 

69h 91c 90d 49r 71h 73h 75h

10 80h 88r 46r 74h 74h 87r 

90d 69h 79h 

46r 49r 76h 77h 64d 88r

1 

86r 

72h 76h 78h 81h 

72h 0.1 

0.01 

0.001 

0.0001 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

or 

URANIUM

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3. HEALTH EFFECTS

Figure 3-1 Levels of Significant Exposure to Uranium - Inhalation (Continued)

Intermediate (15-364 days) 

Systemic 

78
Death 

Respiratory 

Cardiovascular Gastrointestinal Hematological 

Hepatic 

Renal 

mg/m3 

100 

10 

92d 100d

1 

105d 

0.1 

0.01 

0.001 

0.0001 

1E-5 

Systemic 

103d 99r 103d 99r 

93k 100d 93k 100d 93k 

104d 98r 104d 98r 

95r 102d 106d 97r 102d 106d 95r 97r 

103d 

104d 

102d 95r 94r 96r 96r 94r 96r 101d 105d 96r 101d 94r 96r 101d 105d 94r 96r

102d 

101d 105d 94r 96r 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

URANIUM

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3. HEALTH EFFECTS

Figure 3-1 Levels of Significant Exposure to Uranium - Inhalation (Continued)

Chronic (≥365 days) 

79
Endocrine 

Dermal 

Body Weight 

Immuno/Lymphor 

Cancer * 

100 

10 

1 

0.1 

0.01 

0.001 

0.0001 

1E-5 

mg/m3 

103d 99r 108r 

100d 93k 107d 109d 

104d 98r 

102d 95r 97r 

96r 101d 105d 94r 96r 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

*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. 

94r 96r 

URANIUM

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3. HEALTH EFFECTS

Figure 3-1 Levels of Significant Exposure to Uranium - Inhalation (Continued)

Chronic (≥365 days) 

Systemic 

80
 

 

 

 

 

 

 

 

 

 

 

 

 

 

URANIUM 81 

3. HEALTH EFFECTS 

No animal studies were located regarding the endocrine, metabolic, dermal, or ocular effects of uranium 

in animals following acute-duration inhalation exposures to uranium. Nor were any studies located 

regarding the metabolic, dermal, ocular, or other systemic effects in animals following intermediateduration inhalation exposure to uranium. There are animal data for acute-, intermediate-, and chronicduration inhalation exposures to uranium for respiratory, hematological, cardiovascular, gastrointestinal, 

renal, or body weight effects. However, animal data on hepatic effects are limited to acute- and chronicduration inhalation exposures to uranium. 

The highest NOAEL values and all reliable LOAEL values in each species and duration category for 

systemic effects from chemical exposure to uranium by the inhalation route are presented in Table 3-1 

and plotted in Figure 3-1. 

Respiratory Effects. The hazard from inhaled uranium aerosols, or from any noxious agent, is the 

likelihood that the agent will reach the site of its toxic action. Two of the main factors that influence the 

degree of hazard from toxic airborne particles are: (1) the site of deposition in the respiratory tract of the 

particles and (2) the fate of the particles within the lungs. The deposition site within the lungs depends 

mainly on the particle size of the inhaled aerosol, while the subsequent fate of the particle depends mainly 

on the physical and chemical properties of the inhaled particles and the physiological status of the lungs. 

Small particles (about 2 micrometers [μm] or smaller in diameter) tend to be deposited in the alveoli. The 

alveoli, frequently called the “deep respiratory tract,” form the functional part of the lungs where gas 

exchange occurs. As the particle size increases, progressively fewer particles penetrate into the deep 

respiratory tract, and increasingly greater fractions of the inhaled particles are deposited in the upper 

respiratory tract. The respiratory tract is a system of ducts that starts at the nares and includes the 

pharynx, larynx, trachea, and a complex series of bronchi and bronchioles that terminate in several 

thousand alveoli. Three different mechanisms are involved in the removal of particles from the 

respiratory tract. The first is mucociliary action in the upper respiratory tract (trachea, bronchi, 

bronchioles, and terminal bronchioles), which sweeps particles deposited there into the throat, where they 

are either swallowed into the gastrointestinal tract or spat out. The two other clearance mechanisms, 

dissolution (which leads to absorption into the bloodstream) and phagocytosis (removal by specialized 

cells in the process), deal mainly with the particles deposited in the deep respiratory tract (respiratory 

bronchioles, alveolar ducts, and alveolar sacs) (ICRP 1994a; NCRP 1997). The less soluble uranium 

particles may remain in the lungs and in the regional lymph nodes for weeks (uranium trioxide, uranium 

tetrafluoride, uranium tetrachloride) to years (uranium dioxide, triuranium octaoxide). 

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URANIUM 82 

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Human and animal studies have shown that long-term retention in the lungs of large quantities of inhaled 

insoluble uranium particles (e.g., carnotite dust [4% uranium as uranium dioxide and triuranium 

octaoxide, 80–90% quartz, and <10% feldspar]) can lead to serious respiratory effects. However, animals 

exposed to high doses of purified uranium (as uranyl nitrate hexahydrate, uranium tetrachloride, uranium 

dioxide, uranium trioxide, uranium tetraoxide, uranium fluoride, or uranium acetate) through the 

inhalation or oral route in acute-, intermediate-, or chronic-duration exposures failed to develop these 

respiratory ailments. The lack of significant pulmonary injury in animal studies with insoluble 

compounds indicates that other factors, such as diverse inorganic particle abrasion or chemical reactions, 

may contribute to these effects. 

In acute exposures, respiratory disease may be limited to interstitial inflammation of the alveolar 

epithelium, leading eventually to pulmonary fibrosis (Clayton and Clayton 1981; Cooper et al. 1982; 

Dungworth 1989; Wedeen 1992). In studies of the pulmonary effects of airborne uranium dust in 

uranium miners and in animals, the respiratory diseases reported are probably aggravated by the inhalable 

dust particles’ (the form in which uranium is inhaled) toxicity because most of the respiratory diseases 

reported in these studies are consistent with the effects of inhaled dust (Dockery et al. 1993). In some of 

these instances, additional data from the studies show that the workers were exposed to even more potent 

respiratory tract irritants, such as silica and vanadium pentaoxide (Waxweiler et al. 1983). 

The effects of massive acute exposures to uranium in humans, as well as epidemiologic or clinical studies 

of uranium mine workers chronically exposed to mine atmospheres (containing other noxious agents that 

include silica, diesel fumes, cigarette smoke, and radon and its daughters), have been investigated. 

Several epidemiologic studies have reported respiratory diseases in uranium mine and mill workers, who 

were also exposed to significant amounts of dust and other pulmonary irritants, but not in uraniumprocessing workers, who were not exposed to these potential aggravants. 

Accidental exposure of workers to estimated airborne concentrations of 20 mg uranium hexafluoride/m3 

for a 1-minute exposure and 120 mg uranium hexafluoride/m3 for a 60-minute exposure (15.2 and 

91 mg U/m3

, respectively) resulted in acute respiratory irritation, which is attributed to the hydrofluoric 

acid decomposition product. One worker died of pulmonary edema a few hours after the accident 

(USNRC 1986, 1990). In another report, 20 men who were seriously injured following accidental 

exposure to a stream of uranium hexafluoride when a transportation cask ruptured showed signs of 

pulmonary edema, which also was attributed to hydrofluoric acid. After 3 weeks, most had normal 

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URANIUM 83 

3. HEALTH EFFECTS 

clinical findings and were considered to be in excellent health. A follow-up examination 38 years later on 

three of the injured workers showed no detectable uranium deposition and no respiratory findings 

attributable to the exposure (Kathren and Moore 1986). No clinical signs of pulmonary toxicity were 

found in about 100 uranium-processing workers exposed to insoluble uranium dust at levels of 0.5– 

2.5 mg U/m3 for about 5 years (Eisenbud and Quigley 1956). Other reports of workers in the uranium 

processing industry did not show increased deaths due to diseases of the respiratory system related to 

exposure to uranium (Cragle et al. 1988; NIOSH 1987; Polednak and Frome 1981; Scott et al. 1972). 

A 30-year follow-up study in which ionizing radiation hazard was assessed for a study cohort consisting 

of 995 workers in a uranium-processing facility that operated between 1943 and 1949 found statistically 

significant increases in death from all causes. Significantly increased mortality was observed for cancer 

of the larynx and for pneumonia, but not for lung cancer. The workers were exposed to internal radiation 

from the inhaled uranium dust, with an upper limit of 1,000 mSv. The data (external radiation badge) for 

the last 24 months of operation indicated that the highest cumulative external gamma dose for a worker 

was about 20 mSv. Long-term occupational exposure was evaluated in a subcohort that received 

150 mSv/year or more. Because the workers were also exposed to radon-222 (222Ra), chlorine, 

hydrofluoric acid, lead sulfate, nickel, nitric acid and nitrogen oxides, silicon dioxide, and sulfuric acid, 

the etiology of the reported laryngeal disease is uncertain (Dupree et al. 1987). An increased incidence of 

deaths (standard mortality ratios [SMRs]=2.29) from obstructive pulmonary disease was found in 

4,106 workers in a nuclear fuels fabrication plant who were employed for >6 months from 1956 to 1978 

(Hadjimichael et al. 1983). However, the overall death rate and the rate of all cancers combined were 

lower than expected. The association of disease with exposure to uranium was not confirmed. 

Pinkerton et al. (2004) reported significantly increased mortality from nonmalignant respiratory disease 

(100 observed vs. 70.16 expected; SMR 1.43, 95% CI 1.16–1.73) within a cohort of 1,485 workers 

employed in uranium mills in the Colorado Plateau region (Arizona, Colorado, New Mexico) when 

worker mortality was compared to mortality within the U.S. population. The workers were employed for 

at least 1 year; 37% were employed for 3–9 years and 20% for ≥10 years. The latency period (time from 

first employment to evaluation) was at least 20 years for 86% of the cohort. Mortality rates were not 

significantly elevated among the mill workers when compared to Colorado Plateau regional population 

mortality rates. This region is noted for relatively high chronic obstructive pulmonary disease compared 

to other states. 

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URANIUM 84 

3. HEALTH EFFECTS 

Boice et al. (2008) examined mortality in a cohort of mining (1,867 males and females) and milling 

(759 males and females) workers at Grants, New Mexico, compared to mortality rates for the U.S. 

population. All workers were employed for at least 6 months; 47 and 12% of the miners were employed 

for 0.5–1.9 and ≥10 years and 42 and 15% of the millers were employed for 0.5–1.9 and ≥10 years. For 

both groups, the latency period was ≥20 years. After separating the cohort according to type of 

employment (mining, milling), only the group that reported having worked in underground uranium 

mines exhibited significant excess mortality from nonmalignant respiratory disease (55 observed vs. 

33.6 expected; SMR 1.64, 95% CI 1.23–2.13); the mortality ratio for the millers was 1.07 (25 observed 

vs. 23.4 expected; 95% CI 0.69–1.58). The increased mortality from nonmalignant respiratory disease 

among the workers with uranium mining experience is attributable to exposure to mining dusts, radon 

decay products, diesel exhaust, and excessive tobacco use, rather than exposure to uranium. 

The pulmonary toxicity of uranium compounds varies in animals. Reports of pulmonary toxicity in 

animals after acute-duration exposure to uranium are limited to experiments with uranium hexafluoride. 

Gasping and severe irritation to the nasal passages were reported after 10-minute exposures at 637 mg 

U/mg3 in rats and mice (Spiegl 1949) and nasal hemorrhage in rats after a 5-minute exposure to 

54,503 mg/m3 (Leach et al. 1984). Uranium hexafluoride promptly hydrolyzes on contact with water to 

uranyl fluoride and hydrofluoric acid. Thus, the animals were potentially exposed to hydrofluoric acid, a 

potent toxicant to respiratory tract epithelium, which probably contributed to pulmonary tissue destruction 

(Leach et al. 1984; Spiegl 1949; Stokinger et al. 1953). In addition, exposure to fluoride ions can result in 

hypocalcemia, hypomagnesemia, pulmonary edema, metabolic acidosis, ventricular arrhythmia, and death 

(Meditext 1998). 

Intermediate-duration exposure to uranium compounds also caused pulmonary toxicity, particularly when 

exposure was to uranium hexafluoride. Exposure of rats, mice, and guinea pigs to this compound for 

6 hours/day for 30 days at 13.3 mg U/m3 resulted in pulmonary edema, hemorrhage, emphysema, and 

inflammation of the bronchi and alveoli (Spiegl 1949). Exposure to 2.0 mg U/m3 resulted in pulmonary 

edema, hemorrhage, and emphysema in rabbits and slight pneumonia in dogs (Spiegl 1949). Milder 

effects were observed with other uranium compounds in a series of experiments where exposure 

conditions were similar to those found in the workplace (i.e., 5–6 hours/day, 5–6 days/week). For 

example, rhinitis was observed in cats and dogs after 30 days of exposure to 18 mg U/m3 as uranium 

tetrafluoride (Dygert 1949a) and after 5 weeks of exposure to 9.2 mg U/m3 as uranyl fluoride (Rothstein 

1949a); the rhinitis was observed in animals dying early and were associated with other signs of 

morbidity. Histopathological evidence of toxicity was observed in several studies, including slight 

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URANIUM 85 

3. HEALTH EFFECTS 

degenerative changes in the lungs of rats and dogs exposed to 16 mg U/m3 as uranium trioxide (Rothstein 

1949c) and dogs exposed to 9.5 mg U/m3 as uranyl nitrate (Roberts 1949). Uranium dioxide and 

triuranium octaoxide did not cause toxicity (Dygert 1949c; Rothstein 1949b). Carnotite uranium ore did 

not cause toxicity in mice or guinea pigs, but hemorrhagic lungs were observed in dogs (Pozzani 1949). 

The species differences may reflect deeper penetration of this material into the dog respiratory tract. 

Rabbits were more sensitive to respiratory effects of uranium compounds than other species. Severe 

respiratory effects (pulmonary edema, hemorrhage) were observed in this species with exposure to 6.8 mg 

U/m3 as ammonium diuranate (Dygert 1949b), 15.4 mg U/m3 as uranium peroxide (Dygert 1949d), 16 mg 

U/m3 as uranium trioxide (Rothstein 1949c), and 22 mg U/m3 as carnotite uranium ore (Pozzani 1949). 

Uranium dioxide at 19.4 mg U/m3 did not cause respiratory effects in rabbits (Rothstein 1949b). 

In chronic-duration exposure tests, a total of 3,100 test animals, including rats, rabbits, guinea pigs, and 

dogs were exposed to aerosols containing 0.05–10 mg U/m3 of various uranium compounds for 7– 

13 months. No histological damage attributable to uranium exposure were observed in the lungs. There 

was an absence of any other type of histological damage outside the kidneys (Cross et al. 1981a, 1981b; 

Stokinger et al. 1953). Dogs exposed to 15 mg/m3 of carnotite ore dust containing 0.6 mg U/m3 with a 

particle size activity median aerodynamic diameter (AMAD) of 1.5–2.1 μm 4 hours/day, 5 days/week for 

1–4 years showed very slightly increased pulmonary resistance, which may not have been statistically 

significant. Histological findings included vesicular emphysema, which was present to a lesser degree in 

control animals. Fibrosis was not noted at this concentration (Cross et al. 1981a, 1982). 

Exposure of 200 rats, 110 dogs, and 25 monkeys to 5 mg U/m3 as uranium dioxide dust 5.4 hours/day, 

5 days/week for 1–5 years did not result in histological damage in the lungs of the dogs or rats. Minimal 

patchy hyaline fibrosis was occasionally seen in the tracheobronchial lymph nodes of dogs and monkeys 

exposed for >3 years. No atypical epithelial changes were noted (Leach et al. 1970). 

Because particles containing insoluble uranium compounds can reside in the lung for years, it is likely 

that radiotoxicity as well as chemical toxicity can result from inhalation exposure to highly enriched 

uranium compounds. Radiation effects on tissues from the alveolar regions of the lungs were examined 

in Albino HMT (F344) male rats exposed, nose-only, for 100 minutes to an aerosol of to 92.8% 

235U-enriched uranium dioxide with a concentration ranging from 2,273 nCi/m3 (84.1 kBq/m3

) to 

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URANIUM 86 

3. HEALTH EFFECTS 

5,458 nCi/m3 (202 kBq/m3). Increases in the sizes and numbers of lung macrophages and type II3 cells 

and the numbers of macrophages and type I cells, and a significant increase in the size of lysosomal 

granules within the macrophages were reported 8 days postexposure. At 7 days postexposure, 35 of the 

rats were further exposed to thermal neutrons at a fluence of 1.0x1012 neutrons/cm2 over 2.5 minutes in 

order to study the combined effects of radiation and chemical toxicity. The radiation dose due to the 

neutrons and the fission fragments was about 600 rads, which is about 300 times greater than the radiation 

dose from the uranium dioxide alpha particles. No significant difference was found between the uranium 

dioxide-only group and those that were subsequently irradiated with neutrons, indicating that the extra 

radiation exposure caused no immediate pulmonary cellular reaction above that produced by uranium 

dioxide alone. This finding implies that the observed acute pulmonary effects were due to the 

metallotoxicity of the uranium dioxide rather than to the alpha radiation from the uranium (Morris et al. 

1989). 

There is evidence that exposure to highly enriched uranium through inhaled or intratracheally instilled 

enriched uranium compounds adversely affect the epithelium of the lungs. Severe alveolar fibrosis or 

metaplasia was found in 72% of the sampled lung tissues from F344 rats exposed for 100 minutes to an 

aerosol of 92.8% enriched uranium dioxide at a radioactivity concentration of 5 μCi/m3 (137 kBq/m3

; 

~150 mg U/m3

) to 10 μCi/m3 (270 kBq/m3; ~300 mg U/m3). Extensive lung disease of an unspecified 

nature was observed only in animals sacrificed at 720 days postexposure. The radioactivity concentration 

of the mixture was estimated as 1.91 kBq/g (51.6 nCi/mg), and the AMAD of the particles ranged from 

2.7 to 3.2 μm (Morris et al. 1990). 

In other animal studies, changes suggestive of damage from either radiation or diverse inorganic dust 

(fibrosis) were reported in lungs and tracheobronchial lymph nodes in Rhesus monkeys exposed by 

inhalation to 5.1 mg/m3 (as uranium dioxide) corresponding to a radioactivity concentration of 3.4 nCi/m3 

(126 Bq/m3

) for periods >3 years. Estimated cumulative alpha-radiation tissue doses were >500 rads 

(5 Gy) for the lungs and 7,000 rads (70 Gy) for the lymph nodes. Similarly exposed dogs also developed 

slight interstitial and vascular fibrosis of the lungs at lung alpha-radiation tissue doses of 760–1,280 rads 

(7.6–12.8 Gy) (Leach et al. 1970). The effect on the tracheobronchial lymph nodes in animals exposed 

for an additional 2 years ranged from involvement of a single node to complete destruction of all nodes, 

was dose-dependent and showed a similarity to changes seen after inhalation exposure to plutonium as 

3

Type I cells are alveolar lining cells that are involved with the transfer of oxygen and other substances between the 

alveolus and the blood. Type II cells are alveolar cells with two functions: oxidative enzymes for lung metabolism, 

and the production and secretion of the surfactant coating the alveolar surface. 

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URANIUM 87 

3. HEALTH EFFECTS 

238,239Pu dioxide (Leach et al. 1973). Renal damage was not observed in either dogs or monkeys, but 

fibrosis was found in monkey lung and both necrosis and fibrosis were found in dog and monkey lymph 

nodes. It was not clear whether the damage was chemically or radiologically induced, but the magnitude 

of the radiation doses and the presence of lung and lymph node damage in the absence of renal effects 

was suggestive to the authors of long-term radiation damage (Leach et al. 1970). However, such 

degenerative changes in the lungs have also been observed following prolonged exposure to diverse 

inorganic dust. 

For more information about lung effects from plutonium and a review of the hazards associated with 

alpha-emitting radionuclide exposure, see the ATSDR Toxicological Profile for Plutonium (Agency for 

Toxic Substances and Disease Registry 2010) or Appendix D of this profile. 

Cardiovascular Effects. No cardiovascular effects have been reported in humans after inhalation 

exposure to uranium. No effect on blood pressure or pulse rate was observed in a man accidentally 

exposed to powdered uranium tetrafluoride for 5 minutes (Lu and Zhao 1990). Air concentration and 

mean particle size of the powder were not determined. Electrocardiograms and chest x-rays were normal 

shortly after the accident and over a 7.5-year follow-up period. 

No cardiovascular effects were seen in rats exposed to 0.2 mg U/m3 (0.13 nCi U/m3

) as uranium 

hexafluoride for 1 year (Stokinger et al. 1953) or in rats, mice, guinea pigs, and rabbits exposed to 

4.8 mg U/m3 (3.2 nCi U/m3

) triuranium octaoxide for 26 days (Dygert 1949c). 

Gastrointestinal Effects. Inhalation exposure to uranium has generally not resulted in 

gastrointestinal effects in humans although transient effects occurred after one accidental exposure (Lu 

and Zhao 1990). On the sixth day after a male worker at a uranium-enrichment plant was accidentally 

exposed for about 5 minutes in a closed room by inhalation to a high concentration of uranium 

tetrafluoride (natural uranium) powder, the patient reported nausea and loss of appetite. Air concentration 

and mean particle size of the powder were not determined. On postaccident day 8, the clinical findings 

were loss of appetite, abdominal pain, diarrhea, tenesmus, and pus and blood in the stool. On 

postaccident day 9, all parameters returned to normal. The study gave no indication of particle size for 

assessing deposition in the upper lung and no indication of whether fecal uranium analysis was 

undertaken to determine if the noted effects may have been mediated by the mucocilliary clearance of the 

uranium tetrafluoride from the lung and its subsequent swallowing to the gastrointestinal tract in 

accordance with the current ICRP lung model (ICRP 1994a) or whether the signs were the result of 

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URANIUM 88 

3. HEALTH EFFECTS 

another intestinal irritant. Gastrointestinal symptoms were not among the clinical signs reported for other 

workers accidentally exposed to uranium hexafluoride (Eisenbud and Quigley 1956; Moore and Kathren 

1985; USNRC 1986). 

Dogs, but not other species, appear susceptible to gastrointestinal effects after inhalation exposure to high 

concentrations of uranium compounds. Vomiting was observed during intermediate-duration exposure to 

9.5 mg U/m3 uranyl nitrate (Roberts 1949), 18 mg U/m3 uranium tetrafluoride (Dygert 1949a), and 9.2 mg 

U/m3 uranyl fluoride (Rothstein 1949a). It is possible that irritation of the gastrointestinal tract occurred 

either from clearance of uranium particles from the lungs or ingestion of uranium from grooming of 

uranium particulates deposited on the fur during the whole-body exposures. Histopathological 

examination of rat gastrointestinal tissues revealed no changes after 1-year exposures to 0.2 mg U/m3 

uranium hexafluoride or uranium tetrachloride (Stokinger et al. 1953). 

Hematological Effects. Inhalation exposure to uranium compounds has generally had no effect, or 

only minor effects, on hematological parameters in both humans and animals. In human studies, no 

hematological effects were found in a man who was accidentally exposed to powdered uranium 

tetrafluoride for 5 minutes (Lu and Zhao 1990). Air concentration and mean particle size of the powder 

were not determined. Small but significant decreases in the hemoglobin concentration and the mean 

corpuscular hemoglobin concentration and significant increases in red blood cells counts and mean 

corpuscular volume were found in uranium miners who had worked for <5–20 years. All values 

measured were well within the normal range, such that values for individual miners could not be used as 

an estimate of exposure. No evidence of damage to red blood cell formation was found. The ambient 

concentration to which these workers had been exposed was not provided in the study (Vich and Kriklava 

1970). 

A study on the mortality among uranium mill workers found four deaths from lymphatic and 

hematopoietic tissue effects other than leukemia, while only one was statistically expected among these 

workers, who were occupationally exposed to uranium dust at airborne levels corresponding to a 

radioactivity concentration of 0.07 nCi/m3 (0.1 mg/m3

). However, the authors of this study suggest that 

this excess may be due to irradiation of the lymph nodes by thorium-230 (230Th) (Archer et al. 1973b). 

No changes in hematological parameters were observed in humans occupationally exposed to insoluble 

uranium dust at 0.5–10 mg U/m3 (Eisenbud and Quigley 1956). 

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URANIUM 89 

3. HEALTH EFFECTS 

Some intermediate-duration animal studies observed a range of hematological changes. Rats exposed to 

dusts of ammonium diuranate containing 6.8 mg U/m3 for 6 hours/day for 30 days showed a decrease of 

1 million in red blood cell counts and a loss of 4 g of hemoglobin/100 mL of blood (Dygert 1949b). It 

was not stated whether exposure was for 30 consecutive days or on weekdays only. Rats exposed to 

airborne uranyl nitrate hexahydrate containing 9.5 mg U/m3 for 8 hours/day, 5 days/week for 30 exposure 

days showed decreased numbers of erythrocytes and hemoglobin (measured at 24 hours postexposure and 

weekly thereafter) (Roberts 1949). Increased percentages of lymphoid cells and myeloblasts in bone 

marrow were reported at termination in rats exposed to airborne uranium peroxide containing 

15.4 mg U/m3 5 hours/day 5 days/week for 23 days (Dygert 1949d). A 4-week study in rats exposed to 

airborne uranium as uranium trioxide at a concentration corresponding to 16 mg U/m3 6 hours/day 

6 days/week reported similar findings (significant increases in myeloblasts and lymphoid cells of bone 

marrow) (Rothstein 1949c). Rabbits and rats exposed to airborne uranium at a level corresponding to a 

uranium concentration of 0.13 mg/m3 as uranyl nitrate hexahydrate for 30 days exhibited altered blood 

function as indicated by decreased fibrinogen during the final week of exposure (Roberts 1949). 

In contrast to the above findings, most other intermediate-duration animal inhalation studies with soluble 

and insoluble uranium compounds found no adverse effects on the blood. In intermediate-duration 

inhalation studies lasting 23–40 days, exposure to various uranium compounds at the following 

concentrations produced no harmful effects on hematological parameters: 22 mg U/m3 as high-grade 

carnotite uranium ore to rats; 2.8 mg U/m3 as uranium dioxide or triuranium octaoxide to dogs; 

22 mg U/m3 as uranium dioxide or triuranium octaoxide to rabbits; 11 mg U/m3 as uranium tetrachloride 

to rats; 2 mg U/m3 as uranium tetrachloride to rabbits; 1 mg U/m3 as uranium tetrachloride to dogs; 

13.2 mg U/m3 as uranium hexafluoride to rabbits and dogs; 0.1 mg U/m3 as uranium hexafluoride to dogs; 

14.5 mg U/m3 as triuranium octaoxide to mice; 14.5 mg U/m3 as uranium dioxide or triuranium octaoxide 

to rabbits; 14.5 mg U/m3 as triuranium octaoxide to guinea pigs and rabbits; 15.4 mg U/m3 as uranium 

peroxide to dogs, rabbits, and cats; or 4.8 mg/m3 as triuranium octaoxide to rats, mice, guinea pigs, and 

rabbits (Dygert 1949c, 1949d; Pozzani 1949; Rothermel 1949; Spiegl 1949). 

In other intermediate-duration studies, inhalation exposures to uranium dioxide dusts containing 

1 mg U/m3 for 30 weeks and 2 mg U/m3 for 26 weeks in rabbits and guinea pigs, respectively (Stokinger 

et al. 1953), 19.4 mg U/m3 for 5 weeks in mice, and 9.2 mg U/m3 for 5 weeks in dogs and rats had no 

adverse effects on hematological parameters (Rothstein 1949b). Similarly, exposures to 9.2 mg U/m3 for 

5 weeks to rats and dogs (Rothstein 1949a); 16 mg U/m3 for 4 weeks to rats, rabbits, cats, and dogs 

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URANIUM 90 

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(Rothstein 1949c); and 15 mg U/m3 as sodium diuranate to rats had no harmful effects on hematological 

parameters (Rothermel 1949). 

In chronic-duration exposures, dogs exposed to an airborne uranium concentration of 0.2 mg U/m3 as 

uranium hexafluoride for 1 year exhibited a lengthening in blood clotting time with a decrease in blood 

fibrinogen levels (Stokinger et al. 1953). However, hamsters exposed to airborne carnotite uranium ore 

dust containing 0.7 mg U/m3 for 16–27 months exhibited no adverse hematological effects (Cross et al. 

1981b). Similarly, no changes in hematological parameters were observed in rats, dogs, rabbits, and 

monkeys exposed to airborne uranium at concentrations ranging from 1 to 5.1 mg U/m3 for 1–5 years 

(Leach et al. 1970, 1973; Rothstein 1949b; Stokinger et al. 1953). 

Musculoskeletal Effects. No studies were located regarding the chemical or radiation effects of 

uranium on the musculoskeletal system in humans or animals following inhalation exposure for any 

duration. 

Hepatic Effects. No hepatic effects were found in a man accidentally exposed to powdered uranium 

tetrafluoride for 5 minutes (Lu and Zhao 1990). Air concentration and mean particle size of the powder 

were not determined. Serum hepatic enzyme levels and liver function tests were within normal limits 

from the time of the incident through a 3-year follow-up period. 

Data from the available studies provide equivocal evidence that exposure of animals to uranium has 

effects on the liver, although the etiology for this effect is not clear. Urinary catalase, a measure of 

hepatic injury, was significantly increased in rabbits exposed to 0.13 mg U/m3 8 hours/day, 5 days/week 

for 30 days (Roberts 1949). A slight decrease in hepatic lactate content was observed in rabbits following 

exposure to 15 mg U/m3 as sodium diuranate dust (Rothermel 1949). Rabbits exposed to 16 mg U/m3 as 

uranium trioxide dust for 4 weeks suffered moderate fatty livers in 63% of the animals that died 

(Rothstein 1949c). Focal necrosis of the liver was observed in rats exposed to 0.4 mg U/m3 as uranium 

tetrafluoride for 30 days (Dygert 1949a). In other studies, no changes were found in the liver 

morphology, histology, or function in the following animals: rabbits exposed to 0.15 or 2 mg U/m3 as 

uranyl nitrate hexahydrate for 26 weeks; rats exposed to 14.5 mg U/m3 as triuranium octaoxide dust for 

26 days; rats exposed to 16 mg U/m3 as uranium trioxide for 4 weeks; mice and guinea pigs exposed to 

3 mg U/m3 as high-grade uranium ore dust for 30 days; and rabbits exposed for 30 days to 22 mg U/m3 as 

high-grade uranium ore dust (contains uranium dioxide, triuranium octaoxide, and other potentially toxic 

contaminants) (Dygert 1949c; Pozzani 1949; Rothstein 1949c; Stokinger et al. 1953). 

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URANIUM 91 

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In chronic-duration exposure studies with animals, an unspecified strain of dogs exposed to ambient air 

concentrations of 0.05–0.2 mg U/m3 as uranium hexafluoride for 1 year exhibited increased and persistent 

bromosulfalein retention, indicative of impaired biliary function, at the 0.2 mg U/m3 concentration level 

(Stokinger et al. 1953). 

Renal Effects. Uranium has been identified as a nephrotoxic metal, exerting its toxic effect by 

chemical action mostly in the proximal tubules in humans and animals. However, it has been suggested 

that the renal damage from exposure to high-LET alpha-emitting heavy metals, such as uranium, may be 

the complementary effect of both the chemical toxicity and the radiotoxicity of these metals (Wrenn et al. 

1987). 

Several epidemiologic studies found no increased mortality in uranium workers due to renal disease 

(Archer et al. 1973a, 1973b; Checkoway et al. 1988; NIOSH 1987; Pinkerton et al. 2004; Polednak and 

Frome 1981). Also, case studies showed that workers accidentally exposed to high levels of uranium did 

not suffer renal damage, even up to 38 years postexposure (Eisenbud and Quigley 1956; Kathren and 

Moore 1986), although the tests for renal damage used in these studies were not very sensitive. A 

comparison of kidney tissue obtained at autopsy from seven uranium workers and six referents with no 

known exposure to uranium showed that the groups were indistinguishable by pathologists experienced in 

uranium-induced renal pathology (Russell et al. 1996). Three of seven workers and four of six referents 

were categorized as abnormal. Uranium levels in the workers kidney tissue (estimated by alpha particle 

emission) ranged from 0.4 to 249 μg/kg. As reviewed by Eisenbud and Quigley (1956), no evidence of 

renal toxicity was observed in workers exposed to insoluble uranium compounds; 100 workers were 

exposed to 0.5–2.5 mg U/m3 and another 50 workers were exposed to 2.5–10 mg U/m3

. Eisenbud and 

Quigley (1956) did not provide information on the parameters used to assess renal toxicity. A study on 

the kidney function of uranium mill workers chronically exposed to biologically soluble ammonium 

diuranate revealed renal tubular dysfunction as manifested by mild proteinuria, aminoaciduria, and a 

concentration-related clearance of β2-microglobulin relative to that of creatinine when compared to a 

referent group of cement workers. Air levels of uranium dioxide were not reported; the mean (and 

median) urinary uranium levels were 65.2 μg/L (20 μg/L) in 1975 and 7.2 μg/L (6 μg/L) in 1981 after a 

new facility was built. The incidence and severity of these nephrotoxic signs correlated with the length of 

time that the uranium workers had spent in the area where yellowcake was dried and packaged in the old 

mill (prior to mid-1979) (Thun et al. 1985), which is typically the second dustiest area of the uranium mill 

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URANIUM 92 

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following the ore crushing and grinding station. The data from this study are indicative of reduced 

reabsorption in the proximal renal tubules. 

Delayed renal effects were observed after a male worker at a uranium enrichment plant was accidentally 

exposed to a high concentration of uranium tetrafluoride powder for about 5 minutes in a closed room. 

While renal parameters were normal during an initial 30-day observation period, the patient showed signs 

of nephrotoxicity beginning at postaccident day 68 as indicated by significantly elevated levels of urinary 

proteins, nonprotein nitrogen (NPN), and amino acid nitrogen/creatinine, and decreased phenolsulfonpthalein excretion rate. These abnormalities persisted through day 1,065, but gradually returned to 

normal (Lu and Zhao 1990). The authors used uranium urinalysis data and a pharmacokinetic model 

(ICRP 1979) to estimate a kidney dose of 2.6 μg U/g kidney on postaccident day 1. 

Renal effects were not observed in another accidental exposure (USNRC 1990) in which 24 of 31 initially 

exposed workers were followed for 2 years. Estimated airborne concentrations were 20 mg uranium 

hexafluoride/m3 for a 1-minute exposure and 120 mg uranium hexafluoride/m3 for a 60-minute exposure 

(15.2 and 91 mg U/m3

, respectively) (USNRC 1986). Initial intakes of workers involved in the accident 

were estimated from uranium excretion data and ranged from 470 to 24,000 μg uranium. Maximum 

uranium concentrations in the kidney were estimated by a kinetic model to be 0.048–2.5 μg U/g kidney 

tissue (Fisher et al. 1991). 

The pathogenesis of the kidney damage in animals indicates that regeneration of the tubular epithelium 

occurs upon discontinuation of exposure to uranium (Bentley et al. 1985; Dygert 1949b; Maynard and 

Hodge 1949; Pozzani 1949; Rothermel 1949; Rothstein 1949b, 1949c; Spiegl 1949; Stokinger et al. 

1953). The magnitude of uranium intake that causes kidney damage depends on the type of uranium 

compound to which the animal has been exposed, appearing to depend on its solubility and oxidation 

state. For example, in dogs and monkeys, exposure to 5 mg U/m3 as uranium dioxide (insoluble) dust for 

up to 5 years produced no damage to the kidneys, even 6.5 years after the exposure ceased (Leach et al. 

1970, 1973). Similarly, rats and guinea pigs were exposed to ≤10 mg U/m3 as uranium dioxide for 1 year 

without noticeable kidney pathology (Stokinger et al. 1953). Uranium dioxide is relatively insoluble in 

water and is retained in the lungs longer than the other more soluble uranium compounds (uranium 

tetrafluoride, uranyl fluoride, uranium tetrachloride, uranium peroxide, uranyl acetate, and uranyl nitrate 

hexahydrate), thereby causing higher toxicity to the lungs and lower toxicity to distal organs such as the 

kidney. In contrast, relatively soluble uranium compounds have been shown to cause renal tubular 

damage in dogs, guinea pigs, rabbits, and rats (Leach et al. 1984; Morrow et al. 1982a; Roberts 1949; 

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URANIUM 93 

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Stokinger et al. 1953). Apparently, the difference in effect is due to the extent of absorption of uranium 

deposited in the lungs and, thus, the fraction that eventually gets into the blood. Differences in species 

susceptibility have also been suggested to be an additional factor. 

Renal effects can be produced in animals after acute-duration inhalation exposures to uranium. A 

10-minute exposure to 637 mg U/m3 as uranium hexafluoride produced severe degeneration of the 

cortical tubules 5–8 days later in rats (Spiegl 1949). These same effects were observed in dogs 1–3 days 

after a 1-hour exposure to 250 mg U/m3 as uranyl fluoride (Morrow et al. 1982a). Proteinuria and 

glucosuria were also observed in rats after 2–10-minute exposures to uranium hexafluoride (Leach et al. 

1984). 

In intermediate-duration studies with guinea pigs, mice, rats, cats, rabbits, and dogs, inhalation exposures 

to a variety of uranium compounds were damaging to the kidneys. The effects were compound- and 

concentration-dependent and ranged from minimal microscopic lesions in tubular epithelium, increased 

urinary catalase, decreased diodrast (iodopyracet) clearance, and transient increased bromosulfalein 

retention (for low concentrations) to severe necrosis of the tubular epithelium (for high concentrations) in 

several species (Dygert 1949a, 1949b, 1949c; Pozzani 1949; Roberts 1949; Rothermel 1949; Rothstein 

1949a, 1949c; Spiegl 1949; Stokinger et al. 1953). Soluble uranium compounds were more toxic, as 

evidenced by much lower LOAEL values, than the insoluble compounds. In an intermediate-duration 

inhalation exposure study, mice were exposed to uranium tetrachloride dust at ambient air concentrations 

of 0.1, 2.1, or 11 mg U/m3 for 3–7 hours/day 6 days/week for approximately 30 days. The exposure 

resulted in severe degeneration and necrosis of the renal-cortical tubular epithelium, as well as mortality, 

in the 11 mg U/m3 group by the third day. At the end of the study, moderate tubular degeneration was 

observed in the 2.1 mg U/m3 group and minimal degeneration was noted in the 0.1 mg U/m3 group 

(Rothermel 1949). In another intermediate-duration study, rats suffered renal injury (of inconsistent 

severity), which became apparent on or about the 7th day and pronounced by the 25th or 26th day, 

following inhalation exposure to uranyl nitrate hexahydrate at 0.13, 0.2, 0.9, 2.1, or 9.5 mg U/m3 daily for 

8 hours/day, 5 days/week for 30 days. At 0.9 mg U/m3

, the rats showed significant degenerative changes 

only in the renal tubules and no changes to the glomeruli. Rats exposed to 0.2 mg U/m3 exhibited only 

slight damage to the tubular epithelium of the kidneys. At 0.13 mg U/m3

, slight renal tubular 

degeneration was observed in one of the three animals sacrificed after 28 days of exposure. Except for 

the group receiving no dietary supplement, no significant difference in blood CO2 values was seen at 

14 days of exposure to uranium. Thirty days after the start of exposure, all groups exhibited increased 

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URANIUM 94 

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blood NPN levels over 14-day values (maximum 111 mg/mL blood for the unsupplemented diet group). 

No clinical signs of toxicity were observed at any concentration level (Roberts 1949). 

Dogs (of both sexes) exposed to 0.13 mg U/m3 as uranyl nitrate hexahydrate showed mild inner cortex 

changes after 10 days of exposure. The dogs were given full-body exposures to aerosols with an AMAD 

assumed to be 1.5–2.1 μm; the average was 1.8 μm (Pozzani 1949). Severe nephritis masked any damage 

from uranium in one dog sacrificed after 10 days of exposure. The dogs showed a transient elevation in 

protein excretion between days 9 and 12 of exposure. Increased bromosulfalein retention was observed 

during the second and fourth weeks of exposure. No alterations to blood NPN or total blood CO2 were 

observed. Chloride clearance values, which were initially elevated and then became depressed in 

one dog, returned to normal 37 days after the beginning of exposure. Catalase and protein excretion 

increased significantly, but returned to normal at the end of exposure. No significant changes in diodrast 

clearance, inulin clearance, or blood NPN levels were observed. Dogs exposed to 0.9 mg U/m3 exhibited 

mild inner cortex and medullary ray degeneration and necrosis with moderate epithelial regeneration. 

Two of the four animals showed a steady rise in NPN from the beginning of the experiment until they 

were sacrificed 12 days later, at which time NPN values were 252 and 356 mg%, respectively. Urinary 

protein in the dogs significantly increased between the 5th and 24th days. The dogs showed a decrease in 

inulin clearance during the third week of exposure, with a return toward normal values during the fifth 

week. There was decreased diodrast clearance throughout the observation period, indicating a severe 

reduction of the excretory capability for diodrast after 1 week (one dog showed a decrease of 69%). 

Diodrast clearances returned to normal by days 35–37. Two dogs showed a transient decrease in inulin 

clearance during the third week, lasting until the fifth week. All four dogs showed a drop in total blood 

CO2, attaining a minimum value between the first and seventh days. The minimum value was generally 

less than half that of controls, indicating severe acidosis. Glucose tolerance was significantly decreased. 

Large quantities of protein (400–800 mg%) and sugar were excreted. The greatest excretion occurred 

during the first 6 days of exposure and decreased thereafter. There was also a decrease in urinary 

creatinine excretion during the exposure. At the 2 mg U/m3 exposure level, the dogs did not show highly 

elevated NPN and BUN values during exposure. There were no increases in blood NPN or BUN. All 

dogs exposed to 9.5 mg U/m3 had severe renal tubular damage. Four dogs showed renal injury followed 

by repair when they were sacrificed at the end of the exposure (Roberts 1949). 

No treatment-related renal effects were seen in other studies when animals were exposed to uranium 

compounds by inhalation at concentrations as high as 10 mg U/m3 (as uranium dioxide) in guinea pigs for 

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URANIUM 95 

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28 weeks, 2 mg U/m3 (as uranyl nitrate hexahydrate) in guinea pigs for 26 weeks, and 16 mg U/m3 (as 

uranyl nitrate hexahydrate) in rats for 4 weeks (Rothstein 1949c; Stokinger et al. 1953). 

The nephrotoxic effects of uranium in animals may also include damage to the glomerulus as evidenced 

by histopathological signs in the kidneys of rats and rabbits exposed to 15.4 mg U/m3 as uranium dioxide 

for 23 days (Dygert 1949d) and of dogs exposed to 15 mg U/m3 as uranyl fluoride for 5 weeks 

(Rothermel 1949) and to 16 mg U/m3 as uranium trioxide for 4 weeks (Rothstein 1949c). 

In chronic-duration inhalation studies with rats and dogs, uranium (as uranium tetrachloride, uranium 

tetrafluoride, uranyl nitrate hexahydrate, or uranium dioxide) exposures as low as 0.05 mg U/m3 and as 

high as 10 mg U/m3 for 1–5 years were damaging to the kidneys. Nephrotoxic effects found in these 

animals ranged from minimal microscopic lesions in tubular epithelium (for low concentrations) to acute 

tubular necrosis (for high concentrations) (Leach et al. 1970; Stokinger et al. 1953). In one of these 

chronic-duration studies, dogs were exposed to ambient air concentrations of 0.05 or 0.2 mg U/m3 as 

uranium hexafluoride for 1 year for a total of 1,680 exposure hours. The UF6 was rapidly hydrolyzed to 

HF gas and UO2F2 fumes, whose AMAD was 0.1 μm. After 10 days in the study, there was evidence of 

mild tubular injury, which was characterized by desquamation of the epithelium and active regeneration 

in the proximal convoluted tubule in the inner cortex of the kidneys in 86% of animals exposed to 

0.2 mg U/m3

. From the 16th week to the end of the study, regeneration of the tubular epithelium was 

almost complete, with a few flattened atrophic tubules in the inner zone of the cortex. These mild 

nephrotoxic effects were also observed in 12% of the 0.05 mg U/m3 exposed animals. Blood NPN levels 

were normal (elevated blood NPN levels indicate a decrease in renal filtration capacity, similarly to 

elevated BUN). Observed changes in urinary protein were inconsistent and insignificant (Stokinger et al. 

1953). 

In another study, dogs of both sexes (9–12 males, 9–13 females) were exposed to concentrations of 0.04, 

0.15, 0.25, or 2 mg U/m3 as uranyl nitrate for 6 hours/day, 5.5 days/week for 1 year. The AMAD of the 

aerosols was given as 2–5 μm. At the termination of the study, histological and biochemical 

examinations revealed minimal microscopic lesions in the renal tubules and transient increases in blood 

NPN in the 0.25 mg U/m3 concentration-level dogs. Transient increases in blood NPN were also 

observed at higher concentration levels. There were transient decreases in plasma CO2, although liver 

function was normal. No significant weight loss was observed in the dogs (Stokinger et al. 1953). 

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URANIUM 96 

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No treatment-related renal effects were seen when Rhesus monkeys and dogs were exposed to uranium 

dioxide by inhalation at airborne concentrations as high as 5.1 mg U/m3 for 1–5 years (Leach et al. 1973). 

Blood NPN levels were consistently elevated in Rhesus monkeys, although no renal histopathology was 

evident (Leach et al. 1973). 

Endocrine Effects. A single study was found that reported on possible effects of uranium on the 

endocrine system. In this study, no histopathology was seen in the endocrine organs (adrenal, pancreas) 

in rats exposed to 0.2 mg U/m3 as uranium tetrachloride for 1 year (Stokinger et al. 1953). 

Dermal Effects. No dermal effects were found in a man accidentally exposed to powdered uranium 

tetrafluoride for 5 minutes (Lu and Zhao 1990). Histopathologic examination of the skin was normal in 

rats exposed to 0.2 mg U/m3 as uranium tetrachloride for 1 year (Stokinger et al. 1953). 

Ocular Effects. Chemical burns to the eyes were reported in humans after accidental exposure to 

uranium hexafluoride (Kathren and Moore 1986). Conjunctivitis and eye irritation have also been 

reported in animals after exposure to uranium hexafluoride (Spiegl 1949) and uranium tetrachloride 

(Dygert 1949a). Ocular effects were due to direct contact of the eye with vapor or aerosols; because 

uranyl fluoride and hydrogen fluoride (a highly irritating chemical) are produced when uranium 

hexafluoride comes in contact with moisture, it is possible that uranium was not the causative agent for 

the ocular effects. 

Body Weight Effects. In general, inhalation of insoluble uranium compounds did not significantly 

affect body weight in animals. Decreased body weight was observed with the more water-soluble 

compounds. A 30% decrease in body weight was reported for rabbits exposed to 11 mg U/m3 as uranium 

tetrachloride dust for 35–40 days. Mice and guinea pigs experienced unspecified weight loss and 13% 

weight loss, respectively, following exposure to 13 mg U/m3 as uranium hexafluoride for 30 days. 

Rabbits suffered 12% weight loss following exposure to 0.2 mg U/m3 as airborne uranium hexafluoride 

for 30 days (Spiegl 1949). Mild to severe weight loss was observed in several species during exposure to 

uranyl nitrate hexahydrate (Roberts 1949). Rabbits lost 22% of their body weight during a 30-day 

exposure to 0.9 mg U/m3

, dogs and cats lost approximately 25% of their body weight during a similar 

exposure to 9.5 mg U/m3

. Similar effects were observed with uranium tetrafluoride (Dygert 1949a). 

Rabbits, rat, cats, and dogs all experienced a greater than 20% weight loss during 30 days exposure to 

18 mg U/m3

. 

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URANIUM 97 

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Several intermediate-duration animal inhalation studies with soluble and insoluble uranium compounds 

found no significant adverse effects on body weight. In short-term intermediate-duration studies lasting 

23–40 days, exposure to concentrations at the following levels were without significant effects on body 

weight: 22 mg U/m3 as high-grade or carnotite uranium ore to rats, 2.9 mg U/m3 as uranium dioxide or 

triuranium octaoxide to dogs, 22 mg U/m3 as uranium dioxide or triuranium octaoxide to rabbits, 

11 mg U/m3 as uranium tetrachloride to rats, 2.1 mg U/m3 as uranium tetrachloride to rabbits, 

1.1 mg U/m3 as uranium tetrachloride to dogs, 13 mg U/m3 as uranium hexafluoride to rabbits and dogs, 

0.2 mg U/m3 as uranium hexafluoride to dogs and guinea pigs, 14.5 mg U/m3 as triuranium octaoxide to 

mice, and 4.8 mg U/m3 as triuranium octaoxide to guinea pigs and rabbits (Dygert 1949c; Spiegl 1949); 

15 mg U/m3 as uranium peroxide to cats and rabbits (Dygert 1949d); 15 mg U/m3 as carnotite ore (mostly 

uranium dioxide, triuranium octaoxide) to dogs or 22 mg U/m3 as carnotite ore to rabbits for 30 days 

(Pozzani 1949); and 1 mg U/m3 for 30 weeks to rabbits or 2 mg U/m3 for 26 weeks to rabbits and guinea 

pigs (Stokinger et al. 1953). Exposures of rats to 13 mg U/m3 or of rabbits to 0.1 mg U/m3 as uranium 

hexafluoride for 30 days also were without harmful effects (Spiegl 1949). 

No effects on body weight were observed after several intermediate-duration dosing studies that lasted 4– 

5 weeks. These studies researched exposures by the inhalation route as follows: 16 mg U/m3 as uranium 

trioxide to rats, rabbits, dogs, and cats; 19 mg U/m3 as uranium dioxide to mice; 16 mg U/m3 as uranium 

dioxide to guinea pigs; 9.2 mg U/m3 as uranyl fluoride to dogs and rabbits; 2.2 mg U/m3 as uranyl 

fluoride to rats; 9.2 mg U/m3 as uranium dioxide to dogs; 19.2 mg U/m3 as uranium dioxide to rabbits; 

15 mg U/m3 as sodium diuranate to rats and dogs; and 12 mg U/m3 as ammonium diuranate to rats for 

30 days (8 hours/day, 5 days/week for 6 weeks) (Rothermel 1949; Rothstein 1949a, 1949b, 1949c; 

Stokinger et al. 1953). Hamsters exposed to 0.8 mg U/m3 as carnotite uranium ore by inhalation for 16– 

27 months also exhibited no adverse body weight effects (Cross et al. 1981b). Similarly, no changes in 

body weight were observed in rats, dogs, rabbits, and monkeys exposed to airborne uranium dioxide at 

0.1–5 mg U/m3 for 1–5 years (Leach et al. 1970, 1973; Stokinger et al. 1953). 

In chronic-duration studies, exposure of monkeys to concentrations of 3 mg U/m3 as uranium dioxide for 

5 years produced no significant body weight changes (Leach et al. 1970). 

Other Systemic Effects. Several general effects have been attributed to uranium inhalation 

exposure. In animal studies, dogs exposed to 13 mg U/m3 as uranium hexafluoride for 30 days exhibited 

decreased water intake (Spiegl 1949). Reduced food intake was also observed in a 4-week study of rats 

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URANIUM 98 

3. HEALTH EFFECTS 

and mice exposed to 16 mg U/m3 as uranium trioxide (Rothstein 1949c) and in a 5-week study of rats and 

mice exposed to 15 mg U/m3 as sodium diuranate for 6 hours/day, 5.5 days/week (Rothermel 1949). 

3.2.1.3 Immunological and Lymphoreticular Effects 

Although no studies were located that specifically tested immunological effects in humans following 

inhalation exposure to uranium, none of the epidemiologic studies of workers in uranium mines and fuel 

fabrication plants showed increased incidence of death due to diseases of the immune system (Checkoway 

et al. 1988; Keane and Polednak 1983; NIOSH 1987; Polednak and Frome 1981). 

Human studies that assessed damage to cellular immune components following inhalation exposure to 

uranium found no clear evidence of an immunotoxic potential for uranium. No association was found 

between the uranium exposure and the development of abnormal leukocytes in workers employed for 12– 

18 years at a nuclear fuels production facility (Cragle et al. 1988). Increases in the number of fatal 

malignant disease of the lymphatic and hematopoietic tissue reported among uranium mill workers may 

have been caused by other carcinogens in the work environment such as 230Th. The study investigators 

estimated that the workers were exposed to 8–5,100 mg/m3 (median 110 mg/m3

) uranium mill dust, which 

contains 230Th as a natural component (Archer et al. 1973b). 

In animal studies, rats exposed to dusts of ammonium diuranate containing 6.8 mg U/m3 for 6 hours/day, 

5 days/week for 30 days developed a rise in neutrophils, a decrease in lymphocytes, a moderate fall in the 

white blood cell count, and a rise in the number of eosinophils (Dygert 1949b). Rats exposed to airborne 

uranyl nitrate hexahydrate containing 9.5 mg U/m3 8 hours/day, 5 days/week for 30 exposure days 

showed an initial increase and a subsequent decrease in the absolute number of lymphocytes and 

neutrophils (Roberts 1949). Focal necrosis of the spleen and edematous cecal lymph nodes were 

observed in some rats exposed for 30 days for 6 hours/day to 0.4 and 4 mg U/m3 uranium tetrafluoride 

(Dygert 1949a). However, these effects were not observed at 18 mg U/m3

, so the significance of this 

finding is unclear. 

No histopathological changes or accumulation of uranium were evident in the spleens of 110 dogs and 

25 monkeys exposed to uranium dioxide dusts (5 mg U/m3

) for 6 hours/day, 5 days/week for 1–5 years 

and then monitored for up to 6.5 more years. Similar results were seen for rats similarly exposed for 

1 year (Leach et al. 1970, 1973). Rats, rabbits, guinea pigs, and dogs exposed to dusts of various uranium 

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URANIUM 99 

3. HEALTH EFFECTS 

compounds for 7–12 months showed no significant histological changes in the lymph nodes and marrow 

(Stokinger et al. 1953). 

There is some evidence from animal studies that exposure to ≥90% enriched uranium may affect the 

immune system. Increased macrophage activity, associated with localized alpha tracks in all five lobes of 

the lungs, was seen in F344 rats exposed to 6,825.5 nCi/m3 through inhalation exposure to enriched 

uranium dioxide for 100 minutes (Morris et al. 1992). The radioactive material concentration of the 

mixture was estimated as 1.91 kBq/mg (51.6 nCi/mg); the degree of enrichment was calculated based on 

this specific activity. The increased activity was evident from days 1–7, 180, 360, 540, and 720 with 

increases in percent activity of 0.44, 2.15, 19.70, 6.54, and 37.84, respectively. The number and size of 

macrophage clusters in the lung increased with time postexposure. 

Albino HMT (F344) male rats were exposed to 92.8% enriched uranium dioxide with a concentration 

ranging from 2,274.2 nCi/m3 (84.1 kBq/m3

) to 5,458 nCi/m3 (202 kBq/m3). Increases in the sizes and 

numbers of lung macrophages, with a significant increase in the size of lysosomal granules within the 

macrophages, were reported 8 days postexposure (Morris et al. 1989). 

Dogs exposed to airborne uranium dioxide concentrations of 5.1 mg/m3 for 1–5 years showed lymph node 

fibrosis in the lungs. Rhesus monkeys similarly exposed for 5 years showed fibrotic changes in the 

tracheobronchial lymph nodes. The investigators of these studies concluded that although these effects 

could not be extrapolated to humans because of the absence of squamous cell carcinomas in the lungs, the 

changes were suggestive of radiation injury (Leach et al. 1973). However, the morphological changes 

observed in these studies were similar to observations in humans and animals as a result of exposure to 

diverse inorganic dust (Dockery et al. 1993). 

The highest NOAEL values and all reliable LOAEL values in each species and duration category for 

immunological effects from chemical exposures by the inhalation route to uranium are presented in 

Table 3-1 and plotted in Figure 3-1. 

3.2.1.4 Neurological Effects 

Uranium has not been shown to cause damage to the nervous system of humans by metallotoxic or 

radiotoxic action following inhalation exposures for any duration. Although no studies were located that 

specifically tested neurological effects in animals following inhalation exposure to uranium, none of the 

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URANIUM 100 

3. HEALTH EFFECTS 

available studies reported any neurological deficits, such as narcosis, ataxia, or cholinergic signs. Clinical 

signs in humans following acute exposure to enriched uranium included dizziness and anorexia in one 

man 6 days after being exposed for 5 minutes to uranium tetrafluoride by inhalation (Lu and Zhao 1990), 

but did not include neurological effects in others similarly exposed to uranium hexafluoride (Kathren and 

Moore 1986; USNRC 1986). Some of the victims were evaluated for as long as 38 years after exposure 

(Kathren and Moore 1986). In longer-term exposures, epidemiologic studies found no increase in deaths 

from brain tumors or other neurological diseases that could be attributed to uranium in workers at 

uranium-processing plants (Carpenter et al. 1988; Cragle et al. 1988; NIOSH 1987; Polednak and Frome 

1981; Reyes et al. 1984). The autopsy reports also did not reveal any other structural pathology of the 

central nervous system. In a retrospective study, more deaths than expected were found from central and 

peripheral nervous system diseases (SMR=2.98) in employees in a nuclear fuels fabrication plant. 

However, the employees were also concurrently exposed to other radiological and chemical agents. The 

investigators of this study concluded that there was no etiology associated with uranium for the central 

nervous system and peripheral nervous system diseases (Hadjimichael et al. 1983). 

In intermediate-duration animal studies, neurological signs were observed in dogs and cats following 

inhalation exposure to uranium. On the 13th day of a 30-day study, dogs exposed to 0.5, 3, 4, or 

18 mg U/m3 as uranium hexafluoride gas by inhalation exhibited muscular weakness followed by 

instability of gait indicative of neurological dysfunction at the highest concentration tested (Dygert 

1949a). Anorexia observed in of dogs exposed 8 hours/day, 5 days/week for 30 days to 9.5 mg U/m3 as 

uranyl nitrate hexahydrate may also have had its origin in neurological dysfunction (Roberts 1949). 

Similarly, cats exposed to 18 mg U/m3 as uranium tetrafluoride exhibited unsteady gait on the seventh 

day in a 30-day study (Dygert 1949a). In 5-week studies (8 hours/day, 5 days/week), dogs and cats 

exposed to 0.15, 2.2, or 9.2 mg U/m3 as uranyl fluoride suffered anorexia, severe muscle weakness, and 

lassitude at the highest concentration tested (Rothstein 1949a). These neurological effects were observed 

in animals exposed to lethal concentrations. 

In 12 rats exposed to 190 mg U/m3 as depleted uranium dioxide 30 minutes/day, 4 days/week for 3 weeks, 

a significant increase in spontaneous activity (both locomotor and rearing behaviors) was observed on day 

1 postexposure, but not on day 5 postexposure (Monleau et al. 2005). This appeared to correlate with a 

rapid reduction in uranium concentration in the hippocampus, frontal cortex, cerebellum, and olfactory 

bulb; with the exception of the hippocampus, brain uranium levels reached control levels by the 3rd 

postexposure day. A depression of spatial working memory was also observed on day 6 postexposure, 

but not on day 1 postexposure; no alterations in exploratory activity were observed. 

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URANIUM 101 

3. HEALTH EFFECTS 

The highest NOAEL values and all reliable LOAEL values in each species and duration category for 

neurological effects by the inhalation route to uranium are presented in Table 3-1 and plotted in 

Figure 3-1. 

3.2.1.5 Reproductive Effects 

It is unlikely that inhalation of uranium produces a significant effect on reproductive health. Studies of 

one human population group (miners) were located that identified a reproductive effect associated with 

the inhalation exposure of mine air, but the association with uranium compounds was unclear, and the 

other miner studies observed no reproductive effects. 

Three studies of one mining population were located that equivocally associated reproductive effects in 

humans following inhalation exposure to uranium. The studies reported that male uranium miners were 

found to have more first-born female children than expected (Muller et al. 1967; Waxweiler et al. 1981b; 

Wiese and Skipper 1986). In addition, it is not certain if the effect described is from exposure to uranium 

because the workers were also exposed to 222Rn, chlorine, hydrofluoric acid, lead sulfate, nickel, nitric 

acid and nitrogen oxides, silicon dioxide, and sulfuric acid (Dupree et al. 1987). 

No animal studies were located that described reproductive effects following inhalation exposure to 

uranium for any duration of exposure. 

3.2.1.6 Developmental Effects 

No studies were located that specifically reported effects of uranium on development in humans or 

animals following inhalation exposures for any duration. However, the issue of teratogenicity of depleted 

uranium aerosols in humans was reviewed by Hindin et al. (2005). The investigators examined a series of 

reports that included groups of Gulf War veterans from the United States, the United Kingdom, Canada, 

and Australia; reports from Iraqi hospitals and clinics during and after the war; reports of birth defects in a 

New Mexico community living near a depleted uranium weapons testing facility; reports of birth defects 

in infants born in Bosnia and Herzegovina after the Bosnia War or in Kuwait after the Gulf War; and 

other reports. Most of the data from these reports have not been published in peer-reviewed journals; 

some have been published in newspapers or presented at Iraqi conferences. Lacking from all reports was 

documentation of individual depleted uranium exposure and other wartime-generated substances, as well 

as nutritional and environmental factors. Some reports lacked methodologically rigorous investigation, 

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URANIUM 102 

3. HEALTH EFFECTS 

while in others, the incidences of birth defects between purportedly exposed and nonexposed groups were 

not statistically significant. Of particular interest is a report from three major maternity hospitals in 

Basra, Iraq, which noted a dramatic increase in the incidence of total congenital malformations since the 

1991 war. However, Hindin et al. (2005) note that very low incidence reported prewar often reached 

baseline Western levels by 1999–2000. Of note is the case of hydrocephalus, which the report of data 

through 2000 indicates no diagnosed cases of hydrocephalus between 1990 and 1998. This would mean 

that there were no cases of hydrocephalus among about 100,000 births, which was considered 

implausible. Hindin et al. (2005) raised the question of whether the detection of birth defects at the Basra 

study was less than complete, and if so, whether the omissions could have been systematic or random. In 

studies of Gulf War veterans, comparisons were made between deployed versus non-deployed, not 

necessarily between depleted uranium-exposed and non-depleted uranium-exposed; as such, the studies 

are not very informative regarding the potential role of depleted uranium in inducing congenital 

malformations. Hindin et al. (2005) concluded that, overall, the epidemiological evidence is consistent 

with increased risk of birth defects in offspring from persons exposed to depleted uranium. However, 

given the limitations of the data described by the reviewers and confounders that were not addressed, the 

conclusion regarding birth defects may have overlooked other causes for the increase and overstated the 

data. 

Similarly, Busby et al. (2010) examined the incidence of infant mortality and alterations in sex ratio in 

children living in Fallujah, Iraq using data collected from questionnaires completed by 711 households 

with 4,843 persons. An 18% reduction in male:female ratio from the expected ratio (1,055 boys to 

1,000 girls) was found among children aged 0–4 years. In older children, the ratio was close to the 

expected level. An infant mortality (deaths between 0 and 1 year of age) ratio of 80 deaths per 1,000 was 

estimated. The authors state that this is significantly higher than infant mortality ratios in Egypt, Jordan, 

and Kuwait. However, the investigators did not evaluate the potential exposure for depleted uranium or 

have a comparable reference group (i.e., Iraqi households without the potential for exposure to depleted 

uranium); additionally, the investigators did not provide demographic data to support using infant 

mortality data from Egypt, Jordan, and Kuwait as an appropriate reference. The limitations of this study 

preclude using it to establish a causal relationship between exposure to depleted uranium and 

developmental toxicity. 

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3. HEALTH EFFECTS 

3.2.1.7 Cancer 

Human and animal studies have examined the potential carcinogenicity of uranium. Because uranium 

emits predominantly high-LET alpha particles, current theories on gene mutation and apoptotic 

mechanisms of cancer promotion by high-LET alpha radiation suggest a concern for carcinogenesis from 

uranium’s radioactivity (BEIR 1980, 1988, 1990; Otake and Schull 1984; Sanders 1986; UNSCEAR 

1982, 1986, 1988) (see Appendix D for a review of the hazards associated with radionuclide exposure). 

As discussed below, some studies have found significant increases in the risk of lung cancer, although it 

is not clear whether uranium is the causative agent and whether the cancer is due to chemical toxicity or 

radiotoxicity. In general, human and animal studies have not found increases in the risk of cancer in other 

tissues, including the kidney and bone. 

Increased deaths from cancers of the respiratory tract (predominantly lung cancer) have been reported in 

numerous studies of uranium miners (Archer et al. 1973a; Auerbach et al. 1978; Band et al. 1982; Boice 

et al. 2008; Chovil and Chir 1981; Gottlieb and Husen 1982; Grace et al. 1980; Hornung and Meinhardt 

1987; Hornung et al. 1998; Howe and Stager 1996; Howe et al. 1986, 1987; Kusiak et al. 1993; Lundin et 

al. 1969; Moolgavkar et al. 1993; Saccomanno et al. 1971, 1976, 1986, 1988, 1996; Samet et al. 1984a, 

1984b, 1986, 1989, 1991, 1994; Ševc et al. 1993; Tirmarche et al. 1992, 1993; Tomášek et al. 2008; 

Waxweiler et al. 1981a; Whittemore and McMillan 1983; Woodward et al. 1991). However, the miners 

were exposed to cancer-inducing agents such as radon and its decay products, silica and other dusts, and 

diesel engine exhaust fumes. It is generally understood that increased lung cancer in uranium miners is 

attributable to exposure to radon and smoking habits rather than exposure to uranium (refer to the ATSDR 

Toxicological Profile for Radon [Agency for Toxic Substances and Disease Registry 2008] for detailed 

discussion of associations between exposure to radon and cancer). 

Mortality has also been assessed in uranium mill workers without reported employment in uranium 

mining operations. A study of 662 male uranium mill workers employed at one of six uranium mills in 

the Colorado Plateau states (Colorado, Utah, New Mexico, Arizona) found a significant increase in death 

from tumors of the lymphatic and hematopoietic tissue (other than leukemia) during the period of 1950– 

1967 (4 observed vs. 1.02 expected; SMR 392; 95% CI not reported); the study authors noted that none of 

the four men worked near the fusion furnaces where exposure to concentrated uranium dust or fume was 

greatest (Archer et al. 1973b). Waxweiler et al. (1983) performed a study that included 2,002 uranium 

millers employed at one of seven uranium mills in the Colorado Plateau states for at least 1 year after 

January 1, 1940; a nonsignificant excess of deaths from lymphatic malignancies other than leukemia 

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URANIUM 104 

3. HEALTH EFFECTS 

(7 deaths vs. 5.6 expected) was reported for the period through 1977. Pinkerton et al. (2004) reevaluated 

the cohort described by Waxweiler et al. (1983) and determined that a total of 1,485 men fit the criteria 

for inclusion. Nonsignificant excesses of mortality from lymphatic and hematopoietic malignancies other 

than leukemia (16 observed vs. 11.08 expected; SMR 1.44; 95% CI 0.83–2.35) and from respiratory 

cancers that included trachea, bronchus, and lung (78 observed vs. 68.93 expected; SMR 1.13; 95% CI 

0.89–1.41) were reported through 1998. Mortality from these diseases did not increase with length of 

employment, and mortality from lung cancer was higher among workers hired prior to 1955 when 

exposures to uranium, silica, and vanadium were presumably higher. Interpretation of the results of these 

studies of uranium mill workers is limited due to relatively small cohort sizes, inability to estimate 

individual exposures, and lack of smoking data. 

Boice et al. (2008) conducted a cohort mortality study of workers engaged in uranium mining and milling 

activities near Grants, New Mexico between 1955 and 1990. Vital status was determined through 2004 

and SMRs were calculated for 2,745 workers (2,500 males, 245 females) alive after 1978 who were 

employed for at least 6 months. No significant increases in cancer mortality were observed in 

904 uranium milling workers who were not known to have worked at a mine or 106 workers whose 

mining experience was not known. Based on national mortality rates, mortality from respiratory cancers 

(bronchus, trachea, lung) was significantly higher than expected among the uranium mining and milling 

workers known to have been employed in an underground uranium mine (n=1,735) (SMR 2.17; 95% CI 

1.75–2.65). Therefore, the observed increased cancer mortality was considered attributable to historically 

high levels of radon in the mines combined with heavy use of tobacco products. Deaths from other types 

of cancer were not significantly increased in the whole cohort or either subcohort. 

Cancer mortality has been assessed in studies of populations living near uranium mining and milling 

facilities in Uravan, Colorado (Boice et al. 2007a), Montrose County, Colorado (Boice et al. 2007b), 

Karnes County, Texas (Boice et al. 2008), and Grants, New Mexico (Boice et al. 2010). Compared to 

U.S. mortality rates, no significant increase in mortality from cancers was observed among the residents 

of Uravan, Colorado, or among 622 of the residents who had been employed in uranium mills. A 

significant increase in lung cancer (SMR 2.00; 95% CI 1.39–2.78) was found among 459 residents who 

had worked in underground uranium mines and was attributed to historically high levels of radon in the 

mines coupled with heavy use of tobacco products. Similarly, increased mortality from lung cancer was 

noted in males living in Montrose County, Colorado, and Grants, New Mexico, but not in females. 

Occupational exposure to radon and smoking among underground uranium mine workers was considered 

to be the cause of the increased mortality from lung cancer within the population of male residents. The 

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URANIUM 105 

3. HEALTH EFFECTS 

female population of Grants, New Mexico exhibited a significant excess of mortality from stomach 

cancer (SMR 1.30; 95% CI 1.03–1.63), which declined over the 55-year observation period; the stomach 

cancer increase was highest before the uranium mining and milling operations began and then decreased 

to normal levels, indicating that these operations were not the source of the increased mortality from 

stomach cancer. No unusual patterns of cancer mortality were observed in residents of Karnes County, 

Texas from 1950 to 2001 (Boice et al. 2003). 

The issue of cancer risk in nuclear workers occupationally exposed to uranium has recently been 

reviewed by Canu et al. (2008). The authors reviewed 23 epidemiological studies: 18 cohort studies and 

5 nested case-control studies published since 1980. The overall conclusion was that the epidemiological 

studies provide limited evidence of a relationship between site-specific cancer mortality and internal 

exposure to uranium and mixed fission products. The authors identified three main limitations common 

to almost all studies: limited statistical power, relatively low radiation doses, and inaccurate exposure 

assessment. 

Busby et al. (2010) examined the relative risk of cancer among residents living in Fallujah, Iraq between 

2005 and 2010; data were collected from questionnaire completed by 711 households with 4,843 persons. 

As compared to cancer rates from Egypt in 1999, significant increases in the risk of several cancers, 

including childhood cancers, breast cancer, leukemia, lymphoma, and brain cancer, were observed. As 

with the developmental toxicity portion of this study, the investigators did not provide uranium exposure 

level or support for the assumption that the residents were exposed to uranium. Additionally, the study 

did not involve a comparison between cancer incidences in Fallujah with other Iraqi populations not 

exposed to uranium. These limitations preclude establishing a causal relationship between increased 

cancer risk and uranium exposure. 

In intermediate-duration animal studies, golden Syrian hamsters exposed to carnotite uranium ore dust 

(AMAD=1.5–2.1 μm) at a concentration of 19 mg U/m3 by inhalation for 16 months failed to show signs 

of cancer development upon examination of selected tissues including lungs, trachea, liver, kidneys, 

spleen, heart, and any abnormal tissue. As compared to unexposed controls, the hamsters had 

significantly more necrotic liver foci and inflammatory lung responses (Cross et al. 1981b). 

In the same study, the results of exposure of golden Syrian hamsters for 16–27 months to concentrations 

of radon progeny, uranium ore dust (0.5 nCi/m3 [18.5 Bq/m3

]), or a combination of uranium and radon 

progeny provided evidence that, while prolonged exposure to uranium dust causes inflammation and 

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URANIUM 106 

3. HEALTH EFFECTS 

proliferative pulmonary changes, inhalation of radon progeny produced bronchiolar epithelial hyperplasia 

and changes in the alveolar epithelium in hamsters. The authors also concluded that exposure to radon 

progeny and development of squamous metaplasia and carcinoma were related. The animals had 

cumulative radon progeny exposures >8,000 WLMs. Pulmonary neoplasms occurred in the three 

radon-progeny-exposed hamsters and in one hamster exposed to a combination of uranium, radon, and 

radon progeny. Both the hamsters exposed to radon progeny and those exposed to a combination of 

uranium and radon progeny had a significantly greater incidence of adenomatous proliferative changes in 

the alveolar epithelium. Uranium ore-exposed hamsters had significantly more necrotic liver foci and 

inflammatory lung responses than animals from other exposure groups. Specifically, one pheochromocytoma (zero in controls), one melanoma (zero in controls), one hemangioendothelioma (one in controls), 

two reticulum cell sarcomas (three in controls), and one adrenal cell carcinoma (zero in controls) were 

seen in animals exposed to uranium dust alone. Two osteosarcomas (zero in controls) were reported in 

animals exposed to the mixture of uranium ore dust and radon progeny. Four reticulum cell sarcomas 

(three in controls) and one adrenal cell sarcoma (zero in controls) were also seen in these animals. In 

animals exposed to radon progeny alone, one undifferentiated sarcoma (zero in controls), three reticulum 

cell sarcomas (three in controls), and one myelogenous leukemia (one in controls) were observed (Cross 

et al. 1981b). 

Pulmonary adenomas or adenocarcinomas were observed in 4/13 Beagle dogs exposed to 5.1 mg U/m3 as 

uranium dioxide for 5 years (Leach et al. 1973). The neoplasms were observed 22–67 months after 

exposure termination. The lung dose was estimated as 600–700 rads (6–7 Gy). Spontaneous tumors are 

rarely found in dogs, and the incidence found in this study was 50–100 times higher than the expected 

rate of spontaneous tumors. The authors of the study recommended against the extrapolation of these 

findings to humans because these glandular neoplasms do not occur frequently in humans (Leach et al. 

1973). No pulmonary neoplasms were observed in monkeys similarly exposed to 5.1 mg U/m3 as 

uranium dioxide for 5 years (Leach et al. 1973). 

A study was conducted with uranium ore dust in male Sprague-Dawley rats (Mitchel et al. 1999). The 

rats were exposed nose-only to uranium ore dust that was delivered to the rats as an aerosol under positive 

pressure. The ore was without significant radon content. The rats were exposed to 0, 8.4, or 22 mg U/m3 

4.2 hours/day, 5 days/week for 65 weeks and were allowed to live for their natural lifetime. Exposure to 

uranium significantly increased the incidence of malignant and nonmalignant lung tumors. The frequency 

of primary malignant lung tumors was 0.016, 0.175, and 0.328 and the frequency of nonmalignant lung 

tumors was 0.016, 0.135, and 0.131 in the control, low- and high-dose groups, respectively. The main 

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URANIUM 107 

3. HEALTH EFFECTS 

malignant tumor was bronchioalveolar carcinoma. No bronchial lymph node tumors were detected even 

though the lymph node specific burdens were considerably higher than in the lung in the same animal. 

The average absorbed doses for the low- and high-dose groups were 0.87 and 1.64 Gy, respectively, 

resulting in an average risk of malignant lung tumors of about 0.20 tumors per animal per Gy in both 

exposed groups. Lung tumor frequency appeared to be independent of dose, but exhibited a direct linear 

relationship with dose rate (as measured by the lung burden at the end of dust inhalation). Mitchel et al. 

(1999) noted that this suggested that rate may a more important determinant of lung cancer risk than dose. 

CELs for chemical and radiation inhalation exposure to uranium are shown in Table 3-1 and plotted in 

Figure 3-1. 

3.2.2 Oral Exposure 

The oral toxicity of uranium compounds has been evaluated in several animal species following exposure 

in drinking water or via gavage. The oral exposure studies did not report baseline uranium levels in the 

diet or drinking water; thus, baseline exposures were not included in the estimated doses. The levels of 

uranium in the drinking water may vary according to the source of the water (e.g., tap water, mineral 

water); if provided, the source of the drinking water was included in the discussion of individual studies. 

The maximal dosage just failing to be lethal for rats in a 30-day feeding test was about 0.5% uranium 

compound in the diet for the three soluble compounds (uranyl nitrate hexahydrate, uranyl tetrafluoride, 

and uranium tetrachloride) and 20% uranium compound for the three insoluble uranium compounds 

(uranium dioxide, uranium trioxide, and triuranium octaoxide) tested. Some of these studies sweetened 

the feed to make it edible. No amount of insoluble uranium compounds acceptable to the rat was lethal. 

Dietary levels of 1–4% soluble uranium compound produced 50% mortality in 30 days. The marked 

difference in the toxicity of soluble and insoluble uranium compounds is attributable to the ease of 

absorption and, thus, the dose that reaches the target organs. In general, the water-soluble compounds are 

more toxic by the oral route because of the greater ease of absorption in the gastrointestinal tract 

(Domingo et al. 1987, 1989a, 1989b; Goel et al. 1980; Maynard and Hodge 1949; Paternain et al. 1989). 

In a summary of the oral toxicity in both rats and dogs, several uranium compounds were ordered by 

relative toxicity as follows: very toxic compounds included uranium tetrachloride, uranium peroxide, and 

uranyl fluoride; toxic compounds included uranium nitrate hexahydrate, uranyl acetate, ammonium 

diuranate, sodium diuranate, uranium trioxide, and high-grade uranium ore (carnotite); and practically 

nontoxic compounds were uranium tetrafluoride, triuranium octaoxide, and uranium dioxide (Maynard 

and Hodge 1949). 

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URANIUM 108 

3. HEALTH EFFECTS 

3.2.2.1 Death 

There are no reports of human deaths from oral exposure to uranium compounds. However, data from 

animal studies demonstrate that soluble uranium compounds, at very high intake levels, can be lethal to 

animals through the oral route for all durations of exposure. Uranium compounds at these concentrations 

are not palatable to animals and require sweetening. 

Oral LD50 (lethal dose, 50% mortality rate) values of 114 and 136 mg U/kg have been estimated for male 

Sprague-Dawley rats and male Swiss-Webster mice, respectively, following single gavage 

administrations of uranyl acetate dihydrate (Domingo et al. 1987). Mortality occurred in pregnant Swiss 

mice exposed to 0.028, 0.28, 2.8, and 28 mg U/kg/day uranium as uranyl acetate dihydrate by gavage in 

water from gestation day 13 through postnatal day 21. Two dams in the 2.8 mg U/kg/day group and three 

in the 28 mg U/kg/day group died before delivery (Domingo et al. 1989b). Deaths were also reported in 

mice during the first 10 days of feeding studies with uranyl nitrate (8 of 25 at 925 mg U/kg/day) and with 

uranyl fluoride (2 of 25 at 452 mg/kg/day) (Tannenbaum et al. 1951). 

In 30-day oral studies, oral LD50 values for both sexes of rats of an unspecified strain given uranyl 

fluoride or uranyl nitrate hexahydrate have been estimated as 540 and 1,579 mg U/kg/day, respectively. 

Oral LD50 values were 658 and 1,096 mg U/kg/day as uranium tetrachloride for male and female rats, 

respectively, in a similar 30-day study (Maynard and Hodge 1949). Another 30-day study, in which male 

and female rats of an unspecified strain were exposed to oral uranium peroxide doses, oral LD50 values 

were estimated as 827 and 1,103 mg U/kg/day, respectively (Maynard and Hodge 1949). In other 

intermediate-duration feeding studies with rats, 16% mortality was reported in the animals following 

dietary administration of 664 mg U/kg/day for 30 days. Most of the animals died from complications of 

chemically induced kidney damage (Maynard et al. 1953). 

Two-year feeding studies with uranyl fluoride, uranyl nitrate hexahydrate, uranium tetrafluoride, and 

uranium dioxide showed that chronic intake of large amounts of uranium can lead to a decrease in 

lifespan. The largest daily intake that did not affect longevity in the rat was 81 mg U/kg/day as uranyl 

fluoride. For the other uranium compounds studied, the maximum daily intakes that did not affect 

longevity were 1,130 mg U/kg/day as uranyl nitrate, 1,390 mg U/kg/day as uranium tetrafluoride, and 

1,630 mg U/kg/day as uranium dioxide. About 18% of the experimental rats survived for the entire 

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URANIUM 109 

3. HEALTH EFFECTS 

2-year duration of the study, while about 38% of the control animals survived (Maynard and Hodge 

1949). Most of the deaths in the available animal studies resulted from chemically induced renal damage. 

The LD50 values for each species and other LOAEL values for mortality from exposure to uranium by the 

oral route are presented in Table 3-2 and plotted in Figure 3-2. 

3.2.2.2 Systemic Effects 

No human studies were located regarding respiratory, endocrine, dermal, ocular, body weight, or other 

systemic effects in humans following acute-, intermediate-, or chronic-duration oral exposure to uranium 

compounds. 

Animal data are lacking regarding musculoskeletal, metabolic, dermal, or ocular effects following oral 

exposure to uranium and its compounds for all durations. Similarly, no animal studies were located on 

the hematological effects of uranium in animals following acute-duration oral exposure or on the 

cardiovascular, endocrine, or other systemic effects following acute- or chronic-duration oral exposure. 

Data exist for the respiratory, renal, and body weight effects following oral exposure of animals to 

uranium for all durations. However, the existing data on the hematological, cardiovascular, hepatic, and 

other systemic effects of uranium in animals are limited to acute- or chronic-duration inhalation exposure; 

data on the gastrointestinal effects are limited to acute-duration exposure. 

The highest NOAEL values and all reliable LOAEL values in each species and duration category for 

systemic effects from chemical exposures to uranium by the oral route are presented in Table 3-2 and 

plotted in Figure 3-2. 

Respiratory Effects. Respiratory effects from oral exposure to uranium are unlikely. In an acuteduration animal study, no adverse effects on the respiratory system were reported in rats given single oral 

doses of 118 mg uranium/kg body weight/day (U/kg/day) as uranyl acetate dihydrate (Domingo et al. 

1987). 

In intermediate-duration exposures, Sprague-Dawley rats (10/sex/dose) were exposed to uranium as 

uranyl nitrate in the drinking water (males: up to 35.3 mg/kg/day; females: up to 40.0 mg/kg/day) for 

28 days and then sacrificed. No treatment-related histopathological changes were found, and no changes 

in lung weights were noted (Gilman et al. 1998a). In several 30-day dietary studies, no adverse effects on 

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Table 3-2 Levels of Significant Exposure to Uranium - Oral 

Exposure/ LOAEL

Duration/

a

Key to 

Figure

Species

(Strain)

Frequency

(Route)

ACUTE EXPOSURE 

Death

1 Rat

(SpragueDawley)

once(GW)

System

NOAEL

(mg/kg/day)

Less Serious 

(mg/kg/day)

Serious

(mg/kg/day)

114 M (LD50) 

2 Rat

(NS)

once(F) 664 (16% mortality) 

3 Mouse

(SwissWebster)

once(GW) 136 M (LD50) 

4 Mouse

(BALB/c)

once(G) 166 M (100% mortality 3 days post exposure) 

Systemic

5 Human once

(W) Gastro 14.3 M (nausea, vomiting, diarrhea)

6 Rat

(Long- Evans) 

2 wk ad lib (W)

Bd Wt 14 M 28 M (53% reduced body 

weight gain) 

ReferenceChemical Form 

Domingo et al. 1987 Uranyl Acetate Maynard et al. 1953 Uranyl Nitrate Domingo et al. 1987 Uranyl Acetate Martinez et al. 2003 Uranyl Nitrate Butterworth 1955 Uranyl Nitrate Briner and Murray 2005 Uranyl Acetate 
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Table 3-2 Levels of Significant Exposure to Uranium - Oral (continued)

a

Key to Species 

Figure (Strain) 

7 Rat

(SpragueDawley)

8 Rat

(SpragueDawley)

9 Mouse

(SwissWebster)

10 Mouse

(BALB/c)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/kg/day)

Less Serious 

(mg/kg/day)

LOAEL

Serious

(mg/kg/day)

ReferenceChemical Form 

once(GW) Hepatic 118 M (microhemorrhagic foci) Domingo et al. 1987 Uranyl Acetate 

Renal 118 M (Increased urine volume, 

increased plasma creatinine and urea, increased urinary total protein and creatinine, and minimal histological lesions)

Bd Wt 118 M (weight loss) 

1 or 3 d (GW) Metab 97 M (alterations in serum 1,25(OH)2 vitamin D 

levels)

Tissandie et al. 2006 Uranyl Nitrate 

Gd 6-15 (GW) Bd Wt 2.8 F (maternal reduced weight gain and food 

consumption)

Domingo et al. 1989c Uranyl Acetate 

once(G) Renal 166 M (increased blood urea and creatinine levels, 

tubular necrosis) 

Martinez et al. 2003 Uranyl Nitrate 
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Table 3-2 Levels of Significant Exposure to Uranium - Oral (continued)

a

Key to 

Figure

Species

(Strain) System

Exposure/

Duration/

Frequency

(Route)

LOAEL

NOAEL

(mg/kg/day)

Less Serious 

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form 

11 Renal Mouse

(Swiss)

5 d (F) 508 M (increased blood urea nitrogen, creatinine, and 

alkaline phosphatase levels)

Ozmen and Yurekli 199Uranyl Nitrate 

Bd Wt 

Neurological

12 Rat

(Long- Evans) 

2 wk ad lib (W)

508 M 

14 M 28 M (increased motor activity) Briner and Murray 2005 

Uranyl Acetate 

13 Mouse

(SwissWebster)

2 wk ad lib (W)

6 F (increased open field 

activity)

Briner 2009 Uranyl Acetate 

Developmental

14 Rat

(Wistar)

once(GW) 42.7 (delayed tooth eruption and development in 

neonatal rats) 

Pujadas-Bigi et al. 2003 Uranyl Nitrate 

15 Mouse

(SwissWebster)

Gd 6-15 (GW)

b

2.8 (decreased fetal BW; 

increased incidence of external defects) 

Domingo et al. 1989c Uranyl Acetate 

INTERMEDIATE EXPOSURE 

Death

16 Rat

(NS)

30 d (F) 827 M (LD50) Maynard and Hodge 19

Uranium Peroxide 
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Table 3-2 Levels of Significant Exposure to Uranium - Oral (continued)

Exposure/ LOAEL

Duration/

a

Key to 

Figure

1718192021222324

Species

(Strain)

Rat(NS)Rat(NS)Rat(NS)Rat(NS)Rat(NS)Mouse(SwissWebster)Mouse(dba)Mouse(dba)

Frequency

(Route) System

NOAEL

(mg/kg/day)

Less Serious 

(mg/kg/day)

Serious

(mg/kg/day)

30 d (F) 658 M (LD50) 

1096 F (LD50) 

30 d (F) 541 (LD50) 30 d (F) 7858 M (100% mortality) 

1103 F (LD50) 

30 d (F) 1579 (LD50)30 d (F) 664 (increased mortality) 30 d 1x/d(G)

2.8 F (10% mortality) 

48 wk ad lib (F)

452 F (8% mortality) 

48 wk ad lib (F)

925 F (24% mortality) 

ReferenceChemical Form 

Maynard and Hodge 19Uranium Tetrachloride Maynard and Hodge 19Uranyl Fluoride Maynard and Hodge 19Uranyl Acetate Maynard and Hodge 19Uranyl Nitrate Maynard et al. 1953 Uranyl Nitrate Domingo et al. 1989b Uranyl Acetate Tannenbaum et al. 195Uranyl Fluoride Tannenbaum et al. 195Uranyl Nitrate 
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Table 3-2 Levels of Significant Exposure to Uranium - Oral (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/kg/day)

Less Serious 

(mg/kg/day)

LOAEL

Serious

(mg/kg/day)

ReferenceChemical Form 

25 Dog

(Beagle)

30 d 6 d/wk (F)

440 (lethal dose) Maynard and Hodge 19

Uranium Dioxide 

26 Dog

(Beagle)

30 d 6 d/wk (F)

390 (lethal dose) Maynard and Hodge 19

Uranium Peroxide 

27 Dog

(Beagle)

30 d 6 d/wk (F)

5653 (lethal dose) Maynard and Hodge 19

Triuranium Octoxide 

28 Dog

(Beagle)

30 d 6 d/wk (F)

63 (lethal dose) Maynard and Hodge 19

Uranium Tetrachloride 

29 Dog

(Beagle)

30 d 6 d/wk (F)

15.4 (lethal dose) Maynard and Hodge 19

Uranyl Fluoride 

30 Dog

(Beagle)

30 d 6 d/wk (F)

237 (lethal dose) Maynard and Hodge 19

Uranyl Nitrate 

31 Dog

(NS)

138 d (F) 95 (lethal dose) Maynard and Hodge 19

Uranyl Nitrate 

32 Dog

(Beagle)

30 d 6 d/wk (F)

191 (lethal dose) Maynard and Hodge 19

Ammonium Diuranate 
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Table 3-2 Levels of Significant Exposure to Uranium - Oral (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/kg/day)

LOAEL

Less Serious 

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form 

33 Dog

(Beagle)

30 d 6 d/wk (F)

190 (lethal dose) Maynard and Hodge 19

Sodium Uranate 

34 Rabbit

(NS)

30 d (F)

Systemic

35 Rat

(SpragueDawley)

1.5 mo ad lib (W)

Bd Wt 2 M 

14.2 (67% mortality) Maynard and Hodge 19

Uranyl Nitrate Bensoussan et al. 2009 Uranyl Nitrate 

36 Rat

(SpragueDawley)

9 mo (W) Hemato 1 M (20% decreased in erythrocyte levels) Berradi et al. 2008 Depleted uranyl nitrate 

37 Rat

(Long- Evans) 

6 mo ad lib (W)

Bd Wt 14 M 28 M (46% reduced body 

weight gain) 

Briner and Murray 2005 Uranyl Acetate 

38 Rat

(SpragueDawley)

9 mo ad lib (W)

Bd Wt 2.7 M (11% reduced final body 

weight)

Bussy et al. 2006 Uranyl Nitrate 
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Table 3-2 Levels of Significant Exposure to Uranium - Oral (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/kg/day)

Less Serious 

(mg/kg/day)

LOAEL

Serious

(mg/kg/day)

ReferenceChemical Form 

39 Rat

(SpragueDawley)

28 d (W) Resp 35.3 M Gilman et al. 1998a Uranyl Nitrate 

Cardio 35.3 M Gastro 35.3 M Hemato 35.3 M Musc/skelHepaticRenal

35.3 M 35.3 M 35.3 M 40 F (39% increase in serum 

uric acid) 

Endocr 35.3 M Bd Wt 35.3 M 
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Table 3-2 Levels of Significant Exposure to Uranium - Oral (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

40 Rat

(SpragueDawley)

91 d (W) Resp

CardioGastroHematoMusc/skelHepaticRenalEndocrBd WtOther

LOAEL

NOAEL

(mg/kg/day)

Less Serious 

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form 

36.73 M Gilman et al. 1998a 

Uranyl Nitrate 

36.73 M 36.73 M 36.73 M 36.73 M 

0.06 M (anisokaryosis, 

vesiculation, increased portal density, perivenous vacuolation and homogeneity) 

c

0.06 M (nuclear vesiculation, 

cytoplasmic vacuolation, tubular dilation, interstitial lymphoid cuffing) 

0.06 M 0.42 F 

0.31 M (multifocal reduction of 

follicular size, increased epithelial height in thyroid, decreased amount and density of colloid)

2.01 F (multifocal reduction of 

follicular size, increased epithelial height in thyroid, decreased amount)

36.73 M 

7.54 M 36.73 M (sinus hyperplasia in 

spleen)
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Table 3-2 Levels of Significant Exposure to Uranium - Oral (continued)

a

Key to Species 

Figure (Strain) 

41 Rat

(SpragueDawley)

42 Rat

(NS)

43 Rat

(SpragueDawley)

44 Rat

(SpragueDawley)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/kg/day)

Less Serious 

(mg/kg/day)

LOAEL

Serious

(mg/kg/day)

ReferenceChemical Form 

3 months ad lib (W)

Bd Wt 22.5 M Linares et al. 2005 

Uranyl Acetate 

30 d (F) Bd Wt 6637 (retarded growth) Maynard et al. 1953 Uranyl Nitrate 

4 wk (W) Hemato 4.5 M 9 M (5.3 % increased hematocrit, 9% increased 

mean corpuscular hemoglobinconcentration, 7% increased erythrocytes) 

Ortega et al. 1989a Uranyl Acetate 

Hepatic 2.2 M 4.5 M (28% increased blood 

glucose; 34% increased SGOT, 32% increased SGPT)

Renal 1.1 M (6% increased total 

plasma proteins) 

9 mo (W) Hepatic 1 M Racine et al. 2010 Depleted uranyl nitrate 

Metab 1 M (altered cholesterol 

catabolism)
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Table 3-2 Levels of Significant Exposure to Uranium - Oral (continued)

a

Key to 

Figure

45464748495051

Species

(Strain)

Rat(SpragueDawley)Mouse(C57BL/6N)Mouse(B6C3F1)Mouse(dba)Mouse(C3H)Mouse(C3H)Mouse(dba)

Exposure/

Duration/

Frequency

(Route)

9 mo (W)15 wk ad lib (W)30 d ad lib (W)48 wk ad lib (F)18 wk ad lib (F)48 wk ad lib (F)48 wk ad lib (F)

LOAEL

System

NOAEL

(mg/kg/day)

Less Serious 

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form 

Metab 1 M (decreased 

1,25(OH)vitamin D3 levels)

Tissandie et al. 2007 Depleted uranyl nitrate 

Bd Wt 100 F Arnault et al. 2008 

Uranyl Nitrate 

Bd Wt 9.3 F Raymond-Whish et al. 2

Uranyl Nitrate 

Renal 452 M (nodular development on 

kidney surface) 

Tannenbaum et al. 195Uranyl Fluoride 

Bd Wt 925 F Tannenbaum et al. 195

Uranyl Nitrate 

Other 925 F Renal 452 M (nodular development on 

kidney surface) 

Tannenbaum et al. 195Uranyl Fluoride 

Bd Wt 462 F Tannenbaum et al. 195

Uranyl Nitrate 

Other 462 F 
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Table 3-2 Levels of Significant Exposure to Uranium - Oral (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/kg/day)

Less Serious 

(mg/kg/day)

LOAEL

Serious

(mg/kg/day)

ReferenceChemical Form 

52 Rabbit

(NewZealand)

91 d (W) Resp 28.7 M Gilman et al. 1998b Uranyl Nitrate 

Cardio 28.7 M Gastro 28.7 M Hemato 28.7 M Musc/skelHepaticRenal

28.7 M 28.7 M 

0.05 M (cytoplasmic 

vacuolization,anisokaryosis, nuclear vesiculation)

0.49 F (anisokaryosis, nuclear 

vesiculation, atrophy) 

Endocr 28.7 M Bd Wt 28.7 M 
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Table 3-2 Levels of Significant Exposure to Uranium - Oral (continued)

a

Key to Species 

Figure (Strain) 

53 Rabbit

(NewZealand)

Neurological

54 Rat

(SpragueDawley)

55 Rat

(SpragueDawley)

Exposure/

Duration/

Frequency

(Route)

91 d (W)3 mo ad lib (W)1.5 mo ad lib (W)

System

RespCardioGastroHematoMusc/skelHepaticRenalEndocrBd Wt Other

LOAEL

NOAEL

(mg/kg/day)

Less Serious 

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form 

40.98 M Gilman et al. 1998c 

Uranyl Nitrate 

40.98 M 40.98 M 40.98 M 40.98 M 

1.36 M (variation in nuclear size, 

nuclear pyknosis, extensive cytoplasmic vacuolization)

1.36 M 40.38 M (glycosuria, proteinuria, 

anisokaryosis, nuclear hyperchromicity, nuclear pyknosis, tubular atrophy)

40.98 M 40.98 M 40.98 M 

22.4 M Belles et al. 2005 

Uranyl Acetate 

2 M (cholinergic alterations in 

the brain) 

Bensoussan et al. 2009 Uranyl Nitrate 
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Table 3-2 Levels of Significant Exposure to Uranium - Oral (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/kg/day)

Less Serious 

(mg/kg/day)

LOAEL

Serious

(mg/kg/day)

ReferenceChemical Form 

5657

Rat(Long- Evans) 

6 mo ad lib (W)

Rat(SpragueDawley)

9 mo ad lib (W)

14 M 28 M (increased motor activity) 

2.7 M (altered neurotransmitter 

levels in the brain) 

Briner and Murray 2005 Uranyl Acetate Bussy et al. 2006 Uranyl Nitrate 

58 Rat

(SpragueDawley)

1.5 mo ad lib (W)

2.7 (sleep and behavioral 

alterations)

Houpert et al. 2005 Enriched Uranyl Nitrate 

5960

Rat(SpragueDawley)Rat(SpragueDawley)

1.5 mo ad lib (W)9 mo ad lib (W)

2.7

2.5 M (decreased spatial 

working memory) 

Houpert et al. 2005 Depleted uranyl nitrate Houpert et al. 2007b Enriched Uranyl Nitrate 

6162

Rat(SpragueDawley)Rat(SpragueDawley)

90 days (W)90 d ad lib (W)

3.7 M (increase in REM sleep) 5.6 M (increased oxidative 

stress in brain areas). 

Lestaevel et al. 2005a Depleted uranyl nitrate Linares et al. 2007 Uranyl Acetate 
***DRAFT FOR PUBLIC COMMENT***

Table 3-2 Levels of Significant Exposure to Uranium - Oral (continued)

a

Key to Species 

Figure (Strain) 

Reproductive

63 Rat

(SpragueDawley)

64 Rat

(SpragueDawley)

65 Rat

(SpragueDawley)

66 Rat

(SpragueDawley)

67 Rat

(SpragueDawley)

68 Mouse

(C57BL/6N)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/kg/day)

Less Serious 

(mg/kg/day)

LOAEL

Serious

(mg/kg/day)

ReferenceChemical Form 

28 d (W) 35.3 M 

40 F 

Gilman et al. 1998a Uranyl Nitrate 

91 d (W) 36.73 M 

53.56 F 

Gilman et al. 1998a Uranyl Nitrate 

9 mo ad lib (W)9 mo ad lib (W)

1.9 M 

1.9 M (3-fold increase in 

plasma testosterone) 

Grignard et al. 2008 Depleted uranyl nitrate Grignard et al. 2008 Enriched Uranyl Nitrate 

3 months ad lib (W)15 wk ad lib (W)

5.6 M 11.2 M (reduced pregnancy rate) 

1.25 F (slight disturbance in 

ovarian folliculogenesis) 

Linares et al. 2005 Uranyl Acetate 

Arnault et al. 2008 

Uranyl Nitrate 
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Table 3-2 Levels of Significant Exposure to Uranium - Oral (continued)

a

Key to Species 

Figure (Strain) 

69 Mouse

(Hybrid)

70 Mouse

(SwissWebster)

71 Mouse

(SwissWebster)

72 Mouse

(SwissWebster)

73 Rabbit

(NewZealand)

Developmental

74 Rat

(SpragueDawley)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/kg/day)

Less Serious 

(mg/kg/day)

LOAEL

Serious

(mg/kg/day)

ReferenceChemical Form 

49 d ad lib (W)

1.9 F 3.9 F (increased proportion of 

morphologicallyabnormal oocytes) 

Feugier et al. 2008 Uranyl Nitrate 

40 d ad lib (W)

2.5 F (increased oocyte 

dysmorphism and micronuclei in cumulus cells)

Kundt et al. 2009 Uranyl Nitrate 

64 d (W) 5.6 M (significantly reduced pregnancy rate) Llobet et al. 1991 Uranyl Acetate 

60 d (G)

14 Paternain et al. 1989 

Uranyl Acetate 

91 d (W) 28.7 M 

43.02 F 

Gilman et al. 1998b Uranyl Nitrate 

132 d (W) 4.3 F (delayed hyperactivity; decreased spatial 

working memory) 

Houpert et al. 2007a Enriched Uranyl Nitrate 
***DRAFT FOR PUBLIC COMMENT***

Table 3-2 Levels of Significant Exposure to Uranium - Oral (continued)

Exposure/ LOAEL

Duration/

a Frequency Key to Species NOAEL Less Serious (Route) Figure (Strain) System (mg/kg/day) (mg/kg/day) 

75 Rat 70 d 22.5 (13-16% reduction in ad lib (Sprague- pups weight on day 21) Dawley) (W)76 Mouse 15 wk 1.25 F (slight disturbance in ad lib (C57BL/6N) ovarian folliculogenesis) (W)

77 Mouse 30 d 

1x/d (SwissWebster) (G)

78 Mouse 27 d 5.6 F

(Swiss- (G)Webster)

79 Mouse 56 d 2.8 F (reduced pup's weight on (Swiss- (G) PND 21) Webster)

CHRONIC EXPOSURE 

Death

80 Rat 2 yr 

Serious

(mg/kg/day)

28 (decrease in litter size on 

PND 21; decreased day 21 viability index) 

14 F (increased late

resorptions anddecreased live fetuses)

5.6 F (increased neonatal 

death per litter) 

135.2 M (6-12% mortality) (NS) (F)

270 F (57% mortality) 

Rat 2 yr 308 (100% mortality) (NS) (F)

ReferenceChemical Form 

Sanchez et al. 2006 Uranyl Acetate 

Arnault et al. 2008 

Uranyl Nitrate Domingo et al. 1989b Uranyl Acetate Paternain et al. 1989 Uranyl Acetate Paternain et al. 1989 Uranyl Acetate Maynard and Hodge 19Maynard et al. 1953 Uranyl Fluoride Maynard and Hodge 19Maynard et al. 1953 Uranium Dioxide 

81
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Table 3-2 Levels of Significant Exposure to Uranium - Oral (continued)

a

Key to Species 

Figure (Strain) 

Systemic

82 Rat

(NS)

83 Rat

(NS)

84 Rat

(NS)

85 Rat

(NS)

Exposure/

Duration/

Frequency

(Route)

2 yr (F)2 yr (F)2 yr (F)2 yr (F)

System

HematoRenalBd Wt HematoRenalBd Wt HematoRenalBd Wt 

LOAEL

NOAEL

(mg/kg/day)

Less Serious 

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form 

16.6 33 (mild anemia; increased 

leucocyte count) 

Maynard and Hodge 19Maynard et al. 1953 Uranyl Nitrate 

16.6 33 (minimal microscopic 

lesions in tubular epithelium)

135.2 M 

135.2 F 

270 M (30% decrease in body 

weight)

270 F (29% decrease in body 

weight)

Maynard and Hodge 19Maynard et al. 1953 Uranyl Fluoride 

1234112341

Maynard and Hodge 19Maynard et al. 1953 Uranium Dioxide 

12341

10611

1061 10611 (mild renal tubular 

degeneration)

Maynard and Hodge 19Maynard et al. 1953 Uranium Tetrafluoride 

10611
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Table 3-2 Levels of Significant Exposure to Uranium - Oral (continued)

a

Key to 

Figure

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System

NOAEL

(mg/kg/day)

Less Serious 

(mg/kg/day)

LOAEL

Serious

(mg/kg/day)

ReferenceChemical Form 

86 Dog

(NS)

1 yr (F) Renal

Bd Wt 

8

8

Maynard and Hodge 19Maynard et al. 1953 Uranyl Fluoride 

87 Dog

(Beagle)

1 yr (F) Hemato 31 Maynard and Hodge 19

Maynard et al. 1953 Uranium Tetrachloride 

Renal 6.3 31 (mild glucosuria, 

proteinuria)

Reproductive

88 Rat

(NS)

2 yr (F) 331 M (testicular degeneration) Maynard et al. 1953 Uranyl Nitrate 

a The number corresponds to entries in Figure 3-2. b Used to derive an acute-duration oral minimal risk level (MRL) of 0.002 mg/kg/day for soluble uranium compounds based on an average BMDL0.05 of 0.20 mg/kguncertainty factor of 100 (10 for extrapolation from animals to humans and 10 for human variability). c Used to derive an intermediate-duration oral minimal risk level (MRL) of 0.0002 mg/kg/day for soluble uranium compounds based on a LOAEL of 0.06 mg/kg/day factor of 300 (3 for use of a minimal LOAEL, 10 for extrapolation from animals to humans, and 10 for human variability). ad lib = ad libitum; Bd Wt = body weight; Cardio = cardiovascular; d = day(s); Endocr = endocrine; (F) = feed; F = Female; (G) = gavage; Gastro = gastrointestinal; day; (GW) = gavage in water; Hemato = hematological; LD50 = lethal dose, 50% kill; LOAEL = lowest-observed-adverse-effect level; M = male; Metab = metabolicMusc/skel = musculoskeletal; NOAEL = no-observed-adverse-effect level; NS = not specified; PND = post-natal day; Resp = respiratory; (W) = drinking water; wk = time(s); yr = year(s) 
Death 

Gastrointestinal 

Hepatic 

Renal 

Body Weight 

Metabolic 

Neurological 

Developmental 

Systemic 

mg/kg/day 

1000 

2r 

11m 11m 

4m 10m

3m 1r 7r 7r 7r 100 8r 

14r 

6r 12r 

5 6r 12r 

10 

13m 

9m 15m 

1 

0.1 

0.01 

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 

URANIUM

***DRAFT FOR PUBLIC COMMENT***

3. HEALTH EFFECTS

Figure 3-2 Levels of Significant Exposure to Uranium - Oral 

Acute (≤14 days) 

128
Death 

Respiratory 

Cardiovascular Gastrointestinal 

Hematological 

Systemic 

mg/kg/day 

10000 19r 

27d 

20r 

1000 17r 19r 24m 16r 17r 21r 18r 25d 26d 23m

30d 32d 33d 

100 31d 28d 53h 53h 53h 53h 39r 40r 39r 40r 39r 40r 39r 40r

52h 52h 52h 52h 

29d 34h 

10 43r 

43r 

22m 

1 36r 

0.1 

0.01 

0.001 

0.0001 

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 

URANIUM

***DRAFT FOR PUBLIC COMMENT***

3. HEALTH EFFECTS

Figure 3-2 Levels of Significant Exposure to Uranium - Oral (Continued)

Intermediate (15-364 days) 

129
Musculoskeletal 

Hepatic Renal 

Endocrine 

Body Weight 

Metabolic 

Other 

Intermediate (15-364 days) 

Systemic 

mg/kg/day 

10000 

42r 

1000 49m 49m 

48m 50m 51m 51m

100 46m 

53h 53h 53h 40r 39r 53h 40r 40r 53h 39r 39r 39r 39r 39r 52h 52h 52h 37r 52h 41r 

37r 

10 47m 40r 

43r 

38r

43r 40r 35r 

53h 53h 1 44r 43r 44r 45r 

52h 40r

40r 

0.1 

40r 40r 40r 52h 

0.01 

0.001 

0.0001 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

URANIUM

***DRAFT FOR PUBLIC COMMENT***

3. HEALTH EFFECTS

Figure 3-2 Levels of Significant Exposure to Uranium - Oral (Continued)

130
Neurological 

Reproductive Developmental 

mg/kg/day 

10000 

1000 

100 

64r 73h 63r 63r 64r 56r 73h 77m 54r 75r

56r 72m 78m

10 67r

62r 71m 67r 78m 79m

61r 69m 74r

57r 58r 59r 60r 70m 79m 55r 69m 65r 66r 

68m 76m 1 

0.1 

0.01 

0.001 

0.0001 

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 

URANIUM

***DRAFT FOR PUBLIC COMMENT***

3. HEALTH EFFECTS

Figure 3-2 Levels of Significant Exposure to Uranium - Oral (Continued)

Intermediate (15-364 days) 

131
Death 

Hematological 

Renal Body Weight 

Reproductive 

Systemic 

mg/kg/day 

100000 

84r 84r 84r

10000 85r 85r 85r

1000 85r

81r 88r

80r 83r 83r 

80r 83r 83r 

100 

87d 82r 87d 82r

82r 82r 

10 86d 86d 

87d 

1 

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 

URANIUM

***DRAFT FOR PUBLIC COMMENT***

3. HEALTH EFFECTS

Figure 3-2 Levels of Significant Exposure to Uranium - Oral (Continued)

Chronic (≥365 days) 

132
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

URANIUM 133 

3. HEALTH EFFECTS 

the respiratory system were reported in rats exposed to 6,637 mg U/kg/day as uranyl nitrate hexahydrate, 

8,769 mg U/kg/day as uranium tetrachloride, 11,033 mg U/kg/day as uranium peroxide, 10,611 mg 

U/kg/day as uranium tetrafluoride, 10,818 mg U/kg/day as uranyl fluoride, 12,342 mg U/kg/day as 

uranium dioxide, 8.167 mg U/kg/day as uranyl acetate dihydrate, or 11,650 mg U/kg/day as uranium 

trioxide (Maynard and Hodge 1949; Maynard et al. 1953; Stokinger et al. 1953). Lengthening the 

duration of exposure to uranium failed to produce detectable lesions in lungs of laboratory animals. 

Sprague-Dawley rats (15/sex/dose) were exposed to uranium as uranyl nitrate in drinking water (males: 

up to 36.73 mg/kg/day; females: up to 53.56 mg/kg/day) for 91 days and were sacrificed. No treatmentrelated histopathological changes were found in the lungs, and no changes in lung weights were noted 

(Gilman et al. 1998a). In addition, New Zealand rabbits were exposed to uranium as uranyl nitrate in the 

drinking water (males: up to 28.70 mg/kg/day; females: up to 43.02 mg/kg/day) for 91 days. No 

treatment-related histopathological changes were found, and no changes in lung weights were noted 

(Gilman et al. 1998b). Male New Zealand rabbits were also exposed to uranium as uranyl nitrate in 

drinking water (1.36 and 40.98 mg/kg/day) for 91 days, again with no histopathological or organ weight 

changes found (Gilman et al. 1998c). 

In chronic-duration feeding studies, no adverse effects on the respiratory system were reported in 1-year 

studies of dogs given oral doses of 31 mg U/kg/day as uranium tetrachloride, 3,790 mg U/kg/day as 

uranium hexachloride, 8 mg U/kg/day as uranyl fluoride, or 4,407 mg U/kg/day as uranium dioxide 

(Maynard and Hodge 1949; Maynard et al. 1953). In 2-year studies, the respiratory system was 

unaffected in dogs and rats given 2 mg U/kg/day as uranyl nitrate hexahydrate and in rats given 

12,141 mg U/kg/day as uranium dioxide, 664 mg U/kg/day as uranyl nitrate hexahydrate, 

10,611 mg U/kg/day as uranium tetrafluoride, or 405 mg U/kg/day as uranyl fluoride (Maynard and 

Hodge 1949; Maynard et al. 1953; Stokinger et al. 1953). 

Cardiovascular Effects. Cardiovascular effects following intake of uranium are unlikely. One case 

report documented a cardiovascular effect that was possibly related to uranium exposure in a male 

admitted to the hospital following deliberate ingestion of 15 g of uranyl acetate, along with an unknown 

quantity of benzodiazepine, in a failed suicide attempt. While body weight was not reported, the dose 

would be approximately 131 mg U/kg for a 70-kg reference man. Initial blood chemistry was 

unremarkable, and decreased cardiac output was consistent with ingestion of benzodiazepam. The patient 

was reported to have suffered from myocarditis resulting from the uranium ingestion, resolving 6 months 

after the ingestion (Pavlakis et al. 1996). 

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A significant association between urinary uranium levels and increases in diastolic and systolic blood 

pressure were observed among adults living in households with uranium in the drinking water at levels of 

0.03–1,500 μg/L (31% >100 μg/L and 55% >15 μg/L; the median daily intake was 36 μg/day, which is 

roughly equivalent to 0.0005 mg/kg/day assuming a 70-kg body weight) (Kurttio et al. 2006a); however, 

the increases in blood pressure were small and did not appear until urine uranium levels were at least 

1 μg/L. This is consistent with the findings of Kurttio et al. (2002) that a 1 mg/L increase in uranium 

levels in drinking water would be associated with 7.4 and 5.0 mm Hg increases in systolic and diastolic 

blood pressure, respectively. Kurttio et al. (2006a) noted that the increases in blood pressure were 

expectedly greater in older individuals than younger individuals. 

The available studies in animals have found no adverse cardiovascular effects following oral exposures 

for up to 30 days to uranium compounds. In one study, Sprague-Dawley rats (10/sex/dose) were exposed 

to uranium as uranyl nitrate in drinking water (males: up to 35.3 mg/kg/day; females: up to 

40.0 mg/kg/day) for 28 days and sacrificed. No cardiac histopathological changes were found, and no 

changes in heart weights were noted (Gilman et al. 1998a). No changes in the heart or blood vessels were 

observed in rats following oral exposure to doses as high as 9,393 mg U/kg/day as uranyl nitrate 

hexahydrate, 8,769 mg U/kg/day as uranium tetrachloride, 11,033 mg U/kg/day as uranium peroxide, 

10,611 mg U/kg/day as uranium tetrafluoride, 10,819 mg U/kg/day as uranyl fluoride, 

12,342 mg U/kg/day as uranium dioxide, 11,650 mg U/kg/day as uranium trioxide, or 7,859 mg U/kg/day 

as uranyl acetate dihydrate (Maynard and Hodge 1949). Sprague-Dawley rats (15/sex/dose) were 

exposed to uranium as uranyl nitrate in drinking water (males: up to 36.73 mg/kg/day; females: up to 

53.56 mg/kg/day) for 91 days and sacrificed. No uranium-related histopathological changes were found 

in the heart, and no changes in heart weights were noted (Gilman et al. 1998a). In addition, New Zealand 

rabbits were exposed to uranium as uranyl nitrate in the drinking water (males: up to 28.70 mg/kg/day; 

females: up to 43.02 mg/kg/day) for 91 days. No treatment-related cardiac histopathological changes 

were noted, and no changes in heart weights were detected (Gilman et al. 1998b). Male New Zealand 

rabbits also were exposed to uranium as uranyl nitrate in drinking water (1.36 and 40.98 mg/kg/day) for 

91 days, with no histopathological or organ weight changes (Gilman et al. 1998c). 

Gastrointestinal Effects. A volunteer given a single dose of 1 g uranyl nitrate (14.3 mg/kg) and 

observed for clinical signs and symptoms within 24 hours after intake suffered acute nausea, vomiting, 

and diarrhea within a few hours of administration. All clinical signs returned to normal within 24 hours 

after administration of the oral uranyl nitrate dose (Butterworth 1955). Paralytic ileus was reported in a 

male after the deliberate ingestion of 15 g uranyl acetate (Pavlakis et al. 1996). While body weight was 

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not reported, the dose would be approximately 131 mg U/kg for a 70-kg reference man. No other reports 

of gastrointestinal effects after acute-duration exposure to uranium in either humans or laboratory animals 

were available. 

Studies of intermediate-duration exposure to uranium compounds were available for laboratory animals. 

In one study, Sprague-Dawley rats (10/sex/dose) were exposed to uranium as uranyl nitrate in the 

drinking water (males: up to 35.3 mg/kg/day; females: up to 40.0 mg/kg/day) for 28 days and sacrificed. 

No treatment-related histopathological changes were found, and no changes in organ weights were noted 

(Gilman et al. 1998a). In a study of longer duration, Sprague-Dawley rats (15/sex/dose) were exposed to 

uranium as uranyl nitrate in drinking water (males: up to 36.73 mg/kg/day; females: up to 

53.56 mg/kg/day) for 91 days and then sacrificed. No treatment-related histopathological changes were 

found in the gastrointestinal tract, and no changes in stomach and intestinal weights were noted (Gilman 

et al. 1998a). In addition, New Zealand rabbits were exposed to uranium as uranyl nitrate in the drinking 

water (males: up to 28.70 mg/kg/day; females: up to 43.02 mg/kg/day) for 91 days. No treatmentrelated histopathological changes were found, and no changes in organ weights (i.e., colon, duodenum, 

stomach [gastric cardia, fundus, and pylorus]) were noted (Gilman et al. 1998b). Male New Zealand 

rabbits were exposed to uranium as uranyl nitrate in drinking water (1.36 and 40.98 mg/kg/day) for 

91 days, with no histopathological or organ weight changes found (Gilman et al. 1998c). 

Hematological Effects. In one case report, a male (no age or weight given) was admitted to hospital 

following the deliberate ingestion of 15 g of uranyl acetate, along with an unknown quantity of 

benzodiazepine, in a failed suicide attempt. While body weight was not reported, the dose would be 

approximately 131 mg U/kg for a 70-kg reference man. Initial blood chemistry was unremarkable; 

however, an anemia developed and continued to progress over the next 8 weeks, along with persistent 

renal dysfunction (Pavlakis et al. 1996). While the authors attributed the renal dysfunction to uranium 

ingestion, the etiology of the anemia was unknown. The patient also suffered from peptic ulcer disease, 

which may have been related to the anemia. 

The majority of animal studies show no effect of uranium on hematological parameters after oral 

exposure. Exposure to uranium as uranyl nitrate in drinking water had no hematological effects in 

Sprague-Dawley rats after 28 days (up to 40 mg U/kg/day) or 91 days (up to 53 mg U/kg/day) (Gilman et 

al. 1998a), or in New Zealand rabbits after 91 days (up to 43 mg U/kg/day) (Gilman et al. 1998b, 1998c). 

Exposure to a variety of uranium compounds in feed had no effect on hematological parameters in 

intermediate- and chronic-duration studies (Maynard and Hodge 1949). One study reported a significant 

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increase in the hematocrit and hemoglobin values, the mean corpuscular hemoglobin concentration, and 

the number of erythrocytes at 9 mg U/kg/day as uranyl acetate in drinking water for 4 weeks, but not at 

4.5 mg U/kg/day and lower doses (Ortega et al. 1989a). In contrast, a 20% reduction in erythroctye levels 

was observed in male Sprague-Dawley rats exposed to 1 mg U/kg/day as depleted uranyl nitrate 

hexahydrate in mineral water for 9 months (Berradi et al. 2008). The study did not find reductions in 

erythrocyte production in the spleen or bone marrow or evidence of alterations in spleen iron recycling. 

The investigators suggested that the observed hematological effect may be secondary to observed kidney 

damage. 

In a chronic-exposure feeding study, mild anemia and an increased leucocyte count were observed in rats 

given uranyl nitrate hexahydrate doses corresponding to 33 mg U/kg/day for 2 years (Maynard and Hodge 

1949; Maynard et al. 1953). 

Musculoskeletal Effects. In one human case report, a male (no age or weight given) was admitted 

to the hospital following the deliberate ingestion of 15 g of uranyl acetate, along with an unknown 

quantity of benzodiazepine, in a failed suicide attempt. While body weight was not reported, the dose 

would be approximately 131 mg U/kg for a 70-kg reference man. The patient suffered from increasing 

rhabdomyolysis (biochemically characterized by increased creatine kinase). At 6 months following the 

initial toxic insult, the rhabdomyolysis had resolved, and the subject showed no residual signs of muscle 

toxicity (Pavlakis et al. 1996). The etiology of this effect is unknown. 

In a study of adults (146 men and 142 women) living in an area of Finland with elevated uranium levels 

in drinking water (0.002–1,920 μg/L with 27% of concentrations >100 μg/L and 59% >15 μg/L), a 

significant association between elevated serum type I collagen carboxy-terminal telopeptide (CTx) levels 

(biomarker of bone resorption) and levels of uranium in water was observed in males (Kurttio et al. 

2005). A nonsignificant association between increased osteocalcin levels (biomarker of bone formation) 

and uranium levels in drinking water was also observed in males. Other biomarkers of bone resorption 

and formation were not associated with uranium exposure. No statistically significant associations were 

observed in females. Daily uranium intakes ranged from 7 to 207 μg (0.0001–0.003 mg/kg/day, using a 

70-kg reference body weight) and the median intake was 36 μg (0.0005 mg/kg/day). 

There are limited data on the potential of uranium to induce bone or muscle damage following oral 

exposure. A significant decrease in growth cartilage width, metaphyseal bone volume, and percent 

metaphyseal activity in bone formation area and a significant increase in metaphyseal activity in the bone 

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resorption area were observed in male Balb/c mice administered a single gavage dose of 170 mg U/kg as 

uranyl nitrate hexahydrate and sacrificed 48 hours after dosing (Bozal et al. 2005). 

Histopathological examination of muscle after exposure to uranium in drinking water as uranyl nitrate 

showed no effects in Sprague-Dawley rats after 28 days (up to 40 mg U/kg/day) or 91 days (up to 53 mg 

U/kg/day) (Gilman et al. 1998a), or in New Zealand rabbits after 91 days (up to 43 mg U/kg/day) (Gilman 

et al. 1998b, 1998c). 

Hepatic Effects. Few human data are available on the hepatic effects of uranium. In one case report, 

a male (no age or weight given) was admitted to the hospital following the deliberate ingestion of 15 g of 

uranyl acetate, along with an unknown quantity of benzodiazepine, in a failed suicide attempt. While 

body weight was not reported, the dose would be approximately 131 mg U/kg for a 70-kg reference man. 

The patient suffered from increasing liver dysfunction, characterized by increased serum levels of alanine 

aminotransferase (ALT), aspartate aminotransferase (AST), and GGK. Six months following the initial 

toxic insult, the patient had no residual signs of hepatic toxicity (Pavlakis et al. 1996). The etiology of 

this effect is unknown, although histological signs of hepatic toxicity have been observed in animals after 

oral exposure to uranium. 

In the available animal studies, the existing data provide evidence that uranium exposure can damage the 

liver, although the etiology for this effect is not certain. In an acute-duration study in which SpragueDawley rats were given single gavage doses of 5.6 or 118 U/kg as uranyl acetate dihydrate, 

microhemorrhagic foci in the liver were observed at both doses tested (Domingo et al. 1987). 

Ingested uranium was also hepatotoxic to dogs in studies of intermediate-duration exposure. When 

uranyl fluoride was tested at 7.7, 15.4, 77.3, 386.7, or 3,864 mg U/kg/day for 30 days, fatty infiltration 

was seen in dogs at the 15.4 mg U/kg/day dose level (Maynard and Hodge 1949). In other tests, uranium 

tetrachloride induced minimal hepatic lesions at a dose level of 313 mg U/kg/day; uranium peroxide 

induced mild degeneration at a dose level of 386 mg U/kg/day; uranium dioxide induced mild 

degeneration at a dose level of 441 mg U/kg/day; uranium trioxide induced slight fatty infiltration at a 

dose level of 416 mg U/kg/day; triuranium octaoxide induced mild fatty changes at a dose level of 

5,653 mg U/kg/day; sodium diuranate induced mild degeneration at a dose level of 37.5 mg U/kg/day; 

uranium tetrafluoride caused degenerative fatty changes at a dose level of 15,159 mg U/kg/day; and 

uranyl nitrate hexahydrate induced minimal hepatic degeneration at a dose level of 237 mg U/kg/day 

(Maynard and Hodge 1949). 

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Hepatic toxicity was also found in several other studies. In one study, Sprague-Dawley rats (15/sex/dose) 

were exposed to uranium as uranyl nitrate in drinking water (males: up to 36.73 mg/kg/day; females: up 

to 53.56 mg/kg/day) for 91 days and then sacrificed. Hepatic lesions, which included anisokaryosis, 

vesiculation, increased portal density, perivenous vacuolation, and homogeneity, were observed in the 

liver at all doses (Gilman et al. 1998a), although the dose ranging portion of this study found no effects at 

essentially the same doses as those discussed below (Gilman et al. 1998c). However, in New Zealand 

rabbits exposed to uranium as uranyl nitrate in the drinking water (males: 0, 0.05, 0.20, 0.88, 4.82, and 

28.70 mg/kg/day; females: 0, 0.49, 1.32, and 43.02 mg/kg/day) for 91 days, no treatment-related 

histopathological changes were found, and no changes in liver weights were noted (Gilman et al. 1998b). 

In contrast, another study by the same investigator in male New Zealand rabbits exposed to uranium as 

uranyl nitrate in drinking water (1.36 and 40.98 mg/kg/day) for 91 days found irregular accentuation of 

zonation in the liver, accompanied by increased variation in hepatocellular nuclear size, nuclear pyknosis, 

and extensive cytoplasmic vacuolization. These changes were found to be treatment-related but not 

dose-related (Gilman et al. 1998c). 

In other intermediate-duration studies, no effects were seen on the liver of dogs given oral doses of 

9,393 mg U/kg/day as uranyl nitrate hexahydrate or 191 mg U/kg/day as ammonium diuranate for 30 days 

(Maynard and Hodge 1949). Similarly, no effects were seen on the liver of rats given oral doses of 

8,769 mg U/kg/day as uranium tetrachloride, 11,033 mg U/kg/day as triuranium peroxide, 

10,818 mg U/kg/day as uranyl fluoride, 12,342 mg U/kg/day as uranium dioxide, 11,650 mg U/kg/day as 

triuranium trioxide, or 7,859 mg U/kg/day as uranium acetate dihydrate for 30 days (Maynard and Hodge 

1949). Sprague-Dawley rats (10/sex/dose, 60 g) were exposed to uranium as uranyl nitrate in drinking 

water (males: up to 35.3 mg/kg/day; females: up to 40.0 mg/kg/day) for 28 days and then sacrificed. No 

treatment-related histopathological changes were found, and no changes in liver weights were noted 

(Gilman et al. 1998a). 

Significant increases in plasma cholesterol (41%) were observed in rats exposed to approximately 2 mg 

U/kg/day as depleted uranyl nitrate in drinking water for 9 months (Souidi et al. 2005); the toxicological 

significance of this increase is not known. 

Renal Effects. Uranium has been identified as a nephrotoxic metal, exerting its toxic effect by 

chemical action mostly in the renal proximal tubules of humans and animals. In this regard, uranium is a 

less potent nephrotoxin than the classical nephrotoxic metals (cadmium, lead, mercury) (Goodman 1985). 

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Few human data are available that adequately describe the dose-response toxicity of uranium after an oral 

exposure. In one human case report study (Pavlakis et al. 1996), acute nephrotoxicity was diagnosed in a 

male following the intentional ingestion of 15 g of uranyl acetate (approximately 131 mg/kg using a 

reference body weight of 70 kg), along with an unknown quantity of benzodiazepine, in a failed suicide 

attempt. Initial blood chemistry was normal; however, 16 hours after admission, his blood urea levels had 

doubled and creatinine levels had increased 3.5-fold, which suggested renal damage; the patient 

underwent chelation therapy and dialysis. At 6 months following the initial toxic insult, the patient still 

suffered from an incomplete Fanconi syndrome (renal tubular acidosis). A pre-existing peptic ulcer 

disease in this patient may have exacerbated toxicity by increased absorption of uranium through the 

damaged stomach mucosal layer. 

Several epidemiology studies (Kurttio et al. 2002, 2006a; Limson Zamora et al. 1998, 2009; Mao et al. 

1995; Seldén et al. 2009) examined the possible association between chronic exposure to elevated levels 

of uranium in drinking water and alterations in kidney function. Mao et al. (1995) found a significant 

association between cumulative uranium exposure (product of uranium concentration in drinking water, 

reported average number of cups of water consumed per day, and the total years at the current residence) 

and urine albumin levels (expressed as mg/mmol creatinine) in adults living in households with elevated 

uranium levels in drinking water. The mean uranium levels in the drinking water were 19.6 and 

14.7 μg/L in the exposed group and 0.71 μg/L in the control group. Although a significant association 

between cumulative uranium exposure and urinary albumin levels was found, the albumin levels were 

within the normal range for most subjects. 

A significant association between uranium intake levels and urinary glucose, β2-microglobulin, and 

alkaline phosphatase levels were observed in males and females living in an area of high uranium levels 

in the drinking water; total uranium intake ranged from 3 to 570 μg/kg (0.00004–0.0085 mg/kg/day, 

assuming a reference body weight of 70 kg) (Limson Zamora et al. 1998). 

In a second study by this group (Limson Zamora et al. 2009), urine uranium levels (adjusted for fluid 

intake) were significant positively correlated with urine volume, specific gravity, γ-glutamyl transferase, 

and β2-microglobulin levels in a group of 54 residents exposed to various levels of uranium in drinking 

water. The estimated average uranium intake for the group was 0.00065 mg/kg/day; however, uranium 

intake was estimated from data for all subjects, which included eight subjects with a uranium intake of 

<0.0000013 mg/kg/day (1.3 ng/kg/day). 

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No significant differences in kidney function parameters were found in 301 residents consuming drinking 

water from wells drilled in bedrock areas and 153 consuming municipal water (Seldén et al. 2009). When 

the two populations were combined, urinary uranium levels were significantly correlated with 

β2-microglobulin, kappa immunoglobulin light chains, and protein HC levels; however, there was no 

dose-response relationship. Excluding 23 subjects with diabetes resulted in a tendency toward a doseresponse relationship. The median, mean, and range of uranium levels in the drinking water from wells 

were 6.7, 25.2, and <0.20–470 μg/L, respectively; the municipal water uranium levels were below the 

detection limit of 0.2 μg/L. The respective median and geometric mean urine uranium levels were 

0.013 and 0.016 nmol/mmol creatinine in the well water group and 0.0019 and 0.0020 nmol/mmol 

creatinine in the municipal water group. 

A weak significant association between urinary uranium levels and fractional excretion of calcium and 

phosphate were observed in 325 Finnish residents exposed to uranium in drinking water from bored wells 

(Kurttio et al. 2002); a tendency for increased glucose excretion was also observed. However, the lack of 

information on calcium and phosphate levels in the drinking water limits the interpretation of these 

results. The investigators noted that calcium, phosphate, and glucose excretion levels were within the 

normal range. Urinary uranium levels ranged from 1 to 5,650 μg/L (1.9–955 ng/mmol creatinine) and the 

mean and median levels were 424 and 78 μg/L (73 and 13 ng/mmol creatinine), respectively. The mean 

uranium intake was 3.2 mg/kg/day. No significant associations were found for β2-microglobulin levels or 

indicators of glomerular dysfunction (creatinine clearance or urinary albumin). Several years later, 

Kurttio et al. (2006a) examined a subset of these subjects and did not find significant associations 

between urinary uranium levels and calcium, phosphate, and glucose excretion. However, a significant 

association between cumulative uranium intake and urinary glucose levels was found. 

There is sufficient information in animals with high exposures to both soluble and insoluble uranium to 

conclude that uranium is a renal toxicant. The pathogenesis of the kidney damage in animals indicates 

that regeneration of the tubular epithelium occurs in survivors upon discontinuation of exposure to 

uranium (Bentley et al. 1985; Dygert 1949b; Maynard and Hodge 1949; Pozzani 1949; Rothermel 1949; 

Rothstein 1949c; Spiegl 1949; Stokinger et al. 1953). 

Two single exposure studies have reported renal damage. Marked increases in blood urea and creatinine 

levels and tubular necrosis were observed after 2 days in Balb-c mice administered a lethal (animals died 

on day 3) gavage dose of 166 mg U/kg as uranyl nitrate hexahydrate (Martinez et al. 2003). Evidence of 

renal dysfunction (increased urine volume, increased plasma urea and creatinine levels, and increased 

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urinary total protein and creatinine levels) and minimal microscopic lesions (moderate hyperemia and 

discrete microhemorrhagic foci) in the tubular epithelium were observed in male Sprague-Dawley rats 

exposed to a single gavage dose of 5.6 mg U/kg as uranyl acetate dihydrate (Domingo et al. 1987). In a 

repeated exposure acute-duration study, significant increases in BUN, serum creatinine, and serum 

alkaline phosphatase levels were observed in Swiss albino mice exposed to 508 mg U/kg/day as uranyl 

acetate dihydrate in the diet for 5 days (Ozmen and Yurekli 1998). 

The renal toxicity of uranium compounds following intermediate-duration exposure has been examined in 

rats, rabbits, and dogs (Gilman et al. 1998a, 1998b, 1998c; Maynard and Hodge 1949; McDonald-Taylor 

et al. 1992, 1997). No histological alterations were observed in the kidneys of Sprague-Dawley rats 

exposed to doses as high as 35.3 mg U/kg/day (males) or 40.0 mg U/kg/day (females) as uranyl nitrate in 

drinking water for 28 days (Gilman et al. 1998a). The only effect observed was a significant increase in 

serum uric acid in females at 40 mg U/kg/day (1.64 vs. 1.18 mg/dL in controls). Similarly, no 

histological alterations were observed in Sprague-Dawley rats exposed to doses as high as 4.5 mg 

U/kg/day as uranyl acetate in drinking water for 4 weeks (Ortega et al. 1989a); small congestion of the 

kidney and a moderate increase in lysosomal content of the proximal convoluted tubule epithelial cells 

were observed at 9 mg U/kg/day. In addition, a slight, non-dose-related increase in total plasma protein 

levels was observed at ≥1.1 mg U/kg/day. 

Extending the exposure duration to 91 days resulted in a number of kidney effects in Sprague-Dawley rats 

exposed to uranyl nitrate in drinking water (Gilman et al. 1998a). At the lowest dose tested in males 

(0.06 mg U/kg/day), histological alterations were observed in the renal tubules (nuclear vesiculation, 

cytoplasmic vacuolation, and tubular dilation) and interstitium (lymphoid cuffing). Exposure to ≥0.31 mg 

U/kg/day resulted in glomerular adhesions and tubular cytoplasmic degeneration. Although female rats 

were equally susceptible to the renal toxicity of uranyl nitrate, the observed histological alterations 

differed from the males. In the females exposed to ≥0.09 mg U/kg/day, capsular sclerosis, tubular 

anisokaryosis, tubular nuclear vesiculation, and interstitial reticulin sclerosis were observed. The 

differences in renal effects between the male and female rats do not appear to be related to uranium levels 

in the kidney. Although uranium levels were not measured at the lowest dose levels, exposure to 7.54 or 

9.98 mg U/kg/day resulted in kidney uranium levels of 0.42 and 0.42 μg/g in males and females, 

respectively. 

Gender-related differences in the renal toxicity of uranium were also observed in New Zealand rabbits 

exposed to uranyl nitrate in the drinking water for 91 days (Gilman et al. 1998b). Histopathological 

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alterations observed in males exposed to ≥0.05 mg U/kg/day included cytoplasmic vacuolation, 

anisokaryosis, and nuclear vesiculation in proximal tubular cells. At the lowest dose tested in females 

(0.49 mg U/kg/day), anisokarysois, nuclear vesiculation, and atrophy were observed in the proximal 

tubules. At higher doses, interstitial reticulin sclerosis (0.88 and 1.32 mg U/kg/day in males and females) 

and interstitial collagen sclerosis (4.82 and 43.02 mg U/kg/day in males and females) were also observed. 

In contrast to the results of this study, another 91-day study conducted by Gilman et al. (1998c) did not 

find statistically significant increases in the incidence of histological alterations in the kidneys of New 

Zealand rabbits exposed to 1.36 mg U/kg/day as uranyl nitrate in the drinking water for 91 days. 

Exposure to 40.98 mg U/kg/day resulted in increases in the incidence of cytoplasmic vacuolation, 

anisokaryosis, nuclear hyperchromicity, tubular dilation, tubular atrophy, and interstitial collagen and 

reticulum sclerosis. Most of these histological alterations persisted throughout a 91-day recovery period. 

Electron micrographic examination of the glomeruli and proximal tubules were conducted by McDonaldTaylor et al. (1992, 1997). A dose-related increase in the thickness of the glomerular basement 

membrane was observed in the 1.36 and 40.98 mg U/kg/day groups; as compared to the control group, the 

glomerular basement membranes were 20 and 36% thicker in the 1.36 and 40.98 mg U/kg/day groups, 

respectively (McDonald-Taylor et al. 1992). Observed effects in the proximal tubules included lumens 

filled with debris, a reduction in the height of epithelial cells, focal loss of brush border, splitting of the 

basal lamina, and renal interstitial fibrosis (McDonald-Taylor et al. 1997); these alterations were more 

common in the 40.98 mg U/kg/day group, but were also observed in some animals in the 1.36 mg 

U/kg/day group (incidence not reported). At the end of the 91-day recovery period, there was an increase 

in the thickness of the glomerular basement membrane and an increase in the severity of the proximal 

tubule lesions, as compared to values in rabbits killed at the end of the exposure period (McDonaldTaylor et al. 1992, 1997). The results of this study (Gilman et al. 1998c) conflict with the results of this 

group’s previous rabbit study (Gilman et al. 1998b). The investigators suggested that there were 

differences in the ways that animals in the two studies handled the ingested uranium and that the animals 

in the Gilman et al. (1998c) study more effectively cleared the uranium resulting in lower uranium levels 

in the kidney and bone. In this study (Gilman et al. 1998c), the uranium levels in the kidney and bone in 

rabbits ingesting a total intake of 3,557.25 mg U/kg/91 days were 3.48 and 2.89 μg/g, as compared to 

kidney and bone levels of 4.98 and 4.04 μg/g in rabbits ingesting 2,677.87 mg U/kg/91 days (Gilman et 

al. 1998b). Additionally, the investigators noted that some of the rabbits in the Gilman et al. (1998b) 

study were infected with Pasteurella mutocida; although animals with known infections were excluded 

from the study, some of the remaining rabbits may have had subclinical infections that may have affected 

their response to administered uranium. 

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In a longer exposure study, tubular dilation and the presence of hyaline casts were observed in the kidneys 

of male Sprague-Dawley rats exposed to 1 mg U/kg/day as depleted uranyl nitrate hexahydrate in mineral 

water for 9 months (Berradi et al. 2008). Depleted uranium exposed rats had a slightly higher incidence 

of marked tubule-interstitial lesions than controls (3/7 compared to 1/7 for controls). A slight increase in 

the number of animals with slight glomerular lesions (5/7 compared for 3/7 in controls) was also observed 

in the depleted uranium exposed rats. 

Maynard and Hodge (1949) conducted a series of 30-day dietary exposure studies in rats and dogs using 

various uranium compounds. Although the results were poorly reported, the rat studies provide useful 

information for comparing the relative renal toxicity of different uranium compounds. No histological 

alterations were observed in the kidneys of rats exposed to 12,000 mg U/kg/day as uranium dioxide, 

uranium trioxide, or uranyl octaoxide or 11,000 mg U/kg/day as uranium tetrafluoride. Mild to moderate 

renal lesions were found in rats exposed to 440 mg U/kg/day as uranium tetrachloride (NOAEL of 90 mg 

U/kg/day) or 790 mg U/kg/day as uranium acetate (NOAEL of 200 mg U/kg/day). Mild histological 

alterations were observed in rats exposed to 200 mg U/kg/day as uranyl nitrate (NOAEL of 40 mg 

U/kg/day), 270 mg U/kg/day as uranyl fluoride (NOAEL of 140 mg U/kg/day), or 140 mg U/kg/day as 

uranium peroxide (NOAEL of 55 mg U/kg/day). The relative toxicity of the various uranium compounds 

were similar in the dog studies; however, the use of one dog per dose level limits the interpretative value 

of this study. 

Endocrine Effects. No endocrine effects after oral intake of uranium have been reported in humans. 

Few endocrine effects have been reported after uranium exposure in laboratory animals. In animal 

studies, a dose of 0.07 mg U/kg/day as uranyl nitrate hexahydrate for 16 weeks in drinking water resulted 

in degenerative changes in the thyroid epithelium and altered thyroid function in Wistar rats 

(Malenchenko et al. 1978). Sprague-Dawley rats (10/sex/dose) were exposed to uranium as uranyl nitrate 

in drinking water (males: up to 35.3 mg U/kg/day; females: up to 40.0 mg U/kg/day) for 28 days and 

then sacrificed. No treatment-related histopathological changes were found in any of the endocrine 

organs studied (adrenal, pancreas, parathyroid, pituitary, thymus, thyroid), and no treatment-related 

changes in these organ weights were noted (Gilman et al. 1998a). In addition, New Zealand rabbits were 

exposed to uranium as uranyl nitrate in the drinking water (males: up to 28.70 mg U/kg/day; females: up 

to 43.02 mg U/kg/day) for 91 days. No treatment-related histopathological changes were found, and no 

weight changes in the adrenal, pancreas, parathyroid, or pituitary glands were noted (Gilman et al. 

1998b). Male New Zealand rabbits exposed to uranium as uranyl nitrate in drinking water (1.36 and 

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40.98 mg U/kg/day) for 91 days also failed to show any treatment-related histopathological or organ 

weight changes (Gilman et al. 1998c). In another study, Sprague-Dawley rats (15/sex/dose) were exposed 

to uranium as uranyl nitrate in the drinking water (males: up to 36.73 mg U/kg/day; females: up to 

53.56 mg U/kg/day) for 91 days. Thyroid lesions were observed in both sexes (multifocal reduction of 

follicular size, increased epithelial height in males at 0.31 mg U/kg/day and females at 2.01 mg 

U/kg/day). A decreased amount and density of colloid in the thyroid was observed in males only. 

Body Weight Effects. No body weight effects after oral intake of uranium have been reported in 

humans. 

Oral exposure to uranium compounds has caused body weight effects in animals, but these effects are not 

necessarily the result of systemic toxicity. The initial loss of body weight observed in animals exposed to 

high doses of uranium in the diet in acute-, intermediate-, and chronic-duration studies is usually 

accompanied by decreased food consumption in these animals. The decreased food consumption could 

be due to the aversive taste of uranium compounds in food. Subsequent acclimatization of the animals to 

the taste would normalize food intake and, consequently, reverse the initial loss of body weight. Thus, 

the changes in body weight seen in such studies may be a result of reduction in food consumption due to 

distaste rather than of uranium-specific chemical or radiological toxicity. 

Rats given single oral doses of 664 mg U/kg as uranyl nitrate hexahydrate or 55 mg U/kg as uranium 

peroxide (Maynard et al. 1953), 7,859 mg U/kg as uranium acetate dihydrate for 30 days (Maynard and 

Hodge 1949), or 664 mg U/kg as uranyl nitrate hexahydrate for 30 days in the feed suffered unspecified 

decreases in body weight gain (Maynard et al. 1953). In a 2-week drinking water study in rats, doses of 

28 mg U/kg/day as depleted uranyl acetate dihydrate resulted in a 53% reduction in body weight gain in 

males; food consumption data were not provided (Briner and Murray 2005). In the same study, exposure 

for 6 months reduced body weight gain by approximately 46% in males and 36% in females; no 

significant effects were reported at 14 mg U/kg/day either in the 2-week or the 6-month experiments. In a 

developmental study in which rats were administered between 2.8 and 28 mg U/kg/day by gavage doses 

on gestation days 6–15, body weight gain during the treatment period was 33–88% lower than the control 

group (Domingo et al. 1989c); this was associated with significant reductions in food consumption. Body 

weight losses of 18, 35, 27, 20, and 29%, respectively, were observed in rats given oral doses of 886 mg 

U/kg/day as uranium tetrachloride, 1,081 mg U/kg/day as uranyl fluoride, or 664 mg U/kg/day as uranyl 

nitrate hexahydrate for 30 days (Maynard and Hodge 1949); rabbits given oral doses of 14.2 mg U/kg/day 

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as uranyl nitrate hexahydrate for 30 days (Maynard and Hodge 1949); and rats given oral doses of 270 mg 

U/kg/day as uranyl fluoride for 2 years (Maynard and Hodge 1949; Maynard et al. 1953). 

No harmful effects on body weight were seen in rats given 12,342 mg U/kg as uranium dioxide or 

11,650 mg U/kg as uranium trioxide for 30 days (Maynard and Hodge 1949), mice given 1,100 mg U/kg 

as uranyl nitrate hexahydrate for 18 weeks or 462 mg U/kg as uranyl nitrate hexahydrate for 48 weeks 

(Tannenbaum et al. 1951), or Sprague-Dawley rats exposed to uranium as uranyl nitrate in drinking water 

at doses up to 35.3 mg U/kg/day (males) and 40 mg U/kg/day (females) for 28 days or up to 36.73 mg 

U/kg/day (males) and 53.56 mg U/kg/day (females) for 91 days (Gilman et al. 1998a). No alterations in 

body weights were observed in rats given 12,341 mg U/kg as uranium dioxide or 10,611 mg U/kg as 

uranium hexafluoride for 2 years, or dogs given 8 mg U/kg as uranyl fluoride or 95 mg U/kg as uranyl 

nitrate hexahydrate for 1 year (Maynard and Hodge 1949; Maynard et al. 1953). Reduced food intake 

was observed following a single oral dose of 5.6 mg U/kg as uranyl nitrate hexahydrate to rats (Domingo 

et al. 1987) and in a 48-week study in rats and mice at 1,100 mg U/kg/day as uranyl nitrate hexahydrate 

(Tannenbaum et al. 1951). It has been suggested that this reduced food intake is a result of loss of 

appetite due to the unpalatability of the uranium compounds in the animals’ food (Dygert 1949e). In two 

more recent drinking water studies in rats, doses of approximately 2–2.7 mg U/kg/day as uranyl nitrate 

hexahydrate in mineral water for up to 9 months did not significantly affect body weight or food or water 

consumption (Bensoussan et al. 2009; Bussy et al. 2006). In mice, exposure via the drinking water to up 

to 100 mg U/kg/day as uranyl nitrate hexahydrate for 15 weeks had no significant effect on body weight 

(Arnault et al. 2008). 

Metabolic Effects. Tissandié et al. (2006, 2007) found alterations in 1,25(OH)2D3 (active form of 

vitamin D) levels in rats exposed to a single gavage dose of depleted uranyl nitrate or depleted uranyl 

nitrate in mineral water for 9 months. One day after gavage administration of 97 mg U/kg, a significant 

62% increase in 1,25(OH)2D3 level was observed in male Sprague-Dawley rats; 3 days after 

administration, there was a significant decrease (68% compared to controls) in the level (Tissandié et al. 

2006). Significant decreases in serum inorganic phosphate levels (15% at day 1 and 28% at day 3) and 

parathyroid hormone (day 3 only) levels (90%) were also observed. Intermediate-duration exposure to 

1 mg U/kg/day also resulted in significant decreases in 1,25(OH)2D3 levels; however, no alterations in 

25(OH)D3 (vitamin D metabolite), plasma calcium, inorganic phosphate, parathyroid hormone, or 

osteoclacin levels were found (Tissandié et al. 2007). Alterations in mRNA expression levels of cyp24a1 

(encoding the enzyme that directs the catabolism of vitamin D) and vitamin D target genes involved in 

calcium homeostasis were also observed in the 9-month study. 

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Souidi et al. (2005) examined the effect on exposure of rats to approximately 2 mg U/kg/day as depleted 

uranyl nitrate in drinking water for 9 months on gene expression of cytochrome P450 enzymes in the 

brain, lung, liver, kidney, and intestine. Significant increases in mRNA expression were observed for 

CYP3A1 in the brain, liver, and kidneys; CYP3A2 in the lungs and liver; and CYP2B1 in kidneys. No 

significant alterations in CYP1A1 mRNA expression were observed. The nuclear receptors involved in 

gene control of CYP3A and CYP2B, pregnane X receptor and constitutive androstane receptor, were also 

increased. 

3.2.2.3 Immunological and Lymphoreticular Effects 

No information was located regarding the effects of uranium on the immune system in humans following 

oral exposure for any duration. 

In laboratory animals, oral exposure of rats, mice, and rabbits to uranium had no significant effect on 

immune system function. In one study, Sprague-Dawley rats (10/sex/dose) were exposed to uranium as 

uranyl nitrate in drinking water (males: up to 35.3 mg U/kg/day; females: up to 40.0 mg U/kg/day) for 

28 days and then sacrificed. No treatment-related effects were noted in the lymphoreticular tissues 

examined (bone marrow, mesenteric and mediastinal lymph nodes, spleen, and thymus) (Gilman et al. 

1998a). In addition, New Zealand rabbits were exposed to uranium as uranyl nitrate in the drinking water 

(males: up to 28.70 mg U/kg/day; females: up to 43.02 mg U/kg/day) for 91 days. No histopathological 

changes were found, and no changes in the bone marrow, mesenteric and mediastinal lymph nodes, or 

thymus were noted (Gilman et al. 1998b). Rats exposed to oral doses of 0.07 mg U/kg as uranyl nitrate 

hexahydrate for 4 weeks showed an increase in spleen weight but the body weights of both the control 

and test animals were not provided, making it impossible to determine whether the net change in spleen 

weight had any toxicological significance (Malenchenko et al. 1978). Sprague-Dawley rats exposed to 

uranium as uranyl nitrate in drinking water (males: up to 36.73 mg U/kg/day; females: up to 53.56 mg 

U/kg/day) for 91 days showed sinus hyperplasia of the spleen in both sexes at the highest dose (males: 

36.73 mg U/kg/day; females: 53.56 mg U/kg/day). No lesions were observed in bone marrow, 

mesenteric and medistinal lymph nodes, or thymus (Gilman et al. 1998a). In other studies with mice and 

rats, no histological changes in the spleen, lymph nodes, or bone marrow were seen in the animals 

following administration of up to 5,000 mg U/kg of various uranium compounds (uranyl nitrate 

hexahydrate, uranyl fluoride, uranium dioxide, uranium peroxide, uranium tetrafluoride, uranium 

tetrachloride, triuranium octaoxide, or uranium trioxide) in the diet for 48 weeks or 2 years. No 

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consistent hematological changes were found in hematocrit, hemoglobin, or white blood cell counts 

(Maynard et al. 1953; Tannenbaum et al. 1951). No other specific immunological tests were performed. 

3.2.2.4 Neurological Effects 

No studies were located for humans regarding neurological effects following oral exposure to uranium 

compounds. 

There is a limited number of reports of neurological effects in animals following acute oral exposure to 

uranium compounds. A study aimed at determining an oral LD50 for uranyl acetate dihydrate in SpragueDawley rats given single gavage doses ranging from 11 to 717 mg U/kg reported piloerection, tremors, 

hypothermia, pupillary size decreases, and exophthalmos (Domingo et al. 1987). The signs became more 

severe as the number of days posttreatment increased; however, the study did not specify the dose levels 

at which the various clinical signs appeared. 

Two more recent acute-duration studies focused on the neurobehavioral effects of uranium and on effects 

on brain neurotransmitters. Administration of 28 mg U/kg/day (depleted uranyl acetate dihydrate) to 

Long-Evans rats via the drinking water for 2 weeks significantly increased motor activity in males as 

judged by number of lines crossed and rearing frequency, no significant effect was reported at 14 mg 

U/kg/day (Briner and Murray 2005); no significant alterations in open-field behavior were observed in 

females. Lipid oxidation in the brain was significantly increased in males and females dosed with 28 mg 

U/kg/day. According to the investigators, lines crossing and rearing frequency exhibited significant 

correlations with brain lipid oxidation, but the correlation coefficients were only 0.21 and 0.23, 

respectively, indicating that only about 4% of the variance in the behavioral tests could be explained by 

changes in lipid oxidation. Briner and Murray (2005) also exposed rats for 6 months to 14 or 28 mg 

U/kg/day and obtained similar results, except that after 6 months of dosing, lipid oxidation did not 

correlate with line crossing or rearing behavior. In a 2-week study in Swiss-Webster mice that also 

measured neurotransmitters and their metabolites in the midbrain, exposure to 6 mg U/kg/day (depleted 

uranyl acetate dihydrate; only dose level tested) significantly increased open-field line crossing in 

females, but not in males (Briner 2009). Exposure to uranium significantly increased tyrosine and 

decreased 3,4-dihydroxyphenylalanine (DOPA), norepinephrine (NE), and epinephrine (E); it had no 

significant effect on dopamine (DA) or homovanillic acid (HVA). According to the investigator, levels of 

DOPA in the midbrain were inversely related to lines crossed in open field (r2

=0.12). Exposure to 

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uranium significantly increased brain lipid oxidation, but lipid oxidation did not correlate with levels of 

tyrosine, DOPA, NE, E, or HVA. 

Intermediate-duration oral studies that examined the gross and microscopic appearance of the brain of 

animals exposed to uranium have not reported compound-related alterations in male and female 

Sprague-Dawley rats exposed via drinking water to up to 40 mg U/kg/day as uranyl nitrate for 28 days or 

up to 54 mg U/kg/day for 91 days (Gilman et al. 1998a), and in male and female New Zealand rabbits 

similarly exposed to up to 43 mg U/kg/day for 91 days (Gilman et al. 1998b). 

Intermediate-duration studies have also examined the effects of uranium on behavior, transmitter levels in 

the brain, including genes involved in neurotransmitter metabolism, and oxidative stress in the brain. 

A study of neurotransmitter levels in the brain of male Sprague-Dawley rats following 1.5, 6, or 9 months 

of dosing with approximately 2.7 mg U/kg/day as depleted uranyl acetate dehydrate in mineral water; 

only dose level tested) reported that acetylcholinesterase activity was not significantly affected in the 

striatum, hippocampus, or frontal cortex at any time point, but it was significantly decreased in the 

cerebellum at 6 months (Bussy et al. 2006). Of many biochemical measurements conducted, the only 

significant changes were as follows: increased dopamine in the hypothalamus at 1.5 months, decreased 

ratio (3,4-dihydroxyphenylacetic acid [DOPAC]+HVA)/DA in the frontal cortex at 6 months, decreased 

5HIAA and the ratio 5HIAA/5HT in the frontal cortex at 9 months, and decreased DOPAC and 

(DOPAC+HVA)/DA in the striatum at 9 months. Uranium significantly increased in the striatum at 

1.5 months and to a lesser extent at 9 months (not measured at 6 months). Bensoussan et al. (2009) 

examined alterations in cholinergic system in response to a 1.5- or 9-month exposure to 2 mg U/kg/day as 

uranyl nitrate in mineral water. After 1.5 months of exposure, there were significant decreases in 

acetylcholine levels and acetylcholinesterase activity in the cortex; there were no alterations in the 

hippocampus. At 9 months, there was a decrease in acetylcholinesterase activity in the cortex, but no 

changes in acetylcholine levels, and no alterations in the hippocampus. Based on alterations in gene 

expression, the investigators noted that exposure to uranium seemed to induce transcriptional alterations 

in the hippocampus aimed at preserving acetylcholine levels, whereas in the cortex, exposure led mainly 

to translational alterations that increased acetylcholinesterase levels after 9 months of exposure. The 

investigators also noted that the lack of correlation between the increase in genes expressing cortical 

acetylcholinesterase and the decrease in acetylcholinesterase activity in the cortex could be explained by 

the complex relation between mRNA and enzyme activity. 

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A 3-month drinking water study in male Sprague-Dawley rats dosed with up to 22.4 mg U/kg/day (uranyl 

acetate dihydrate) that conducted behavioral tests including open-field activity, passive avoidance, and 

Morris water maze reported that exposure to uranium did not significantly affect any of the behavioral 

tests (Belles et al. 2005). A study that compared the effects of depleted and 4% enriched uranium (2.7 mg 

U/kg/day in mineral water for 1.5 months) in Sprague-Dawley rats reported that whole brain of controls 

had comparable amounts of uranium as brains of rats exposed to depleted or enriched uranium (Houpert 

et al. 2005). However, uranium was 1.5–2 times higher in the hypothalamus and hippocampus from rats 

dosed with enriched uranium than in control rats or rats exposed to depleted uranium. No significant 

increases in uranium levels were observed in the cortex, striatum, brainstem, or cerebellum were observed 

in the enriched or depleted uranium groups. Rats exposed to enriched uranium had a significant increase 

in the amount of paradoxical sleep (37%) compared to controls. In addition, exposure to enriched, but not 

depleted, uranium significantly decreased spatial working memory capacities and increased anxiety. In 

an additional study by the same group of investigators, male Sprague-Dawley rats exposed to 2.5 mg 

U/kg/day as 5.26% enriched uranyl nitrate for 9 months via the mineral water (Houpert et al. 2007b). 

Four neurobehavioral tests (activity in open field, a two-object recognition task, a test for spatial working 

memory in a Y-maze, and a forced swimming test) were conducted before dosing started and at 3, 6, and 

9 months. The only test that was affected by exposure to uranium was the spatial working memory test 

after 3 and 9 months of exposure, but not after 6 months. The investigators suggested that the results may 

indicate that enriched uranium disrupts memory in a spatial task involving the hippocampus but does not 

affect memory in another task in which hippocampal functioning is less crucial. 

In a study examining the effects of uranium on the sleep cycle, Sprague-Dawley rats were exposed to 

uranium in drinking water for 90 days. An increase in the amount of time spent in rapid eye movement 

(REM) sleep was observed in rats exposed to 3.7 mg U/kg/day as 4.92% enriched uranyl nitrate in 

mineral water for 30 or 60 days; a nonsignificant increase was observed after 90 days of exposure 

(Lestaevel et al. 2005). This increase in REM sleep was due to the number of REM sleep episodes rather 

than an increase in the duration of REM episodes. The increases in the amount of REM sleep primarily 

occurred during the light period (normal sleeping period for rats), suggesting that the circadian rhythms 

were not affected by uranium exposure. 

The highest NOAEL values and all reliable LOAEL values in each species and duration category for 

neurological effects from exposure to uranium by the oral route are presented in Table 3-2 and plotted in 

Figure 3-2. 

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3.2.2.5 Reproductive Effects 

No human studies were located regarding reproductive effects following oral exposure to uranium 

compounds. 

Some animal studies, mostly in rodents, have shown effects on some aspects of male and female 

reproductive function following exposure to uranium. For the most part, general toxicity studies that 

conducted gross and microscopic examination of the reproductive organs did not report adverse effects. 

For example, no histopathology or changes in reproductive organ weight were reported in SpragueDawley rats exposed to uranium as uranyl nitrate in the drinking water (males: up to 35.3 mg U/kg/day; 

females: up to 40.0 mg U/kg/day) for 28 days (Gilman et al. 1998a). No reproductive effects or changes 

in reproductive organ weights were found in the epididymis, testes, ovary, or uterus of Sprague-Dawley 

rats (15/sex/dose) exposed to uranium as uranyl nitrate in drinking water (males: up to 36.73 mg 

U/kg/day; females: up to 53.56 mg U/kg/day) for 91 days (Gilman et al. 1998a). New Zealand rabbits 

exposed to uranium as uranyl nitrate in the drinking water (males: up to 28.70 mg U/kg/day; females: up 

to 43.02 mg U/kg/day) for 91 days showed no histopathological or organ weight changes in the 

epididymis, ovary, testes, or uterus (Gilman et al. 1998b). 

Fertility has been assessed in a few studies. Fertility was not significantly affected in a study in which 

male Swiss mice were given gavage doses of up to 14 mg U/kg/day as uranyl acetate dihydrate for 

60 days before mating with females that had received the same doses for 14 days (Paternain et al. 1989). 

In a 64-day drinking-water study with Swiss-Webster mice, treatment of males with ≥5.6 mg U/kg/day 

(uranyl acetate) followed by mating with untreated females resulted in significant reductions in pregnancy 

rates, which were associated with significant reductions in spermatozoa counts and reduced epididymal 

weights (Llobet et al. 1991). Treatment of male Sprague-Dawley rats with 11.2 mg U/kg/day (uranyl 

acetate) in the drinking water for 3 months before mating with untreated females also resulted in a 

significant reduction in pregnancy rate; no significant effect was reported at 5.6 mg U/kg/day (Linares et 

al. 2005). In this study, there were no significant effects on the number of total implants/litter or number 

of viable and nonviable implants/litter. Neither the absolute nor relative weight of the testes and 

epididymis was significantly affected; a significant decrease in the number of spermatid/testis was 

observed at ≥11.2 mg U/kg/day. Microscopic examination of the testes showed a progressive, but not 

significant, loss of Sertoli cells or germinal cells with cytoplasmic vacuolization. 

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The effects of uranium on ovarian function have also been studied. Exposure of female C57Bl x CBA 

mice to ≥1.25 mg U/kg/day (uranyl nitrate hexahydrate) in drinking water for 15 weeks resulted in slight 

disturbance in ovarian folliculogenesis (Arnault et al. 2008). In a similar study, exposure of female Swiss 

mice to up to 10 mg U/kg/day (uranyl nitrate hexahydrate) for 40 days in drinking water did not alter the 

mean number of oocytes ovulated per female (Kundt et al. 2009). However, doses of ≥2.5 mg U/kg/day 

significantly increased (more than doubled) the percentage of dysmorphic oocytes; the increases consisted 

of increases in perivitaline space at ≥5 mg U/kg/day, lysed oocytes at 2.5 and 5 mg U/kg/day, fragmented 

oocytes at 10 mg U/kg/day, and nonspherical oocytes at ≥2.5 mg U/kg/day. Exposure to uranium also 

significantly increased the incidence of micronuclei in cumulus cells (oocyte-supporting cells); a strong 

correlation between the number of micronuclei and dose was found. The mitotic index in cumulus cells 

was significantly decreased in the mid- and high-dose groups in a dose-related fashion. Uranium also 

increased the number of metaphase plate abnormalities in oocytes arrested in metaphase II. In yet another 

study, exposure of hybrid female mice to up to 6.9 mg U/kg/day (uranyl nitrate hexahydrate) for 49 days 

in drinking water did not affect the number of ovulated oocytes (Feugier et al. 2008). Oocyte quality was 

not affected by the lowest dose tested (1.9 mg U/kg/day), but the proportion of healthy oocytes was 

reduced by half at doses ≥3.9 mg U/kg/day. Absence of the first polar body and abnormal perivitaline 

space were the main morphological alterations. An increase from the 3.9 to 6.9 mg U/kg/day dose did not 

increase the proportion of oocytes with abnormalities, but led to a diversification in oocyte abnormalities. 

Both Arnault et al. (2008) and Feugier et al. (2008) measured uranium in the ovaries and reported no 

significant accumulation of the chemical. Effects of uranium on ovarian folliculogenesis were also 

studied by Raymond-Whish et al. (2007). Administration of approximately 0.08 or 0.39 mg U/kg/day as 

depleted uranyl nitrate hexahydrate to 28-day-old B6C3F1 mice in tap water for 30 days significantly 

decreased the number of large primary follicles in the ovary, whereas a larger dose of 1.9 mg U/kg/day 

increased secondary or growing follicles. No significant alterations were observed at 9.3 mg U/kg/day. 

In a different experiment, female mice were exposed to much smaller doses (0.00008–0.009 mg 

U/kg/day) of uranium for 30 days prior to mating with untreated males and then continued to be dosed 

during gestation. Necropsy of dams on postnatal day 5 showed that doses ≥0.00039 mg U/kg/day 

significantly reduced the number of small primary follicles; however, all other follicle populations 

including primordial, secondary/growing, healthy, and atretic were unchanged. 

Raymond-Whish et al. (2007) also examined the potential estrogenic properties of uranium. Exposure of 

ovariectomized (at 28-days of age) mice to 0.009 mg U/kg/day as depleted uranyl nitrate hexahydrate for 

30 days significantly increased proliferation of the epithelial cell lining of the uterus, and uterus weight 

increased 3-fold; however, significant effects were not observed at 0.09 or 0.9 mg U/kg/day. In addition, 

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mice exposed to 0.005 and 0.009 mg U/kg/day had significantly increased presence of cornified vaginal 

cells, indicative of estrogenic effects of uranium. In a similar experiment, exposure of ovariectomized 

C57Bl/6J mice to 0.005 mg U/kg/day for 10 days beginning at 50 days of age significantly increased 

uterine weight and exposure to 0.009 mg U/kg/day significantly accelerated vaginal opening; both effects 

were blocked by intraperitoneal injections of an antiestrogenic drug. These effects were observed at 

doses that are several orders of magnitude lower than the adverse effect levels of other studies and were 

not observed at higher uranium doses. Additional research is needed to confirm these results; thus, the 

LOAEL values are not presented in Table 3-2 or plotted in Figure 3-2. 

A study was conducted to distinguish chemical versus radiological effects of uranium on the metabolism 

of steroids in rat testes (Grignard et al. 2008). Sprague-Dawley rats were exposed to 0 or 1.9 mg depleted 

or 4.24% enriched U/kg/day (uranyl nitrate hexahydrate) in the drinking water for 9 months. Exposure to 

depleted uranium did not significantly affect blood levels of testosterone or 17β-estradiol. Exposure to 

depleted uranium also did not significantly affect the levels of genes encoding proteins regulating steroid 

synthesis. In addition, depleted uranium did not significantly alter the expression levels of transcription 

factors regulating the expression of the genes that were monitored. Exposure to enriched uranium did not 

significantly affect blood levels of 17β-estradiol, but significantly increased testosterone levels and the 

expression of genes involved in steroidogenesis. In addition, enriched uranium significantly increased the 

expression of transcription factors involved in the regulation of steroidogenic genes. These results led the 

investigators to suggest that the adverse effects were mainly due to the radiological activity of the 

compounds. 

In chronic-duration studies, male rats given high oral doses (331 mg U/kg/day) of uranyl nitrate 

hexahydrate in the diet for 2 years developed testicular degeneration; female rats given oral doses of 

664 mg U/kg/day as uranyl nitrate hexahydrate for 2 years had reduced litter sizes (Maynard et al. 1953). 

Since incidence and dose-response data were not provided in this report, its significance is unclear. 

The highest NOAEL values and all reliable LOAEL values in each species and duration category for 

reproductive effects from exposure to uranium by the oral route are presented in Table 3-2 and plotted in 

Figure 3-2. 

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3.2.2.6 Developmental Effects 

No studies were located that reported developmental effects in humans following oral exposure to 

uranium for any duration. Animal studies indicate that oral exposure to uranium can cause developmental 

effects, but only at relatively high doses. 

Pregnant Swiss mice were exposed to uranium as uranyl acetate dihydrate by gavage in water at a dose of 

0.028, 0.28, 2.8, or 28 mg U/kg/day from gestation day 13 through postnatal day 21 (Domingo et al. 

1989b). Treatment had no significant effects on mean litter size at birth or on day 4, but litter size was 

significantly decreased at postnatal day 21 at 28 mg U/kg/day (5.5 vs. 8.8 in water-only controls). The 

viability index (number of pups viable at day 21/number of pups born) and the lactation index (number of 

pups viable at day 21/number of pups retained at day 4) were significantly decreased in the 

28 mg U/kg/day group. No significant differences were observed in developmental milestones (pinnae 

unfolding, lower incisor eruption, eye opening) or in pup weight or body length. Structural variations 

were not assessed in this report. Two dams in the 2.8 mg U/kg/day group and three in the 28 mg 

U/kg/day group died during the last period of gestation. Although the cause of death was not determined, 

it was attributed to the administration of uranium. Yet, the investigators stated that maternal toxicity was 

not evident from changes in body weight and/or food consumption. 

Increased late resorptions and decreased live fetuses were reported in Swiss mice administered 14 mg 

U/kg/day (uranyl acetate dihydrate) by gavage for 14 days before mating with males that received the 

same doses for 60 days; the females were sacrificed on gestation day 13 (Paternain et al. 1989). No 

significant effects were reported at 5.6 mg U/kg/day. In dams that were allowed to give birth and nurse 

the offspring until 21 days of age (dams’ exposure continued during gestation and lactation), doses of 

5.6 mg U/kg/day significantly increased neonatal death per litter, and the lowest dose tested, 2.8 mg 

U/kg/day, significantly reduced pup weight on postnatal day 21 (Paternain et al. 1989). No information 

was provided in this study regarding maternal effects. Dose-related fetotoxicity, manifested as reduced 

fetal body weight and length, increased incidence of stunted fetuses and external and skeletal 

malformations, and increased incidence of developmental variations were reported in the offspring of 

20 pregnant Swiss mice given uranyl acetate dihydrate (2.8, 5.6, 14, and 28 mg U/kg/day) by gavage on 

gestation days 6–15 and sacrificed on gestation day 18 (Domingo et al. 1989c). A significant increase in 

the number of external defects was observed at ≥2.8 mg U/kg/day. The external malformations included 

a significant increase in the incidence of cleft palate ( ≥5.6mg U/kg/day) and hematomas (at 2.8 and 

28 mg U/kg/day). A significant increase in the incidence of skeletal abnormalities (bipartite sternebrae 

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and reduced or delayed ossification of the hindlimb, forelimb, skull, and tail) was seen in the 14 and 

28 mg U/kg/day groups. Embryolethality was not found at any of the dose levels tested. Maternal 

toxicity was evident in all treated groups, as a dose-related significant reduction in maternal weight gain 

during exposure occurred (43% reduction in the lowest dose group, 82% in the highest dose group); this 

may have played a role in the observed developmental effects. 

More recent studies also provide information on the developmental effects of uranium. Exposure of 

female Sprague-Dawley rats to doses of 0, 22.5, or 45 mg U/kg/day (uranyl acetate dihydrate) in the 

drinking water for 4 weeks before mating with untreated males and continued dosing during gestation and 

lactation had no significant effect on pup developmental landmarks such as pinna detachment, incisor 

eruption, and eye opening (Sánchez et al. 2006). Neuromotor maturation was also not affected, but 

passive avoidance acquisition and retention time 24 hours after the test were significantly modified. The 

lowest dose tested significantly reduced pup body weight on postnatal day 21, but not on postnatal day 1. 

The only maternal effects reported in this study were a significant dose-related increase in body weight 

gain on gestation days 0–14 and a significant increase in gravid uterine weight at 45 mg U/kg/day; no data 

were provided regarding food consumption. Neurodevelopment was also examined by Houpert et al. 

(2007a) in offspring from Sprague-Dawley rats exposed to 0 or approximately 4.3 mg U/kg/day as 4.24% 

enriched uranyl nitrate hexahydrate in mineral water for 3 months before mating and during gestation and 

lactation. Behavioral tests were performed in male offspring at 2, 5, and 9 months. Rats were tested for 

locomotor activity and rearing indices, a spatial working memory test, and an elevated plus-maze test. At 

2 months, when the tests began, exposed pups were comparable to control pups in body weight and organ 

weight (brain, kidneys, femur, and skull). Uranium did not accumulate in the brain. The results of the 

motor and behavioral tests showed that exposure to uranium induced delayed hyperactivity in the 

offspring at 5 months and was more evident at 9 months. This was evidenced by increased rearing 

indices and activity in the open field, and increased activity in the two mazes. The results also showed a 

reversible slight decrease in spatial working memory. The only information regarding the dams in this 

study was that body weight gain during gestation was comparable between treated and control groups. 

Two studies reported effects on ovarian folliculogenesis in female offspring from exposed mice. Arnault 

et al. (2008) exposed C57Bl x CBA mice to 0, 1.25, 12.5, or 100 mg U/kg/day (uranyl nitrate 

hexahydrate) in the drinking water for 15 weeks. Mice were then mated to untreated males, and dams and 

female pups were sacrificed 3 months later. Microscopic examination of the ovaries of the female pups 

showed that pups from exposed dams had a significantly decreased percentage of the largest follicles. 

The investigators noted that the effect could be due either to a direct effect of transplacental transfer of 

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URANIUM 155 

3. HEALTH EFFECTS 

uranium or to an indirect effect resulting from uranium-induced physiological disturbances in the dams, 

or both. In the other study, B6C3F1 mice were exposed via the tap water to low uranium doses ranging 

from approximately 0.00008 to 0.00093 mg U/kg/day as depleted uranyl nitrate hexahydrate for 30 days 

prior to breeding with untreated males (Raymond-Whish et al. 2007); treatment continued during 

gestation. In female pups, sacrificed on postnatal day 5, exposure to 0.00008 or 0.00093 mg U/kg/day 

significantly reduced primordial follicles. Nonsignificant decreases in primordial follicles were observed 

at 0.00039 and 0.00019 mg U/kg/day. The investigators noted that neonatal mouse ovaries only have 

oogonia and primordial follicles. These results in pups are analogous to the results in mouse dams, notmated mice, and immature mice. 

A study is available that examined the effect of a high dose of uranium on tooth eruption and 

development in young Wistar rats (Pujadas Bigi et al. 2003). One- or 7-day-old rats were administered a 

single gavage dose of 0 or approximately 42.7 mg U/kg (uranyl nitrate hexahydrate) in water and were 

sacrificed on days 7 or 14, respectively. Hemimandibles were resected and processed for microscopic 

examination. Bone formation was significantly reduced in the bucal and lingual aspects of 7-day-old 

treated rats. Bone resorption was significantly higher in the occlusal and lingual aspects of both 1- and 

7-day-old treated rats. Tooth eruption was significantly lower in both treated groups compared with 

controls. Tooth development was also found to be significantly diminished in both treated groups 

compared with controls. The investigators suggested that the delay in tooth eruption may be due to 

decreased bone formation in the developing alveolar bone. They further speculated that the diminished 

tooth development may be caused by a toxic effect on Hertwig's sheath cells, odontoblasts, and 

cementoblasts. In a more recent study, the investigators showed that the delay in tooth eruption, dental 

development, and mandibular growth observed 7 days postdosing with uranium was no longer evident 

after day 27 (Pujadas Bigi and Ubios 2007). 

The highest NOAEL values and all reliable LOAEL values in each species and duration category for 

developmental effects from exposure to uranium by the oral route are presented in Table 3-2 and plotted 

in Figure 3-2. 

3.2.2.7 Cancer 

No evidence linking oral exposure to uranium to human cancer has been found. Although natural, 

depleted, or enriched uranium and uranium compounds have not been evaluated in rodent cancer 

bioassays by any route by the NTP (BEIR 1980, 1988, 1990; Hahn 1989; Sanders 1986; UNSCEAR 

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URANIUM 156 

3. HEALTH EFFECTS 

1982, 1986, 1988), there is potential for the carcinogenicity of uranium, since it emits primarily alpha 

radiation. Nevertheless, no evidence has been found to associate human exposure to uranium compounds 

and carcinogenesis. The National Academy of Sciences has determined that bone sarcoma is the most 

likely cancer from oral exposure to uranium; however, their report noted that this cancer has not been 

observed in exposed humans and concluded that exposure to natural uranium may have no measurable 

effect (BEIR IV). 

Similarly, the results of several oral studies with uranium in several species were negative for evidence of 

cancer induction (Maynard and Hodge 1949; Maynard et al. 1953; Tannenbaum et al. 1951). 

No studies were located that provided evidence that oral exposure of humans to uranium as an 

alpha-emitting radiation source causes cancer. The available human data on the relative potential of 

ingested radium and uranium isotopes to induce cancers in humans concluded that the cumulative lifetime 

risk to 1 million people, each ingesting 5 pCi of a radium isotope (226Ra, 228Ra, and 224Ra) per day, for the 

induction of skeletal cancers (bone sarcomas and carcinomas of the head sinuses) is 9 bone sarcomas and 

12 head carcinomas for 226Ra, 22 bone sarcomas for 228Ra, and 1.6 bone sarcomas for 224Ra. Assuming 

that the risk per rad of the average skeletal dose is equal for 226Ra and uranium isotopes with half-lives 

exceeding 1,000 years, and that the equilibrium skeletal content is 25 times the daily ingestion of 226Ra 

but 11 times the daily ingestion of long-lived uranium, the cumulative lifespan risk to 1 million people, 

each ingesting 5 pCi/day of 234U (0.0008 μg), 235U (2.3 μg), or 238U (15 μg), is estimated to be about 

1.5 bone sarcomas. However, no cancers would be expected if the incidence is found to vary with the 

square of the dose instead of linearly (Mays et al. 1985). The BEIR IV report came to the same 

conclusion, but reserved the opinion that bone sarcomas might be caused by highly enriched uranium. 

The report estimated a lifetime risk of excess bone sarcomas per million people of 1.5 if soluble uranium 

isotopes were ingested at a constant daily rate of 1 pCi/day (0.037 Bq/day). The number of bone 

sarcomas that occur naturally in a population of a million people is 750. However, no quantitative risk 

coefficient estimates for developing human exposure protection benchmarks were provided in this report. 

In addition, the BEIR IV analysis was presumably based on generic short-lived alpha-emitting sources, 

such as radon that have a higher potential for inducing cancer, and not on radionuclides with relatively 

longer radioactive half-lives like 238U, 235U, and 234U. Perhaps more importantly, the BEIR IV report 

concluded that “...exposure to natural uranium is unlikely to be a significant health risk in the population 

and may well have no measurable effect” (BEIR IV 1988). 

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URANIUM 157 

3. HEALTH EFFECTS 

The available long-term feeding studies in rats, mice, dogs, and rabbits found no evidence of cancer 

induction upon histopathological examination of selected organs and tissues. The available studies tested 

mice, dogs, and rabbits with extreme intakes of uranium corresponding to radioactivity exposures of as 

high as 1.0x104 nCi/kg/day (3.7x105 Bq/kg/day; 1.5x104 mg U/kg/day) for 30 days (Maynard and Hodge 

1949; Tannenbaum et al. 1951) or rats and dogs at 8.2x103 nCi/kg/day (3x105 Bq/kg/day; 1.2x104 mg 

U/kg/day) for 2 years (Maynard and Hodge 1949; Maynard et al. 1953). 

3.2.3 Dermal Exposure 

3.2.3.1 Death 

No deaths have been reported in humans as a result of dermal exposure to uranium. 

Deaths have occurred in animals after dermal exposure to uranium compounds from both single and 

repeated exposures. Generally, the more water-soluble uranium compounds were the most toxic and the 

rabbit was the most sensitive species. Deaths were due to renal failure. 

In a series of 4-hour exposures to uranium compounds followed by washing with detergent and a 30-day 

observation period, the lowest reported LD50 value was 28 mg U/kg as uranyl nitrate in an ethereal 

solution in New Zealand rabbits (Orcutt 1949). Calculated LD50 values for identical exposures to uranyl 

nitrate were 1,190 mg U/kg for guinea pigs and 4,286 mg U/kg for mice. Insufficient fatalities occurred 

to calculate an LD50 for rats, but the mortality curve fell between that of the rabbits and the guinea pigs. 

Deaths mainly occurred 5–7 days after exposure and were due to renal failure. Similar experiments with 

other uranium compounds in rabbits using a lanolin vehicle showed that water-soluble compounds (uranyl 

fluoride, uranium tetrachloride, uranium pentachloride) were the most toxic; the slightly soluble 

compounds (uranium trioxide, sodium diuranate, ammonium diuranate) had intermediate toxicity; and the 

water-insoluble compounds (uranium tetrafluoride, uranium dioxide, uranium peroxide, triuranium 

octoxide) caused no deaths (Orcutt 1949). 

Decreased survival was observed in female Wistar rats following dermal application of 280 mg U as 

uranyl nitrate hexahydrate diluted in an oil-water emulsion; survival was inversely related to the duration 

of exposure and the application area (Lopez et al. 2000). A 24-hour application to 0.5, 1, 2, 4, 6, 8, or 

16 cm2 area resulted in survival rates of 80, 83, 67, 29, 33, 0, and 0%, respectively; application to 8 cm2 

for 1 minute, 7 minutes, 15 minutes, 30 minutes, 1 hour, 8 hours, or 24 hours resulted in survival rates of 

100, 100, 100, 67, 45, 43, 10, and 0%, respectively. 

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URANIUM 158 

3. HEALTH EFFECTS 

Chemically induced renal failure caused 100% mortality in male Wistar rats after five daily exposures to 

237 or 1,928 mg U/kg/day as uranyl nitrate hexahydrate or ammonium uranyl tricarbonate, respectively, 

applied in a water-Vaseline® emulsion (De Rey et al. 1983). A 60% mortality rate was also reported for 

other male Wistar rats that received daily applications of 1,965 mg U/kg as uranyl acetate dihydrate for 1– 

11 days. No deaths were reported for other Wistar rats similarly treated with 2,103 mg U/kg/day as 

ammonium diuranate or to an unspecified dose of uranium dioxide (De Rey et al. 1983). 

Intermediate-duration dermal exposure in guinea pigs indicated that smaller repeated doses were better 

tolerated than a large single dose when the total exposure was the same. In a 4-week experiment where 

exposure was to 379 mg U/kg as uranyl nitrate for 3 days/week, 14% mortality was observed (Orcutt 

1949). If the same cumulative dose (4,741 mg U/kg) had been given in a single application, 86% 

mortality would have been expected. 

The LD50 values for each species and other LOAEL values for mortality from exposure to uranium 

through the dermal route are presented in Table 3-3. 

3.2.3.2 Systemic Effects 

No studies were located regarding systemic effects in humans following dermal exposure to uranium 

compounds for acute, intermediate, or chronic durations. 

No studies were located regarding the respiratory, cardiovascular, gastrointestinal, hematological, hepatic, 

or endocrine effects of uranium in animals following acute-, intermediate-, or chronic-duration exposure. 

The existing animal data on musculoskeletal, renal, dermal, and body weight effects are limited to acuteand intermediate-duration exposures. 

The highest NOAEL values and all reliable LOAEL values in each species and duration category for 

adverse systemic effects from chemical exposure to uranium by the dermal route are presented in 

Table 3-3. 

Musculoskeletal Effects. Statistically significant decreases in bone volumes were observed in 

female Wistar rats following an application of 280 mg U as uranyl nitrate hexahydrate diluted in an oil-

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Table 3-3 Levels of Significant Exposure to Uranium - Dermal 

Species

(Strain)

Exposure/

Duration/

Frequency

(Route)

ACUTE EXPOSURE 

Death

(Wistar)Rat 1-11 d 

1x/d

System NOAEL Less Serious 

LOAEL

1965 M 

mg/kg

Serious

(60% mortality in 11 

days)

ReferenceChemical Form 

De Rey et al. 1983 Uranyl Acetate 

(Wistar)Rat 1-11 d 

1x/d 1928 M 

mg/kg

(100% mortality in 5 

days)

De Rey et al. 1983 

Ammonium Uranyl 

Tricarbonate

(Wistar)Rat 1-11 d 

1x/d 237 M 

mg/kg

(100% mortality in 5 days)

De Rey et al. 1983 Uranyl Nitrate 

(Wistar)Rat

(EPICU)4 hr 

101 F 

mg/kg

(LD50) Orcutt 1949 

Uranyl Nitrate 

(albino)Mouse

(EPICU)4 hr 

4286 F 

mg/kg

(LD50) Orcutt 1949 

Uranyl Nitrate 

Gn Pig 

(EPICU)4 hr 

2520

mg/kg

(LD50) Orcutt 1949 

Uranium Tetrachloride 

(NS)Gn Pig 

(EPICU)once

1190

mg/kg

(LD50) Orcutt 1949 

Uranyl Nitrate 

(NewZealand)Rabbit

(EPICU)4 hr 

188

mg/kg

(50% mortality) Orcutt 1949 

Uranium Tetrachloride 
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Table 3-3 Levels of Significant Exposure to Uranium - Dermal (continued)

Exposure/ LOAEL

Duration/

Species Frequency Reference (Route) (Strain) System NOAEL Less Serious Serious Chemical Form 

Rabbit(New Zealand white,red,chec

Rabbit(NewZealand)Rabbit(NewZealand)Rabbit(NewZealand)Rabbit(NewZealand)

Systemic

Rat(Wistar)

(EPICU)4 hr 

3091

mg/kg

(83% mortality) Orcutt 1949 

Uranyl Fluoride 

(EPICU)4 hr 

28

mg/kg

(LD50) Orcutt 1949 

Uranyl Nitrate 

(EPICU)once 4 hr 

198

mg/kg

(33% mortality) Orcutt 1949 

Ammonium Diuranate 

(EPICU)4 hr 

344

mg/kg

(67% mortality) Orcutt 1949 UCl5

(EPICU)4 hr 

666

mg/kg

(67% mortality) Orcutt 1949

 Uranium Trioxide 

1-11 d 1x/d Renal 237 M 

mg/kg

(renal failure) De Rey et al. 1983 

Uranyl Nitrate 

Dermal 237 M (mild lesion) 

mg/kg
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Table 3-3 Levels of Significant Exposure to Uranium - Dermal (continued)

Exposure/ LOAEL

Duration/

Species Frequency Reference (Route) (Strain) System NOAEL Less Serious Serious Chemical Form 

(Wistar)Rat 1-11 d 

1x/d Dermal 1928 M 

mg/kg

De Rey et al. 1983 

Ammonium Uranyl 

Tricarbonate

Bd Wt 1928 M (slight initial weight loss)

mg/kg

(Wistar)Rat 1-11 d 

1x/d Renal 1965 M 

mg/kg

(renal failure) De Rey et al. 1983 

Uranyl Acetate 

Dermal 3929 M 

mg/kg

Bd Wt 1965 M (70% weight loss) 

mg/kg

(Wistar)Rat 1-11 d 

1x/d Renal 2670 M 

mg/kg

(renal failure) De Rey et al. 1983 

Ammonium Diuranate 

Dermal 2670 M (mild lesions) 

mg/kg

Bd Wt 2670 M (severe weight loss) 

mg/kg
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Table 3-3 Levels of Significant Exposure to Uranium - Dermal (continued)

Exposure/ LOAEL

Duration/

Species Frequency Reference (Route) (Strain) System NOAEL Less Serious Serious Chemical Form 

Rat once(Wistar) (EPICU)

Mouse 4 hr (albino) (EPICU)Gn Pig 4 hr (NS) (EPICU)Gn Pig 4 hr (NS) (EPICU)

RenalBd Wt RenalBd Wt RenalBd Wt Renal 450

mg/kg

Bd Wt 450

mg/kg

85 F 

mg/kg

85 F 

mg/kg

948 F 

mg/kg

948

mg/kg

660

mg/kg

660

mg/kg

616

mg/kg

616

mg/kg

(proteinuria; minimal microscopic lesions in renal tubular epithelium)

(unspecified decreased body weight gain) (moderate tubular degeneration)(unspecified decreased body weight gain) (proteinurea)(10-20% reduction in weight gain) 

(proteinuria)(unspecified decreased body weight gain) 

Orcutt 1949 Uranyl Nitrate Orcutt 1949 Uranyl Nitrate Orcutt 1949 Uranium Tetrachloride 

Orcutt 1949 Uranyl Nitrate 
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Table 3-3 Levels of Significant Exposure to Uranium - Dermal (continued)

Exposure/ LOAEL

Duration/

Species Frequency Reference (Route) (Strain) System NOAEL Less Serious Serious Chemical Form 

Gn Pig (NS)

Rabbit(NewZealand)Rabbit(NewZealand)Rabbit(NewZealand)

4 hr (EPICU)4 hr (EPICU)4 hr (EPICU)4 hr (EPICU)

RenalBd Wt RenalDermalRenalDermalRenalDermal

Orcutt 1949 689 (proteinuria) 

mg/kg Uranium Tetrachloride

689 (10-20% decreased bod

mg/kg weight gain)

Orcutt 1949 410

mg/kg Uranium Peroxide

410

mg/kg

Orcutt 1949 458

mg/kg Uranium Dioxide

458

mg/kg

Orcutt 1949 98

mg/kg Uranium Tetrafluoride

98

mg/kg
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Table 3-3 Levels of Significant Exposure to Uranium - Dermal (continued)

Exposure/ LOAEL

Duration/

Species Frequency Reference (Route) (Strain) System NOAEL Less Serious Serious Chemical Form 

Rabbit(NewZealand)

Rabbit(NewZealand)Rabbit(NewZealand)Rabbit(NewZealand)

4 hr (EPICU)4 hr (EPICU)4 hr (EPICU)4 hr (EPICU)

RenalDermalRenalDermalRenalDermalRenalDermal

195

mg/kg

666

mg/kg

147

mg/kg

147

mg/kg

195

mg/kg

666

mg/kg

344.1

mg/kg

344.1

mg/kg

(proteinuria)(proteinuria)

(proteinuria)(moderate skin irritation)

Orcutt 1949 Sodium Uranate Orcutt 1949 Uranium Trioxide Orcutt 1949 Triuranium Octoxide Orcutt 1949 UCl5
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Table 3-3 Levels of Significant Exposure to Uranium - Dermal (continued)

Exposure/ LOAEL

Duration/

Species Frequency Reference (Route) (Strain) System NOAEL Less Serious Serious Chemical Form 

(NewZealand)Rabbit

(EPICU)once Renal 618

mg/kg

(proteinuria) Orcutt 1949 

Uranyl Fluoride 

Dermal 618

mg/kg

(NewZealand)Rabbit

(EPICU)4 hr Renal 1.4

mg/kg

(proteinuria) Orcutt 1949 

Uranyl Nitrate 

Dermal 1.4

mg/kg

(moderate erythema) 

Bd Wt 6

mg/kg

30

mg/kg

(decreased body weight 

gain)

(NewZealand)Rabbit

(EPICU)4 hr Renal 169

mg/kg

(proteinuria) Orcutt 1949 

Ammonium Diuranate 

Dermal 169

mg/kg

INTERMEDIATE EXPOSURE 

Death

(NS)Gn Pig 

(EPICU)4 wk 3 d/wk 47

mg/kg

(12% mortality) Orcutt 1949 

Uranyl Nitrate 
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Table 3-3 Levels of Significant Exposure to Uranium - Dermal (continued)

Exposure/ LOAEL

Duration/

Species Frequency Reference (Route) (Strain) System NOAEL Less Serious Serious Chemical Form 

(NS)Gn Pig 

(EPICU)4 wk 3 d/wk 379

mg/kg

(14% mortality) Orcutt 1949 

Uranyl Nitrate 

Systemic

(NS)Gn Pig 

(EPICU)4 wk 3-6 d/wk Renal 47

mg/kg/day

(proteinuria) Orcutt 1949 

Uranyl Nitrate 

Dermal 47 (skin irritation) 

mg/kg/day

Bd Wt 47 161.2 (transitory weight loss) 

mg/kg/day mg/kg/day

(NewZealand)Rabbit

(EPICU)5 wk 5 d/wk Renal 2.3

mg/kg/day

(proteinuria) Orcutt 1949 

Uranyl Nitrate 

Dermal 2.3 (severe dermal ulcers) 

mg/kg/day

Bd Wt 2.3 (temporary weight loss) 

mg/kg/day

Bd Wt = body weight; d = day(s); Gn Pig = guinea pig; hr = hour(s); LD50 = lethal dose, 50% kill; LOAEL = lowest-observed-adverse-effect level; M = male; NOAEL no-observed-adverse-effect level; NS = not specified; wk = week(s); x = time(s) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

URANIUM 167 

3. HEALTH EFFECTS 

water emulsion to a 1 or 2 cm2 area for 24 hours or an 8 cm2 area for 24 hours, but not after 30 minutes, 

1 hour, or 8 hours (Lopez et al. 2000). 

Renal Effects. Vascular congestion and vacuolization of the tubules in the corticomedullary boundary 

were observed in female Wistar rats following a 1–30-minute application of 280 mg U as uranyl nitrate 

hexahydrate diluted in an oil-water emulsion to an 8 cm2 area or following 24 hours of exposure to uranyl 

nitrate applied to a 0.5 or 1 cm2 area (Lopez et al. 2000). Application of uranyl nitrate to an 8 cm2 area 

for 1–24 hours or to a 2–16 cm2 area for 24 hours resulted in formation of hyaline bodies and necrosis. 

Rabbits, guinea pigs, rats, and mice dermally exposed to uranyl nitrate hexahydrate for 1 day showed 

proteinuria for up to 10 days, followed by recovery to control values. The degree of proteinuria did not 

correlate well with the applied dose of uranium. Rabbits had elevated blood NPN at doses 

>270 mg U/kg. The animals that died from dermal exposure to uranium had microscopic renal damage 

typical of uranium poisoning. The kidneys of the animals that did not die were essentially normal, which 

may reflect repair of acute renal injury (Orcutt 1949). Kidney lesions were also observed in female 

Wistar rats dermally exposed to 600 mg uranyl nitrate hexahydrate in an oil-water emulsion; the severity 

of the renal lesions increased with increasing exposure durations or increasing amount of exposed skin 

(Lopez et al. 2000). Chemically induced renal failure caused 100% mortality in male Wistar rats after 

five daily exposures to 237 or 1,928 mg U/kg/day as uranyl nitrate hexahydrate or ammonium uranyl 

tricarbonate, respectively, applied in a water-Vaseline® emulsion (De Rey et al. 1983). Deaths from renal 

failure were also reported in this study for male Wistar rats that received daily applications of 

1,965 mg U/kg as uranyl acetate dihydrate for 1–11 days. 

Dermal Effects. Although no human studies were located regarding the dermal effects of uranium; no 

dermal effects were reported in studies of uranium miners, millers, and processors exposed to airborne 

uranium. 

In animal studies, application of 41 mg U/kg as uranium pentachloride to the shaved backs of New 

Zealand white rabbits resulted in mild skin irritation (Orcutt 1949). Dermally applied uranium was also 

damaging to the epidermis in other animal studies. Application of 56.4 mg U/kg as uranyl nitrate 

hexahydrate to another group of rabbits resulted in superficial coagulation necrosis and inflammation of 

the epidermis, while a dose of 4.2 mg U/kg as uranyl nitrate hexahydrate applied in single or multiple 

sites for 5 weeks resulted in severe dermal ulcers. No untreated controls were used in the 5-week study 

(Orcutt 1949). Moderate erythema was observed in male and female New Zealand white rabbits after 

single applications of 1.4 mg U/kg as uranyl nitrate hexahydrate to their uncovered clipped skins (Orcutt 

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URANIUM 168 

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1949). An applied dose of 2,670 mg U/kg as ammonium diuranate for 1–10 daily applications to the 

shaved backs of a group of rats resulted in mild lesions on the skin of the rats, while a dose of 

237 mg U/kg as uranyl nitrate hexahydrate resulted in disrupted membranes in the cell, mitochondria, and 

cell nucleus, as revealed by transmission electron microscopy (TEM). Light microscopy revealed swollen 

and vacuolated epidermal cells and damage to hair follicles and sebaceous glands in the uranyl nitrate 

hexahydrate-treated animals (De Rey et al. 1983). 

No dermal effects were seen following application of a single dose of 618 mg U/kg as uranyl fluoride, 

666 mg U/kg as uranium trioxide, 195 mg U/kg as sodium diuranate, 198 mg U/kg as ammonium 

diuranate, 410 mg U/kg as uranium peroxide, 458 mg U/kg as uranium dioxide, or 147 mg U/kg as 

triuranium octaoxide in 50% aqueous solution to the shaved skin of New Zealand white rabbits (Orcutt 

1949). No dermal effects were observed on the shaved backs of New Zealand white rabbits to which a 

single dose of 98 mg U/kg as a 65% concentration of the uranium tetrafluoride in lanolin was applied 

(Orcutt 1949). Similarly, application of 3,929 mg U/kg as uranyl acetate dihydrate or 2,103 mg U/kg as 

ammonium uranyl tricarbonate in water-Vaseline® emulsion to a 3 cm2 shaved area of the uncovered 

backs of 20 male Wistar rats in 1–10 daily applications had no effect on the skin of the rats (De Rey et al. 

1983). 

Body Weight Effects. In animal studies, significant weight loss was reported in rats after the 

following dermal applications over a 3 cm2 area: 3,948 mg U/kg as uranyl nitrate hexahydrate, 

3,929 mg U/kg as uranyl acetate dihydrate, 2,103 mg U/kg as ammonium uranyl tricarbonate, or 

2,670 mg U/kg as ammonium uranate to rats for 1–10 days (De Rey et al. 1983). Weight loss was also 

observed after single applications of 660 or 689 mg U/kg as uranium tetrachloride to guinea pigs, 616 or 

948 mg U/kg as uranyl nitrate hexahydrate to mice, 85 mg U/kg as uranyl nitrate hexahydrate to rats, and 

43 mg U/kg as uranyl nitrate hexahydrate to rabbits (Orcutt 1949). 

Uranium (4.2 mg U/kg/day) applied as uranyl nitrate hexahydrate to the clipped backs of New Zealand 

white rabbits for 5 weeks also induced significant weight loss that peaked at 10–15 days after beginning 

treatment (Orcutt 1949). However, in several other animal studies, no changes in body weight in New 

Zealand white rabbits were reported following single dermal applications of 618 or 804 mg U/kg as 

uranyl fluoride, 344 mg U/kg as uranium pentachloride, 666 mg U/kg as uranium trioxide or uranyl 

fluoride, 344 mg U/kg as uranyl pentachloride, 195 mg U/kg as sodium diuranate, 198 mg U/kg as 

ammonium diuranate, 410 mg U/kg as uranium peroxide, 458 mg U/kg as uranium dioxide, or 147 mg 

U/kg as triuranium octaoxide (Orcutt 1949). 

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URANIUM 169 

3. HEALTH EFFECTS 

3.2.3.3 Immunological and Lymphoreticular Effects 

No information was located regarding the effects of uranium on the immunological and lymphoreticular 

system in humans and animals following dermal exposure for any duration. 

3.2.3.4 Neurological Effects 

No studies were located for humans regarding neurological effects following dermal exposure to uranium 

compounds. 

In animal studies, neurological signs including irritability, hyperactivity, upset equilibrium, limb rigidity, 

and respiratory arrest were observed in rabbits exposed to lethal doses of uranyl nitrate hexahydrate 

(Orcutt 1949); decreases in food and water intake and body weight were also observed in these animals. 

3.2.3.5 Reproductive Effects 

No studies were located for humans and animals that described reproductive effects following dermal 

exposure to uranium for any duration. 

3.2.3.6 Developmental Effects 

No studies were located regarding effects of uranium on development in humans or animals following 

dermal exposure for any duration. 

3.2.3.7 Cancer 

No information on the cancer effects in humans or animals following dermal exposure to uranium for all 

durations of exposure was located; however, such effects have not been observed in studies involving 

uranium mining, milling, and production. 

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URANIUM 170 

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3.2.4 Other Routes of Exposure 

Embedded/Implanted Uranium 

A cohort of Gulf War I veterans exposed to depleted uranium were initially examined in 1994 (Hooper et 

al. 1999) and re-examined every 2 years beginning in 1997 (McDiarmid et al. 2000, 2001a, 2004b, 2006, 

2007, 2009). The veterans were in or on armored tanks and fighting vehicles when they were fired upon 

by other U.S. forces using depleted uranium penetrators. These veterans may have been exposed to 

depleted uranium via inhalation, ingestion, fragment penetration wounds, and wound exposure to dust; 

some of the soldiers who were injured were left with multiple tiny fragments of uranium and other 

substances in muscle and/or soft tissue. Urinary uranium levels have been consistently elevated in the 

veterans with embedded depleted uranium fragments. Urine uranium levels in the cohort ranged from 

0.001 to 60 μg/g creatinine (McDiarmid et al. 2000, 2001a, 2004b, 2006, 2007, 2009); however, urinary 

uranium levels in the veterans with depleted uranium fragments were typically >0.1 μg/g creatinine. In 

comparison, the geometric mean urine uranium levels in the U.S. males (National Health and Nutrition 

Examination Surveys [NHANES] sampling periods of 1999–2008) were 0.005–0.007 μg/g creatinine 

(CDC 2011) and the 95th percentile values were 0.035–0.020 μg/g creatinine. A number of parameters 

were examined to evaluate potential adverse health effects associated with exposure to depleted uranium; 

potential targets included renal function, liver effects, hematological alterations, neuroendocrine hormone 

levels, semen characteristics, bone function, neurocogntive effects, and genotoxicity. The effect of 

uranium exposure on these parameters was examined by dividing the veterans into two groups: low 

exposure (urine uranium levels of <0.1 μg/g creatinine) and high exposure (urine uranium levels of 

≥0.1 μg/g creatinine). The results of these studies for each end point are discussed in the following 

sections. Animal studies involving exposure to uranium from implanted uranium are also discussed in the 

following sections. 

Hematological Effects. As summarized in Table 3-4, no consistent alterations in hematological 

parameters were found in the Gulf War veterans (Hooper et al. 1999; McDiarmid et al. 2000, 2001a, 

2004b, 2006, 2007, 2009). 

Musculoskeletal Effects. The latest study of the Gulf War veterans (McDiarmid et al. 2009) 

examined biomarkers of bone turnover and bone metabolism. A nonsignificant decrease in bone-specific 

serum alkaline phosphatase levels (measure of osteoblast function) was observed in the veterans with 

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3. HEALTH EFFECTS 

Table 3-4. Summary of Significant Observations in Studies of a Cohort of Gulf
 

War Veterans Exposed to Depleted Uraniuma
 

Evaluation year 

Clinical parameter 1994b 1997c 1999d 2001e 2003f 2005g 2007h 

Renal function 

Urine creatinine NS NS l>h (p=0.07) NS NS NS NS 

Creatinine clearance – – – – – NS NS 

Glomerular filtration rate – – – – – NS 

Urine glucose – – – – – NS NS 

Urine calcium – – – NS NS NS NS 

Urine phosphate – – – NS NS NS NS 

Urine β2-microglobulin NS NS NS NS NS NS h>l (p=0.11) 

Urine intestinal alkaline – – NS NS NS NS NS 

phosphatase 

Urine NAG – – NS NS NS NS NS 

Urine total protein NS NS NS h>l (p=0.06) l>h (p=0.21) NS NS 

Urine microalbumin – – – – na NS NS 

Retinol binding protein – NS NS h>l (p=0.06) h>l NS NS h>l (p=0.07) 

Serum creatinine NS NS NS L>H NS NS NS 

Serum calcium NS NS H>L NS NS NS NS 

Serum phosphate NS NS NS NS H>L NS NS 

Serum uric acid NS NS NS NS – NS NS 

Serum chemistry 

Alanine NS NS NS NS NS NS NS 

aminotransferase 

Aspartate NS NS NS NS h>l NS NS NS 

aminotransferase 

Lactate dehydrogenase NS NS L>H L>H NS NS NS 

Alkaline phosphatase NS NS NS NS NS NS NS 

Hematological parameters 

Hematocrit NS NS NS L>H NS NS NS 

Hemoglobin NS NS NS L>H NS NS NS 

White blood cells H>L NS NS NS NS NS NS 

Lymphocytes L>H NS L>H NS NS NS NS 

Neutrophils H>L NS H>L NS NS NS NS 

Basophils NS NS NS NS NS NS NS 

Eosinophils NS H>L NS NS NS NS NS 

Monocytes L>H NS L>H NS NS NS NS 

Platelets NS NS NS NS NS NS NS 

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Table 3-4. Summary of Significant Observations in Studies of a Cohort of Gulf
 

War Veterans Exposed to Depleted Uraniuma
 

Clinical parameter 

Bone markers 

1994b 1997c 1999d 

Evaluation year 

2001e 2003f 2005g 2007h 

Estradiol – – – – – – NS 

Bone specific-alkaline 

phosphatase 

– – – – – – NS 

1,25-Dihydroxy 

vitamin D 

– – – – – – H>L 

25-Hydroxy vitamin D 

Parathyroid hormone 

Urine N-teleopeptide 

Neuroendocrine hormones 

– 

– 

– 

– 

– 

– 

– 

– 

– 

– 

– 

– 

– 

– 

– 

– 

– 

– 

NS 

NS 

NS 

Follicle stimulating 

hormone 

– NS NS NS NS NS NS 

Luteinizing hormone – NS NS l>h (p=0.06) NS NS NS 

Testosterone – NS NS NS NS NS NS 

Thyroid stimulating 

hormone 

– – NS NS NS NS NS 

Free thyroxine – – NS L>H NS NS NS 

Semen characteristics 

Semen volume – NS NS NS NS NS NS 

Sperm concentration – H>L h>l (p=0.09) h>l NS h>l NS NS NS 

Total sperm count – NS H>L h>l 

(p=0.06) 

h>l NS NS NS 

Percent motile sperm – NS NS NS NS NS NS 

Total progressive sperm – NS H>L NS NS NS NS 

Percent progressive 

sperm 

Total rapid progressive 

sperm 

– 

– 

NS 

NS 

NS 

H>L 

NS 

NS 

NS 

NS 

NS 

NS 

NS 

NS 

Percent rapid 

progressive sperm 

– NS NS NS NS NS NS 

a

Table modified from Squibb and McDiarmid (2006); lower case letters indicate nonsignificant findings; upper case 

letters indicate significant findings (p<0.05).

b

Hooper et al. 1999.
 c

McDiarmid et al. 2000.
 d

McDiarmid et al. 2001a.
 e

McDiarmid et al. 2004b.
 f

McDiarmid et al. 2006.
 g

McDiarmid et al. 2007.
 h

McDiarmid et al. 2009.
 

h,H = high urine uranium (≥0.1 μg/g creatinine); l, L = low urine uranium group (<0.1 μg/g creatinine);
 

NAG = N-acetyl-β-glucosaminidase; NS = not significant
 

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embedded shrapnel; however, no alteration in N-telopeptide levels (biomarker of collagen breakdown and 

bone resorption) was found. The investigators suggested that the increase in osteoblast activity without 

an alteration in osteoclast activity may be a clinically insignificant uncoupling of the bone turnover 

process. A significant increase in 1,25-dihydroxy vitamin D levels was observed in the veterans with 

embedded shrapnel; the increased 1,25-dihydroxy vitamin D levels were within the normal range. The 

increase in 1,25-dihydroxy vitamin D levels, in the absence of changes in parathyroid hormone levels, 

may be a due to an alteration in renal function rather than an alteration in bone metabolism. 

Decreased tibia growth and impaired mandibular growth were observed in female Wistar rats 

administered 110 mg U/kg as uranium dioxide implanted directly into the subcutaneous tissue of dorsal 

skin for 30 days (Díaz Sylvester et al. 2002). The decrease in bone growth was probably related to a 

marked decrease in active osteoblasts, which were replaced with a large increase in bone lining cells. 

Hepatic Effects. There are limited data on the potential hepatotoxicity of embedded depleted 

uranium; no consistent alterations in several clinical chemistry parameters (ALT, AST, lactate 

dehydrogenase, alkaline phosphatase) were found in Gulf War veterans (Hooper et al. 1999; McDiarmid 

et al. 2000, 2001a, 2004b, 2006, 2007, 2009). 

Renal Effects. In general, no significant alterations in parameters of kidney function were observed 

among Gulf War veterans (Hooper et al. 1999; McDiarmid et al. 2000, 2001a, 2004b, 2006, 2007, 2009); 

a summary of these data are presented in Table 3-4. However, the increases in several parameters, 

including urinary retinol binding protein and β-2-microglobulin levels approached statistical significance 

in the veterans with embedded shrapnel. No alterations in N-acetyl-β-glucosaminidase levels (a 

biomarker of renal proximal tubule cell cytotoxicity) were found (McDiarmid et al. 2009). Of the 

biomarkers of renal function, only urine retinol binding protein and β-2-microglobulin levels were in the 

direction that would be indicative of renal damage (McDiarmid et al. 2009), and retinol binding protein 

levels were altered at several examination periods. During the period of 2001–2007, increases in retinol 

binding protein excretion were observed in the high exposure group at three of the four examinations. 

Urine retinol binding protein levels at the 2001, 2003, and 2007 examinations were 46.13, 27.33, and 

31.00 μg/g creatinine in the low exposure group and 65.68, 80.51, and 48.11 μg/g creatinine in the high 

exposure group. The difference between the two groups did not reach statistical significance and the 

levels are within the normal range (<610 μg/g creatinine, McDiarmid et al. 2009). Although the 

difference was not statistically significant and values were within the normal range, there is concern 

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(Squibb and McDiarmid 2006) because retinol binding protein may be a potential sentinel marker of 

proximal tubular effects from uranium. 

Alterations in renal function and histopathology were observed in rats 90, 180, or 360 days after 0.1, 0.2, 

or 0.3 g depleted uranium fragments were embedded in the gastrocnemius muscle (Zhu et al. 2009b). The 

histological alterations included swollen glomeruli with infiltrated inflammatory cells, turgidity and 

epithelial necrosis in the tubules, and interstitial fibrosis (360 days after fragment implantation). 

Significant increases in urinary β2-microglobulin levels were observed in the 0.3 g group 180 and 

360 days after implantation, and an increase in urinary albumin levels was observed in the 0.3 g group 

after 90 days (but not after the longer exposure durations); however, there were large standard deviations 

for these measurements. Additionally, significant increases in serum creatinine levels were observed in 

all three exposed groups at 90 days, in the 0.3 g group at 180 days, and in the 0.2 and 0.3 g groups at 

360 days; BUN levels were significantly increased in the 0.3 g group at 90 days and 0.2 and 0.3 g groups 

at 360 days (no significant alterations were observed at 180 days). Another study by this group also 

found significant decreases in 1-α-hydroxylase activity (responsible for the hydroxylation of 25(OH)D3 to 

1α,25(OH)2D3 the active form of vitamin D) in the kidneys of rats exposed to 0.2 or 0.3 g depleted 

uranium embedded in the gastrocnemius muscle for 3 months (Yan et al. 2010); no significant alterations 

were observed at 6 or 12 months or in the 1 g group at any time period. 

Endocrine Effects. As summarized in Table 3-4, no consistent alterations in neuroendocrine 

hormone levels have been found in the Gulf War veterans with embedded uranium (Hooper et al. 1999; 

McDiarmid et al. 2000, 2001a, 2004b, 2006, 2007, 2009). 

Body Weight Effects. Significant decreases in body weight gain were observed in rats 90 days 

following implantation of 0.1, 0.2, or 0.3 g depleted uranium fragments in the gastrocnemius muscle (Zhu 

et al. 2009b); the exposed rats weighed 11–21% less than controls with 0.3 g of biologically inert 

tantalum (Ta) fragments embedded in the gastrocnemius. One year after implantation, decreases in body 

weight gain (10–11%) were only observed in the 0.2 and 0.3 g groups. 

A 25% decrease body weight gain was also observed in rats following implantation of 110 mg U/kg/day 

as uranium dioxide into the subcutaneous tissue of the dorsal skin for 30 days (Díaz Sylvester et al. 2002). 

Neurological Effects. The results of neurocognitive tests in the Gulf War veterans cohort have not 

found significant differences between the high and low exposure groups (McDiarmid et al. 2000, 2001a, 

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2004b, 2006, 2007, 2009). Significant associations between urine uranium levels and accuracy scores on 

neurocognitive tests were observed at several examinations; however, this association was strongly 

influenced by two subjects with extremely high uranium levels and severely complex co-morbid 

conditions due to combat injuries. 

An animal study examined the effects of implanted depleted uranium alloy pellets on neurobehavior in 

adult rats (Arfsten et al. 2007). Groups of Sprague-Dawley rats (18–84 males and 17–42 females per 

group) were implanted with pellets of depleted uranium in the gastrocnemius muscle for up to 150 days. 

Males received 12 or 20 pellets and females received 4, 8, 12, or 20 pellets. Controls were implanted 

with tantalum pellets. Beginning on postimplantation day 150, a portion of males and females were 

evaluated for spontaneous locomotor activity in an open field, acoustic startle/prepulse inhibition, and 

conspecific social approach. The results of the behavioral testing did not show definite evidence of 

neurobehavioral perturbations associated with depleted uranium implantation. 

In another study of rats with implanted depleted uranium pellets, 4, 10, or 20 pellets were implanted in the 

gastrocnemius muscle for 6, 12, or 18 months (Pellmar et al. 1999b). Neurophysiological changes 

(impairment of ability of the synaptic potential to elicit the population spike, EPSP/spike coupling) were 

detected in the hippocampus 6 or 12 months after implantation; no effects were observed after 18 months, 

which may have been due to the effect of aging. 

Reproductive/Developmental Effects. In the studies of the Gulf War veterans cohort (McDiarmid 

et al. 2000, 2001a, 2004b, 2006, 2007, 2009), differences in semen quality have been observed at a 

number of examinations (data summarized in Table 3-4); however, these data suggest improved quality in 

the high exposure group. No significant alterations were found for follicle stimulating hormone, 

luteinizing hormone, or testosterone. Although prolactin levels were elevated in the 1997 cohort, no 

differences were found in later evaluations. 

The reproductive/developmental effects of implanted depleted uranium pellets have been studied in rats 

(Arfsten et al. 2006, 2009). Groups of Sprague-Dawley rats (6–18/sex/group) were implanted with 0, 4, 

8, 12, or 20 depleted uranium pellets (1x2 mm) in the gastrocnemius muscle. Inert implant controls were 

implanted with 12 or 20 Ta pellets; sham-operated controls were also used. Urine was collected from 

F0 rats on day 27 and 117 for uranium analysis. Rats were mated on postimplantation day 120. Body 

weight of pregnant females was checked throughout pregnancy. F0 males were kept until necropsy on 

postnatal day 200. The pups were counted and weighed immediately after birth; sex ratio was also 

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determined; pups were also examined for gross malformations during postnatal days 1–20. F0 females 

that did not deliver a litter were kept until necropsy on postnatal day 200. On postnatal day 2, F0 females 

and their offspring underwent maternal retrieval testing. On postnatal day 4, litters were culled to eight 

pups (four/sex); discarded pups were killed and the whole carcasses were analyzed for uranium. The 

remaining pups were kept with their mothers through postnatal day 20. On postnatal day 20, two 

pups/sex were killed and used for whole-body uranium analysis, gross examination of all major organs, 

and examination of the ribcage. Subsets of F1 pups underwent neurobehavioral testing on postnatal 

days 4–63. These tests assess developmental markers for basic proprioceptive coordination, social 

bonding, social interaction, and the developmental milestone of eye opening. F0 dams were necropsied 

on postnatal day 200. Survival and body weight of F1 pups were monitored until postnatal day 120. On 

postnatal day 120, F0 and F1 males were killed and sperm motility and concentration were examined. 

Major organs of males and females were examined and weighed. The F2 generation was produced by 

mating F1 males with F1 females on postnatal day 70. F2 pups were subjected to the same tests as F1 

except the maternal retrieval test. F1 males and females were killed on postnatal day 120. One male and 

one female per F2 litter were killed on postnatal day 90. 

No clinical signs of toxicity were seen in F0 rats during the postimplantation period. Three male and 

4 female F0 rats died during the study, but necropsy did not show an obvious cause of death. Depleted 

uranium had no significant effect on mating index. There were no significant differences among the 

groups regarding gestational index, gestation duration, or gestation weight gain. Viability of F1 pups to 

postnatal days 4 and 20 was similar across groups. Pup body weight gain during postnatal days 4–20 also 

was similar across groups. In F1 pups sacrificed on postnatal day 20, there were no gross abnormalities 

in the major organs and no alterations in the ribcage. Results of the neurobehavioral tests showed no 

significant depleted uranium-related effects. Evaluation of sperm parameters in F0 males on postnatal 

day 200 did not show compound-related effects. Histological examination of major organs from controls 

and rats implanted with 20 depleted uranium pellets and 20 Ta pellets only showed tissue reactions to the 

foreign body; neither depleted uranium nor Ta pellet implantation sites showed evidence of proliferative 

of preneoplastic processes taking place in or around the site. Body weight gain and body weight of F1 

pups during postnatal days 20–120 were comparable among all groups. Eight of 414 F1 rats died before 

necropsy on postnatal day 120 of unknown causes. No gross abnormalities were seen in the remaining 

F1 rats. There did not seem to be compound-related effects on F1 organ weights or in histology of 

kidneys, spleen, thymus, bone marrow, ovaries, and testes. An increase in mean relative heart weight was 

observed in the highest dose F1 females, when compared to the sham-operated controls; however, there 

was no change in absolute heart weight and no difference in absolute or relative heart weight when 

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compared to the inert pellet control group. Neither sperm motility nor concentration was significantly 

affected by depleted uranium in male F1 rats on postnatal day 120. Overall mating success of F1 rats was 

lower than F0 rats, but was comparable among all groups. No significant developmental effects were 

reported in F2 pups at birth or during postnatal days 0–20. Gross necropsy of F2 pups on postnatal day 

20 showed no significant alterations; examination of the ribcage also showed no abnormalities. Necropsy 

of F2 rats on postnatal day 90 did not show consistent depleted uranium-related effects on organ weights; 

an increase in relative heart weight was observed in the highest dosed F2 males, but there was no change 

in absolute heart weight. Sperm motility parameters and sperm concentration were not significantly 

different among F2 groups. 

A study was conducted in mice to determine whether paternal exposure to uranium could result in genetic 

damage to the offspring (Miller et al. 2010). The authors used a transgenic mouse system that employs a 

λ shuttle vector that allows mutations to be analyzed in vitro. Transgenic male mice were implanted with 

depleted uranium pellets (two, four, or six pellets) in the gastrocnemius muscle for 7 months and were 

then mated with untreated non-transgenic females to produce the F1 generation. Controls received 

implants of biologically inert tantalum. Litters from depleted uranium-implanted fathers were smaller in 

a dose-dependent manner than un-implanted or tantalum-implanted fathers. Paternal exposure to depleted 

uranium did not result in fetal malformations and no significant increase in offspring hematopoietic 

malignancies in weaned offspring was observed. At the age of 4–5 months, deoxyribonucleic acid (DNA) 

from bone marrow cells from F1 mice was screened for mutations. A significantly higher mutation 

frequency relative to controls was observed in mid- and high-dose F1 mice, comparable to the frequency 

seen in offspring of male mice exposed to 4 Gy of 60Co gamma radiation delivered at 0.06 Gy/minute. 

Since the depleted uranium would have delivered a much lower radiation dose than the 60Co, the 

comparable results are supportive of uranium effects being primarily chemical in nature. 

Cancer. The carcinogenicity of implanted depleted uranium was studied in rats (Hahn et al. 2002). 

Groups of male Wistar rats (50/group) were implanted in the thigh muscle with fragments of depleted 

uranium (alloyed with 0.75% titanium) of two different sizes (2.5x2.5x1 mm or 5.0x5.0x1.5 mm) or a 

pellet (2.0x1 mm) for life. A negative control group was implanted with Ta; a positive control group 

received an intramuscular injection of radioactive thorium dioxide (Th). Rats were weighed every other 

month. At death, complete necropsies were performed with drainage of lymph nodes of all organ 

systems. Histological examination was conducted of the implantation site, draining lymph nodes, 

neoplasms, and kidney urinary bladder, prostate, seminal vesicles, testes, epididymus, spleen, muscle, 

liver, and lungs. Uranium was also measured in the kidneys. 

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None of the treatments significantly affected body weight. Survival was also not affected. Depleted 

uranium fragments grew in size due to surface corrosion. Depleted uranium and Ta implants were 

encapsulated with connective tissue at the time of death. The capsules around depleted uranium were 

characterized histologically by fibrosis, inflammation, degeneration, and mineralization. All implants 

(depleted uranium, Th, or Ta) had soft tissue tumors associated with the implants. The most prevalent 

was malignant fibrous histiocytoma, which was significantly increased in the high-dose depleted uranium 

fragment rats (5.0x5.0x1.5 mm) and in the positive control. There was no increase in tumors related to 

depleted uranium in tissues not associated with implant sites. The results showed that depleted uranium 

fragments of sufficient size cause localized proliferative reactions and soft tissue sarcomas that can be 

detected with radiography. 

3.3 GENOTOXICITY 

Because uranium is predominantly an alpha-emitting element, current theories on gene mutation and 

chromosomal aberrations by high-LET alpha radiation suggest a concern for genotoxicity from uranium’s 

radioactivity (BEIR 1980, 1988, 1990; Leach et al. 1970; Morris et al. 1990; Muller et al. 1967; Otake 

and Schull 1984; Sanders 1986; Stokinger et al. 1953; UNSCEAR 1982, 1986, 1988) (see Appendix D for 

a review of the hazards associated with radionuclide exposure). 

Prospective evaluation of Gulf War veterans with retained depleted uranium metal shrapnel fragments has 

provided inconsistent results (McDiarmid et al. 2000, 2001a, 2004b, 2007, 2009). Tests have been 

conducted in peripheral blood lymphocytes and included evaluations of sister chromatid exchanges 

(SCEs), chromosomal aberrations (traditional measures as well as those identified through fluorescent in 

situ hybridization), and hypoxanthine-guanine phosphoribosyl transferase (HPRT) mutation frequency. 

Earlier assessment of SCEs yielded inconsistent results as a function of uranium body burden. More 

recent use of HRPT showed higher mutation frequencies in high-exposure groups, but the difference 

between high- and low-exposure groups never reached statistical significance. Evaluations of 

chromosomal aberrations also have been inconsistent in showing associations between aberration 

frequencies and uranium body burden. McDiarmid et al. (2009) concluded that, overall, the body of 

evidence in this cohort shows relatively weak genotoxic effects from exposure to uranium. 

Schröder et al. (2003) examined 16 war veteran volunteers suspected of exposures to depleted uranium. 

Since a control group subjected to the same multiple-agent exposures except for depleted uranium was 

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not available, the investigators chose subjects from their own laboratory as controls. Compared to the 

controls, there was a statistically significant increase in the frequency of dicentric chromosomes and 

centric ring chromosomes among veterans; SCEs were not increased. The results suggested previous 

exposure to ionizing radiation, but the different sources of exposure could not be ascertained. Four 

additional small studies from individuals in the former Republic of Yugoslavia who were exposed to 

depleted uranium either via consumption of contaminated food and/or clean-up operations reported 

increased frequencies of chromosomal aberrations in peripheral blood cells from the exposed subjects 

compared with unexposed controls (Krunić et al. 2005; Milačić 2008; Milačić and Simić 2009; Milačić et 

al. 2004). A cytogenic study of men occupationally exposed to uranium in a fuel production plant and in 

a fuel enrichment plant found higher levels of chromosome aberrations in the exposed workers than in 

controls (Martin et al. 1991). However, the possible role of smoking could not be assessed with certainty. 

In an early animal study, male BALB/c mice injected intraperitoneally with doses ranging from 0.05 to 

1.0 μg U/kg as 18.9% enriched uranyl fluoride showed a general tendency for an increase in chromosome 

breaks in sperm cells with an increasing dose of 18.9% enriched uranyl fluoride. At high dose levels, the 

statistically significant difference of break frequencies between treated and control mice disappeared 

60 days after treatment (Hu and Zhu 1990). More recently, Monleau et al. (2006a) exposed male 

Sprague-Dawley rats nose-only to an aerosol of uranium dioxide at concentrations of 0, 190 mg/m3 

(0.5 hours), or 375 mg/m3 (2 and 3 hours) and examined DNA damage in epithelial nasal cells, bronchoalveolar lavage cells (BAL), and kidney cells at various times postexposure. Groups of rats were also 

exposed repeatedly for 3 weeks to depleted uranium dioxide (190 mg/m3

; insoluble depleted uranium) and 

to uranium peroxide (116 mg/m3

; soluble depleted uranium) for 0.5 hours. No DNA damage occurred in 

nasal epithelial cells under any exposure scenario. BAL cells from rats exposed to 375 mg/m3 uranium 

dioxide for 3 hours showed significant DNA damage 1 and 8, but not 3, days postexposure. A single 

0.5-hour exposure to uranium peroxide did cause DNA damage in BAL cells. Repeated exposure to 

190 mg/m3 uranium dioxide produced DNA damage in BAL cells assessed 1, 4, 8, or 14 days 

postexposure. Kidney cells showed DNA damage only after repeated exposures to uranium dioxide. 

DNA damage consisted partly of double strand breaks, suggesting that radiation could be a contributor to 

the effects. These results suggested that there may be a threshold for effects of single exposure on BAL 

cells and that repeated inhalation exposure seemed to potentiate the effect of uranium in BAL and kidney 

cells. Since uranium exposure also increased the expression of cytokines involved in inflammatory 

responses in lung tissue and of peroxides, the investigators suggested that DNA damage may have been 

partly a consequence of inflammatory processes and production of reactive oxygen species. Another 

study from the same group of investigators reported that repeated exposure to uranium dioxide increased 

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the genotoxic effects of uranium peroxide inhalation in all three types of cells examined, when a single 

exposure to uranium peroxide had no significant effect (Monleau et al. 2006b). The investigators 

suggested that pre-exposure to insoluble uranium could slightly disturb the biokinetics of subsequently 

inhaled soluble uranium in the kidneys, gastrointestinal tract, and excreta. 

In another study, groups of male and female Wistar rats were fed a diet that provided 0, 4, or 40 mg 

U/kg/day (depleted uranyl nitrate hexahydrate) for 4 months, at which time they were mated to produce 

the F1 generation (Hao et al. 2009). The offspring were treated in the same manner for 4 months. 

Exposure to uranium induced a statistically significant dose-related increase in the incidence of 

micronuclei in bone marrow from both the parental and F1 generations. It also induced DNA damage in 

the sperm from both generations in a dose-related manner. The effects were more pronounced in the 

F1 generation than in the parental groups. Analyses of uranium in urine and kidneys after the 4-month 

exposure period showed dose-related accumulation in the kidney, significantly higher in the F1 than in the 

parental generation. Hao et al. (2009) did not elaborate as to why the effects were more pronounced in 

the F1 generation than in the parental rats. One possible explanation could be that the F1 generation also 

could have been exposed during preweaning via the maternal milk. 

A study was conducted in mice to determine whether paternal exposure to uranium could result in genetic 

damage to the offspring (Miller et al. 2010). The authors used a transgenic mouse system that employs a 

λ shuttle vector that allows mutations to be analyzed in vitro. Transgenic male mice were implanted 

depleted uranium pellets (two, four, or six pellets) in the gastrocnemius muscle for 7 months and were 

then mated with untreated females to produce the F1 generation. At the age of 4–5 months, DNA from 

bone marrow cells from F1 mice was screened for mutations. A significantly higher mutation frequency 

relative to controls was observed in mid- and high-dose F1 mice, comparable to the frequency seen in 

offspring of male mice exposed to 60Co gamma radiation. To assess the role of radiation in the observed 

effects of depleted uranium, male mice were exposed to equal concentrations of depleted or enriched 

uranium in the drinking water (approximately 1 mg U/mouse) for 2 months. Exposure to either form of 

uranium significantly increased the frequency of mutations compared with controls and also suggested 

that the increase was specific-activity dependent. While this experiment showed that radiation can play a 

role in the observed effects of depleted uranium, the investigators noted that the mutation model used 

measures point mutations and cannot measure large deletions characteristic of radiation damage, the role 

of the chemical effects of depleted uranium may also be significant. 

Table 3-5 presents results of genotoxicity tests conducted in vivo. 

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Table 3-5. Genotoxicity of Uranium In Vivo 

Exposure 

Species (test system) End point route Results Reference 

Mammalian systems:
 

Human peripheral lymphocytes Chromosomal aberrations Inhalation + Schröder et al.
 

(DU) 2003
 

Human peripheral lymphocytes Sister chromatid exchange Inhalation – Schröder et al.
 

(DU) 2003
 

Human peripheral lymphocytes Chromosomal aberrations Oral + Milačić et al.
	

(DU) 2004
 

Human peripheral lymphocytes Chromosomal aberrations Inhalation + Milačić 2008
	

(DU)
 

Human peripheral lymphocytes Chromosomal aberrations Inhalation + Milačić and Simić
	

(DU) 2009
 

Human peripheral lymphocytes Chromosomal aberrations Retained metal ± McDiarmid et al.
 

(DU) fragment 2009
 

Human peripheral lymphocytes Sister chromatid exchange Retained metal ± McDiarmid et al.
 

(DU) fragment 2009
 

Human peripheral lymphocytes HPRT mutation frequency Retained metal ± McDiarmid et al.
 

(DU) fragment 2009
 

Human peripheral lymphocytes Chromosomal aberrations Inhalation + Krunić et al. 2005
	

(DU)
 

Human peripheral lymphocytes Chromosomal aberrations Inhalation + Martin et al. 1991
 

Human peripheral lymphocytes Sister chromatid exchange Inhalation + Martin et al. 1991
 

Mouse (BALB/c) (EU) Sperm DNA damage Intraperitoneal + Hu and Zhu 1990
 

Rat epithelial nasal cells (DU) DNA damage Inhalation – Monleau et al.
 

2006a 

Rat broncho-alveolar lavage DNA damage Inhalation + Monleau et al.
 

(BAL) cells (DU) 2006a
 

Rat kidney cells (DU) DNA damagea Inhalation – Monleau et al.
 

2006a 

Rat kidney cells (DU) DNA damageb Inhalation + Monleau et al. 

2006a 

Rat bone marrow (DU) Micronuclei Oral + Hao et al. 2009 

Rat sperm cells (DU) DNA damage Oral + Hao et al. 2009 

Mouse bone marrow cellsc (DU) Point mutations Oral + Miller et al. 2010 

Mouse bone marrow cellsc (EU) Point mutations Oral + Miller et al. 2010 

Mouse bone marrow cellsc Point mutations Implanted DU + Miller et al. 2010 

pellets 

a

Single exposure.

b

Repeated exposures.
 c

From offspring of exposed males.
 

+ = positive result; − = negative result; ± = weak or inconclusive result; DU = depleted uranium; EU = enriched 

uranium 

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With few exceptions, studies of genotoxicity of uranium in eukaryotic cells in vitro have yielded positive 

results (Table 3-6). For example, incubation of Chinese hamster ovary (CHO) cells with uranyl nitrate 

hexahydrate resulted in significant dose-dependent increases in micronuclei, SCEs, and chromosomal 

aberrations (Lin et al. 1993). Incubation of human osteosarcoma (HOS) cells with depleted uranium for 

24 hours resulted in cell transformation into a tumorigenic phenotype and in significant increases in 

micronuclei, SCEs, and chromosomal aberrations in the form of dicentrics (Miller et al. 2002a). The 

increase in dicentrics suggested that the radiological component may play a role in depleted uranium’s 

ability to induce both DNA damage and neoplastic transformation. To further study the role of the 

radiological component in the genotoxicity of depleted uranium, the same group of investigators 

incubated HOS cells with one of three uranyl nitrate compounds at the same concentration but varying in 

specific activity (Miller et al. 2002b). The results showed a statistically significant difference in 

transformation frequency between the three uranyl nitrates that was specific activity-dependent, indicating 

that radiation can play a role in the genotoxicity of depleted uranium. A subsequent report from these 

investigators showed that depleted uranium induced de novo genomic instability in HOS progeny cells 

(Miller et al. 2003). Delayed reproductive death was evident for many generations. A similar effect was 

induced by nickel or gamma radiation. Depleted uranium stimulated delayed production of micronuclei 

up to 26 days after exposure, longer than the 12 days it took the cells to return to normal after exposure to 

nickel or gamma radiation. Miller et al. (2003) noted that the precise mechanism by which depleted 

uranium induced genomic instability is unknown but it might be similar to that for radiation. 

Studies conducted with particulate (water-insoluble) and water-soluble depleted uranium showed that 

while both forms were cytotoxic to human bronchial cells in vitro, only the particulate form induced 

chromosome aberrations above background levels (LaCerte et al. 2010; Wise et al. 2007). Wise et al. 

(2007) speculated that the different results may be related to different uptake mechanisms by the cell. 

Particulate depleted uranium would be able to enter the cell by phagocytosis, whereas soluble uranium 

would not. 

In addition to causing DNA strand breaks in CHO cells, depleted uranium also produced uranium-DNA 

adducts. Incubation of CHO cells with depleted uranyl acetate showed the presence of DNA adducts on 

the order of a few uranium atoms per thousand nucleotides (Stearns et al. 2005). The formation of 

adducts was concentration- and time-dependent. Characterization of the uranium-induced mutation in 

CHO cells showed the mutation spectrum to be different from the spectra generated spontaneously or by 

exposure to hydrogen peroxide or alpha and beta particles (Coryell and Stearns 2006). This suggested 

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Table 3-6. Genotoxicity of Uranium In Vitro 

Results 

With Without 

Species (test system) End point activation activation Reference 

Eukaryotic cells: 

Human osteosarcoma Micronucleus test ND + Miller et al. 2002a, 2002b,
 

(HOS) cells (DU) 2003
 

HOS cell line (DU) Cell transformation ND + Miller et al. 1998b, 2002a,
 

2002b
 

HOS cell line (DU) Sister chromatid ND + Miller et al. 2002a
 

exchange
 

HOS cell line (DU) DNA damage ND + Miller et al. 2002a
 

Human bronchial Chromosomal ND + Wise et al. 2007
 

fibroblasts aberrations 

(particulate DU)
 

Human bronchial Chromosomal ND – Wise et al. 2007
 

fibroblasts aberrations
 

(soluble DU)
 

Human bronchial Chromosomal ND + LaCerte et al. 2010
 

epithelial cells aberrations
 

(particulate DU)
 

CHO cells Sister chromatid ND + Lin et al. 1993 

exchange 

CHO cells Chromosomal ND + Lin et al. 1993 

aberrations 

CHO cells Micronuclei ND + Lin et al. 1993 

CHO EM9 cell line (DU) Mutation at hprt locus ND ± Stearns et al. 2005; Coryell 

and Stearns 2006 

CHO EM9 cell line (DU) DNA damage; DNA ND + Stearns et al. 2005 

adducts
 

Rat kidney proximal DNA damage ND + Thiébault et al. 2007
 

cells (DU)
 

Rat kidney proximal Micronuclei ND – Thiébault et al. 2007
 

cells (DU)
 

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Table 3-6. Genotoxicity of Uranium In Vitro 

Results 

With Without 

Species (test system) End point activation activation Reference 

Prokaryotic organisms: 

pBluescript SK+ DNA damage ND + Yazzie et al. 2003 

plasmid from E. coli 

TOP10F’ (DU)a 

Salmonella Reverse mutationb ND + Miller et al. 1998a 

typhimurium TA98 (DU) 

Salmonella TA7001- Reverse mutationb ND + Miller et al. 1998a 

7006 (DU) 

Salmonella TA98 (DU) Reverse mutationc ND – Miller et al. 1998a 

Salmonella TA7001- Reverse mutationc ND – Miller et al. 1998a 

7006 (DU) 

a

Incubated with ascorbate.
 b

Urine from rats implanted DU was tested.
 c

Serum from rats implanted DU was tested.
 

+ = positive result; ± = weakly positive; CHO = Chinese hamster ovary; DU = depleted uranium; ND = no data 

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that depleted uranyl acetate had distinct effects on cells that result in a mutagenic response. A study that 

assessed DNA damage in rat kidney (NRK-52E

) proximal cells using several methods reported DNA 

damage and apoptosis occurring in a concentration-dependent manner (Thiébault et al. 2007). Apoptosis 

cell death was caspase-dependent and activated via the intrinsic pathway of the cells. 

Implantation of depleted uranium pellets in rats resulted in an increase in the mutagenic potential of urine 

towards the Salmonella tester strain TA98 (Miller et al. 1998a). Responses were dose- and timedependent and strongly correlated with levels of uranium in the urine. In contrast to urine, tests 

conducted with rats’ serum showed no significant increase in mutations, which was consistent with the 

low levels of uranium in blood. In support of the view that uranium in the urine and not other factor was 

responsible for the urine mutagenicity was the fact that the urine from controls, both non-surgical and 

implanted with an inert tantalum pellet, did not show an increase in mutagenic activity. 

3.4 TOXICOKINETICS 

Overview. Absorption of uranium is low by all exposure routes (inhalation, oral, and dermal). 

Absorption of inhaled uranium compounds takes place in the respiratory tract via transfer across cell 

membranes. The deposition of inhalable uranium dust particles in the lungs depends on the particle size, 

and its absorption depends on its solubility in biological fluids (ICRP 1994a, 1996). Estimates of 

systemic absorption from inhaled uranium-containing dusts in occupational settings based on urinary 

excretion of uranium range from 0.76 to 5%. A comprehensive review of the available data for a 

pharmacokinetic model used lung absorption factors of 2–4% for 3-month-old children and 0.2–2% for 

adults, based on compound absorbability (ICRP 1996). Gastrointestinal absorption of uranium can vary 

from <0.1 to 6%, depending on the solubility of the uranium compound. Studies in volunteers indicate 

that approximately 2% of the uranium from drinking water and dietary sources is absorbed in humans 

(Leggett and Harrison 1995; Spencer et al. 1990; Wrenn et al. 1989), while a comprehensive review 

indicates that the absorption is 0.2% for insoluble compounds and 2% for soluble hexavalent compounds 

(ICRP 1996). There are limited data on the dermal absorption of uranium. In hairless rats, dermal 

exposure to uranyl nitrate resulted in 0.4% of the dose being absorbed (Petitot et al. 2007a); damage to the 

skin resulted in higher absorption efficiencies. Once in the blood, uranium is distributed to the organs of 

the body. Uranium in body fluids generally exists as the uranyl ion (UO2)

2+ complexed with anions such 

as citrate and bicarbonate. Approximately 67% of uranium in the blood is filtered in the kidneys and 

leaves the body in urine within 24 hours; the remainder distributes to tissues. Uranium preferentially 

distributes to bone, liver, and kidney. Half-times for retention of uranium are estimated to be 11 days in 

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bone and 2–6 days in the kidney. The human body burden of uranium is approximately 90 μg; it is 

estimated that 66% of this total is in the skeleton, 16% is in the liver, 8% is in the kidneys, and 10% is in 

other tissues. The large majority of uranium (>95%) that enters the body is not absorbed and is 

eliminated from the body via the feces. Excretion of absorbed uranium is mainly via the kidney. The 

case of Gulf War veterans who were exposed to depleted uranium from inhalation, ingestion, and wounds, 

showed average urinary excretion, 7 years postexposure, of 0.08 μg U/g creatinine, with the highest rates 

around 30 μg/g (McDiarmid et al. 1999b). 

3.4.1 Absorption 

3.4.1.1 Inhalation Exposure 

The deposition of inhalable uranium dust particles in the various regions of the lungs (extrathoracic, 

tracheobronchial, and deep pulmonary or alveolar) depends on the size of the particles. Particles >10 μm 

are likely to be transported out of the tracheobronchial region by mucocilliary action and swallowed. 

Particles that are sufficiently small to reach the alveolar region (≤10 μm AMAD) may transfer rapidly or 

slowly into the blood, depending on the solubility of the uranium compound. According to the ICRP 

(1996), a more soluble compound (uranium hexafluoride, uranyl fluoride, uranium tetrachloride, uranyl 

nitrate hexahydrate) is likely to be absorbed into the blood from the alveoli within days and is designated 

inhalation Type F (fast dissolution). A less soluble compound (uranium tetrafluoride, uranium dioxide, 

uranium trioxide, triuranium octaoxide) is likely to remain in the lung tissue and associated lymph glands 

for weeks and is designated Type M (medium dissolution). A relatively insoluble compound (uranium 

dioxide, triuranium octaoxide) may remain in the lungs for years and is designated Type S (slow 

dissolution). 

Analysis of excreta of active uranium mill crushermen exposed to ore dust indicated that 1–5% of 

uranium entering the lungs was absorbed systemically and excreted in the urine and 95–99% was 

eliminated in the feces. Absorption could have taken place in the lungs or in the gastrointestinal tract 

from swallowed particles cleared from the lungs (Fisher et al. 1983). Uranium workers exposed to high 

levels of uranium dust had a very low lung burden of uranium, indicating that only a small fraction 

penetrates into the alveolar region (West and Scott 1969) and remains there without being cleared (or 

being very slowly cleared) via retrograde tracheobronchial mucus transport to the gastrointestinal tract, 

into lymph nodes, or dissolved into the circulating blood. 

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Estimates of absorption into the blood were derived from the excretion data of uranium mill workers 

(Wrenn et al. 1985). The authors’ estimated daily mean absorption of inhaled uranium by mill workers 

was 24 μg U/day (0.34 μg U/kg for 70-kg reference man) based on measured excretion in feces and 

workplace ambient air concentrations. The absorption of uranium by these workers was estimated as 

0.76% (range, 0.4–1.6%). Control subjects in a study of differential metabolism of 230Th, 234U, and 

238U inhaled in uranium ore dust included three retired uranium mill workers (4–14 years since last 

employment as uranium ore crushermen), and three volunteers who lived in uranium milling communities 

but had no uranium work history. Two consecutive 24-hour urine and fecal collections were obtained and 

analyzed for 234U and 238U. The apparent total intakes of uranium of these individuals ranged from 11 to 

18 μg U/day for the controls and from 5.3 to 71 μg U/day for the retirees. Although large compared to 

uranium intakes estimated for city dwellers, the uranium intakes of these individuals are not unreasonable 

because uranium in potable waters and locally grown foods tends to be higher in uranium mining and 

milling communities. The mean uranium absorption calculated for the controls (0.82%; range, 0.6–1%) 

was not significantly different from that calculated for the retired uranium workers (0.94%; range, 0.55– 

1.6%) (Wrenn et al. 1985). 

Urinary excretion data were used to estimate the absorption of uranium by workers accidentally exposed 

to uranium hexafluoride (USNRC 1990). Estimated airborne concentrations were 20 mg uranium 

hexafluoride/m3 for a 1-minute exposure and 120 mg uranium hexafluoride/m3 for a 60-minute exposure 

(15.2 and 91 mg U/m3

, respectively) (USNRC 1986). Initial intakes of workers involved in the accident 

ranged from 470 to 24,000 μg uranium. 

Higher absorption of uranium occurred in animal studies using aerosols of purified uranium compounds. 

In these studies, as in human studies, the solubility of the uranium compound and the size of the inhaled 

particles determined absorption. Reported absorption of the inhaled dose was 18–40% in rats and 20– 

31% in guinea pigs for uranium hexafluoride (Leach et al. 1984) and 23% for uranium trioxide in dogs 

(Morrow et al. 1972). One month following a single intratracheal instillation, the percentage of the dose 

transferred to the blood from the lungs was 73.7–74.8% for uranium peroxide (7.6 or 195 μg 

administered) and 38.8–43.9% for uranium tetrafluoride (32 or 301 μg administered); the percent 

absorbed was not influenced by the instillation concentration (Houpert et al. 1999). 

In addition to the uptake of uranium from the lungs, there is some evidence from a study of rats exposed 

via nose-only exposure to 190 mg/m3 depleted uranium dioxide 30 minutes/day, 4 days/week for 

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30 weeks (Houpert et al. 2007c) that uranium may be taken up by the olfactory epithelial pathway and 

travel along the olfactory neuron to the olfactory bulb. 

3.4.1.2 Oral Exposure 

Experimental studies in humans consistently show that absorption of uranium by the oral route is <5%. 

Reported fractional absorptions include a range of 0.005–0.05 (0.5–5%) in a group of 4 males ingesting 

10.8 mg uranium in a soft drink (Hursh et al. 1969), 0.001–0.06 (median of 0.009) in 50 males and 

females exposed to uranium in the diet and drinking water (Limson Zamora et al. 2002, 2003), 0.001– 

0.005 in 4 subjects ingesting a single dose of 100 mg uranium as depleted uranyl nitrate dissolved in a 

grapefruit drink (Karpas et al. 1998), <0.0025–0.04 in a group of 12 volunteers given drinking water high 

in uranium (Wrenn et al. 1989), and 0.005–0.05 in another drinking water study (Harduin et al. 1994). 

Similar results were obtained in dietary balance studies (Leggett and Harrison 1995; Spencer et al. 1990; 

Wrenn et al. 1989). A study comparing uranium absorption between subjects primarily exposed to 

uranium in the diet and subjects exposed to elevated levels of uranium in the drinking water (Limson 

Zamora et al. 2002, 2003) did not find significant differences in fractional absorption between the two 

subroutes. This study also found no significant differences in uranium fractional absorption related to 

gender or age (subjects <25 years compared to those >25 years). A review of human data conducted by 

the ICRP determined that a fractional absorption of 0.02 for soluble compounds and 0.002 for insoluble 

compounds should be used in modeling the kinetics of dietary uranium in humans (ICRP 1995). A rapid 

absorption rate (5–15 hours) was estimated in four individuals ingesting a single dose of depleted uranyl 

nitrate (Karpas et al. 1998). 

In animal studies, absorption generally increases with increasing solubility of the compound, being 

greatest for uranium ingested as uranyl nitrate hexahydrate, uranium hexafluoride or uranyl fluoride, 

about half as great for uranium tetroxide or uranium trioxide, and 1–2 orders of magnitude lower for 

uranium tetrachloride, triuranium octaoxide, and uranium tetrafluoride (ICRP 1995). Increased 

absorption of uranium has been demonstrated in neonatal rats and pigs (ICRP 1995). Fractional 

absorption in 2-day-old rats given uranyl nitrate was estimated as 0.01–0.07, 2 orders of magnitude 

greater than for adults (ICRP 1995). 

Evidence from several animal studies showed that the amount of uranium absorbed from the 

gastrointestinal tract was about 1% (Harrison and Stather 1981; Houpert et al. 2001; Larsen et al. 1984; 

La Touche et al. 1987; Maynard et al. 1953; Sullivan 1980a), although other studies have reported lower 

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absorption efficiencies. Frelon et al. (2005) estimated that 0.43% of the depleted uranyl nitrate in 

drinking water was absorbed by rats. A range of gastrointestinal absorption rates of 0.038–0.078% has 

been estimated by others based on data from a 2-year study in which rats were fed diets containing 0.05– 

0.5% of soluble uranium compounds (uranyl fluoride or 0.5–2% of uranyl nitrate). The rate of absorption 

appeared to be independent of concentration of uranium in the diet (Wrenn et al. 1985). Absorption 

factors in rats that were exposed by gavage to doses of 233U-uranyl nitrate hexahydrate (where this 

anthropogenic radionuclide provided increased sensitivity without competition with natural isotopes) 

increased 3.4 times over normal in rats that were iron-deficient (Sullivan and Ruemmler 1988), doubled 

in rats that were fasted (Sullivan et al. 1986), and increased 3.6 times in neonates as compared to adults 

(Sullivan 1980b). Adult baboons (fed normally) absorbed about 0.5%, whereas fasted baboons absorbed 

an average of 4.5% (Bhattacharyya et al. 1989). Consistent with the results in baboons, fed and 24-hour 

fasted male B6CF1/ANL mice absorbed 0.069 and 0.80%, respectively (Bhattacharyya et al. 1989). 

Studies in rats suggest that the primary pathway for gastrointestinal absorption of soluble uranium as 

depleted uranyl nitrate is through the small intestinal epithelium (Dublineau et al. 2005, 2006) via the 

transcellular pathway (Dublineau et al. 2005). Uranium was not absorbed from the buccal cavity, 

stomach, or large intestine (Dublineau et al. 2005). Ex vivo experiments provide evidence that uranium is 

equally absorbed in all regions of the small intestine (Dublineau et al. 2005). 

3.4.1.3 Dermal Exposure 

Absorption of uranium through the skin has not been characterized in humans. Dermal absorption in 

animal models can be inferred from the appearance of toxicity in mice, rats, rabbits, and guinea pigs after 

dermal exposure to uranium compounds (Orcutt 1949). Absorption was also shown to occur through the 

conjunctival sac of the eye. 

Electron microscopy and x-ray microanalytical methods showed that uranium as uranyl nitrate 

hexahydrate penetrated the stratum corneum within 15 minutes and accumulated in the intracellular space 

between the viable epidermis and the stratum corneum (De Rey et al. 1983). As is the case with 

inhalation and oral absorption, water solubility is an important determinant of absorption, and no 

penetration was observed with the insoluble compounds uranium dioxide, uranyl acetate, or ammonium 

diuranate. After 48 hours, uranium applied as uranyl nitrate was no longer found in the skin and toxicity 

developed, indicating that the uranium had been absorbed into the blood. 

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A series of in vitro and in vivo studies conducted by Petitot et al. (2004, 2007a, 2007b) demonstrated that 

uranyl nitrate is absorbed through the skin. In vitro, the first transfer of uranium across hairless rat skin 

and pig ear skin occurred 3 or 4 hours, respectively, after application of uranyl nitrate (Petitot et al. 2004). 

However, uranium was transferred across excoriated skin (stratum corneum removed to simulate a 

wound) in 30 minutes for both rat and pig skin. Application of depleted uranium to the skin of hairless 

rats in vivo resulted in significant increases in uranium levels in muscle at the contamination site 6 hours 

after application to intact skin and within 30 minutes after application on excoriated skin (Petitot et al. 

2007a). Twenty-four hours after application, 0.4% of the dose was absorbed through intact skin (Petitot 

et al. 2007a). A higher percentage of uranium was absorbed through wounded skin; 38% absorbed 

through excoriated skin and 2–4% through skin damaged from application of a mild acid solution. In 

contrast, severely damage skin from exposure to a strong acid or base, resulted in lower absorption 

efficiencies than intact skin. 

3.4.2 Distribution 

Absorbed uranium is found in all human tissues, but preferentially deposits in bone and kidney, regardless 

of the route of exposure (ICRP 1995, 1996). Although uranium also distributes significantly to liver, this 

organ is not a major repository for uranium; however, for modeling purposes, tissue contents are often 

normalized to liver concentration because the latter is reported in almost all studies of uranium 

biokinetics. The normal adult body burden is considered to be approximately 90 μg. It is estimated that 

about 66% of this total is in bone, 16% is in the liver, 8% is in the kidneys, and 10% is in other tissues 

(ICRP 1979, 1995, 1996). It is not known if maternal bone stores of uranium (like those of calcium and 

lead) are mobilized during pregnancy and lactation. Uranium can cross the placenta after parenteral 

administration in animals; no information was located on distribution of uranium in breast milk for either 

humans or animals. 

3.4.2.1 Inhalation Exposure 

Autopsy data from individuals occupationally exposed to uranium indicates that bone is the primary site 

of long term retention of absorbed uranium (ICRP 1995). Inhalation exposure may also result in some 

retention of insoluble uranium particles in the lungs. An evaluation of the postmortem data from a 

uranium worker who had inhaled a total of 220 mg (147 pCi) uranium over a 3-year period found 11 μg 

(7 pCi) uranium in the lungs 13 years after the end of exposure. The total calculated dose equivalent from 

the inhaled uranium was 35 rem (0.35 Sv) (Keane and Polednak 1983). 

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In a comprehensive study of tissues from two long-time residents of New Mexico without known 

occupational exposure, the skeleton was the primary depot for uranium (Kathren 1997). Approximately 

80 soft tissue samples and 90 bone samples were analyzed from each subject. The mean uranium 

concentrations in bone were 4.8 and 5.8 ng/g wet weight for the two subjects, respectively. Highest 

concentrations of uranium in soft tissues were in the tracheobronchial and other pulmonary related lymph 

nodes indicating uranium-bearing particulate clearance from the lungs. Concentrations in pulmonary 

lymph nodes ranged from 16–28 ng/g in one individual to 29–259 ng/g wet weight in the other. In 

another comprehensive autopsy study of a worker at a facility involved in the processing and handling of 

radioactive material, the highest levels of uranium in soft tissues was found in the respiratory tract, 

particularly the tracheobronchial lymph nodes (Russell and Kathren 2004). The relative amounts of 

uranium in the body were lung > skeleton > spleen > liver > kidney. Relatively high levels of uranium 

were also found in the urinary bladder, blood, and thyroid. A study of uranium process workers and 

nearby residents chronically exposed to depleted uranium aerosols detected depleted uranium levels in the 

urine 20 years after exposure (Parrish et al. 2008), suggesting long-term storage and distribution of 

uranium. 

Urinary excretion data were used in a kinetic model to estimate the maximum uranium kidney 

concentrations of workers accidentally exposed to uranium hexafluoride (USNRC 1990). Initial intakes 

of workers involved in the accident ranged from 470 to 24,000 μg uranium. The model estimated the 

maximum kidney concentrations in the workers as ranging from 0.048 to 2.5 μg U/g in kidney tissue; 

renal toxicity was not observed in any of the workers (USNRC 1990). 

In animals, uranium that has been absorbed from the lungs leaves the blood very quickly for distribution 

to body tissues. Following a single intratracheal instillation, uranium was removed from the lung with 

retention half-times of 0.6–1.3 (63.6–71.6% absorbed) and 30–35 days (36.4–29.4% absorbed) following 

instillation of 32 or 301 μg uranium tetrafluoride, and 0.5–1.2 (96.6–90.3% absorbed) and 27–38 days 

(3.4–9.7% absorbed) following instillation of 7.6 or 195 μg uranium peroxide (Houpert et al. 1999). One 

month after instillation of either uranium compound, 11.3–20.4% of the uranium dose remained in the 

carcass, 1.5–4.4% was found in the kidney, and 75.9–84.3% was excreted in the urine. The amount of 

uranium found in the bones of dogs and rats exposed to uranium for 1 year was related to the solubility of 

the uranium solubility (Stokinger et al. 1953). The concentrations of uranium in bone were 2.0 and 

2.7 μg/g in rats exposed to uranyl nitrate (0.25 mg U/m3

) and uranyl fluoride (0.2 mg U/m3), respectively; 

however, exposure to a similar concentration of uranium tetrachloride (0.2 mg U/m3

) resulted in a 10-fold 

reduction in uranium bone levels (0.2 μg/g). Uranium has also been shown to accumulate in the 

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tracheobronchial lymph nodes, lungs, bones, and kidneys of rats, dogs, and monkeys exposed to uranium 

dioxide at 5.1 mg U/m3 for 1–5 years (Leach et al. 1970, 1973). In rats exposed to yellowcake, the U3O8 

portion of the yellowcake cleared from the lung with a half-time of 110–240 days (Damon et al. 1984). 

Mice given inhaled doses of U3O8 equivalent to about 0.2 mg U/kg exhibited uranium tissue distribution 

(in μg/g tissue) as follows: lung, 6.05; liver, 0.051; spleen, 1.45; kidney, 0.536; tibia, 0.731; urine, 0.519; 

and feces, 2.20 (Walinder 1989). In an inhalation study using highly enriched uranium dioxide particles 

(92.8% 235U), rat lungs were found to clear the uranium particles at a rate of 0.28% per day over a period 

of 720 days. At 720 days postexposure, 82% of the uranium remained in the lungs and thoracic lymph 

nodes of the rats. The highest mass of extrapulmonary uranium dioxide was detected in rats sacrificed up 

to 11 days postexposure. This was mainly found in the intestinal tract and the carcass. The authors found 

that the pulmonary clearance rate of highly enriched uranium dioxide particles was about the same as the 

clearance rate for natural or unenriched uranium dioxide particles (Morris et al. 1990), as would be 

expected since they are the same chemical compound. 

One site of deposition for the soluble compounds (uranyl nitrate, uranium tetrachloride, uranium 

hexafluoride) in animals was the skeleton, but accumulation was not seen in bone at levels below 

0.25 mg U/m3 over a period of 2 years in rats exposed to soluble compounds (uranyl nitrate, uranium 

tetrachloride, uranium hexafluoride) in one study. The insoluble compounds (uranium hexafluoride, 

uranium dioxide) were found to accumulate in the lungs and lymph nodes after the inhalation exposure. 

For uranyl nitrate exposure, no retention was found in the soft tissues. Accumulation of uranium was also 

found in the skeleton (Stokinger et al. 1953). The amount distributed in the skeleton has been reported to 

be 23–45% of the intake in dogs (Morrow et al. 1972); 28–78% in rats (Leach et al. 1984); and 34–43% in 

guinea pigs (Leach et al. 1984). A biological half-time of 150–200 days (Ballou et al. 1986) or 70 days 

(Morrow et al. 1982a) in the skeleton has been reported following inhalation exposure to soluble uranium 

compounds (e.g., uranium hexafluoride). 

A 5-year exposure of Beagle dogs and monkeys, and a 1-year exposure of rats, to 5.8 mg uranium 

dioxide/m3 (5.1 mg U/m3

) as uranium dioxide dust (AMAD=1 μm) resulted in rapid lung buildup during 

the first few months, which approached maximal values of 2, 3.6, and 0.8 mg U/g in dogs, monkeys, and 

rats, respectively, at the end of year 1. Buildup in the tracheobronchial lymph nodes reached peak values 

in year 4 of 50–70 mg U/g in both dogs and monkeys. For each, the peak radiation dose rates reached 

1.8 and 3.3 rads/week (0.018 and 0.033 Gy/week) to lungs and 55 and 64 rads/week (0.55 and 

0.65 Gy/week) to lymph nodes, while the total radiation dose for the 5 years approached 500 and 900 rads 

(5 and 9 Gy) to lungs and 10,000 rads (10 Gy) to lymph nodes. A reevaluation of the study data also 

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showed a rapid accumulation of uranium in the lungs and tracheobronchial lymph nodes during the first 

few months of exposure. The accumulation in these organs was highest (0.8 mg/g in lungs and 1.5 mg/g 

in lymph nodes) at the end of 1 year of exposure. The uranium content in the lungs decreased with a halftime of approximately 480 days. In the lymph nodes, uranium depletion showed a trend similar to the 

lungs in dogs exposed for 2 and 5 years and a biphasic pattern in dogs exposed for 1 year. Comparatively 

low levels of uranium were found in the kidney, femur, liver, and spleen, and these decreased with time 

(Leach et al. 1973). 

In other studies, no significant accumulation was found in the spleen or liver of rats, dogs, or guinea pigs 

(Ballou et al. 1986; Diamond et al. 1989; Leach et al. 1973, 1984; Morrow et al. 1972; Wrenn et al. 

1987). Uranium has been shown to increase in the brain following intermediate-duration inhalation 

exposure to depleted uranium dioxide; however, the levels rapidly decrease following exposure 

termination (Monleau et al. 2005). Uranium is unequally distributed in the brain, with the highest levels 

found in the olfactory bulbs, followed by the hippocampus, cortex, and cerebellum. 

3.4.2.2 Oral Exposure 

Uranium levels have been measured in tissues from humans, with no occupational exposure where the 

source of uranium was assumed to be dietary and environmental. 

In a comprehensive study of tissues from two long-time residents of New Mexico, the skeleton was the 

primary depot for uranium (Kathren 1997). Approximately 80 soft tissue samples and 90 bone samples 

were analyzed from each subject. The mean uranium concentrations in bone were 4.8 and 5.8 ng/g wet 

weight for the two subjects, respectively. Highest concentrations of uranium in soft tissues were in the 

tracheobronchial and other pulmonary related lymph nodes, indicating uranium-bearing particulate 

clearance from the lungs. Concentrations in pulmonary lymph nodes ranged from 16 to 28 ng/g in one 

individual to 29–259 ng/g wet weight in the other. An unexpectedly high concentration was found in the 

thyroid of one subject. In both subjects, uranium was widely distributed among the soft tissues; liver 

concentrations were lower than those in the kidney (approximately 0.1 and 0.9 ng/g wet weight, 

respectively). 

The concentrations of uranium in human blood from New York City donors averaged 0.14 mg U/kg in 

both whole blood and red cells, compared to values ranging from <0.04 to 86 mg U/kg globally (Fisenne 

and Perry 1985). The median concentrations of uranium in the lungs, liver, kidneys, and vertebra from 

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New York City residents among all age groups were reported to be 0.33, 0.13, 0.32, and 0.29 mg U/kg, 

respectively (Fisenne and Welford 1986). 

In an evaluation of two human skeletal tissues, it was observed that the sacrum contained the highest 

concentrations of 238U and 234U (4.9 mBq/g ash; 0.13 pCi/g ash; 0.20 μg/g ash). The concentration of 238U 

was lowest (0.1 mBq/g ash; 0.0027 pCi/g ash; 0.004 μg/g ash) in the right femur (Singh et al. 1987b). In 

the United Kingdom, the mean uranium concentration in wet bone was reported to be 0.33 μg U/kg 

(Fisenne and Welford 1986). 

Data on laboratory animals indicate that a substantial portion of uranium leaving the blood may initially 

distribute throughout soft tissues, but a few days after absorption or injection into the blood, most of the 

systemic content is found in the kidneys and skeleton (Bhattacharyya et al. 1989; ICRP 1995). 

In animals, a substantial fraction of plasma uranium is associated with the ultrafilterable low-molecularweight fraction, and the remainder is weakly associated with transferrin and other plasma proteins. Data 

on baboons indicate that ≥50% of the uranium in blood is associated with the red blood cells during the 

period 10–1,000 hours after injection. These data have been interpreted to mean that about 0.7% of the 

uranium leaving the plasma attaches to red blood cells and is returned to plasma with a half-time slightly 

greater than 1 day (ICRP 1995). 

In animals, absorbed uranium is osteotropic, accumulating largely on the surface of all types of bone of 

the animals. Eventually, the uranium on the bone surface diffuses into the mineral portion of the bone. 

Autoradiography provides confirming evidence that, in the long-term, uranium is a bone volume seeker 

(Wrenn et al. 1987). Kinetic models of uranium distribution predict that, for the short-term, uranium 

distributes to the bone surface and bone marrow, while the deep bone is the long-term depot (Sontag 

1986). These results suggest that the macro distribution of uranium in the human skeleton is not uniform. 

In some ways, the skeletal behavior of uranium is quantitatively similar to that of alkaline earths. It is 

known that the uranyl ion (UO2

2+) exchanges with Ca2+ on the surfaces of bone mineral crystals, although 

it does not participate in crystal formation or enter existing crystals. The early distribution of uranium in 

different parts of the skeleton is similar to that of calcium. Uranium initially deposits on all bone surfaces 

but is most highly concentrated in areas of growth. Depending on the microscopic structure of the bone 

of each species, uranium on bone surfaces may gradually diffuse into bone volume; such diffusion has 

been observed in dogs but not in rats or mice. As with calcium, a substantial portion of uranium 

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deposited in bone is lost to plasma by processes that occur more rapidly than bone resorption (see 

Section 3.4.5). In human subjects injected with uranium, an estimated 80–90% of the original skeletal 

deposition was lost from bone over the first 1.5 years (ICRP 1995). 

In a study with female mice exposed orally in feed to uranyl nitrate hexahydrate at a dosage of 462 mg 

U/kg/day for 36–44 weeks, average uranium accumulations were 6 μg per pair of kidneys, 46 μg/g bone, 

and 0–0.5 μg in whole liver, respectively. No significant organ accumulation was found for the lower 

dose levels (Tannenbaum et al. 1951). Maximal concentrations of 77 μg per pair of kidneys and 216 μg/g 

in bone were estimated at 50 weeks in male mice that were orally exposed to uranyl nitrate hexahydrate at 

925 mg U/kg/day for 48 weeks. One mouse with small kidneys showed levels of 395 μg/pair of kidneys 

and 1,440 μg/g bone (Tannenbaum et al. 1951). Average uranium accumulations in the kidneys and bone 

of male mice exposed to uranyl fluoride orally at 452 mg U/kg/day for 28 weeks were 33 μg/pair of 

kidneys and 145 μg/g bone at 20 weeks (Tannenbaum et al. 1951). Maximal concentrations of 6 μg/pair 

of kidneys at 50 weeks and 29 μg/g bone at 14 weeks were found in female mice given oral uranium 

tetrachloride at 978 mg U/kg/day for 48 weeks (Tannenbaum et al. 1951). 

Paquet et al. (2006) examined the distribution of uranium in rats following chronic ingestion of 2.0– 

2.9 mg U/kg/day as uranyl nitrate in drinking water. In addition to the elevated levels of uranium found 

in the kidney and bones, uranium accumulated in the teeth and brain. Uranium concentrations in teeth 

were higher than in the skeleton, suggesting that uranium was deposited on the enamel. Accumulation of 

uranium in the whole body and individual tissues followed a nonmonotonous pattern that was not 

predictable by biokinetic models. In the whole body, peak levels were found after 3, 10, and 19 months 

of exposure. Total uranium levels in the whole body were 51.0, 182, 42.2, 134, 3.8, and 200 ng/g tissue 

after 1, 3, 6, 10, 12, and 19 months of exposure, respectively. Different patterns of uranium accumulation 

were found in the lumbar vertebrae and femur (diaphysis and epiphysis regions). In the vertebrae, 

uranium levels did not significantly change until 570 days of exposure; in contrast, uranium levels in the 

femur peaked at day 95, decreased at day 186, and increased at days 312 and 570. In the kidneys, 

uranium levels decreased between months 1 and 12 (220 ng/g tissue to 72.4 ng/g) and then increased 

again (311 ng/g) at 19 months. The investigators noted that the results could not be adequately explained 

and that further studies should be conducted. Elevated levels of uranium in the brain were also observed 

in rats exposed to 3.7 mg U/kg/day as 4.92% enriched uranyl nitrate in mineral water for 90 days 

(Lestaevel et al. 2005). The levels of uranium in the brain increased from 75.4 to 86.1 ng; the levels of 

uranium in the kidneys were also significantly increased from 101.9 to 579.0 ng. 

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The insoluble compounds of uranium accumulated to a lesser extent in tissues. Only small amounts of 

uranium were found in the kidneys (3–9 μg/pair of kidneys) of female mice that were exposed orally to 

uranium tetrafluoride at 4,437 mg U/kg/day for 48 weeks. No uranium was found in the bone 

(Tannenbaum et al. 1951). Only small amounts of uranium were found in kidney (1–3 μg/pair of 

kidneys) of female mice that were exposed orally to triuranium octaoxide at 1,655 mg U/kg/day for 

48 weeks. No uranium was found in the bone (Tannenbaum et al. 1951). 

Arruda-Neto et al. (2004a) examined the accumulation of uranium in bones as a function of uranium dose 

in young rats exposed to uranyl nitrate in the diet at doses of 0.1–26 mg U/kg/day for 60 days and found a 

biphasic relationship. The inflexion point was at approximately 6 mg/kg/day and accumulation of 

uranium in the bone increased linearly at doses higher than 6 mg/kg/day. Another study by this group 

(Arruda-Neto et al. 2004b) found that uranium was equally distributed in the bone and bone marrow in 

dogs following a long-term exposure to uranyl nitrate in the diet. 

Oral exposure to uranyl nitrate in mineral water for 9 months resulted in significant increases in uranium 

levels in the hippocampus and cortex; a 1.5-month exposure resulted in nonsignificant increases in 

uranium in these brain areas (Bensoussan et al. 2009). Bellés et al. (2005) also reported significant 

increases in brain uranium levels, as compared to controls, following a 3-month exposure to uranyl 

acetate; however, there was no statistical relationship between dose and brain uranium levels. 

The uranium blood:tissue transfer coefficients were estimated in Wistar rats exposed to 0.5–26 mg 

U/kg/day as uranyl nitrate in the diet for 60 days (Arruda-Neto et al. 2001). The highest transfer 

coefficients were found in the kidneys and liver. A plot of the transfer coefficients for skin, brain, 

intestine, heart, liver, and kidneys exhibited concave shapes with the point of deflection occurring at the 

5 mg U/kg/day dose level in all tissues except the intestines. Additionally, the slope of the uranium tissue 

concentration versus dietary concentration increased gradually at the lower doses (<5 mg U/kg/day) and 

steeply at doses of 5–26 mg U/kg/day; increases in occult blood levels in the urine were also observed at 

the higher doses, suggesting that the sharp increase in tissue uranium levels may be due to renal damage. 

3.4.2.3 Dermal Exposure 

No studies were located regarding distribution of uranium after dermal exposure in humans. In hairless 

rats dermally exposed to depleted uranium in a nitric acid solution, increased levels of uranium were 

detected in the kidneys and bone 6 hours after application to intact skin; the highest concentrations were 

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found in the kidney (Petitot et al. 2007a). Application to wounded skin (via mechanical abrasion or 

exposure to weak acids) resulted in significant increases in uranium levels in the kidneys and bone within 

30 minutes of exposure. 

3.4.2.4 Other Routes of Exposure 

Intravenously injected uranium is rapidly taken up by the tissues or excreted in the urine (ICRP 1995). 

Typically, 25% of intravenously injected uranium (as uranyl nitrate) remained in blood of human subjects 

after 5 minutes, 5% after 5 hours, 1% after 20 hours, and <0.5% after 100 hours although inter-subject 

variation was high (AEC 1948, 1957). Measurements of systemic distribution of uranium made at 

autopsy in one terminally ill human given a single intravenous injection of uranium indicated that the 

skeleton, kidneys, and other soft tissues after 2.5 hours contained about 10, 14, and 6%, respectively, of 

the dose. Distribution data taken from another human subject 18 hours after a single intravenous injection 

uranium showed that the bones, kidneys, and other soft tissues contained about 4–13, 6, and 4%, 

respectively, of the amount injected. At 566 days postinjection, uranium distribution in the skeleton, 

kidneys, and other soft tissues declined to about 1.4, 0.3, and 0.3%, respectively. 

The distribution of uranium following implantation of depleted uranium pellets into the gastrocnemius 

muscle has been investigated in rats (Pellmar et al. 1999a; Zhu et al. 2009a). Within 1 day of 

implantation, uranium was measurable in kidney and bone but not in the other tissues. At later time 

points, significant amounts of uranium were found in the other tissues, especially the spleen, liver, and 

lung; the levels were always highest in the kidney and bone. The amount of uranium in the kidney and 

bone was significantly correlated with the uranium dose. Tissue uranium levels peaked 90 days after 

implantation and gradually decreased; however, the levels were still elevated 360 days postimplantation 

(Zhu et al. 2009a). 

3.4.3 Metabolism 

Uranium is usually found in compounds that can be metabolized and recomplexed to form other 

compounds. In body fluids, tetravalent uranium is likely to oxidize to the hexavalent form followed by 

formation of uranyl ion. Uranium generally complexes with citrate, bicarbonates, or protein in plasma 

(Cooper et al. 1982; Dounce and Flagg 1949; Stevens et al. 1980). The stability of the carbonate complex 

depends on the pH of the solution, which will differ in different parts of the body (BEIR IV 1988). The 

low-molecular-weight bicarbonate complex can be filtered at the renal glomerulus and be excreted in 

urine at levels dependent on the pH of the urine. The uranium bound to the protein (primarily transferrin) 

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is less easily filtered and is more likely to remain in blood. In the blood, the uranyl ion binds to 

circulating transferrin, and to proteins and phospholipids in the proximal tubule (Wedeen 1992). 

3.4.4 Elimination and Excretion 

Two-thirds of uranium, intravenously injected as uranyl nitrate in human subjects was typically excreted 

in urine in the first 24 hours. Approximately 10% more was excreted over a period of 5 days. Fecal 

excretion accounted for <1% of the excretion (ICRP 1995). 

3.4.4.1 Inhalation Exposure 

In a study of 7,231 uranium workers, the urinary concentration of uranium ranged from 5 μg/L in 

4,556 workers to >100 μg/L in 32 workers. Samples were taken weekly over a 6-year period. Among a 

control group of 600 non-uranium workers, none had urinary uranium concentrations that exceeded 

40 μg/L. The author concluded that urinary uranium concentrations >100 μg/L are definitely indicative of 

recent absorption, and that pathological albuminuria is rare, except when the urinary uranium 

concentration exceeds 1,000 μg/L. Albuminuria, when seen, was transient, and did not persist 

(Butterworth 1955). 

Urinary excretion in crushermen (about 0.2 nCi/day [7 Bq/day; 0.3 mg/day]) is about 1/100th of fecal 

excretion (about 13.5 nCi/day [500 Bq/day; 20 mg/day]). The activity of 234U in urine was slightly higher 

than that of 238U. Active crushermen excreted higher levels of 234U, 238U, and 230Th than retired 

crushermen or controls (Fisher et al. 1983). Most of the inhalation doses of female employees at the Oak 

Ridge plant were excreted in the feces, indicating that ciliary action in the lungs, followed by fecal 

excretion, was an important mechanism of body clearance (West and Scott 1969). 

Lu and Zhao (1990) reported on the excretion of uranium in an occupationally exposed worker. A 

23-year-old man who weighed 60 kg, dressed in protective clothing, mask, and gloves, was accidentally 

exposed to pure uranium tetrafluoride powder for 5 minutes. The uranium tetrafluoride powder cloud was 

reported to contain natural uranium. Urinary excretion was reported as 112 μg/L or 156.8 μg in the first 

24 hours, gradually increasing through postaccident day 60 and returning to normal at about postaccident 

day 1,065. The total urinary excretion of uranium through day 1,065 was calculated to be 86.7 mg. The 

excretion data was used to calculate total absorption and kidney content by use of a kinetic model (ICRP 

1979). The kidney content on postaccident day 1 was reported as 804.2 μg or approximately 2.6 μg/g of 

kidney. 

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Depleted uranium was detected in the urine of uranium process workers and nearby residents 20 years 

after chronic exposure to depleted uranium aerosols (Parrish et al. 2008). The biological half-time of 

uranium dioxide in human lungs (occupational exposure) at German fuel fabrication facilities was 

estimated to be 109 days. Body burden measurements of uranium taken from 12 people who handled 

uranium oxides for 5–15 years were used for this determination. Twice a year for 6 years, urinalysis was 

conducted on workers exposed to uranium. In vivo lung counting was performed on the last day before 

and the first day after a holiday period. Levels of uranium in feces were measured during the first 3 days 

and the last 3 days of a holiday period and the first 3 days after the restart of work. For some employees, 

the levels of uranium in feces were measured during 3–4 days one-half year after the holiday period 

(Schieferdecker et al. 1985). 

In animals, most of absorbed uranium is excreted in urine. Inhaled larger particles (≥10 μm) are 

transported out of the respiratory system by mucocilliary action, then swallowed, and eliminated in the 

feces (Ballou et al. 1986; Downs et al. 1967; Morrow et al. 1982a). Deposition sites of inhaled aerosols, 

and hence the clearance kinetics, are determined in part by particle size of the inhaled particles. As the 

AMAD increases, the amount deposited in the upper respiratory tract increases, and the amount deposited 

in the deep respiratory tracts of the lungs decreases. This study used both 232U and 233U dusts. The 

233U dust deposition in the upper respiratory tract increased from 21 to 62% of the total amount of dust 

deposited with increasing particle size; deposition in the deep lung decreased from 22 to 7% with 

increasing particle size. The 232U dust deposition in the upper respiratory tract increased from 10 to 32% 

with increasing particle size; deposition in the deep lung decreased from 23 to 9% with increasing particle 

size. The differences were less marked for 232U dust, presumably because the particle size was much 

more uniform than that for the 233U dust. A large amount of the initial lung burden was preferentially 

cleared via the feces following clearance from the upper respiratory tract to the gastrointestinal tract 

(higher fecal excretion with higher AMAD) by mucocilliary action. Urinary excretion was 25–50% of 

initial lung burden on day 1 and less with larger particles. By day 7, 25–80% of the uranium uptake was 

cleared in urine; most of the uranium was eliminated in the feces (Ballou et al. 1986). In one study with 

rats, most of the inhaled uranium, as uranium dioxide, was excreted in the urine. In dogs, <10% was 

excreted in feces (presumably cleared by mucocilliary action) (Cooper et al. 1982). About 60% of the 

retained uranium, as uranyl nitrate hexahydrate (Ballou et al. 1986), uranium hexafluoride (Leach et al. 

1984), and uranium trioxide (Morrow et al. 1982a), was excreted in urine within 1 day in other studies 

with rats, dogs, and guinea pigs. Most of the retained uranium in rats exposed via intratracheal intubation 

with uranium dioxide or uranyl nitrate hexahydrate was excreted in the urine. Less than 10% was 

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excreted in feces (presumably cleared by mucocilliary action) (Cooper et al. 1982). The fraction of 

insoluble compounds (uranium tetrafluoride, uranium dioxide) retained in the lungs and lymph nodes was 

independent of the exposure concentration. More than 90% of the uranium retained at the end of the first 

year of exposure to uranium dioxide was cleared by the end of the second year despite continued 

exposure to uranyl nitrate hexahydrate. All of the uranium retained following 1 year of exposure to 

uranium tetrafluoride was cleared by the end of the second year. For uranyl nitrate hexahydrate exposure, 

no retention was found in the soft tissues (Stokinger et al. 1953). 

Once deposited in the lungs, uranium compounds clear from the various biological compartments by 

solubility. The ICRP lung model recognizes three clearance classification types: F, M, and S. Type F 

compounds (uranium hexafluoride, uranyl fluoride, uranium trioxide, possibly uranium tetrafluoride, 

possibly triuranium octaoxide) show 100% absorption with a half-time of 10 minutes. Type M compounds 

(uranyl nitrate, ammonium diuranate, possibly uranium tetrafluoride, possibly triuranium octaoxide) show 

10% absorption with a half-time of 10 minutes, 90% with a half-time of 140 days, and about 70% of the 

material in the alveoli eventually reached body fluid. Type S compounds (uranium dioxide) show 0.1% 

absorption with a half-time of 1 minute, 99.9% with a half-time of 7,000 days, and 10% of that deposited 

in the alveoli reaches body fluid (ICRP 1996). The half-time of uranium in the lungs has also been 

calculated to be 1–5 days for soluble compounds like uranyl nitrate hexahydrate in rats (Ballou et al. 

1986), ammonium diuranate in hamsters (Stradling et al. 1984), and uranyl fluoride in dogs (Morrow et al. 

1982a). It is longer for the less soluble uranium dioxide: 141–289 days in rats (Downs et al. 1967) and 

480 days in dogs (Leach et al. 1973). In the kidney, uranium selectively accumulates in the proximal 

tubule with a biological half-time of about 1 week (Wedeen 1992). The half-time of uranyl fluoride in the 

kidneys has been reported to be 2–5 days in rats (Diamond et al. 1989) and 9 days in dogs. In dogs, 

<1% of the uranium remained in the kidneys after 30 days (Morrow et al. 1982a). 

In rats receiving an intratracheal instillation of uranium tetrafluoride or uranium peroxide, urinary 

excretion of uranium steadily increased during the first 8 days after instillation and then remained 

constant until the end of the study (postexposure day 30) (Houpert et al. 1999). Two dose levels were 

administered for each compound, and despite signs of renal toxicity at the high dose level, there were no 

difference in the K/K+U ratio (K is the percent of uranium retained in the kidneys and U is the percent 

excreted in urine) between the groups. 

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3.4.4.2 Oral Exposure 

The available evidence on the excretion of ingested uranium suggests that most (≥95%) is excreted in the 

feces, and the remainder in urine (Wrenn et al. 1985). Urinary uranium excretion rates from 

nonoccupationally exposed persons in three villages near uranium mining and refining facilities and a 

control village in Japan were <0.02–0.24 and <0.02–0.04 mg U/day per person, respectively (Masuda 

1971c). The half-time in the kidneys has been estimated to be 1–6 days for 99% of the uranium in the 

kidneys and 1,500 days for the remainder (ICRP 1979). Most of the uranium doses, given as 900 mL of 

water containing 90 pCi (3.3 Bq) 234U and 90 pCi (3.3 Bq) 238U (180 pCi or 6.6 Bq uranium) to drink over 

a period of 6 hours, was excreted in feces within 2 days (Singh and Wrenn 1987). Four volunteers who 

ingested 10.8 mg of uranium mixed with Coca-Cola excreted the uranium in both feces and urine over a 

25-day period (Hursh et al. 1969). Urinary excretion after oral exposure is generally low and has been 

estimated as 2% of total excretion (Spencer et al. 1990). 

Animal studies have shown that most ingested uranium (99%) is not absorbed in rats, but is eliminated in 

the feces without being cycled through the bile. In rats, most of the absorbed uranium leaves the body 

within a few days in urine; half is excreted in 2–6 days (Durbin and Wrenn 1975) and 98% is excreted 

within 7 days (Sullivan et al. 1986). About 95% of the uranium in the kidneys of rats is excreted in urine 

within 1 week, and very little remains in any other organ (La Touche et al. 1987; Sullivan 1980a; Sullivan 

et al. 1986). 

Data from parenteral studies provide further indication that uranium retention in animal kidneys is 

described by a two-compartment exponential curve. Reported biological half-times for the compartments 

are 2 and 50–60 days (Diamond et al. 1989), 2 and 13 days (Bentley et al. 1985), or 3 and 103 days (DOE 

1986b). 

A nonmonotonous pattern of uranium excretion was observed in rats chronically exposed to 2.0–2.9 mg 

U/kg/day as uranyl nitrate in drinking water (Paquet et al. 2006). The highest excretion levels were 

observed after 6 months of exposure (200 ng U/mL), after which time the levels steadily declined. At 

approximately 13 months of exposure, the levels remained constant at 30 ng U/mL for the last 6 months 

of the study. 

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3.4.4.3 Dermal Exposure 

No studies were located describing the excretion of uranium following dermal exposure in humans. 

Application of depleted uranium or uranium in a nitric acid solution resulted in significant increases in the 

urinary excretion of uranium within 24 hours of exposure in hairless rats (Petitot et al. 2007a, 2007b). 

Application to intact skin resulted in increases in urinary uranium within 2 hours of exposure; application 

to wounded skin (via mechanical abrasion or exposure to low concentration of an acid solution) resulted 

in increases in urinary uranium within 30 minutes of exposure. In contrast, severe damage to the skin 

resulted in low levels of uranium in the urine, first detected 6 hours after exposure. 

3.4.4.4 Other Routes of Exposure 

One day after depleted uranium pellets were implanted in the gastrocnemius muscle of rats, increased 

levels of uranium were measured in the urine (Zhu et al. 2009a). Urinary excretion peaked 90 days after 

implantation and remained elevated 360 days after implantation. 

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. 

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. 

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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. 

Figures 3-3 through 3-9 show models for radionuclides in general or specifically for uranium. 

If PBPK models for uranium exist, the overall results and individual models are discussed in this section 

in terms of their use in risk assessment, tissue dosimetry, and dose, route, and species extrapolations. 

The ICRP (1994a, 1996) developed a Human Respiratory Tract Model (HRTM) for Radiological 

Protection, which contains respiratory tract deposition and clearance compartmental models for inhalation 

exposure that may be applied to uranium. The ICRP (1995) also developed a biokinetic model for human 

oral exposure that applies to uranium. Several more recent enhancements to the oral exposure model 

have been reported. A multicompartmental gastrointestinal tract model was developed to replace what 

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Figure 3-3. 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 

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was originally a single parameter model (Human Alimentary Tract Model, HATM; ICRP, 2006a). A hair 

compartment was developed to support biomonitoring of ingestion intakes (e.g., drinking water 

exposures, Li et al. 2009a). Drinking water and dietary exposure models and Bayesian approaches have 

been developed to improve uranium dose assessments made with the ICRP model (Little et al. 2003, 

2007). A biokinetics model for embedded uranium has been developed based on studies of uranium 

kinetics in rats that received implants of depleted uranium pellets (Leggett and Pellmar 2002; Squibb et 

al. 2005). An adaptation of the ICRP human model for simulating biokinetics of inhaled uranium in rats 

has been reported (Monleau et al. 2006b) and the rat model was used to evaluate the general assumption 

of linear kinetics in the ICRP model (i.e., kinetics are independent of the dose history). Several 

quantitative uncertainty analyses of the ICRP model have been reported (Davesne et al. 2009; Farfan et al. 

2003; Puncher et al. 2008). The ICRP model performance has been evaluated against data on urinary 

excretion of uranium and data on uranium levels in tissues obtained from autopsy studies (Li et al. 2005, 

2006, 2009a; Russell and Kathren 2004). Several recent applications of the ICRP model to exposure and 

risk assessment have been reported. The model has been applied to simulate uranium body burdens and 

radiation doses associated with exposure scenarios of releases of depleted uranium in vehicles impacted 

by depleted uranium munitions (Guilmette et al. 2009). The embedded uranium model developed by 

Leggett and Pellmar (2002) has been extended to humans and has been applied to predicting kidney 

uranium burdens in military veterans who received shrapnel wounds resulting from vehicles impacted 

with depleted uranium munitions (Squibb et al. 2005). An extension of the ICRP model that includes 

simulation of the transfer of uranium to hair has been used to estimate uranium dose coefficients for 

ingestion of uranium in drinking water (Li et al. 2009a). The model has been used to predict radiation 

doses associated with exposures to uranium in drinking water and uranium body burdens associated with 

ingestion and inhalation exposures (Chen et al. 2004; Li et al. 2009b). 

The NCRP has also developed a respiratory tract and biokinetics model for inhaled radionuclides (NCRP 

1997, 2007). Four other compartmental models (Fisher et al. 1991; Sontag 1986; Valdés 2009; Wrenn et 

al. 1994) are also described below. 

Human Respiratory Tract Model for Radiological Protection (ICRP 1994a, 1996) 

Deposition. The ICRP 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. ICRP provides inhalation dose coefficients that can be used to 

estimate the committed equivalent and effective doses to organs and tissues throughout the body based on 

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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 can be adjusted for 

various segments of the population (e.g., sex, age, 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 particles containing uranium, but was developed for a wide variety of 

radionuclides and their chemical forms. 

The ICRP deposition model estimates the amount of inhaled material that initially enters each 

compartment (see Figure 3-4). 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 from each region and 

redistributed either upward into the respiratory tree or to the lymphatic system and blood by different 

particle removal mechanisms. 

For extrathoracic deposition, the model uses experimental data, where deposition is related to particle size 

and airflow parameters, and scales deposition for women and children from adult male data. Similarly 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 3-7 provides reference respiratory values for the general Caucasian population under several levels 

of activity. 

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. Figure 3-5 presents the compartmental model and is linked to the deposition model 

(Figure 3-4) and to reference values presented in Table 3-8. Table 3-8 provides clearance rates and 

deposition fractions for each compartment for insoluble particles. The table provides rates of insoluble 

particle transport for each of the compartments, expressed as a fraction per day and also as half-time. 

ICRP 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. 

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Figure 3-4. Respiratory Tract Compartments in Which Particles May be 

Deposited*
 

*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 3-8. 

Source: ICRP 1994a 

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Table 3-7. Reference Respiratory Values for a General Caucasian Population at
 

Different Levels of Activity
 

10 Years 15 Years Adult Breathing 

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 (m3

hour-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 (m3

hour-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 1994a) for data from which these reference values were derived. 

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Figure 3-5. Environmental Pathways for Potential Human Health Effects from
 

Uranium
 

See Table 3-8 for rates, half-lives, and fractions by compartment. 

Source: ICRP 1994a 

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Table 3-8. 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 

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Table 3-8. 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 1994a) 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 = 05 . for d ae ≤ 2 5 . ρ / χ μm and 

0 . 63 (d ρ χ −2 5 . ) ae f s = 05 . e / 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 1994a 

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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. 

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 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 mucocilliary action rapidly transports most particles deposited here toward the pharynx, a 

fraction of these particles are 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 many as half of the bronchi- and bronchiole-deposited particles. In 

human bronchi and bronchiole regions, mucus moves more slowly the closer to the alveoli it is. 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 and both 

with 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. The one mechanism by which particles are physically 

resuspended and removed from the AI region is coughing. For modeling purposes, the AI region is 

divided into three subcompartments to represent different clearance rates, all of which are slow. 

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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 given 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 two-stage process, as shown in Figure 3-6. First, there is a dissociation (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), and S (slow): 

	 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 and 50% for mouth breathing. Type F 

uranium compounds include uranium hexafluoride, its mixture with uranyl fluoride, uranyl nitrate 

(which can behave as Type M), pure uranium trioxide, and uranium tetrafluoride (which can 

behave at Type M). 

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. Type M compounds include unpure uranium trioxide, uranyl nitrate (which 

can behave as Type F), ammonium diuranate, uranium oxtaoxide (which can behave as Type S), 

and uranium tetrafluoride (which can behave as Type F). 

	 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. Type S compounds include uranium dioxide and uranium octaoxide (which can 

behave as Type M). 

Human Alimentary Tract Model for Radiological Protection (ICRP 2006a) 

The ICRP HATM is a generic multicompartment gastrointestinal tract model that was developed for 

applications to radiation risk assessments of radionuclides. The model replaced an earlier gastrointestinal 

absorption model that consisted of single compartment and single parameter representation of absorption 

of radionuclides into the central plasma compartment from the small intestine. The structure of the 

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3. HEALTH EFFECTS 

Figure 3-6. The Human Respiratory Tract Model: Absorption into Blood 

Particulate Material 

Dissociated Material 

Bound Material 

Blood 

Uptake 

Dissolution 

Source: ICRP 1994a 

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3. HEALTH EFFECTS 

multicompartment model is shown in Figure 3-7. The model simulates the following major processes that 

can contribute to absorption of radionuclides from the gastrointestinal tract and contact and retention 

radionuclides in the gastrointestinal tract tissues (i.e., which could contribute to radiation dose to these 

tissues): 

	 Entry of a radionuclide into the mouth by ingestion, or into the esophagus after mechanical 

clearance from the respiratory tract; sequential transfer of the radionuclide through the contents of 

the oral cavity, esophagus, stomach, small intestine, and segments of the colon, followed by 

excretion in feces. 

	 Deposition and retention on or between the teeth and return to the oral cavity. 

	 Deposition and retention in the oral mucosa or walls of the stomach and intestines. 

	 Transfer from the oral mucosa or walls of the stomach and intestines back into the luminal 

contents or into blood (absorption). 

	 Transfer from various secretary organs or blood into the contents of certain segments of the 

alimentary tract (secretion). 

Biokinetic Model for Uranium (ICRP 1995, 2006a) 

The ICRP biokinetic model for uranium is based on the generic model structure for alkaline earth 

elements described in Publication 67 (ICRP 1994b, 1995) linked to a generic multicompartmental 

alimentary tract model (HATM) described in Publication 100 (ICRP 2006a). The structure of the model 

is shown in Figure 3-8. Uranium (as the UO2

2+ ion) is similar to calcium (Ca2+) with regard to skeletal 

kinetics. 

Some transfer rates in the biokinetic model for uranium are equated with bone formation rates. The early 

behavior of uranium in human circulation is represented reasonably well by treating plasma as a 

uniformly mixed pool, where uranium is removed at a rate of 35 d-1 (ICRP 1995) and where a soft tissue 

compartment (ST0) is in relatively rapid exchange with plasma. Compartment ST0 is assumed to receive 

30% of uranium leaving plasma and to have a removal half-time of 2 hours (from ST0 to plasma). ICRP 

assumed that 1% of uranium leaving the circulation (or 0.7% leaving plasma) deposits in red blood cells 

(ICRP 1995). The removal half-time from red blood cells to plasma is assumed to be 2 days. 

Urinary excretion of uranium is assumed to arise from uranium moving directly from plasma to the 

urinary bladder contents. Approximately 60% of uranium leaves the blood directly to the bladder and 

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3. HEALTH EFFECTS 

Figure 3-7. Structure of the Human Alimentary Tract Model (HATM) 

Ingestion 

Oral Cavity 

Contents 

Respiratory 

Tract 

Oral Mucosa 

Esophagus 

Stomach Wall Stomach 

Contents 

Teeth 

General 

Circulation 

Small Intestine 

Wall 

Right Colon 

Wall 

Left Colon Wall 

Sigmoid Colon 

Wall 

Blood or 

Secretory 

Organs 

(Including 

Liver) 

Small Intestine 

Contents 

Right Colon 

Contents 

Left Colon 

Contents 

Rectosigmoid 

Contents 

Liver 

Portal Vein 

Feces 

Source: ICRP 2006a 

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Figure 3-8. Biokinetic Model for Uranium after Uptake to Blood 

Intermediate 

Turnover 

(ST1) 

Rapid 

Turnover 

(ST0) 

Tenacious 

Retention 

(ST2) 

Red 

Blood 

Cells 

Liver 2 

Liver 1 

Cortical 

Surface 

Trabecular 

Surface 

Other Kidney 

Tissue 

Urinary Path 

Urinary 

Bladder 

Contents 

Urine

 Cortical Volume 

Nonexchange Exchange

 Trabecular Volume 

Nonexchange Exchange 

Gastrointestinal 

Tract Contents 

Feces 

Plasma 

Kidneys 

Skeleton 

Other 

Soft 

Tissues 

Source: ICRP 1995
 

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3. HEALTH EFFECTS 

another 12% is retained temporarily in the renal tubules before excretion. The liver is assumed to consist 

of two compartments: Liver 1 and Liver 2. The liver receives an estimated 1.5% of uranium leaving the 

blood, with over 90% returning to circulation. 

Little direct information on the kinetics of uranium in children exists. Age-specific deposition of uranium 

in the skeleton is assumed to be proportional to the deposition of the alkaline earth elements. The rate of 

removal from deep bone is assumed to be the same as the age-specific bone turnover rate. Because 

children have higher amounts of uranium taken up by bone, deposition in soft tissues and excreta are 

likely lower in children than for adults. 

Valdés (2009) Lung Model 

A multicompartment model for predicting lung burdens of uranium resulting for exposure to depleted 

uranium aerosols was proposed by Valdés (2009). Clearance of uranium particles deposited in the lung is 

assumed to occur by mechanical clearance by the mucociliary escalator and by cellular transport of 

uranium particles to lymph nodes after phagocytosis by macrophages. The model assumes that 

phagocytosis is sufficiently rapid that essentially all absorption of uranium can be assumed to occur from 

macrophages after intracellular dissolution of uranium oxides to uranyl ion in macrophage lysosomes. 

The macrophage plasma membrane is assumed to be transparent to uranyl ion (i.e., absorption to the 

systemic circulation is considered to be essentially instantaneous). Therefore, the rate of absorption of 

uranium into the systemic circulation is determined by the dissolution rate, which is assumed to have fast 

and slow rate components. This representation of fast and slow dissolution kinetics and essentially 

instantaneous absorption of dissolved uranium is conceptually similar to the ICRP HRTM (ICRP 1995, 

1996). A competing process within macrophages is precipitation of uranyl phosphates within lysosomes. 

Uranyl phosphate precipitates are assumed to be kinetically inert and are stored permanently in lymph 

nodes. Uranium absorbed into the systemic circulation is distributed and excreted according to the 

systemic biokinetics model based on the model developed by Wrenn et al. (1994). 

The lung model is implemented as a series of first-order differential equations, the core of which are as 

follows. The amounts of uranium oxides in lungs (L) and lymph nodes (N) at time, t, following initial 

deposition in the lung of amount A0 are given by: 

L(t) =A0(0.0142e-2.1512t + 0.3042e-0.00201t + 0.0261e-0.2812t + 0.0107e-0.0023t) 

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-0.0023t N(t) =A0[0.0024(e ) + -2.15t - e-2.1512t) + 0.0018(e-0.0011t - e 

0.0567(e-0.00081t -0.2812t - e )] -0.00201t) + 0.0044(e-0.28t - e 

A similar set of expressions represents the amount of insoluble uranyl phosphates in lungs (PL) and lymph 

nodes (PN) at time, t, following initial deposition in the lung of amount A0: 

PL(t) =A0(1.460e-0.0012t - 1.419e-0.00201t - 0.0238e-2.1512t - 0.0094e-0.2812t - 0.008e-0.0023t) 

-0.2812t PN(t) =A0(0.1015 + 2.2164x10 + -6e-2.1512t + 0.1412e-0.00201t + 6.6816x10-6e 

0.0007e-0.0023t - 0.2434e-0.0012t) 

The Valdés (2009) model has been applied to estimating initial and current body burdens of uranium in 

military veterans who were exposed to depleted uranium aerosols, based on time history of urinary 

uranium measurements. 

Wrenn et al. (1994) Pharmacokinetic Model 

A multicompartment model of distribution and excretion of absorbed uranium was proposed by Wrenn et 

al. (1994), based on data collected in studies conducted in nonhuman primates and in other animal models 

and data on tissue levels and urinary excretion of uranium in humans. The model includes a central 

compartment consisting of plasma and extracellular fluid (ECF), which exchanges uranium with the 

skeleton, kidney, and a lumped compartment representing all other soft tissues (see Figure 3-9). The 

skeleton is represented as a single compartment, unlike the ICRP model (ICRP, 1995), which 

subsequently adopted a multicompartment representation for the skeleton. The kidney includes slow and 

fast kinetics compartments, both of which contribute to urinary uranium. Uranium is also transferred to 

urine directly from plasma. 

Sontag (1986) Pharmacokinetic Model 

An extended multicompartmental model (see Figure 3-10) describing the kinetic behavior of uranium 

(absorption, distribution, and excretion as a function of time) in the organs of male and female rats was 

developed using data taken from experiments performed on 13-month-old male and female SpragueDawley rats intravenously injected with 1.54 mCi/kg (57 kBq/kg) 233U-uranyl citrate and sacrificed at 7, 

28, 84, 168, or 336 days after injection. 

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Figure 3-9. Multicompartmental Model for Uranium after Uptake to Blood 

Plasma + 

ECF + 

Labile 

Surfaces 

0.2 d 

Skeleton 

882 d 

Other 

180 d 

0.076 0.015 

Kidney-1 

3.0 d 

Kidney-2 

70 d 

Urine 

0.280 0.617 0.012 

Source: Wrenn et al. 1994
 

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Bone 2 

B2 

6 


 


 

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3. HEALTH EFFECTS 

Figure 3-10. Multicompartmental Model 

Input 

Blood 

BP 

1 

ƒ12 ƒ21 ƒ13 ƒ31 ƒ10 ƒ14 ƒ41 ƒ15 ƒ51 

Bone 1 

B1 

ƒ2,6 ƒ6,2 ƒ37 ƒ73 ƒ48 ƒ84 ƒ59 ƒ95 

Liver 2
 

L2
 

7 

Kidney 2 

K2 

8 

Liver 1 

L1 

3 

Excretion 

EC 

0 

Kidney 1 

K1 

4 

Residual 1 

R1 

5 

Residual 2 

R2 

9 

ƒ = transfer coefficient (unitless) 

Source: Sontag 1986 

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The model is composed of 10 compartments. These 10 compartments are connected by 17 linear transfer 

coefficients using 21 parameters. The whole system describes the flux of compounds between a central 

compartment (the blood) and outer compartments which connect with the central compartment only. The 

10 compartments are labeled blood, bone 1, bone 2, liver 1, liver 2, kidney 1, kidney 2, residual 1, 

residual 2, and excretion. The organs are divided into two compartments: one compartment represents the 

short term and one represents the long term. For example, the short-term compartment for the bone is the 

bone surface and bone marrow, and the long-term compartment is the deep bone. In the liver, the shortterm compartment is assumed to be the lysosomes, and the long-term compartment is assumed to be the 

telolysosomes. Separation of these organs into two components helps to account for the reabsorption and 

rapid excretion. Using the symbols BP=blood, EC=excretion, B1=bone 1, L1=liver 1, K1=kidney 1, 

R1=residual 1, B2=bone 2, L2=liver 2, K2=kidney, and R2=residual 2, the calculated transfer coefficients 

for this model are shown in Table 3-9. 

Parallel evaluations produced two different values (ranges) for each of the 21 parameters. The maximum 

fractions of uranium in various compartments were as follows: bone, 0.0710 or 0.0735; liver, 0.0160 or 

0.0146; kidney, 0.1777 or 0.4789; residual compartment, 0.0358 or 0.0481; and excretion compartment, 

0.6995 or 0.3849 (if no back transfer to the blood compartment occurred). The time at which the 

maximum amount of the uranium in the organ is reduced to one-half is 0.0009 or 0.0013 days in the 

blood, 165 or 93 days in the bone, 6 or 7 days in the liver, 11 or 5 days in the kidney, and 5 or 6 days in 

the residual compartment. The cumulative radiation absorbed dose in the organ 365 days after injection 

of 56.6 kBq/kg body weight was 0.0002 or 0.0004 Gy to blood, 0.730 or 1.29 Gy to bone, 0.0268 or 

0.0308 Gy to liver, 1.32 or 1.77 Gy to kidney, and 0.0061 or 0.0076 Gy to residual compartment. The 

ratio of single injection/continuous intake calculated for the same dose 1 year after the first injection was 

0.018 or 0.003 to blood, 0.619 or 0.812 to bone, 0.422 or 0.355 to liver, 0.256 or 0.231 to kidney, 

0.726 or 0.585 to residual compartment, and 1.024 or 1.023 to excretion compartment (Sontag 1986). 

Fisher et al. (1991) Biokinetic Model 

A modified biokinetic model for uranium was developed for inhaled soluble uranium based on human 

data from an accidental release of uranium hexafluoride in Oklahoma. Urinary excretion data from 

31 exposed workers were used to test two previously published compartmental models for inhalation 

exposure to uranium (ICRP 1979; Wrenn et al. 1989). Urinary uranium was measured periodically for 

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Table 3-9. Sensitivity and Calculated Transfer Coefficients (d-1) 

Transfer from-to Symbol Experimental value 1 Experimental value 2 Sensitivity 

BP-EC f10 555 209 0.2 

BP-B1 f12 56.3 39.9 5.9 

BP-L1 f13 12.7 7.94 3.3 

BP-K1 f14 141 2.60 1.5 

BP-R1 f15 28.4 26.1 17.5 

B1-BP f21 0.00979 0.0184 1.9 

L1-BP f31 0.187 0.270 5.6 

K1-BP f41 0.0948 0.365 0.5 

R1-BP f51 0.225 0.341 3.4 

B1-B2 f26 0.00565 0.00649 2.2 

L1-L2 f37 0.00863 0.00940 2.7 

K1-K2 f48 0.00114 0.00122 2.2 

R1-R2 f59 0.0103 0.00860 6.1 

B2-B1 f62 0.00261 4.43x10-6 5.0 

L2-L1 f73 0.00284 0.00349 43.7 

K2-K1 f84 0.000972 0.00122 4.8 

R2-R1 f95 0.000716 0.00138 2.3 

Varinz V 0.00663 0.00465 Not applicable 

Source: Sontag 1986 

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2 years following the accident. Statistical analysis showed that the Wrenn et al. (1989) model produced a 

better fit to the excretion data than the ICRP (1979) model. 

Parameters of the (Wrenn et al. 1989) model were then modified to further improve the fit to the workers 

excretion data. Changing the retention half-time in the kidney from 15 to 6 days and the clearance halftime in the lung from 0.5 to 0.03 days optimized the fit of the model to the experimental data. The model 

may be summarized with the following five-term exponential equation: 

-0.000139t yu(t) = 1.5e-2.77t + 0.028e-0.116t + 0.0069e-0.0347t + (4.8x10-7e-0.000462t) + 3.2x10-6e 

where, yu(t) is fractional daily uranium excretion rate at t days after intake; the excretion constants in the 

five exponents corresponding to compartments with retention half-times of 0.25, 6, 20, 1,500, and 

5,000 days. 

The model was used to estimate uranium intakes; uranium burdens in the lungs, kidneys, and bones; and 

effective dose equivalent for each worker in the accident. Initial intakes of workers involved in the 

accident ranged from 470 to 24,000 μg uranium. The model estimated the maximum kidney 

concentrations in the workers as ranging from 0.048 to 2.5 μg U/g kidney tissue; renal toxicity was not 

observed in any of the workers (Fisher et al. 1991; USNRC 1990). 

Based on this same data base, the USNRC determined that the maximum uranium dose equivalent of 

workers on-site was 28 mrem (0.28 mSv). The maximum uranium dose equivalent of off-site individuals 

was 1.4 mrem (0.014 mSv). However, these radiological doses were small compared to the background 

radiation level of 106 mrem/year (1.06 mSv/year), excluding radon, in the area from which the data were 

collected (USNRC 1986). 

3.5 MECHANISMS OF ACTION 

3.5.1 Pharmacokinetic Mechanisms 

On the average, a given amount of an ingested uranium compound appears to be less toxic than the same 

amount of an inhaled uranium compound (Maynard and Hodge 1949; Stokinger et al. 1953). This finding 

may be partly attributable to the relatively low gastrointestinal absorption of uranium compounds. Only 

0.1–6% of even the more soluble uranium compounds are absorbed in the gastrointestinal tract (EPA 

1988d; Harrison and Stather 1981; Hursh et al. 1969; ICRP 1979; Larsen et al. 1984; La Touche et al. 

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1987; Leggett and Harrison 1995; Maynard et al. 1953; Sullivan 1980a; Wrenn et al. 1985). The ICRP 

(1995) recommends a gastrointestinal absorption reference fraction of 0.02 for uranium ingested in 

relatively soluble form and 0.002 for insoluble compounds. On the basis of the toxicity of different 

uranium salts in animals, it was concluded that the relatively more soluble salts (uranyl nitrate 

hexahydrate, uranyl fluoride, uranium tetrachloride, uranium pentachloride) were most toxic, the slightly 

soluble compounds (uranium trioxide, sodium diuranate, ammonium diuranate) were of intermediate 

toxicity, and the insoluble compounds (uranium tetrafluoride, uranium dioxide, uranium tetrachloride, 

triuranium octaoxide) were nontoxic (Orcutt 1949). 

In inhalation exposures, uranium compounds are usually inhalable aerosols. Thus, particle size plays a 

vital role in tissue dose. Particles >5 μm AMAD are likely to be transported out of the tracheobronchial 

region by mucocilliary action and swallowed into the gastrointestinal tract, where absorption is minimal 

(ICRP 1979). The less soluble compounds (uranium trioxide, uranium tetrafluoride), designated Type M 

by the ICRP (1995), are more likely to remain in the lung tissue and associated lymph glands for weeks. 

The relatively insoluble compounds (uranium dioxide, triuranium octaoxide), designated Type S by the 

(ICRP 1995), are likely to remain in the lungs for years (Eidson 1994). This retention of uranium in the 

lung can lead to a significant pulmonary radiation dose. 

In addition, the sequestration patterns of the different uranium compounds are important determinants for 

the target organ chemical and radiological toxicities of these compounds. The site of deposition for the 

soluble uranium compounds (uranyl nitrate, uranium tetrachloride, uranium hexafluoride) is the bone, 

while the insoluble compounds (uranium hexafluoride, uranium dioxide) accumulate in the lungs and 

lymph nodes (Stokinger et al. 1953). 

3.5.2 Mechanisms of Toxicity 

The dual modes of uranium chemical and radiological toxicity are not usually separately identifiable by 

end point. The renal and respiratory effects from exposure of humans and animals to uranium are usually 

attributed to the chemical properties of uranium, while the theoretically potential excess cancers are 

usually attributed to the radiation properties of this substance. Although the net effects on the lungs and 

kidneys have been suggested to be a cooperative action of the chemical and radiation properties, with a 

complementary mechanism of action, this relationship has not been demonstrated experimentally (Ballou 

et al. 1986; Dockery et al. 1993; Dungworth 1989; Filippova et al. 1978; Leach et al. 1984; Spoor and 

Hursh 1973; Spiegl 1949; Stokinger et al. 1953). UNSCEAR has considered that limits for natural (and 

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depleted) uranium in drinking water (the most important source of human exposure) should be based on 

the chemical toxicity rather than on a radiological toxicity, which has not been observed in either humans 

or animals (UNSCEAR 1993; Wrenn et al. 1985). 

The most sensitive target of uranium toxicity to mammals, and perhaps humans, is the kidney. While 

acute, high-level exposure to uranium compounds can clearly cause nephrotoxicity in humans (Lu and 

Zhao 1990; Pavlakis et al. 1996), the evidence for similar toxicity as the result of long-term, lower-level 

occupational exposures is equivocal. Epidemiologic studies have not noted an increase in deaths from 

urogenital or renal diseases (Checkoway et al. 1988; Dupree et al. 1987; Lundin et al. 1969; NIOSH 1987; 

Polednak and Frome 1981), and follow-up studies have failed to identify significant damage to human 

kidneys following occupational exposure to uranium (Eisenbud and Quigley 1956; Hursh and Spoor 

1973; Luessenhop et al. 1958), or after war-related exposures (McDiarmid et al. 2000, 2001a, 2004b, 

2006, 2007, 2009). A comparison of autopsy kidney tissue samples revealed no differences between 

seven uranium workers and six referents with no known exposure to uranium (Russell et al. 1996). One 

epidemiologic study provided evidence of nephrotoxicity following occupational exposure to uranium. 

Nephrotoxicity, indicated by β2-microglobulinuria and aminoaciduria due to decreased tubular 

reabsorption, was reported in a group of 39 male uranium mill workers exposed for >1 year to uranium 

concentrations exceeding the occupational standard of 3.7 Bq/m3 (currently 5 Bq/m3 [0.2 mg/m3

]) by 

≤8-fold. Cement workers were used as controls in this study (Thun et al. 1985). 

Many animal studies have shown that inhalation, oral, or dermal exposure to uranium results in kidney 

damage. The damage was histologically manifested as glomerular and tubular wall degeneration. 

Ultrastructural analysis showed damage to the endothelial cells in the glomerulus, such as loss of cell 

processes, and reduction in the density of the endothelial fenestrae (Avasthi et al. 1980; Haley 1982; 

Haley et al. 1982; Kobayashi et al. 1984). In the terminal segments of the proximal convoluted tubules, 

there was a loss of the brush border, cellular vacuolization, and necrosis. Tubular reabsorption of solutes 

was disrupted. Functionally, this process led to a disruption of the tubular solute reabsorption and to a 

decrease in the filtration rate of the glomerulus, as assessed by creatinine or inulin clearance or by 

proteinuria (Bentley et al. 1985; Blantz 1975; Leach et al. 1973; Morrow et al. 1982a). Excessive urinary 

excretion of protein, glucose, amino acids, or enzymes, such as catalase or alkaline phosphatase are 

additional indicators of uranium-induced renal pathology (Maynard et al. 1953) by inhalation exposure 

(Bentley et al. 1985; Diamond et al. 1989; Haley et al. 1982; Leach et al. 1984; Maynard et al. 1953; 

Morrow et al. 1982a). 

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A mechanism involving bicarbonate activity in the kidneys has been proposed for uranium-induced renal 

toxicity. Uranium is usually combined with either bicarbonate or a plasma protein in the blood. In the 

kidneys, uranium is released from bicarbonate and is free to combine to form complexes with phosphate 

ligands and proteins in the tubular wall to cause damage. Uranium is not tightly bound and is released 

again within a few days. Within a week following exposure, uranium is largely cleared from the kidneys, 

and the tubules begin to regenerate. Although the regenerated epithelium has histological differences 

from its normal state, it is often difficult to detect histological signs of kidney damage a month after 

exposure because all remaining functional damage is subtle. An alternative mechanism through which 

uranium exerts its renal toxicity has been suggested by the results of a study conducted with rabbit kidney 

cells in vitro. In this study, uranyl nitrate hexahydrate inhibited both sodium transport-dependent and 

-independent ATP utilization and mitochondrial oxidative phosphorylation in the renal proximal tubule. 

Ouabain-insensitive adenosine triphosphatase (ATPase) activity exhibited the greatest sensitivity to 

uranyl nitrate hexahydrate and was significantly inhibited at submillimolar concentrations (Brady et al. 

1989). Perhaps both of these activities combine to cause renal damage. In addition, because uranium is a 

predominantly alpha-emitting radionuclide, current theories on cellular necrosis by high-LET alpha 

radiation imply a contributory role to the cellular degenerative nephrotoxic changes (BEIR 1980, 1988, 

1990; Filippova et al. 1978; Sanders 1986; UNSCEAR 1982, 1986, 1988). 

Most studies of respiratory diseases reported for uranium involve noncancerous alveolar epithelium 

damage in type II cells. These changes are characterized by interstitial inflammation of the alveolar 

epithelium leading eventually to pulmonary fibrosis in acute exposures or to hyperplasia, hypertrophy, 

and transdifferentiation (metaplasia) in chronic exposures (Clayton and Clayton 1981; Cooper et al. 1982; 

Dungworth 1989; Wedeen 1992). However, the lack of significant pulmonary injury in most inhalation 

animal studies indicates that other potentially toxic contaminants such as inhalable dust particles, radium, 

or radon may contribute to these effects. 

Large doses of ionizing radiation have the actual or theoretical potential of being carcinogenic, 

teratogenic, and mutagenic. Since uranium has a low specific activity but emits high LET alpha particles 

that are densely ionizing along their track length, studies have been conducted to determine if uranium 

can produce these effects in humans and animals. The 4–8 MeV alpha particles from uranium travel 

through 40–70 μm in soft tissue, incrementally transferring their kinetic energy to the series of atoms and 

molecules with which they interact along their short, straight paths. Consequently, only structures within 

this range from the site of the deposition of uranium may be affected. If a DNA molecule is intersected 

and damaged without resulting in cell death, a range of theoretical effects can result. DNA has been 

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found to be the most radiosensitive biological molecule, and ionizing radiation has been observed to 

damage individual chromosomes. The main result from low level ionizing radiation exposure is DNA 

damage or fragmentation. Viable cells repair the damage, but repair errors can result which produce gene 

mutations or chromosomal aberrations. Such events may result in such highly rare events as 

carcinogenesis or teratogenesis, but there is currently no evidence for radiation mutagenesis in humans. 

Chromosomal aberrations following large radiation doses have been demonstrated in humans and in 

research animals, showing that ionizing radiation can both initiate and promote carcinogenesis, and 

interfere with reproduction and development. 

3.5.3 Animal-to-Human Extrapolations 

Kidney damage and respiratory disease are the most significant health effects in animals from the 

metallotoxicity of uranium. Because the biological systems through which these effects are mediated are 

common to both animals and humans (Brady et al. 1989; Clayton and Clayton 1981; Cooper et al. 1982; 

Dungworth 1989; Wedeen 1992), it is reasonable that animals are appropriate surrogates for humans in 

this regard. This assumption is consistent with evidence in humans for respiratory (Kathren and Moore 

1986, Waxweiler et al. 1981a) and renal (AEC 1957; Fisher et al. 1991; Kathren and Moore 1986; Lu and 

Zhao 1990; Luessenhop et al. 1958; Thun et al. 1985; USNRC 1986; Waxweiler et al. 1981a) effects. 

The data from these studies support the assumption of biological similarity in the renal toxicity of 

uranium in animals and humans. Nevertheless, a considerable uncertainty is associated with animal-tohuman extrapolation regarding the renal toxicity of uranium exposure because the renal toxicity of 

animals varies with species. 

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 

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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 1997d). 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). 

Only one study was located that provided information regarding potential neuroendocrine effects of 

uranium (Raymond-Whish et al. 2007). In that study, 28-day-old ovariectomized female mice received 

doses of approximately 0.005, 0.009, 0.09, or 0.9 mg U/kg/day in tap water for 30 days. Ovariectomy 

was performed to remove the endogenous source of estrogen. A group of mice was also exposed to 

diethylstilbestrol (DES) as a positive control. Exposure to 0.009 mg U/kg/day significantly increased 

uterine weight, but the higher doses were without significant effect. In addition, mice exposed to 0.005 or 

0.009 mg U/kg/day had significantly increased presence of cornified vaginal cells relative to controls, 

which indicated an estrogenic effect of uranium. In a different experimental series, the investigators 

studied the dependency of the estrogen-like effects of uranium on estrogen receptor (ER) activation. 

Ovariectomized mice received the same doses for 10 days beginning at 50 days of age. A group of mice 

also received injections of an anti-estrogenic drug. Doses of 0.005 mg U/kg/day, but not higher doses, 

significantly increased uterine weight and the effect could be blocked by the anti-estrogenic compound. 

Also, exposure to 0.009 mg U/kg/day significantly accelerated vaginal opening, which was also blocked 

by the anti-estrogenic drug. A mechanism by which uranium evoked estrogenic responses was not 

defined. 

No in vitro studies were located regarding endocrine disruption of uranium. 

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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, 

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particularly in newborns who all have a low glomerular filtration rate and have not developed efficient 

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). 

Specific information is not available on whether children are more susceptible than adults to the effects of 

uranium. No reports were located describing toxicity in children as the result of uranium exposure. It is 

probable, however, that if exposure levels were high enough, signs of renal toxicity would be observed 

similar to those seen in adults exposed accidentally (Lu and Zhao 1990) or intentionally (Pavlakis et al. 

1996). No reports are available of studies where toxic responses of young animals to uranium were 

directly compared to those of adults. 

Several investigators (as reviewed by Busby et al. 2010; Hindin et al. 2005) have examined the possible 

association between exposure to depleted uranium and birth defects. Interpretation of these data is limited 

by the lack of adequate controls, monitoring data to determine whether the subjects were exposed to 

depleted uranium and at what level, potential exposure to other agents, and other possible confounding 

factors, such as poor nutrition. Animal studies have examined the developmental toxicity of uranium 

compounds following oral exposure or intramuscular implantation. Developmental effects (described in 

greater detail in Section 3.2.2.6) have been observed in rats and mice following oral exposure (gavage or 

drinking water administration) to soluble uranium compounds; the effects include decreases in viability or 

embryolethality (Domingo et al. 1989b, 1989c; Paternain et al. 1989), decreases in fetal body weight 

(Domingo et al. 1989c; Paternain et al. 1989), increases in the number of litters with visceral and skeletal 

defects (e.g., cleft palate, bipartite sternebrae, reduced ossification) (Domingo et al. 1989c), alterations in 

performance on neurobehavioral tests (Houpert et al. 2007a; Sánchez et al. 2006), alterations in ovarian 

folliculogenesis (Arnault et al. 2008; Raymond-Whish et al. 2007), and delayed tooth eruption (Pujadas 

Bigi and Ubios 2007; Pujadas Bigi et al. 2003). No developmental effects were observed in offspring of 

rats following implantation of depleted uranium pellets in the gastrocnemius muscle (Arfsten et al. 2009). 

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Information on the pharmacokinetics of uranium in children is very limited. Since the skeletons of 

children are growing (higher rate of bone formation), it is possible that a higher fraction of circulating 

uranium will be deposited in bone than in adults. A study of uranium content in bone from three age 

groups (<13, 13–20, 20–25 years old) reported somewhat higher uranium content in the youngest 

compared to the oldest age group (approximately 1.5–3 fold); however, there were only 2–4 subjects in 

each group and the differences were not statistically significant (Broadway and Strong 1983). The 

fractional absorption of uranium by the oral route was higher in neonatal swine and rats than in adult 

animals (Sullivan 1980b; Sullivan and Gorham 1982). 

Transfer of uranium across the placenta was investigated in an animal study, but no information is 

available for humans. In the animal study, only 0.01–0.03% of an intravenous dose of uranium to rat 

dams crossed the placenta (Sikov and Mahlum 1968). In contrast, another oral exposure study (Sánchez 

et al. 2006) found elevated uranium levels in the offspring of rats exposed to uranyl acetate prior to 

mating and throughout gestation and lactation, suggesting transplacental and/or lactational transfer of 

uranium. No studies were located regarding uranium in breast milk. Based on the chemical properties of 

uranium, it seems unlikely that there would be preferential distribution from the blood to this high-fat 

compartment. It is not known if uranium has any effect on the active transport of calcium into breast 

milk. Most of the adult body burden of uranium is stored in bone (ICRP 1979, 1995, 1996). It is not 

known if maternal bone stores of uranium (like those of calcium and lead) are mobilized during 

pregnancy and lactation. 

Age-related differences in the pharmacokinetics of uranium have been incorporated into existing PBPK 

models (ICRP 1995, 1996) so that they can be applied to children. Two adjustments were made: 

1.	 The value for the fractional absorption of ingested uranium (f1) was adjusted from the adult value 

of 0.02 (2%) to a value of 0.04 (4%) for children under the age of 1 year. This adjustment was 

made based on animal data (Sullivan 1980b; Sullivan and Gorham 1982) and information on 

postnatal changes in the human gastrointestinal tract. For ages over 1 year, the adult value for 

fractional absorption was used. 

2.	 Parameters for transfer of uranium into and out of bone were assumed to be proportional to those 

of alkaline earth elements such as calcium (the UO2

2+ ion can substitute for the Ca2+ ion at bone 

surfaces). Age-specific bone turnover rates developed for a generic alkaline-earth model (ICRP 

1994b) were incorporated into the uranium model to predict distribution to the tissues. As a 

result of this change, a greater proportion of uranium distributes to bone and a lesser proportion to 

soft tissues at ages under 25 years, compared to adults. 

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The mechanism for the renal toxicity observed in cases of adult exposure to uranium is believed to be due 

to the retention of uranium in the kidney. This is the result of the reabsorption of bicarbonate from the 

ultrafiltrate in the proximal tubule and the resulting release of the UO2

2+ ion from a bicarbonate complex. 

Newborn humans have relatively inefficient tubular secretion and reabsorption compared to older children 

or adults, and whether this would increase or decrease the susceptibility of newborns to uranium toxicity 

is not known. 

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). 

The National Report on Human Exposure to Environmental Chemicals provides an ongoing assessment 

of the exposure of the U.S. population to environmental chemicals using biomonitoring. This report is 

available at http://www.cdc.gov/exposurereport/. The biomonitoring data for uranium from this report is 

discussed in Section 6.5. 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 uranium are discussed in Section 3.9.1. 

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 

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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 uranium 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 Uranium 

Biomarkers of exposure to uranium include the chemical or radiological detection of uranium in the urine 

because uranium absorbed through the oral, dermal, and inhalation routes is excreted in urine mostly as 

uranyl ions (Ballou et al. 1986; Cooper et al. 1982; Downs et al. 1967; Leach et al. 1984; Morrow et al. 

1982a; Stradling et al. 1984, 1987; West and Scott 1969; Wrenn et al. 1985). Uranium urinalysis data 

have been shown to correlate with airborne uranium exposures when averaged over a period of time when 

the ingested quantity is insignificant. Thus, this method of analysis can be used to verify the adequacy of 

air sampling and as a noninvasive method for exposure estimates (Atomic Energy Control Board 1985; 

Chase 1989; Schieferdecker et al. 1985; Thind 1987). 

Chemical detection methods for uranium include fluorimetry and kinetic phosphorescence analysis 

(KPA), while the primary radiological methods are inductively coupled plasma mass spectroscopy 

(ICP-MS) and alpha spectroscopy. Some of the more capital-intensive and sophisticated techniques that 

will allow isotope quantification in very small fecal, urine, or tissue samples are isotope dilution alpha 

spectrometry; neutron activation analysis; and isotope-dilution, inductively coupled plasma mass 

spectrometry (used by NHANES), and atomic absorption spectrometry. The mass spectrometric, KPA, 

and neutron activation techniques are probably the most sensitive and accurate for the quantification of 

uranium isotopes (Wessman 1984). 

According to USNRC Regulatory Guide 8.22, the acceptable methods for the quantification of uranium in 

urine must have a detection limit of 5 μg/mL and a precision of 30% (Kressin 1984). A urinary 

concentration >100 μg/L is indicative of recent absorption, while a concentration of <40 μg/L may be due 

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either to slow uptake from the site of absorption or to bone mobilization (Butterworth 1955). Variations 

in background levels of uranium from drinking water in different locations may also result in higher or 

lower urinary concentrations of uranium. 

Twenty-four hour urine samples, corrected per gram creatinine concentration, are considered the “gold 

standard” for assessing uranium body burden. To evaluate the accuracy of spot urine samples for 

assessing uranium body burden, McDiarmid et al. (1999b) examined 22 non-uranium exposed veterans 

and 29 veterans exposed to depleted uranium. In both groups, the median and mean urine uranium levels 

were similar in the creatinine-corrected 24-hour samples and spot samples. When both groups were 

combined, the 24-hour creatinine-corrected urine uranium levels were highly correlated (R2

=0.97) with 

the creatinine-corrected spot urine uranium levels. However, lower correlation coefficients were found in 

the non-exposed group (R2

=0.44) and in exposed veterans with 24-hour urine uranium levels of <0.05 μg 

U/g creatinine (R2

=0.48). In contrast, the correlation coefficient was 0.99 in the veterans with 24-hour 

urine uranium levels of ≥0.05 μg/g creatinine. 

Uranium content in soft tissue and bone could also be used as biomarkers of exposure to uranium since 

uranium also distributes to these tissues and other organs (Ballou et al. 1986; Diamond et al. 1989; Leach 

et al. 1973, 1984; Morris et al. 1990; Morrow et al. 1972; Stokinger et al. 1953; Walinder 1989; Wrenn et 

al. 1987). Although soft tissues and bone are the most frequently analyzed biological media after urine 

and feces, these tissues are usually available for analysis only at autopsy. Therefore, this method is 

impractical and not used for routine screening purposes. 

3.8.2 Biomarkers Used to Characterize Effects Caused by Uranium 

Currently, there are no available biomarkers for specific exposure to the metallotoxic or radiotoxic effects 

of uranium. 

Functional damage to the kidneys has been documented in humans (Lu and Zhao 1990; Pavlakis et al. 

1996; Thun et al. 1985; Waxweiler et al. 1981a) and in animal (Leach et al. 1970, 1973, 1984; Morrow et 

al. 1982a; Stokinger et al. 1953) studies. Increases in the urinary excretion of several biomarkers, 

including β2 microglobulin, protein HC, and retinol binding protein, have been observed in populations 

consuming elevated levels of uranium in drinking water (Kurttio et al. 2002; Limson Zamora et al. 1998, 

2009; Mao et al. 1995; Seldén et al. 2009). These biomarkers, although not specific to uranium, could be 

used to as sensitive biomarkers of renal dysfunction. 

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Very high doses of uranium may interfere with liver function in humans (Pavlakis et al. 1996), but renal 

effects are far more sensitive. No specific biomarker is currently available for the liver as a target of 

uranium toxicity. Because uranium has no appreciable effect on the nervous system, no biomarkers of 

effect are needed for this end point. For more information on biomarkers for renal effects of chemicals, 

see ATSDR/CDC Subcommittee Report on Biological Indicators of Organ Damage (Agency for Toxic 

Substances and Disease Registry 1990d). Simultaneous analysis of multiple parameters, such as urinary 

glucose, alkaline phosphatase, and β2-microglobulin, which may be more specific to proximal tubular 

damage (Limson Zamora et al. 1998), should be considered for evaluating subjects in future studies. 

3.9 INTERACTIONS WITH OTHER CHEMICALS 

Co-administration of uranium (5 mg/kg uranyl acetate dehydrate administered via subcutaneous injection) 

and melatonin (10 or 20 mg/kg administered via intraperitoneal injection) resulted in a decrease in 

uranium-induced kidney damage (Bellés et al. 2007). A significant reduction in the uranium-induced 

increase in urine volume and a reduction in the severity of renal tubular necrosis were observed. No 

information was located regarding the modulation of the toxicity of uranium by other chemicals or vice 

versa. It is possible that co-exposure to other heavy metal nephrotoxicants (e.g., lead, cadmium) could 

have an additive effect on uranium toxicity. 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to uranium than will most persons 

exposed to the same level of uranium 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 uranium, or compromised function of organs 

affected by uranium. Populations who are at greater risk due to their unusually high exposure to uranium 

are discussed in Section 6.7, Populations with Potentially High Exposures. 

Populations susceptible to uranium toxicosis would include people with impaired renal function or renal 

disease. People with stomach ulcers are thought to have elevated absorption of some toxic metals and 

might be unusually susceptible to uranium toxicity. The potential for children=s susceptibility is discussed 

in Section 3.6. 

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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 uranium. 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 uranium. 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 uranium: 

Began D. 2002. Dermatologic principles. In: Goldfrank LR, Flomenbaum NE, Lewin NA, et al., eds. 

Goldfrank’s toxicologic emergencies. 7th ed. New York, NY: McGraw-Hill, 432-440. 

Goans RE. 2007. Medical management of radiation incidents. In: Shannon MW, Borron SW, Burns 

MJ, eds. Haddad and Winchester's clinical management of poisoning and drug overdose. 4th ed. 

Philadelphia, PA: Saunders, 1467-1485. 

NCRP. 2010. Management of persons contaminated with radionuclides: Handbook. NCRP Report No. 

161. National Council on Radiation Protection and Measurements, 128-137, 176-236. 

http://www.ncrponline.org/Publications/161press.html. February 11, 2010. 

3.11.1 Reducing Peak Absorption Following Exposure 

No specific recommendations have been reported for reducing the peak absorption following acute 

inhalation or oral exposure to uranium. The only specific recommendation reported regarding reducing 

absorption of uranium following exposure is to not wash the skin with water following dermal exposure 

to dusts of pure uranium because it will ignite or explode when contacted by water (Began 2002). Thus, 

it is recommended that any residual metal should be removed with forceps, gauze, or towels and stored in 

mineral oil. 

Houpert et al. (2001, 2004) investigated the use of chelating agents to decrease the transfer of uranium 

from a wound to blood. Wound contamination with uranium was simulated by an intramuscular injection 

of 0.66 μg U as uranyl nitrate or 63 μg U as industrial-grade uranium peroxide in the hind leg of rats 

(Houpert et al. 2001). Following exposure to uranium, the rats received an intramuscular or 

intraperitoneal injection or carballylic amido bis phosphonic acid (CAPBP). A significant increase in the 

amount of uranium retained at the wound site was found following the intramuscular injection of CAPBP; 

significant reductions in uranium levels in the kidneys, femur, carcass, and urine were also observed. 

Intraperitoneal administration of CAPBP did not significantly reduce uranium absorption or alter uranium 

tissue levels. In the second study (Houpert et al. 2004), the hind leg skin was incised and industrial-grade 

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uranium peroxide was deposited in the underlying muscle; the wound was then covered for 1 hour with a 

dressing or paste composed of carboxymethylcellulose-based hydrocolloids, which are highly absorbant; 

in two groups, the paste was mixed with CAPBP or ethane-1-hydroxy-1,1-bisphosphonate. Although the 

dressing and paste were effective in decreasing the amount uranium at the wound site and uranium levels 

in the kidneys, adding the chelating agent to the paste did not alter its efficiency. 

3.11.2 Reducing Body Burden 

Administration of bicarbonate is applicable to reducing uranium body burdens from acute exposures. 

Bicarbonate ions complex with uranium and alkalize the blood, both of which enhance the excretion from 

the kidneys by glomerular filtration (Cooper et al. 1982) and such an application was described in a case 

of prophylactic treatment (Fisher et al. 1991). Experimental evidence in animals indicates that chelation 

therapy may reduce the body burden of uranium. Several compounds were found to enhance the urinary 

and fecal excretion of uranium, if administered soon after uranium exposure. When given immediately 

after exposure to uranium, Tiron® (sodium 4,5-dihydroxybenzene-1,3-disulphonate) resulted in the 

greatest reduction in renal and bone levels of uranium and acute lethal effects in animals (Domingo et al. 

1992; Ortega et al. 1989a). None of the chelating agents affected bone levels of uranium when given 

≥24 hours after exposure to uranium (Domingo et al. 1992). Bicarbonate treatment is also limited to very 

near-term exposures. Another study that tested Tiron® alone and in conjunction with either DTPA or 

ethylenediamine-N,N=-bis(2-hydroxyphenylacetic acid) (EDHPA) found that it reduced the uranium body 

burden no more than about 35%, indicating that the administration of Tiron® is of limited practical value 

for the treatment of uranium exposures that do not greatly exceed the permitted intake level (Stradling et 

al. 1991). 

Other studies have reported the efficiency of other chelating agents on reducing toxicity or tissue levels of 

uranium. Administration of catechol-3,6-bis-(methyleiminodiacetic acid) (CBMIDA) or ethane1-hydroxy-1,1-bisphosphonate (EHBP) for 28 days after an intramuscular injection of 2 mg U/kg resulted 

in a reduction in mortality and decreases in uranium levels in the kidney, bone, and liver (Fukuda et al. 

2005). Fukuda et al. (2009) also demonstrated that oral or intraperitoneal administration of CBMIDA for 

6 days significantly increased excretion of uranium and decreased tissue uranium levels in rats 

administered 8 mg/kg depleted uranium via intraperitoneal or intramuscular injection. 

Administration of bicarbonate for 3 days following an intramuscular injection of 4 mg/kg depleted 

uranium did not result in a significant reduction in uranium tissue levels or improvement in renal function 

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in rats (Fukuda et al. 2008). However, co-administration of bicarbonate with the chelating agent, 

deferiprone, resulted in decreased uranium tissue levels and increased urinary uranium excretion 

compared to groups of depleted uranium exposed rats administered bicarbonate only or deferiprone only. 

Co-administration of bicarbonate and 4,6-dimethyl-1-hydroxyprimidin-2(1H)-one resulted in an increase 

in uranium excretion but did not affect tissue levels or organ function. Bicarbonate did not increase the 

efficiency of CBMIDA and was found to decrease the efficiency of EHBP. 

Administration of a 500 mg/kg oral dose or 50 mg/kg subcutaneous dose of bisodic etidronate 

immediately following administration of a 170 mg U/kg dose of uranyl nitrate hexahydrate resulted in a 

50% reduction in mortality and an improvement in the uranium-induced reduction in growth cartilage 

width, metaphyseal bone volume, and metaphyseal bone activity in male Balb/c mice (Bozal et al. 2005). 

Similarly, oral or subcutaneous administration of EHBP (Martinez et al. 2000, 2003) or bisodic etidronate 

(Martinez et al. 2003) immediately following administration of a single 170 mg U/kg as uranyl nitrate 

oral dose resulted in a decrease in mortality and a lessening of the severity of kidney lesions. 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects 

No studies that examined methods for interfering with the mechanisms of action were identified. 

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 uranium is available. Where adequate information is not 

available, ATSDR, in conjunction with the National Toxicology Program (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 uranium. 

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. 

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3.12.1 Existing Information on Health Effects of Uranium 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

uranium are summarized in Figure 3-11. The purpose of this figure is to illustrate the existing 

information concerning the health effects of uranium. 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 depicts the existing health effects information on uranium for a specific route and duration of 

exposure. There are limited data on uranium toxicity in humans following inhalation or oral exposure; no 

dermal exposure studies were identified. Several available studies that investigated the health effects in 

humans of inhalation exposure to uranium are limited to occupational settings (miners, millers, 

processors). The subjects of some of these studies were also concurrently exposed to other potentially 

toxic substances, rendering it difficult to establish the etiology for the effects reported in these studies; 

however, studies of processors who were not concurrently exposed to those toxicants are useful in this 

regard. Although three human studies presented limited evidence of reproductive effects (damage to sex 

chromosomes) in uranium mine workers, no empirical evidence was presented for evaluation. Oral 

studies are limited to several ecological studies of communities exposed to elevated uranium in drinking 

water. Although the studies did find significant associations, particularly for biomarkers of renal 

dysfunction, the studies do not provide reliable dose-response data. Information on the systemic effects 

of uranium through the inhalation, oral, and dermal routes of exposure are available in a number of 

animal species. Several studies have examined the neurological, reproductive, and developmental 

toxicity of uranium following oral exposure. Reproductive and developmental end points have not been 

examined following inhalation or dermal exposure. Non-specific neurological symptoms have been 

reported in animals exposed via the inhalation or dermal routes to lethal concentrations of uranium. The 

carcinogenicity of uranium has been investigated in inhalation studies, but not in oral or dermal studies. 

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Figure 3-11. Existing Information on Health Effects of Uranium 

Inhalation 

Oral 

Dermal 

Death 

Acute 

Intermediate

Chronic 

Immunologic/Lymphoretic

Neurologic

Reproductive

Developmental

Genotoxic

Cancer 

Systemic 

Human 

Inhalation 

Oral 

Dermal 

Death 

Acute 

Intermediate

Chronic 

Immunologic/Lymphoretic

Neurologic

Reproductive

Developmental

Genotoxic

Cancer 

Systemic 

Animal 

Existing Studies 

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3.12.2 Identification of Data Needs 

Acute-Duration Exposure. Human fatalities from acute accidental exposure to airborne uranium 

hexafluoride have been reported, although the deaths were attributed to the sheer force of the explosions 

in the accident and the highly toxic hydrofluoric acid generated from the spontaneous decomposition of 

uranium hexafluoride upon contact with atmospheric moisture (Kathren and Moore 1986; Moore and 

Kathren 1985; USNRC 1986). Two poisoning incidents, an inhalation exposure to powdered uranium 

tetrafluoride (Lu and Zhao 1990) and an intentional ingestion of approximately 131 mg U/kg as uranyl 

acetate (Pavlakis et al. 1996), resulted in renal toxicity. Acute-duration studies in animals mainly 

examined lethality. Inhalation acute-duration lethality studies in rats and guinea pigs are available for 

uranium hexafluoride for short durations (<2 hours) (Leach et al. 1984; Spiegl 1949); oral acute-duration 

lethality data are available for rats and rabbits (Domingo et al. 1987; Maynard and Hodge 1949; Orcutt 

1949); and dermal acute-duration lethality studies in rats, mice, guinea pigs, and rabbits (De Rey et al. 

1983; Orcutt 1949) are available. Additionally, there are acute oral studies examining systemic toxicity 

(Ozmen and Yurekli 1998), neurological effects (Briner 2009; Briner and Murray 2005), and 

developmental toxicity (Domingo et al. 1989c; Pujadas Bigi et al. 2003). The inhalation studies were 

inadequate for derivation of an MRL because the exposure durations were very short. An acute oral MRL 

was derived based on a developmental toxicity study (Domingo et al. 1989c). Acute-duration studies that 

define threshold values for renal toxicity by the inhalation and oral routes would be useful for assessment 

of brief exposures. Dermal exposure to uranium-contaminated soil is also possible. While dermal 

exposure to purified uranium compounds can cause toxicity in animals (De Rey et al. 1983; Orcutt 1949), 

the need for further dermal studies should be assessed after information is obtained on the bioavailability 

of uranium from uranium-contaminated soil. 

Intermediate-Duration Exposure. No studies are available describing the effects of intermediateduration exposure to uranium in humans for any route. However, an extensive animal database for this 

duration for all routes demonstrates that renal toxicity is a concern for intermediate-duration human 

exposure. A number of animal studies have evaluated the toxicity of various uranium compounds in a 

number of animal species (Dygert 1949a, 1949b, 1949d; Roberts 1949; Rothstein 1949a, 1949b, 1949c; 

Spiegl 1949; Stokinger et al. 1953). Threshold values from these studies were used to derive inhalation 

MRLs for insoluble and soluble uranium compounds (see Chapter 2 and Appendix A); however, 

additional inhalation studies are needed to better define concentration-response relationships. The animal 

database for intermediate-duration oral exposure is less extensive in terms of species and compounds 

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examined. Comprehensive studies are available for the effects of uranyl nitrate in rats and rabbits 

(Gilman et al. 1998a, 1998b, 1998c). The severity of histopathological alterations in the kidney increased 

with dose, although tests of kidney function (dye clearance, urinalysis) were normal in all dosed groups. 

Additionally, histopathological effects were seen in the lower dose groups without a significant increase 

in kidney uranium content over controls. Inconsistent results were found in the rabbit studies (Gilman et 

al. 1998b, 1998c), which the investigators attributed to a possible subclinical infection. No threshold for 

the histopathological effects was observed; the lowest dose tested in the rats was considered a minimal 

effect and was used to derive an oral MRL for this duration (see Chapter 2 and Appendix A). Further 

studies are needed to elucidate the time-course of the development of these histopathological effects; in 

rats, these changes were seen after 91 days, but not at 28 days, and to validate the results of the rabbit 

studies. No reliable studies examining the oral toxicity of insoluble uranium compounds were identified; 

studies providing dose-response data would be useful for establishing an MRL for insoluble compounds. 

Dermal exposure to uranium-contaminated soil is also possible. While dermal exposure to purified 

uranium compounds can cause toxicity in animals (De Rey et al. 1983; Lopez et al. 2000; Orcutt 1949), 

the need for further dermal studies should be assessed after information is obtained on the bioavailability 

of uranium from uranium-contaminated soil. 

Chronic-Duration Exposure and Cancer. A small number of occupational exposure studies have 

examined renal toxicity. No evidence of renal toxicity was reported in workers exposed to relatively low 

concentrations of insoluble uranium compounds (Eisenbud and Quigley 1956). However, significant 

increases in urinary biomarkers of renal dysfunction were observed in workers exposed to ammonium 

diuranate (Thun et al. 1985). Future studies of uranium workers should include exposure assessments and 

measurement of sensitive biomarkers of renal damage. The available studies have linked respiratory 

diseases, fatal in some cases, in uranium miners to exposure to dust-containing uranium (and other 

noxious substances) (Waxweiler et al. 1981a). In several of these studies, the investigators concluded 

that, although uranium mining may elevate the risk for nonmalignant respiratory disease, the etiology of 

the excess risk is not clearly identifiable because the miners were also concurrently exposed to known 

potent respiratory tract irritants such as diverse inhalable dust particles, silica, nickel oxide, cobalt oxide, 

and vanadium pentaoxide (Waxweiler et al. 1983). Studies of underground uranium miners have not yet 

accounted for confounding by silica dust, especially freshly cracked silica dust, which was in high 

concentrations in mine air. A small number of studies have examined the chronic toxicity of inhaled 

uranium in animals. Studies involving exposure to soluble uranium compounds have identified the 

kidney as the most sensitive target (Stokinger et al. 1953) and were used to derive a chronic-duration 

MRL for soluble compounds. Data for insoluble compounds suggest that at low concentration and long 

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exposure duration (≥3.5 years), the lung may be a more sensitive target than the kidney (Leach et al. 

1970). However, the lung effects may be due to radiotoxicity rather than chemical toxicity. Additional 

mechanistic studies are needed to identify the causative agent. The data were considered adequate for 

derivation of an MRL for insoluble uranium compounds; however, additional studies are needed to better 

define the concentration-response relationship for pulmonary and renal effects. Several ecological studies 

have examined the possible association between elevated levels of uranium in drinking water and 

impaired kidney function (Kurttio et al. 2002, 2006a; Limson Zamora et al. 1998, 2009; Mao et al. 1995; 

Seldén et al. 2009). Several studies have sound significant association. A common limitation of the 

studies is a lack of accurate dose-response data. No animal studies have examined the chronic oral 

toxicity. Oral exposure studies examining a variety of end points including sensitive end points of renal 

toxicity are needed for soluble and insoluble uranium compounds. No chronic-duration dermal toxicity 

studies were identified in humans and animals. 

A number of epidemiological studies are available for workers exposed to uranium (miners, millers, 

processors). A number of studies reported death from lung cancers from occupational inhalation 

exposure of mine workers (Archer et al. 1973a; Gottlieb and Husen 1982; Lundin et al. 1969; Samet et al. 

1984a, 1986); however, the available studies document no lung cancers solely from inhaled uraniumbearing dust. It is generally accepted that lung cancers developed subsequent to inhalation of uraniumcontaining dusts were principally due to radon daughters and long-term cigarette smoking, and not to 

uranium metallotoxicity or uranium radioactive emissions. Existing epidemiologic studies that reported 

lung cancers in uranium miners, millers, and processors are inadequate for use in assessing the 

carcinogenic potential of uranium because the subjects were also concurrently exposed to other potential 

carcinogens such as radon progeny and thorium (Archer et al. 1973a; Auerbach et al. 1978; Cookfair et al. 

1983; Howe et al. 1986; Polednak et al. 1982; Saccomanno et al. 1971, 1976, 1988; Samet et al. 1986; 

Wrenn et al. 1983). There are limited animal data on the carcinogenicity of uranium following inhalation 

exposure and no oral or dermal exposure studies. Pulmonary neoplasms were observed in dogs (Leach et 

al. 1973) and rats (Mitchel et al. 1999). 

Genotoxicity. Limited data exist regarding in vivo genotoxicity in humans following exposure to 

uranium. The only cases in which there were documented exposures to uranium are those of the Gulf 

War veterans who retained depleted uranium shrapnel fragments (McDiarmid et al. 2000, 2001a, 2004b, 

2007, 2009). Prospective tests for clastogenicity and mutations in blood cells from this group yielded 

inconsistent results that led the investigators to conclude that the body of evidence in that cohort showed 

relatively weak genotoxic effects from uranium exposure. Future assessments are unlikely to provide key 

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new information. Other assessments of small cohorts presumed to have been exposed to depleted 

uranium provided positive evidence of clastogenicity (Krunić et al. 2005; Milačić 2008; Milačić and 

Simić 2009; Milačić et al. 2004; Schröder et al. 2003). Studies of populations in areas with high levels of 

uranium in drinking water or soil would be valuable. In vivo studies in animals provided positive 

evidence of genotoxicity after inhalation and oral exposure to depleted uranium (Hao et al. 2009; Miller et 

al. 2010; Monleau et al. 2006a). Miller et al. (2010) also showed that implantation of depleted uranium 

pellets in male mice for 7 months followed by mating with untreated females resulted in transmission of 

genetic damage to somatic cells of offspring; the exact mechanism by which this occurred is not known, 

so further studies in this area are warranted. In addition, similar studies in mice exposed to uranium by 

routes relevant to general population exposure (contaminated drinking water or food) would be valuable. 

Studies of genotoxicity in vitro, both with mammalian cells (LaCerte et al. 2010; Lin et al. 1993; Miller et 

al. 2002a, 2002b, 2003; Stearns et al. 2005; Thiébault et al. 2007; Wise et al. 2007) and prokaryotic 

organisms (Miller et al. 1998a; Yazzie et al. 2003) have yielded positive results. Studies with HOS cells 

showed that depleted uranium induced de novo genomic instability in the cells, which led to delayed 

reproductive death for many generations (Miller et al. 2003). Further studies aimed at elucidating the 

mechanism by which this can occur are needed. Some studies showed differences in genotoxic capacity 

between water-soluble and -insoluble uranium compounds (LaCerte et al. 2010; Wise et al. 2007). The 

investigators speculated that the difference may be related to differences in kinetics between the two types 

of uranium compounds; research in this area would be helpful. A study in CHO cells showed that 

uranium can form adducts with DNA (Stearns et al. 2005). Further research in this area can provide 

information regarding possible sensitive biomarkers for uranium exposure. 

Reproductive Toxicity. Existing human data from male uranium miners, millers, and processors 

(Muller et al. 1967; Waxweiler et al. 1981b; Wiese and Skipper 1986) and from men exposed to depleted 

uranium in the Gulf War via retained metal shrapnel fragments (McDiarmid et al. 2000, 2001a, 2004b, 

2007, 2009) have not suggested adverse uranium-induced reproductive effects. The Gulf War veterans 

were subjected to longitudinal analyses of sex hormone levels in blood and sperm parameters; however, 

no assessments of fertility have been conducted. It would be helpful to have that information, if available. 

Exposure to uranium reduced fertility in male mice (Llobet et al. 1991) and male rats (Linares et al. 2005) 

exposed via the drinking water. In the former study, reduced fertility was associated with reduced 

spermatozoa counts; in the latter, there were morphological alterations in Sertoli or germinal cells. 

Fertility was not affected in mice dosed with uranium by gavage (Paternain et al. 1989) or in a 

2-generation reproductive toxicity study in rats implanted depleted uranium pellets (Arfsten et al. 2009). 

Differences in exposure routes may have played a role in the difference results obtained. Clearly, 

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drinking water studies are more relevant to potential exposures of the general population than exposures 

by gavage or through an embedded uranium pellet. Of the four studies mentioned above (Arfsten et al. 

2009; Linares et al. 2005; Llobet et al. 1991; Paternain et al. 1989), urinary uranium, as a biomarker of 

exposure, was only monitored by Arfsten et al. (2009). Studies are also available that reported that 

exposure to uranium altered ovarian folliculogenesis in mice (Arnault et al. 2008; Feugier et al. 2008; 

Kundt et al. 2009; Raymond-Whish et al. 2007). The study conducted by Raymond-Whish et al. (2007) 

reported slight alterations in ovarian folliculogenesis in mice administered doses as low as 0.39 μg 

U/kg/day. These authors also reported estrogenic effects in mice treated with 5 μg U/kg/day. Since these 

doses are orders of magnitude lower than those used in other studies, it would be reassuring if the findings 

of Raymond-Whish et al. (2007) can be replicated by other laboratories. A study in rats reported that 

enriched uranium, but not depleted uranium, increased serum testosterone and the expression of genes 

involved in steroidogenesis (Grignard et al. 2008). In addition, enriched uranium significantly increased 

the expression of transcription factors involved in the regulation of steroidogenic genes. This is the only 

study available that compared the effects of enriched versus depleted uranium on some reproductive end 

points. Additional studies comparing the effects of depleted and enriched uranium on other reproductive 

end points (i.e., fertility, sperm parameters, microscopic morphology of reproductive organs, 

estrogenicity, levels of sex hormones) would be valuable to distinguish between chemical and 

radiological activity. 

Developmental Toxicity. There are no studies of developmental effects in humans with documented 

exposure to uranium. Several reports have been published regarding increased incidence of teratogenicity 

in populations presumed to have been exposed to depleted uranium; this subject was reviewed by Hindin 

et al. (2005). It should be noted that all of the reports lack documentation of individual exposure to 

depleted uranium, some reports lacked methodologically rigorous investigation (like exposure to other 

chemicals and other confounders), and in the incidences of birth defects between supposedly exposed and 

nonexposed groups was not statistically significant in other reports. Yet, Hindin et al. (2005) concluded 

that the evidence linking exposure to depleted uranium and birth defects, albeit imperfect, indicates a high 

probability of substantial risk. Studies could be conducted of offspring of women living in areas with 

documented high uranium in the drinking water or the soil to evaluate possible associations between 

uranium and birth defects in humans. 

Maternal exposure to uranium during pregnancy has induced fetotoxicity, teratogenicity, and reduced 

neonatal viability in mice (Domingo et al. 1989b, 1989c; Paternain et al. 1989). An issue that is not 

totally clear is whether this occurs at doses not causing maternal toxicity. An additional issue that has not 

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been explored is evaluation of the contribution of gestational exposure versus lactational exposure to the 

uranium-induced decreased neonatal viability. Valuable information could be collected to address this 

question by conducting cross-fostering studies. Gestational exposure to uranium did not affect 

developmental landmarks in mice (Domingo et al. 1989b) or rats (Sánchez et al. 2006). However, in rats, 

perinatal exposure altered the results of some neurobehavioral tests conducted in the offspring (Houpert et 

al. 2007a; Sánchez et al. 2006). Histological examination of different brain areas of the offspring as well 

as measurements of neurotransmitters could provide information regarding possible mechanisms involved 

in the neurobehavioral effects of perinatal exposure to uranium. In contrast with the findings of Houpert 

et al. (2007a) and Sánchez et al. (2006), a study in rats implanted depleted uranium pellets for 120 days 

before mating reported no significant alterations in neurobehavioral tests conducted on the offspring on 

postnatal days 4–63 (Arfsten et al. 2009). This 2-generation reproductive study also did not report 

significant alterations in viability of the F1 generation or in histology of selected organs or sperm 

parameters on postnatal day 120. Different results between studies are not totally unexpected since 

exposure protocols were different. Sánchez et al. (2006) exposed only females via drinking water for 

4 weeks, Houpert et al. (2007a) exposed males and females via drinking water for 3 months, and Arfsten 

et al. (2009) implanted uranium pellets in both males and females. Information regarding uranium body 

burdens in the parental generation, such as urinary uranium levels, would be helpful for comparing 

studies with differing exposure protocols. Studies also showed that in mice, gestational exposure to 

uranium can alter ovarian folliculogenesis in the female offspring (Arnault et al. 2008; Raymond-Whish 

et al. 2007). In one of these studies (Raymond-Whish et al. 2007), effects occurred at doses much lower 

than those tested in any other animal study. It would be useful to try to replicate these findings. Neonatal 

exposure of rats to uranium interfered with tooth eruption and development (Pujadas Bigi and Ubios 

2007; Pujadas Bigi et al. 2003), but only one dose level was tested so that a NOAEL was not defined. 

Studies designed to define a NOAEL and to allow construction of a dose-response curve would be 

helpful. Recently, it was shown that paternal exposure to uranium via implantation of depleted uranium 

pellets resulted in transmission of genetic damage to somatic cells of unexposed offspring (Miller et al. 

2010). The investigators noted that studies investigating the effects of depleted uranium exposure on 

germ cell mutagenesis and direct DNA damage to sperm are being completed. It would be valuable if 

similar studies are conducted with male mice exposed by a route more relevant to exposures of the 

general population such as via contaminated drinking water or food. 

Immunotoxicity. There are limited data on the immunotoxic potential of uranium. Epidemiology 

studies that examined white blood cell levels or mortality from immune disease have not reported adverse 

effects following inhalation, oral, or dermal exposure (Archer et al. 1973b; Checkoway et al. 1988; Cragle 

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URANIUM 248 

3. HEALTH EFFECTS 

et al. 1988; Keane and Polednak 1983; NIOSH 1987; Polednak and Frome 1981; Vich and Kriklava 

1970). The available inhalation studies in animals also found no evidence of histological changes in the 

spleens of rats, dogs, and monkeys exposed to uranium dioxide dusts (Leach et al. 1970, 1973). 

Intermediate-duration exposure of rats, rabbits, guinea pigs, and dogs to dusts containing various uranium 

compounds for 7–12 months produced no significant histological changes in the lymph nodes, bone 

marrow, or spleen, and no build-up of uranium was seen in these tissues (Stokinger et al. 1953). 

Similarly, rats and mice exposed to oral doses of soluble or insoluble compounds of uranium for 

intermediate- and chronic-duration exposures suffered no immunological damage (Malenchenko et al. 

1978; Maynard et al. 1953; Tannenbaum et al. 1951). No studies are available that evaluated the 

immunological and lymphoreticular effects in animals following acute- or intermediate-duration 

inhalation exposure, the oral exposure of humans for any duration, the inhalation or oral exposure of 

animals for acute durations, or the dermal exposure of humans and animals to uranium compounds for 

any duration. Additional animal studies would be useful that use current techniques to evaluate the 

immunological and lymphoreticular dysfunctions that may occur with exposure to uranium compounds. 

Neurotoxicity. In general, studies of uranium workers have not provided evidence of adverse 

neurological effects, although tests to detect subtle neurological alterations were not conducted (Carpenter 

et al. 1988; Cragle et al. 1988; Hadjimichael et al. 1983; Kathren and Moore 1986; NIOSH 1987; 

Polednak and Frome 1981; Reyes et al. 1984; USNRC 1986). Workers were presumed to have been 

exposed mainly by the inhalation and dermal routes. Longitudinal assessments of Gulf War veterans who 

retained depleted uranium fragments and were excreting elevated urinary levels of uranium years after the 

first exposure provided inconsistent results in neurobehavioral tests (McDiarmid et al. 2000, 2001a, 

2004b, 2007, 2009). Surveillance of this group of subjects should continue to try to identify potentially 

late-appearing effects or normal aging signs that might manifest prematurely. No information was 

located regarding neurological effects in humans exposed orally to uranium. Early inhalation studies in 

animals exposed to dusts of fluoride salts of uranium reported frank neurological effects, but did not 

consider the possible contribution of fluoride (Dygert 1949a; Rothstein 1949a). More recent oral studies 

in animals have reported changes in biochemical parameters, including levels of neurotransmitters and 

their metabolites, in various areas of the brain following acute- and intermediate-duration exposure to 

uranium (Briner 2009; Briner and Murray 2005; Bussy et al. 2006; Linares et al. 2007). Studies also have 

examined neurobehavioral parameters following exposure to uranium; some reported neurobehavioral 

alterations (Briner 2009; Briner and Murray 2005; Houpert et al. 2005, 2007b), while others did not 

(Arfsten et al. 2007; Belles et al. 2005). An area of the brain that has been suggested might be involved in 

uranium-induced effects is the hippocampus (Houper et al. 2007b; Linares et al. 2007; Pellmar et al. 

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URANIUM 249 

3. HEALTH EFFECTS 

1999a). Studies are needed that conduct morphological, electrophysiological, and biochemical 

evaluations in the same animals following exposure to uranium to shed light into possible mechanism(s) 

of action for uranium-induced neurological effects. No studies were located that examined neurological 

parameters in animals following chronic-duration exposure to uranium. Such studies would provide 

information regarding long-term, low-level exposure as could occur to populations exposed to excessive 

uranium in the drinking water or through consumption of food grown in areas with elevated 

concentrations of uranium in the soil. 

Epidemiologic and Human Dosimetry Studies. Epidemiologic studies of uranium miners, 

millers, and processors are available on the health effects from exposure to airborne uranium and radon 

daughters (Archer et al. 1973a, 1973b; Checkoway et al. 1988; Cragle et al. 1988; Gottlieb and Husen 

1982; Hadjimichael et al. 1983; Lundin et al. 1969; NIOSH 1987; Polednak and Frome 1981; Samet et al. 

1984a, 1986; Scott et al. 1972; Waxweiler et al. 1983). However, some of the studies of miners and 

millers contain confounding factors and lack adequate quantitative exposure information compared with 

the studies of processors, which had fewer confounders and clearly identified an absence of toxic effects 

such as cancer. New studies that account for these confounding factors, such as effects of inhalable dust 

particles other than uranium, other sources of ionizing radiation, and other potentially pulmonary-toxic 

substances to which these workers are concurrently exposed, and that provide a more accurate 

measurement of the airborne concentrations of uranium to which these workers are exposed would be 

useful. Animal studies provide strong evidence that the kidney is the most sensitive target of uranium 

toxicity. Alterations in sensitive biomarkers of renal dysfunction have been observed in workers exposed 

to airborne soluble uranium compounds (Thun et al. 1985) and in residents consuming drinking water 

with elevated uranium levels (Limson Zamora et al. 1998, 2009; Mao et al. 1995). However, 

occupational exposure studies of workers exposed to insoluble uranium (as reviewed by Eisenbud and 

Quigley 1956) and ecological drinking water studies (Kurttio et al. 2006a; Seldén et al. 2009) have not 

found significant kidney effects. Most of these studies provide limited dose-response data, and studies 

examining sensitive end points of renal toxicity, as well as other potential targets of toxicity, are needed 

to assess the relative sensitivity of humans to uranium toxicity as compared to animal species, which are 

used to derive MRLs for uranium. Also, simple and accurate monitoring methods should be developed 

for workers that would determine the relationship among atmospheric concentration, particle size, 

distribution, physical properties of the uranium aerosol, body burden, and excretion rates and pathways. 

The use of depleted uranium munitions by the military has resulted in the potential uranium exposure to 

military personnel and civilians; additional research regarding the health effects of acute-duration 

inhalation exposure to depleted uranium would be useful to assess the potential for toxicity. These 

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URANIUM 250 

3. HEALTH EFFECTS 

studies should include toxicological end points, lung doses, metabolic fate, and techniques to detect and 

monitor lung exposures. 

Biomarkers of Exposure and Effect. 

Exposure. Because uranium is primarily excreted in the urine following inhalation, oral, or dermal 

exposure, measurement of urine uranium levels can accurately estimate uranium body burden (Ballou et 

al. 1986; Cooper et al. 1982; Downs et al. 1967; Leach et al. 1984; McDiarmid et al. 1999b; Morrow et al. 

1982a; Stradling et al. 1984, 1987; West and Scott 1969; Wrenn et al. 1985). Several methods have been 

developed for chemical detection (e.g., fluorimetry and kinetic phosphorescence analysis) and 

radiological detection (e.g., ICP-MS and alpha spectroscopy). Although correlations between uranium 

intake and urinary levels have been reported, additional studies are needed that would allow for the 

development of a biokinetic model, which would allow estimation of uranium intake based on urinary 

uranium levels. 

Uranium content in soft tissue and bone could also be used as biomarkers of exposure to uranium (Ballou 

et al. 1986; Diamond et al. 1989; Leach et al. 1973, 1984; Morris et al. 1990; Morrow et al. 1972; 

Stokinger et al. 1953; Walinder 1989; Wrenn et al. 1987). Although soft tissues and bone are the most 

frequently analyzed biological media after urine and feces, these tissues are usually available for analysis 

only at autopsy. Therefore, this method is impractical and not used for routine screening purposes. 

Effect. Currently, there are no available biomarkers for specific exposure to the metallotoxic or 

radiotoxic effects of uranium. Although the kidney is the most sensitive target of uranium toxicity, 

biomarkers of renal dysfunction such as β2 microglobulin, protein HC, and retinol binding protein are not 

specific to uranium. Additional studies are needed to correlated these alterations with renal damage and 

establish dose-response relationships. 

Absorption, Distribution, Metabolism, and Excretion. Information is needed on the 

comparative absorption of uranium compounds by the oral route, along with an assessment of its 

clearance from the skeleton. Quantitative data on the bioavailability of uranium from contaminated soil 

by the oral and dermal routes are also necessary to assess the risk of uranium-contaminated soil at 

hazardous waste sites. 

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3. HEALTH EFFECTS 

Comparative Toxicokinetics. Numerous species (mice, rats, rabbits, guinea pigs, dogs, and 

monkeys) have been tested for their response to inhaled or ingested uranium. The results from these 

studies clearly demonstrate that there is a considerable difference in toxic responses among species. For 

example, rabbits appear to be unusually susceptible to the lethal effects of uranium (Maynard and Hodge 

1949; Orcutt 1949; Stokinger et al. 1953), whereas dogs developed glandular neoplasms of the lungs 

(Leach et al. 1973), a type of lung cancer that is not observed in humans, and guinea pigs required far 

greater air concentrations (15x) for 2-minute exposures than did rats to produce an effect (Leach et al. 

1984). 

Methods for Reducing Toxic Effects. Most of the available research on methods for reducing the 

toxic effects of uranium have focused on the effectiveness of chelating agents on reducing the 

accumulation of uranium in the body (Bozal et al. 2005; Domingo et al. 1992; Fukuda et al. 2005, 2009; 

Martinez et al. 2000, 2003; Ortega et al. 1989a; Stradling et al. 1991). Several agents including Tiron, 

CBMIDA, EHBP, and bisodic etidronate have significantly reduced tissue uranium levels, decreased 

renal toxicity, and increased survival when the chelating agent was administered shortly after exposure. 

The effectiveness of bicarbonate in facilitating the excretion of uranium has also been investigated 

(Cooper et al. 1982; Fisher et al. 1991; Fukuda et al. 2008). However, few studies have investigated the 

effectiveness of these agents when they are administered after long-term uranium exposure and more 

studies are needed. No studies investigating methods for reducing peak absorption following inhalation 

or oral exposure were identified. Houpert et al. (2001, 2004) explored the use of dressings with or 

without chelating agents on decreasing the absorption of uranium from wounds. No studies researching 

methods for interfering with the toxic mechanisms of action were identified. Further research is needed 

to validate, refute, or refine method(s) for reducing the body burden, particularly following long-term 

exposure, and research is needed on methods for decreasing absorption and interfering with the 

mechanism of toxicity. 

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. 

Specific information is not available on whether children are more susceptible than adults to the effects of 

uranium. No reports were located describing toxicity in children as the result of uranium exposure. It is 

probable, however, that if exposure levels were high enough, signs of renal toxicity would be observed 

similar to that seen in adults exposed accidentally (Lu and Zhao 1990) or intentionally (Pavlakis et al. 

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URANIUM 252 

3. HEALTH EFFECTS 

1996). Because children undergo periods of rapid bone growth and remodeling and uranium is stored in 

bone, there is a need to examine the potential toxicity of uranium to bone. However, few studies have 

examined this end point and additional studies are needed. 

A study by the oral route establishing a threshold for renal effects in weanling and adult rats of the same 

strain is needed to determine if susceptibility to uranium toxicity varies with age. Histopathological 

studies and urinalysis should be performed, as well as measurement of uranium in excreta for both 

groups. At termination in this study, uranium content should be measured in tissues, particularly bone 

and kidney. This will provide information on whether retention of uranium in bone is age-dependent (as 

assumed by analogy with calcium in PBPK models) and on whether kidney burden associated with 

uranium toxicity is age-related. 

More information on the absorption of various forms of uranium in young animals would be useful. Also, 

studies are needed on whether maternally stored bone uranium is mobilized to blood during pregnancy 

and lactation and whether this can increase exposure to the fetus and neonate. 

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 

Ongoing studies are examining possible kidney toxicity in residents living near uranium mining sites, 

genotoxicity of depleted uranium, and adverse health outcomes in Gulf War veterans exposed to depleted 

uranium. 

ATSDR will conduct a prospective birth cohort study involving non-occupational uranium exposure in 

the Navajo Nation. The key objectives of the study include quantifying the potential association between 

environmental exposure to uranium and reproductive health effects and mitigating uranium exposure and 

increase positive prenatal and reproductive health outcomes on the Navajo Reservation. 

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URANIUM 253 

4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION 

4.1 CHEMICAL IDENTITY 

Uranium is a naturally occurring element that makes up approximately 2–4 ppm of the earth=s crust. It is 

more plentiful than silver and about as abundant as molybdenum or arsenic. Uranium is an actinide 

element, and has the highest atomic mass of any naturally occurring element. In its refined state, it is a 

heavy, silvery-white metal that is malleable, ductile, slightly paramagnetic, and very dense, second only 

to tungsten. In nature, it is found in rocks and ores throughout the earth, with the greatest concentrations 

in the United States in the western states of Colorado, Arizona, Wyoming, Texas, Utah, and New Mexico 

(Lide 2008). In its natural state, crustal uranium occurs as a component of several minerals, such as 

carnotite, uraninite, and pitchblend, but is not found in the metallic state. The chemical information for 

uranium metal is listed in Table 4-1. 

4.2 PHYSICAL, CHEMICAL, AND RADIOLOGICAL PROPERTIES 

The physical properties of uranium and uranium compounds important in the nuclear fuel cycle and 

defense programs are listed in Table 4-2. The percent occurrence and radioactive properties of naturally 

occurring isotopes of uranium are listed in Table 4-3. The two decay series for the naturally occurring 

isotopes of uranium are shown in Table 4-4. 

Metallurgically, uranium metal may exist in three allotropic forms: orthorhombic, tetragonal, or bodycentered cubic (Lide 2008), and may be alloyed with other metals to alter its structural and physical 

properties to suit the application. Like aluminum metal powder, uranium metal powder is autopyrophoric 

and can burn spontaneously at room temperature in the presence of air, oxygen, and water. In the same 

manner, the surface of bulk metal, when first exposed to the atmosphere, rapidly oxidizes and produces a 

thin surface layer of UO2, which resists oxygen penetration and protects the inner metal from oxidation. 

At temperatures of 200–400 C, uranium powder may self-ignite in atmospheres of CO2 and N2. In order 

to prevent autoignition, uranium machining chips can be stored in open containers and under machine oil 

or water to prevent hydrogen gas buildup. Burning uranium may be placed under water until 

extinguished, which may be delayed by hydrolysis of the water, which provides some oxygen and 

hydrogen for continued burning. Water spray, CO2, and halon are ineffective, and halon discharge can be 

explosive and produce toxic gases (DOE 2001). 

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URANIUM 254 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Uranium Metal 

Value Reference 

Chemical name Uranium 

Natural isotopes Uranium-238; uranium-235; uranium-234 HSDB 2011 

Synonyms Uranium; 238U; 238U element; uranium-238; uranium-234; HSDB 2011 

uranium-235; uranium, elemental; uranium, metal, 

pyrophoric; uranium, radioactive; uranium, natural 

Trade names No data 

Chemical formula U HSDB 2011 

Chemical structure Not applicable 

Identification numbers 

CAS registry 7440-61-1 HSDB 2011 

NIOSH RTECS NIOSH/YR3490000 NIOSH 2010a 

EPA hazardous waste No data HSDB 2011 

OHM/TADS 7217196 HSDB 1995 

DOT/UN/NA/IMO shipping UN2979; uranium metal, pyrophoric HSDB 2011 

HSDB 2553; 7404, uranium, radioactive HSDB 2011 

NCI No data HSDB 2011 

STCC 4926187; uranium metal, pyrophoric (uranium metal scrap, HSDB 1995 

neither irradiated nor requiring protective shielding) 

CAS = Chemical Abstracts Service; DOT/UN/NA/IMCO = Department of Transportation/United Nations/North 

America/International Maritime Dangerous Goods Code; 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; STCC = Standard Transportation Commodity Code 

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URANIUM 255 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Selected Uranium Compounds 

Uranium Uranium Triuranium Uranium 

Property Uranium dioxide trioxide octaoxide tetrafluoride 

Atomic/molecular 238.0289a 270.028 286.027 842.08 314.023 

weight 

Chemical formula U UO2 UO3 U3O8 UF4 

Synonyms Uranium Ia Uranium(IV) 

oxide 

Uranyl(VI) 

oxide 

Uranium 

octaoxide; 

Uranium(IV) 

fluoridea 

uranium oxide 

Common names Brown oxide Orange oxide Yellow cake; Green salta 

Block oxide 

CAS Registry No. 7440-61-1a 1344-57-6 1344-58-7 1344-59-8 10049-14-6 

Color Silvery-white Brown Orange-yellow Olive green-black Green 

Physical state Solida Solid crystal Solid crystal Solid Solid crystal 

Odor No data No data No data No data No data 

Melting point, °C 1,135a 2,847 Decomposes Decomposes at 1,036 

1,300 

Boiling point, °C 4,131a ~3,800 °K Not relevant Not relevant 1,417 

Autoignition 

temperature 

20 °C (cloud), 

100 °Ca 

(layer)a 

Not relevant Not relevant Not relevant Not relevant 

Solubility: 

Water Insoluble Insoluble Insoluble Insoluble 0.01 g/100 g H2O 

Other solvents Soluble in Soluble in Soluble in acid Soluble in HNO3, Soluble in 

concentrated concentrated H2SO4 concentrated 

acids; acids acids and alkalis 

insoluble in 

alkalis, 

alcoholsa 

Density, g/cm3 18.06–19.1a 10.97 ~7.3 8.30 6.7 

Partition Not relevant Not relevant Not relevant Not relevant No data 

coefficients 

Vapor pressure 0 mmHg at 0.463 atm at Not relevant Not relevant Not relevant 

20 °C; 2,847 °C 

1 mmHg at 

2,450 °Ca 

Henry’s law Not relevant Not relevant Not relevant Not relevant Not relevant 

constant 

Refractive index No data No data No data No data No data 

Flashpoint No data No data No data No data No data 

Flammability limits Not relevanta No data No data No data No data 

Conversion factorb 1 μg=0.67 pCi 1 μg=0.59 pCi 1 μg=0.56 pCi 1 μg=0.57 pCi 1 μg=0.45 pCi 

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URANIUM 256 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Selected Uranium Compounds 

Uranium Uranium Uranyl Uranyl acetate, Uranyl nitrate 

Property hexafluoride tetrachloride fluoridec dihydrate hexahydrate 

Atomic/molecular 352.019 379.841 308.0245 424.146 502.129 

weight 

Chemical formula UF6 UCl4 UO2F2 UO2(CH3COO)22 UO2(NO3)26H2O 

H2O 

Synonyms Uranium(VI) Uranium (IV) Uranium bis(Acetate-B) bis(Nitrate-O) 

fluoride chloride oxyfluoride; dioxouranium dioxouranium; 

uranium hexahydrate 

fluoride oxide 

Common names No data Green salt No data No data No data 

CAS Registry No. 7783-81-5 10026-10-5 13536-84-0a 6159-44-0 13520-83-7 

Color White Green Yellowa Yellow Yellow 

crystallinea 

Physical state Solida Octahedral Solida Solid crystal Solid crystal 

crystal 

Odor No data No data No data No data No data 

Melting point, °C 64.5 at 2 atma 590 °C Decomposes Loses 2H2O at 60 

at 300 110 

Boiling point, °C 56.2 791 Not relevant Decomposes at Decomposes at 

sublimation 275 118 

pointa 

Autoignition No data No data No data No data No data 

temperature 

Solubility: 

Water Reacts with Reacts with 64.4 g/100 g at 7.7 g/100 mL at 127 g/100 gH2O 

H2O water 20 °C 15 °C 

Other solvents Soluble in Soluble in Soluble in Soluble in ethanol Soluble in 

CCl4, TCE, ethanol ethanol and ethanol and ether 

and benzenea 

chloroforma 

Density g/cm3 5.09 at 4.72 6.37 2.893 g/cm3 at 2.81 g/cm3 at 

20.7 °C; 3.595 15 °C 13 °C 

at 70 °C 

Partition Not relevant Not relevant Not relevant Not relevant Not relevant 

coefficients 

Vapor pressure 115 mmHg at No data No data No data No data 

25 °Cc 

Henry’s law Not relevant Not relevant Not relevant Not relevant Not relevant 

constant 

Refractive index No data No data No data No data 1.4967 

Flashpoint No data No data No data No data No data 

Flammability limits No data No data No data No data No data 

Conversion factorb 1 μg=0.45 pCi 1 μg=0.42 pCi 1 μg=0.52 pCi 1 μg=0.38 pCi 1 μg=0.32 pCi 

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URANIUM 257 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Selected Uranium Compounds 

Property 

Uranyl nitrate 

(not hexahydrate) 

Ammonium 

diuranate 

Uranium 

peroxide Uranyl acetate 

Atomic/molecular 

weight 

Chemical formula 

394.037 

(UO2)(NO3)2 

624.131 

(NH4)2U2O7 

302.03a 

UO4 

a 

388.12a 

C4H6O6Ua 

Synonyms No data Ammonium 

uranate(VI) 

No data No data 

Common names No data No data No data No data 

CAS Registry No. 

Color 

10102-06-4 

Yellow 

7783-22-4 19525-15-6a 

Reddish yellow Pale yellowa 

541-09-3a 

Yellowa 

Physical state 

Odor 

Solid crystal 

No data 

Amorphous 

powder 

No data 

Solid 

No data 

Solid crystalsa 

Vinegar-likea 

Melting point, °C No data No data Decomposes at 

90–195 °Ca 

No data 

Boiling point, °C No data No data No data Decomposes at 

<275a 

Autoignition 

temperature 

Not relevant Not relevant Not relevant Not relevant 

Solubility: 

Water 127 g/100 g H2O Insoluble 0.0006 g/100 cc at 

20 °C; 0.008 g/cc 

at 90 °Ca 

7.694/100 mL at 

15°Ca 

Other solvents Soluble in ether Insoluble in 

alkali; soluble 

in acids 

No data Very soluble in 

alcohola 

Density g/cm3 No data No data 11.66 

(calculated)a 2.893 at 15°Ca 

Partition 

coefficients 

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 

Refractive index No data No data No data No data 

Flashpoint No data No data No data No data 

Flammability limits 

Conversion factorb 

No data 

1 μg ≡ 0.51 pCi 

No data No data 

1 μg ≡ 0.51 pCi 1 μg ≡ 0.53 pCi 

No data 

No data 

a

HSDB (2011).

b

Calculated from National Nuclear Data Center data (NNDC 2011).
 c

Argonne National Laboratory (2011).
 

Source: Lide (2008), unless annotated 

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URANIUM	 258 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-3. Percent Occurrence and Radioactive Properties of Naturally Occurring
 

Isotopes of Uranium
 

Percent of total uranium in crustal rock	 Alpha energies, Gamma energies, Half-life 

Isotope By weight By radioactivity keV (abundance) keV (abundance) (years) 

234U 0.0054 49.03	 4772.4 (28.42%) 13.0 (10.0%) 2.455x105 

4774.6 (71.38%) 

235U 0.7204 2.27	 4214.7 (5.7%) 13.0 (37.00%) 7.038x108 

4366.1 (17.0%) 93.35 (5.60%) 

4397.8 (55%) 143.76 (10.96%) 

4556.0 (4.2%) 163.33 (5.08%) 

4596.4 (5.0%) 185.715 (57.20%) 

Others (13.1%) 205.311 (5.01%) 

238U 99.2742 48.70	 4151 (21%) 4772.4 (28.42%) 4.468x109 

4198 (79%) 4774.6 (71.38%) 

Sources: NNDC 2011 

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URANIUM 259
 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-4. 238U Decay Series Showing Sources and Decay Products 

238Uranium-238 series, includes uranium-234 series Uranium-235 series 

Np 

U 

238U 

4.47x 

109 y 

234U 

2.46x 

105 y 

235U 

7.04x 

108 y 

Pa 234mPa 

1.16 m 

231Pa 

3.28x 

104 y 

Th 

234Th 

24.1 d 

230Th 

7.54x 

104 y 

231Th 

25.5 h 

227Th 

18.7 d 

Ac 

227Ac 

21.8 y 

Ra 

226Ra 

1,600 y 

223Ra 

11.4 d 

Fr 

223Fr 

22.0 m 

Rn 

222Rn 

3.82 d 

219Rn 

3.96 s 

At 

218At 

1.5 s 

215At 

1x10-4 s 

Po 

218Po 

3.10 m 

214Po 

1.64x 

10-4 s 

210Po 

138 d 

215Po 

17.8x 

10-3 s 

211Po 

0.5 s 

Bi 

214Bi 

19.9 m 

210Bi 

5.01 d 

211Bi 

2.14 m 

Pb 

214Pb 

26.8 m 

210Pb 

22.2 y 

206Pb 

stable 

211Pb 

36.1 m 

207Pb 

stable 

Tl 

210Tl 

1.30 m 

206Tl 

4.20 m 

207Tl 

4.77 m 

= alpha decay; = beta decay; half-life (d = days; h = hours; m = minutes; s = seconds; y = years) 

Sources: Aieta et al. 1987; Argonne National Laboratory 2005; half-life data from NNDC 2011
 

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URANIUM 260 

4. CHEMICAL AND PHYSICAL INFORMATION 

Uranium can exist in five oxidation states: +2, +3, +4, +5, and +6 (Lide 2008); however, only the +4 and 

+6 states are stable enough to be of practical importance. Tetravalent uranium is reasonably stable and 

forms hydroxides, hydrated fluorides, and phosphates of low solubility. Hexavalent uranium is the most 

stable state, and the most commonly occurring state is U3O8, although there are a few localized storage 

locations for anthropogenic uranium hexafluoride (UF6) in the United States (DOE 2011a). Major 

compounds of uranium include oxides, fluorides, carbides, nitrates, chlorides, acetates, and others. One 

of the characteristics of UO2

+2 ions is their ability to fluoresce under ultraviolet light. 

Although the element uranium was discovered in 1789 by Klaproth, who named it “uranium” after the 

newly discovered planet Uranus, it was not until 1896 that Becquerel discovered that uranium is 

radioactive. There are 22 known isotopes of uranium, only 3 of which occur naturally (NNDC 2011). 

These three isotopes, 234U, 235U, and 238U, have relative mass abundances within the earth=s undisturbed 

crustal rock of 0.005, 0.72, and 99.275%, respectively. One gram of natural uranium having this relative 

isotopic abundance has an activity of 0.67 μCi. Of this 0.67 μCi, 48.9% of the activity is attributable to 

234U, 2.27% of the activity is attributable to 235U, and 48.7% of the activity is attributable to 238U (Agency 

for Toxic Substances and Disease Registry 2011). This ratio is for undisturbed crustal rock only. 

Although the relative mass abundance of 234U is only 0.005%, it accounts for approximately one-half of 

the total activity. The relative isotopic abundances given above can be altered to some extent by natural 

processes that are not fully understood, but which can cause different ratios in air, water, and soil as 

demonstrated in EPA reports (EPA 1994a, 2007a). 

235U is an isotope of particular interest because it is fissile (capable of being fissioned) and, consequently, 

can sustain a nuclear chain reaction in the presence of appropriate energy neutrons. The predominant 

isotope of uranium found in nature, 238U, is not readily fissionable, but a small portion of its 

transformations result in spontaneous fission rather than the typical alpha decay; these neutrons can be 

sufficient to initiate a chain reaction under appropriate concentration, mass, and neutron thermalization 

conditions. Consequently, for uranium to be used as a fuel in nuclear reactors, the ratio of 235U to 238U is 

increased from 0.72 to 2–4% by a process called enrichment. The enrichment process most used in the 

United States is called gaseous diffusion, but other enrichment processes involving thermal, centrifuge, 

and laser methods can be used, and other countries are actively involved in producing enriched uranium. 

Uranium ore is processed to uranium oxide (U3O8) and then fluorinated to UF6; next, a stream of UF6 gas 

containing all three isotopic compounds is passed through a long series of diffusion stages through which 

the 234U and 235U pass more quickly than the 238U. Thus, the front end of the stream has an enhanced 235U 

concentration and is called enriched uranium hexafluoride, while the back end of the stream has a reduced 

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4. CHEMICAL AND PHYSICAL INFORMATION 

235U concentration and is called depleted uranium hexafluoride. The percent enrichment is a measure of 

the mass percentage of 235U in the final product, and the degree of enrichment is determined by the use. 

Enriched UF6 is typically converted to uranium metal or oxide for power reactor fuel or to metal for 

weapons applications. Depleted UF6 is either converted to uranium metal for a variety of civilian and 

military applications or stored for future use. Low enriched uranium (2–4% enriched) is used in civilian 

nuclear power reactors (DOE 2000), while high enriched uranium (>90% enriched) is used in special 

research reactors (most of which have been removed from operation), nuclear submarine reactor cores, 

and nuclear weapons. Depleted uranium metal is used as radiation shielding, missile projectiles, target 

elements in plutonium production reactors, a gyroscope component, and counterweights or stabilizers in 

aircraft. 

Uranium continuously undergoes transformation through the decay process whereby it releases energy to 

ultimately become a stable or nonradioactive element. For the uranium isotopes, this is a complex 

process involving the serial production of a chain of decay products, called progeny, until a final stable 

element is formed. The decay products of the uranium isotopes, which are also radioactive, are shown in 

Table 4-4. 238U is the parent isotope of the uranium series (234U is a decay product of 238U), while 235U is 

the parent isotope of the actinium decay series. All natural uranium isotopes and some of their progeny 

decay by emission of alpha particles; the other members of both series decay by emission of beta particles 

and gamma rays (NNDC 2011). Both the uranium and the actinium decay series have three features in 

common. Each series begins with a long-lived parent, 235U or 238U, each series contains an isotope of the 

noble gas radon, and each series ends with a stable isotope of lead, 207Pb or 206Pb. 

The amount of time required for one-half of the atoms of a radionuclide to transform is called its 

radioactive half-life. The rate of decay, and thus the half-life, for each radionuclide is unique. The halflife of 238U is very long, 4.5x109 years; the half-lives of 235U and 234U are orders of magnitude lower, 

7.0x108 and 2.5x105 years, respectively. Since the activity of a given mass of uranium depends on the 

mass and half-life of each isotope present, the greater the relative abundance of the more rapidly decaying 

234U and 235U, the higher the activity will be. Thus, depleted uranium is less radioactive than natural 

uranium and enriched uranium is more radioactive. 

Uranium is unusual among the elements because it is both a chemical and a radioactive material. The 

hazards associated with uranium are dependent upon uranium’s chemical and physical form, route of 

intake, and level of enrichment. The chemical form of uranium determines its solubility and, thus, 

transportability in body fluids as well as retention in the body and various organs. Uranium’s chemical 

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4. CHEMICAL AND PHYSICAL INFORMATION 

toxicity is the principal health concern, because soluble uranium compounds cause heavy metal damage 

to renal tissue. The radiological hazards of uranium may be a primary concern when inhaled, enriched 

(DOE 2001) and insoluble uranium compounds are retained long-term in the lungs and associated 

lymphatics. 

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5.1 PRODUCTION 

No information is available in the TRI database on facilities that manufacture or process uranium, 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 

1998c). 

Uranium is present in the earth’s crust at approximately 3 ppm (2 pCi/g) (Clark et al. 2006; du Preez 

1989; WNA 2011). Of the more than 100 uranium ores, the primary (brannerite, carnotite, coffinite, 

davidite, pitchblende, thucholite, uraninite) and secondary (tobernite, autunite, tyuyamunite) are the main 

ores of commercial interest. The main ores are described in Table 5-1. The most economically attractive 

uranium ores have uranium concentrations >1,000 ppm (700 pCi/g) (Clayton and Clayton 1981; Weigel 

1983; WNA 2011). In the United States, the major ore deposits are located in Colorado, Utah, Arizona, 

New Mexico, Wyoming, Nebraska, and Texas (EPA 1985a). The steps necessary to produce uranium for 

its various uses include mining, milling, conversion to uranium hexafluoride (UF6), enrichment, reduction 

to metal or oxidation to uranium oxide, and fabrication into the desired shape. The steps for preparing 

commercial reactor grade, submarine reactor grade, or weapons-grade uranium are the same, except the 

last two require a more aggressive enrichment process. Depleted uranium metal is produced by reducing 

the depleted uranium hexafluoride byproduct. Conventional fabrication methods are used to configure the 

uranium for specific uses, such as rectangular solid blocks for helicopter rotor counterbalances and 

parabolic or cylindrical solids for military depleted uranium projectiles. 

Mining. Open-pit mining, in situ leaching, and underground mining are three techniques that have been 

used for mining uranium-containing ores (EPA 1985a; WNA 2011). Uranium is found in all soil and 

rock, but the higher concentrations found in phosphate rock, lignite, and monazite sands are sufficient in 

some areas for commercial extraction (Lide and Frederikse 1994). The choice of mining method is 

influenced by factors such as the size, shape, grade, depth, thickness, disaggregation, and permeability of 

the ore deposits and the proximity to groundwater (Grey 1993; WNA 2011). Historically, open-pit and 

underground mining have been most commonly used mining methods. However, most uranium in the 

United States is currently mined through in situ leaching, which results in little disturbance to the surface 

and generates no tailings or waste rock (Grey 1993; EIA 2010b; WNA 2011). In situ leaching involves 

leaching (or dissolving) uranium from the host rock with liquids without removing the rock from the 

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Table 5-1. Uranium Ores 

Ore Composition Description 

Primary ores 

Uraninite UO2 + UO3 A steel-, velvet-, to brownish-black in color; major ore of 

uranium and radium 

Pitchblende UO2 + UO3 Essentially the same as uraninite 

Brannerite U(TiFe)2O2 A black, brownish, olive greenish ore; primary mineral in 

granite, associated with uraninite 

Coffinite U(SiO4)1-x(OH)4x A black or pale-to-dark brown mineral in sandstone, 

associated with uraninite 

Davidite (CeLa)U(TiFe3+)20(O,OH)38 A black-brownish mineral in granite, associated with 

ilmenite and others 

Thucholite Mixture of petroleum 

hydrocarbons, uraninite, and 

sulfides 

Black mixture, acronym stands for thorium, uranium, 

carbon, and hydrogen 

Carnotite K2O $ 2U2O3 $ V2O5 $ 3 H2O 

(uranium potassium vanadate) 

Bright-, lemon-, or greenish-yellow mineral in sandstone 

assocuated with tyuyamunite and U-V oxides 

Secondary ores 

Autunite Ca (UO2)2 (PO4)2 $ 10 H2O Yellow-to-greenish mineral produced under oxidizing 

conditions and associated with tormernite 

Torbernite Cu (UO2)2 (PO4)2 $ 10 H2O An emerald-, grassy-, to apple-green mineral formed in 

an oxidized zone and associated with uraninite and 

autunite 

Tyuyamunite Ca(UO2)2 (VO4)2 $ 5B8 H2O 

(uranium calcium vanadate) 

A canary-, lemon-, to greenish-yellow mineral associated 

with carnotite 

Sources: Amethyst Galleries 1995; Mindat 2011; MSA 2011; Stockinger 1981; Uranium Institute 1996 

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ground and can only be carried out on unconsolidated sandstone uranium deposits located below the 

water table in a confined aquifer. A leaching solution is introduced into or below the deposit and pumped 

to the surface, where the uranium-pregnant liquor is processed in a conventional mill to precipitate the 

uranium as yellowcake (U3O8 and other oxides) (DOE 1995b; Grey 1993; WNA 2011). 

Milling. Ore mined in an open-pit or underground mine is crushed and leached in a uranium mill. The 

initial step in conventional milling involves crushing, grinding, and wet and/or dry classification of the 

crude ore to produce uniformly sized particles that are similar in size to beach sand (Clark et al. 2006; 

WNA 2011). A slurry generated in the grinding circuit is transferred to a series of tanks for leaching by 

either an alkaline or acid process (Clark et al. 2006; WNA 2011). Generally, leaching is a simple process 

whereby uranyl ions are extracted by a solvent. Uranyl ions are stripped from the extraction solvent and 

precipitated as yellowcake, predominantly U3O8 (Clark et al. 2006; EPA 1995d; WNA 2011). 

Yellowcake is pressed, dried, banded, and shipped for refinement and enrichment. The byproduct of this 

process is the leftover sand, known as tailings (Clark et al. 2006; WNA 2011). Thus, tailings are the 

original sand minus much of the uranium plus residual process chemicals. Tailings are less radioactive 

than the original ore (Uranium metal production in a conversion facility is done postenrichment.) 

Generalized flow charts for the alkaline and acid leaching processes for ore concentration and uranium 

production are shown in Figure 5-1. 

Enrichment. Next, the U3O8 is chemically converted to UF6. The enrichment process increases, or 

enriches, the percentage of the fissionable 235U isotope, as well as 234U. Until recently, the major process 

used for uranium enrichment in the United States has been gaseous diffusion. The mechanism for 

enrichment is based on the fact that a UF6 molecule containing 235U or 234U is lighter and smaller, and has, 

therefore, a slightly higher thermal velocity than a UF6 molecule containing 238U (WNA 2011). As the 

UF6 passes through the series of diffusion stages, the 234UF6 and 235UF6 molecules gradually become more 

concentrated downstream and less concentrated upstream, while the 238UF6 concentrates conversely. The 

lead portion of the stream is collected and recycled to reach the desired enrichment. The tail portion 

containing a reduced 235UF6 content, called depleted UF6, can be stored in the vicinity of the gaseous 

diffusion plant sites (DOE 1994b). There are an estimated 686,500 metric tons of depleted uranium 

currently in storage as UF6 (ANL 2011). A second enrichment technology, gas centrifuge separation, is 

now replacing gas diffusion in the United States and is expected to be the dominant enrichment process in 

coming years (WNA 2011). During gas centrifuge enrichment, UF6 gas is fed into centrifuge cylinders 

containing rotors that are spun at 50,000–70,000 rpm (WNA 2011). The heavier 238UF6 molecules 

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Figure 5-1. Uranium Ore Processing 

Crushing and grinding 

Separate solids 

Leaching 

Open pit mining Underground mining 

Extract and 

concentrate uranium in 

liquor 

Tailing disposal 

Recycle barren liquor 

Precipitate uranium 

Wash solids, separate 

Drying, pressing, and 

heating 

In situ leach mining 

Recycle barren rinsate 

Yellow cake 

Uranium ore concentrate 

Sources: Agency for Toxic Substances and Disease Registry 1997; Uranium Institute1996; WNA 2010 

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concentrate toward the cylinder's outer edge while the lighter 235UF6 molecules concentrate toward the 

center (Clark et al. 2006; WNA 2011). At the same time, a countercurrent circulation flow along the 

length of the rotor creates a vertical separation of the isotopes as well allowing for them to be drawn off at 

separate ends (Clark et al. 2006; WNA 2011). The two major advantages of the gas centrifuge are that it 

is much more efficient in both its energy requirements and its ability to separate the isotopes than gas 

diffusion enrichment (WNA 2011). A third technology, laser separation, is currently under development 

(DOE 1995b; WNA 2011). A fourth technology, thermal separation, is inefficient and no longer used. 

Fuel Fabrication. In most cases, the enriched UF6 is oxidized to uranium dioxide and formed into pellets 

of ceramic uranium dioxide (UO2). The pellets are then stacked and sealed inside metal tubes that are 

mounted into special fuel assemblies ready for use in a nuclear reactor (DOE 1995b; Uranium Institute 

1996; WNA 2011). 

Product Fabrication. Uranium metal has commercial and industrial uses due to its great density and 

strength. It is alloyed with a range of metals to meet other commercial and industrial needs (Clark et al. 

2006). As with steel, uranium can be formed and fashioned by drop forging, dye casting, and machining 

and is often painted to minimize oxidation. Some well-known uses for these products are military armor 

and armor piercing munitions, helicopter rotor blade counterbalances, weights in airplane control 

surfaces, and radiation shields for high radioactivity sources (e.g., industrial radiography) (Parkhurst and 

Guilmette 2009a; WNA 2011). 

Production. Uranium production from 1975 to 2009 is shown in Table 5-2. Peak production of uranium 

occurred in 1980 at 21,852 short tons (1.98x107 kg) and decreased until 1993. This was the same period 

when the planning and construction of new nuclear power plants ceased in the United States. Production 

of U3O8 had decreased to 4,443 short tons (4.03x106 kg) in 1990 and to 1,534 short tons (1.39x106 kg) in 

1993, a 65% reduction (ABMS 1994; EPA 1985a). In 1996, U.S. uranium production was 3,160 short 

tons (2.87x106 kg), an increase of 5% from the 1995 level and the highest level since 1991 (DOE 1996a). 

Underground and open-pit mining have been the two most commonly used methods of mining uranium 

ores. However, by 1994, uranium was produced primarily by in situ leaching methods. A summary of 

U.S. mine production from 1985 through 1996 (see Table 5-3) illustrates the shift from underground and 

open-pit mining to in situ leaching. U.S. uranium production fell to a low of 1,100 short tons in 2003 

before climbing back to just over 2,000 short tons by the end of the decade (EIA 2010b). 

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Table 5-2. Uranium Production in the United States by Uranium Mills and Other
 

Sources
 

Year Short tonsa of U3O8 Kilograms of U3O8 

1975 11,600 1.05x107 

1976 12,747 1.16x107 

1977 14,939 1.35x107 

1978 18,486 1.68x107 

1979 18,736 1.70x107 

1980 21,852 1.97x107 

1981 19,237 1.74x107 

1982 13,434 1.22x107 

1983 1,0579 9.60x106 

1989 6,919 6.28x106 

1990 4,443 4.03x106 

1991 3,976 3.61x106 

1992 2,823 2.56x106 

1993 1,534 1.39x106 

1994 1,676 1.52x106 

1995 3,022 2.74x106 

1996 3,160 2.87x106 

1997 2,820 2.56x106 

1998 2,550 2.13x106 

1999 2,250 2.04x106 

2000 1,550 1.41x106 

2001 1,300 1.18x106 

2002 1,200 1.09x106 

2003 1,100 9.98x105 

2004 1,250 1.13x106 

2005 1,500 1.36x106 

2006 2,350 2.13x106 

2007 2,250 2.04x106 

2008 1,950 1.77x106 

2009 2,050 1.86x106 

a

Short ton = 2,000 lbs = 907 kg. 

Sources: ABMS 1994; DOE 1996a, 1997b, 1999a; EIA 2010b; EPA 1985a 

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

Table 5-3. Uranium Mining Production, 1985–2009a 

Mining Percentage of total 

method 1985 1986 1987 1988 1990 1991 1992 1994 1996 1998 2003 2005 2006 2009 

Underground 52.3 77.8 81.7 56.8 Wb W W 0 W W W W W W 

Open-pit 23.3 W W W 32.0 48.8 W 0 0 0 0 0 0 

In situ No No W W W W W 96.9 93.1 77.8 W 88.0 90.8 W 

leaching data data 

a

Does not include uranium sources such as mine water, mill site cleanup, mill tailings, or well field restoration.

b

Data withheld. 

Sources: DOE 1995, 1996a, 1997b, 1999b; EIA 2010b 

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Leached uranium concentrate was produced in 1996 in Wyoming, Louisiana, Nebraska, New Mexico, and 

Texas. At the end of 1996, two phosphate byproduct plants and five in situ leaching plants were in 

operation. In addition, seven phosphate byproduct and in situ leaching plants were inactive, and seven 

conventional uranium mills were being maintained in stand-by mode (DOE 1997b). During 2010, one 

conventional uranium mill and four uranium in situ leach plants were reported to be in operation in the 

United States (EIA 2010b). 

5.2 IMPORT/EXPORT 

The importation of uranium increased significantly in the 1980s (EPA 1985a). In 1983, 3,960 short tons 

of U3O8 equivalent were imported into the United States (USDOC 1984), which was about 37% of the 

domestic production. In 1987, the amount of U3O8 equivalent imported into the United States was 

5,630 short tons (USDOC 1988). The amounts of uranium and uranium compounds imported into the 

United States during the period 1989–1997 are presented in Table 5-4 (USDOC 1995, 1997). The 

importation of uranium and uranium compounds peaked in 1990 at about 23 million kg (about 1 million 

tons) and has remained approximately the same, with some fluctuation, since that time. Actual uranium 

import values for more recent years have not been located; however, amounts of foreign-origin uranium 

purchased by U.S. suppliers and owners and operators of U.S. Civilian Nuclear Power Reactors are 

available (EIA 2010a). These data (located in Table 5-6) suggest uranium imports have remained steady 

over the previous two decades. Close to 27 million kg of foreign-origin uranium was purchased in 2009. 

The amount of uranium and uranium compounds exported from the United States during 1989–1993 is 

shown in Table 5-5. The total volume of uranium and uranium compounds exported during 1989–1993 

was 2 orders of magnitude lower than the quantities imported during this same time period. Exports in 

1996 were 5.2 million kg. Most of the foreign sales (Canada, France, Germany, Japan, South Korea, 

United Kingdom) occurred after the uranium entered the U.S. market as imports (DOE 1999b). Amounts 

of uranium sold to firms located outside the United States (Table 5-6) suggest exports have remained 

steady since the mid 1990s (EIA 2010a). Approximately 10 million kg of uranium were sold in 2009. 

5.3 USE 

Uranium has been produced for use in the commercial nuclear power industry as low-enriched metal or 

ceramic UO2 fuel pellets; smaller quantities of high-enriched fuel are produced for U.S. Navy ships and 

for weapons manufacture (Clayton and Clayton 1981; EPA 1985b; Peehs et al. 2007; WNA 2011). 

Uranium fuel lasts months to years before refueling is needed, and then only a small fraction of the 

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Table 5-4. Import of Uranium and Compounds (in kg) into the United States 

(1990–1998)a 

Year 

Substance 1990 1991 1992 1993 1994 1995 1996 1997 1998 

U-metal 18,343 9,673 9,008 4,458 1,735 792 1,572 36,359 508 

(depleted) 

U-alloys, 5 2,444 9 25 No data No data 309,681 10 2 

dispersions, 

and ceramic 

materials 

U-oxide 8,459,924 12,630,433 10,043,472 7,925,762 9,713,406 8,992,532 8,880,669 9,259,002 No data 

(natural) 

U-oxide 204,592 200,733 63,875 35,779 14,214 97,976 57,241 158,082 36,121 

(enriched) 

U-oxide 886,853 19,410 608,472 495 0 0 11,253 0 0 

(depleted) 

U-fluoride 9,432,470 8,109,402 5,844,985 10,827,786 9,583,669 11,140,026 10,936,114 12,210,369 12,965,093 

(natural) 

U-fluoride 598,763 874,251 875,831 868,652 1,000,950 934,046 1,024,148 858,807 1,252,438 

(enriched) 

U-fluoride 479,601 4,523 125,466 0 0 58,000 0 0 147,691 

(depleted) 

U- 42,277 191,221 847,425 1,275,137 121,439 86,935 324 446,812 253,211 

compounds 

(not 

otherwise 

stated) 

U- 159,220 28,950 6 6 69,063 0 6,800 29,682 No data 

compounds 

(enriched) 

U- 4,731 294 1,666 107 0 122 245 100 248 

compounds 

(depleted) 

Ores and 2,763,185 1,344,927 0 0 No data No data 0 212,434 0 

concentrates 

Mixture 0 0 0 4,431 No data No data No data No data No data 

(depleted) 

Spent fuel 16,401 5,033 0 115 45 0 23 306 No data 

a

Import data for more recent years were not located. See Table 5-6 for amounts of uranium sold to firms located 

outside the United States in recent years. 

Sources: USDOC 1995, 1997, 1999 

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Table 5-5. Export of Uranium and Compounds (in kg) (1990–1998)a 

Year 

Substance 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 

U-oxide 6,302 318 0 96,748 6,196 690,449 351,169 192,296 250,443 0 

(natural) 

U-oxide 0 0 85 26,596 64 418,873 299,175 323,990 903,810 646,984 

(enriched) 

U-fluoride 85 0 20,175 186,530 4,231 No data No data 0 688,873 53,800 

(natural) 

U-fluoride 15,698 39,262 0 175,445 90,459 No data No data No data No data No data 

(enriched) 

U-compounds 0 9,801 12,596 8,019 0 No data No data No data No data No data 

(not otherwise 

stated) 

U-compounds 28,221 0 6,609 3 0 0 66,893 418,447 10,506 99,456 

(enriched) 

U-compounds 0 90 160 0 0 246,765 379,530 406,079 30,426 41,674 

(depleted) 

U-metal No data No data No data No data No data 270 496 299,117 3,159 0 

U-ores and No data No data No data No data No data 59,461 0 0 0 0 

concentrates 

Alloys, No data No data No data No data No data 74,712 45,424 29,759 152,920 0 

dispersions, 

ceramicsb 

Spent fuel 0 21,576 0 0 0 No data No data No data No data No data 

a

Export data for more recent years were not located. See Table 5-6 for amounts of uranium purchased from firms
 

located outside the United States in recent years. b

Alloys, dispersions (including cermets), ceramic products, and mixtures containing natural uranium compounds,
 

Nesoi (SIC2819).
 

Sources: USDOC 1995, 1999
 

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Table 5-6. Foreign Purchases and Foreign Sales of Uranium (kg U3O8 Equivalent) 

by U.S. Suppliers and Owners and Operators of U.S. Civilian Nuclear Power 

Reactors, 1994–2009 

Year Foreign purchasesa Foreign salesb 

1994 1.66x107 8.03x106 

1995 1.87x107 4.44x106 

1996 2.06x107 5.22x106 

1997 1.95x107 7.71x106 

1998 1.98x107 6.85x106 

1999 2.16x107 3.85x106 

2000 2.04x107 6.17x106 

2001 2.12x107 5.31x106 

2002 2.39x107 6.98x106 

2003 2.40x107 5.99x106 

2004 3.00x107 5.99x106 

2005 2.97x107 9.30x106 

2006 2.94x107 8.48x106 

2007 2.45x107 6.71x106 

2008 2.59x107 7.80x106 

2009 2.67x107 1.07x107 

a

Purchases of foreign origin uranium from a firm located outside the United States. b

Sales of uranium to a firm located outside the United States. 

Sources: EIA 2010a 

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uranium has actually been fissioned, making fuel reprocessing an option used in other countries (WNA 

2011). One pound of completely fissioned uranium produces the same amount of energy as 1,500 tons of 

coal (Lide and Frederikse 1994). Depleted uranium is used in the manufacture of armor-piercing 

ammunition for the military, in inertial guidance devices and gyro compasses, as counterbalances for 

helicopter rotors, as counterweights for aircraft control surfaces, as radiation shielding material, and as 

x-ray targets (EPA 1985b; Parkhurst and Guilmette 2009a; Peehs et al. 2007; USDI 1980; WNA 2011). 

In the past, uranium salts have been used to produce colored ceramics and glasses (Clark et al. 2006). 

Additionally, uranium was used in dental porcelains for many years, but this practice has been 

discontinued (FDA 1976; WNA 2011). According to the USDI (1980), the major uses of depleted 

uranium in 1978 were military ammunition, 71.8%; counterweights, 11.4%; radiation shielding, 13.6%; 

and chemical catalysts, 3.2%, although this ratio may shift to support war efforts. 

5.4 DISPOSAL 

Radioactive waste containing uranium is usually grouped into three categories: uranium mill tailings, 

low-level waste, and, in the case of spent reactor fuel, high-level waste (USNRC 2002, 2007). 

Uranium mill tailings are the residual sand and trace chemicals from the processing of uranium ore. 

About 150 tons of enriched uranium are required per year to fuel a 1,000-megawatt electric nuclear power 

reactor, and about 500 times that amount of ore is required to obtain the uranium. The total accumulation 

of uranium in licensed mill tailings piles in the United States is approximately 200 million tons (EPA 

2011ee; Murray 1994). Tailings from mines and mills that process other metals should also be expected 

to contain elevated concentrations of uranium and its progeny, although this may not be readily 

recognized. 

Disposal methods for processed uranium tailings have been discussed by Bearman (1979). In the late 

1940s, mainly unconfined disposal systems were used. Untreated solid wastes were stored as open piles 

and, in some cases, were spread in urban areas where they were used as fill and as the sand in concrete 

used to build roads, walks, drives, and concrete block, and in brick mortar. As a result of the Animas 

River Survey in the United States, tailing control programs were instituted in 1959 to prevent airborne 

and waterborne dispersal of the wastes. Confined disposal methods were devised to reduce the exposure 

and dispersion of wastes and to reduce seepage of toxic materials into groundwater to the maximum 

extent reasonably achievable. Under the Uranium Mill Tailings Radiation Control Act (UMTRCA) of 

1978, the U.S. Department of Energy (DOE) designated 24 inactive tailings piles for cleanup. These 

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URANIUM 275 

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

24 sites contained a total of about 28 million tons of tailings and covered a total of approximately 

1,000 acres (EPA 1985b). Two of the sites have been withdrawn from the list and others have combined 

tailings piles, reducing the number of sites to 19 (USNRC 2006). According to a report by the USNRC 

(2006), cleanup has been completed at all but two of these locations. 

In 1977, the EPA issued Environmental Radiation Protection Standards to limit the total individual 

radiation dose due to emissions from uranium fuel cycle facilities, including licensed uranium mills. This 

standard specified that the “annual dose equivalent does not exceed 25 millirems (0.25 mSv) to the whole 

body, 75 millirems (0.75 mSv) to the thyroid, and 25 millirems (0.25 mSv) to any other organ of any 

member of the public as the result of exposures of planned discharges of radioactive materials “to the 

general environment” (40 CFR 190). The EPA also established environmental standards for cleanup of 

open lands and buildings contaminated with residual radioactivity from inactive uranium processing sites 

(40 CFR 192). 

Low-level radioactive waste (LLRW), which may contain uranium, is disposed of at DOE facilities and at 

commercial disposal facilities (USNRC 2002, 2007). Since 1963, seven commercial LLRW facilities 

have operated, but only three are currently receiving waste for disposal (USNRC 2007). A 1992 report 

listed the total volume of LLRW buried at six of the sites to be approximately 50 million cubic feet 

(Murray 1994). The current total amount of LLRW stored at the seven LLRW facilities was not located; 

however, the yearly total amount stored at the three operating locations was reported to be 4.01, 4.05, 

2.63, and 2.09 million cubic feet in 2005, 2006, 2007, and 2008, respectively (USNRC 2011). Only a 

small fraction of the LLRW contains uranium. The method of disposal for commercial and DOE LLRW 

has been shallow land burial, in which the waste is disposed of in large trenches and covered. This 

method of disposal relies upon natural features to isolate the waste. Although USNRC regulations for 

LLRW disposal (10 CFR 61) permit shallow land burial, many states have enacted more stringent 

regulations that require artificial containment of the waste in addition to natural containment (Murray 

1994; USNRC 2002, 2007). 

High-level radioactive waste (HLRW) includes spent fuel, which is the uranium fuel rods that have been 

used in a nuclear reactor (USNRC 2007). When the fuel rods are removed from the reactor for refueling, 

they still contain most of the original unfissioned uranium. However, the hazard from the large activity of 

fission products and plutonium that have been produced in the fuel rods overshadows that of uranium. 

Approximately 47,000 metric tons of spent fuel have been removed from U.S. power reactors through 

2002 (EIA 2010d). There is currently no permanent disposal facility for HLRW in the United States; 

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URANIUM 276 

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

these wastes are being stored at commercial nuclear power plants and DOE facilities where they were 

produced (EIA 2010d). The USNRC has issued standards for the disposal of HLRW (10 CFR 60), and 

the DOE is pursuing the establishment of an HLRW facility. Efforts to establish an HLRW facility, 

which began over 2 decades ago, have experienced many delays. 

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6. POTENTIAL FOR HUMAN EXPOSURE 

6.1 OVERVIEW 

Uranium been identified in at least 67 of the 1,699 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 uranium is not known. The frequency of these sites can be seen in Figure 6-1. 

Uranium is a naturally occurring radioactive element that is present in nearly all rocks and soils; it has an 

average concentration in U.S. soils of about 2 pCi/g (3 ppm) (du Preez 1989; NCRP 1984a). Some parts 

of the United States, particularly the western portion, exhibit higher than average uranium levels due to 

natural geological formations. Most uranium ores contain between 0.05 and 0.2% uranium, up to 

1,000 times the levels normally found in soil (Uranium Institute 1996). 

Uranium can undergo oxidation-reduction reactions in the environment or microbial reactions to form 

complexes with organic matter (Premuzie et al. 1995). The only mechanism for decreasing the 

radioactivity of uranium is radioactive decay. Since all three of the naturally occurring uranium isotopes 

have very long half-lives (234U, 2.4x105

; 235U, 7.0x108; and 238U, 4.5x109 years), the rate at which the 

radioactivity diminishes is very slow (Clark et al. 2006; NCRP 1984a; Peehs et al. 2007). Therefore, the 

activity of uranium remains essentially unchanged over periods of thousands of years. 

Uranium may be redistributed in the environment by both anthropogenic and natural processes. The three 

primary industrial processes that cause this redistribution are operations associated with the nuclear fuel 

cycle that include the mining, milling, and processing of uranium ores or uranium end products; the 

production of phosphate fertilizers for which the phosphorus is extracted from phosphate rocks containing 

uranium; and the improper disposal of uranium mine tailings (DOE 1981c; Hart et al. 1986; NCRP 1984a; 

Yang and Edwards 1984; USGS 2008, 2009, 2010c). Essentially no uranium is released from nuclear 

power plants because of the fuel assembly design and the chemical and physical nature of the uranium 

oxide fuel. Examples of uranium redistribution by natural processes include activities and processes that 

move soil and rock, such as resuspension of soils containing uranium through wind and water erosion, 

volcanic eruptions (Kuroda et al. 1984; USGS 2010a, 2010b, 2010c), operation of coal-burning power 

plants (coal containing significant quantities of uranium), and construction of roads and dams. 

Uranium becomes airborne due to direct releases into the air from these processes. Deposition of 

atmospheric uranium may occur by wet (rain, sleet, or snow) or dry (gravitation or wind turbulence) 

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URANIUM 278 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-1. Frequency of NPL Sites with Uranium Contamination 

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6. POTENTIAL FOR HUMAN EXPOSURE 

processes. The rate of uranium deposition is dependent upon such factors as particle size, particle 

density, particle concentration, wind turbulence, and chemical form. Data are lacking on residence times 

of particulate uranium in the atmosphere, although UNSCEAR (1988) assumed that it behaves like 

atmospheric dust, for which meteorological models exist. 

Uranium deposited by wet or dry precipitation will be deposited on land or in surface waters. If land 

deposition occurs, the uranium can be reincorporated into soil, resuspended in the atmosphere (typically 

factors are around 10-6), washed from the land into surface water, incorporated into groundwater, or 

deposited on or adsorbed onto plant roots (little or none enters the plant through leaves or roots). 

Conditions that increase the rate of formation of soluble complexes and decrease the rate of sorption of 

labile uranium in soil and sediment enhance the mobility of uranium. Significant reactions of uranium in 

soil are formation of complexes with anions and ligands (e.g., CO3

-2, OH-1) or humic acid, and reduction 

of U+6 to U+4. Other factors that control the mobility of uranium in soil are the oxidation-reduction 

potential, the pH, and the sorbing characteristics of the sediments and soils (Allard et al. 1979, 1982; 

Brunskill and Wilkinson 1987; Herczeg et al. 1988; Premuzie et al. 1995; USGS 2008). 

Uranium in surface water can disperse over large distances to ponds, rivers, and oceans. The transport 

and dispersion of uranium in surface water and groundwater are affected by adsorption and desorption of 

uranium on aquatic sediments. As with soil, factors that control mobility of uranium in water include 

oxidation-reduction potential, pH, and sorbing characteristics of sediments and the suspended solids in the 

water (Brunskill and Wilkinson 1987; Swanson 1985; USGS 2008). In one study of a stream with low 

concentrations of inorganics, low pH, and high concentrations of dissolved organic matter, the 

concentration of uranium in sediments and suspended solids was several orders of magnitude higher than 

in the surrounding water because the uranium was adsorbed onto the surface of the sediments and 

suspended particles (Brunskill and Wilkinson 1987). 

The levels of uranium in aquatic organisms decline with each successive trophic level because of very 

low assimilation efficiencies in higher trophic animals. Bioconcentration factors measured in fish were 

low (Mahon 1982; Poston 1982; Waite et al. 1988) and were thought to arise from the extraction of 

uranium from the water or simply from the accumulation of uranium on gill surfaces (Ahsanullah and 

Williams 1989). In plants, uptake of uranium may be restricted to the root system and may actually 

represent adsorption to the outer root membrane rather than incorporation into the interior of the root 

system (Sheppard et al. 1983). Most of this uranium may be removed by washing the vegetable surfaces; 

cutting away the outer membrane will essentially result in complete removal. No significant translocation 

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URANIUM 280 

6. POTENTIAL FOR HUMAN EXPOSURE 

of uranium from soil to the aboveground parts of plants has been observed (Van Netten and Morley 

1983). 

The EPA has established a nationwide network called RadNet (formerly ERAMS) for obtaining data 

concerning radionuclides, including natural uranium isotopes, in environmental media. Sampling 

locations for RadNet were selected to provide optimal population coverage (i.e., located near population 

centers). Airborne uranium concentrations and precipitation levels of uranium were quite low, in the 

attocurie/m3 (10-3 nanoBq/m3

) and 0.006–0.098 picocurie/L (0.0002–0.004 Bq/L/m3) ranges, respectively 

(EPA 1994). However, both air and water samples taken near facilities producing uranium ore or 

processing uranium were found to be higher, in the pCi/L range (EPA 1979; Lapham et al. 1989; Laul 

1994; NCRP 1984a; Tracy and Meyerhof 1987). The RadNet reports document 234U to 238U 

concentration ratios in drinking water that deviate from the equilibrium value of unity found in 

undisturbed crustal rock. Theories proposed to account for this natural phenomenon involve water 

contact with soil and permeable rock containing uranium. The 238U atoms transform through 234Th to 

234U, and any process that removes either of these radionuclides from the solid changes the 234U to 238U 

ratio. 238U atoms at the solid-liquid interface that emit decay alpha particles inward may experience a 

kinetic energy recoil sufficient to either tear the 234Th progeny from the solid or fracture the surficial solid 

layer, making the 234Th more accessible for the enhanced dissolution that thorium typically experiences 

relative to uranium in mineral matrices. Either process can enhance the relative 234U content of the liquid. 

Should that liquid stabilize in another location and evaporate, the localized solids could show an enhanced 

234U ratio. 

A large drinking water study was performed in which data from the National Uranium Resource 

Evaluation (NURE) program plus data prepared for the EPA (DOE 1981b; USGS 2006) were compiled 

for a total of over 90,000 water samples. Domestic water supplies were represented by 28,000 samples 

and averaged 1.7 pCi/L (2.5 μg/L) uranium, with a population weighted mean value for finished waters, 

based on 100 measurements, of 0.8 pCi/L (1.2 μg/L). Other studies show the population-weighted 

average concentration of uranium in U.S. community drinking water to range from 0.3 to 2.0 pCi/L (0.4– 

3.0 μg/L) (Ohanian 1989), while concentrations of uranium from selected drinking water supplies 

analyzed by EPA laboratories were generally <1 pCi/L (1.5 μg/L) (EPA 1985j, 1997e, 2005a, 2010). 

The uranium content of food has been studied extensively; human daily intake has been estimated to 

range from 0.6 to 1.0 (0.9–1.5 μg/day) pCi/day of natural uranium. Uranium is adsorbed onto the roots of 

plants; thus, unwashed potatoes, radishes, and other root vegetables that retain their surface membrane are 

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6. POTENTIAL FOR HUMAN EXPOSURE 

a primary source of uranium in the diet. Based on consumption rates, potatoes constitute the highest 

dietary intake of uranium (EPA 1985). One study showed that the concentration of uranium in plant roots 

was proportional to the uranium concentration in the soil (NCRP 1984a), while a second study did not 

support a linear relationship (Mortvedt 1994). 

Estimates of uranium intake for drinking water vary widely, but the mean is approximately 0.8 pCi/L 

uranium. Drinking water intake is in the range of 0.6–1.0 pCi/day (0.9–1.5 μg/day). Uranium intake 

from food and water sources is approximately equal (EPA 1991b). Compared with food and drinking 

water, intake of uranium by the inhalation route is small, with values reported at 0.007 pCi/day 

(0.010 μg/day) (Cothern 1987) and 0.0007 pCi/day (0.0010 μg/day) (UNSCEAR 1988). 

Higher rates of uranium intake have been reported for some populations. The potential for uranium 

intake is greater for individuals who consume foods grown in areas with elevated concentrations of 

uranium in the soil, and for individuals with elevated concentrations of uranium in their drinking water 

(EPA 1985; NCRP 1984a). Workers engaged in the extraction and processing of uranium are 

occupationally exposed to uranium. Industries where uranium exposure are known to have occurred are 

uranium mining and milling, uranium conversion and enrichment, uranium fuel fabrication, and uranium 

weapons production (BEIR IV 1988; Miller 1977; NCRP 1984a; West et al. 1979). Other groups with the 

potential for exposure due to technologically enhanced natural background radioactivity include 

populations involved in producing and using phosphate fertilizers, and individuals living and working 

near fossil fuel plants (Jaworowski and Grzybowska 1977; NCRP 1984a; Tadmor 1986; Weissman et al. 

1983). 

6.2 RELEASES TO THE ENVIRONMENT 

The Toxics Release Inventory (TRI) data should be used with caution because only certain types of 

facilities are required to report (EPA 2005b). This is not an exhaustive list. Manufacturing and 

processing facilities are required to report information to the TRI only if they employ 10 or more full-time 

employees; if their facility is included in Standard Industrial Classification (SIC) Codes 10 (except 1011, 

1081, and 1094), 12 (except 1241), 20–39, 4911 (limited to facilities that combust coal and/or oil for the 

purpose of generating electricity for distribution in commerce), 4931 (limited to facilities that combust 

coal and/or oil for the purpose of generating electricity for distribution in commerce), 4939 (limited to 

facilities that combust coal and/or oil for the purpose of generating electricity for distribution in 

commerce), 4953 (limited to facilities regulated under RCRA Subtitle C, 42 U.S.C. section 6921 et seq.), 

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6. POTENTIAL FOR HUMAN EXPOSURE 

5169, 5171, and 7389 (limited S.C. section 6921 et seq.), 5169, 5171, and 7389 (limited to facilities 

primarily engaged in solvents recovery services on a contract or fee basis); and if their facility produces, 

imports, or processes ≥25,000 pounds of any TRI chemical or otherwise uses >10,000 pounds of a TRI 

chemical in a calendar year (EPA 2005b). 

Throughout this chapter, the units used to express concentration or intake of uranium are the same units 

reported by the authors, and are sometimes followed by converted units obtained using a conversion 

factor based on the information provided about the isotopic mixture. In some cases, values are expressed 

in mass units, while in other cases, values are expressed as activities. In the case of natural uranium with 

a fixed abundance of the three isotopes, conversion from one unit to the other is possible using the 

conversion factor of 1 μg uranium being equivalent to an activity of 0.68 pCi (EPA 1991b). Likewise, 

1 ppm is equivalent to 1 μg/g and, therefore, to 0.68 pCi/g for natural uranium. Other conversion values 

have been used, such as 1 μg of uranium being equivalent to 0.72 pCi (EPA 1985b) and 0.67 pCi (NCRP 

1984a). These different values are largely accounted for by the periodic refinement of values for uranium 

isotopic half-lives and relative percentages in crustal rock. 

6.2.1 Air 

There is no information on releases of uranium to the atmosphere from manufacturing and processing 

facilities because these releases are not required to be reported (EPA 1998c). 

Uranium is introduced into the atmosphere primarily by resuspension of soil, but also by the intentional or 

accidental release of uranium from mining and milling activities, by uranium processing facilities, or by 

burning coal. 

Natural processes that involve the weathering of crustal rock and soil can change the crustal ratio of 

uranium isotopes. In some cases, human activities have also altered the normal crustal distribution of 

naturally occurring radioactive materials, resulting in what has been termed technologically enhanced 

naturally-occurring radioactive material (TNORM) (NCRP 1984a). No new radioactivity is produced by 

the enhancement, but uranium, its isotopes, and its progeny are redistributed in such a way that real 

exposure or the potential for human exposure may increase. A major localized source of enhanced 

natural uranium can result from mining and milling operations (Table 6-1). 

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6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Normalized Uranium Effluent Discharges from Uranium Mining, 

Milling, Conversion, Enrichment, and Fuel Fabrication
 

Uranium-238a Curies per GWy(e)b 

Atmospheric releases 

Mining — 

Milling 1.8x10-2 

Mill tailings 1.9x10-5 

Conversion 2.0x10-3 

Enrichment 9.9x10-4 

Fabrication 2.0x10-5 

Liquid releases 

Conversion 2.2x10-2 

Enrichment 9.9x10-3 

Fabrication 9.9x10-3 

a

In equilibrium with progeny through U-234. b

GWy(e) = gigawatts (109 watts) of electricity generated for 1 year.
 

Source: UNSCEAR 1982 

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URANIUM 284 

6. POTENTIAL FOR HUMAN EXPOSURE 

Uranium ore with concentrations of uranium up to 1,000 times the average concentration normally found 

in soil (NCRP 1984a) is removed from its natural location during open-pit, in-situ leach, or underground 

mining operations. The primary sources of airborne releases from these sources are from the actual 

mining, from ore crushing and grinding, from high-temperature processes such as calcining or sintering, 

and from yellowcake drying and packaging at the mill. Ore stockpiles can also be a source of airborne 

emissions (NCRP 1993). 

Production in the front end of the nuclear fuel cycle (uranium mining and milling) has undergone a 

significant reduction since its peak in the early 1980s (ABMS 1994; EPA 1985a). Mining and milling 

activities represent a source of minimal uranium release. Uranium is mined using in situ leaching 

methods and uranium is recovered as a byproduct of the processing of phosphate ore (DOE 1995). In 

2010, one conventional uranium mill, which recovers uranium from ores mined from the ground, and four 

uranium in situ leach plants were in operation in the United States (EIA 2010). 

As part of the nuclear fuel cycle, uranium conversion (EPA 1980b), uranium enrichment (MMES 1985), 

and fuel fabrication facilities also release small amounts of uranium to the atmosphere (Table 6-1). 

Uranium is converted to uranium hexafluoride (UF6) prior to enrichment. There is the potential for 

release of some UF6 to the atmosphere during the conversion process or from storage of the depleted UF6. 

Upon release to the atmosphere, gaseous UF6 is rapidly hydrolyzed to UO2F2 (particulate) and 

hydrofluoric acid (gas) (Bostick et al. 1985). Uranium is enriched in the United States by the gaseous 

diffusion process, which produces appropriate enrichments for use in both commercial and governmentoperated facilities. A large amount of depleted uranium is the byproduct of the enrichment process; the 

depleted uranium is kept in storage for further potential use (DOE 1994) or used in commercial or 

military applications. In one study, concentrations of uranium in the air near a uranium refinery (crude 

U refined to highly pure UO3) were found to be 200 times higher than background concentrations, which 

are typically low (Tracy and Meyerhof 1987). 

In addition to gaseous diffusion operations, the DOE is involved in other activities that release uranium to 

the atmosphere. These include activities at two national laboratories, sites undergoing remedial actions, 

weapons facilities, facilities classified as waste management operations (active facilities), or 

environmental restoration sites (inactive and surplus facilities). DOE facilities are present in many states 

with operations ranging from small laboratories to large, highly complex processing plants (Figure 6-2). 

Uranium activities may not occur at all DOE facilities. 

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URANIUM 285 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-2. Major DOE Offices, Facilities, and Laboratories 

Operations Offices (O)
 

Oakland, CA
 

Idaho Falls, IH
 

Chicago, IL
 

Las Vegas, NV
 

Albuquerque, NM
 

Savannah, SC
 

Oak Ridge, TN
 

Richland, WA
 

Laboratories/National
 

Laboratories (♦)
	

Lawrence Berkeley National Lab,
 

Berkeley CA 

Lawrence Livermore National Lab, 

Berkeley CA 

Stanford Linear Accelerator Menlo 

Park, CA 

Natl Renewable Energy Lab, 

Golden, CO 

Idaho National Energy & 

Environmental Lab, IH 

Fermi National Accelerator Lab, 

Batavia, IL 

Argonne National Lab, Argonne IL 

Ames Laboratory, Ames, IA 

MIT Bates Lab, Cambridge, MA 

Princeton Plasma Physics Lab, NJ 

Source: DOE 1999b 

Inhalation Toxicology Research 

Institute, Albuquerque, NM 

Los Alamos Nat Lab, Los Alamos, NM 

Sandia Nat Labs, Albuquerque, NM 

Livermore, CA 

Brookhaven Nat Lab, Brookhaven, NY 

Oak Ridge Nat Lab, Oak Ridge, TN 

T Jefferson Natl Accelerator, Newport 

News, VA 

Pacific Northwest Nat Lab, Richland, 

WA 

Special Purpose Offices () 

Energy Technology Eng Center, Los 

Angeles, CA 

Naval Petroleum Reserves 1&2, 

Kern Co., CA 

Naval Oil Shale Reserves 1&3, Rifle, 

CO 

Yucca Mountain Project, NV 

Nat Petroleum Technology Office, 

Tulsa, OK 

Federal Energy Technology Centers, 

Pittsburgh, PA, Morgantown, WV 

Oak Ridge Inst for Science & 

Education, TN 

Naval Oil Shale Reserves 2, Vernal, UT 

Naval Petroleum Reserve 3, 

Casper, WY 

Facilities (+) 

Grand Junction, CO 

Rocky Flats, CO 

Pinellas, FL 

Idaho Falls, IH 

Kansas City Plant Kansas 

City, MO 

Las Vegas, NV 

Waste Isolation Pilot Plant, 

Carlsbad, NM 

Fernald Environmental 

Management 

Project, Cincinnati, OH 

Miamisburg Environmental 

Managemnt Project, OH 

Savannah River, SC 

Oak Ridge Reservation, Oak Ridge, 

TN 

Pantex Plant, Amarillo, TX 

Hanford, WA 

Field Offices (#) 

Rocky Flats, CO 

Golden, CO 

Ohio (four sites in OH, one site 

in New York) 

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URANIUM 286 

6. POTENTIAL FOR HUMAN EXPOSURE 

Another method by which uranium may be introduced into the atmosphere is the natural process of 

erosion and wind activity (USGS 2010b, 2010c). In geographic areas that contain higher levels of 

uranium in the rocks and soil, such as the western United States, additional natural uranium is introduced 

into the air. Wind erosion of tailings at uranium mining and milling activities will also result in the 

resuspension of uranium and uranium progeny (e.g., radium-226 and radon-222) (Bigu et al. 1984; Hans 

et al. 1979; USGS 2010b, 2010c). Approximately 5–10% of the uranium initially present ends up in the 

mill tailing (Uranium Institute 1996). 

Volcanic eruption is another natural phenomenon that may increase the concentration of natural uranium 

in the air (USGS 2010a). After the eruption of Mount St. Helens, increased levels of 238U were observed 

in rainwater at Fayetteville, Arkansas, due to precipitation of 238U from the atmosphere (Essien et al. 

1985; Kuroda et al. 1984). Other studies indicated that long-lived natural radionuclide (232Th, 226Ra, and 

40K) content in the ash was comparable to that of crustal material (Fruchter et al. 1980). 

Uranium releases occur as a result of phosphate mining for production of phosphorous, which is used in 

phosphoric acid and phosphate fertilizers (NCRP 1984a). Phosphate rock from Florida, Texas, and 

southeastern Idaho contains as much as 120 ppm (80 pCi/g) uranium, a concentration sufficiently high to 

be considered as a commercial source of uranium (NCRP 1975). 

Coal also contains variable amounts of uranium and other elements such as sulfur. The amount 

discharged to the atmosphere depends on the concentration in the coal, the amount burned, the method of 

combustion, the plant design, and the efficiency of fly ash recovery. Approximately 90% of the coal mass 

is consumed during combustion. Retained uranium concentrates in the nonvolatile fraction or ash. The 

uranium concentration of the fly ash, which has been quantified by several investigators (Jaworowski and 

Grzybowska 1977; Tadmor 1986; Weissman et al. 1983), has been found to be higher than in the original 

coal (NCRP 1984a), indicating that <90% of the uranium is released to the atmosphere. A 550 MWe 

plant with a coal input of 1.5 million tons/year with a uranium content of approximately 3 tons may 

release 0.06–0.2 Ci (90–300 kg) of 238U and 234U per year (NCRP 1984a), indicating that modern coal 

power plants release more like 10% of the uranium. A nuclear power plant by comparison releases 

essentially no uranium. 

Raw shale oil is also known to contain uranium, and retorting operations may result in the release of 

uranium to the environment. Studies indicate that shale oil processing operations may increase 

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6. POTENTIAL FOR HUMAN EXPOSURE 

atmospheric levels of 238U and 234U by a maximum of 0.04 fCi/m3 over background levels of uranium 

(Gogolak 1985). 

Uranium has been detected in air at 25 of 67 hazardous waste sites where uranium has been identified in 

some environmental component (HazDat 2007). 

Various regulations identified in Chapter 8 are designed to limit human exposure to uranium. Guidance 

documents, such as the American National Standard Institute (ANSI 1999) air sampling standard, are 

available to aid in establishing monitoring programs for assessing discharges from nuclear facilities. 

6.2.2 Water 

There is no information on releases of uranium to the water from manufacturing and processing facilities 

because these releases are not required to be reported (EPA 1998c). 

The redistribution of uranium and uranium progeny to both surface water and groundwater occurs 

primarily from the natural erosion of rock and soil; some redistribution also comes from the mining, 

milling, and, to a lesser extent, conversion portions of the nuclear fuel cycle (Table 6-1). Contamination 

of surface water and groundwater by effluents from uranium mining, milling, and production operations 

has been documented (Brandvold et al. 1981; Eadie and Kaufmann 1977; Hart et al. 1986; Swanson 1985; 

Yang and Edwards 1984). 

Uranium is discharged to surface water and/or groundwater during mining operations. If an open-pit or 

underground mine extends below the water table, groundwater must be removed to permit mining 

operations to continue. This is usually accomplished by pumping and discharging excess water into the 

ground or nearby bodies of water. Since mine water is generally concentrated with uranium, its 

introduction into surface water bodies may produce measurable increases in uranium levels. 

Waste waters from open-pit mines are typically one to two orders of magnitude greater in volume and 

radioactivity content than waters from shaft or underground mines (AEC 1974). A typical open-pit mine 

may discharge a million gallons of water daily, giving releases of approximately 0.5 mCi/day or 

200 mCi/year, these releases consist of less uranium than other elements like radium and radon (AEC 

1974). 

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6. POTENTIAL FOR HUMAN EXPOSURE 

Liquid releases from uranium mills have been implicated in contamination of surface water and nearby 

wells and groundwater (Table 6-1). Contamination of groundwater and surface water can also occur by 

water erosion of tailings piles (Goode and Wilder 1987; Veska and Eaton 1991; Waite et al. 1988). Since 

extraction of uranium ore during the milling process averages 90–95% recovery, the primary 

contaminants from uranium tailings disposal sites are uranium progeny (e.g., radium-226). 

Generation of liquid waste from the uranium conversion process (see Table 6-1) is generally small and is 

handled by placing liquid effluent in lined ponds with sealed bottoms. The pond effluent is chemically 

neutralized to precipitate out uranium and uranium progeny in pond sludge. Water in the ponds is 

permitted to evaporate and sludge is disposed of as waste under controlled conditions (AEC 1974). 

Liquid discharges containing uranium resulting from uranium enrichment and fuel fabrication are 

generally quite small (see Table 6-1). 

In addition to processes of the nuclear fuel cycle, release of uranium has been detected in surface water 

adjacent to a radioactive waste disposal site in Massachusetts (DOE 1981c). 238U measurements indicated 

that surface water located adjacent to the waste disposal site had concentrations of up to 155 pCi/L. 

Additionally, groundwater measurements of 238U and 235U at the disposal site were 4,400 pCi/L and 

2,400 pCi/L, respectively. These values were elevated compared to values obtained in a study performed 

for the EPA (DOE 1981b). For the EPA study, a total of 35,000 surface water samples from across the 

United States were analyzed; the average total uranium concentration was 1.1 pCi/L (range 0.01– 

582 pCi/L). Of these, 28,000 were considered samples of domestic water supplies. In this same study, 

55,000 groundwater samples had a total mean uranium concentration of 3.2 pCi/L (range 0.01– 

635 pCi/L). 

Uranium has been detected in surface water samples at 22 of 67 hazardous waste sites and in groundwater 

samples at 37 of 67 hazardous waste sites where uranium has been identified in some environmental 

component (HazDat 2007). Examples of uranium values in groundwater and surface water include the 

Uravan site (uranium levels ranged from 1,500 to 16,000 pCi/L) and the tailings pond of the United 

Nuclear site (uranium concentrations were as high as 3,900 pCi/L). A break in the tailings pond dam in 

1979 sent 93 million gallons of tailings liquid into the Rio Puerco (EPA 1988b). The distribution of 

Superfund NPL sites is shown in Figure 6-1. 

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6.2.3 Soil 

There is no information on releases of uranium to the soil from manufacturing and processing facilities 

because these releases are not required to be reported (EPA 1998c). 

Uranium is a naturally occurring radionuclide that is present in nearly all rocks and soils (soils being 

derived from erosion of the rocks). The average concentration in U.S. soils is about 2 pCi/g (3 ppm); 

however, much higher levels are found in areas such as the Colorado Plateau and lands supporting current 

and previous phosphate mining in Florida, Texas, and South Carolina. Lower concentrations of uranium 

are found in basic rocks (e.g., basalt, 0.02–0.03 pCi/g), while acidic rocks contain higher uranium 

concentrations (e.g., sedimentary 1.0 pCi/g) (Clayton and Clayton 1981; NCRP 1984a). The uranium 

present in the rocks and soil as a natural constituent represents natural background levels. 

Contamination of the soil can occur either from deposition of uranium originally discharged into the 

atmosphere, or from waste products discharged directly into or on the ground (e.g., water containing 

uranium from either underground or open-pit mines). Examples of industrial activities that may result in 

soil deposition include uranium mining and milling, uranium processing, phosphate mining, heavy metal 

mining, coal use, and inappropriate waste disposal. 

In the process of mining uranium, when the depth of the mine is below the water table (either an open-pit 

or underground mine), the resulting water is pumped from the mine and often discharged directly to the 

ground or into surface water. For uranium milling, uranium in the ore is extracted (currently 90–95%, 

originally >50%) so that wastes from uranium milling contain only low levels of uranium; however, the 

levels of uranium progeny (e.g., radium) remain essentially unchanged. Uncontrolled erosion of these 

wastes from open tailings piles not protected from the weather occurred at a Shiprock, New Mexico, 

uranium mill site, resulting in contamination of the surrounding area (Hans et al. 1979). Uncontrolled 

erosion also occurred in storage areas such as the St. Louis Airport Storage Site in Missouri (Seeley and 

Kelmers 1985). Increased levels of uranium, radium, radon, and other decay products of uranium have 

also been measured around these sites, particularly in the soil. A number of controlled disposal locations 

on government-owned mill sites exist, but the ones identified involved uncontrolled disposal. 

At various facilities that process uranium for defense programs, uranium is released to the atmosphere 

under controlled conditions, resulting in deposition on the soil and surface waters. Monitoring data from 

the area surrounding the Fernald Environmental Management Project (formerly the Fernald Feed 

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6. POTENTIAL FOR HUMAN EXPOSURE 

Materials Production Center) showed that soil contained uranium released from the facility (Stevenson 

and Hardy 1993). 

The uranium content of phosphate rock, a source of phosphorus for fertilizers and phosphoric acid for the 

chemical industry, ranges from several pCi/g to 130 pCi/g (several ~200 μg/g) (Boothe 1977; UNSCEAR 

1977, 1982). During milling, much of the uranium content becomes concentrated in slag byproducts 

(Melville et al. 1981). The slag byproducts are often used for bedrock in the paving of roads, thus 

transferring the uranium-rich slag to the soil (DOE 1986a; Melville et al. 1981). Because of the large 

amounts of phosphate fertilizer produced annually (12–15 million tons), trace amounts of uranium 

progeny remaining in the fertilizer result in the distribution of about 120 Ci (180 metric tons) per year 

over U.S. agricultural lands (Kathren 1984). 

Combustion of coal is a significant source of enhanced natural radioactivity (especially combustion of 

coal from the western United States, which contains significantly more uranium than coal from the 

eastern United States). When coal is burned, some of the radioactivity is released directly to the 

atmosphere, but a significant fraction is retained in the bottom ash. Enhanced concentrations of uranium 

have been found on the ground around coal-fired power plants (UNSCEAR 1982). 

Unauthorized landfill disposal of uranium processing wastes (e.g., Shpack Landfill in Norton, 

Massachusetts, and the Middlesex Municipal Landfill in Middlesex, New Jersey) has resulted in soil 

contamination (DOE 1981c, 1984c). Also, elevated uranium concentrations have been measured in soil 

samples collected at 45 of 67 hazardous waste sites and in sediment samples at 25 of 67 hazardous waste 

sites (HazDat 2007). In several cases, the uranium concentrations in soils were significantly elevated. 

For example, uranium concentrations from the Shpack/ALI site were found to be 16,460 pCi/g 

(24,000 μg/g). At the United States Radium Corporation site (New Jersey), uranium concentrations 

ranged from 90 to 12,000 pCi/g (130–18,000 μg/g); for the Monticello site (Utah), uranium levels were 

reported to range from 1 to 24,000 pCi/g (1.5–36,000 μg/g) (HazDat 2007). 

The use of depleted uranium ammunition during military conflicts and training exercises will result in the 

localized release of depleted uranium to soil at those locations (Carvalho and Oliveira 2010; Oliver et al. 

2007, 2008a, 2008b; Parrish et al. 2008; Radenkovic et al. 2008; Sansone et al. 2001). 

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6.3 ENVIRONMENTAL FATE 

6.3.1 Transport and Partitioning 

The components of an ecosystem can be divided into several major compartments (Figure 6-3) (NCRP 

1984b). None of the environmental compartments exist as separate entities; they have functional 

connections or interchanges between them. Figure 6-3 also shows the transport pathways between the 

released uranium and the environmental compartments as well as the mechanisms that lead to intakes by 

the population. Initial uranium deposition in a compartment, as well as exchanges between compartments 

(mobility), are dependent upon numerous factors such as chemical and physical form of the uranium, 

environmental media, organic material present, oxidation-reduction potential, nature of sorbing materials, 

and size and composition of sorbing particles. 

Natural processes of wind and water erosion, dissolution, precipitation, and volcanic action acting on 

natural uranium in rock and soil redistribute far more uranium in the total environment than the industries 

in the nuclear fuel cycle. However, those industries may release large quantities of uranium in specific 

locations, mainly in the form of solids placed on tailings piles, followed by liquids released to tailings 

ponds and then airborne releases, both directly from the facilities and by wind erosion of the tailings piles. 

Although solid releases represent the largest quantity of uranium redistribution, they remain on the 

facility grounds and are normally inaccessible to the public. It is the airborne (direct and wind erosion on 

tailings piles) and liquid releases (tailings pond runoff and water erosion of tailings) that most likely 

represent the important pathways for public exposure (i.e., inhalation and ingestion) if pathways can be 

completed. 

While entrained in the air, particulate uranium represents an inhalation source for humans, the extent of 

which is dependent upon concentration and particle size. For particulate uranium to be an inhalation 

hazard to humans, the particulates must be in the size range of 1–10 μm (Bigu and Duport 1992; ICRP 

1979). In some cases, the solid tailings have been removed from the site for use as fill or construction 

material, which can lead to external radiation exposures primarily from the uranium progeny. 

Deposition of the atmospheric uranium can occur by dry deposition or wet deposition (Essien et al. 1985). 

Dry deposition results from gravitational settling and impaction on surfaces exposed to turbulent 

atmospheric flow. The rate of dry deposition is dependent upon particle size distribution, chemical form, 

particle density, and degree of air turbulence. Few experimental data on the particle size and residence 

time of uranium and uranium compounds present in ambient atmospheres are available; however, 

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6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-3. Environmental Pathways for Potential Human Health Effects from
 

Uranium
 

Deposition on 

terrestrial surfaces and 

in sediment 

Atmospheric transport Surface water transport Groundwater transport 

Bioaccumulation in 

food products 

Usage rates for 

individuals 

Uptake rates for 

individuals 

(food ingestion) 

(inhalation) (water ingestion)

(uptake by plants and animals) 

(irrigation) 

(erosion directly by 

streams and rivers) 

Source term 

Dose rate factors 

Health effects 

Source: NCRP 1984b 

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uranium particles are expected to behave like other particles for which data are available, which show that 

smaller uranium particles (<5 μm) travel longer distances than larger particles because of their longer 

residence time in the atmosphere due to their low settling velocity. 

The chemical form of the uranium affects the atmospheric residence time. One uranium compound for 

which there are data regarding residence time and particle size is uranium hexafluoride, a soluble 

compound, which will hydrolyze in the atmosphere to particulate UO2F2$nH2O and hydrogen fluoride gas 

(Bostick et al. 1985). In the case of UO2F2, although the particles were small (<2.5 μm), its atmospheric 

residence time was estimated to be only 35 minutes as a result of rapid hydration and agglomeration to 

larger particles that have faster settling velocities (Bostick et al. 1985). 

In wet deposition of airborne contaminants, the uranium is washed from the atmosphere by rain, sleet, 

snow, or other forms of moisture. The rate of wet deposition depends upon particle size and solubility 

(chemical form). 

Uranium thus deposited (dry or wet) will usually reside on land or be deposited on surface waters. If land 

deposition occurs, the uranium can incorporate into the soil or adhere to plant surfaces, be resuspended in 

the atmosphere as a result of wind action, or be washed from the land into surface water and groundwater. 

Resuspension factors are typically quite low (10-6) and protective against significant exposures, but this 

may not apply to windy and arid areas. Resuspension into the air can be an inhalation source even after 

the plume or source has disappeared. 

In addition to the migration of dissolved or suspended uranium due to the movement of water in the 

environment, the transport and dispersion of uranium in surface water and groundwater are affected by 

adsorption and desorption of the uranium on surface water sediments. On the other hand, migration of 

uranium in soil and subsoil and uptake in vegetation are usually quite local involving distances from 

several centimeters to several meters. 

In most waters, sediments act as a sink for uranium and the uranium concentrations in sediments and 

suspended solids are several orders of magnitude higher than in surrounding water (Brunskill and 

Wilkinson 1987; Swanson 1985). Factors that control the mobility of uranium from sediment to the water 

phase are the oxidation-reduction potential, the pH, the characteristics of complexing agents or ligands, 

and the nature of sorbing materials in the water. Inorganic or organic ligands that can form soluble 

complexes with uranium will result in mobilization of the uranium in water. However, the stability of 

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6. POTENTIAL FOR HUMAN EXPOSURE 

such complexes is dependent on the pH. For example, uranium is likely to be in solution as a carbonate 

complex in oxygenated water with high alkalinity (Herczeg et al. 1988); however, in acidic waters 

(pH <6 containing low concentrations of inorganic ions and high concentrations of dissolved organic 

matter), the uranium is in solution as the soluble organic complex (Brunskill and Wilkinson 1987). 

The oxidation-reduction potential of water is important in controlling the mobility of uranium. In anoxic 

waters where the aquatic environment is reductive, U(VI) will be reduced to U(IV) (e.g., changed from a 

soluble compound to an insoluble one). The U(IV) will be deposited into the sediment due to the 

insolubility of the resulting U(IV) salts (Allard et al. 1979; Herczeg et al. 1988). Mobilization and 

deposition of uranium as defined by the oxidation-reduction potential of the water has been observed by 

several investigators (Barnes and Cochran 1993; Shaw et al. 1994). Uranium can also be removed from 

solution by physical adsorption processes, such as adsorption onto oxides of iron or manganese that occur 

as coatings on the particles of soil and sediment (Ames et al. 1982). 

The mobility of uranium in soil and its vertical transport (leaching) to groundwater depend on properties 

of the soil such as pH, oxidation-reduction potential, concentration of complexing anions, porosity of the 

soil, soil particle size, and sorption properties, as well as the amount of water available (Allard et al. 1982; 

Bednar et al. 2007; Crancon et al. 2010; DOE 1992; Schimmack et al. 2007). Retention of uranium by 

the soil may be due to adsorption, chemisorption, ion exchange, or a combination of mechanisms (Allard 

et al. 1982). Any soil property that alters the sorption mechanism will also alter the mobility of uranium 

in the soil. The sorption of uranium in most soils is such that it may not leach readily from soil surface to 

groundwater, particularly in soils containing clay and iron oxide (Sheppard et al. 1987), although other 

geological materials such as silica, shale, and granite have poor sorption characteristics (DOE 1992; Erdal 

et al. 1979; Silva et al. 1979; Ticknor 1994). 

Sorption in most soils attains a maximum when the neutral hydroxy complex of uranium is at a 

maximum. However, at pH 6 and above, and in the presence of high carbonate or hydroxide 

concentrations, uranium may form anionic complexes such as [UO2(OH)4]

-2 . The mobility of anionic 

uranium complexes in soil is dependent upon the nature of the soil. For example, the decrease in sorption 

in soil with little anion-exchange capacity may result in increased mobility; however, increased sorption 

in soil with high anion-exchange may result in decreased mobility (Allard et al. 1982; Ames et al. 1982; 

Brookins et al. 1993; Ho and Doern 1985; Hsi and Langmuir 1985; Ticknor 1994). 

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Other factors also affect the mobility of uranium in soil. A field study performed near an active carbonate 

leach uranium mill showed that uranium in an alkali matrix can migrate to the groundwater (Dreesen et al. 

1982). Uranium mobility may also be increased due to the formation of soluble complexes with chelating 

agents produced by microorganisms in the soil (Premuzie et al. 1995). 

Uranium may be transported to vegetation by air or by water. It can be deposited on the plants 

themselves by direct deposition or resuspension, or it can adhere to the outer membrane of the plant’s root 

system with potential limited absorption. Similarly, uranium deposited on aquatic plants or water may be 

adsorbed or taken up from the water. The plants, aquatic or terrestrial, may be eaten directly by humans 

or consumed by land or aquatic animals, which provide food for humans. The uptake or bioconcentration 

of uranium by plants or animals is the mechanism by which uranium in soil, air, and water enters into the 

food chain of humans. 

Numerous factors influence the bioaccumulation of uranium, such as the chemical and physical form of 

the uranium; the season of the year and other climatic factors such as temperature, age of the organism, 

specific tissue or organs involved; and the specific characteristics of the local ecosystem, such as total 

suspended and dissolved solids. Bioconcentration factors for uranium have been measured by several 

investigators in various aquatic organisms. Mahon (1982) measured bioconcentration factors of 

1,576 and 459 in algae and plankton, respectively. Horikoshi et al. (1981) determined bioconcentration 

factors in several species of bacteria that ranged from 2,794 to 354,000. However, bioconcentration by 

the bacteria represented adsorption onto the cell surfaces of the bacteria rather than true biological uptake. 

Low bioconcentration factors for uranium were observed in fish. The highest bioconcentration factors 

observed in fillet of rainbow trout (Salmo gairdneri), white and finescale suckers (Castastomus 

catactomus), and lake whitefish (Coregonus clupeaformis) did not exceed a value of 38 (Mahon 1982; 

Poston 1982; Swanson 1983, 1985). Ahsanullah and Williams (1989) concluded that the primary source 

of uranium for crab (Pachygrapsus laevimanus) and zebra winkle (Austrocochlea constricta) was from 

water since both fed and starved animals took up uranium at the same rate. 

Uranium is transported poorly from soils to plants (Dreesen et al. 1982; Moffett and Tellier 1977). As 

with aquatic organisms, the uptake of uranium by plants is dependent on the nature of the soils (soil 

texture and organic content), the pH, and the concentration of uranium in the soil. Greater plant uptake is 

expected to occur in soils that contain higher levels of available uranium (i.e., less sorption of uranium to 

soil particles or formation of soluble uranium complexes). Swiss chard grown in sandy soils contained 

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80 times the levels of uranium found in Swiss chard grown in peat soil (Sheppard et al. 1983). The 

uptake of uranium by native plants, expressed as plant/soil concentration ratio (CR), grown near a mining 

and milling complex was 0.8 compared to a CR of 0.09 for plants grown in soil with background levels of 

uranium (Ibrahim and Wicker 1988). The effect of soil and plant type on CR values has been reviewed 

by Mortvedt (1994). 

Reported CR values for plant/soil interaction vary widely (range, 0.0025–0.81) (Garten 1978; Ibrahim and 

Wicker 1988; Mortvedt 1994). Although some studies indicate that CR values in plants do not vary 

linearly with the concentration of uranium in the soil (Mortvedt 1994), other reported studies show a 

linear relationship between plant content and soil content of uranium (NCRP 1984a). It has been 

postulated that uranium uptake by plants may be limited to the outer membrane of the root system and 

may not occur on the interior of the root at all (Van Netten and Morley 1983; Sheppard et al. 1983). 

However, other investigators have reported the transfer of uranium from soil to the stems and leaves of 

plants in which the CR decreased in the following order: fruit < leaf < root (Morishima et al. 1977). 

Because of the higher root sorption of uranium, it has been postulated that consumption of radishes and 

other root vegetables grown in uranium-containing soils may be a source of human exposure (Van Netten 

and Morley 1983). Thorough cleansing of the plant exterior, especially if performed in conjunction with 

removal of the outer membrane, may remove most or all of the uranium. 

6.3.2 Transformation and Degradation 

6.3.2.1 Air 

The presence of uranium and uranium compounds in the atmosphere results from activities associated 

with uranium mining, milling, processing, and use. There is limited information available regarding the 

abiotic transformation and degradation of uranium and uranium compounds, except for uranium 

hexafluoride. Uranium hexafluoride immediately hydrolyzes on contact with moisture in the air to form 

uranyl fluoride (UO2F2) and hydrofluoric acid (HF). Uranyl fluoride is hygroscopic and will absorb 

moisture from the air, resulting in an increased settling velocity associated with the larger particle size. 

The half-life of a release of airborne UF6 is about 35 minutes (Bostick et al. 1985). Uranyl fluoride is a 

stable oxohalide compound of uranium which is soluble in water, a factor that will increase its mobility in 

the environment once deposition from the air has occurred. 

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6.3.2.2 Water 

The principal abiotic processes that transform uranium in water are formation of complexes and 

oxidation-reduction reactions that have been described in Section 6.3.1. In seawater at pH 8.2, it was 

shown that U(IV) exists as 100% neutral hydroxo complexes, and UO2

+2 and U(VI) exist as 

100% carbonato complexes. In freshwater at pH 6, U(IV) was shown to exist as 100% hydroxo 

complexes, and UO2

+2 existed as 12% hydrated complexes, 18% hydroxo complexes, 8% fluoro 

complexes, and 60% carbonato complexes. In freshwater at pH 9, U(IV) exists as 100% hydroxo 

complexes, but UO2

+2 exists as 100% carbonato complexes (Boniforti 1987). 

Oxidation-reduction conditions are important in the geologic transport and deposition of uranium. 

Oxidized forms of uranium (U[VI]) are relatively soluble and can be leached from the rocks to migrate in 

the environment. When strong reducing conditions are encountered (e.g., presence of carbonaceous 

materials or H2S), precipitation of the soluble uranium will occur. 

6.3.2.3 Sediment and Soil 

The primary abiotic and biological processes that transform uranium in soil are oxidation-reduction 

reactions that convert U(VI) (soluble) to U(IV) (insoluble). Reduction of U(VI) to U(IV) can occur as a 

result of microbial action under anaerobic soil or sediment conditions, thereby reducing the mobility of 

uranium in its matrix (Barnes and Cochran 1993; Francis et al. 1989; Gavrilescu et al. 2009). Further 

abiotic and biological processes that can transform uranium in the environment are the reactions that form 

complexes with inorganic and organic ligands (see Section 6.3.1). 

Certain microorganisms (e.g., Thiobacillus ferrooxidans) can facilitate the oxidation of Fe+2 to Fe+3. The 

Fe+3 ion, in turn, can convert insoluble uranium dioxide to soluble UO2

+2 ions by the following reaction: 

2Fe+3 + UO2  UO2

+2 + 2Fe+2 

This reaction enhances the mobility of uranium in soil from mining and milling wastes (Barnes and 

Cochran 1993; de Siloniz et al. 1991; Scharer and Ibbotson 1982). Uranium may be removed from the 

pore water of sediments under sulfate reduction conditions; microbes may control this process indirectly 

(Barnes and Cochran 1993). 

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Handley-Sidhu et al. (2009) observed the oxidation of UO2 from depleted uranium penetrator surfaces in 

waterlogged soils resulting in the formation of mobile U(VI) species. 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

Reliable evaluation of the potential for human exposure to uranium depends in part on the reliability of 

supporting analytical data from environmental samples and biological specimens. Concentrations of 

uranium 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 uranium 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 uranium in 

a variety of environmental media are detailed in Chapter 7. 

In 1973, the EPA established the nationwide network RadNet (formerly called ERAMS) for obtaining 

data in environmental samples. RadNet consists of a network of sampling stations that provide air, 

surface and drinking water, and milk samples that the EPA uses to obtain environmental concentrations of 

radioactive material. The objective of this system is to identify trends in the accumulation of long-lived 

radionuclides in the environment (EPA 2007b, 2010j). Sampling locations for RadNet are located near 

primary population centers to provide optimal population coverage. 

The ratio of 234U to 238U would be expected to be unity as long as the uranium stays locked inside 

undisturbed crustal rock in secular equilibrium with its progeny, but measurements show that the ratio is 

typically different than unity (EPA 1997e, 2007b). This disequilibrium occurs when the rock is disturbed 

by chemical or physical changes involving water. In the environment, a portion of the 234U separates 

from the 238U by what is theorized to be a physical process (alpha recoil ejection of the 232Th decay 

product from surfaces of soil particles) or a combination of physical and chemical processes (a 238U 

transformation at the soil particle surface fractures the surface allowing access for water to dissolve the 

more soluble 234Th product) (NCRP 1984a). These processes can change the uranium isotope ratios in 

air, soil, and water. 

6.4.1 Air 

For airborne particles collected for the RadNet program, 234U, 235U, and 238U analyses are performed on 

semiannually composited air filters collected from continuously operating airborne particulate samplers. 

Following chemical separation, the uranium is quantified by α-spectroscopy. 

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Table 6-2 shows the results of monitoring for uranium in airborne particles for the October to December 

2007 composites as published in Report 132 (EPA 2007b). Results from October through December 

1997 are included as well (EPA 1997e). The locations of air samples with the highest total uranium 

concentrations were Las Vegas, Nevada; El Paso, Texas; Ross, Ohio; Lynchburg, Virginia; and Phoenix, 

Arizona (listed in descending concentrations of airborne total uranium). In all cases, atmospheric levels 

of total uranium were low, in the attocurie/m3 range. The airborne data show 234U to 238U ratios that range 

from 1.0 to 7.4, many of which are significantly different from the one-to-one ratio found in crustal rock. 

Uranium in airborne dust appears to result from resuspension of soil and, consequently, airborne dust has 

the same uranium concentration as the soil particles that produce it. Airborne dust near uranium mining 

or milling operations would be expected to contain higher than background levels of total uranium and 

have an isotope ratio the same as crustal rock as long as the surface material from which it originated had 

not experienced significant weathering by moisture. Some examples of airborne uranium levels near 

mining and milling operations when the industry was actively producing uranium ore are included below 

for comparison with EPA values in Table 6-2. The annual average concentration of uranium in ambient 

air taken near the Jackpile Open Pit mine (New Mexico) was 2.4 fCi/m3 (EPA 1979), and the 

concentration of uranium in air measured near a Canadian refinery ranged between 1.3 and 134 fCi/m3 

(2–200 ng/m3

) with a geometric mean of 13 fCi/m3 (20 ng/m3) (Tracy and Meyerhof 1987). Air samples 

taken near a uranium mill tailings pile showed a uranium concentration of 1 pCi/m3 (NCRP 1984a). Near 

the Paducah Gaseous Diffusion Plant in Kentucky, where uranium enrichment is performed, the 

maximum total air alpha activity in 1979 at one location was 0.7 pCi/m3 (DOE 1981a). 

6.4.2 Water 

Until the early 1980s, uranium in drinking water was not often measured except when contamination was 

suspected. Welford and Baird (1967) found a concentration of 0.02 pCi/L in New York City tap water. 

UNSCEAR (1977) reported that tap water usually contains <0.03 pCi/L. 

A large study was performed in which data from the NURE program plus data prepared for the EPA 

(DOE 1981b) were compiled. Over 90,000 water samples were analyzed for uranium. The total data 

included approximately 35,000 surface water samples that averaged 1.1 pCi/L and approximately 

55,000 groundwater samples that averaged 3.2 pCi/L (NCRP 1984a). The population-weighted average 

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Table 6-2. Uranium in Airborne Particles (Composites) 

aCi/m3 

January–December 1997 January–December 2007 

Location 234U 235U 238U 234U 235U 238U 

Fairbanks, Alaska 13.3 1.79 11.6 — — — 

Birmingham, Alabama — — — 44 2.3 29.4 

Montgomery, Alabama 19.7 2.5 15.7 13.8 1.3 6.8 

Little Rock, Arkansas 22.9 1.6 21.6 93 7.4 88 

Phoenix, Arizona 66 6.3 50 64 0.7 42 

Berkeley, California 8.7 0.64 6.3 — — — 

Los Angeles, California 26.8 2.4 20.5 39 1.7 26 

Richmond, California — — — 9.6 1 4.1 

San Diego, California — — — 21.8 3 26.1 

San Francisco, California — — — 9.6 1.7 6.9 

Denver, Colorado 35.6 3.7 31.9 18.2 3.7 16.4 

Hartford, Connecticut 14 1.9 12.3 15.6 0.5 10.7 

Washington, District of Columbia 13.1 0 9.9 

Wilmington, Delaware 14.7 2.7 12.8 16.9 1.9 13.8 

Jacksonville, Florida 10.5 0.56 9.7 14.5 0.8 9.6 

Miami, Florida 10.1 0.78 9.2 21 0.9 17.4 

Orlando, Florida — — — 11.8 2.5 8.6 

Atlanta, Georgia — — — 26.3 3.1 18.4 

Honolulu, Hawaii 3.01 0.47 2.33 — — — 

Des Moines, Iowa — — — 16 1.9 16 

Iowa City, Iowa 19.1 2.5 14.9 18.6 2.6 16.1 

Boise, Idaho 22.6 0.94 19.7 — — — 

Idaho Falls, Idaho 16.8 1.4 19.6 — — — 

Chicago, Illinois — — — 43 7.2 38 

Indianapolis, Indiana 26.8 2.5 22.8 29.5 2.5 28.1 

Kansas City, Kansas — — — 26.7 2.4 27.4 

Topeka, Kansas 17.1 2.5 15.6 20.8 2.7 17 

Boston, Massachusetts — — — 8.8 0.37 5.9 

Baltimore, Maryland — — — 14.4 0.19 8.9 

Augusta, Maine 25 2.8 22.1 — — — 

Detroit, Michigan — — — 16.7 2 19.7 

Lansing, Michigan 14.7 1.25 13 12.5 0.92 11.3 

Minneapolis, Minnesota 9.3 1.04 6.6 

St. Paul, Minnesota — — — 12.7 1.1 13.2 

Welch, Minnesota 14.5 1.75 15.5 — — — 

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Table 6-2. Uranium in Airborne Particles (Composites) 

aCi/m3 

January–December 1997 January–December 2007 

234U 235U 238U 234U 235U 238 Location U

Welch, Minnesota 4.25 0.24 4.22 — — — 

St. Louis, Missouri — — — 10 0.75 11.3 

Jackson, Mississippi 17.9 2.9 17.1 14.5 -0.15 11.9 

Charlotte, North Carolina 22.9 1.6 21.3 20.9 1.8 20.5 

Wilmington, North Carolina 23.1 1.2 20.6 12 0 13.3 

Bismarck, North Dakota 17.1 1.7 15.9 23.3 2.3 21.4 

Concord, New Hampshire 9.9 1.29 9.6 10.2 1.1 9.2 

Edison, New Jersey — — — 10.7 0.53 9.0 

Trenton, New Jersey 19.3 1.1 16 15.5 1.7 12.3 

Santa Fe, New Mexico 35.2 2.2 31.5 19.4 0.67 18.7 

Las Vegas, Nevada 44.4 2.9 32.8 55 4.4 36.1 

Albany, New York — — — 11.3 1.2 10 

Lockport, New York — — — 4 0.69 5.7 

New York City, New York 13.1 0.47 14.5 18.5 1.8 21.4 

Syracuse, New York 10.1 1.01 10.3 — — — 

Yaphank, New York 6.9 0.41 5.7 7.9 0.16 3.7 

Cincinnati, Ohio — — — 11.5 0.54 9.2 

Cleveland, Ohio — — — 24.0 0.83 22.7 

Columbus, Ohio 20.7 1.86 17.2 19.7 1.9 20.6 

Painesville, Ohio 11.2 0.9 9.6 13.3 0.37 11.2 

Ross, Ohio 34.4 2.3 30.7 17.8 3.1 18.1 

Oklahoma City, Oklahoma — — — 12.6 0.99 9.0 

Portland, Oregon — — — 9.1 0.4 9.2 

Harrisburg, Pennsylvania 10.7 0.84 11.5 8.1 1.7 10.1 

Pittsburgh, Pennsylvania — — — 18.3 0.9 14.1 

San Juan, Puerto Rico — — — 6.2 0.32 5.6 

Providence, Rhode Island — — — 13.1 1.2 10.1 

Barnwell, South Carolina 13.1 1.29 11.2 7.7 0.4 7.9 

Columbia, South Carolina 33.4 2.5 31.9 32.0 2.7 26.3 

Pierre, South Dakota 14.1 0.96 11.3 19.3 1.2 18.9 

Knoxville, Tennessee 24.1 2.6 17.7 26.9 5.5 20.1 

Memphis, Tennessee — — — 20.7 3.7 21.3 

Nashville, Tennessee 17.2 1.4 16.2 12.6 0.3 11.7 

Oak Ridge/Bethel, Tennessee 11.5 2.14 7.4 12.3 1.1 12.4 

Oak Ridge/K25, Tennessee 19.6 1.34 23.1 25.5 3.0 52.6 

Oak Ridge/Melton, Tennessee 7.6 0.4 7 9.9 0.7 8.3 

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Table 6-2. Uranium in Airborne Particles (Composites) 

aCi/m3 

January–December 1997 January–December 2007 

234U 235U 238U 234U 235U 238 Location U

Oak Ridge/Y12 E, Tennessee 27.5 2.8 17.6 65 6.6 20.1 

Oak Ridge/Y12 W, Tennessee 84.2 5.5 29.8 13.0 1.1 9.1 

Austin, Texas 9.8 0.6 8.6 12.7 0.15 8.6 

Austin/Concordia, Texas — — — 12.2 0.74 12.3 

Dallas, Texas — — — 13.7 1.07 12.7 

El Paso, Texas 57 2.8 48.6 66 4.0 48 

Ft. Worth, Texas — — — 12.2 1.03 13.3 

Houston, Texas — — — 22.4 1.1 22.6 

Salt Lake City, Utah 35.4 1.8 30.1 33.5 2.3 27.2 

Lynchburg, Virginia 86.2 4.1 10.1 47.9 1.3 9.8 

Richmond, Virginia — — — 15.3 0.75 13.6 

Virginia Beach, Virginia — — — 10.9 0.37 10.5 

Olympia, Washington 3.8 0.29 2.29 — — — 

Spokane, Washington 16.6 1.8 13.4 17.8 0.4 18.1 

Madison, Wisconsin 10.7 1.03 11.9 — — — 

Milwaukee, Wisconsin — — — 11.5 0.48 11.5 

aCi = attocurie, 10-18 curie 

Sources: EPA 1986d, 1994a 

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concentration was 0.8 pCi/L, which was higher than the 0.03 pCi/L reported by UNSCEAR (1977). 

Ohanian (1989) reported a population-weighted average concentration of uranium in U.S. community 

drinking water ranging from 0.3 to 2.0 pCi/L. Another study showed that the average uranium 

concentrations in drinking water exceeded 2 pCi/L in South Dakota, Nevada, New Mexico, California, 

Wyoming, Texas, Arizona, and Oklahoma. States in which the average drinking water uranium levels 

exceeded 1 pCi/L are shown in Figure 6-4 (Cothern and Lappenbusch 1983; EPA 1985j). In another 

study based on NURE data, the mean uranium concentration in samples of more than 28,000 domestic 

water supplies was 1.73 pCi/L, with a median concentration range of 0.1–0.2 pCi/L (Cothern and 

Lappenbusch 1983). The level of uranium in 2,228 water supplies was ≥10 pCi/L, while in 979 water 

supplies, the uranium concentrations were ≥20 pCi/L. Most of these water supplies were in small towns 

and served less than a few thousand people (Cothern and Lappenbusch 1983; EPA 1985j). 

The EPA RadNet program reports the uranium content of drinking water samples collected at selected 

U.S. population centers (EPA 1997e, 2005a, 2010j). The data for 234U, 235U, and 238U measured during 

January through December 1997 and during October through December 2005 are presented in Table 6-3. 

The RadNet program collects drinking water samples from 78 population centers across the United States; 

however, analysis of uranium is only performed in samples that show elevated gross alpha radioactivity of 

greater than 2pCi/L (EPA 2010j). Therefore, the levels listed here represent the upper bound of uranium 

concentrations in all drinking water samples collected under the RadNet program. The RadNet data are in 

agreement with the earlier measurements reported above that the average concentration of uranium in 

U.S. drinking water is generally <1 pCi/L. The drinking water samples with the highest total uranium 

concentrations were obtained from Santa Fe, New Mexico; Lincoln, Nebraska; Las Vegas, Nevada; and 

Los Angeles, California (listed in descending concentration of total uranium). 

Older data sets compiled by the EPA RadNet program include measurements of the uranium content of 

precipitation (EPA 1994a, 1996b). Precipitation samples were only collected during the months of March 

through May since these spring rain months usually contain the year’s highest concentrations of uranium 

(EPA 1994a). The data for 234U, 235U, and 238U for 1996 are presented in Table 6-4. In all cases, the 

uranium concentrations were low, confirming that the atmospheric content of airborne uranium is small. 

In some surface waters that have been contaminated by waste discharge and in groundwaters from natural 

uranium-bearing aquifers, the concentrations of uranium may be higher than the average natural 

background levels for that area. For example, higher levels of uranium have been observed in water from 

Ambrosia Lake in New Mexico (uranium milling and mining) (Lapham et al. 1989), the agricultural 

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Figure 6-4. Average Uranium Concentrations in Drinking Water for States Where 

Concentration Exceeds 1 pCi/L 

Source: NCRP 1984b 

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Table 6-3. Uranium in Drinking Water (Composites) 

pCi/L 

January–December 1997 January–December 2006 

Location 234U 235U 238U 234U 235U 238U 

Los Angeles, California 1.78 0.098 1.48 1.48 0.071 1.14 

Tampa, Florida — — — 0.174 0.009 0.134 

Baxley, Georgia 0.144 0.035 0.065 0.086 0.027 0.018 

Idaho Falls, Idaho 0.8 0.027 0.306 — — — 

Morris, Illinois 0.6 0.033 0.03 0.58 0.009 0.078 

W. Chicago, Illinois 1.42 0.04 0.14 0.114 0.002 0.024 

New Orleans, Louisiana — — — 1.05 0.052 0.69 

Augusta, Maine — — — 1.11 0.035 0.93 

Red Wing, Minnesota 0.43 0.028 0.113 — — — 

Port Gibson, Mississippi — — — 0.131 0.010 0.044 

Lincoln, Nebraska 5.11 0.358 3.26 2.96 0.097 1.98 

Santa Fe, New Mexico 6.57 0.285 3.65 6.52 0.123 2.64 

Las Vegas, Nevada 2.76 0.061 1.55 3.12 0.089 1.69 

Jenkinsville, South Carolina 0.596 0.027 0.277 — — — 

Genoa, Wisconsin 0.63 0.115 0.345 — — — 

Madison, Wisconsin 1.25 0.016 0.255 — — — 

Sources: EPA 1986d, 1994a 

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Table 6-4. Uranium Analyses of Select Precipitation Composite Samples March–
 

May 1996
 

pCi/L 

Location 234U 235U 238U 

Montgomery, Alabama 0.0163 0.004 0.0036 

Little Rock, Arkansas 0.0096 0.0044 0.0065 

Berkeley, California 0.0153 0.0038 0.0043 

Denver, Colorado 0.092 0.026 0.044 

Hartford, Connecticut 0.0169 0.0012 0.0045 

Wilmington, Delaware 0.02 0.0025 0.0023 

Jacksonville, Florida 0.008 0.0067 0.0051 

Miami, Florida 0.022 0.0027 0.0086 

Honolulu, Hawaii 0.0156 0.0037 0.0014 

Boise, Idaho 0.0114 0.01 0.0057 

Idaho Falls, Idaho 0.0311 0.0111 0.0065 

Augusta, Maine 0.023 0.0067 0.0086 

Lansing, Michigan 0.0138 0.0016 0.0097 

Minneapolis, Minnesota 0.0202 0.002 0.0132 

Welch, Minnesota 0.047 0.013 0.024 

Jackson, Mississippi 0.0145 0.0134 0.0137 

Charlotte, North Carolina 0.0101 0.0085 0.0151 

Wilmington, North Carolina 0.0218 0.0047 0.0106 

Bismarck, North Dakota 0.079 0.019 0.043 

Lincoln, Nebraska 0.049 0.0129 0.028 

Concord, New Hampshire 0.0195 0.0113 0.024 

Trenton, New Jersey 0.0123 0.0018 0.0044 

Las Vegas, Nevada 0.261 0.018 0.101 

Albany, New York 0.0229 0.0043 0.0094 

Yaphank, New York 0.0141 0.0051 0.0077 

Painesville, Ohio 0.0077 0.0083 0.0035 

Portland, Oregon 0.03 0.0111 0.0129 

Harrisburg, Pennsylvania 0.038 0.0103 0.0098 

Barnwell, South Carolina 0.0153 0.0069 0.0085 

Columbia, South Carolina 0.0126 0.007 0.0039 

Knoxville, Tennessee 0.0111 0.0043 0.0043 

Nashville, Tennessee 0.0074 0.0014 0.0016 

Austin, Texas 0.0119 0.0017 0.0061 

El Paso, Texas 0.043 0.012 0.036 

Salt Lake City, Utah 0.0196 0.0021 0.0102 

Lynchburg, Virginia 0.05 0.0083 0.008 

Olympia, Washington 0.0176 0.0051 0.0052 

Madison, Wisconsin 0.0209 0.0039 0.0065 

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draining and evaporation pond water of the San Joaquin Valley in California (Bradford et al. 1990), 

groundwater from Rocky Flats, Colorado (Laul 1994), and groundwater from the Nambe region of 

northern New Mexico (Hakonson-Hayes et al. 2002). The concentration of uranium in creek waters that 

lead to the Ohio River near the Paducah Gaseous Diffusion Plant in Kentucky ranged from <0.7 to 

470 pCi/L (1–700 μg/L) (DOE 1981a). Mono Lake, a natural alkaline, saline lake in California, 

contained 185 pCi/L 238U and 222 pCi/L 234U during the period 1978–1980 (Simpson et al. 1982). 

Analysis of water from the Colorado River and its tributaries during 1985 and 1986 showed that the levels 

of total uranium ranged from 3.4 to 60 pCi/L (Stewart et al. 1988). 

The U.S. Geological Service measured uranium concentrations above 30 μg/L in 65 out of 350 wells 

(19%) located in the Eastern San Joaquin Valley, California during sampling from 2004 to 2008 (Jurgens 

et al. 2010). Median and maximum concentrations were 18.0 and 2,500 μg/L in 98 observation wells, 

8.7 and 503 μg/L, respectively, in 122 domestic wells, and 1.8 and 41.3 μg/L, respectively, in 121 public 

supply wells. 

Discharge of dewatering effluents from underground uranium mines and runoff from uranium mine 

tailings piles have contaminated surface waters and aquifers in New Mexico with elevated levels of gross 

alpha activity and uranium (NMHED 1989). The concentration of uranium in mine discharge water in 

New Mexico was 31,500 μg/L (equivalent to 22,680 pCi/L, assuming that the uranium content is natural 

uranium) (EPA 1985j). Groundwater from an aquifer adjacent to a uranium mill tailings pile in Falls 

City, Texas, was also found to have concentrations of uranium above natural background levels (DOE 

1994). 

The concentrations of 234U and 238U in groundwater from Cambrian-Ordovician sandstone aquifers in 

Illinois range from <0.1 to 8.0 pCi/L (Gilkeson and Cowart 1987). The ratio of the activity of 234U to 238U 

ranged from 2.0 to >40. The lowest ratios were found in unconfined aquifers in primary recharge zones, 

while ratios >20 were found in the confined zones aquifer. It was suggested that glacial recharge in 

unconfined zones might be responsible for the high 234U to 238U ratios (Gilkeson and Cowart 1987). 

Fifty-five groundwater samples from the Lockatong and Passaic Formation in the Newark Basin in New 

Jersey were analyzed during 1985–1987. These samples were found to contain 0.1–40 pCi/L total 

uranium, with a median value of 2.1 pCi/L (Szabo and Zapecza 1987). Uranium concentrations measured 

in seven samples of groundwater from the Raymond Basin in California ranged from 5.3 to 43.7 pCi/L 

(Wiegand et al. 1987). 

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6. POTENTIAL FOR HUMAN EXPOSURE 

Water in a private well in Maine, thought to be of geologic origin, was reported to contain as much as 

403 μg/L uranium (approximately 270 pCi/L) (Lowry et al. 1987). Uranium concentrations as high as 

1,160 μg/L were measured in drinking water from a home in northwestern Connecticut (Magdo et al. 

2007). The source of the uranium was found to be a 500-foot well carrying groundwater from the 

Brookfield Gneiss geological formation. Hughes et al. (2005) measured elevated uranium concentrations 

ranging from 44.3 to 5,570 μg/L in water from nine private wells located near Simpsonville, South 

Carolina. Elevated levels of uranium measured in waters from private wells in northern and northeastern 

Nebraska were thought to be due to the upward migration of uranium from bedrock and heavy use of 

phosphate fertilizers. Uranium values up to 110 pCi/L were measured (NEDH 1989). The concentrations 

of uranium in U.S. groundwaters were estimated using a conceptual model based on the geochemical and 

hydrological characteristics of aquifers. 

The population-weighted average uranium concentration in groundwaters used as sources of drinking 

water in all 50 states was found to range from 0.05 to 4.6 pCi/L, with a mean value of 0.55 pCi/L 

(Longtin 1988). This mean is lower than the population-weighted uranium value for finished waters of 

0.8 pCi/L (NCRP 1984a). Some methods that may be suitable for reducing the concentration of uranium 

in drinking water include lime softening, coagulation/precipitation, and filtering; however, these methods 

may not efficiently remove the uranium. 

Concentrations of 238U and 234U measured in bottled water samples from 17 locations in Italy were 

generally <120 mBq/kg (Forte et al. 2001). The highest reported concentrations of these isotopes were 

1,936 and 2,842 mBq/kg, respectively. 

Jia et al. (2006) measured concentrations of 0.27–16.2 mBq/L for 238U, 0.41–15.6 mBq/L for 234U, and 

0.012–0.695 mBq/L for 235U in water samples collected in Bosnia and Herzegovina. Two water samples 

were reported to contain depleted uranium. Carvalho and Oliveira (2010) reported mean uranium 

concentrations of 0.5 and 0.4 mg/kg measured in public drinking water supplies from Kosovo and BosniaHerzegovina during 2001. These levels are similar to those reported in other countries and do not reflect 

enhanced presence of uranium resulting from the use of depleted uranium in these areas during the 1999 

military conflict (Carvalho and Oliveira 2010; Sahoo et al. 2007). 

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6. POTENTIAL FOR HUMAN EXPOSURE 

6.4.3 Sediment and Soil 

Table 6-5 shows the average concentrations of uranium in several types of rocks and soils (NCRP 1984a). 

The radioactivity in soils is similar to that in the rocks, usually bedrock, from which it derives. The 

average soil concentration of 234U from Table 6-5 is 0.6 pCi/g. Since the activity of 234U accounts for 

approximately one-half of the total activity in natural uranium (see Chapter 4), the value in Table 6-5 may 

be multiplied by two to obtain the total uranium in soils (approximately 1.2 pCi/g). 

There are wide variations from the values presented in the table, particularly in areas where uranium 

minerals are more concentrated. Concentrations of uranium in Louisiana soils ranged from 2.35 to 

3.98 μg/g (1.6–2.7 pCi/g) (Meriwether et al. 1988), while uranium concentrations in phosphate rock in 

north and central Florida ranged from 4.5 to 83.4 pCi/g (6.8–124 μg/g) (EPA 1985j). 

Soil samples adjacent to Los Alamos, New Mexico, taken during 1974–1977 contained total uranium in 

the range of 0.1–5.1 μg/g (0.067–3.4 pCi/g), with a mean concentration of 1.6 pCi/g (2.4 μg/g) (Purtymun 

et al. 1987). The concentrations of uranium in soils adjacent to the Hanford Fuel Fabrication Facility near 

Richland, Washington, that were collected during 1978–1981 ranged from 0.51 to 3.1 pCi/g (0.76– 

4.6 μg/g), with a median value of 1.2 pCi/g (1.8 μg/g). The control samples for the Hanford Fuel 

Fabrication Study contained uranium at concentrations of 0.21–0.86 pCi/g (0.32–1.128 μg/g), with a 

median value of 0.49 pCi/g (0.73 μg/g) (Price and Kinnison 1982). Uranium in the soil within the 

property boundary of the Paducah Gaseous Diffusion Plant in Kentucky ranged from 3.3 to 4.8 pCi/g 

(4.9–7.1 μg/g), whereas off-site samples taken as far as 12 miles away contained uranium at levels of 3.8– 

6.0 pCi/g (6.4–9.0 μg/g) (DOE 1981a). Soil monitoring data from the area surrounding the Feed Material 

Production Center at Fernald, Ohio, showed that the uranium concentrations within an 8-km2 area were 

between 3 and 23 pCi/g (4.5–34 μg/g) compared to an mean of 2.2 pCi/g (3.3 μg/g) for natural 

background levels (Stevenson and Hardy 1993). Other investigators have detected uranium levels in 

surface soils at the Fernald site as high as 50 times natural background levels (Miller et al. 1994). Moon 

et al. (2006) measured uranium concentrations as high as 300 μg/g at a soil depth of 6 inches at the Oak 

Ridge Reservation in Oak Ridge, Tennessee. The contamination was attributed to past waste disposal 

activities at the site. 

Carvalho and Oliveira (2010) reported mean uranium concentrations of 1.8 and 3 mg/kg measured in soils 

from Kosovo and Bosnia-Herzegovina during 2001. Higher uranium concentrations were localized to 

areas impacted by depleted uranium ammunition (Carvalho and Oliveira 2010; Sansone et al. 2001). 

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URANIUM 310 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-5. Uranium in Rocks and Soils 

Material pCi/g 238Ua 

Igneous rocks 

Basalt (crustal average) 0.2–0.3 

Maficb 0.2–0.3 

Salicb 1.3–1.6 

Granite (crustal average) 1 

Sedimentary rocks 

Shale 1 

Sandstones 

Clean quartz <0.3 

Dirty quartz 1.0c 

Arkose 0.3–0.7c 

Beach sands (unconsolidated) 1 

Carbonate rocks 0.7 

Soils 0.6 

a

To obtain the series equilibrium radioactivity for total alpha, beta, or approximate gamma emission (excluding 

bremsstrahlung and x-rays), multiply by 8, 6, or 3, respectively. b

The median and mean value are given.
 c

Indicates that the values are not well defined.
 

Source: NCRP 1975 

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6. POTENTIAL FOR HUMAN EXPOSURE 

6.4.4 Other Environmental Media 

Concentrations of uranium have been determined in meat and fish (Table 6-6). The uranium content 

measured in tissues of cattle herds grazing in pastures close to the Rocky Flats Plant in Colorado was 

slightly higher than in other cattle, reflecting possible contamination from this source (Smith and Black 

1975). The average concentrations of uranium in game fish (surface feeders) collected from a reservoir at 

locations upstream and downstream from the Los Alamos National Laboratory were 2.9 ng/g dry weight 

(dw) (0.0019 pCi/g) and 4.9 ng/g dw (0.0033 pCi/g), respectively (Fresquez et al. 1994). The 

corresponding values in nongame, bottom-feeding fish were 7.9 ng/g dw (0.0058 pCi/g) and 17.7 ng/g dw 

(0.012 pCi/g), respectively. The concentrations of uranium in fish muscle (dw) from a Canadian lake 

receiving uranium mill effluents were 7–11 times higher than in fish caught in uncontaminated lakes, but 

this uranium may have only been attached to the gills (Swanson 1985). 

The mean uranium concentration in vegetation from Ambrosia Lake, New Mexico (a site of mining and 

milling activities) was measured at 0.3 pCi/g dw compared to 4 fCi/g dw for vegetation from a control 

site (Lapham et al. 1989). Although the concentrations of uranium in muscle from exposed cattle were 

indistinguishable from uranium levels in muscle from control cattle, levels of uranium in liver and kidney 

tissues were 4 times higher in exposed cattle than in control cattle, and levels of uranium in femur 

samples were 13 times higher than in controls, indicating that kidney and liver slightly bioconcentrate 

uranium while muscle does not (Lapham et al. 1989). Thomas et al. (2005) detected uranium 

concentrations >1 μg/g in bone, liver, kidney, muscle, and rumen content samples from 14 out of 

45 Saskatchewan moose and 4 out of 4 Saskatchewan cattle. 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

General population exposure to uranium occurs by ingestion of food and drinking water and by inhalation 

of air. The pathways are shown in Figure 6-3. 

Table 6-6 depicts uranium levels in various types of food in the United States. Measurements of normal 

levels of dietary 234U and 238U indicate that foods consumed contain about 0.3–0.5 pCi/day for each 

uranium isotope (0.6–1.0 pCi/day [0.9–1.5 μg/day] total uranium) (EPA 1985j; Welford and Baird 1967). 

Based on consumption rates, root crops such as potatoes, parsnips, turnips, and sweet potatoes contribute 

approximately 38% of total dietary intake of uranium (EPA 1985j). 

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6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-6. Concentrations of Uranium in Some Foods 

Uranium concentration 

Type of food (ng/g raw weight) Reference 

Whole grain products 1.45 NCRP 1984a 

Potatoes 2.66–2.92; 15B18 EPA 1985j; NCRP 1984a 

Carrots 7.7 EPA 1985j 

Root vegetables 0.94–1.20 NCRP 1984a 

Cabbage 4.7 EPA 1985j 

Meat 0.58–1.32; 20 EPA 1985j; NCRP 1984a 

Poultry 0.14–0.42 NCRP 1984a 

Beef 14 EPA 1985j 

Beef liver 26 EPA 1985j 

Beef kidney 70 EPA 1985j 

Eggs 0.23; 9.6 EPA 1985j; NCRP 1984a 

Dairy products 0.08–0.31 NCRP 1984a 

Cow milk 4 EPA 1985j 

Milk 1–2 EPA 1985j 

Fresh fish 0.43–0.85; 11 EPA 1985j; NCRP 1984a 

Shellfish 9.5–31.0 NCRP 1984a 

Welsh onion 69 EPA 1985j 

Flour 0.25–0.68 NCRP 1984a 

Wheat bread 19 EPA 1985j 

Baked products 1.32–1.5; 12 EPA 1985j; NCRP 1984a 

Polished rice 1.43–6.0; 15 EPA 1985j; NCRP 1984a 

Macaroni 0.4–0.63 NCRP 1984a 

Tea 5 EPA 1985j 

Coffee 6 EPA 1985j 

Parsley 60 EPA 1985j 

Red pepper 5 EPA 1985j 

Mustard 0.2 EPA 1985j 

Table salt 40 EPA 1985j 

Canned vegetables 0.09–0.18 NCRP 1984a 

Fruit juices 0.04–0.12 NCRP 1984a 

Canned fruits 0.18–0.29 NCRP 1984a 

Fresh fruits 0.71–1.29 NCRP 1984a 

Dried beans 1.5–3.67 NCRP 1984a 

Fresh vegetables 0.52–0.92 NCRP 1984a 

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URANIUM 313 

6. POTENTIAL FOR HUMAN EXPOSURE 

Ingestion of food grown in the vicinity of a uranium mill may lead to an intake up to 3 pCi/day uranium 

(Rayno 1983). Other investigators have estimated a dietary intake of 2.86–4.55 mg/day for individuals 

living near a uranium mine (Yamamoto et al. 1971). 

An alternate method for estimating uranium intake is to measure the daily excretion of uranium in urine 

and feces. Using this method in a study of 12 subjects in Utah, it was estimated that the average dietary 

intake for the Salt Lake City population was 4.4±0.6 μg, an intake that is higher than that reported for 

New York City, Chicago, and San Francisco residents (1.3–1.4 μg) (Singh et al. 1990). 

Intakes of uranium in food may also increase when certain ceramic glazed dishes are used for serving or 

storing food (Landa and Councell 1992). Leaching occurs on contact with acidic foods or beverages. 

Experiments show that when a ceramic glazed plate was kept in contact with a 4% acetic acid solution for 

24 hours, the concentration of uranium in the leachate was 31.8 mg/L (Landa and Councell 1992). 

Uranium glazed commercial ceramic dinnerware is no longer made and sold because it was determined 

that the uranium is leachable by acidic foods and beverages (Landa and Councell 1992). Experiments 

show that when a Fiesta tableware plate was kept in contact with 20 mL of 4% acetic acid solution for 

24 hours, the quantity of uranium in the leachate was 600 μg (400 pCi). Other liquids were much less 

effective at leaching uranium, with water giving a value over 3 orders of magnitude lower, and other 

uranium glazed ceramics were much less leachable (Landa and Councell 1992). 

Uranium intakes from food in Japanese diets from two control areas ranged from 0.86 to 1.02 μg/day 

(Yamamoto et al. 1971). Another study reported a mean value of 0.71 μg/day for Japanese males from 

31 prefectures (Shiraishi et al. 1992). Galletti et al. (2003) estimated a total dietary intake of uranium in 

the range of 2.9–4.8 μg/day for the Italian population. Worldwide intake values for uranium have been 

reported at an average of 1 pCi/day (1.5 μg/day) (range 0.6–3.2 pCi/day [0.9–4.8 μg/day]) (Linsalata 

1994). 

Concentrations of uranium from selected drinking water supplies in the United States were analyzed by 

the EPA laboratories and found to be generally <1 pCi/L (EPA 1985j, 1997e, 2005a, 2010). Based on 

data obtained from the NURE program plus data prepared for the EPA (DOE 1981b; USGS 2006), a 

population-weighted average of 0.8 pCi/L uranium was determined. In another study, Ohanian (1989) 

reported population-weighted average concentrations of uranium in U.S. community drinking water 

ranging from 0.3 to 2.0 pCi/L. Considering an individual water intake of approximately 1.7 L/day, and an 

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6. POTENTIAL FOR HUMAN EXPOSURE 

average intake of uranium from drinking water of 0.8 pCi/L as reported in the EPA study, the total intake 

of uranium for an individual from drinking water each day is approximately 1.4 pCi. 

Uranium is also taken into the body by the inhalation route. The average daily intake of uranium from 

inhalation of air has been estimated to range from 0.007 pCi/day (0.010 μg/day) (Cothern 1987) to 

0.0007 pCi/day (0.0010 μg/day) (UNSCEAR 1988). This value may be somewhat higher for persons 

living near sources of uranium emission. Glass makers and potters who use uranium-containing enamels 

may be exposed to small amounts of uranium from handling the powder or from fuming operations in 

glass making (Rossol 1997). In general, however, exposure to uranium from inhalation is small 

compared to exposure from food and drinking water. 

Measurements of concentrations of uranium have been made in human tissues and body fluids resulting 

from consumption of food and water and from natural background sources. Levels of uranium measured 

between 1999 and 2008 in the urine of members of the general U.S. population from the National Health 

and Nutrition Examination Survey (NHANES) are listed in Tables 6-7 and 6-8 (CDC 2011). The ranges 

of geometric mean and 95th percentile values are 0.006–0.008 and 0.026–0.040 μg/g creatinine, 

respectively. 

Two longtime residents of Los Alamos, New Mexico (one a smoker and one nonsmoker) were shown to 

have uranium tissue concentrations for the skeleton (average 5.8 μg/g wet weight) and liver (average 

0.08 μg/kg) in closer agreement with the Reference Man (Kathren 1997; ICRP 1975) than those reported 

in New York City residents (Fisenne and Welford 1986). Values of uranium in whole blood measured in 

New York City residents and Illinois residents averaged 0.14 μg/kg (0.09 pCi/kg) and 0.1 μg/kg 

(0.07 pCi/kg), respectively, compared to a mean value worldwide of 0.58 μg/kg (Fisenne 1988). Mean 

concentrations of uranium were measured in the organs of persons representing all age groups from 

different parts of the United States. The uranium values for lungs, liver, kidney, and bone (vertebrae, rib, 

and skeleton) were 0.5–1.17 μg/kg (0.34–0.78 pCi/kg), 0.12–0.33 μg/kg (0.08–0.22 pCi/kg), 0.39– 

1.00 μg/kg (0.26–0.67 pCi/kg), and 0.25–1.9 μg/kg (0.17–1.3 pCi/kg), respectively (Fisenne and Welford 

1986; Fisenne 1988; Singh et al. 1986b). These differences reflect dietary variations. 

Workers engaged in the extraction and processing of uranium are occupationally exposed to uranium. 

Industries where uranium exposures are known to have occurred are uranium mining and milling, 

uranium conversion and enrichment, uranium fuel fabrication, and nuclear weapons production. 

***DRAFT FOR PUBLIC COMMENT*** 
 


 


 


 
 
 
 
 
 
 
 
 


 
 
 
 
 


 


 


 
 
 
 
 
 
 
 
 


 
 
 
 
 

URANIUM 315 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-7. Geometric Mean and Selected Percentile of Urinary Concentrations of
 

Uranium (μg/g Creatinine) for the U.S. Population from the National Health 

and Nutrition Examination Survey (NHANES)
 

Geometric Selected percentiles (95% confidence interval) 

mean (95% 

Survey confidence Sample 

years interval) 50th 75th 90th 95th size 

Total 99–00 0.007
 (0.006–
 0.007
 (0.006–
 0.013
 (0.010–
 0.024
 (0.019–
 0.034 (0.027–
 

0.009)
 0.009)
 0.016)
 0.030)
 0.053)
 

2,464 

01–02 0.008 (0.007– 

0.010) 

0.007 (0.006– 

0.009) 

0.014 (0.011– 

0.018) 

0.026 (0.020– 

0.034) 

0.040 (0.028– 

0.058) 

2,689 

03–04 0.008 (0.007– 

0.008) 

0.007 (0.006– 

0.008) 

0.012 (0.010– 

0.014) 

0.021 (0.017– 

0.025) 

0.029 (0.023– 

0.039) 

2,557 

05–06 0.006 (0.005– 

0.006) 

0.005 (0.005– 

0.006) 

0.009 (0.008– 

0.010) 

0.017 (0.014– 

0.020) 

0.026 (0.020– 

0.039) 

2,576 

07–08 0.007 (0.006– 

0.009) 

0.006 (0.005– 

0.008) 

0.012 (0.009– 

0.016) 

0.024 (0.016– 

0.037) 

0.038 (0.025– 

0.065) 

2,627 

Age group 

6–11 years 99–00 0.009 (0.007– 

0.012) 

0.008 (0.006– 

0.011) 

0.015 (0.010– 

0.024) 

0.030 (0.016– 

0.044) 

0.037 (0.030– 

0.077) 

340 

01–02 0.010 (0.008– 

0.011) 

0.010 (0.008– 

0.012) 

0.015 (0.013– 

0.019) 

0.027 (0.018– 

0.032) 

0.033 (0.027– 

0.048) 

368 

03–04 0.009 (0.008– 

0.010) 

0.008 (0.007– 

0.010) 

0.013 (0.011– 

0.017) 

0.024 (0.016– 

0.039) 

0.033 (0.022– 

0.050) 

289 

05–06 0.007 (0.006– 

0.008) 

0.006 (0.005– 

0.008) 

0.010 (0.008– 

0.014) 

0.018 (0.013– 

0.035) 

0.034 (0.018– 

0.048) 

355 

07–08 0.009 (0.007– 

0.011) 

0.008 (0.007– 

0.010) 

0.014 (0.010– 

0.022) 

0.026 (0.017– 

0.053) 

0.043 (0.025– 

0.069) 

394 

12–19 years 99–00 0.007 (0.006– 

0.008) 

0.006 (0.005– 

0.008) 

0.010 (0.009– 

0.014) 

0.020 (0.014– 

0.030) 

0.030 (0.019– 

0.074) 

719 

01–02 0.007 (0.006– 

0.008) 

0.007 (0.006– 

0.008) 

0.012 (0.009– 

0.016) 

0.020 (0.015– 

0.026) 

0.026 (0.020– 

0.042) 

762 

03–04 0.007 (0.006– 

0.008) 

0.006 (0.005– 

0.007) 

0.010 (0.008– 

0.013) 

0.019 (0.015– 

0.027) 

0.034 (0.022– 

0.041) 

725 

05–06 0.006 (0.005– 

0.007) 

0.005 (0.005– 

0.006) 

0.009 (0.007– 

0.012) 

0.017 (0.013– 

0.022) 

0.023 (0.019– 

0.026) 

701 

07–08 0.007 (0.006– 

0.009) 

0.006 (0.005– 

0.008) 

0.012 (0.009– 

0.017) 

0.025 (0.013– 

0.050) 

0.034 (0.022– 

0.085) 

376 

≥20 years 99–00 0.007 (0.006– 

0.009) 

0.007 (0.006– 

0.009) 

0.013 (0.010– 

0.016) 

0.024 (0.019– 

0.029) 

0.034 (0.025– 

0.051) 

1,405 

01–02 0.008 (0.007– 

0.010) 

0.007 (0.006– 

0.009) 

0.014 (0.011– 

0.019) 

0.027 (0.020– 

0.039) 

0.043 (0.030– 

0.063) 

1,559 

03–04 a 0.007 (0.006– 

0.008) 

0.012 (0.010– 

0.014) 

0.020 (0.017– 

0.024) 

0.028 (0.022– 

0.038) 

1,543 

05–06 0.006 (0.005– 

0.006) 

0.005 (0.005– 

0.006) 

0.009 (0.008– 

0.010) 

0.016 (0.014– 

0.019) 

0.026 (0.020– 

0.039) 

1,520 

07–08 0.007 (0.006– 

0.008) 

0.006 (0.005– 

0.008) 

0.012 (0.009– 

0.016) 

0.024 (0.016– 

0.036) 

0.037 (0.025– 

0.063) 

1,857 

Gender 

Males 99–00 0.007 (0.006– 

0.009) 

0.006 (0.005– 

0.008) 

0.011 (0.009– 

0.015) 

0.021 (0.017– 

0.028) 

0.035 (0.024– 

0.056) 

1,227 

01–02 0.007 (0.006– 0.007 (0.006– 0.012 (0.010– 0.022 (0.018– 0.033 (0.025– 

0.008) 0.008) 0.015) 0.028) 0.047) 

1,334 

03–04 0.007 (0.006– 

0.008) 

0.006 (0.006– 

0.007) 

0.010 (0.009– 

0.012) 

0.019 (0.015– 

0.024) 

0.026 (0.019– 

0.039) 

1,280 

***DRAFT FOR PUBLIC COMMENT*** 
 


 


 

URANIUM 316 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-7. Geometric Mean and Selected Percentile of Urinary Concentrations of
 

Uranium (μg/g Creatinine) for the U.S. Population from the National Health 

and Nutrition Examination Survey (NHANES)
 

Geometric Selected percentiles (95% confidence interval) 

mean (95% 

Survey confidence Sample 

years interval) 50th 75th 90th 95th size 

05–06 0.005 (0.005– 0.005 (0.004– 0.008 (0.007– 0.014 (0.013– 0.021 (0.016– 

0.005) 0.005) 0.009) 0.016) 0.031) 

1,271 

07–08 0.007 (0.005– 

0.008) 

0.006 (0.005– 

0.007) 

0.012 (0.009– 

0.015) 

0.022 (0.016– 

0.031) 

0.032 (0.024– 

0.056) 

1,327 

Females 99–00 0.008 (0.007– 

0.010) 

0.007 (0.006– 

0.010) 

0.013 (0.010– 

0.017) 

0.025 (0.019– 

0.033) 

0.034 (0.027– 

0.054) 

1,237 

01–02 0.009 (0.008– 

0.011) 

0.009 (0.007– 

0.011) 

0.016 (0.012– 

0.021) 

0.029 (0.021– 

0.042) 

0.045 (0.031– 

0.067) 

1,355 

03–04 a 0.008 (0.007– 

0.009) 

0.013 (0.011– 

0.016) 

0.022 (0.018– 

0.028) 

0.031 (0.025– 

0.041) 

1,277 

05–06 0.006 (0.006– 

0.007) 

0.006 (0.005– 

0.006) 

0.010 (0.009– 

0.011) 

0.019 (0.015– 

0.024) 

0.035 (0.022– 

0.041) 

1,305 

07–08 0.008 (0.006– 0.007 (0.006– 0.013 (0.010– 0.026 (0.017– 0.042 (0.024– 

0.009) 0.008) 0.018) 0.043) 0.085) 

1,300 

Race/ethnicity 

Mexican 

Americans 

99–00 

01–02 

0.015 (0.011– 

0.022) 

0.015 (0.011– 

0.020) 

0.029 (0.016– 

0.058) 

0.059 (0.027– 

0.146) 

0.100 (0.042– 

0.270) 

0.012 (0.010– 

0.016) 

0.012 (0.009– 

0.016) 

0.021 (0.015– 

0.028) 

0.033 (0.024– 

0.053) 

0.050 (0.034– 

0.080) 

883 

682 

03–04 0.013 (0.010– 

0.016) 

0.013 (0.009– 

0.017) 

0.022 (0.016– 

0.029) 

0.035 (0.026– 

0.051) 

0.051 (0.034– 

0.061) 

618 

05–06 0.008 (0.007– 

0.009) 

0.007 (0.006– 

0.008) 

0.013 (0.010– 

0.015) 

0.022 (0.016– 

0.031) 

0.035 (0.025– 

0.060) 

652 

07–08 0.010 (0.008– 

0.012) 

0.009 (0.007– 

0.011) 

0.017 (0.014– 

0.022) 

0.032 (0.020– 

0.053) 

0.047 (0.027– 

0.097) 

515 

Non-Hispanic 

blacks 

99–00 0.006 (0.004– 0.005 (0.004– 0.008 (0.006– 0.017 (0.011– 0.028 (0.018– 

0.007) 0.006) 0.013) 0.029) 0.048) 

568 

01–02 0.005 (0.005– 0.005 (0.005– 0.008 (0.007– 0.013 (0.011– 0.017 (0.014– 

0.006) 0.006) 0.010) 0.014) 0.029) 

667 

03–04 0.006 (0.005– 

0.006) 

0.005 (0.005– 

0.006) 

0.009 (0.008– 

0.009) 

0.013 (0.012– 

0.015) 

0.018 (0.014– 

0.024) 

722 

05–06 0.004 (0.004– 

0.005) 

0.004 (0.003– 

0.005) 

0.006 (0.006– 

0.007) 

0.011 (0.009– 

0.015) 

0.017 (0.012– 

0.021) 

692 

07–08 0.005 (0.005– 

0.006) 

0.005 (0.004– 

0.006) 

0.009 (0.007– 

0.011) 

0.014 (0.011– 

0.017) 

0.018 (0.014– 

0.041) 

589 

Non-Hispanic 

whites 

99–00 0.007 (0.006– 0.007 (0.006– 0.012 (0.010– 0.021 (0.017– 0.030 (0.024– 

0.009) 0.009) 0.015) 0.027) 0.050) 

822 

01–02 0.008 (0.007– 0.007 (0.006– 0.013 (0.011– 0.025 (0.018– 0.034 (0.025– 

0.009) 0.009) 0.016) 0.032) 0.051) 

03–04 a 0.007 (0.006– 0.011 (0.010– 0.019 (0.015– 0.027 (0.020– 

0.008) 0.013) 0.024) 0.040) 

05–06 0.006 (0.005– 0.005 (0.005– 0.009 (0.008– 0.016 (0.013– 0.024 (0.019– 

0.006) 0.006) 0.010) 0.020) 0.039) 

07–08 0.007 (0.006– 0.006 (0.005– 0.012 (0.009– 0.025 (0.015– 0.039 (0.024– 

0.009) 0.008) 0.019) 0.043) 0.078) 

a

Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Source: CDC 2011 

1,132 

1,074 

1,041 

1,095 

***DRAFT FOR PUBLIC COMMENT*** 
 


 


 

URANIUM 317 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-8. Geometric Mean and Selected Percentile of Urinary Concentrations of
 

Uranium (μg/L) for the U.S. Population from the National Health and Nutrition 

Examination Survey (NHANES)
 

Survey Geometric Selected percentiles 

years mean (95% confidence interval) 

(95% 

confidence Sample 

interval) 50th 75th 90th 95th size 

Total 99–00 0.008 (0.007– 

0.009) 

0.007 (0.006– 

0.008) 

0.013 (0.010– 

0.017) 

0.027 (0.021– 

0.038) 

0.046 (0.037– 

0.056) 

2,464 

01–02 0.009 (0.007– 

0.010) 

0.008 (0.007– 

0.009) 

0.014 (0.012– 

0.018) 

0.030 (0.023– 

0.039) 

0.046 (0.034– 

0.062) 

2,690 

03–04 0.008 (0.007– 

0.008) 

0.007 (0.006– 

0.007) 

0.011 (0.010– 

0.013) 

0.021 (0.017– 

0.026) 

0.031 (0.026– 

0.037) 

2,557 

05–06 0.006 (0.005– 

0.006) 

0.005 (0.005– 

0.006) 

0.010 (0.009– 

0.012) 

0.019 (0.016– 

0.022) 

0.033 (0.023– 

0.041) 

2,576 

07–08 0.007 (0.006– 

0.008) 

0.007 (0.005– 

0.008) 

0.013 (0.011– 

0.015) 

0.025 (0.018– 

0.033) 

0.039 (0.026– 

0.056) 

2,627 

Age group 

6–11 years 99–00 0.009 (0.007– 

0.011) 

0.007 (0.006– 

0.009) 

0.013 (0.009– 

0.022) 

0.032 (0.019– 

0.048) 

0.048 (0.033– 

0.066) 

340 

01–02 0.008 (0.007– 

0.010) 

0.008 (0.006– 

0.010) 

0.014 (0.010– 

0.020) 

0.026 (0.020– 

0.036) 

0.040 (0.025– 

0.049) 

368 

03–04 0.008 (0.007– 0.007 (0.006– 0.012 (0.009– 0.020 (0.016– 0.028 (0.020– 

0.009) 0.009) 0.016) 0.026) 0.039) 

289 

05–06 

07–08 

12–19 years 99–00 

01–02 

03–04 

05–06 0.007 (0.006– 

0.008) 

0.007 (0.006– 

0.008) 

0.013 (0.011– 

0.015) 

0.023 (0.018– 

0.032) 

0.034 (0.027– 

0.045) 

701 

07–08 0.009 (0.007– 

0.011) 

0.008 (0.007– 

0.011) 

0.016 (0.014– 

0.020) 

0.029 (0.022– 

0.056) 

0.056 (0.027– 

0.156) 

376 

≥20 years 99–00 0.008 (0.006– 

0.009) 

0.007 (0.005– 

0.008) 

0.013 (0.010– 

0.017) 

0.027 (0.021– 

0.040) 

0.046 (0.036– 

0.056) 

1,405 

0.006 (0.005– 

0.007) 

0.005 (0.004– 

0.007) 

0.010 (0.008– 

0.011) 

0.015 (0.012– 

0.031) 

0.031 (0.013– 

0.051) 

0.007 (0.006– 0.006 (0.005– 0.012 (0.009– 0.021 (0.016– 0.030 (0.022– 

0.008) 0.008) 0.016) 0.030) 0.039) 

0.009 (0.008– 

0.011) 

0.009 (0.008– 

0.010) 

0.015 (0.012– 

0.018) 

0.026 (0.020– 

0.043) 

0.044 (0.028– 

0.072) 

0.010 (0.008– 0.010 (0.008– 0.017 (0.013– 0.030 (0.022– 0.042 (0.027– 

0.012) 0.012) 0.023) 0.042) 0.088) 

0.010 (0.009– 

0.011) 

0.009 (0.008– 

0.010) 

0.015 (0.012– 

0.018) 

0.028 (0.023– 

0.036) 

0.038 (0.036– 

0.053) 

355 

394 

719 

762 

725 

01–02 0.009 (0.007– 

0.010) 

0.008 (0.007– 

0.009) 

0.014 (0.012– 

0.017) 

0.031 (0.022– 

0.040) 

0.046 (0.034– 

0.065) 

1,560 

03–04 a 0.006 (0.005– 

0.007) 

0.011 (0.009– 

0.012) 

0.019 (0.016– 

0.026) 

0.029 (0.024– 

0.038) 

1,543 

05–06 0.006 (0.005– 

0.006) 

0.005 (0.005– 

0.006) 

0.010 (0.008– 

0.012) 

0.019 (0.015– 

0.022) 

0.032 (0.022– 

0.041) 

1,520 

07–08 0.007 (0.005– 

0.008) 

0.006 (0.005– 

0.008) 

0.013 (0.010– 

0.015) 

0.024 (0.018– 

0.035) 

0.039 (0.026– 

0.052) 

1,857 

Gender 

Males 99–00 0.009 (0.008– 0.008 (0.007– 0.015 (0.012– 0.036 (0.024– 0.053 (0.040– 

0.011) 0.010) 0.021) 0.046) 0.067) 

1,227 

01–02 0.009 (0.008– 

0.011) 

0.009 (0.007– 

0.010) 

0.015 (0.013– 

0.021) 

0.033 (0.024– 

0.045) 

0.047 (0.035– 

0.065) 

1,335 

***DRAFT FOR PUBLIC COMMENT*** 

 

URANIUM 318 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-8. Geometric Mean and Selected Percentile of Urinary Concentrations of 

Uranium (μg/L) for the U.S. Population from the National Health and Nutrition 

Examination Survey (NHANES)
 

Survey Geometric Selected percentiles 

years mean (95% confidence interval) 

(95% 

confidence Sample 

interval) 50th 75th 90th 95th size 

03–04 0.008 (0.007– 

0.009) 

0.007 (0.006– 

0.008) 

0.013 (0.011– 

0.016) 

0.023 (0.019– 

0.027) 

0.031 (0.027– 

0.035) 

1,280 

05–06 0.006 (0.006– 

0.007) 

0.006 (0.005– 

0.006) 

0.011 (0.009– 

0.012) 

0.019 (0.015– 

0.022) 

0.030 (0.021– 

0.043) 

1,271 

07–08 0.007 (0.006– 

0.009) 

0.007 (0.006– 

0.009) 

0.014 (0.013– 

0.016) 

0.026 (0.021– 

0.037) 

0.046 (0.030– 

0.056) 

1,327 

Females 99–00 0.007 (0.006– 

0.008) 

0.006 (0.005– 

0.007) 

0.012 (0.009– 

0.015) 

0.023 (0.016– 

0.033) 

0.036 (0.026– 

0.050) 

1,237 

01–02 0.008 (0.007– 

0.010) 

0.008 (0.006– 

0.009) 

0.014 (0.011– 

0.017) 

0.027 (0.019– 

0.037) 

0.041 (0.029– 

0.063) 

1,355 

03–04 a 0.006 (0.005– 

0.007) 

0.010 (0.009– 

0.011) 

0.018 (0.013– 

0.027) 

0.031 (0.022– 

0.039) 

1,277 

05–06 

07–08 0.006 (0.005– 

0.008) 

0.006 (0.005– 

0.007) 

0.011 (0.009– 

0.015) 

0.024 (0.016– 

0.033) 

0.035 (0.023– 

0.060) 

1,300 

Race/ethnicity 

0.005 (0.005– 0.005 (0.004– 0.010 (0.008– 0.019 (0.016– 0.034 (0.025– 

0.006) 0.006) 0.011) 0.023) 0.040) 

1,305 

Mexican Americans 99–00 0.017 (0.012– 0.016 (0.011– 0.033 (0.020– 0.060 (0.040– 0.114 (0.054– 

0.023) 0.021) 0.054) 0.127) 0.279) 

883 

01–02 0.013 (0.010– 

0.016) 

0.012 (0.009– 

0.016) 

0.022 (0.017– 

0.030) 

0.040 (0.031– 

0.054) 

0.055 (0.046– 

0.069) 

683 

03–04 0.014 (0.011– 

0.017) 

0.013 (0.009– 

0.018) 

0.024 (0.017– 

0.034) 

0.041 (0.028– 

0.073) 

0.064 (0.039– 

0.158) 

618 

05–06 0.008 (0.007– 

0.009) 

0.009 (0.007– 

0.010) 

0.014 (0.013– 

0.017) 

0.025 (0.021– 

0.033) 

0.042 (0.028– 

0.051) 

652 

07–08 0.009 (0.008– 

0.011) 

0.009 (0.008– 

0.010) 

0.017 (0.014– 

0.022) 

0.032 (0.026– 

0.040) 

0.048 (0.031– 

0.074) 

515 

Non-Hispanic 

blacks 

99–00 0.009 (0.007– 

0.011) 

0.008 (0.006– 

0.010) 

0.014 (0.010– 

0.020) 

0.028 (0.018– 

0.049) 

0.052 (0.030– 

0.067) 

568 

01–02 0.008 (0.007– 

0.009) 

0.008 (0.007– 

0.009) 

0.012 (0.011– 

0.015) 

0.021 (0.017– 

0.027) 

0.030 (0.023– 

0.037) 

667 

03–04 0.008 (0.008– 

0.009) 

0.007 (0.007– 

0.008) 

0.012 (0.011– 

0.013) 

0.021 (0.017– 

0.027) 

0.031 (0.023– 

0.045) 

722 

05–06 0.006 (0.005– 

0.007) 

0.006 (0.005– 

0.007) 

0.010 (0.009– 

0.011) 

0.016 (0.014– 

0.020) 

0.023 (0.018– 

0.031) 

692 

07–08 0.007 (0.006– 

0.009) 

0.007 (0.006– 

0.008) 

0.013 (0.010– 

0.016) 

0.024 (0.016– 

0.038) 

0.038 (0.025– 

0.055) 

589 

***DRAFT FOR PUBLIC COMMENT*** 
 

 


 

URANIUM 319 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-8. Geometric Mean and Selected Percentile of Urinary Concentrations of 

Uranium (μg/L) for the U.S. Population from the National Health and Nutrition 

Examination Survey (NHANES)
 

Survey Geometric Selected percentiles 

years mean (95% confidence interval) 

(95% 

confidence Sample 

interval) 50th 75th 90th 95th size 

Non-Hispanic 

whites 

99–00 0.007 (0.006– 

0.009) 

0.007 (0.006– 

0.007) 

0.012 (0.009– 

0.016) 

0.023 (0.017– 

0.037) 

0.043 (0.027– 

0.051) 

822 

01–02 0.008 (0.007– 

0.009) 

0.007 (0.006– 

0.009) 

0.013 (0.011– 

0.016) 

0.026 (0.019– 

0.035) 

0.037 (0.029– 

0.050) 

1,132 

03–04 a 0.006 (0.005– 

0.007) 

0.010 (0.009– 

0.012) 

0.018 (0.015– 

0.023) 

0.027 (0.020– 

0.036) 

1,074 

05–06 0.005 (0.005– 

0.006) 

0.005 (0.004– 

0.006) 

0.010 (0.008– 

0.012) 

0.018 (0.014– 

0.022) 

0.033 (0.021– 

0.043) 

1,041 

07–08 0.006 (0.005– 

0.008) 

0.006 (0.005– 

0.008) 

0.013 (0.009– 

0.016) 

0.023 (0.015– 

0.039) 

0.038 (0.022– 

0.086) 

1,095 

a

Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Note: Limit of detection for survey years 99–00, 01–02, 03–04, 05–06, and 07–08 are 0.004, 0.004, 0.005, 0.002, and 0.002, 

respectively 

Source: CDC 2011 

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6. POTENTIAL FOR HUMAN EXPOSURE 

Epidemiologic surveys were initiated in the United States as early as 1950 to study the effects of uranium 

exposure on uranium millers, and similar studies were performed of workers at the Oak Ridge Gaseous 

Diffusion Plant in Oak Ridge, Tennessee, where uranium conversion and enrichment were performed. 

Those studies attributed the health decrement to radon progeny and other toxicants and not directly to the 

uranium (BEIR IV 1988). 

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). 

As for adults in the general population, small exposures occur from normal ingestion of food and drinking 

water and inhaling air. These exposures may be higher in areas with naturally high uranium soil levels or 

near uranium processing sites and hazardous waste sites containing uranium. Levels of uranium 

measured between 1999 and 2008 in the urine of various ages of the U.S. population from NHANES are 

listed in Tables 6-7 and 6-8 (CDC 2011). Concentrations measured in children aged 6–11 and 12–19 

years were similar to those measured in adults aged ≥20 years. 

A study of uranium content in bone from three age groups (<13, 13–20, and 20–25 years old) reported 

somewhat higher uranium content in the youngest compared to the oldest age group (approximately 1.5– 

3-fold); however, there were only 2–4 subjects in each group and the results were not statistically 

significant (Broadway and Strong 1983). No information on uranium levels in amniotic fluid, meconium, 

cord blood, neonatal blood, or breast milk was located. 

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6. POTENTIAL FOR HUMAN EXPOSURE 

At hazardous waste sites, uranium that is found in excess of natural background levels is most likely to be 

in soil and presents a special hazard for young children. Hand-to-mouth activity and eating contaminated 

dirt will result in oral exposure to uranium. The hazard in this case depends on the form of uranium 

present at the waste site. Soluble uranium compounds (e.g., uranyl nitrate) are absorbed by the 

gastrointestinal tract to a much greater degree than insoluble uranium compounds (e.g., insoluble oxides 

of uranium), and a large toxicity database in animals supports the higher toxicity of the soluble forms (see 

Chapter 3). Uranium in soil at non-hazardous waste sites is almost entirely (>99%) in the form of 

insoluble oxides of uranium, which have very low bioavailability. 

As for adults, the potential for uranium exposure is greater for children who consume foods grown in 

areas with elevated concentrations of uranium in the soil and for children with elevated concentrations of 

uranium in their drinking water (EPA 1985; NCRP 1984a). Other home exposures are unlikely since no 

household products or products used in crafts, hobbies, or cottage industries contain significant amounts 

of uranium, except in cases where uranium-bearing rocks are used in and around the home for decorative, 

collection, or construction purposes (Agency for Toxic Substances and Disease Registry 1997). 

No information is available on whether children differ from adults in their weight-adjusted intake of 

uranium. The fractional absorption of uranium (as uranyl nitrate and uranyl citrate) by the oral route was 

higher in neonatal than in adult rats and swine (Sullivan 1980b; Sullivan and Gorham 1982). In a 

mathematical model developed by the ICRP for risk assessment, one of the assumptions is that the 

fractional absorption of ingested uranium is twice as high in children under the age of 1 year compared to 

adults. 

Uranium exposure to children from parents’ work clothes, skin, hair, tools, or other objects from the 

workplace is possible if the parent uses uranium at work. However, in a comprehensive review of 

incidents of home contamination by workers (NIOSH 1997), no cases of uranium contamination were 

described. 

As a radionuclide, uranium is potentially genotoxic and thus, it is important to know if parental exposure 

to uranium could affect the developing fetus or germ cells. However, epidemiological studies of workers 

exposed to uranium show no evidence of genotoxic effects. This is most likely due to the very low 

specific activity, the low systemic absorption of uranium, and the lack of concentration of uranium in the 

germ cells. Genotoxic effects to parental germ cells or to a developing fetus are not likely at probable 

levels of exposure to uranium from the environment or at hazardous waste sites. Some uranium is stored 

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URANIUM 322 

6. POTENTIAL FOR HUMAN EXPOSURE 

in bone, but it is not known if this uranium is released during pregnancy and lactation, when it could 

result in exposure to the fetus or infant. 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

Higher rates of uranium exposure have been reported for some populations. The potential for uranium 

exposure is greater for individuals who consume foods grown in areas with elevated concentrations of 

uranium in the soil, and for individuals with elevated concentrations of uranium in their drinking water 

(EPA 1985; NCRP 1984a; Orloff et al. 2004). Industries where higher exposures to uranium are known 

to occur include uranium mining and milling, uranium conversion and enrichment, uranium fuel 

fabrication, and nuclear weapons production (BEIR IV 1988; Miller 1977; NCRP 1984a; West et al. 

1979). Other groups with the potentially higher exposures include persons involved in producing and 

using phosphate fertilizers and individuals living and working near fossil fuel plants (Jaworowski and 

Grzybowska 1977; NCRP 1984a; Tadmor 1986; Weissman et al. 1983). Uranium compounds were 

previously used in dental appliances, and individuals with dental work of this kind have potentially higher 

exposures (Sairenji et al. 1980). 

The use of depleted uranium in high-density tank armor and armor piercing munitions is expected to 

result in higher exposures of military personnel who handle this equipment or are located nearby, 

especially during combat. The primary routes of exposure to depleted uranium include inhalation of 

aerosols formed during the high energy collisions of depleted uranium munitions with vehicle armor, 

embedding of depleted uranium fragments in wounds to the body, and ingestion resulting from contact 

with depleted uranium residue on contaminated surfaces (Parkhurst and Guilmette 2009a; Szrom et al. 

2009). 

The Capstone Depleted Uranium Aerosol Characterization and Risk Assessment Study, begun in 

November 2000, was conducted to determine the level of exposure to depleted uranium aerosols resulting 

from perforation of armored Abrams Tanks and Bradley Fighting Vehicles with large caliber depleted 

uranium munitions (Guilmette and Parkhurst 2007; Parkhurst and Guilmette 2009a). Results of the 

Capstone study show mean depleted uranium concentrations measured inside the unventilated combat 

vehicles ranging from 3.0 to 16 g/m3 10 seconds after perforation and falling to 0.020–0.15 g/m3 within 

30 minutes (Parkhurst et al. 2009). Levels were much lower in a ventilated Abrams tank with a maximum 

concentration of 0.22 g/m3 measured 1 minute after perforation and 0.011 g/m3 after 30 minutes 

(Guilmette and Parkhurst 2007; Parkhurst et al. 2009). Based on the aerosol measurements, median 

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inhalation intakes of depleted uranium were determined to be 10–280 mg for a combat vehicle crew 

member exiting 1 minute after perforation, 43–710 mg for a combat vehicle crew member exiting 

5 minutes after perforation, and 27–200 mg for a first responder entering 5 minutes after perforation and 

remaining in the combat vehicle for 10 minutes (Guilmette et al. 2009; Parkhurst and Guilmette 2009b). 

A depleted uranium inhalation intake rate ranging from 0.447 to 14.5 mg/hour was estimated for military 

personnel and civilian employees located near vehicles containing depleted uranium fragments but not 

directly involved in the perforation incident (Szrom et al. 2009). Ingestion intake rates for these 

individuals were estimated to be 1.78–38.9 mg/hour resulting from hand-to-mouth transfer from contact 

with depleted uranium contaminated surfaces (Szrom et al. 2009). 

Depleted uranium was reportedly used in the military conflicts in Iraq during 1991 and 2003, in Bosnia 

during 1994, and in Kosovo during 1999 (Oeh et al. 2007b). Several studies have monitored the levels of 

uranium in the urine of individuals with reported exposure to the depleted uranium used during these 

conflicts (Hooper et al. 1999; McDiarmid et al. 1999b, 2001b, 2004a; Miller et al. 2008; Oeh et al. 2007a, 

2007b; Toohey 2003). Table 6-9 lists urinary concentrations measured in these studies. In general, the 

levels of uranium measured in the urine of individuals reporting exposure were not different than levels in 

non-exposed individuals. A notable exception is seen with individuals having depleted uraniumcontaining shrapnel embedded within their bodies (Hooper et al. 1999; McDiarmid et al. 1999b, 2004a; 

Toohey 2003). Measured urinary uranium levels in these individuals are consistently elevated, reaching 

as high as 30 μg U/g creatinine. 

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 uranium 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 uranium. 

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 

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6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-9. Urinary Levels of Uranium in Individuals Exposed through Military Use 

of Depleted Uranium 

Number of Concentration (μg U/g creatinine) 

Location individuals Mean Minimum Maximum Reference 

U.S. Gulf War veterans, Hooper et al. 1999 

1993–1994 

Reported depleted uranium 10 0.03 — — 

exposure without 

embedded shrapnel 

With embedded depleted 15 4.47 — 22.48 

uranium shrapnel 

1997 McDiarmid et al. 

1999b; Toohey 2003 

Non-exposed 22 0.02 0.01 0.05 

Reported depleted uranium 29 3.59 0.01 30.74a 

exposurea 

1997–1999 Toohey 2003 

With embedded depleted 7 — 0.46 24.77 

uranium shrapnel (30-840 

mg) 

1998–1999 McDiarmid et al. 

2001b 

Reported depleted uranium 169 0.01b 0.001 0.432 

exposure 

1998–2002 McDiarmid et al. 

2004a 

Reported depleted uranium 440 0.001 0.005c 0.042d 

exposure without 

embedded shrapnel 

With embedded depleted 6 0.083 0.008c 2.895 

uranium shrapnel 

Peacekeepers and residents Oeh et al. 2007a, 

in Kosovo, 1999–2006 2007b 

German peacekeepers 726 0.0139 0.006 0.1715 

Kosovo residents 25 0.0251 0.00292 0.2668 

Unexposed controls from 63 0.0128 0.0014 0.775 

southern Germany 

British Forces Miller et al. 2008 

Military personnel not 732 0.0027b <0.001 0.556 

having served in Iraq 

a

All values >1.0 μg U/g creatinine occurred in nine veterans containing embedded shrapnel.

b

Median value.
 c

10th percentile value.

d

95th percentile value.
 

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6. POTENTIAL FOR HUMAN EXPOSURE 

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. Pertinent data on the physical and chemical properties of 

uranium and uranium compounds are available in the literature. 

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 2010, became available in May of 2008. This database is updated yearly and should 

provide a list of industrial production facilities and emissions. 

Data regarding the past and present production (ABMS 1994; EPA 1985a) and import/export volumes 

(USDOC 1995) for uranium are available. The uses of uranium and uranium compounds are well known 

(Clayton and Clayton 1981; EPA 1985j; USDI 1980). Other than glazed ceramic foodware and 

decorative items (Landa and Councell 1992) and dental appliances (Sairenji et al. 1980), consumer 

contact with uranium products is negligible. Since uranium is not covered under SARA, Title III, 

manufacturers and users are not required to report releases to the EPA. There is a lack of data on the 

release and disposal of uranium during mining, milling, and chemical processing and its use during fuel 

cycle operations. The disposal of uranium is governed by the USNRC regulations (10 CFR 61), and 

releases of uranium to the environment are governed by USNRC and EPA regulations (10 CFR 20, 

Appendix B; 40 CFR 190; 40 CFR 192). Since significant amounts of depleted uranium are used on 

modern battlefields, it would be useful to have more information on the export of depleted uranium to 

other nations, the disposal of related wastes in the United States, and the mass of depleted uranium 

released to long-distance air transport when projectiles are used against different target types. 

Environmental Fate. For solids, there is a need to determine uptake factors into edible portions of 

plants and not just adherence to the root structure. For the solid-liquid interface, a method is needed to 

determine a method by which 234U to 238U ratio deviates from unity such that the EPA ERAMS water 

sample results indicate disequilibrium. Uranium enters the atmosphere in particulate form from natural 

sources and from uranium mining, milling, and processing. Dry or wet deposition from the atmosphere to 

soil and water can occur (Essien et al. 1985). Little experimental data on the particle size and residence 

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URANIUM 326 

6. POTENTIAL FOR HUMAN EXPOSURE 

time of uranium and uranium compounds present in ambient atmospheres are available. Additional data 

regarding the measured particle size of uranium compounds in ambient air, settling velocity, and 

knowledge of the chemical forms and lifetime of the particles in air would be useful. Although some 

studies have characterized the oxidation states and chemical forms of some uranium compounds (UO2 and 

UO3) (Dodge and Francis 1994; Wersin et al. 1994), more data identifying the chemical forms of uranium 

in the environment are needed to better understand the fate and transport of uranium. Since significant 

amounts of depleted uranium are used on modern battlefields, it would be useful to have more 

information on the export of depleted uranium to other nations and the disposal of related wastes in the 

United States, as well as estimates of projectile quantities that aerosolize to a significant extent and 

associated downwind air contamination levels. 

Bioavailability from Environmental Media. The absorption and distribution of uranium as a result 

of inhalation and ingestion exposures have been discussed in Sections 3.5.1 and 3.5.2. However, 

quantitative data relating to physical/chemical properties such as particle size, chemical form, and degree 

of absorption with the bioavailability of uranium from inhaled air particles and inhaled and/or ingested 

soil particles, are lacking. Such studies would be useful in assessing potential public health impact of 

uranium to people living near a hazardous waste site. 

Food Chain Bioaccumulation. Information about uranium bioaccumulation in fish (Mahon 1982; 

Poston 1982; Swanson 1983; Waite et al. 1988) is available. Data concerning levels of uranium in 

various foods (EPA 1985j) are also available. These data indicate that uranium does not biomagnify in 

the food chain (Ahsanullah and Williams 1989; Morishima et al. 1977; Swanson 1983, 1985). Data on 

the levels of uranium in food grown in contaminated areas are limited. Additional data are needed on 

whether the uptake of uranium in fish is restricted to the gills and how much actually distributes to the 

meat. 

Exposure Levels in Environmental Media. Reliable monitoring data for the levels of uranium in 

contaminated media at hazardous waste sites are needed so that the information obtained on levels of 

uranium in the environment can be used in combination with the known body burden of uranium to assess 

the potential risk of adverse health effects in populations living in the vicinity of hazardous waste sites. 

The levels of uranium in airborne particles and precipitation have been monitored since 1973 (EPA 1986, 

1994). Data from several large studies of uranium in domestic water supplies are available (Cothern and 

Lappenbusch 1983; DOE 1981b), as are data from studies of groundwater and surface water (NCRP 

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6. POTENTIAL FOR HUMAN EXPOSURE 

1984a). The primary source of information on the occurrence of uranium in drinking water is the 

National Inorganics and Radionuclides Survey (NIRS) conducted by EPA (EPA 1991b). Some 

monitoring data are available for uranium-contaminated soils and sediments associated with the nuclear 

fuel cycle. Better information on background levels in the environment and speciation of uranium in soils 

and sediments would be useful for determining which species lead to actual public exposure. 

Exposure Levels in Humans. Although some data on the urinary levels of uranium in humans 

exposed to natural background levels (food, water, and air) are available (CDC 2011), these data are 

nationally representative and don’t reflect high exposures, such as those experienced in the Southwest 

area of the United States. Biomonitoring studies are needed in areas with higher natural uranium 

exposure to develop a baseline for comparison. Additionally, there are limited data on the uranium 

content in human tissues in the general population and in populations living in areas with higher 

background uranium levels. The principal source of information about occupationally exposed 

individuals is the U.S. Transuranium and Uranium Registries (USTUR) Tissue Program and database, 

established to document uranium levels and distribution in human tissues for occupationally exposed 

workers (PNL 1981). Several major database files are available. The Radiochemical file contains 

information about radiochemical analysis of tissue donations from occupationally exposed individuals. 

The Health Physics file contains bioassay and other health physics data. These two databases are 

regularly updated. The Medical file contains abstracted personal, medical, and clinical data; the 

Pathology file contains autopsy and pathology information; and the Skeletal Estimate file contains 

estimated actinide concentrations for unanalyzed half skeletons from donors (USTUR 1999). 

This information is necessary for assessing the need to conduct health studies on these populations. 

Exposures of Children. Children will be exposed to uranium in the same manner as adults in the 

general population (i.e., ingestion of food and water and inhalation of air). Concentrations measured in 

the urine of children aged 6–11 and 12–19 years during the National Health and Nutrition Examination 

Survey (NHANES) were similar to those measured in adults aged 20 years and older (CDC 2011). A 

study of uranium content in bone from three age groups (<13, 13–20, and 20–25 years old) reported 

somewhat higher uranium content in the youngest compared to the oldest age group (approximately 1.5– 

3-fold); however, there were only 2–4 subjects in each group and the results were not statistically 

significant (Broadway and Strong 1983). Since the skeletons of children are growing (higher rate of bone 

formation), it is possible that a higher fraction of circulating uranium will be deposited in bone than in 

adults. Further information is needed on bone levels of uranium in children to determine if this is the 

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URANIUM 328 

6. POTENTIAL FOR HUMAN EXPOSURE 

case. Uranium is found in all soil, and at potentially higher levels at some hazardous waste sites. Since 

children may have oral exposure to soil through hand-to-mouth activity, bioavailability studies of 

uranium in soil may be useful to assess the risk of this type of exposure. There is some evidence that 

neonatal animals absorb uranium in the gastrointestinal tract to a greater extent than adults. Experiments 

to confirm this finding and to determine how long into maturation a difference exists would help refine 

risk assessment for uranium exposure in children. 

Child health data needs relating to susceptibility are discussed in Section 3.12.2, Identification of Data 

Needs: Children’s Susceptibility. 

Exposure Registries. A voluntary exposure registry, the USTUR for occupationally exposed 

individuals, was established at Richland, Washington, in 1968 as the National Plutonium Registry for 

investigation of the potential hazards for occupational exposure to uranium. In 1971, additional 

radiochemistry support was provided by Los Alamos National Laboratory. The U.S. Uranium Registry 

was created as a separate entity in 1978, and the two registries operated in parallel until 1987, when a 

single director was given responsibility for both registries. In 1992, the management and operation of the 

registries was combined at Washington State University under a grant from the U.S. DOE. The primary 

goals are to develop information on the distribution and dose of uranium and transuranic elements in 

humans, providing data for verification or development of radiation protection standards, and to 

determine and evaluate health effects due to exposure to these radioactive elements. 

6.8.2 Ongoing Studies 

Ongoing studies are examining the levels of potential exposure to depleted uranium used for military 

purposes. 

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URANIUM 329 

7. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting, 

measuring, and/or monitoring uranium, its metabolites, and other biomarkers of exposure and effect to 

uranium. 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. 

7.1 BIOLOGICAL MATERIALS 

Uranium can enter the human body through inhalation, ingestion, or penetration through the skin. 

Measurement of the quantities of uranium in the body can be performed by two primary methods, in vivo 

measurements and in vitro measurements. These types of measurements are called bioassays. In vivo 

techniques measure the quantities of internally deposited uranium directly using a whole-body counter, 

while in vitro techniques permit estimation of internally deposited uranium by analysis of body fluids, 

excreta, or (in rare instances) tissues obtained through biopsy or postmortem tissue sectioning (NCRP 

1987; USTUR 2011). Some of these analytical methods are summarized in Table 7-1. 

The accurate and precise quantification of uranium in biological materials by either in vivo or in vitro 

methodologies requires that standard, certified sources with known concentrations of appropriate 

radionuclides be available and used appropriately on properly calibrated equipment. The U.S. national 

primary standards laboratories for developing and disseminating ionizing radiation standards include 

DOE laboratories for special nuclear materials standards and the National Institute of Standards and 

Technology (NIST) for the remaining standards. Also, the Health Physics Society accredits secondary 

standards laboratories for developing and disseminating NIST-traceable radioactive sources (HPS 2011). 

DOE does not produce Certified Reference Materials for biological matrices. However, NIST does 

produce human biological standard reference materials (SRMs) for uranium in two matrices (human lung 

powder [SRM4351, 234U and 238U each 1.0x10-4 Bq/g] and urine [SRM2668, two concentrations] (NIST 

2011). 

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7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Uranium in Biological Samples 

Sample 

matrix Sample preparation 

Analytical 

method 

Detection 

limit Accuracy Reference 

Urine Enrichment on an anion 

exchange column, 

solvent extraction 

α-Counting 

(total uranium) 

Not given 92% at 0.9 dpm 

spike 

Hinton 1983 

Urine Spiked urine wet ashed; 

sample clean-up by 

coprecipitation, solvent 

extraction and electroα-Spectrometry 

(total uranium) 

0.02 dpm/L 

for 238Ua 78% Singh and Wrenn 

1988 

deposition 

Urine Sample treated with HCl 

and H2O2, clean-up on 

anion exchange resin 

column 

Spectrophotometric 

(total uranium) 

5 μg/L 87% at 11 μg/L Kressin 1984 

Urine Sample wet ashed, 

enrichment on anion 

exchange column, 

purification by solvent 

extraction 

Fluorometric 

(total uranium) 

0.1 μg/L 75% at 

0.1B100 μg/L 

Dupzyk and 

Dupzyk 1979 

Urine Sample digestion with 

K2S2O8 and dissolution in 

water 

Laser-induced 

fluorometry 

(total uranium) 

1 μg/L 86% at 7 μg/L Hinton and White 

1981 

Urine Wet-ashed; solubilized KPA ~0.050 μg/L 90B110% Birkenfeld et al. 

1995 

Urine Acid digestion, 

purification by 

coprecipitation and 

column chromatography 

NAA (isotopic 

quantification) 

<6 μg/L 80% at 2 μg 

added uranium 

Pleskach 1985 

Urine Sample with 232U spike 

wet ashed, clean-up by 

anion exchange 

chromatography 

Isotope 

dilution-MS 

(isotopic 

quantification) 

5 pg (10-6 μg) 

uranium (total 

chemical 

blank) 

No data Kelly et al. 1987 

Urine Acidification; dilution ICP-MS 3 ng/L No data Karpas et al. 

1996 

Urine Dilution with acid, tritonX-100 ICP-MS 0.004 μg/L 3.71 RSD (%) at 

0.08 μg/L 

Caldwell et al. 

2005 

Urine Compilation from 

ANSI, DOE, EPA, IAEA, 

ICRP 

Not provided 0.04–1 pCi/L 

(0.0007– 

0.07 Bq/L) 

Not provided HPS 1996 

Soft tissue Spiked tissues wet 

ashed; clean-up by 

coprecipitation, solvent 

extraction and electroα-Spectrometry 

(total uranium) 

0.03 μg/ 

sample 

85B92% Singh and Wrenn 

1988 

deposition 

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7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Uranium in Biological Samples 

Sample 

matrix Sample preparation 

Analytical 

method 

Detection 

limit Accuracy Reference 

Soft tissue Spiked sample wet 

digested; purification by 

anion exchange; loaded 

into a single ionexchange bead as a point 

source for MS 

Isotope 

dilution-MS 

(isotopic 

quantification) 

<5 pg/L 77% Kelley and 

Fassett 1983 

Bones Spiked sample dry 

ashed; clean-up by 

coprecipitation, solvent 

extraction and 

α-Spectrometry 

(isotopic 

quantification) 

0.03 μg/ 

sample 

60B93% Singh and Wrenn 

1988; Singh et al. 

1984 

electrodeposition 

Bone ash Spiked sample wet 

ashed; clean-up by 

solvent extraction and 

electrodeposition 

α-Spectrometry 

(isotopic 

quantification) 

0.4 μg/kg for

238U 

>95% Fisenne et al. 

1980 

Feces Spiked sample dry and 

wet ashed; clean-up by 

coprecipitation, solvent 

extraction and electroα-Spectrometry 

(isotopic 

quantification) 

0.03 μg/ 

sample 

58% Singh and Wrenn 

1988 

deposition 

Bone ash Sampled dried; wetashed; homogenization; 

dissolution in acid 

ICP-MS 3 ng/g No data Twiss et al. 1994 

Feces Sample wet or dry ashed, 

irradiation 

3

He neutron 

analyzer 

0.04 ng/ 

sample 

No data Gonzales et al. 

1988 

a

This detection limit was reported by Melgard 1988. 

ANSI = American National Standard Institute; DOE = Department of Energy; EPA = Environmental Protection 

Agency; IAEA = International Atomic Energy Agency; ICP = inductively coupled plasma spectrometry; 

ICRP = International Commission on Radiological Protection; KPA = kinetic phosphorescence analysis; MS = mass 

spectrometry; NAA = neutron activation analysis 

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7. ANALYTICAL METHODS 

7.1.1 Internal Uranium Measurements 

In vivo or direct measurements of uranium in the body are made with radiation detector systems and 

associated electronics called whole-body counters that measure radiation as it leaves the body from 

internally deposited uranium. In vivo assays are the most direct method of quantifying internally 

deposited radioactive materials. However, not all radionuclides emit radiations than may be detected with 

sufficient accuracy outside the body (234U and 238U due to low-energy, low-intensity gamma emissions, 

for example) (NCRP 1978). 

The most commonly used detectors for uranium in vivo counting are sodium iodide, phoswich (NaI and 

CsI sandwich), and hyperpure germanium, which measure the gamma rays emitted during uranium decay 

(DOE 1988, 2009). Since the gamma radiations emitted from uranium and a number of its progeny are 

the same as those emitted by uranium in the environment, shielded rooms are normally used to house the 

uranium internal monitoring equipment to ensure that background radiation is as low as possible (DOE 

1999; Marlap 2004; Parrington et al. 1996). Although whole-body counters may be made in many 

configurations, a chest counter is usually used for inhaled uranium. In vivo analysis is widely used 

throughout the nuclear industry, both commercial and government, for quantifying levels of insoluble 

uranium in the body. In vitro analysis (see Section 7.1.2) is often used in conjunction with whole-body 

counting for monitoring workers handling uranium (DOE 2009). 

In vivo counting systems are calibrated using tissue-equivalent phantoms. These phantoms have shapes 

similar to the human torso and are made of polystyrene or other tissue equivalent material. Standard 

uranium sources of known activity are inserted into the phantom at locations where uranium would be 

expected to accumulate in a human body (DOE 1988). Relationships are determined between the 

uranium activity measured by the detection system and the known activity in the phantom (DOE 1988; 

HPS 1996). 

There are limitations associated with in vivo counting uranium measurements. First, soluble uranium is 

readily excreted, with fractions retained for varying periods in the bone and kidney, so detectability 

depends on factors such as intake quantity, chemical and physical form, biodistribution fraction, time 

since intake, background uranium contribution, analysis time, and detection system efficiency. Second, 

only the 235U isotope is typically evaluated using sodium iodide or hyperpure germanium detector 

systems, since 234U and 238U decay results in the emission of gamma rays of such low intensity and energy 

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that they are difficult for these systems to quantify (NCRP 1987). In such cases, indirect in vitro methods 

can be used for measuring uranium in urine or feces (DOE 2009). Analytical equipment and procedures 

vary widely among laboratories and often require individual-specific input (NCRP 1987). Routine 

bioassay monitoring is recommended for uranium processing facility workers at high risk of incurring an 

intake when the quantity of uranium handled reaches 0.5 kg (320 μCi), 5 kg (3,200 μCi), or 50 kg 

(32,000 μCi), respectively, when the process occurs in an open room or on a bench top with possible 

escape from a process vessel, in a fume hood, or in a glove box (DOE 2009). The Minimum Testing 

Level (amount of radioactive material a test laboratory should be able to measure in a performance test) 

for laboratories engaged in biomonitoring is 0.81 nCi (30 Bq) for in vivo lung monitoring (HPS 1996). 

The radiological limit is based on 50-rems to bone surfaces for class F uranium (formerly class D 

uranium), 5-rems to the whole body for class M uranium (formerly class W uranium), and 50-rems to the 

extrathoracic portion of the respiratory tract for class S uranium (formerly class Y uranium) (DOE 2009). 

7.1.2 External Measurements 

In vitro uranium analyses are routinely performed in support of a personnel monitoring program, or in 

cases where the size of an operation does not justify the cost of whole-body counter facilities. These 

analyses are usually done on urine samples, but other types of body materials may also be used (e.g., 

feces or blood). Urinalysis is effective for analysis of transportable or soluble uranium. A fraction of 

insoluble uranium also appears in the urine (DOE 2009). 

The excretion of uranium in fecal material results primarily from intakes by ingestion, and includes 

uranium swallowed after inhalation. Uranium will usually appear in feces within hours after intake, thus 

providing a rapid means of determining whether an intake has occurred. Fecal analysis requires 

prechemistry preparation that includes ashing of the sample, cleaning by co-precipitation, and solvent 

extraction followed by electrodeposition. Alpha spectroscopy is then performed (Singh and Wrenn 

1988). In the other methods, electrodeposition is replaced with an equipment-specific step, such as direct 

injection for ICP-MS and mixing with a scintillation cocktail for liquid scintillation. Urinalysis is 

typically favored over both fecal and blood analysis because it is generally more sensitive and less costly, 

and because fecal analysis provides no uptake or retention information and blood analyses is invasive. 

The analysis of uranium is rarely performed in favor of modeling using biokinetic and biodynamic 

parameters linked to bioassay results, unless it is conducted as part of an autopsy. The U.S. Transuranium 

and Uranium Registries (USTUR) maintains the bodies and tissues of uranium workers who donated their 

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7. ANALYTICAL METHODS 

bodies to scientific research. USTUR has developed methods for accepting, handling, storing, preparing, 

analyzing, and disposing of donated human tissues. Tissues analyzed for uranium content are prepared by 

ashing, anion exchange, and electrodeposition followed by alpha spectroscopy (USTUR 2011). 

Several methods that do not require chemical separation are available for measuring uranium in urine (in 

units of total mass or total activity). These methods include spectrophotometric (total mass), fluorometric 

(total mass), kinetic phosphorescence analysis (KPA) (total mass), and gross alpha (total activity) 

analyses (DOE 2009; Elliston et al. 2001, 2005; MARLAP 2004; Wessman 1984). Photometric 

techniques such as fluorometry and phosphorometry are not frequently used, but kinetic phosphorescence 

analysis is widely used. Measurements of total uranium do not provide the relative isotopic abundance of 

the uranium isotopes, but this may only be important when converting between activity and mass when 

the isotopic ratios are uncertain, or when differentiating between natural and depleted uranium (Magnoni 

et al. 2001; Roth et al. 2003). 

If quantification of an individual uranium isotope is needed (e.g., 234U, 235U, or 238U), the most commonly 

used methods require chemical separation followed by α-spectrometry, or chemical separation and 

electrodeposition followed by α-spectrometry (see Table 7-1). Mass spectrometers are more expensive, 

but provide sensitive, accurate, low-level analysis of uranium isotopes in much less time and with greater 

throughput than other methods due to greatly reduced sample preparation and analysis times (Twiss et al. 

1994; MARLAP 2004; MARSSIM 2000). 

The Minimum Testing Level for laboratories engaged in in vitro analysis of 234U, 235U, and 238U in 

biological samples using α-spectroscopy is 0.54 pCi (0.02 Bq) per liter or per sample (HPS 1996). An 

acceptable minimum testing level of 20 μg/L of urine has also been established for natural uranium based 

on mass determination (HPS 1996). 

7.2 ENVIRONMENTAL SAMPLES 

Two types of methods are commonly used for measurement of uranium in environmental samples. The 

first are field surveys using portable survey instruments, and the second is analysis of samples procured in 

the field that are returned to the laboratory for quantification. 

Accurately measuring the uranium in the field and in environmental samples requires that standard, 

certified radioactive sources with known concentrations of uranium, or other appropriate radionuclides, be 

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available and used properly. The U.S. national primary standards laboratories for developing and 

disseminating ionizing radiation standards are the DOE (for special nuclear materials only) and the NIST 

for the remainder. Also, the Health Physics Society accredits secondary standards laboratories for 

calibrating portable radiation meters and developing and disseminating NIST-traceable radioactive 

sources (HPS 2011). DOE can provide environmental uranium standards for metal (natural and depleted 

uranium), compounds (hexafluoride, oxide, nitrate, and octaoxide), isotopic mixtures, and minerals 

(phosphate rock, carnotite, pitchblende, monazite, and octaoxide) (DOE 2011b). NIST produces 

environmental uranium standards in 4 matrices (aqueous solution [SRM3164, SRM4321c] and natural 

water [SRM1640a], coal [SRMs 1632c and 1635], glass [SRMs 610 and 612-617], and urban particulate 

matter [SRM1648]) (NIST 2011). Specifics for these include: SRM3164 (natural uranium aqueous 

solution; 9.994 mg/g), SRM 4321b (natural uranium aqueous solution; 234, 235, and 238U; 6.5, 0.3, 6.3 nCi/g; 

242.0, 11.14, 233.1 Bq/g, respectively), SRM 617 (trace elements in glass, 0.02 ppm uranium), SRM1635 

(trace elements in coal, uranium, 0.24 mg/kg) (NIST 2011). 

7.2.1 Field Measurements of Uranium 

Uranium measurements in the field are typically qualitative in nature in that the instruments simply 

respond to alpha emissions, regardless of their isotopic origin. However, the levels can be measured 

quantitatively if key parameters are known, such as relative abundances of all alpha-emitting isotopes 

present, thickness of the layer being assessed, and detection efficiency of the instrument for the type of 

surface being assessed. Measurements in the past have typically been made using a portable, hand-held 

alpha scintillation detector (e.g., ZnS) equipped with a count rate meter, which detects alpha radiation 

while discriminating against beta-emitters in the same area. However, the need for low detection limits in 

radiological remediation efforts has found a more suitable and sensitive instrument in the large-area gasflow proportional counter. These instruments can be carried by an individual or attached to a holder for 

maintaining a selected surface-to-detector distance. The latter method can be integrated into a system 

which moves along a surface at a predetermined velocity recording spatially-related real-time data for 

later graphical imaging of absolute surface activity distributions (DOE 1988). These surveys can also be 

performed on people whose skin or clothing is contaminated. Survey instruments can provide a quick 

estimate or a measure of the level of activity that might be present. However, more accurate 

measurement of uranium activity may require that samples be taken for laboratory analyses. Under 

normal usage, the lowest level of uranium that can be reliably detected using an alpha scintillation survey 

meter is 200–500 disintegrations per minute/100 cm2 (0.09–0.23 nCi/100 cm2

) (DOE 1988); however, 

detection of levels several time lower is practical with gas flow proportional counters, especially when 

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7. ANALYTICAL METHODS 

used in the integrate mode. Detection capability varies with the type of detector used, the active area of 

the probe, the electronics, etc. 

Several limitations are associated with the measurement of uranium by portable survey instruments. First, 

the uranium must be present on the surface of the material being surveyed. Since uranium decays by 

emission of α particles, which travel only short distances in materials, any uranium that is imbedded in the 

surface being surveyed will be partially or completely masked. Secondly, when performing surveys, it 

must be possible to place the detector very close to the surface being surveyed (i.e., approximately onequarter of an inch) (DOE 1988, 1994), and uneven surfaces that are unintentionally touched can tear the 

detector window, disabling the instrument. Additional information is available in MARSSIM (2000) on 

the use and usefulness of field survey instruments. 

7.2.2 Collection of Environmental Samples 

The Multi-Agency Radiological Laboratory Analytical Protocols Manual (MARLAP 2004) recommends 

that a field sampling plan be developed to provide comprehensive guidance for collecting, preparing, 

preserving, shipping, and tracking field samples and recording field data. The principal objective is to 

provide representative samples of the proper size for analysis. The design should address input and 

recommendations of representatives from the field sampling team, health physics professional staff, 

analytical laboratory, statistical and data analysts, quality assurance personnel, and end-users of data. 

Field organizations conduct operations according to standard operating procedures that may include but 

should not be limited to the following: 

• Developing a technical basis for defining the size of individual samples; 

• Selecting field equipment and instrumentation; 

• Using proper sample containers and preservatives; 

• Using consistent container labels and sample identification codes; 

• Documenting field sample conditions and exceptions; 

• Documenting sample location; 

• Tracking, accountability, custody, and shipment forms; 

• Providing legal accountability, such as chain-of-custody record, when required; 

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• Selecting samples for field quality control (QC) program; 

• Decontaminating equipment and avoiding sample cross-contamination; 

• Specifying sample packaging, radiological surveys of samples, shipping, and tracking; and 

• Documenting the health and safety plan. 

The in situ high purity germanium (HPGe) gamma spectrometry system is used to assess concentrations 

of radioactive materials in undisturbed soils (MARSSIM 2000). The detector is able to discriminate 

among different radionuclides on the basis of characteristic gamma and x-ray energies. Another in situ 

technology, Laser Ablation-ICP-Atomic Emission Spectrometry or MS (LA-ICP-AES/MS), sends a 

probe to various soil depths where a laser ablates a 1 m3 sample (MARSSIM 2000). The material is then 

passed through a plasma torch where it becomes ionized and electrically excited, producing an ionic 

emission spectrum. As with the in situ HPGe system, the surface material is not consumed during the 

operation and results can be obtained in real-time. 

7.2.3 Laboratory Analysis of Environmental Samples 

Analytical methods for measuring uranium in environmental samples are summarized in Table 7-2. The 

available methods can be divided into two groups: chemical methods to determine the total mass of 

uranium in a sample, and radiological methods to determine amounts of individual isotopes. 

Environmental media that have been tested for uranium include air filters, swipes, biota, water, soil, and 

others; a full range of laboratory analysis methods has been used to quantify the total uranium or its 

individual isotopes. The equipment and methods tend to improve over time. The radiological analysis 

methods include alpha counting (with ionization, proportional, scintillation, or other solid state detectors), 

alpha spectroscopy, beta counting (with thin-window GM, ionization, proportional, and solid state 

detectors), beta spectrometry, or gamma spectroscopy (with NaI or HPGe systems). The equipment and 

method selection depends on the results needed and the non-uranium radionuclides that may be present 

(DOE 2009). The use of high resolution α-spectroscopy is common, although gamma spectroscopy is 

usable with great care. The chemical methods which are often used include spectrophotometry, 

fluorometry, and kinetic phosphorescence, with the addition of various mass spectrometer applications 

(ICP-MS, AES-MS, and accelerator-MS). If conversions between mass and activity are to be made 

accurately, prior knowledge of the relative abundance of the various uranium isotopes must be available 

or measured radiologically. A few media-specific methods that have been used successfully for 

measuring uranium concentrations in environmental samples are described below. The current trend, 

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Table 7-2. Analytical Methods for Determining Uranium in Environmental
 

Samples
 

Sample 

matrix Sample preparation 

Analytical 

method 

Sample 

detection limit Accuracy Reference 

Air Air particulate collection on 

glass fiber filter; digestion in 

HNO3 

ICP-MS (total 

uranium) 

0.1 μg/L in 

final solution 

No data Boomer and 

Powell 1987 

Air Spiked air particulate dry 

and wet ashed; dissolution; 

coprecipitation with iron 

hydroxide and Ca oxalate, 

purification by solvent 

extraction and 

α-Spectrometry 

(isotope 

quantification) 

0.02 dpm/Lb 

for 238U in 

solution 

No data Singh and 

Wrenn 1988 

electrodeposition onto 

platinum 

Air Sample collection on 

cellulose filters; ashing; 

extraction with 

α-Spectroscopy 0.015 pCi No data EPA 1984b 

triisooctylamine; purification 

by anion exchange 

chromatography and 

coprecipitation. 

Air Collection on cellulose filters INAA 0.03 μg per 

filter 

No data Querol et al. 

1997 

Rainwater Coprecipitation with iron 

hydroxide, radiochemical, 

ion-exchange and solvent 

extractive purification, and 

electrodeposition on steel 

α-Spectrometry 

(isotope 

quantification) 

0.02 dpm/L for

238U in 

solutiona 

68% Jiang et al. 

1986 

Drinking 

water 

Direct analysis or 

concentration by coprecipitation and solvent 

extraction; fusion 

Fluorometry 

(total uranium) 

<20 μg/L 

(direct); 

0.1 μg/L 

(cleaned) 

104% 

(cleaned) 

EPA 1980c 

(EPA Method 

908.1) 

Drinking 

water 

Concentrated by coprecipitation; separation; 

clean-up by ion-exchange 

Gross 

α-counting (total 

uranium) 

1 pCi/L 92.6% EPA 1980c 

(EPA Method 

908.0) 

Drinking 

water 

Sample chelation in EDTA; 

addition of Fluron 

Laser-induced 

fluorometry 

0.08 μg/L 100% at 

1 μg/L 

EPA 1984e 

(EPA Method 

908.2) 

Natural 

waters 

Sample concentration by 

cation-exchange resin, 

separation by ion-exchange 

resin and complexation with 

Arsenazo III 

Spectrophotometry (total 

uranium) 

0.1 μg/L 80% Paunescu 

1986 

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7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Uranium in Environmental
 

Samples
 

Sample Analytical Sample 

matrix Sample preparation method detection limit Accuracy Reference 

Water	 Sample fusion with NaF and Fluorometry 5 μg/L 117.5% at ASTM 1986 

LiF (total uranium) 6.3 μg/L		 (ASTM 

Method 

D2907-83) 

Water	 Coprecipitation with iron α-Spectrometry 0.02 dpm/L 97.7B108% ASTM 1986 

hydroxide; purification by (isotope at 0.028B (EPA Method 

ion-exchange quantification) 0.044 Bq/L D3972-82) 

chromatography and 

electrodeposition 

Water	 Solvent extraction; α-Spectrometry 0.02 dpm/Lb No data Stewart et al. 

coprecipitation with BaSO4; (isotope for 238U 1988 

dissolution in HClO4; quantification) 

reprecipitation with TiF3; 

filtration 

Water	 Preconcentration by NAA (total 3 μg/L >80% Holzbecher 

complexation with oxine and uranium) and Ryan 

adsorption on activated 1980 

carbon 

Water	 Preconcentration by ion- NAA (235U and No data No data Gladney et al. 238 exchange chromatography; U) 1983 

purification by ion-exchange 

and solvent extraction 

Water	 Extraction by ion-exchange; Delayed neutron 0.4 μg/L No data Zielinski and 

dissolution in low oxygen analysis (total McKown 1984 

solvent; irradiation uranium) 

Water Wet-ashed; reaction with Pulsed-laser 0.05 ppb 103% ASTM 1994 

complexant phosphorimetry (average) (Method 

5174-91) 

Water Solvent extraction Fluorescence 6.1–10.5 ppm No data ASTM 1994 

(uranyl spectroscopy (Method 

nitrate) D4763-88) 

Ground- Separation on resin; FI-ICP-MS 0.3 ng/L for ±1.8% Aldstadt et al. 

238 water automated	 (isotope U 1996 

quantification) 

Ground- Separation and Spectro- 1B2 μg/L No data Kerr et al. 

water	 concentration on two HPLC photometry (total 1988 

columns; complexation with uranium) 

Arsenazo III 

Water and Acid digestion; filtration ICP-MS (total 0.1 μg/L 105B110% EPA 1991a 

wastes (dissolved); acid digestion uranium) (EPA Method 

(total recoverable) 200.8) 

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URANIUM	 340 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Uranium in Environmental
 

Samples
 

Sample Analytical Sample 

matrix Sample preparation method detection limit Accuracy Reference 

Seawater	 Uranium enriched by 

chelation with APDC in the 

presence of Fe+2, 

complexation with APDC 

followed by adsorption on 

activated carbon 

Seawater	 Oxine addition 

Sediment	 Sediment dried and wellmixed; dissolution in 

HCl-HClO4-HF; purification 

by coprecipitation, ion 

exchange and 

electrodeposition 

Soil	 Soil leached with HCl-HNO3-

HF; purification by ionexchange, and solvent 

extraction, and 

electrodeposition 

Soil	 Dissolution in HCl-HNO3-HF; 

purification by 

coprecipitation, solvent 

extraction and 

electrodeposition 

Soil,	 Ashing; fusion with KF and 

sediment,	 K2S2O7; purification by 

and biota	 extraction with 

triisooctylamine, anion 

exchange chromatography 

and coprecipitation. 

Soil,	 Ashing; extraction into 

sediment,	 triisooctylamine, strip from 

and biota	 triisooctylamine with HNO3 

and coprecipitation with 

lanthanum. 

Minerals	 Dissolution in HNO3-HFHClO4; purification by 

solvent extraction 

Low level	 Dissolution; purification by 

radioactive coprecipitation, ionwaste	 exchange and electrodeposition 

X-ray 

fluorescence 

(total uranium) 

Cathodic 

stripping 

voltametry (total 

uranium) 

α-Spectrometry 

(isotope 

quantification) 

α-Spectrometry 

(isotope 

quantification) 

α-Spectrometry 

(isotope 

quantification) 

α-Spectroscopy 

gross 

α-Spectroscopy 

or 

α-spectroscopy 

Laser 

fluorometry (total 

uranium) 

α-Spectrometry 

(isotope 

quantification) 

0.56B

0.64 μg/L 

0.02B0.2 nM 

No data 

No data 

0.03 μg/ 

sample 

No data 

No data 

No data 

0.03 dpm 

No data	 Nagj et al. 

1986 

No data	 Van den Berg 

and Nimmo 

1987 

No data	 Anderson and 

Fleer 1982 

No data	 Golchert et al. 

1980 

67%	 Singh and 

Wrenn 1988 

No data	 EPA 1984b 

No data	 EPA 1984b 

No data	 Veselsky et al. 

1988 

No data	 Wessman 

1984 

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Table 7-2. Analytical Methods for Determining Uranium in Environmental
 

Samples
 

Sample Analytical Sample 

matrix Sample preparation method detection limit Accuracy Reference 

Building Wet ashing with HNO3-H2O- α-Spectrometry 0.03 μg/ 54B73% Singh and 

materials HF; purification by (isotope sample Wrenn 1988 

and lichen coprecipitation, solvent quantification) 

extraction and electrodeposition 

Vegetation Sample dried and ICP-MS (total 0.1 μg/L in No data Boomer and 

homogenized; dry and wet uranium) final solution Powell 1987 

ashing 

Vegetation Sample dried and Laser 0.05 mg/kg in No data Harms et al. 

homogenized; wet ashing fluorometry (total plant ash 1981 

and purification by solvent uranium) 

extraction 

Process Dilution and filtration water Laser 0.01 μg/Lb No data Hinton and 

water fluorometry (total White 1981 

soluble uranium) 

Process Direct analysis Ion 0.04 mg/L No data Byerley et al. 

water chromatography 1988 

spectrophotometric detection 

(U+

6) 

Field survey None Scintillation 200B500 dpm/ No data ANSI 1978 

detector and 100 cm2 (ANSI 

count rate meter (scintillation Standard 

detector) N323) 

a

This detection limit was reported by Melgard 1988.

b

This detection limit was reported by Wessman 1984. 

APDC = ammonium pyrrolidine dithiocarbamate; Bq = Bequerel and 1 pCi = 0.37 Bq; dpm = disintegration per 

minute and 1 pCi = 2.22 dpm; EDTA = ethylenediaminetetraacetic acid; FI = flow injection; HPLC = high 

performance liquid chromatography; ICP = inductively coupled plasma spectrometry; INAA = instrumental neutron 

activation and analysis; MS = mass spectrometry; NAA = neutron activation analysis; nM = nanomole or 10-9 of a 

mol 

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however, is away from prescriptive methods and toward performance-based methods which enable the 

user to optimize their available analytical tools. 

A cornerstone of this method is the development of Data Quality Objectives and the use of Data Quality 

Assessment to ensure that the selected method is properly developed and the results are of the appropriate 

quality (DOE 2010; EPA 2000, 2006a, 2006b). Field sampling quality assurance (QA) addresses a range 

of practices aimed at minimizing errors and evaluating sampling performance, and is a responsibility of 

all individuals involved. Aspects of field QA/QC include the use of standard operating procedures for 

sample collection and analysis; chain-of-custody and sample-identification procedures; instrument 

standardization, calibration, and verification; technician and analyst training; sample preservation, 

handling, and decontamination; and QC samples such as field and trip blanks, duplicates, and equipment 

rinses (ORNL 2011). 

DOE’s method for analyzing environmental materials is based on the methods of Hindman (1983), Sill 

and Williams (1981), and Welford et al. (1960) and involves preparing vegetation, soft tissue, and water 

samples by concentrating or isolating uranium from the media prior to separation in an anion exchange 

column, followed by alpha spectrometry (DOE 2000). 

In one analytical method for air filters, the air filters are ashed, silica content is volatilized with hydrogen 

fluoride, and uranium is extracted with triisooctylamine, purified by anion exchange chromatography and 

co-precipitated with lanthanum as fluoride. The precipitated uranium is collected by filtration, dried, and 

α-spectroscopy is performed (EPA 1984b). The activities of 234U, 235U, and 238U are determined based on 

the number of counts that appear in the α energy region unique to each isotope. This method is used by 

the EPA National Air and Radiation Environmental Laboratory for measurement of uranium in air as part 

of the Environmental Radiation Ambient Monitoring System (see Chapter 6). 

Singh and Wrenn (1988) describe a method for uranium isotopic analysis of air filters. Air filters are 

ashed, redissolved, and co-precipitated with iron hydroxide and calcium oxalate. The uranium is further 

purified by solvent extraction and electrodeposition. An alpha spectroscopy detection level of 

0.02 dpm/L for 238U in solution was reported (Singh and Wrenn 1988). 

Considerable work has been done to develop methods for analysis of uranium in water. In 1980, the EPA 

published standardized procedures for measurement of radioactivity in drinking water, which included 

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uranium analysis by both radiochemical and fluorometric methods (EPA 1980c), and more recently 

developed an ICP-MS method. An example of each is provided below. 

The radiochemical method quantifies gross α activity utilizing either a gas flow proportional counter or a 

scintillation detection system following chemical separation. In the EPA radiochemical method, the 

uranium is co-precipitated with ferric hydroxide, purified through anion exchange chromatography, and 

converted to a nitrate salt. The residue is transferred to a stainless steel planchet, dried, flamed, and 

counted for α particle activity (EPA 1980c). 

For the fluorometric method, uranium is concentrated by co-precipitation with aluminum phosphate and 

dissolved in diluted nitric acid containing magnesium nitrate as a salting agent, and the co-precipitated 

uranium is extracted into ethyl acetate and dried. The uranium is dissolved in nitric acid, sodium fluoride 

flux is added, and the samples are fused over a heat source (EPA 1980b). 

The ICP-MS method was developed for measuring total uranium in water and wastes. The sample 

preparation is minimalCfiltration for dissolved uranium and acid digestion for total recoverable uranium. 

Recovery is quantitative (near 100%) for a variety of aqueous and solid matrices and detection limits are 

low, 0.1 μg/L for aqueous samples and 0.05 mg/kg for solid samples (EPA 1991a). 

The EPA developed two methods for the radiochemical analysis of uranium in soils, vegetation, ores, and 

biota, using the equipment described above. The first is a fusion method in which the sample is ashed, 

the silica is volatilized, the sample is fused with potassium fluoride and pyrosulphate, a 236U tracer is 

added, and the uranium is extracted with triisooctylamine, purified on an anion exchange column, 

coprecipitated with lanthanum, filtered, and prepared in a planchet. Individual uranium isotopes are 

separately quantified by high resolution α-spectroscopy and the sample concentration calculated using the 

236U yield. The second is a nonfusion method in which the sample is ashed, the silica is volatilized, a 236U 

tracer is added, and the uranium is extracted with triisooctylamine, stripped with nitric acid, coprecipitated with lanthanum, transferred to a planchet, and analyzed in the same way by high resolution 

α-spectroscopy (EPA 1984). 

The detection capability of any measurement process is an important performance characteristics, along 

with precision and accuracy. The lower limit of detection (LLD) has been adopted to refer to the intrinsic 

detection capability of the measurement process (sampling through data reduction and reporting) 

(USNRC 1984). Factors that influence the LLD include background count rate, sensitivity of detector, 

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and, particularly, the length of time a sample and background are counted. Because of these variables, 

LLDs between laboratories, employing the same or similar chemical separation procedures, will vary. 

Additional examples of the techniques for quantification of uranium (as described above) are available, as 

well as examples of less frequently used techniques. These are identified in Table 7-3. 

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 uranium 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 uranium. 

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 

Methods for Determining Biomarkers of Exposure and Effect. Analytical methods with 

satisfactory sensitivity and precision are available to determine the levels of uranium in human tissues and 

body fluids. However, improved methods are needed to assess the biological effects of uranium in 

tissues. 

Uranium is in essentially all food, water, and air, so everyone is exposed to some levels. In a study 

reported by NIOSH (1981) and Thun et al. (1985), enhanced levels of β2-microglobulin levels were 

observed in the urine of uranium workers. It was postulated that enhanced excretion of β2-microglobulin 

might be used as an indication of uranium exposure; however, NIOSH (1981) and Thun et al. (1985) were 

unable to establish a dose-response correlation between level of exposure and excretion of the β2-microglobulin. Limson Zamora et al. (1998) identified changes in several potential biomarkers of effect 

following exposure to uranium, in which each individual biomarker could be affected by a range of 

chemicals, but the results suggested that it may be possible to identify a series of biomarkers whose 

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URANIUM 345 

7. ANALYTICAL METHODS 

Table 7-3. Additional Analytical Methods for Determining Uranium in 

Environmental Samples
 

Sample matrix Preparation method 

Analytical 

method 

Sample 

detection 

limit 

Percent 

recovery Reference 

Rocks, minerals, 

nuclear fission 

products, biological 

material 

Solvent extraction as 

MHFA complex; 

optional purification by 

back-extraction 

Spectrophotometric 0.0062 mg/L 

(with backextraction) 

99–103% Abbassi 1989 

Ore leachates Separation as arsenazo 

III complex 

Flow 

injection; 

6.6 μg/L No data 

spectrophotometric 

Aqueous solutions Complexation with 

o-hydroxypropiophenone 

isonicotinoyl-hydrazone 

Spectrophotometric 

No data No data 

et al. 1993 

Natural waters Co-precipitation with 

Fe(OH)3; selective 

separation by 

precipitation; 

determined as 

Laser 

fluorometry 

5 ppb No data Eral 1989 

dibenzoyl methane 

complex 

Rocks, minerals, 

nuclear fission 

products and 

biological material 

Solvent extraction as 

MHFA complex; 

optional purification by 

back-extraction 

Atomic 

absorption 

spectrometry 

<0.08 mg/L No data Abbassi 1989 

Phosphate rock 

and phosphoric 

acid 

Wet digestion; 

separation by extraction 

with trioctylphosphine 

oxide; destruction of 

complex prior to 

analysis 

Argon 

plasma 

emission 

spectrometry 

No data 98–100% Woodis et a 

1980 

Uranium tailings 

(U3O8) 

Wet digestion; solvent 

extraction 

ICP-OES No data 101% Feeney et a 

1983 

Phosphate rock Wet digestion; 

extraction with 

dc argon ICP <1 ppm 99–106% Norman et 

1983 

trioctylphosphine oxide; 

back-extraction with 

stripping solution 

Ground, mine 

waters 

Direct analysis ICP low ppm No data Greene et a 

1985 

Coal ash Acid digestion; 

separation with 

s-thenoyltrifluoric 

acetone; backICP 29 μg/L 98% Kamata et 

1987 

extraction 

Seawater Separation on chelate 

fiber 

ICP-OES 5 μg/L No data 

Perez et al. 1990 

Ramachandraiah 

l. 

l. 

al. 

l. 

al. 

Chang et al. 1990 

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URANIUM 346 

7. ANALYTICAL METHODS 

Table 7-3. Additional Analytical Methods for Determining Uranium in 

Environmental Samples
 

Sample 

Analytical detection Percent 

Sample matrix Preparation method method limit recovery Reference 

Apatite minerals Extraction with ICP-AES 0.02 mg/L No data Fujino et al. 1994 

3-phenyl-4-benzoyls-isoxazolone 

Natural waters Extraction with Stripping 10-10 mol/dm3 ≈90% Mlakar and 

s-thenoyltrifluoric voltametry Branica 1989 

acetone and tri-n-butyl 

phosphate 

Groundwater, soil Separation as propyl Stripping subnanomolar No data Wang et al. 1994 

gallate complex voltametry 

Surface soils in situ Gamma 0.1 Bq/g No data Miller et al. 1994 

spectrometry 

Ceramic and plastic None NAA with 0.02 ppb No data Riley 1982 

semiconductor fission track 

packaging material counting 

River sediments None Instrumental No data ≈70% Labrecque et al. 

NAA (certified 1986 

materials) 

Air samples Sample collection on Instrumental 2 ng/sample 95% Landsberger and 

filters NAA Wu 1993 

Sediment, pore Dilution ICP-MS 40 pg/mL 99% Toole et al. 1991 

water 

Soil None Proton No data No data Lazo et al. 1991 

induced 

fluorescent 

x-rays 

Soil Isotope Wessman 1984 

dilution MS 

Biological and Complexation with Laser Sensitivity No data Bushaw 1984 

10-12 environmental phosphoric acid phosphori- g 

samples metry 

AES = atomic emission spectrometry; Bq = Bequerel; ICP = inductively coupled plasma (spectrometry); 

MHFA = N-p-methoxyphenyl-2-furylacrylohydroxamic acid; MS = mass spectrometry; NAA = neutron activation 

analysis; OES = optical emission spectrometry 

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URANIUM 347 

7. ANALYTICAL METHODS 

combined responses could serve as a single uranium-specific biomarker of effect. Development of new or 

combination biomarkers for high uranium exposures would be useful. 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. Analytical methods with the required sensitivity and accuracy are available for quantification 

of uranium, both total and isotopic, in environmental matrices (Table 7-2). Knowledge of the levels of 

uranium in various environmental media, along with the appropriate modeling (see Chapters 3 and 5), can 

be used to evaluate potential human exposures through inhalation and ingestion pathways. 

Whether in the environment or in the human body, uranium will undergo radioactive decay to form a 

series of radioactive nuclides that end in a stable isotope of lead (see Chapter 4). Examples of these 

include radioactive isotopes of the elements thorium, radium, radon, polonium, and lead. Analytical 

methods with the required sensitivity and accuracy are also available for quantification of these elements 

in the environment where large sample are normally available (EPA 1980b, 1984), but not necessarily for 

the levels from the decay of uranium in the body. More sensitive analytical methods are needed for 

accurately measuring very low levels of these radionuclides. 

7.3.2 Ongoing Studies 

No ongoing studies were identified. 

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URANIUM 348 

7. ANALYTICAL METHODS 

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URANIUM 349 

8. REGULATIONS, ADVISORIES, AND GUIDELINES
 

MRLs are substance specific estimates, which are intended to serve as screening levels, are used by 

ATSDR health assessors and other responders to identify contaminants and potential health effects that 

may be of concern at hazardous waste sites. 

The international and national regulations, advisories, and guidelines regarding uranium in air, water, and 

other media are summarized in Table 8-1. 

ATSDR has derived an MRL of 0.002 mg U/m3 for intermediate-duration inhalation exposure to 

insoluble uranium compounds based on a NOAEL of 1.1 mg U/m3 and a LOAEL of 8.2 mg U/m3 for 

renal effects in dogs exposed to uranium dioxide 6 hours/day, 6 days/week for 5 weeks (Rothstein 1949b) 

and an uncertainty factor of 100 (10 for extrapolation from animals to humans and 10 for human 

variability). 

ATSDR has derived an MRL of 0.0001 mg U/m3 for intermediate-duration inhalation exposure to soluble 

uranium compounds based on a LOAEL of 0.15 mg U/m3 for renal effects in dogs exposed to uranyl 

fluoride 6 hours/day, 6 days/week for 5 weeks (Rothstein 1949a) and an uncertainty factor of 300 (3 for 

the use of a minimal LOAEL, 10 for extrapolation from animals to humans, and 10 for human 

variability). 

ATSDR has derived an MRL of 0.0008 mg U/m3 for chronic-duration inhalation exposure to insoluble 

uranium compounds based on a LOAEL of 5.1 mg U/m3 for lung fibrosis in monkeys exposed to uranium 

dioxide 5.4 hours/day, 5 days/week for 5 years (Leach et al. 1970, 1973) and an uncertainty factor of 

1,000 (10 for the use of a LOAEL, 10 for extrapolation from animals to humans, and 10 for human 

variability). 

ATSDR has derived an MRL of 0.00004 mg U/m3 for chronic-duration inhalation exposure to soluble 

uranium compounds based on a BMCL10 of 0.019 mg U/m3 for renal effects in dogs exposed to uranium 

tetrachloride 33 hours/week for 1 year (Stokinger et al. 1953) and an uncertainty factor of 100 (10 for 

extrapolation from animals to humans and 10 for human variability). 

ATSDR has derived an MRL of 0.002 mg/kg/day for acute-duration oral exposure to soluble uranium 

compounds based on an average BMDL05 of 0.2 mg U/kg/day for developmental effects in the offspring of 
 

 

 

 

URANIUM	 350 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Uranium 

Agency Description Information References 

INTERNATIONAL 

Guidelines: 

WHO TDI 

Provisional drinking water 

guideline 

ICRP	 Occupational 

Public 

NATIONAL 

Regulations: 

a. Air: 

EPA OAR Standards of performance 

for new stationary sources: 

General provisions: 

priority list: prioritized 

major source categories 

Metallic mineral 

processing plants 

NESHAPs: 

Radon emissions from 

underground uranium 

mines 

Radionuclide emissions 

other than radon from 

DOE facilities 

Radionuclide emissions 

from federal facilities 

other than USNRC 

licensees and not covered 

by Subpart H 

0.6 μg/kg/day 

15 μg/L water 

50 mSv/year whole body 

150 mSv/year lens of eye 

500 mSv hands and feet 

500 mSv/year skin averaged over 

1 cm2 

0.5 Gy/year averaged over 10 cm2 

at 70 mm depth 

1 mSv/year, or exceptionally more 

if 5-year average does not exceed 

1 mSv/year 

15 mSv/year lens of eye 

50 mSv/year skin 

Priority #56: Uranium refining 

At uranium ore processing plants, 

all facilities subsequent to and 

including the beneficiation of 

uranium ore are exempted from the 

provisions of this subpart 

10 mrem/year effective dose 

equivalent to public from radon-222 

10 mrem/year to public from other 

than radon-222 

10 mrem/year to public from 

radionuclides including iodine 

3 mrem/year to public from iodine 

WHO 2003, 2004 

WHO 2008 

ICRP 1991, 

2006b 

40 CFR 60, 

Subpart A 

EPA 2011k 

40 CFR 60, 

Subpart LL 

EPA 2011x 

40 CFR 61, 

Subpart B 

EPA 2011n 

40 CFR 61, 

Subpart H 

EPA 2011v 

40 CFR 61, 

Subpart I 

EPA 2011w 

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URANIUM 351 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Uranium 

Agency Description Information References 

NATIONAL (cont.) 

Radon emissions from 

DOE facilities 

Radon emissions from 

phosphogypsum stacks 

Radon emissions from 

disposal of uranium mill 

tailings 

Radon emissions from 

operating mill tailing 

Environmental radiation 

protection standards for 

nuclear power operations: 

environmental standards for 

uranium fuel cycle: 

standards for normal 

operation 

Quantity of radioactive 

material entering 

environment per gigawattyear 

Environmental radiation 

protection standards for 

management and disposal 

of spent nuclear fuel, highlevel and transuranic wastes 

Definitions 

Standards for control of 

residual radioactive 

materials from inactive 

uranium processing sites 

Standards (for control of 

residual radioactive 

materials and their listed 

constituents) 

20 pCi/m2

-second of radon-222 

20 pCi/m2

-second of radon-222 

20 pCi/m2-second of radon-222 for 

tailings pile or impoundment no 

longer operations 

20 pCi/m2-second of radon-222 

Specifies number, total area, and 

uncovered area of impoundments 

50,000 Ci krypton-85 

5 mCi plutonium-239 and other 

alpha-emissions with half-lives 

>1 year 

Defined heavy metal as uranium, 

plutonium, or thorium placed into a 

nuclear reactor 

Applies to designated processing or 

depository sites under §108 of 

UMTRCA and restoration of sites 

after mineral use 

20 pCi/m2

/second radon-222 

annual average above disposal site 

from residual 

0.5 pCi/L radon-222 annual 

average above background outside 

disposal area 

40 CFR 61, 

Subpart Q 

EPA 2011y 

40 CFR 61, 

Subpart R 

EPA 2011z 

40 CFR 61, 

Subpart T 

EPA 2011aa 

40 CFR 61, 

Subpart W 

EPA 2011bb 

40 CFR 190, 

Subpart B 

EPA 2011o 

40 CFR 191.12 

EPA 2011d 

40 CFR 192, 

Subpart A 

EPA 2011l 

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URANIUM 352 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Uranium 

Agency Description Information References 

NATIONAL (cont.) 

Standards for cleanup of Applies to land and buildings that 40 CFR 192, 

land and buildings are part of the processing site and Subpart B 

contaminated with residual most of uranium was produced for EPA 2011p 

radioactive materials from Federal government 

inactive uranium processing 

sites 

Standards 0.02 working level of radon decay 

products (0.03 working level 

including background) in habitable 

buildings 

Guidance for Yes 40 CFR 192, 

implementation Subpart C 

EPA 2011r 

Additional listed constituents Combined uranium-234 and 

(replacement list of uranium-238 

constituents for screening 

purposes) 

Standards for management Yes 40 CFR 192, 

of uranium byproduct Subpart D 

materials pursuant to EPA 2011t 

Section 84 of the Atomic 

Energy Act of 1954, as 

amended 

Standards (for application 5 pCi/L combined radium-226 and 

during processing radium-228 

operations and prior to 20 pCi/m2

-second radon-222 after 

the end of the closure permanent radon barrier installed 

period—concentration 

limits) 

20 pCi/m2

-second radon-222 for 

200 years, and to extent feasible 

for 1,000 years 

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URANIUM 353 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Uranium 

Agency Description Information References 

NATIONAL (cont.) 

USNRC and DOE Occupational ALIs (μCi) and 

DACs (μCi/m3

) for inhalation 

for uranium compounds of 

Class D, W, and Y, for 

Isotope 

U-230 

Class 

D 

W 

Y 

ALI 

6x10-1 

4x10-1 

3x10-1 

DAC 

2x10-10 

1x10-10 

1x10-10 

which the class refers to U-231 D 8x10-3 3x10-6 

retention times W 6x10-3 2x10-6 

(approximately days, weeks, 

or years) in the pulmonary 

region of the lung 

U-232 

Y 

D 

W 

5x10-3 

4x10-1 

4x10-1 

2x10-6 

9x10-11 

2x10-10 

Y 8x10-3 3x10-12 

U-233 D 2x100 5x10-10 

W 7x10-1 3x10-10 

Y 4x10-2 2x10-11 

U-234 D 2x100 5x10-10 

W 7x10-1 3x10-10 

Y 4x10-2 2x10-11 

U-235 D 2x100 6x10-10 

W 8x10-1 3x10-10 

Y 4x10-2 2x10-11 

U-236 D 2x100 5x10-10 

W 8x10-1 3x10-10 

Y 4x10-2 2x10-11 

U-237 D 3x10-3 1x10-6 

W 2x10-3 7x10-7 

Y 2x10-3 6x10-7 

U-238 D 2x100 6x10-10 

W 8x10-1 3x10-10 

Y 4x10-2 2x10-11 

U-239 D 2x105 8x10-5 

W 2x105 7x10-5 

Y 2x105 6x10-5 

U-240 D 4x103 2x10-6 

W 3x103 1x10-6 

Y 2x103 1x10-6 

Unatural D 

W 

2x100 

8x10-1 

5x10-10 

3x10-10 

Y 5x10-2 2x10-11 

10 CFR 20 

Appendix B 

USNRC 2010a 

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URANIUM	 354 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Uranium 

Agency Description Information	 References 

NATIONAL (cont.) 

OSHA Effluent concentrations 

(μCi/mL) for uranium 

compounds of Class D, W, 

and Y, for which the class 

refers to retention times 

(approximately days, weeks, 

or years) in the pulmonary 

region of the lung 

OSHA	 Radioactive materials: Post 

caution radioactive material 

signs for natural uranium 

Isotope	 Class Concentration 

U-230	 D 5x10-13 

W 5x10-13 

Y 5x10-14 

U-231	 D 1x10-8 

W 8x10-9 

Y 6x10-9 

U-232	 D 6x10-13 

W 5x10-13 

Y 1x10-14 

U-233	 D 3x10-12 

W 1x10-12 

Y 5x10-14 

U-234	 D 3x10-12 

W 1x10-12 

Y 5x10-14 

U-235	 D 3x10-12 

W 1x10-12 

Y 6x10-14 

U-236	 D 3x10-12 

W 1x10-12 

Y 6x10-14 

U-237	 D 4x10-9 

W 2x10-9 

Y 2x10-9 

U-238 D 3x10-12 

1x10-12 W 

6x10-14 Y 

U-239	 D 3x10-7 

W 3x10-7 

Y 3x10-7 

U-240	 D 5x10-9 

W 4x10-9 

Y 3x10-9 

Ex10-12 Unatural D 

9x10-13 W 

Y 9x10-14 

Post sign on room containing 

natural uranium exceeding 

100 times value in 10 CFR 20 

Post sign on container containing 

natural uranium exceeding 10 times 

value in 10 CFR 20 Appendix C 

10 CFR 20 

Appendix B 

USNRC 2010a 

29 CFR 

1910.1096 

OSHA 2010c 

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URANIUM	 355 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Uranium 

Agency Description Information References 

NATIONAL (cont.) 

PEL TWA (corrected rule) 

Soluble uranium 

Insoluble uranium 

STEL 

Occupational safety and 

health standards for 

shipyard employment— 

8-hour TWA for air 

contaminants 

Soluble uranium 

Insoluble uranium 

Safety and health 

regulations for 

construction—TWA TLVs for 

airborne contaminants 

Soluble uranium 

Insoluble uranium 

b. Water: 

EPA National primary drinking 

water regulations 

Monitoring and analytical 

requirements: analytical 

methods for radioactivity, 

uranium 

Maximum contaminant 

level goals for 

radionuclides 

Maximum contaminant 

levels for radionuclides 

BAT for reducing uranium 

in water 

EPA administered permit 

programs: NPDES 

0.05 mg/m3 

0.25 mg/m3

0.6 mg/m3

 insoluble 

0.2 mg/m3 

0.2 mg/m3 

0.2 mg/m3 

0.2 mg/m3 

Approved methodology 

(radiochemical, fluormetric, 

inductively coupled plasma-mass 

spectrometry, alpha spectrometry, 

laser phosphorimetry) and 

procedures for analyzing uranium 

in drinking water 

Alternate analysis procedures for 

uranium in drinking water 

Zero for uranium 

30 μg/L uranium 

Ion exchange, reverse osmosis, 

lime softening, coagulation/filtration 

Uranium is in Table V—toxic 

pollutants and hazardous 

substances required to be identified 

by existing dischargers if expected 

to be present 

29 CFR 

1910.1000 

OSHA 2000d 

29 CFR 

1915.1000 

OSHA 2010a 

29 CFR 1926.55, 

Appendix A 

OSHA 2010b 

40 CFR 141.25 

EPA 2010a 

40 CFR 141 

Subpart C, 

Appendix A 

EPA 2010b 

40 CFR 141.55 

EPA 2010g 

40 CFR 141.66 

EPA 2010h 

40 CFR 141.66 

EPA 2010h 

40 CFR 122, 

Appendix D 

EPA 2010c 

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URANIUM 356 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Uranium 

Agency Description Information References 

NATIONAL (cont.) 

Criteria and standards for Criteria and standards for 40 CFR 125 

NPDES technology-based treatment EPA 2011c 

requirements in permits under 

section 301(b) of Clean Water Act, 

not specific to uranium 

Underground injection 

control program: criteria and 

standards 

Classification of injection Class III wells inject for extraction 40 CFR 146.5 

wells of minerals, including in situ EPA 2010e 

production of uranium or other 

metals from ore bodies that have 

not been conventionally mined 

State, tribal, and EPAadministered underground 

injection control programs: 

Subpart HHH—Lands of the 

Navajo, Ute Mountain Ute, 

and All Other New Mexico 

Tribes 

Aquifer exemptions Applicants for uranium mining 40 CFR 

permit requiring an aquifer 147.3003 

exemption must submit a plugging EPA 2010d 

and abandonment plan 

Plugging and Addresses requirements for 40 CFR 

abandonment of Class III plugging and abandoning the wells 147.3011 

wells EPA 2010i 

Environmental radiation 40 CFR 190, 

protection standards for Subpart B 

nuclear power operations: EPA 2011o 

environmental standards for 

uranium fuel cycle: 

standards for normal 

operation 

Quantity of radioactive 5 mCi plutonium-239 and other 

material entering alpha-emissions with half-lives 

environment per >1 year 

gigawatt-year 

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URANIUM 357 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Uranium 

Agency Description Information References 

NATIONAL (cont.) 

Standards for cleanup of 

land and buildings 

contaminated with residual 

radioactive materials from 

inactive uranium processing 

sites 

Maximum concentration 

of constituents for 

groundwater protection 

Environmental radiation 

protection standards for 

management and disposal 

of spent nuclear fuel, highlevel and transuranic wastes 

Definitions 

Environmental standards 

for groundwater 

protection 

Designation, reportable 

quantities, and notification of 

hazardous substances 

30 pCi/L combined uranium-234 

and uranium-238
 

5 pCi/L combined radium-226 and 

radium-228
 

15 pCi/L gross alpha excluding 

radon and uranium
 

Defines heavy metal as uranium,
 

plutonium, or thorium placed into a
 

nuclear reactor
 

Applies to radioactive 

contamination of underground 

sources of drinking water
 

10,000 years design basis for
 

undisturbed performance
 

100 Ci/10,000 years cumulative 

release limit for uranium isotopes
 

(233, 234, 235, 236, or 238) per
 

1,000 metric tons of heavy metal
 

Reportable quantities for uranium
 

isotopes in Curies (Bq):
 

U-230 1 (3.7x1010) 

U-231 1,000 (3.7x1013) 

U-232 0.01 (3.7x108

) 

U-233 0.1 (3.7x109

) 

U-234 0.1 (3.7x109

) 

U-235 0.1 (3.7x109

) 

U-236 0.1 (3.7x109

) 

U-237 100 (3.7x1012) 

U-238 0.1 (3.7x109

) 

U-239 1,000 (3.7x1013) 

U-240 1,000 (3.7x1013)
 

40 CFR 192 

Subpart A 

EPA 2011l 

40 CFR 191.12 

EPA 2011dd 

40 CFR 191 

Subpart C 

EPA 2011q 

40 CFR 302.4 

Appendix B 

EPA 2011b 

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URANIUM 358 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Uranium 

Agency Description Information References 

NATIONAL (cont.) 

Procedures for EPA to 

reimburse local 

governments for certain 

emergency response costs 

Nonferrous metals 

manufacturing point source 

category: 

Secondary uranium 

subcategory 

Secondary uranium 

subcategory: effluent 

limitations attainable by 

BPT (control) 

Secondary uranium 

subcategory: effluent 

limitations attainable by 

BAT 

Secondary uranium 

subcategory: standards 

of performance for new 

source 

Secondary uranium 

subcategory: 

pretreatment standards 

for new sources 

Effluent guidelines and 

standards: ore mining and 

dressing point source 

category: uranium, radium, 

and vanadium ores 

subcategory 

Description of uranium 

ore subcategory 

Uranium effluent limits 

attainable by applicability 

of BPT (control) 

Uranium effluent limits 

attainable by applicability 

of BAT 

NSPS 

Excludes from this section releases 

of source, byproduct, or special 

nuclear material under Atomic 

Energy Act or UMTRCA regulations 

Applicable to discharges resulting 

from production of uranium 

(including depleted uranium) by 

secondary uranium facilities 

Limits for Cr, Cu, Ni, F, total 

suspended solids, and pH 

Limits for Cr, Cu, Ni, and F 

Limits for Cr, Cu, Ni, F, total 

suspended solids, and pH 

Limits for Cr, Cu, Ni, and F 

Applies to discharges from mines 

that produce uranium, radium, or 

vanadium ores and mills that 

extract these metals 

4 mg/L; maximum for 1 day 

2 mg/L; average for 30 consecutive 

days 

4.0 mg/L; maximum for 1 day 

2.0 mg/L; average for 

30 consecutive days 

4.0 mg/L; maximum for 1 day 

2.0 mg/L; average for 

30 consecutive days 

40 CFR 310.3 

EPA 2010k 

40 CFR 421, 

Subpart AD 

EPA 2011m 

40 CFR 421.322 

EPA 2011e 

40 CFR 421.323 

EPA 2011f 

40 CFR 421.324 

EPA 2011j 

40 CFR 421.326 

EPA 2011h 

40 CFR 440 

Subpart C 

EPA 2011s 

40 CFR 440 

Subpart C 

EPA 2011s 

40 CFR 440 

Subpart C 

EPA 2011s 

40 CFR 440 

Subpart C 

EPA 2011s 

40 CFR 440 

Subpart C 

EPA 2011s 

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URANIUM	 359 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Uranium 

Agency Description Information	 References 

NATIONAL (cont.) 

Nonferrous metals forming 

and metal powders effluent 

guidelines and standards 

Uranium forming 

subcategory: 

Effluent limitations 

representing the 

degree of effluent 

reduction attainable by 

the application of the 

BPT (control) currently 

available 

Effluent limitations 

representing the 

degree of effluent 

reduction attainable by 

the application of the 

BAT economically 

achievable 

PSNS 

USNRC	 Occupational ALIs for oral 

ingestion 

Applies to non-uranium pollutants 

or pollutant properties present in 

effluent waste water from uranium 

forming processes; limits are 

provided as follows: 

Maxima for any 1 day or monthly 

average for metals, fluoride, oils 

and greases, and pH 

Maxima for any 1 day or monthly 

average for metals, fluoride, oils 

and greases, and pH 

Maxima for any 1 day or monthly 

average for metals, fluoride, oils 

and greases, and pH 

Maxima for any 1 day or monthly 

average for metals, fluoride, oils 

and greases, and pH 

U-230 6 μCi 

U-231 4,000 μCi 

U-232 4 μCi 

U-233 2 μCi 

U-234 20 μCi 

U-235 20 μCi 

U-236 20 μCi 

U-237 2,000 μCi 

U-238 20 μCi 

U-239 7 μCi 

U-240 1,000 μCi 

Unatural 20 μCi 

40 CFR 471 

Subpart G 

EPA 2011u 

40 CFR 471 

Subpart G 

EPA 2011u 

40 CFR 471 

Subpart G 

EPA 2011u 

40 CFR 471 

Subpart G 

EPA 2011u 

40 CFR 471.75 

EPA 2011i 

10 CFR 20 

Appendix B 

USNRC 2010a 

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8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Uranium 

Agency Description Information	 References 

NATIONAL (cont.) 

Effluent concentrations	 U-230 8x10-8 μCi/mL 10 CFR 20 

U-231 6x10-5 μCi/mL Appendix B 

U-232 6x10-8 μCi/mL USNRC 2010a 

U-233 3x10-7 μCi/mL 

U-234 3x10-7 μCi/mL 

U-235 3x10-7 μCi/mL 

U-236 3x10-7 μCi/mL 

U-237 3x10-5 μCi/mL 

U-238 3x10-7 μCi/mL 

U-239 9x10-4 μCi/mL 

U-240 2x10-5 μCi/mL 

Unatural 3x10-7 μCi/mL 

Releases to sewers U-230 8x10-7 μCi/mL 

(monthly average U-231 6x10-4 μCi/mL 

concentration) U-232 6x10-7 μCi/mL 

U-233 3x10-6 μCi/mL 

U-234 3x10-6 μCi/mL 

U-235 3x10-6 μCi/mL 

U-236 3x10-6 μCi/mL 

U-237 3x10-4 μCi/mL 

U-238 3x10-6 μCi/mL 

U-239 9x10-3 μCi/mL 

U-240 2x10-4 μCi/mL 

Unatural 3x10-6 μCi/mL 

c. Other: 

DOI Office of Abandoned mine Uncertified states/tribes may not 30 CFR 875.16 

Surface Mine reclamation: Exclusion of use funds from §872.29 to reclaim DOI 2011 

Reclamation and certain non-coal reclamation sites designated for remediation 

Enforcement sites under UMTRCA or CERCLA 

EPA	 Environmental radiation 40 CFR 190 

protection standards for Subpart B 

nuclear power operations: EPA 2011o 

environmental standards for 

uranium fuel cycle: 

standards for normal 

operation 

Annual dose equivalent limit 25 mrems whole body 

to members of the public 75 mrems thyroid 

25 mrems any other organ 

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URANIUM	 361 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Uranium 

Agency Description Information	 References 

NATIONAL (cont.) 

EPA	 Standards for cleanup of 

land and buildings 

contaminated with residual 

radioactive materials from 

inactive uranium processing 

sites 

Standards 

EPA OSWER	 Exclusion from identification 

and listing of uranium as a 

hazardous waste 

Land disposal restriction 

phase IV: Final rule 

promulgating treatment 

standards for metal wastes 

and mineral processing 

wastes 

Uncontrolled hazardous 

waste site ranking system: 

definitions 

National oil and hazardous 

substance pollution 

contingency plan: definitions 

EPA Timing of Administration Act 

under Uranium Mill Tailing 

Radiation Control Act of 

1978 

USNRC	 Standards for protection 

against radiation 

Definition of byproduct 

material 

Dose limits for individual 

members of the public— 

total effective dose 

equivalent 

Applies to land and buildings that 

are part of the processing site and 

most of uranium was produced for 

Federal government 

5 pCi/g radium-226 averaged over 

top 15 cm of soil 

15 pCi/g radium-226 over lower 

15 cm layers of soil 

20 μR/hour gamma radiation above 

background 

Yes 

Yes 

Lists relevant sections of the 

Uranium Mill Tailings Radiation 

Control Act Standards as part of 

EPA hazard ranking system used 

to place sites on NPL 

Excludes releases of substances 

regulated under UMTRCA 

Date/time of promulgation shall be 

1 pm Eastern time 2 weeks after 

notice published in Federal 

Register 

Includes tailings or waste from U or 

Th ore processed primarily for its 

source material content 

0.1 rem/year from licensed 

operation 

0.1 rem for access to controlled 

areas 

0.5 rem when visiting any one 

patient who is restricted for 

containing medical radioactive 

material 

40 CFR 192, 

Subpart B 

EPA 2011p 

40 CFR 261.4 

EPA 2011g 

63 FR 28556 

EPA 1998d 

40 CFR 300 

Appendix A, §1.1 

EPA 2011a 

40 CFR 300.5 

EPA 2011d 

40 CFR 23.8 

EPA 2011cc 

10 CFR 20.1003 

USNRC 2010c 

10 CFR 20.1301 

USNRC 2010e 

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URANIUM 362 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Uranium 

Agency Description Information References 

NATIONAL (cont.) 

Occupational dose limits 

for adults 

5 rem/year total effective dose 

equivalent; 

50 rem/year deep dose equivalent 

plus committed dose equivalent 

(other than lens of eye); 

15 rem/year lens dose equivalent; 

50 rem/year skin dose equivalent; 

ALI and DAC limits apply; 

10 mg/week intake of soluble 

uranium 

10 CFR 20.1201, 

Subpart C 

USNRC 2010h; 

10 CFR 20.1206 

USNRC 2010g 

Planned special 

exposures 

Dose in excess of the 10 CFR 

20.1201 limit can equal the 10 CFR 

20.1201 limit in any 1 year up to 

5 times the annual limit in a lifetime 

10 CFR 20.1206 

USNRC 2010g 

Occupational dose 

limits to minors 

10% of annual dose limits in 

10 CFR 20.1201 

10 CFR 20.1207 

USNRC 2010f 

Dose equivalent to 

embryo/fetus 

0.5 rem for entire pregnancy; if 

dose exceeds 0.45 rem when 

female declares pregnancy to 

licensee, 0.05 rem additional is 

10 CFR 20.1208 

USNRC 2011d 

allowed 

Radiological criteria for 

license termination— 

applicability 

Not applicable to U/Th extraction 

facilities subject to 10 CFR 40 

Appendix A or to U solution 

extraction facilities 

10 CFR 20, 

Subpart E 

USNRC 2000i 

Requirements for 

transfers of low-level 

radioactive waste 

Requires reporting U-233 and 

U-235 masses in special nuclear 

material and total uranium and 

10 CFR 20, 

Appendix G 

USNRC 2010b 

intended for disposal at 

licensed land disposal 

facilities and manifests 

thorium masses in each waste 

container or in uncontainerized 

waste 

Guidelines: 

a. Air: 

ACGIH Soluble and insoluble ACGIH 2011 

TLV-TWA 0.2 mg/m3 

Ceiling 0.6 mg/m3 

NIOSH Insoluble NIOSH 2010a, 

REL-TWA (insoluble) 0.2 mg/m3 2010b 

REL-STEL 0.6 mg/m3 

Soluble 

REL-TWA (soluble) 0.05 mg/m3 

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8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Uranium 

Agency Description Information	 References 

NATIONAL (cont.) 

b. Other 

EPA-OSWER Use of soil cleanup criteria OSWER Directive 9200.4-25 EPA 1998e 

in 40 CFR Part 192 as 

remediation goals for 

CERCLA cleanup 

Establishment of cleanup OSWER Directive 9200.4-18 EPA 1997f 

levels for CERCLA site with 

radioactive contamination 

ACGIH Cancer classification A1a ACGIH 2011 

EPA-IRIS Cancer classification Withdrawn IRIS 2011 

NIOSH Cancer classification Cab NIOSH 2010a, 

2010b 

a

A1 cancer classification indicates that the agent is a confirmed human carcinogen. b

Ca cancer classification indicates that the agent is a potential occupational carcinogen. 

ACGIH = American Conference of Governmental Industrial Hygienists; ALI = annual limits on intake; BAT = best 

available technology; BPT = best practicable technology; CERCLA = Comprehensive Environmental Response, 

Compensation, and Liability Act; DAC = derived air concentration; DOE = Department of Energy; DOI = Department 

of the Interior; EPA = Environmental Protection Agency; ICRP = International Commission on Radiological 

Protection; IRIS = Integrated Risk Information System; Gy = gray; Sv = sievert; NESHAP = National Emission 

Standards for Hazardous Air Pollutants; NIOSH = National Institute for Occupational Safety and Health; 

NPDES = National Pollutant Discharge Elimination System; NPL = National Priorities List; NSPS = New Source 

Performance Standard; OAR = Office of Air and Radiation; OPPTS = Office of Pollution Prevention and Toxic 

Substances; OSHA = Occupational Safety and Health Administration; OSWER = Office of Solid Waste and 

Emergency Response; PEL = permissible exposure limit; PSNS = Pretreatment Standards for New Sources; 

REL = recommended exposure limit; STEL = short-term exposure limit; TDI = tolerable daily intake; TLV = Threshold 

Limit Values; TWA = time-weighted average; UMTRCA = Uranium Mill Tailings Radiation Control Act; USNRC = U.S. 

Nuclear Regulatory Commission; WHO = World Health Organization 

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URANIUM 364 

8. REGULATIONS AND ADVISORIES 

mice administered via gavage uranyl acetate dehydrate on gestation days 6–15 (Domingo et al. 1989c) 

and an uncertainty factor of 100 (10 for extrapolation from animals to humans and 10 for human 

variability). 

ATSDR has derived an MRL of 0.0002 mg/kg/day for intermediate-duration oral exposure to soluble 

uranium compounds based on a LOAEL of 0.06 mg U/kg/day for renal effects in rats exposed to uranyl 

nitrate hexahydrate in drinking water for 91 days (Gilman et al. 1998a) and an uncertainty factor of 300 

(3 for use of a minimal LOAEL, 10 for extrapolation from animals to humans, and 10 for human 

variability). 

EPA derived a reference dose (RfD) of 0.003 mg/kg/day for uranium based on a LOAEL of 

2.8 mg/kg/day for initial weight loss and moderate nephrotoxicity in rabbits exposed to uranium in the 

diet for 30 days (Maynard and Hodge 1949) and an uncertainty factor of 1,000 (10 for the use of a 

LOAEL, 10 for intraspecies variability and 10 for interspecies variability) (IRIS 2011). This RfD 

(developed in 1989) is currently under review by EPA. 

IARC, the U.S. Department of Human and Health Services, and the NTP have not classified uranium as 

to its carcinogenicity. According to the IRIS database, the EPA withdrew its carcinogenic assessment of 

uranium in 1993 (IRIS 2011). 

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regions of the rat lung. Human Toxicol 6:479-482. 

+*Ellender M, Haines JW, Harrison JD. 1995. The distribution and retention of plutonium, americium 

and uranium in cba/h mice. Hum Exp Toxicol 14(1):38-48. 

*Elliston JT, Glover SE, Filby RH. 2001. The determination of natural uranium in human tissues by 

recovery corrected kinetic phosphorescence analysis. J Radioanal Nucl Chem 248(2):487-491. 

*Elliston JT, Glover SE, Filby RH. 2005. Comparison of direct kinetic phosphorescence analysis and 

recovery corrected kinetic phosphorescence analysis and recovery corrected kinetic phosphorescence 

analysis for the determination of natural uranium in human tissues. J Radioanal Nucl Chem 263(2):301­

306. 

EPA. 1977a. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 141.15. 

EPA. 1977b. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 190, 

Subpart B. 

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EPA. 1979a. Ambient airborne radioactivity measurements in the vicinity of the jackpile open pit 

uranium mine New Mexico. Las Vegas, NV: U.S. Environmental Protection Agency. ISS ORP/LV79/2. PB292379. 

EPA. 1979b. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 125. 

+*EPA. 1980a. A combined methodology for estimating dose rates and health effects for exposure to 

radioactive pollutants. Oak Ridge, TN: U.S. Environmental Protection Agency. EPA78DX0231. 

ORNL/RM-7105. 

*EPA. 1980b. Source category survey: Uranium refining industry. Research Triangle Park, NC: U.S. 

Environmental Protection Agency. EPA450380010. PB80192867. 

*EPA. 1980c. Prescribed procedures for measurement of radioactivity in drinking water. Cincinnati, 

OH: U.S. Environmental Protection Agency. EPA600480032. PB80224744. 

EPA. 1980d. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 141.25. 

EPA. 1980e. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 146.5. 

EPA. 1981. Radioactivity in drinking water. Office of Drinking Water, U.S. Environmental Protection 

Agency, Washington, DC. NTIS PB81-192833. 

EPA. 1982a. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 60, Subpart 

A. 

EPA. 1982b. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 440, 

Subpart C. 

EPA. 1982c. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 440, 

Subpart H. 

EPA. 1982d. U.S. Environmental Protection Agency. 1982. Ore mining and dressing point source 

category effluent limitations guidelines and new source performance standards. Fed Reg 

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EPA. 1983a. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 122, 

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EPA. 1983b. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 192, 

Subpart A. 

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Prepared by the Office of Health and Environmental Assessment, Cincinnati, OH, for the Office of Solid 

Waste and Emergency Response, Washington, DC. 

EPA. 1984a. U.S. Environmental Protection Agency Code of Federal Regulations. 40 CFR 60 Subpart 

LL. 

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*EPA. 1984b. U.S. Environmental Protection Agency. Radionuclides: Background information 

document for final rules. Vol 1. U.S. Environmental Protection Agency, Office of Radiation Program, 

Washington, DC. EPA 520/1-84-022-1. NTIS PB85-165751. 

EPA. 1984c. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 147.3011. 

EPA. 1984d. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 147.3003. 

*EPA. 1984e. Determination of uranium in drinking water by laser induced fluorometry. EPA Method 

908.2. Cincinnati, OH: Environmental Monitoring and Support Laboratory, Physical and Chemical 

Methods Branch, U.S. Environmental Protection Agency. 

*EPA. 1985a. U.S. Environmental Protection Agency Code of Federal Regulations. 40 CFR 302.3. 

*EPA. 1985b. U.S. Environmental Protection Agency Code of Federal Regulation CFR 421, Subpart 

AD. 

EPA. 1985c. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 471,
 

Subpart G.
 

EPA. 1985d. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 471.71.
 

EPA. 1985e. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 471.72. 

EPA. 1985f. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 471.73. 

EPA. 1985g. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 471.75. 

EPA. 1985h. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 23.8. 

EPA. 1985i. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 191.12. 

*EPA. 1985j. Drinking water criteria document for uranium. Washington, DC: U.S. Environmental 

Protection Agency. PB86241049.
 

EPA. 1986a. U.S. Environmental Protection Agency. Reference values for risk assessment. Prepared by 

Environmental Criteria and Assessment Office, Office of Solid Waste, Washington, DC. 

EPA. 1986b. U.S. Environmental Protection Agency. Final rule for radon-222 emissions from licensed 

uranium mill tailings. Background information document. Report. EPA 520/1-86-009. NTIS 

PB87-207569. 

EPA. 1986c. U.S. Environmental Protection Agency. Proposed rules: Water pollution control; natural 

primary drinking water regulations; radionuclides. 40 CFR 141. Fed Regist 34836.
 

EPA. 1987a. U.S. Environmental Protection Agency. Reportable quantity adjustments for radionuclides. 

Fed Regist 52(50):8176.
 

EPA. 1987b. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 146.6. 

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EPA. 1988a. U.S. Environmental Protection Agency. Analysis of clean water act effluent guidelines 

pollutants: Summary of the chemicals regulated by industrial point source category. Prepared by the 

Industrial technology Division (WH 552), Office of Water Regulations and Standards, Office of Water, 

Washington, DC. 40 CFR Parts 400-475. 

*EPA. 1988b. U.S. Environmental Protection Agency. Limiting values of radionuclide intake and air 

concentration and dose conversion factors for inhalation, submersion, and ingestion. EPA-520/1-88-020. 

U.S. Environmental Protection Agency. Washington, DC. 

EPA. 1988c. U.S. Environmental Protection Agency. Environmental radiation protection standards for 

nuclear power operations. 40 CFR 190. 

+*EPA. 1988d. Gastrointestinal absorption of soluble uranium from drinking water. Research Triangle 

Park, NC: U.S. Environmental Protection Agency. EPA600D88G78. PB8201231. 

EPA. 1989a. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 61, Subpart 

B. 

EPA. 1989b. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 61, 

Subpart I. 

EPA. 1989c. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 61, Subpart 

Q. 

EPA. 1989d. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 61, 

Subpart T. 

EPA. 1989e. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 61, Subpart 

W. 

EPA. 1989f. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 302.4. 

EPA. 1989g. U.S. Environmental Protection Agency. Interim methods for development of inhalation 

references doses. U.S. Environmental Protection Agency, Office of Health and Environmental 

Assessment. Washington, DC. EPA 600/8-88-066F. 

EPA. 1990a. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 300, 

Appendix A. 

EPA. 1990b. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 300.5. 

EPA. 1990c. U.S. Environmental Protection Agency. Summary of state and federal drinking water 

standards and guidelines. 

*EPA. 1990d. Interim methods for development of inhalation reference concentrations. Washington, 

DC: U.S. Environmental Protection Agency, Office of Health and Environmental Assessment, Office of 

Research and Development, Environmental Criteria and Assessment Office. EPA600890066A. 

*EPA. 1991b. U.S. Environmental Protection Agency. Radionuclides in drinking water fact sheet. 

National Primary Drinking Water Regulations for Radionuclides, Proposed Rule, June, 1991. 

EPA570991700. Washington, DC. 

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*EPA. 1991a. Method 200.8: Determination of trace elements in waters and wastes by inductively 

coupled plasma-mass spectometry (revision 4.4). Cincinnati, OH: Environmental Monitoring Systems 

Laboratory, Office of Research and Development, U.S. Environmental Protection Agency. 

EPA. 1993a. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 310.11. 

Retrieval in Progress) 

EPA. 1993b. U.S. Environmental Protection Agency. Standards for management of uranium byproduct 

material pursuant to section 84 of the Atomic Energy act of 1954, as amended. Code of Federal 

Regulations. 40 CFR 192, Subpart D. 

EPA. 1993c. U.S. Environmental Protection Agency. Fed Regist 58 FR 34018 (proposed). 

EPA. 1993d. U.S. Environmental Protection Agency. Fed Regist 58 FR 54072 (proposed). 

EPA. 1993e. U.S. Environmental Protection Agency. Fed Regist 59 FR 32622 (proposed). 

*EPA. 1994a. U.S. Environmental Protection Agency. Environmental radiation data report 74, 

April-June 1993. National Air and Radiation Environmental Laboratory. EPA 402-R-93-093, August 

1994. 

*EPA. 1994b. U.S. Environmental Protection Agency. EPA requirements for quality assurance project 

plans for environmental data operations. EPA QA/R-5, draft interim final, Quality Assurance 

Management Staff, Washington, D.C. 

EPA. 1994c. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 300, 

Appendix B. 

EPA. 1994d. U.S. Environmental Protection Agency. Methods for derivation of inhalation reference 

concentrations and applications of inhalation dosimetry. EPA600890066F. 

EPA. 1995a. U.S. Environmental Protection Agency. Standards for cleanup of land and buildings 

contaminated with residual radioactive materials from inactive uranium processing sites. Code of Federal 

Regulations. 40 CFR 192, Subpart B. 

EPA. 1995b. Implementation. U.S. Environmental Protection Agency. Code of Federal Regulations. 

40 CFR 192, Subpart C. 

EPA. 1995c. U.S. Environmental Protection Agency. Standards for the control of residual radioactive 

materials from inactive uranium processing sites. Code of Federal Regulations. 40 CFR 192, Subpart A. 

*EPA. 1995d. U.S. Environmental Protection Agency. Technical resource document, extraction and 

beneficiation of ores and minerals. EPA 530-R-94-032, NTIS PB94-2008987. 

*EPA. 1996a. U.S. Environmental Protection Agency. Guidance for data quality assessment: Practical 

methods for data analysis. EPA QA/G-9 QA96 Version, EPA/600/R-96/084, Quality Assurance 

Management Staff, Washington, D.C. 

*EPA. 1996b. Environmental radiation data. Report 86. U.S. Environmental Protection Agency. 

http://www.epa.gov/narel/radnet/erd/erd86.pdf. January 28, 2011. 

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*EPA 1997a. U.S. Environmental Protection Agency. Announcement of draft drinking water 

contaminant candidate list; Notice. Fed Regist 62 FR 52194. October 6, 1997. 

*EPA. 1997b. U.S. Environmental Protection Agency. Establishment of cleanup levels for CERCLA 

sites with radioactive contamination (memorandum and attachments). OSWER No. 9200.4-18. Office of 

Solid Waste and Emergency Response. Office of Emergency and Remedial Response. 

http://www.epa.gov/superfund/. 

*EPA. 1997c. U.S. Environmental Protection Agency. National primary drinking water regulations: 

Analytical methods for radionuclides; final rule and proposed rule. Fed Regist 62 FR 10168. 

*EPA. 1997d. Special report on environmental endocrine disruption: An effects assessment and 

analysis. Washington, DC: U.S. Environmental Protection Agency, Risk Assessment Forum. 

EPA630R96012. Endocrine section 

*EPA. 1997e. Environmental radiation data. Report 92. U.S. Environmental Protection Agency. 

http://www.epa.gov/narel/radnet/erd/erd92.pdf. January 28, 2011. 

*EPA. 1997f. Establishment of cleanup levels for CERCLA sites with radioactive contamination. U.S. 

Environmental Protection Agency. OSWER No. 9200.4-18. 

*EPA. 1998c. Automated Form R for Windows: User’s guide (RY97). Washington, DC: U.S. 

Environmental Protection Agency, Office of Pollution Prevention and Toxics. 

*EPA. 1998a. Memorandum: Use of soil cleanup criteria in 40 CFR 192 as remediation goals for 

CERCLA sites. Washington, DC: U.S. Environmental Protection Agency, Office of Solid Waste and 

Emergency Response. Directive No. 9200.4-25. 

http://www.epa.gov/superfund/resources/soil/cleanup.htm. October 22, 1998. 

EPA. 1998b. U.S. Environmental Protection Agency. Land disposal restrictions phase IV: Final rule 

promulgating treatment standards for metal wastes and mineral processing wastes; mineral processing 

secondary materials and bevill exclusion issues; treatment standards for hazardous soils, and exclusion of 

recycled wood preserving wastewaters; final rule. Fed Regist 63 FR 28556. May 26, 1998. 

*EPA. 1998d. Land disposal restrictions phase IV: final rule promulgating treatment standards for metal 

wastes and mineral processing wastes; mineral processing secondary materials and Bevill Exclusion 

Issues; treatment standards for hazardous soils, and exclusion of recycled wood preserving wastewaters. 

U.S. Environmental Protection Agency. Fed Regist 63:28556-28753. 

*EPA. 1998e. Use of soil cleanup criteria in 40 CFR part 192 as remediation goals for CERCLA sites. 

U.S. Environmental Protection Agency. OSWER No. 9200.4-25. 

*EPA. 2000. Data quality objectives process for hazardous waste site investigations. Washington, DC: 

U.S. Environmental Protection Agency, Office of Environmental Information. EPA600R00007. 

www.epa.gov/quality/qs-docs/g4hw-final.pdf. March 23, 2011. 

*EPA. 2005a. Environmental radiation data. Report 124. U.S. Environmental Protection Agency. 

http://www.epa.gov/narel/radnet/erd/erd124.pdf. January 28, 2011. 

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*EPA. 2005b. Toxic chemical release inventory reporting forms and instructions: Revised 2004 version. 

Section 313 of the Emergency Planning and Community Right-to-Know Act (Title III of the Superfund 

Amendments and Reauthorization Act of 1986). U.S. Environmental Protection Agency. Office of 

Environmental Information. EPA260B05001. 

*EPA. 2006a. Data quality assessment: A reviewer's guide. Washington, DC: U.S. Environmental 

Protection Agency, Office of Environmental Information. EPA240B06002. 

www.epa.gov/QUALITY/qs-docs/g9r-final.pdf. March 23, 2011. 

*EPA. 2006b. Data quality assessment: Statistical methods for practitioners. Washington, DC: U.S. 

Environmental Protection Agency, Office of Environmental Information. EPA240B06003. 

www.epa.gov/quality/qs-docs/g9s-final.pdf. March 23, 2011. 

*EPA. 2007. Environmental radiation data. Report 132. U.S. Environmental Protection Agency. 

http://www.epa.gov/narel/radnet/erd/erd132.pdf. January 28, 2011. 

*EPA. 2010a. Analytical methods for radioactivity. U.S. Environmental Protection Agency. Code of 

Federal Regulations 40 CFR 141.25 http://edocket.access.gpo.gov/cfr_2010/julqtr/pdf/40cfr141.25.pdf. 

January 27, 2011. 

*EPA. 2010b. Appendix A to subpart C of part 141—Alternative testing methods approved for analyses 

under the safe drinking water act. U.S. Environmental Protection Agency. Code of Federal Regulations 

40 CFR 141, Subpart C, Appendix A 

http://edocket.access.gpo.gov/cfr_2010/julqtr/pdf/40cfr141CAppA.pdf. January 27, 2011. 

*EPA. 2010c. Appendix D to part 122—NPDES permit application testing requirements. U.S. 

Environmental Protection Agency. Code of Federal Regulations 40 CFR 122, Appendix D 

http://edocket.access.gpo.gov/cfr_2010/julqtr/pdf/40cfr122AppD.pdf. January 27, 2011. 

*EPA. 2010d. Aquifer exemptions. U.S. Environmental Protection Agency. Code of Federal 

Regulations 40 CFR 147.3003 http://edocket.access.gpo.gov/cfr_2010/julqtr/pdf/40cfr147.3003.pdf. 

January 27, 2011. 

*EPA. 2010e. Classification of injection wells. U.S. Environmental Protection Agency. Code of 

Federal Regulations 40 CFR 146.5 http://edocket.access.gpo.gov/cfr_2010/julqtr/pdf/40cfr146.5.pdf. 

January 27, 2011. 

*EPA. 2010f. Designation of hazardous substances. U.S. Environmental Protection Agency. Code of 

Federal Regulations 40 CFR 302.4. http://edocket.access.gpo.gov/cfr_2010/julqtr/pdf/40cfr302.4.pdf. 

January 27, 2011. 

*EPA. 2010g. Maximum contaminant level goals for radionuclides. U.S. Environmental Protection 

Agency. Code of Federal Regulations 40 CFR 141.55 

http://edocket.access.gpo.gov/cfr_2010/julqtr/pdf/40cfr141.55.pdf. January 27, 2011. 

*EPA. 2010h. Maximum contaminant levels for radionuclides. U.S. Environmental Protection Agency. 

Code of Federal Regulations 40 CFR 141.66 

http://edocket.access.gpo.gov/cfr_2010/julqtr/pdf/40cfr141.66.pdf. January 27, 2011. 

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*EPA. 2010i. Plugging and abandonment of Class III wells. U.S. Environmental Protection Agency. 

Code of Federal Regulations 40 CFR 147.3011 

http://edocket.access.gpo.gov/cfr_2010/julqtr/pdf/40cfr147.3011.pdf. January 27, 2011. 

*EPA. 2010j. RadNet-tracking environmental radiation nationwide. U.S. Environmental Protection 

Agency. http://www.epa.gov/narel/radnet/aboutus.html. January 28, 2011. 

*EPA. 2010k. What terms have specific definitions? U.S. Environmental Protection Agency. Code of 

Federal Regulations 40 CFR 310.3 http://edocket.access.gpo.gov/cfr_2010/julqtr/pdf/40cfr310.3.pdf. 

*EPA. 2011a. Appendix A to part 300—The hazard ranking system. U.S. Environmental Protection 

Agency. Code of Federal Regulations 40 CFR 300, Appendix A. 

*EPA. 2011b. Appendix B to 302.4—Radionuclides. U.S. Environmental Protection Agency. Code of 

Federal Regulations 40 CFR 302.4, Appendix B. 

*EPA. 2011c. Criteria and standards for the national pollutant discharge elimination system. U.S. 

Environmental Protection Agency. Code of Federal Regulations 40 CFR 125. 

*EPA. 2011d. Definitions. U.S. Environmental Protection Agency. Code of Federal Regulations 40 

CFR 300.5. 

*EPA. 2011e. Effluent limitations guidelines representing the degree of effluent reduction attainable by 

the application of the best practicable control technology currently available. U.S. Environmental 

Protection Agency. Code of Federal Regulations 40 CFR 421.322. 

*EPA. 2011f. Effluent limitations guidelines representing the degree of effluent reduction attainable by 

the application of the best available technology economically achievable. U.S. Environmental Protection 

Agency. Code of Federal Regulations 40 CFR 421.323. 

*EPA. 2011g. Exclusions. U.S. Environmental Protection Agency. Code of Federal Regulations 40 

CFR 261.4. 

*EPA. 2011h. Pretreatment standards for new sources. U.S. Environmental Protection Agency. Code of 

Federal Regulations 40 CFR 421.326. 

*EPA. 2011i. Pretreatment standards for new sources (PSNS). U.S. Environmental Protection Agency. 

Code of Federal Regulations 40 CFR 471.75. 

*EPA. 2011j. Standards of performance for new sources. U.S. Environmental Protection Agency. Code 

of Federal Regulations 40 CFR 421.324. 

*EPA. 2011k. Subpart A—General provisions. U.S. Environmental Protection Agency. Code of 

Federal Regulations 40 CFR 60, Subpart A. 

*EPA. 2011l. Subpart A—Standards for the control of residual radioactive materials from inactive 

uranium processing sites. U.S. Environmental Protection Agency. Code of Federal Regulations 40 CFR 

192, Subpart A. 

*EPA. 2011m. Subpart AD - Secondary uranium subcategory. U.S. Environmental Protection Agency. 

Code of Federal Regulations 40 CFR 421, Subpart AD. 

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*EPA. 2011n. Subpart B—National emission standards for radon emissions from underground uranium 

mines. U.S. Environmental Protection Agency. Code of Federal Regulations 40 CFR 61, Subpart B. 

*EPA. 2011o. Subpart B—Environmental standards for the uranium fuel cycle. U.S. Environmental 

Protection Agency. Code of Federal Regulations 40 CFR 190, Subpart B. 

*EPA. 2011p. Subpart B—Standards for cleanup of land and buildings contaminated with residual 

radioactive materials from inactive uranium processing sites. U.S. Environmental Protection Agency. 

Code of Federal Regulations 40 CFR 192, Subpart B. 

*EPA. 2011q. Subpart C—Environmental standards for ground-water protection. U.S. Environmental 

Protection Agency. Code of Federal Regulations 40 CFR 191, Subpart C. 

*EPA. 2011r. Subpart C—Implementation. U.S. Environmental Protection Agency. Code of Federal 

Regulations 40 CFR 192, Subpart C. 

*EPA. 2011s. Subpart C—Uranium, radium and vanadium ores subcategory. U.S. Environmental 

Protection Agency. Code of Federal Regulations 40 CFR 440, Subpart C. 

*EPA. 2011t. Subpart D—Standards for management of uranium byproduct materials pursuant to 

Section 84 of the Atomic Energy Act of 1954, as amended. U.S. Environmental Protection Agency. 

Code of Federal Regulations 40 CFR 192, Subpart D. 

*EPA. 2011u. Subpart G—Uranium forming subcategory. U.S. Environmental Protection Agency. 

Code of Federal Regulations 40 CFR 471, Subpart G. 

*EPA. 2011v. Subpart H—National emission standards for emissions of radionuclides other than radon 

from Department of Energy. U.S. Environmental Protection Agency. Code of Federal Regulations 40 

CFR 61, Subpart H. 

*EPA. 2011w. Subpart I—National emission standards for radionuclide emissions from federal facilities 

other than Nuclear Regulatory Commission licensees and not covered by Subpart H. U.S. Environmental 

Protection Agency. Code of Federal Regulations 40 CFR 61, Subpart I. 

*EPA. 2011x. Subpart LL—Standards of performance for metallic mineral processing plants. U.S. 

Environmental Protection Agency. Code of Federal Regulations 40 CFR 60, Subpart LL. 

*EPA. 2011y. Subpart Q—National emission standards for radon emissions from Department of Energy 

facilities. U.S. Environmental Protection Agency. Code of Federal Regulations 40 CFR 61, Subpart Q. 

*EPA. 2011z. Subpart R—National emission standards for radon emissions from phosphogypsum 

stacks. U.S. Environmental Protection Agency. Code of Federal Regulations 40 CFR 61, Subpart R. 

*EPA. 2011aa. Subpart T—National emission standards for radon emissions from the disposal of 

uranium mill tailings. U.S. Environmental Protection Agency. Code of Federal Regulations 40 CFR 61, 

Subpart T. 

*EPA. 2011bb. Subpart W—National emission standards for radon emissions from operating mill 

tailings. U.S. Environmental Protection Agency. Code of Federal Regulations 40 CFR 61, Subpart W. 

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Woods DA. 1986. Final product dust activity median aerodynamic diameters in the product packing 

areas of two Australian uranium mills. Health Phys 51:352-356. 

*Woodward A, Roder D, McMichael AJ, et al. 1991. Radon daughter exposures at the Radium Hill 

uranium mine and lung cancer rates among former workers, 1982-1987. Cancer Causes Control 2(4):213­

220. 

*Wrenn ME, Bertelli L, Durbin PW, et al. 1994. A comprehensive metabolic model for uranium 

metabolism and dosimetry based on human and animal data. Radiat Prot Dosimetry 53(1-4):255-258. 

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+*Wrenn ME, Durbin PW, Howard B. 1985. Metabolism of ingested uranium and radium. Health Phys 

48:601-633. 

+*Wrenn ME, Durbin PW, Willis DL, et al. 1987. The potential toxicity of uranium in water. Am 

Water Works Assoc J 79:177-184. 

*Wrenn ME, Singh NP, Ruth H, et al. 1989. Gastrointestinal absorption of soluble uranium from 

drinking water by man. Radiat Prot Dosim 26:119-122. 

+*Wrenn ME, Singh NP, Saccomanno G. 1983. Uranium and thorium isotopes and their state of 

equilibria in lungs from uranium miners. Health Phys 44(Suppl 1):385-389. 

+*Yamamoto T, Masuda K, Nukada K. 1971. Studies on environmental contamination by uranium. 6. 

Uranium in total diet and human urine from nonoccupationally exposed persons in Okayama Prefecture 

(1969-1971). J Radiation Res 13(1):5. 

Yamamoto T, Masuda K, Onishi N. 1968. Studies on environmental contamination by uranium. J 

Environ Surv of Uranium in Kamiscaibara Village, Okayama Prefecture. J Rad Res 9:92-99. 

*Yan M, Zhong G, Gao L, et al. 2010. The effects of depleted uranium on 1α-hydroxylase in kidney of 

rats. Hum Exp Toxicol [epub ahead of print]. 

*Yang IC, Edwards KW. 1984. Releases of radium and uranium into Ralston Creek and Reservoir 

Colorado, from uranium mining. In: Barney GS, Navratil JD, Schulz W, eds. ACS Symposium Series 

246. Geochemical behavior of disposed radioactive waste. Washington, DC: American Chemical 

Society, 271-286. 

*Yazzie M, Gamble SL, Civitello ER, et al. 2003. Uranyl acetate causes DNA single strand breaks in 

vitro in the presence of ascorbate (vitamin C). Chem Res Toxicol 16(4):524-530. 

+Yu RC, Sherwood RJ. 1996. The relationships between urinary elimination, airborne concentration, 

and radioactive hand contamination for workers exposed to uranium. AIHA 57(7):615-620. 

Yuile CL. 1973. Animal experiments. In: Hodge HC, Stannard JN, Hursh JB, eds. Handbook of 

experimental pharmacology, Vol. 36. Berlin: Springer-Verlag, 165-196. 

+Zalups RK. 1991. An evaluation of Tiron (sodium 4,5-dihydroxybenzene-1,3-disulfonate) as a rescue 

agent for the nephropathy induced by uranyl fluoride (UO2F2) in rats. Res Commun Chem Pathol 

Pharmacol 72(1):125-128. 

*Zhu G, Tan M, Li Y, et al. 2009a. Accumulation and distribution of uranium in rats after implantation 

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*Zhu G, Xiang X, Chen X, et al. 2009b. Renal dysfunction induced by long-term exposure to depleted 

uranium in rats. Arch Toxicol 83(1):37-46. 

*Ziegler EE, Edwards BB, Jensen RL, et al. 1978. Absorption and retention of lead by infants. Pediatr 

Res 12(1):29-34. 

*Zielinski RA, McKown DM. 1984. Determination of uranium concentration in water by liquid 

anion-exchange-delayed-neutron analysis. J Radioanal Nucl Chem 84:207-212. 

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Some terms in this glossary are generic and may not be used in this profile. 

Absorbed Dose, Chemical—The amount of a substance that is either absorbed into the body or placed in 

contact with the skin. For oral or inhalation routes, this is normally the product of the intake quantity and 

the uptake fraction divided by the body weight and, if appropriate, the time, expressed as mg/kg for a 

single intake or mg/kg/day for multiple intakes. For dermal exposure, this is the amount of material 

applied to the skin, and is normally divided by the body mass and expressed as mg/kg. 

Absorbed Dose, Radiation—The mean energy imparted to the irradiated medium, per unit mass, by 

ionizing radiation. Units: rad (rad), gray (Gy). 

Absorbed Fraction—A term used in internal dosimetry. It is that fraction of the photon energy (emitted 

within a specified volume of material) which is absorbed by the volume. The absorbed fraction depends 

on the source distribution, the photon energy, and the size, shape and composition of the volume. 

Absorption—The process by which a chemical penetrates the exchange boundaries of an organism after 

contact, or the process by which radiation imparts some or all of its energy to any material through which 

it passes. 

Absorption Coefficient—Fractional absorption of the energy of an unscattered beam of x- or gammaradiation per unit thickness (linear absorption coefficient), per unit mass (mass absorption coefficient), or 

per atom (atomic absorption coefficient) of absorber, due to transfer of energy to the absorber. The total 

absorption coefficient is the sum of individual energy absorption processes (see Compton Effect, 

Photoelectric Effect, and Pair Production). 

Absorption Coefficient, Linear—A factor expressing the fraction of a beam of x- or gamma radiation 

absorbed in a unit thickness of material. In the expression I=Ioe

-μx, Io is the initial intensity, I the intensity 

of the beam after passage through a thickness of the material x, and μ is the linear absorption coefficient. 

Absorption Coefficient, Mass—The linear absorption coefficient per cm divided by the density of the 

absorber in grams per cubic centimeter. It is frequently expressed as μ/ρ, where μ is the linear absorption 

coefficient and ρ the absorber density. 

Absorption Ratio, Differential—Ratio of concentration of a nuclide in a given organ or tissue to the 

concentration that would be obtained if the same administered quantity of this nuclide were uniformly 

distributed throughout the body. 

Activation—The process of making a material radioactive by bombardment with neutrons or protons. 

Activity—The number of radioactive nuclear transformations occurring in a material per unit time (see 

Curie, Becquerel). The term for activity per unit mass is specific activity. 

Activity Median Aerodynamic Diameter (AMAD)—The diameter of a unit-density sphere with the 

same terminal settling velocity in air as that of the aerosol particle whose activity is the median for the 

entire size distribution of the aerosol. 

Acute Exposure, Chemical—Exposure to a chemical for a duration of 14 days or less, as specified in the 

Toxicological Profiles. 

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Acute Exposure, Radiation—The absorption of a relatively large amount of radiation (or intake of a 

radioactive material) over a short period of time. 

Acute Radiation Syndrome—The symptoms which taken together characterize a person suffering from 

the effects of intense radiation. The effects occur within hours or days. 

Ad libitum—Available in excess and freely accessible. 

Adsorption Coefficient (Koc)—The ratio of the amount of a chemical adsorbed per unit surface area or 

per unit weight of organic carbon of a specific particle size in the soil or sediment to the concentration of 

the chemical in solution at equilibrium. 

Adsorption Ratio (Kd)—See Distribution Coefficient 

Alpha Particle—A positively charged particle ejected spontaneously from the nuclei of some radioactive 

elements. It is identical to a helium nucleus, i.e., 2 neutrons and two protons, with a mass number of 4 

and an electrostatic charge of +2. 

Alpha Track—The track of ionized atoms (pattern of ionization) left in a medium by an alpha particle 

that has traveled through the medium. 

Annihilation (Positron-Electron)—An interaction between a positive and a negative electron in which 

they both disappear; their rest mass, being converted into electromagnetic radiation (called annihilation 

radiation) with two 0.51 MeV gamma photons emitted at an angle of 180 to each other. 

Annual Limit on Intake (ALI)—The derived limit for the amount of radioactive material taken into the 

body of an adult worker by inhalation or ingestion in a year. It is the smaller value of intake of a given 

radionuclide in a year by the reference man that would result in a committed effective dose equivalent of 

5 rem or a committed dose equivalent of 50 rem to any organ or tissue. 

Atom—The smallest particle of an element that cannot be divided or broken up by chemical means. It 

consists of a central core called the nucleus, which contains protons and neutrons and an outer shell of 

electrons. 

Atomic Mass (u)—The mass of a neutral atom of a nuclide, usually expressed in terms of "atomic mass 

units." The "atomic mass unit" is one-twelfth the mass of one neutral atom of carbon-12; equivalent to 

1.6604x10-24 g. 

Atomic Mass Number—See Mass Number. 

Atomic Number—The number of protons in the nucleus of an atom. The "effective atomic number" is 

calculated from the composition and atomic numbers of a compound or mixture. An element of this 

atomic number would interact with photons in the same way as the compound or mixture. (Symbol: Z). 

Atomic Weight—The weighted mean of the masses of the neutral isotopes of an element expressed in 

atomic mass units. 

Attenuation—A process by which a beam from a source of radiation is reduced in intensity by 

absorption and scattering when passing through some material. 

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Attenuation Coefficient—The fractional reduction in the intensity of a beam of radiation as it passes 

through an absorbing medium. It may be expressed as reduction per unit distance, per unit mass 

thickness, or per atom, and is called the linear, mass, or atomic attenuation coefficient, respectively. 

Auger Effect—The emission of an electron from the extranuclear portion of an excited atom when the 

atom undergoes a transition to a less excited state. 

Background Radiation—The amount of radiation to which a member of the general population is 

exposed from natural sources, such as terrestrial radiation from naturally occurring radionuclides in the 

soil, cosmic radiation originating from outer space, and naturally occurring radionuclides deposited in the 

human body. 

Becquerel (Bq)—International System of Units unit of activity and equals that quantity of radioactive 

material in which one transformation (disintegration) occurs per second (see Units). 

Terabecquerel (TBq)—One trillion becquerel. 

Gigabecquerel (GBq)—One billion becquerel. 

Megabecquerel (MBq)—One million becquerel. 

Kilobecquerel (kBq))—One thousand becquerel. 

Millibecquerel (mBq)—One-thousandth of a becquerel. 

Microbecquerel (μBq)—One-millionth of a becquerel. 

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. 

Beta Particle—An electron that is emitted from the nucleus of an atom during one type of radioactive 

transformation. A beta particle has a mass and charge equal in magnitude to that of the electron. The 

charge may be either +1 or -1. Beta particles with +1 charges are called positrons (symbolized β+

), and 

beta particles with -1 charges are called negatrons (symbolized β-

). 

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. 

Biologic Effectiveness of Radiation—See Relative Biological Effectiveness. 

Biological Half-time—The time required for a biological system, such as that of a human, to eliminate by 

natural process half of the amount of a substance (such as a chemical substance, either stable or 

radioactive) that has entered it. 

Biomagnification—The progressive increase in the concentration of a bioaccumulated chemical in 

organisms as that chemical is passed from the bottom to the top of the food web. 

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. 

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Body Burden, Chemical—The total amount of a chemical found in an animal or human body. 

Body Burden, Radioactivity—The amount of radioactive material found in an animal or human body. 

Bone Seeker—Any compound or ion which migrates in the body and preferentially deposits into bone. 

Branching—The occurrence of two or more modes by which a radionuclide can undergo radioactive 

decay. For example, 214Bi can undergo alpha or beta minus decay, 64Cu can undergo beta minus, beta 

plus, or electron capture decay. An individual atom of a nuclide exhibiting branching disintegrates by one 

mode only. The fraction disintegrating by a particular mode is the "branching fraction" for that mode. 

The "branching ratio" is the ratio of two specified branching fractions (also called multiple 

disintegration). 

Bremsstrahlung—X rays that are produced when a charged particle accelerates (speeds up, slows down, 

or changes direction) in the strong field of a nucleus. 

Buildup Factor—The ratio of the radiation intensity, including both primary and scattered radiation, to 

the intensity of the primary (unscattered) radiation. 

Cancer Effect Level (CEL)—The lowest dose of chemical or radiation 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. 

Capture, Electron—A mode of radioactive decay involving the capture of an orbital electron by its 

nucleus. Capture from a particular electron shell, e.g., K or L shells, is designated as "K-electron capture" 

or "L-electron capture." 

Capture, K-Electron—Electron capture from the K shell by the nucleus of the atom. Also loosely used 

to designate any orbital electron capture process. 

Carcinogen—A chemical or radiation that is capable of inducing cancer. 

Carcinoma—Malignant neoplasm composed of epithelial cells, regardless of their derivation. 

Case-Control Study—A type of epidemiological study which 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. 

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. 

Cataract—A clouding of the crystalline lens of the eye which obstructs the passage of light. 

Ceiling Value—A concentration of a substance that should not be exceeded, even temporarily. 

Charged Particle—A nuclear particle, atom, or molecule carrying a positive or negative charge. 

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Chronic Exposure—A long-term, continuous exposure to a chemical or radioactive material. For 

example, 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. 

Collective Dose—The sum of the individual doses received in a given period of time by a specified 

population from exposure to a specified source of radiation. Collective dose is expressed in units such as 

man-rem and person-sievert. 

Compton Effect—An attenuation process observed for x- or gamma radiation in which an incident 

photon interacts with an orbital electron of an atom to produce a recoil electron and a scattered photon 

whose energy is less than the incident photon. 

Containment—The confinement of a chemical or radioactive substance in such a way that it is prevented 

from being dispersed from its container or into the environment, or is released only at a specified rate. 

Contamination—Deposition of a stable or radioactive substance in any place where it is not desired. 

Cosmic Rays—High-energy particulate and electromagnetic radiations that originate outside the earth's 

atmosphere and interact with the atmosphere to produce a shower of secondary cosmic rays. 

Count (Radiation Measurements)—The external indication of a radiation-measuring device designed to 

enumerate ionizing events. It refers to a single detected event. The term “count rate” refers to the total 

number registered in a given period of time. The term is sometimes erroneously used to designate a 

disintegration, ionizing event, or voltage pulse. 

Counter, Gas-flow Proportional (GPC)—An instrument for detecting beta particle radiation. Beta 

particles are detected by ionization of the counter gas which results in an electrical impulse at an anode 

wire. 

Counter, Geiger-Mueller (GM counter)—Highly sensitive, gas-filled radiation-measuring device that 

detects (counts) individual photons or particulate radiation. 

Counter, Scintillation—The combination of a crystal or phosphor, photomultiplier tube, and associated 

circuits for counting light emissions produced in the phosphors by ionizing radiation. Scintillation 

counters generally are more sensitive than GM counters for gamma radiation. 

Counting, Cerenkov—Relatively energetic β-particles pass through a transparent medium of high 

refractive index and a highly-directional, bluish-white light ("Cerenkov" light) is emitted. This light is 

detected using liquid scintillation counting equipment. 

Cross-sectional Study—A type of epidemiological study of a group or groups which examines the 

relationship between exposure and outcome to a chemical or to chemicals at one point in time. 

Curie (Ci)—A unit of radioactivity. One curie equals that quantity of radioactive material in which there 

are 3.7x1010 nuclear transformations per second. The activity of 1 gram of radium is approximately 1 Ci. 

Attocurie (aCi)—One-thousandth of a femtocurie (3.7x10-8 disintegrations per second). 

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Femtocurie (fCi)—One-billionth of a microcurie (3.7x10-5 disintegrations per second). 

Megacurie (MCi)—One million curies (3.7x1016 disintegrations per second). 

Microcurie (μCi)—One-millionth of a curie (3.7x104 disintegrations per second). 

Millicurie (mCi)—One-thousandth of a curie (3.7x107 disintegrations per second). 

Nanocurie (nCi)—One-billionth of a curie (3.7x101 disintegrations per second). 

Picocurie (pCi)—One-millionth of a microcurie (3.7x10-2 disintegrations per second). 

Data Needs—Substance-specific informational needs that if met would reduce the uncertainties of human 

health assessment. 

Daughter Products—See Progeny and Decay Product 

Decay Chain or Decay Series—A sequence of radioactive decays (transformations) beginning with one 

nucleus. The initial nucleus, the parent, decays into a daughter or progeny nucleus that differs from the 

first by whatever particles were emitted during the decay. If further decays take place, the subsequent 

nuclei are also usually called daughters or progeny. Sometimes, to distinguish the sequence, the daughter 

of the first daughter is called the granddaughter, etc. 

Decay Constant (λ)—The fraction of the number of atoms of a radioactive nuclide which decay in unit 

time (see Disintegration Constant). 

Decay Product, Daughter Product, Progeny—A new nuclide formed as a result of radioactive decay. 

A nuclide resulting from the radioactive transformation of a radionuclide, formed either directly or as the 

result of successive transformations in a radioactive series. A decay product (daughter product or 

progeny) may be either radioactive or stable. 

Decay, Radioactive—Transformation of the nucleus of an unstable nuclide by spontaneous emission of 

radiation, such as charged particles and/or photons (see Disintegration). 

Delta Ray—An electron removed from an atom of a medium that is irradiated, or through which 

radiation passes, during the process of ionization (also called secondary electron). Delta rays cause a 

track of ionizations along their path. 

Derived Air Concentration (DAC)—The concentration of radioactive material in air that, if breathed by 

the reference man for a working year of 2000 hours under conditions of light work (at a rate of 1.2 liters 

of air per hour), would result in an intake of one ALI (see Annual Limit on Intake). 

Deterministic Effect—A health effect, the severity of which varies with the dose and for which a 

threshold is believed to exist (also called a non-stochastic effect). 

Developmental Toxicity—The occurrence of adverse effects on the developing organism that may result 

from exposure to a chemical or radiation 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. 

Disintegration Constant—Synonymous with decay constant. The fraction of the number of atoms of a 

radioactive material that decays per unit time (see Decay Constant.) 

Disintegration, Nuclear—A spontaneous nuclear transformation (radioactivity) characterized by the 

emission of energy and mass from the nucleus. When large numbers of nuclei are involved, the process is 

characterized by a definite half-life (see Transformation, Nuclear). 

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Distribution Coefficient (Kd)—Describes the distribution of a chemical between the solid and aqueous 

phase at thermodynamic equilibrium, is given as follows: 

[C] s Kd = [C] w , Units = (L solution)/(kg solid), 

where [C]s is the concentration of the chemical associated with the solid phase in units of (mg)/(kg solid), 

and [C]w is the concentration of the chemical in the aqueous phase in units of (mg)/(L solution). As the 

magnitude of Kd decreases, the potential mobility of the chemical to groundwater systems increases and 

vice versa. 

Dose—A general term denoting the quantity of a substance, radiation, or energy absorbed. For special 

purposes it must be appropriately qualified. If unqualified, it refers to radiation absorbed dose. 

Absorbed Dose—The energy imparted to matter by ionizing radiation per unit mass of irradiated 

material at the place of interest. The unit of absorbed dose is the rad. One rad equals 100 ergs 

per gram. In SI units, the absorbed dose is the gray which is 1 J/kg (see Rad). 

Cumulative Dose (Radiation)—The total dose resulting from repeated or continuous exposures 

to radiation. 

Dose Assessment—An estimate of the radiation dose to an individual or a population group usually by 

means of predictive modeling techniques, sometimes supplemented by the results of measurement. 

Dose Equivalent (DE)—A quantity used in radiation safety practice to account for the relative biological 

effectiveness of the several types of radiation. It expresses all radiations on a common scale for 

calculating the effective absorbed dose. The NRC defines it as the product of the absorbed dose, the 

quality factor, and all other modifying factors at the location of interest. ICRP has changed its definition 

to be the product of the absorbed dose and the radiation weighting factor. (The unit of dose equivalent is 

the rem. In SI units, the dose equivalent is the sievert, which equals 100 rem.) 

Dose, Fractionation—A method of administering therapeutic radiation in which relatively small doses 

are given daily or at longer intervals. 

Dose, Protraction—A method of administering therapeutic radiation by delivering it continuously over a 

relatively long period at a low dose rate. 

Dose, Radiation—The amount of energy imparted to matter by ionizing radiation per unit mass of the 

matter, usually expressed as the unit rad, or in SI units, the gray. 100 rad1 gray (Gy) (see Absorbed 

Dose). 

Committed Dose Equivalent (HT,50)—The dose equivalent to organs or tissues of reference (T) 

that will be received from an intake of radioactive material by an individual during the 50 years 

following the intake. 

Committed Effective Dose Equivalent (HE,50)—The sum of the products of the weighting 

factors applicable to each of the body organs or tissues that are irradiated and the committed dose 

equivalent to those organs or tissues. 

Effective Dose —A dose value that attempts to normalize the detriment to the body (for cancer 

mortality and morbidity, hereditary effects, and years of life lost) from a non-uniform exposure to 

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URANIUM 438 

10. GLOSSARY 

that of a uniform whole body exposure. Effective dose is calculated as the sum of products of the 

equivalent dose and the tissue weighting factor (wT) for each tissue exposed. (E = ∑DT,R wR wT)). 

Effective Dose Equivalent (HE)—This dose type is limited to internal exposures and is the sum 

of the products of the dose equivalent to the organ or tissue (HT) and the weighting factors (wT) 

applicable to each of the body organs or tissues that are irradiated. (HE = ∑wT HT). 

Equivalent Dose—A dose quantity that places the biological effect of all radiation types on a 

common scale for calculating tissue damage. Alpha particles, for example, are considered to 

cause 20 times more damage than gamma rays. Equivalent dose is calculated as the sum of 

products of the average absorbed dose (in gray) in an organ or tissue (DT,R) from each type of 

radiation and the radiation weighting factor (wR) for that radiation (∑DT,R wR). 

External Dose—That portion of the dose equivalent received from radiation sources outside the 

body. 

Internal Dose—That portion of the dose equivalent received from radioactive material taken into 

the body. 

Limit—A permissible upper bound on the radiation dose. 

Maximum Permissible Dose (MPD)—The greatest dose equivalent that a person or specified 

part thereof shall be allowed to receive in a given period of time. 

Median Lethal Dose (MLD)—Dose of radiation required to kill, within a specified period 

(usually 30 days), 50% of the individuals in a large group of animals or organisms. Also called 

the LD50, or LD50/30 if for 30 days. 

Threshold Dose—The minimum absorbed dose that will produce a detectable degree of any 

given effect. 

Tissue Dose—Absorbed dose received by tissue in the region of interest, expressed in rad (see 

Dose, Gray, and Rad). 

Dose Rate—The amount of radiation dose delivered per unit time. Generically, the rate at which 

radiation dose is delivered to any material or tissue. 

Dose-Response Relationship—The quantitative relationship between the amount of exposure to a 

toxicant and the incidence of the adverse effects. 

Dosimetry—Quantification of radiation doses to cells, tissues, organs, individuals or populations 

resulting from radiation exposures. 

Early Effects (of radiation exposure)—Effects that appear within 60 days of an acute exposure. 

Electron—A stable elementary particle having an electric charge equal to ±1.60210x10-19 C (Coulombs) 

and a rest mass equal to 9.1091x10-31 kg. A positron is a positively charged "electron" (see Positron). 

Electron Volt—A unit of energy equivalent to the energy gained by an electron in passing through a 

potential difference of one volt. Larger multiple units of the electron volt are frequently used: keV for 

thousand or kilo electron volts; MeV for million or mega electron volts (eV). 1 eV=1.6x10-12 erg. 

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Embryotoxicity and Fetotoxicity—Any toxic effect on the conceptus 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 occurred. The terms, as used here, include malformations and variations, altered growth, and in 

utero death. 

Energy—Capacity for doing work. Gravitationally, "potential energy" is the energy inherent in a mass 

because of its spatial relation to other masses. Chemically or radiologically, “potential energy” is the 

energy released when a chemical reaction or radiological transformation goes to completion. "Kinetic 

energy" is the energy possessed by a mass because of its motion (SI unit: joules): 

Binding Energy (Electron)—The amount of energy that must be expended to remove an 

electron from an atom. 

Binding Energy (Nuclear)—The energy represented by the difference in mass between the sum 

of the component parts and the actual mass of the nucleus. It represents the amount of energy 

that must be expended to break a nucleus into its component neutrons and protons. 

Excitation Energy—The energy required to change a system from its ground state to an excited 

state. Each different excited state has a different excitation energy. 

Ionizing Energy—The energy required to knock an electron out of an atom. The average energy 

lost by electrons or beta particles in producing an ion pair in air or in soft tissue is about 34 eV. 

Radiant Energy—The energy of electromagnetic radiation, such as radio waves, visible light, x 

and gamma rays. 

Enrichment, Isotopic—An isotopic separation process by which the relative abundances of the isotopes 

of a given element are altered, thus producing a form of the element that has been enriched in one or more 

isotopes and depleted in others. In uranium enrichment, the percentage of uranium-235 in natural 

uranium can be increased from 0.7% to >90% in a gaseous diffusion process based on the different 

thermal velocities of the constituents of natural uranium (234U, 235U, 238U) in the molecular form UF6. 

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. 

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. 

Equilibrium, Radioactive—In a radioactive series, the state which prevails when the ratios between the 

activities of two or more successive members of the series remains constant. 

Secular Equilibrium—If a parent element has a very much longer half-life than the daughters 

(so there is not appreciable change in its amount in the time interval required for later products to 

attain equilibrium) then, after equilibrium is reached, equal numbers of atoms of all members of 

the series disintegrate in unit time. This condition is never exactly attained, but is essentially 

established in such a case as 226Ra and its transformation series to stable 206Pb. The half-life of 

226Ra is about 1,600 years; of 222Rn, approximately 3.82 days, and of each of the subsequent 

members, a few minutes. After about a month, essentially the equilibrium amount of radon is 

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URANIUM 440 

10. GLOSSARY 

present; then (and for a long time) all members of the series disintegrate the same number of 

atoms per unit time. At this time, the activity of the daughter is equal to the activity of the parent. 

Transient Equilibrium—If the half-life of the parent is short enough so the quantity present 

decreases appreciably during the period under consideration, but is still longer than that of 

successive members of the series, a stage of equilibrium will be reached after which all members 

of the series decrease in activity exponentially with the period of the parent. At this time, the 

ratio of the parent activity to the daughter activity is constant. 

Equilibrium, Electron—The condition in a radiation field where the energy of the electrons entering a 

volume equals the energy of the electrons leaving that volume. 

Excitation—The addition of energy to a system, thereby transferring it from its ground state to an excited 

state. Excitation of a nucleus, an atom, or a molecule can result from absorption of photons or from 

inelastic collisions with other particles. The excited state of an atom is an unstable or metastable state and 

will return to ground state by radiation of the excess energy. 

Exposure (Chemical)—Contact of an organism with a chemical or physical agent. Exposure is 

quantified as the amount of the agent available at the exchange boundaries of the organism (e.g., skin, 

lungs, gut) and available for absorption. 

Exposure (Radiation)—Subjection to ionizing radiation or to a radioactive material. For example, 

exposure in air is a measure of the ionization produced in air by x or gamma radiation; the sum of the 

electric charges on all ions of one sign produced in air when all electrons liberated by photons in a 

volume of air are completely stopped in air (dQ), divided by the mass of the air in the volume (dm). The 

unit of exposure in air is the roentgen, or coulomb per kilogram (SI units). One roentgen is equal to 

2.58x10-4 coulomb per kilogram (C/kg). 

Fission, Nuclear—A nuclear transformation characterized by the splitting of a nucleus into at least two 

other nuclei with emission of several neutrons, accompanied by the release of a relatively large amount of 

energy. 

Gamma Ray, Penetrating—Short wavelength electromagnetic radiation of nuclear origin. 

Genetic Effect of Radiation—Inheritable change, chiefly mutations, produced by the absorption of 

ionizing radiation by germ cells. Genetic effects have not been observed in any human population 

exposed at any dose level. 

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. 

Gray (Gy)—SI unit of absorbed dose, 1 J/kg. One gray equals 100 rad (see Units). 

Half-life, Effective—See Half-Time, Effective. 

Half-life, Radioactive—Time required for a radioactive substance to lose 50% of its activity by decay. 

Each radio-nuclide has a unique physical half-life. Known also as physical half-time and symbolized as 

Tr or Trad. 

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Half-time, Biological—Time required for an organ, tissue, or the whole body to eliminate one-half of any 

absorbed substance by regular processes of elimination. This is the same for both stable and radioactive 

isotopes of a particular element, and is sometimes referred to as half-time, symbolized as tbiol or Tb. 

Half-time, Effective—Time required for a radioactive element in an organ, tissue, or the whole body to 

be diminished 50% as a result of the combined action of radioactive decay and biological elimination, 

symbolized as Te or Teff. 

Biological half-time × Radioactive half-life Effective half-time = Biological half-time + Radioactive half-life 

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. 

Intensity—Amount of energy per unit time passing through a unit area perpendicular to the line of 

propagation at the point in question. 

Intermediate Exposure—Exposure to a chemical for a duration of 15–364 days, as specified in the 

Toxicological Profiles. 

Internal Conversion—Process in which a gamma ray knocks an electron out of the same atom from 

which the gamma ray was emitted. The ratio of the number of internal conversion electrons to the 

number of gamma quanta emitted in the de-excitation of the nucleus is called the "conversion ratio." 

In Vitro—Isolated from the living organism and artificially maintained, as in a test tube. Literally, “in 

glass.” 

In Vivo—Occurring within the living organism. Literally, “in life.” 

Ion—Atomic particle, atom or chemical radical bearing a net electrical charge, either negative or positive. 

Ion Pair—Two particles of opposite charge, usually referring to the electron and positive atomic or 

molecular residue resulting after the interaction of ionizing radiation with the orbital electrons of atoms. 

Ionization—The process by which a neutral atom or molecule acquires a positive or negative charge. 

Primary Ionization—(1) In collision theory: the ionization produced by the primary particles as 

contrasted to the "total ionization" which includes the "secondary ionization" produced by delta 

rays. (2) In counter tubes: the total ionization produced by incident radiation without gas 

amplification. 

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Specific Ionization—Number of ion pairs per unit length of path of ionizing radiation in a 

medium; e.g., per centimeter of air or per micrometer of tissue. 

Total Ionization—The total electric charge of one sign on the ions produced by radiation in the 

process of losing its kinetic energy. For a given gas, the total ionization is closely proportional to 

the initial ionization and is nearly independent of the nature of the ionizing radiation. It is 

frequently used as a measure of absorption of radiation energy. 

Ionization Density—Number of ion pairs per unit volume. 

Ionization Path (Track)—The trail of ion pairs produced by an ionizing particle in its passage through 

matter. 

Ionizing Radiation—Any radiation capable of knocking electrons out of atoms and producing ions. 

Examples: alpha, beta, gamma and x rays, and neutrons. 

Isobars—Nuclides having the same mass number but different atomic numbers. 

Isomers—Nuclides having the same number of neutrons and protons but capable of existing, for a 

measurable time, in different quantum states with different energies and radioactive properties. 

Commonly the isomer of higher energy decays to one with lower energy by the process of isomeric 

transition. 

Isotopes—Nuclides having the same number of protons in their nuclei, and hence the same atomic 

number, but differing in the number of neutrons, and therefore in the mass number. Identical chemical 

properties exist in isotopes of a particular element. The term should not be used as a synonym for nuclide 

because isotopes refer specifically to different nuclei of the same element. 

Stable Isotope—A nonradioactive isotope of an element. 

Joule—The S.I. unit for work and energy. It is equal to the work done by raising a mass of one newton 

through a distance of one meter (J = Nm), which corresponds to about 0.7 ft-pound. 

Kerma (k)—A measure of the kinetic energy transferred from gamma rays or neutrons to a unit mass of 

absorbing medium in the initial collision between the radiation and the absorber atoms. The SI unit is 

J/kg. The special name of this unit is the rad (traditional system of units) or Gray (SI). 

Labeled Compound—A compound containing one or more radioactive atoms intentionally added to its 

structure. By observations of radioactivity or isotopic composition, this compound or its fragments may 

be followed through physical, chemical, or biological processes. 

Late Effects (of radiation exposure)—Effects which appear 60 days or more following an acute 

exposure. 

LD50/30—The dose of a chemical or radiation expected to cause 50% mortality in those exposed within 

30 days. For radiation, this is about 350 rad (3.5 gray) received by humans over a short period of time. 

Lethal Concentration(Lo) (LCLo)—The lowest concentration of a chemical in air that has been reported 

to have caused death in humans or animals. 

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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 

within a specified time, usually 30 days. 

Lethal Dose(Lo) (LDLo)—The lowest dose of a chemical introduced by a route other than inhalation that is 

expected to have caused death in humans or animals within a specified time, usually 30 days. 

Lethal Dose(50) (LD50)—The dose of a chemical which 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. 

Linear Energy Transfer (LET)—A measure of the energy that a charged particle transfers to a material 

per unit path length. 

Average LET—The energy of a charged particle divided by the length of the path over which it 

deposits all its energy in a material. This is averaged over a number of particles. 

High-LET—Energy transfer characteristic of heavy charged particles such as protons and alpha 

particles where the distance between ionizing events is small on the scale of a cellular nucleus. 

Low-LET—Energy transfer characteristic of light charged particles such as electrons produced 

by x and gamma rays where the distance between ionizing events is large on the scale of a 

cellular nucleus. 

Lowest-Observed-Adverse-Effect Level (LOAEL)—The lowest dose 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. 

Lung Clearance Class (fast, F; medium, M; slow, S)—A classification scheme for inhaled material 

according to its rate of clearance from the pulmonary region of the lungs to the blood and the 

gastrointestinal tract. 

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. 

Mass Numbers (A)—The number of nucleons (protons and neutrons) in the nucleus of an atom. 

Minimal Risk Level—An estimate of daily human exposure to a substance that is likely to be without an 

appreciable risk of adverse noncancerous effects over a specified 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. 

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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 changes (mutations) in the genetic material in a cell. 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 

substance. 

Neutrino (ν)—A neutral particle of infinitesimally small rest mass emitted during beta plus or beta minus 

decay. This particle accounts for conservation of energy in beta plus and beta minus decays. It plays no 

role in damage from radiation. 

No-Observed-Adverse-Effect Level (NOAEL)—The dose of a substance 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. 

Nuclear Reactor—A power plant that heats the medium (typically water) by using the energy released 

from the nuclear fission of uranium or plutonium isotopes instead of burning coal, oil, or natural gas. All 

of these sources of energy simply heat water and use the steam which is produced to turn turbines that 

make electricity or propel a ship. 

Nucleon—Common name for a constituent particle of the nucleus. Applied to a proton or neutron. 

Nuclide—A species of atom characterized by the constitution of its nucleus. The nuclear constitution is 

specified by the number of protons (Z), number of neutrons (N), and energy content; or, alternatively, by 

the atomic number (Z), mass number A(N+Z), and atomic mass. To be regarded as a distinct nuclide, the 

atom must be capable of existing for a measurable time. Thus, nuclear isomers are separate nuclides, 

whereas promptly decaying excited nuclear states and unstable intermediates in nuclear reactions are not 

so considered. 

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) which 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 odds ratio of greater than 1 is considered to indicate greater risk 

of disease in the exposed group compared to the unexposed. 

Organophosphate or Organophosphorus Compound—A phosphorus-containing organic compound 

and especially a pesticide that acts by inhibiting cholinesterase. 

Pair Production—An absorption process for x- and gamma radiation in which the incident photon is 

absorbed in the vicinity of the nucleus of the absorbing atom, with subsequent production of an electron 

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URANIUM 445 

10. GLOSSARY 

and positron pair (see annihilation). This reaction can only occur for incident photon energies exceeding 

1.02 MeV. 

Parent—Any radionuclide nuclide which, upon disintegration, yields a new nuclide (termed the progeny 

or daughter), either directly or as a later member of a radioactive series. 

Permissible Exposure Limit (PEL)—A maximum allowable atmospheric level of a substance in 

workplace air averaged over an 8-hour shift. 

Pesticide—General classification of chemicals specifically developed and produced for use in the control 

of agricultural and public health pests. 

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. 

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. 

Physiologically Based Pharmacodynamic (PBPD) Model—A type of physiologically-based doseresponse model which 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—A model comprising 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. 

Photoelectric Effect—An attenuation process observed for x and gamma radiation in which an incident 

photon interacts with a tightly bound inner orbital electron of an atom delivering all of its energy to knock 

the electron out of the atom. The incident photon disappears in the process. 

Photon—A quantum of electromagnetic energy (E) whose value is the product of its frequency (ν) in 

hertz and Planck's constant (h). The equation is: E = hν. 

Population dose—See Collective dose. 

Positron—A positively charged electron. 

Potential, Ionization—The energy expressed as electron volts (eV) necessary to separate one electron 

from an atom, resulting in the formation of an ion pair. 

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Power, Stopping—A measure of the ability of a material to absorb energy from an ionizing particle 

passing through it; the greater the stopping power, the greater the energy absorbing ability (see Linear 

Energy Transfer). 

Prevalence—The number of cases of a disease or condition in a population at one point in time. 

Progeny—The decay product or daughter products resulting after a radioactive decay or a series of 

radioactive decays. The progeny can also be radioactive, and the chain continues until a stable nuclide is 

formed. 

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. 

Proton—Elementary nuclear particle with a positive electric charge equal numerically to the charge of 

the electron and a rest mass of 1.007 mass units. 

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). 

Quality—A term describing the distribution of the energy deposited by a particle along its track; 

radiations that produce different densities of ionization per unit intensity are said to have different 

"qualities." 

Quality Factor (Q)—The linear-energy-transfer-dependent factor by which absorbed doses are 

multiplied to obtain (for radiation protection purposes) a quantity that expresses - on a common scale for 

all ionizing radiation - the approximate biological effectiveness of the absorbed dose. 

Type of radiation Quality Factor 

X, gamma, or beta 1 

Alpha particles 20 

Neutrons of unknown energy 10 

High energy protons 10 

Rad—The traditional unit of absorbed dose equal to 100 ergs per gram, or 0.01 joule per kilogram (0.01 

Gy) in any medium (see Absorbed Dose). 

Radiation—The emission and propagation of energy through space or through a material medium in the 

form of waves (e.g., the emission and propagation of electromagnetic waves, or of sound and elastic 

waves). The term radiation or radiant energy, when unqualified, usually refers to electromagnetic 

radiation. Such radiation commonly is classified according to frequency, as microwaves, infrared, visible 

(light), ultraviolet, and x and gamma rays (see Photon.) and, by extension, corpuscular emission, such as 

alpha and beta radiation, neutrons, or rays of mixed or unknown type, as cosmic radiation. 

Radiation, Annihilation—Photons produced when an electron and a positron unite and cease to 

exist. The annihilation of a positron-electron pair results in the production of two photons, each 

of 0.51 MeV energy. 

Radiation, Background—See Background Radiation. 

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Radiation, Characteristic (Discrete)—Radiation originating from an excited atom after removal 

of an electron from an atom. The wavelength of the emitted radiation is specific, depending only 

on the element and particular energy levels involved. 

Radiation, External—Radiation from a source outside the body. 

Radiation, Internal—Radiation from a source within the body (as a result of deposition of 

radionuclides in body tissues). 

Radiation, Ionizing—Any electromagnetic or particulate radiation capable of producing ions, 

directly or indirectly, in its passage through matter (see Radiation). 

Radiation, Monoenergetic—Radiation of a given type in which all particles or photons originate 

with and have the same energy. 

Radiation, Scattered—Radiation which during its passage through a substance, has been 

deviated in direction. It may also have been modified by a decrease in energy. 

Radiation, Secondary—A particle or ray that is produced when the primary radiation interacts 

with a material, and which has sufficient energy to produce its own ionization, such as 

bremsstrahlung or electrons knocked from atomic orbitals with enough energy to then produce 

ionization (see Delta Rays). 

Radiation Weighting Factor (also called Quality Factor)—In radiation protection, a factor (1 for xrays, gamma rays, beta particles; 20 for alpha particles) weighting the absorbed dose of radiation of a 

specific type and energy for its effect on tissue. 

Radioactive Material—Material containing radioactive atoms. 

Radioactivity—Spontaneous nuclear transformations that result in the formation of new elements. These 

transformations are accomplished by emission of alpha or beta particles from the nucleus or by the 

capture of an orbital electron. Each of these reactions may or may not be accompanied by a gamma 

photon. 

Radioactivity, Artificial—Man-made radioactivity produced by particle bombardment or 

nuclear fission, as opposed to naturally occurring radioactivity. 

Radioactivity, Induced—Radioactivity produced in a substance after bombardment with 

neutrons or other particles. The resulting activity is "natural radioactivity" if formed by nuclear 

reactions occurring in nature and "artificial radioactivity" if the reactions are caused by man. 

Radioactivity, Natural—The property of radioactivity exhibited by more than 50 naturally 

occurring radionuclides. 

Radioisotope—An unstable or radioactive isotope of an element that decays or disintegrates 

spontaneously, emitting radiation. 

Radionuclide—Any radioactive isotope of any element. Approximately 5,000 natural and artificial 

radioisotopes have been identified. 

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Radiosensitivity—Relative susceptibility of cells, tissues, organs, organisms, or any living substance to 

the injurious action of radiation. Radiosensitivity and its antonym, radioresistance, are used 

comparatively, rather than absolutely. 

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 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 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 professional judgment of the entire database on the chemical. The RfDs are not applicable to nonthreshold effects such as cancer. 

Relative Biological Effectiveness (RBE)—The RBE is a factor used to compare the biological 

effectiveness of absorbed radiation doses (i.e., rad) due to different types of ionizing radiation. More 

specifically, it is the experimentally determined ratio of an absorbed dose of a radiation in question to the 

absorbed dose of a reference radiation (typically 60Co gamma rays or 200 kVp x rays) required to produce 

an identical biological effect in a particular experimental organism or tissue (see Quality Factor). 

Rem—The traditional unit of dose equivalent that is used in the regulatory, administrative, and 

engineering design aspects of radiation safety practice. The dose equivalent in rem is numerically equal 

to the absorbed dose in rad multiplied by the quality factor (1 rem is equal to 0.01 sievert). 

Reportable Quantity (RQ)—The quantity of a hazardous substance that is considered reportable under 

CERCLA. Reportable quantities are (1) 1 pound or greater or (2) for selected substances, an amount 

established by regulation either under CERCLA or under Sect. 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. 

Roentgen (R)—A unit of exposure (in air) to ionizing radiation. It is the amount of x or gamma rays 

required to produce ions carrying 1 electrostatic unit of electrical charge in 1 cubic centimeter of dry air 

under standard conditions. Named after William Roentgen, a German scientist who discovered x rays in 

1895. 

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. 

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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. 

Self-Absorption—Absorption of radiation (emitted by radioactive atoms) by the material in which the 

atoms are located; in particular, the absorption of radiation within a sample being assayed. 

Short-Term Exposure Limit (STEL)—The 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 TLV-TWA may not be exceeded. 

SI Units—The International System of Units as defined by the General Conference of Weights and 

Measures in 1960. These units are generally based on the meter/kilogram/second units, with special 

quantities for radiation including the becquerel, gray, and sievert. 

Sickness, Acute Radiation (Syndrome)—The complex symptoms and signs characterizing the condition 

resulting from excessive exposure of the whole body (or large part) to ionizing radiation. The earliest of 

these symptoms are nausea, fatigue, vomiting, and diarrhea, and may be followed by loss of hair 

(epilation), hemorrhage, inflammation of the mouth and throat, and general loss of energy. In severe 

cases, where the radiation dose is relatively high (over several hundred rad or several gray), death may 

occur within two to four weeks. Those who survive six weeks after exposure of a single high dose of 

radiation may generally be expected to recover. 

Sievert (Sv)—The SI unit of any of the quantities expressed as dose equivalent. The dose equivalent in 

sieverts is equal to the absorbed dose, in gray, multiplied by the quality factor (1 sievert equals 100 rem). 

The sievert is also the SI unit for effective dose equivalent, which is the sum of the products of the dose 

equivalent to each organ or tissue and its corresponding tissue weighting factor. 

Specific-Activity—Radioactivity per unit mass of a radionuclide, expressed, for example, as Ci/gram or 

Bq/kilogram. 

Specific Energy—The actual energy per unit mass deposited per unit volume in a small target, such as 

the cell or cell nucleus, as the result of one or more energy-depositing events. This is a stochastic 

quantity as opposed to the average value over a large number of instance (i.e., the absorbed dose). 

Standardized Mortality Ratio (SMR)—A ratio of the observed number of deaths and the expected 

number of deaths in a specific standard population. 

Stochastic Effect—A health effect that occurs randomly and for which the probability of the effect 

occurring, rather than its severity, is assumed to be a linear function of dose without a threshold (also 

called a nondeterministic effect). 

Stopping Power—The average rate of energy loss of a charged particle per unit thickness of a material or 

per unit mass of material traversed. 

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Surface-seeking Radionuclide—A bone-seeking internal emitter that deposits and remains on the bone 

surface for a long period of time, although it may eventually diffuse into the bone mineral. This contrasts 

with a volume seeker, which deposits more uniformly throughout the bone volume. 

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. 

Target Theory (Hit Theory)—A theory explaining some biological effects of radiation on the basis that 

ionization, occurring in a discrete volume (the target) within the cell, directly causes a lesion which 

subsequently results in a physiological response to the damage at that location. One, two, or more "hits" 

(ionizing events within the target) may be necessary to elicit the response. 

Teratogen—A chemical that causes birth defects. 

Threshold Limit Value (TLV)—The maximum concentration of a substance to which most workers can 

be exposed without adverse effect. TLV is a term used exclusively by the ACGIH. Other terms used to 

express similar concepts are the MAC (Maximum Allowable Concentration) and PEL (Permissible 

Exposure Limits). 

Time-Weighted Average (TWA)—An allowable exposure concentration averaged over a normal 8-hour 

workday or 40-hour workweek. 

Tissue Weighting Factor (Wt)—Organ- or tissue-specific factor by which the equivalent dose is 

multiplied to give the portion of the effective dose for that organ or tissue. Recommended values of 

tissue weighting factors are: 

Tissue/Organ Tissue Weighting Factor 

Gonads 0.70 

Bone marrow (red) 0.12 

Colon 0.12 

Lung 0.12 

Stomach 0.12 

Bladder 0.05 

Breast 0.05 

Liver 0.05 

Esophagus 0.05 

Thyroid 0.05 

Skin 0.01 

Bone surface 0.01 

Remainder (adrenals, brain, upper large 0.05 

intestine, small intestine, pancreas, spleen, 

thymus, and uterus) 

Toxic Dose (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. 

Toxicosis—A diseased condition resulting from poisoning. 

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Transformation, Nuclear—The process of radioactive decay by which a nuclide is transformed into a 

different nuclide by absorbing or emitting particulate or electromagnetic radiation. 

Transition, Isomeric—The process by which a nuclide decays to an isomeric nuclide (i.e., one of the 

same mass number and atomic number) of lower quantum energy. Isomeric transitions (often abbreviated 

I.T.) proceed by gamma ray and internal conversion electron emission. 

Tritium—The hydrogen isotope with one proton and two neutrons in the nucleus (Symbol: 3

H). It is 

radioactive and has a physical half-life of 12.3 years. 

Unattached Fraction—That fraction of the radon daughters, usually 218Po and 214Po, which has not yet 

attached to a dust particle or to water vapor. As a free atom, it has a high probability of being exhaled and 

not retained within the lung. It is the attached fraction which is primarily retained. 

Uncertainty Factor (UF)—A factor used in operationally deriving the RfD 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 

LOAEL data rather than NOAEL data. Usually each of these factors is set equal to 10. 

Units, Prefixes—Many units of measure are expressed as submultiples or multiples of the primary unit 

(e.g., 10-3 curie is 1 mCi and 103 becquerel is 1 kBq). 

Factor Prefix Symbol Factor Prefix Symbol 

10-18 atto A 103 kilo k 

10-15 femto F 106 mega M 

10-12 pico p 109 giga G 

10-9 nano N 1012 tera T 

10-6 micro Μ 1015 peta P 

10-3 milli M 1018 exa E 

10-2 centi C 

Units, Radiological— 

Units Equivalents 

Becquerel* (Bq) 1 disintegration per second = 2.7x10-11 Ci 

Curie (Ci) 3.7x1010 disintegrations per second = 3.7x1010 Bq 

Gray* (Gy) 1 J/kg = 100 rad 

Rad (rad) 100 erg/g = 0.01 Gy 

Rem (rem) 0.01 sievert 

Sievert* (Sv) 100 rem 

*International Units, designated (SI) 

Working Level (WL)—Any combination of short-lived radon daughters in 1 liter of air that will result in 

the ultimate emission of 1.3x105 MeV of potential alpha energy. 

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URANIUM 452 

10. GLOSSARY 

Working Level Month (WLM)—A unit of exposure to radon daughters corresponding to the product of 

the radon daughter concentration in Working Level (WL) and the exposure time in nominal months 

(1 nominal month = 170 hours). Inhalation of air with a concentration of 1 WL of radon daughters for 

170 working hours results in an exposure of 1 WLM. 

Xenobiotic—Any chemical that is foreign to the biological system. 

X rays—Penetrating electromagnetic radiations whose wave lengths are very much shorter than those of 

visible light. They are usually produced by bombarding a metallic target with fast electrons in a high 

vacuum. X rays (called characteristic x rays) are also produced when an orbital electron falls from a high 

energy level to a low energy level. 

Zero-Threshold Linear Hypothesis (or No-Threshold Linear Hypothesis)—The assumption that a 

dose-response curve derived from data in the high dose and high dose-rate ranges may be extrapolated 

through the low dose and low dose range to zero, implying that, theoretically, any amount of radiation 

will cause some damage. 

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URANIUM 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 

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URANIUM 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. 

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URANIUM A-3 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Uranium (insoluble forms) 

CAS Numbers: Multiple 

Date: March 2011 

Profile Status: Draft for Public Comment 

Route: [X] Inhalation [ ] Oral 

Duration: [ ] Acute [X] Intermediate [ ] Chronic 

Graph Key: 66 

Species: Dog 

Minimal Risk Level: 0.002 [ ] mg/kg/day [ ] ppm [X] mg/m3 

Reference: Rothstein A. 1949b. Uranium dioxide. In: Voegtlin C, Hodge HC, eds. Pharmacology and 

toxicology of uranium compounds. National Nuclear Energy Series: Manhattan Project Technical 

Section, Division VI, Vol. 1. New York, NY: McGraw-Hill. pp. 614-621. 

Experimental design: Groups of 6–19 dogs of unspecified strain and gender were exposed to 1.3, 9.3, or 

10.4 mg/m3 uranium dioxide (1.1, 8.2, or 9.2 mg U/m3

) 6 days/week for 5 weeks. Based on other studies 

conducted by this investigator (Rothermel 1949; Rothstein 1949c), it is assumed that the animals were 

exposed for 6 hours/day. Exposure to 8.2 mg U/m3 was conducted in head-only exposure units and 

exposure to 1.1 or 9.2 mg U/m3 were performed in full-body exposure units. The median particle size 

was 0.4 μm with a geometric standard deviation of 2. The following parameters were used to assess 

toxicity: mortality, body weight changes, standard hematology (except in the 8.2 mg U/m3 group), 

clinical chemistry (serum nonprotein nitrogen and urea nitrogen levels), urinalysis (protein, amino acid, 

catalase, phosphate, and ketone levels), and histopathology. Separate control studies were conducted 

(Sprague 1949) in which animals were exposed in control chambers by full or head-only exposure for a 

duration similar to study conditions. Body weight, mortality, biochemical, hematological, and 

histopathological data were collected. Dogs (n = 6–19; unspecified sex and strain) were exposed to 

uranium dioxide dust at concentrations of 1.1, 8.2, or 9.2 mg U/m3 for 5 weeks, 6 days/weeks, 

6 hours/day. (Doses were analytically determined, not estimated.) Studies conducted at 8.2 mg U/m3 

were conducted in head exposure units. Studies conducted at the other concentrations were performed in 

full exposure units. The AMAD for the particles is assumed to be 1.5–2.1 μm; average 1.8 μm (see 

Pozzani 1949). Mortality, body weight changes, standard hematology (except in the 8.2 mg U/m3 group), 

blood and urine chemistries, pathology, and uranium distribution in tissues were measured. 

Effect noted in study and corresponding doses: No dogs died from exposure to uranium dioxide dust. 

Additionally, no alterations in body weight gain or hematology, serum clinical chemistry, or urinalysis 

parameters were noted. Histopathological alterations were limited to the kidneys; “very slight” renal 

tubular degeneration was observed in two of six dogs at 8.2 mg U/m3

; no alterations were observed in two 

dogs examined from the 9.2 mg U/m3 group. 

Dose and end point used for MRL derivation: 

[X] NOAEL [ ] LOAEL 

The study identified a NOAEL of 1.1 mg U/m3 and a LOAEL of 8.2 mg/m3 for minimal microscopic 

lesions in the renal tubules. The NOAEL of 1.1 mg U/m3 was used as the point of departure for the MRL; 

BMD modeling was not used to estimate the point of departure due to the limited reporting of incidence 

data. 

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URANIUM A-4 

APPENDIX A 

Uncertainty Factors used in MRL derivation: 

[ ] 10 for use of a LOAEL 

[x] 10 for extrapolation from animals to humans 

[x] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? Not applicable. 

If an inhalation study in animals, list conversion factors used in determining human equivalent 

concentration: Human equivalent values were not calculated because regional deposited dose ratios are 

not available for dogs (EPA 1994d); thus, the NOAELADJ was used as the point of departure with an 

uncertainty factor of 10 for extrapolation from animals to humans. 

Was a conversion used from intermittent to continuous exposure? The NOAEL was adjusted for 

intermittent exposure: 

NOAELADJ = (1.1 mg/m3

) * (6 hours/24 hours) * (6 days/7 days) = 0.24 mg/m3 

Other additional studies or pertinent information that lend support to this MRL: Intermediate-duration 

inhalation studies in animals have examined the toxicity of various insoluble uranium compounds 

including uranium dioxide, uranium peroxide, uranium trioxide, and triuranium octaoxide in several 

animal species (Dygert 1949c, 1949d; Rothstein 1949b, 1949c; Stokinger et al. 1953). The results of 

these studies suggest that the kidney and the respiratory tract are sensitive targets of uranium toxicity, 

with the kidney being the most sensitive target. Very slight renal tubular damage was observed in dogs 

exposed to 8.2 mg U/m3 as uranium dioxide for 5 weeks (Rothstein 1949b), moderate tubular necrosis 

was observed in rabbits exposed to 15.4 mg U/m3 as uranium peroxide for 23 days (Dygert 1949d), 

moderate necrosis was observed in rats, rabbits, and dogs exposed to 16 mg U/m3 as uranium trioxide for 

4 weeks (Rothstein 1949c), and marked tubular necrosis was observed in rabbits exposed to 19.4 mg 

U/m3 as uranium dioxide for 5 weeks (Rothstein 1949b). Although there are limited data to make species 

comparisons, data for uranium dioxide suggest that rabbits are more sensitive than rats, mice, or guinea 

pigs; the data do not allow for a comparison between rabbits and dogs. In addition to the renal effects 

observed in rats, rabbits, and dogs exposed to uranium trioxide, very slight pulmonary lesions were 

observed in dogs and rats exposed to 16 mg U/m3 and severe effects were observed in rabbits dying early 

after exposure to 16 mg U/m3 (Rothstein 1949c). Additionally, the results of the Rothstein (1949b) study 

which is the basis of the MRL are supported by the findings of slight to mild tubular degeneration in dogs 

exposed to 10 mg U/m3 as uranium dioxide for 1 year; no effects were observed at 1 mg U/m3 (Stokinger 

et al. 1953). 

Agency Contacts (Chemical Managers): Sam Keith, Obaid Faroon, Nickolette Roney, Franco 

Scinicariello, Sharon Wilbur 

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URANIUM A-5 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Uranium (soluble forms) 

CAS Numbers: Multiple 

Date: March 2011 

Profile Status: Draft for Public Comment 

Route: [X] Inhalation [ ] Oral 

Duration: [ ] Acute [X] Intermediate [ ] Chronic 

Graph Key: 67 

Species: Dog 

Minimal Risk Level: 0.0001 [ ] mg/kg/day [ ] ppm [X] mg/m3 

Reference: Rothstein A. 1949a. Uranyl fluoride. In: Voegtlin C, Hodge HC, eds. Pharmacology and 

toxicology of uranium compounds. National Nuclear Energy Series: Manhattan Project Technical 

Section, Division VI, Vol 1. New York, NY: McGraw-Hill. pp. 548-560. 

Experimental design: Groups of 2–6 dogs per group (strain and gender not specified) were exposed to 

0.19, 2.8, or 12.2 mg/m3 of uranyl fluoride dust (0.15, 2.2, or 9.2 mg U/m3

) for 6 hours/day, 6 days/week 

for 5 weeks. (Doses were analytically determined, not estimated.) The AMAD for the particles is 

assumed to be 1.5–2.1 μm; average 1.8 μm (see Pozzani 1949). Separate control studies were conducted 

(Sprague 1949) in which animals were exposed in control chambers by full or head-only exposure for a 

duration similar to study conditions. Clinical signs of toxicity, mortality, body weight changes, 

hematology, and blood and urine chemistries were monitored. At the termination of the study, the 

animals were sacrificed, selected organs were histopathologically examined, and uranium levels were 

determined. 

Effect noted in study and corresponding doses: Anorexia, rhinitis, and polydipsia were observed in the 

two dogs exposed to 9.2 mg U/m3

; prior to death, vomiting blood, severe muscle weakness, and exhibited 

lassitude were observed. No deaths or clinical signs were observed at 0.15 or 2.2 mg U/m3

. Severe 

weight loss was also observed at 9.2 mg U/m3

; no alterations in body weight gain were observed at 

0.15 or 2.2 mg U/m3

. At 9.2 mg U/m3, both dogs had increased blood NPN levels with the maximum 

value over 200 mg%. At 2.2 mg U/m3

, blood NPN and urinary amino acid levels were normal while one 

of three dogs had increased urinary protein levels. At 9.2 mg U/m3

, severe renal damage was seen in 

dogs. Moderate renal damage (no additional information provided) was observed at 2.2 mg U/m3 and 

very slight damage was observed in about 50% of the dogs at 0.15 mg U/m3

. 

Dose and end point used for MRL derivation: 

[ ] NOAEL [X] LOAEL 

The study identified a LOAEL of 0.15 mg U/m3 for minimal microscopic lesions in the renal tubules; 

BMD modeling was not used to estimate the point of departure because incidence data were not available 

for all groups. 

Uncertainty Factors used in MRL derivation: 

[x] 3 for use of a minimal LOAEL 

[x] 10 for extrapolation from animals to humans 

[x] 10 for human variability 

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URANIUM A-6 

APPENDIX A 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? Not applicable. 

If an inhalation study in animals, list conversion factors used in determining human equivalent 

concentration: Human equivalent values were not calculated because regional deposited dose ratios are 

not available for dogs (EPA 1994d); thus, the LOAELADJ was used as the point of departure with an 

uncertainty factor of 10 for extrapolation from animals to humans. 

Was a conversion used from intermittent to continuous exposure? The LOAEL was adjusted for 

intermittent exposure: 

LOAELADJ = (0.15 mg/m3

) * (6 hours/24 hours) * (6 days/7 days) = 0.032 mg/m3 

Other additional studies or pertinent information that lend support to this MRL: The toxicity of various 

soluble and poorly soluble uranium compounds has been tested in several animal species (Dygert 1949a, 

1949b; Roberts 1949; Rothermel 1949; Rothstein 1949a; Spiegl 1949; Stokinger et al. 1953). These 

studies identify the kidney and respiratory tract as the most sensitive targets of uranium toxicity. The 

renal effects consisted of tubular degeneration and necrosis at concentrations of ≥0.2 mg U/m3

. 

Compound and species differences in toxicity were found. The more soluble compounds were more toxic 

and dogs and rabbits were more sensitive than rats, mice, and guinea pigs. 

In addition to the renal effects, pulmonary toxicity has been observed in animals particularly after 

exposure to uranium hexafluoride. Exposure to 2 mg U/m3 for 30 days resulted in severe pulmonary 

edema in rabbits and slight pneumonia in dogs (Spiegl 1949). At higher concentrations (13.3 mg U/m3

), 

lung edema, hemorrhage, and emphysema were observed in rats, rabbits, and guinea pigs (Spiegl 1949). 

Since uranium hexafluoride is readily hydrolyzed to uranyl fluoride and hydrogen fluoride and hydrogen 

fluoride is a strong respiratory irritant resulting in pulmonary edema, it is likely that the observed 

respiratory effects are due to the hydrogen fluoride exposure. Respiratory effects have also been observed 

in rabbits and rats exposed to 6.8 mg U/m3 as ammonium diuranate (Dygert 1949b). In rabbits, 

ammonium diuranate exposure (6.8 mg U/m3

) resulted in extensive respiratory tract irritation, evidence 

by nasal bleeding and pulmonary edema, hemorrhage, and necrosis. Respiratory irritation (nasal bleeding 

and interstitial bronchiopneumonia) was also observed in rats exposed to 6.8 mg U/m3

. It is possible that 

these effects were secondary to the release of the ammonium ion, rather than uranium toxicity. 

Respiratory effects have not been consistently observed following exposure to other uranium compounds. 

The kidney effects were observed at lower concentrations than the respiratory effects and the dogs were 

the most sensitive species. The lowest LOAEL values identified in dogs are 0.13 mg U/m3 as uranyl 

nitrate for proteinuria (Roberts 1949) and 0.15 mg U/m3 as uranyl fluoride for tubular damage (Rothstein 

1949a). In the Roberts (1949) study, an increase in urinary protein excretion was observed between days 

9 and 12 and then returned to normal; very mild histological changes which the investigator noted was not 

of sufficient severity to be of concern were observed in the renal cortex in two dogs exposed for 10 days. 

Since the two LOAEL values are almost identical, the Rothstein (1949a) study was selected as the basis 

of the MRL because it included histological examination of dogs exposed for an intermediate duration 

(the one dog examined at the end of the Roberts study had severe chronic nephritis, which masked an 

uranium-induced renal effects). Although the lowest LOAEL value in rats (0.13 mg U/m3

) was similar to 

the lowest LOAEL values in dogs, the intermediate and chronic databases for soluble uranium 

compounds provide strong evidence that dogs are more sensitive than rats. 

Agency Contacts (Chemical Managers): Sam Keith, Obaid Faroon, Nickolette Roney, Franco 

Scinicariello, Sharon Wilbur 

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URANIUM A-7 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Uranium (insoluble forms) 

CAS Numbers: Multiple 

Date: March 2011 

Profile Status: Draft for Public Comment 

Route: [X] Inhalation [ ] Oral 

Duration: [ ] Acute [ ] Intermediate [X] Chronic 

Graph Key: 93 

Species: Monkey 

Minimal Risk Level: 0.0008 [ ] mg/kg/day [ ] ppm [X] mg/m3 

Reference: Leach LJ, Maynard EA, Hodge HC, et al. 1970. A five-year inhalation study with natural 

uranium dioxide (UO2) dust. I. Retention and biological effects in the monkey, dog, and rat. Health 

Physics 18:599-612. 

Leach LJ, Yuile CL, Hodge HC, et al. 1973. A five-year inhalation study with natural uranium dioxide 

(UO2) dust. II. Postexposure retention and biologic effects in the monkey, dog, and rat. Health Physics 

25: 239-258. 

Experimental design: Rhesus monkeys (5 males, 20 females) were exposed to 5.8 mg/m3 uranium 

dioxide (5.1 mg U/m3

) 5.4 hours/day, 5 days/week for 5 years; the mass median particle diameter was 

1.03 μm with a geometric standard deviation of 2.40. Another group of one male and five female 

monkeys served as controls. Groups of 1–2 monkeys were killed after 1 day, 4 days, 15 days, 1 month, 

2 months, 3 months, 5 months, 1 year, 1.5 years, 1.8 years, 1.9 years, 3.6 years, 4.1 years, or 4.7 years; 

two monkeys were killed at 5 years. Six monkeys were observed for 6.5 years after exposure termination; 

two were killed after 12 months, one after 6 years, and three after 6.5 years; the results of the recovery 

period examinations were reported in Leach et al. (1973). The following parameters were used to assess 

toxicity: general health, body weight, peripheral hematology, blood NPN levels, and histopathology of 

major tissues and organs. No uranium dioxide-related deaths were observed. 

Effect noted in study and corresponding doses: No alterations in body weight, hematological parameters, 

or blood NPN levels were found. Histological alterations were limited to the lungs and tracheobronchial 

lymph nodes. After 2–3 months of exposure, granular black pigment accumulations were found in the 

lungs and tracheobronchial lymph nodes. After 3.6 years of exposure, slight fibrosis was observed in the 

lungs and hyaline fibrosis was observed in the tracheobronchial lymph nodes; the severity of the fibrosis 

increased with exposure duration and was not observed in the controls. Fibrosis was still present in the 

lungs and tracheobronchial lymph nodes 6.5 years postexposure. 

Dose and end point used for MRL derivation: 

[ ] NOAEL [X] LOAEL 

The study identified a LOAEL of 5.1 mg U/m3 for fibrosis in the lungs and tracheobronchial lymph 

nodes; BMD modeling was not used due to the small number of animals sacrificed at each time period. 

Uncertainty Factors used in MRL derivation: 

[x] 10 for use of a LOAEL 

[x] 10 for extrapolation from animals to humans 

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URANIUM A-8 

APPENDIX A 

[x] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? Not applicable. 

If an inhalation study in animals, list conversion factors used in determining human equivalent 

concentration: Human equivalent values were not calculated because regional deposited dose ratios are 

not available for monkeys (EPA 1994d). The LOAELADJ was used as the point of departure with an 

uncertainty factor of 10 for extrapolation from animals to humans. 

Was a conversion used from intermittent to continuous exposure? The LOAEL was adjusted for 

intermittent exposure: 

LOAELADJ = (5.1 mg U/m3

) * (5.4 hours/24 hours) * (5 days/7 days) = 0.82 mg U/m3 

Other additional studies or pertinent information that lend support to this MRL: There are limited data 

available to assess the toxicity of chronic exposure to insoluble uranium compounds. Slight to mild renal 

tubular degeneration was observed in dogs exposed to 10 mg U/m3 as uranium dioxide for 1 year 

(Stokinger et al. 1953); no alterations were observed at 1 mg U/m3

. Although several tissues were 

examined histologically, significant alterations were only noted for the kidneys. Stokinger et al. (1953) 

also exposed rats to 1 or 10 mg U/m3 as uranium dioxide, but no uranium-related alterations were 

observed. In a second chronic duration study, no adverse effects were observed in rats or dogs exposed to 

5.1 mg U/m3 as uranium dioxide for 1–5 years (Leach et al. 1970). However, fibrosis in the 

tracheobronchial lymph nodes and fibrosis and metaplasia in the lungs were observed in dogs during a 

6.5-year postexposure period (Leach et al. 1973). In monkeys, exposure to 5.1 mg U/m3 resulted in lung 

fibrosis beginning after 3.6 years of exposure (Leach et al. 1970); the severity of the fibrosis increased 

with exposure duration. Fibrosis was also present in the lungs and tracheobronchial lymph nodes in 

monkeys sacrificed during the 6.5-year postexposure period (Leach et al. 1973). The investigators noted 

that the fibrosis may have been a radiotoxic effect based on the magnitude of the radiation dose, the 

absence of renal effects, and the similarity of the lesions to those observed following exposure to 

plutonium dioxide; the alpha-radiation tissue doses were >500 rads (5 Gy) for the lungs and 7,000 rads 

(70 Gy) for the lymph nodes. However, it is unclear whether the damage was chemically or 

radiologically induced (or both); similar degenerative effects in the lungs have also been observed 

following prolonged exposure to diverse inorganic dusts. An elevation of blood nonprotein nitrogen level 

was also observed in the monkeys during the postexposure period, but no histological alterations were 

observed in the kidneys (Leach et al. 1973). 

Agency Contacts (Chemical Managers): Sam Keith, Obaid Faroon, Nickolette Roney, Franco 

Scinicariello, Sharon Wilbur 

***DRAFT FOR PUBLIC COMMENT*** 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

URANIUM A-9 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Uranium (soluble forms) 

CAS Numbers: Multiple 

Date: March 2011 

Profile Status: Draft for Public Comment 

Route: [X] Inhalation [ ] Oral 

Duration: [ ] Acute [ ] Intermediate [X] Chronic 

Graph Key: 101 

Species: Dog 

Minimal Risk Level: 0.00004 [ ] mg/kg/day [ ] ppm [X] mg/m3 

Reference: Stokinger HC, Baxter RC, Dygert HP, et al. 1953. Uranium Tetrachloride: Toxicity 

following inhalation for 1 and 2 years. In: Voegtlin C, Hodge HC, eds. Pharmacology and toxicology of 

uranium compounds. National Nuclear Energy Series: Manhattan Project Technical Section, Division VI, 

Vol 1. New York, NY: McGraw-Hill. pp. 1522-1553. 

Experimental design: Dogs of both sexes (11–12 males, 9–10 females) were exposed to uranium 

tetrachloride in inhalation chambers for 33 hours/week for 1 year at concentrations of 0.05 and 

0.20 mg U/m3

. (Doses were analytically determined, not estimated.) A control group of five male and 

seven female dogs were similar exposed to chamber air in a separate experiment. The size-mass median 

particle size of uranium tetrachloride dust was 1.58 μm (range of 1.19–2.21 μm; geometric standard 

deviation of 2.24) for the 0.05 mg U/m3 exposures and 1.83 μm (range of 1.07–3.35 μm; geometric 

standard deviation of 2.25) for the 0.2 mg U/m3 exposures. The animals were monitored for body weight 

alterations, clinical signs of toxicity, and biochemical alterations in the blood and urine. At the 

termination of the study, the animals were sacrificed and selected organs were histopathologically 

examined. 

Effect noted in study and corresponding doses: All dogs survived the 1-year exposure period. No 

alterations in body weight gain, hematological parameters, or blood NPN levels were observed. Urinary 

protein levels were elevated, as compared to controls; however, pre-exposure levels were also elevated, 

precluding evaluating the clinical significance of the effect. Alterations in bromsulfalein retention test, 

indicating impaired liver function, were observed in the four dogs tested (0.2 mg U/m3 group); no 

alterations in blood clotting times were observed. In the absence of histological evidence of liver damage, 

the change was not considered clinically significant. Renal tubular atrophy was observed in 2/16 dogs 

exposed to 0.05 mg U/m3 (not statistically significant using Fisher Exact test). Slight tubular atrophy in 

the inner cortex was observed in 7/14 dogs exposed to 0.2 mg U/m3

. 

Dose and end point used for MRL derivation: 

[ ] NOAEL [ ] LOAEL [X] BMCL10 0.019 mg U/m3 for renal toxicity 

Data for the incidence of renal tubular atrophy were analyzed using all available dichotomous models in 

the EPA BMDS (version 2.1.2) using the extra risk option. The multistage model was run for all 

polynomial degrees up to n-1 (where n is the number of dose groups including control). Adequate model 

fit was judged by three criteria: goodness-of-fit p-value (p>0.1), visual inspection of the dose-response 

curve, and scaled residual at the data point (except the control) closest to the predefined benchmark 

response (BMR). Among all of the models meeting adequate fit criteria, the BMCL from the model with 

the lowest Akaike Information Criteria (AIC) was chosen. BMCs and lower bounds on the BMC 

(BMCLs) associated with a BMR of 10% extra risk were calculated for all models and are presented in 

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URANIUM A-10 

APPENDIX A 

Table A-1. As assessed by the chi-square goodness-of-fit statistic, all of the models provided adequate fit 

to the data. The BMCs ranged from 0.032 to 0.082 mg U/m3 and the BMCLs ranged from 0.019 to 

0.054 mg U/m3

. The quantal-linear and the multistage (1-degree polynomial) had the lowest AIC values; 

the BMCL10 of 0.019 mg U/m3 estimated for both models was selected as a point of departure. The fit of 

the quantal-linear model is presented in Figure A-1. 

Table A-1. Model Predictions for the Incidence of Renal Tubular Atrophy in Dogs 

Exposed to Uranium Tetrachloride for 1 Year (Stokinger et al. 1953) 

χ

2 GoodnessModel of-fit p-valuea AIC BMC10 (mg U/m3

) BMCL10 (mg U/m3) 

Gammab 35.4648 1 35.4648 0.0411568 0.0196557 

Logistic 36.7375 0.3616 36.7375 0.0825225 0.054177 

Log Logistic 35.4648 1 35.4648 0.0418036 0.0146656 

Log Probit 35.4648 1 35.4648 0.0426877 0.00300431 

Multistage (1 degree 

polynomial) 35.4648 0.9485 33.5743 0.0324681 0.019467 

Multistage (2 degree 

polynomial) 33.5743 1 35.4648 0.0402323 0.0196557 

Probit 36.5663 0.3921 36.5663 0.0756112 0.0502782 

Weibullb 35.4648 1 35.4648 0.0409589 0.0196557 

Quantal-Linear 33.5743 0.9485 33.5743 0.0324681 0.019467 

a

Values <0.10 fail to meet conventional goodness-of-fit criteria. b

Power restricted to ≥1. 

AIC = Akaike Information Criteria; BMC = benchmark concentration associated with the selected benchmark 

response of 10% extra risk; BMCL = 95% lower confidence limit on the BMC 

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URANIUM A-11 

APPENDIX A 

Figure A-1. Predicted (Quantal-Linear Model) and Observed Incidence of Renal
 

Tubular Atrophy*

 0.8

 0.7

 0.6

 0.5

 0.4

 0.3

 0.2

 0.1

 0

 0 0.05 0.1 0.15 0.2 

dose 

Quantal Linear Model with 0.95 Confidence Level 

BMDL BMD 

Quantal Linear 

Fraction Affected 

09:14 01/10 2011 

*BMC and BMCL indicated are associated with 10% extra risk and are in units of mg U/m3. 

Uncertainty Factors used in MRL derivation: 

[ ] 10 for use of a LOAEL 

[x] 10 for extrapolation from animals to humans 

[x] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? Not applicable. 

If an inhalation study in animals, list conversion factors used in determining human equivalent 

concentration: Human equivalent values were not calculated because regional deposited dose ratios are 

not available for dogs (EPA 1994d). The BMCLADJ was used as the point of departure with an 

uncertainty factor of 10 for extrapolation from animals to humans. 

Was a conversion used from intermittent to continuous exposure? The BMCL was adjusted for 

intermittent exposure: 

BMCLADJ = (0.019 mg U/m3

) * (33 hours/168 hours) = 0.0037 mg U/m3 

Other additional studies or pertinent information that lend support to this MRL: There are limited human 

data on the chronic toxicity of soluble uranium. Thun et al. (1985) examined uranium mill workers 

exposed to yellowcake (26–86% ammonium diuranate), which was considered biologically soluble, for at 

least 1 year. Significant increases in urinary excretion of β2-microglobulin and amino acids were 

observed in the uranium workers, suggesting impaired renal tubular function. Clearance of 

β-2-microglobulin relative to that of creatinine was significantly associated with the length of time that 

***DRAFT FOR PUBLIC COMMENT*** 
 

URANIUM A-12 

APPENDIX A 

the uranium workers had spent in the yellowcake area. Although urinary uranium levels were reported, 

atmospheric concentrations were not reported. 

Stokinger et al. (1953) examined the chronic toxicity of uranium hexafluoride, uranium tetrachloride, and 

uranyl nitrate in dogs and rats following a 1-year exposure. Slight to mild renal tubular atrophy was 

observed in dogs and rats exposed to 0.2 mg U/m3 as uranium hexafluoride or uranium tetrachloride; no 

effects were observed at 0.05 mg U/m3

. Exposure to uranyl nitrate resulted in mild to moderate tubular 

atrophy in dogs exposed to 0.25 mg U/m3 (NOAEL of 0.15 mg U/m3

) and mild to marked tubular atrophy 

in rats exposed to 2 mg U/m3 (NOAEL of 0.25 mg U/m3

). 

Agency Contacts (Chemical Managers): Sam Keith, Obaid Faroon, Nickolette Roney, Franco 

Scinicariello, Sharon Wilbur 

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URANIUM A-13 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Uranium (soluble forms) 

CAS Numbers: Multiple 

Date: March 2011 

Profile Status: Draft for Public Comment 

Route: [ ] Inhalation [X] Oral 

Duration: [X] Acute [ ] Intermediate [ ] Chronic 

Graph Key: 15 

Species: Mouse 

Minimal Risk Level: 0.002 [X] mg/kg/day [ ] ppm [ ] mg/m3 

Reference: Domingo JL, Paternain JL, Llobet JM, et al. 1989c. The developmental toxicity of uranium 

in mice. Toxicol 55:143-152. 

Experimental design: Groups of 20 pregnant Swiss mice were administered via gavage 0, 5, 10, 25, or 

50 mg/kg/day uranyl acetate dihydrate (0, 2.8, 5.6, 14, or 28 mg U/kg/day) on gestation days 6–15. Body 

weights, food consumption, and general appearance were monitored daily. At termination, maternal liver 

and kidney weights were measured and uterine contents (number of implantation sites, resorptions, dead 

fetuses, and live fetuses) were evaluated. Live fetuses were evaluated for body weight, body length, sex, 

gross morphological abnormalities, visceral malformations, visceral anomalies (evaluated in 1/3 of 

fetuses), and skeletal defects (evaluated in 2/3 of fetuses). 

Effect noted in study and corresponding doses: Significant decreases in maternal body weight were 

observed in all uranium groups; during the exposure period, the dams in the 2.6, 5.6, 14, and 28 mg 

U/kg/day groups weighed 33, 53, 75, and 88% less than controls, respectively. Significant decreases in 

food intake were also observed in the dams exposed to ≥5.6 mg U/kg/day. A significant decrease in the 

number of live fetuses was observed at 5.6 mg U/kg/day, but was not observed at the two higher dose 

levels. No significant alterations in the number of early or late resorptions, number of dead fetuses, or sex 

ratio were observed. Significant decreases in fetal body weight were observed at ≥2.8 mg U/kg/day and 

decreases in fetal length were observed at ≥5.6 mg U/kg/day. Significant increases in the incidences of 

external defects were observed at 2.8 mg U/kg/day. The alterations included cleft palate (significant at 

≥5.6 mg U/kg/day) and hematomas (significant at 2.8 and 28 mg U/kg/day). The total number of skeletal 

defects was significantly increased at 14 and 28 mg U/kg/day; skeletal defects included bipartite 

sternebrae (significant at 2.8, 14, and 28 mg U/kg/day), some metatarsal of hindlimb poorly ossified 

(significant at 14 and 28 mg U/kg/day), delayed ossification of skull (significant at 14 and 28 mg 

U/kg/day), and caudal reduced ossification (significant at 14 and 28 mg U/kg/day). 

Dose and end point used for MRL derivation: 

[ ] NOAEL [ ] LOAEL [X] BMDL 0.2 mg U/kg/day for developmental toxicity 

The results of the Domingo et al. (1989c) study suggest maternal body weight gain and fetal body weight 

and external and skeletal alterations as sensitive end points of uranium toxicity. It is possible that the 

developmental effects were secondary to the maternal toxicity; however, some of these effects may also 

be primary effects of uranium on the developing fetus. Thus, maternal and fetal end points were 

considered as the basis of possible points of departure for the acute-duration MRL. Data for the number 

of litters with total external alterations, cleft palate, total skeletal defects, and bipartite sternebrae 

(summarized in Table A-2) were analyzed using all available dichotomous models in the EPA BMDS 

(version 2.1.2) using the extra risk option. The multistage model was run for all polynomial degrees up to 

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URANIUM A-14 

APPENDIX A 

n-1 (where n is the number of dose groups including control). Adequate model fit was judged by three 

criteria: goodness-of-fit p-value (p>0.1), visual inspection of the dose-response curve, and scaled residual 

at the data point (except the control) closest to the predefined BMR. For a given end point, the BMDL 

from the model with the lowest AIC (among all of the models meeting adequate fit criteria) was chosen. 

BMDs and lower bounds on the BMD (BMDLs) associated with a BMR of 5% extra risk for dichotomous 

data were calculated for all models and are presented in Table A-3. 

Table A-2. Fetal Body Weights and Incidence of Litters with External or Skeletal
 

Defects
 

Dose level 

(mg U/kg/day) 0 2.8 5.6 14 28 

Number of litters 18 17 18 18 18 

Fetal body weight (g) ± 1.40±0.15 1.04±0.25a 0.93±0.24a 0.84±0.11a 0.77±0.17a 

standard deviation 

Total external defects 0 8b 14c 14c 17a 

Cleft palate 0 2 13c 13c 16c 

Total skeletal defects 4 11 15 18b 18b 

Bipartite sternebrae 0 6b 3 9c 13c 

a

Significantly different from controls (p<0.001).

b

Significantly different from controls (p<0.05). c

Significantly different from controls (p<0.01). 

Source: Domingo et al. 1989c 

Table A-3. Model Predictions for Developmental Effects in the Offspring of Mice 

Administered Uranyl Acetate via Gavage on Gestation Days 6–15 (Domingo et 

al. 1989c) 

χ2 

Goodness- BMD05 BMDL05 

Model AIC of-fit p-valuea (mg U/kg/day) (mg U/kg/day) 

Total external defects 

Gammab 78.58 8.4 0.078 ND (GF) ND (GF) 

Logistic 92.24 14.56 0.0022 ND (LSR) ND (LSR) 

Log Logistic 75.06 1.71 0.6339 0.16 0.08 

Log Probit 76.43 6.1 0.1919 0.73 0.54 

Multistage (1 degree 78.58 8.4 0.078 ND (GF) ND (GF) 

polynomial) 

Multistage (2 degree 78.58 8.4 0.078 ND (GF) ND (GF) 

polynomial) 

Multistage (3 degree 78.58 8.4 0.078 ND (GF) ND (GF) 

polynomial) 

Multistage (4 degree 78.58 8.4 0.078 ND (GF) ND (GF) 

polynomial) 

Probit 93.38 15.41 0.0015 ND (LSR) ND (LSR) 

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URANIUM A-15 

APPENDIX A 

Table A-3. Model Predictions for Developmental Effects in the Offspring of Mice 

Administered Uranyl Acetate via Gavage on Gestation Days 6–15 (Domingo et 

al. 1989c) 

χ2 

Goodness- BMD05 BMDL05 

Model AIC of-fit p-valuea (mg U/kg/day) (mg U/kg/day) 

Weibullb 78.58 8.4 0.078 ND (GF) ND (GF) 

Quantal-Linear 78.58 8.4 0.078 ND (GF) ND (GF) 

Cleft palate 

Gammab 78.21 8.69 0.0693 ND (GF) ND (GF) 

Logistic 92.12 18.44 0.0004 ND (GF) ND (GF) 

Log Logistic 77.98 6.15 0.1047 0.75 0.20 

Log Probit 76.56 7.06 0.133 ND (LSR) ND (LSR) 

Multistage (1 degree 78.21 8.69 0.0693 ND (GF) ND (GF) 

polynomial) 

Multistage (2 degree 78.21 8.69 0.0693 ND (GF) ND (GF) 

polynomial) 

Multistage (3 degree 78.21 8.69 0.0693 ND (GF) ND (GF) 

polynomial) 

Multistage (4 degree 78.21 8.69 0.0693 ND (GF) ND (GF) 

polynomial) 

Probit 92.80 18.94 0.0003 ND (GF) ND (GF) 

Weibullb 78.21 8.69 0.0693 ND (GF) ND (GF) 

Quantal-Linear 78.58 8.4 0.078 ND (GF) ND (GF) 

Total skeletal defects 

Gammab 63.69 0.24 0.889 0.39 0.12 

Logistic 61.85 0.46 0.9275 0.37 0.25 

Log Logistic 64.42 0.77 0.6808 0.84 0.12 

Log Probit 64.02 0.49 0.7828 0.85 0.30 

Multistage (1 degree 61.87 0.29 0.9617 0.17 0.12 

polynomial) 

Multistage (2 degree 63.54 0.14 0.9326 0.23 0.12 

polynomial) 

Multistage (3 degree 63.45 0.07 0.9653 0.20 0.12 

polynomial) 

Multistage (4 degree 63.40 0.03 0.9848 0.19 0.12 

polynomial) 

Probit 61.86 0.49 0.9205 0.36 0.26 

Weibullb 63.64 0.21 0.902 0.33 0.12 

Quantal-Linear 61.87 0.29 0.9617 0.17 0.12 

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URANIUM A-16 

APPENDIX A 

Table A-3. Model Predictions for Developmental Effects in the Offspring of Mice 

Administered Uranyl Acetate via Gavage on Gestation Days 6–15 (Domingo et 

al. 1989c) 

χ2 

Goodness- BMD05 BMDL05 

Model AIC of-fit p-valuea (mg U/kg/day) (mg U/kg/day) 

Bipartite sternebrae 

Gammab 94.61 7.49 0.0578 ND (GF) ND (GF) 

Logistic 97.86 7.44 0.0591 ND (GF) ND (GF) 

Log Logistic 93.02 4.37 0.224 0.37 0.42 

Log Probit 97.82 8.65 0.0343 ND (GF) ND (GF) 

Multistage (1 degree 94.61 7.49 ND (GF) ND (GF) 

polynomial) 0.0578 

Multistage (2 degree 94.61 7.49 ND (GF) ND (GF) 

polynomial) 0.0578 

Multistage (3 degree 94.61 7.49 ND (GF) ND (GF) 

polynomial) 0.0578 

Multistage (4 degree 94.61 7.49 ND (GF) ND (GF) 

polynomial) 0.0578 

Probit 97.69 7.43 0.0595 2.80 2.11 

Weibullb 94.61 7.49 0.0578 ND (GF) ND (GF) 

Quantal-Linear 94.61 7.49 0.0578 ND (GF) ND (GF) 

a

Values <0.10 fail to meet conventional goodness-of-fit criteria. b

Power restricted to ≥1. 

AIC = Akaike Information Criteria; BMD = benchmark dose associated with the selected benchmark response of 5% 

extra risk; BMDL = 95% lower confidence limit on the BMC ND (GF) = not determined, goodness-of-fit criteria <0.10; 

ND (LSR) = not determined, largest scaled residual >2 

The fetal body weight data (summarized in Table A-2) and maternal body weight gain data were fit to all 

available continuous models in EPA’s Benchmark Dose Software (BMDS, version 2.1.2). The following 

procedure for fitting continuous data was used: the simplest model (linear) was first applied to the data 

while assuming constant variance; if the data were consistent with the assumption of constant variance 

(p≥0.1), then the fit of the linear model to the means was evaluated and the polynomial, power, and Hill 

models were fit to the data while assuming constant variance. Adequate model fit was judged by three 

criteria: goodness-of-fit p-value (p>0.1), visual inspection of the dose-response curve, and scaled residual 

at the data point (except the control) closest to the predefined BMR. Among all of the models providing 

adequate fit to the data, the BMDL from the model with the lowest AIC was chosen. If the test for 

constant variance was negative, then the linear model was run again while applying the power model 

integrated into the BMDS to account for nonhomogenous variance. If the nonhomogenous variance 

model provided an adequate fit (p≥0.1) to the variance data, then the fit of the linear model to the means 

was evaluated and the polynomial, power, and Hill models were fit to the data and evaluated while the 

variance model was applied. Model fit and point of departure selection proceeded as described earlier. If 

the test for constant variance was negative and the nonhomogenous variance model did not provide an 

adequate fit to the variance data, then the data set was considered unsuitable for modeling. For all fetal 

body weight models, a BMR of 5% relative deviation was used; a BMR of 10% was used for all maternal 

body weight gain models. Although the Hill model with constant variance or nonconstant variance 

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 0

 


 


 

URANIUM A-17 

APPENDIX A 

provided an adequate fit to means for the fetal body weight data, the models did not provide adequate fit 

to the variance and were not considered suitable for identifying a point of departure for an MRL. None of 

the available models provided adequate fit for the maternal body weight gain data. 

Using the benchmark modeling results for external and skeletal defects, several points of departure were 

considered; these are summarized in Table A-4. The BMDL values ranged from 0.08 to 0.42 mg 

U/kg/day and the average of these values (0.2 mg U/kg/day) was selected as the point of departure. The 

fit of the log logistics model to the cleft palate data and the logistic model for the total skeletal defects 

data are presented in Figures A-2 and A-3, respectively. 

Table A-4. Summary of BMDLs Considered for the Point of Departure for an 

Acute-Duration Oral MRL
 

BMDL 

Effect Model (mg U/kg/day) 

Total external defects Log logistic 0.08 

Cleft palate Log logistic 0.20 

Total skeletal defects Logistic 0.25 

Bipartite sternebrae Log logistic 0.42 

Figure A-2. Predicted (Log Logistic Model) and Observed Incidence of Cleft
 

Palate*
 

Fraction Affected 

0.8

 0.6

 0.4

 0.2 

0

 1

 5 10 15 20 25 

dose 

Log-Logistic Model with 0.95 Confidence Level 

BMDL BMD 

Log-Logistic 

10:15 01/24 2011 

*BMD and BMDL indicated are associated with 5% extra risk and are in units of mg U/kg/day. 

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 0

 

 

 


 


 

URANIUM A-18 

APPENDIX A 

Figure A-3. Predicted (Logistic Model) and Observed Incidence of Skeletal
 

Defects*
 

Fraction Affected 

0.8

 0.6

 0.4

 0.2

 0

 1

 5 10 15 20 25 

dose 

Logistic Model with 0.95 Confidence Level 

BMDL BMD 

Logistic 

10:33 01/24 2011 

*BMD and BMDL indicated are associated with 5% extra risk and are in units of mg U/kg/day. 

Uncertainty Factors used in MRL derivation: 

[ ] 3 for use of a LOAEL 

[x] 10 for extrapolation from animals to humans 

[x] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? No. 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: Not 

applicable. 

Was a conversion used from intermittent to continuous exposure? Not applicable. 

Other additional studies or pertinent information that lend support to this MRL: There are limited human 

data on the oral toxicity of uranium. Signs of gastrointestinal irritation (nausea, vomiting, diarrhea) were 

observed in a subject ingesting 14.3 mg U/kg as uranyl nitrate in drinking water (Butterworth 1955); other 

potential targets of toxicity were not examined. Acute oral exposure studies in rats and mice have 

examined the lethality, systemic toxicity, neurotoxicity, and developmental toxicity of uranium. 

Information on the systemic toxicity is limited to two single-exposure toxicity study in rats (Domingo et 

al. 1987) and mice (Martinez et al. 2003) administered lethal doses and a repeated exposure study in mice 

(Ozmen and Yurekli 1998). In the 2 weeks following administration of a single gavage dose of 118 mg 

U/kg as uranyl acetate to rats, significant increases in urine volume (in the absence of changes in water 

consumption), plasma creatinine and urea, and urinary total protein and creatinine were observed; 

hyperemia and microhemorrhagic foci were also observed in the liver and kidneys at the end of the 

2-week observation period (Domingo et al. 1987). In mice, administration of 166 mg U/kg as uranyl 

nitrate resulted in increases in blood urea and creatinine levels and proximal tubular necrosis (Martinez et 

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URANIUM A-19 

APPENDIX A 

al. 2003). Similarly, significant increases in BUN and creatinine levels were observed in mice exposed to 

508 mg U/kg/day as uranyl acetate in the diet for 5 days (Ozmen and Yurekli 1998); the study did not 

include a histological examination of the kidney or other tissues. Neurological effects consisted of 

increased motor activity (Briner and Murray 2005) and increased open field activity (Briner 2009) in mice 

administered 28 or 6 mg U/kg/day, respectively, as depleted uranyl acetate in drinking water for 2 weeks; 

exposure to 28 mg U/kg/day also resulted in a 53% decrease in body weight gain. Gestational exposure 

to ≥2.8 mg U/kg/day as uranyl acetate resulted in significant decreases in fetal body weights and increases 

in the occurrence hematomas in the fetuses of mice exposed on gestation days 6–15 (Domingo et al. 

1989a); increases in the incidence of cleft palate were observed at ≥5.6 mg U/kg/day. Decreases in 

maternal body weight gain were observed at ≥2.8 mg U/kg/day. Exposure of neonatal rats (1 or 7 days of 

age) to 42.7 mg U/kg/day as uranyl nitrate administered via gavage in water, resulted in significant 

reductions in bone formation, increases in bone resorption, and diminished tooth development (Pujadas 

Bigi et al. 2003). 

Agency Contacts (Chemical Managers): Sam Keith, Obaid Faroon, Nickolette Roney, Franco 

Scinicariello, Sharon Wilbur 

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URANIUM A-20 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Uranium (soluble forms) 

CAS Numbers: Multiple 

Date: March 2011 

Profile Status: Draft for Public Comment 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [X] Intermediate [ ] Chronic 

Graph Key: 40 

Species: Rat 

Minimal Risk Level: 0.0002 [X] mg/kg/day [ ] ppm [ ] mg/m3 

Reference: Gilman AP, Villeneuve DC, Secours VE, et al. 1998a. Uranyl nitrate 28-day and 91-day 

toxicity studies in the Sprague-Dawley rat. Toxicol Sci 41(1):117-128. 

Experimental design: Five groups of Sprague-Dawley rats (15/sex/dose, 60 g) were exposed to uranium 

as uranyl nitrate in drinking water (0, 0.96, 4.8, 24, 120, and 600 mg/L) for 91 days. Time-weighted 

average doses calculated by the authors from fluid intake data were <0.0001 (control group), 0.06, 0.31, 

1.52, 7.54, and 36.73 mg U/kg/day in males and <0.0001 (control), 0.09, 0.42, 2.01, 9.98, and 53.56 mg 

U/kg/day in females. Clinical signs were monitored daily and body weights were measured weekly; fluid 

intake and feed consumption were also measured, but the frequency was not reported. Hematological 

parameters serum clinical chemistry (sodium, potassium, phosphate, bilirubin, alkaline phosphatase, 

aspirate aminotransferase, total protein, calcium, cholesterol, glucose, uric acid, lactate dehydrogenase, 

sorbitol dehydrogenase), organ weights, and histopathology (tissues examined: adrenal, brain [three 

sections], bone marrow, bronchi, colon, duodenum, epididymis, stomach [gastric cardia, fundus, and 

pylorus], heart, kidney, liver, lungs, mesenteric and mediastinal lymph nodes, ovary, pancreas, 

parathyroid, pituitary, salivary glands, skeletal muscle, spleen, testes, thoracic aorta, thymus, thyroid, 

trachea, and uterus) were assessed at termination. Uranium residues were measured in samples of brain, 

liver, spleen, liver, kidney, and bone in the control and two highest dose groups. 

Effect noted in study and corresponding doses: Hematological and biochemical parameters were not 

affected in a significant exposure-related manner. Statistically significant increases in renal lesions 

included cytoplasmic vacuolization (0/15, 9/15, 7/15, 12/15, 9/15, 7/15), tubular dilation (0/15, 4/15, 

5/15, 10/15, 4/15, 5/15), and lymphoid cuffing (0/15, 6/15, 6/15, 2/15, 7/15, 10/15) in males at ≥0.06 mg 

U/kg/day; capsular sclerosis (0/15, 5/15, 4/15, 3/15, 6/14, 5/14), tubular anisokaryosis (0/15, 5/15, 4/15, 

3/15, 6/14, 5/14; not significant at 2.01 mg U/kg/day), and interstitial reticulin sclerosis (1/15, 9/15, 8/15, 

7/15, 6/14, 5/14) in females at ≥0.09 mg U/kg/day; nuclear vesiculation in males (0/15, 6/15, 10/15, 6/15, 

8/15) and females (0/15, 6/15, 6/15, 7/15, 4/14, 7/14) at ≥0.06/0.09 mg U/kg/day; and glomerular 

adhesions (2/15, 4/15, 10/15, 10/15, 10/15, 11/15) and cytoplasmic degeneration (0/15, 2/15, 11/15, 

13/15, 7/15, 7/15) in males at ≥0.31 mg U/kg/day. Lesions were also observed in the liver at all doses 

including anisokaryosis, vesiculation, increased portal density, perivenous vacuolation, and homogeneity; 

the investigators considered these adaptive and likely reversible. Thyroid lesions were observed in both 

sexes (multifocal reduction of follicular size, increased epithelial height in males at 0.31 mg/kg/day and 

females at 2.01 mg/kg/day). A decreased amount and density of colloid in the thyroid was observed in 

males only. Sinus hyperplasia of the spleen was observed in males and females at 

36.73/53.56 mg/kg/day. 

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URANIUM A-21 

APPENDIX A 

Dose and end point used for MRL derivation: 0.06 mg U/kg/day, renal toxicity. This is considered a 

minimal LOAEL. 

[ ] NOAEL [X] LOAEL 

Uncertainty Factors used in MRL derivation: 

[x] 3 for use of a minimal LOAEL 

[x] 10 for extrapolation from animals to humans 

[x] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? No, doses were 

calculated by the authors on the basis of measured water intake. 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: Not 

applicable. 

Was a conversion used from intermittent to continuous exposure? Not applicable. 

Other additional studies or pertinent information that lend support to this MRL: No studies have been 

identified that examined the toxicity of uranium in humans following an intermediate-duration oral 

exposure. A number of studies have examined the intermediate-duration oral toxicity of uranium in 

laboratory animals. Most of these studies involved exposure to soluble uranium compounds such as 

uranyl nitrate and uranyl acetate; there are limited data on moderately soluble or insoluble uranium 

compounds. The available data suggest that the kidney is the most sensitive target of uranium toxicity; at 

higher dose levels, neurological, reproductive, and developmental effects have been reported. At lower 

concentrations, histological alterations have been observed in the proximal tubules, glomerulus, and/or 

renal interstitium in rats and mice exposed to uranyl nitrate in drinking water (Gilman et al. 1998a, 1998b, 

1998c; McDonald-Taylor et al. 1992, 1997). At higher concentrations (40.38 mg U/kg/day), evidence of 

renal dysfunction (e.g., glycosuria, proteinuria) has also been observed (Gilman et al. 1998c). The 

Gilman et al. (1998a, 1998b) studies identified the LOAELs of 0.06 and 0.05 mg U/kg/day for renal 

effects in rats and rabbits, respectively; neither study identified NOAEL values. 

The LOAELs for neurological, reproductive, and developmental effects are similar and are about 50-fold 

higher than the LOAEL for renal effects. Neurological effects such as sleep and behavior alterations and 

decreased spatial memory were observed in rats exposed to 2.5–2.7 mg U/kg/day as enriched uranyl 

nitrate (Houpert et al. 2005, 2007b). However, no neurological effects were observed in rats similarly 

exposed to the same dose of depleted uranyl nitrate (Houpert et al. 2005). The investigators suggest that 

the observed effects may have been related to radiological activity. The reproductive effects consisted of 

decreases in male fertility in rats and mice following exposure to ≥5.6 mg U/kg/day as uranyl acetate 

(Linares et al. 2005; Llobet et al. 1991) and alterations in ovarian folliculogenesis in mice at ≥1.25 mg 

U/kg/day as uranyl nitrate (Arnault et al. 2008; Feugier et al. 2008; Kundt et al. 2009). A recent study by 

Raymond-Whish et al. (2007) also reported alterations in ovarian folliculogenesis in mice, but the effects 

were at an extremely low dose (0.00039 mg U/kg/day). Additional data are needed to support whether 

reproductive effects occur at this dose level and to evaluate the toxicological significance of the observed 

effect (reduced number of small primary follicles, but no effect on primordial, secondary/growing, 

healthy, or atretic follicle populations). Developmental effects have been observed in rats and mice; most 

effects occurred at maternally toxic doses. The observed effects included neurobehavioral effects in the 

offspring of rats exposed premating and during gestation and lactation to 4.3 mg U/kg/day as enriched 

uranyl nitrate (Houpert et al. 2007a), decreases in pup body weight at ≥2.8 mg U/kg/day as uranyl acetate 

(Paternain et al. 1989; Sanchez et al. 2006), decreases in litter size, live fetuses, or viability at ≥14 mg 

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URANIUM A-22 

APPENDIX A 

U/kg/day as uranyl acetate (Domingo et al. 1989b; Paternain et al. 1989), and altered ovarian 

folliculogenesis in 3-month-old pups of dams exposed to 1.25 mg U/kg/day as uranyl nitrate (Arnault et 

al. 2008). 

The LOAELs of 0.05 and 0.06 mg U/kg/day for kidney effects in rats and rabbits (Gilman et al. 1998a, 

1998b) were considered as possible points of departure for an intermediate-duration oral MRL for soluble 

uranium compounds. Although the rabbit study identified the slightly lower LOAEL, the rat LOAEL was 

selected as the point of departure for the MRL due to possible subclinical infection in the rabbits. Gilman 

et al. (1998b, 1998c) conducted two 91-day studies in rabbits. The kidney uranium levels for the two 

studies were not comparable; rabbits in the first study (Gilman et al. 1998b) had higher kidney uranium 

levels than in the second study (Gilman et al. 1998c) even though the dose was lower in the first study 

(28.70 mg U/kg/day dose and 4.98 μg U/g kidney level in the Gilman et al. 1998b study compared to 

40.98 mg U/kg/day dose and 3.48 μg U/g kidney level in the Gilman et al. 1998c study). In the Gilman et 

al. (1998b) study, the male rabbits were not SPF derived and four animals developed Pasteurella 

multocida infections during the study; Gilman et al. (1998c) suggested that even though the affected 

rabbits were removed from the study, it is possible that other animals had a subclinical infection and that 

this may have increased sensitivity. Thus, the rat study was selected as the basis of the MRL; the rats 

used in the Gilman et al. (1998a) study were SPF derived. The Raymond-Whish et al. (2007) study was 

not selected as the point of departure because there are no other data to support this extremely low value 

and the toxicological significance of this slight change in one follicle population is not known. 

Agency Contacts (Chemical Managers): Sam Keith, Obaid Faroon, Nickolette Roney, Franco 

Scinicariello, Sharon Wilbur 

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URANIUM	 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. 

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URANIUM 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. 

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URANIUM	 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"). 

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URANIUM	 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. 

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URANIUM	 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. 

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1 2 3 4 

→

SAMPLE 

Table 3-1. Levels of Significant Exposure to [Chemical x] – Inhalation 

→→

Exposure 

Key to frequency/ figurea Species duration 

INTERMEDIATE EXPOSURE 

5 6 

Systemic ↓ ↓

NOAEL 

System (ppm) 

7 8 ↓ ↓

LOAEL (effect) Less serious (ppm) 

9 

↓

Serious (ppm) 

Re

10 

↓

→→

18 Rat 13 wk Resp 3b 10 (hyperplasia) 

5 d/wk Nit6 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 

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). 

12 
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APPENDIX B 

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URANIUM 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 

ALT alanine aminotransferase 

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 benchmark dose 

BMR benchmark response 

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 

CML chronic myeloid leukemia 

CPSC Consumer Products Safety Commission 

CWA Clean Water Act 

DHEW Department of Health, Education, and Welfare 

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/IMCO North America/Intergovernmental Maritime Dangerous Goods Code 

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URANIUM C-2 

APPENDIX C 

DWEL 

ECD 

ECG/EKG 

EEG 

EEGL 

EPA 

F F1 

FAO 

FDA 

FEMA 

FIFRA 

FPD 

fpm 

FR 

FSH 

g 

GC 

gd 

GLC 

GPC 

HPLC 

HRGC 

HSDB 

IARC 

IDLH 

ILO 

IRIS 

Kd 

kg 

kkg Koc Kow 

L 

LC 

LC50 

LCLo 

LD50 

LDLo 

LDH 

LH 

LOAEL 

LSE 

LT50 

m 

MA 

MAL 

mCi 

MCL 

MCLG 

MF 

drinking water exposure level 

electron capture detection 

electrocardiogram 

electroencephalogram 

Emergency Exposure Guidance Level 

Environmental Protection Agency 

Fahrenheit 

first-filial generation 

Food and Agricultural Organization of the United Nations 

Food and Drug Administration 

Federal Emergency Management Agency 

Federal Insecticide, Fungicide, and Rodenticide Act 

flame photometric detection 

feet per minute 

Federal Register 

follicle stimulating hormone 

gram 

gas chromatography 

gestational day 

gas liquid chromatography 

gel permeation chromatography 

high-performance liquid chromatography 

high resolution gas chromatography 

Hazardous Substance Data Bank 

International Agency for Research on Cancer 

immediately dangerous to life and health 

International Labor Organization 

Integrated Risk Information System 

adsorption ratio 

kilogram 

metric ton 

organic carbon partition coefficient 

octanol-water partition coefficient 

liter 

liquid chromatography 

lethal concentration, 50% kill 

lethal concentration, low 

lethal dose, 50% kill 

lethal dose, low 

lactic dehydrogenase 

luteinizing hormone 

lowest-observed-adverse-effect level 

Levels of Significant Exposure 

lethal time, 50% kill 

meter 

trans,trans-muconic acid 

maximum allowable level 

millicurie 

maximum contaminant level 

maximum contaminant level goal 

modifying factor 

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URANIUM C-3 

APPENDIX C 

MFO mixed function oxidase 

mg milligram 

mL milliliter 

mm millimeter 

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 

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 

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 

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URANIUM C-4 

APPENDIX C 

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 

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 

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 

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 

VOC volatile organic compound 

WBC white blood cell 

WHO World Health Organization 

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URANIUM C-5 

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 

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APPENDIX C 

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URANIUM 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 

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URANIUM D-2 

APPENDIX D 

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. 

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. 

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URANIUM 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 

939.55 MeV min 

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 fined 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. 

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URANIUM D-4 

APPENDIX D 

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. 

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 

Hydrogen 3b 

Kidney 

Whole body 

4,460,000,000 y 

12.3 y 

4 d 

10 d 

4 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 

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APPENDIX D 

particles. Indirectly ionizing radiations are always more penetrating than directly ionizing particulate 

radiations. 

Mass, charge, and velocity of a particle 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.4 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. 

4 Neutrinos also accompany negative beta particles and positron emissions 

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APPENDIX D 

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 

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 

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URANIUM D-7 

APPENDIX D 

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 

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 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 

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URANIUM D-8 

APPENDIX D 

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 

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 

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URANIUM D-9 

APPENDIX D 

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 

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 and Dose Equivalent Rate 

Dose equivalent or rem 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 ICRU has defined 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 dose equivalent concept is applicable 

only to doses that are not great enough to produce biomedical effects. 

The quality 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 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. 

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URANIUM D-10
 

APPENDIX D
 

Table D-3. Quality Factors (Q) and Absorbed Dose Equivalencies 

Absorbed dose equal to a unit dose 

Type of radiation Quality factor (Q) equivalent* 

X, gamma, or beta radiation 1 1 

Alpha particles, multiple- 20 0.05 

charged particles, fission 

fragments and heavy particles of 

unknown charge 

Neutrons of unknown energy 10 0.1 

High-energy protons 10 0.1 

*Absorbed dose in rad equal to 1 rem or the absorbed dose in gray equal to 1 sievert. 

Source: USNRC. 1999. Standards for the protection against radiation, table 1004(b).1. 10 

CFR 20.1004. U.S. Nuclear Regulatory Commission, Washington, D.C. 

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 

used in calculations of dose equivalents 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 and Effective Dose Equivalent Rate 

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) has 

derived a concept of effective dose equivalent. The effective dose equivalent, HE, is 

HE = (the sum of) Wt Ht 

where Ht is the dose equivalent in the tissue, Wt is the weighting factor, which represents the estimated 

proportion of the stochastic risk resulting from tissue, T, to the stochastic risk when the whole body is 

uniformly irradiated for occupational exposures under certain conditions (ICRP 1977). 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. 

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URANIUM D-11
 

APPENDIX D
 

Table D-4. Weighting Factors for Calculating Effective Dose
 

Equivalent for Selected Tissues
 

Weighting factor 

Tissue ICRP60 NCRP115/ ICRP60 NRC 

Bladder 0.040 0.05 – 

Bone marrow 0.143 0.12 0.12 

Bone surface 0.009 0.01 0.03 

Breast 0.050 0.05 0.15 

Colon 0.141 0.12 – 

Liver 0.022 0.05 – 

Lung 0.111 0.12 0.12 

Esophagus 0.034 0.05 – 

Ovary 0.020 0.05 – 

Skin 0.006 0.01 – 

Stomach 0.139 0.12 – 

Thyroid 0.021 0.05 0.03 

Gonads 0.183 0.20 0.25 

subtotal 0.969 1 0.70 

Remainder 0.031 0.05 0.30 

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 

Table D-5. Comparison of Common and SI Units for Radiation Quantities 

Customary 

Quantity 

Activity (A) 

units 

curie (Ci) 

Definition 

3.7x1010 

SI units 

becquerel (Bq) 

Definition 

s -1 

transformations s1 

Absorbed dose rad (rad) 10-2 Jkg-1 gray (Gy) Jkg-1 

(D) 

Absorbed dose 

rate (Ď) 

Dose equivalent 

rad per second 

(rad s-1) 

rem (rem) 

10-2 Jkg-1s -1 

10-2 Jkg-1 

gray per second 

(Gy s-1) 

sievert (Sv) 

Jkg-1 s -1 

Jkg-1 

(H) 

Dose equivalent 

rate () 

Linear energy 

rem per second 

(rem s-1) 

kiloelectron volts 

10-2 Jkg-1s -1 

1.602x10-10 Jm-1 

sievert per second 

(Sv s-1) 

kiloelectron volts 

Jkg-1 s -1 

1.602x10-10 Jm-1 

transfer (LET) 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 

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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. 

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URANIUM D-13 

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. 

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URANIUM D-14 

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. 

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URANIUM E-1 

APPENDIX E. INDEX
 

absorbed dose............................................................................................................................ 107, 222, 234
 

acetylcholine ....................................................................................................................................... 16, 148
 

acetylcholinesterase ............................................................................................................................ 16, 148
 

active transport..........................................................................................................................................232
 

adenocarcinomas.......................................................................................................................................106
 

adsorbed.......................................................................................................................... 3, 11, 279, 280, 295
 

adsorption.......................................................................................................... 279, 293, 294, 295, 339, 340
 

alanine aminotransferase (see ALT) .........................................................................................................137
 

ALT (see alanine aminotransferase) ................................................................................................. 137, 173
 

ambient air .............................................................................................................. 91, 93, 95, 187, 299, 326
 

anaerobic...................................................................................................................................................297
 

anemia............................................................................................................................................... 135, 136
 

antiestrogenic ............................................................................................................................................152
 

aspartate aminotransferase (see AST).......................................................................................................137
 

AST (see aspartate aminotransferase)............................................................................................... 137, 173
 

bioaccumulation................................................................................................................................ 295, 326
 

bioavailability ................................................................................................... 242, 243, 250, 321, 326, 328
 

bioconcentration factor .............................................................................................................................295
 

biodistribution...........................................................................................................................................332
 

biokinetic .......................................................................... 180, 190, 195, 203, 205, 215, 218, 222, 250, 333
 

biological half-time........................................................................................................... 192, 199, 200, 201
 

biomarker ...............13, 35, 136, 170, 173, 233, 234, 235, 236, 240, 243, 245, 246, 249, 250, 329, 344, 347
 

blood cell count............................................................................................................................. 89, 98, 147
 

body weight effects........................................................................... 32, 81, 96, 97, 109, 144, 158, 168, 174
 

breast milk................................................................................................................................. 190, 232, 320
 

cancer.................................... 6, 18, 41, 42, 83, 103, 104, 105, 107, 155, 156, 157, 169, 231, 249, 251, 363
 

carcinogen.................................................................................................................................................363
 

carcinogenic ............................................................................................................ 18, 39, 40, 227, 244, 364
 

carcinogenicity.................................................................................................. 103, 156, 177, 240, 244, 364
 

carcinoma............................................................................................................................ 99, 106, 107, 156
 

cardiovascular ................................................................................................. 44, 81, 87, 109, 133, 134, 158
 

cardiovascular effects.................................................................................................................. 87, 133, 134
 

chromosomal aberrations.................................................................................................. 178, 179, 182, 228
 

clearance ...................................................... 81, 87, 88, 91, 93, 94, 140, 171, 191, 192, 193, 198, 199, 200, 

203, 206, 207, 211, 212, 213, 215, 218, 224, 226, 243, 250
 

death.......................27, 39, 40, 41, 42, 43, 44, 83, 84, 98, 103, 153, 176, 177, 178, 182, 185, 227, 244, 245
 

deoxyribonucleic acid (see DNA).............................................................................................................177
 

dermal effects.............................................................................................................................. 96, 167, 168
 

developmental effects ................................... 32, 33, 101, 153, 154, 155, 169, 175, 177, 231, 246, 251, 349
 

DNA (see deoxyribonucleic acid)..................... 177, 179, 180, 181, 182, 183, 184, 185, 227, 234, 245, 247
 

dopamine........................................................................................................................................... 147, 148
 

endocrine................................................................................................. 44, 81, 96, 109, 143, 158, 228, 229
 

endocrine effects ................................................................................................................. 96, 143, 158, 174
 

erythema....................................................................................................................................................167
 

estrogen receptor.......................................................................................................................................229
 

estrogenic ............................................................................................................................ 17, 151, 229, 246
 

fetus............................................................................................................................. 32, 230, 252, 321, 362
 

follicle stimulating hormone .....................................................................................................................175
 

fractional absorption ................................................................................................................. 188, 232, 321
 

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URANIUM E-2 

APPENDIX E 

gastrointestinal effects .................................................................................................. 87, 88, 109, 134, 135
 

general population............................................................................................... 11, 245, 246, 247, 320, 327
 

genotoxic..................................................................................................................... 39, 178, 180, 244, 321
 

genotoxicity....................................................................................................... 170, 178, 180, 182, 244, 252
 

germinal cell...................................................................................................................................... 150, 245
 

groundwater .............................................. 263, 274, 279, 287, 288, 293, 294, 295, 299, 307, 308, 326, 357
 

half-life................................................................................................................ 38, 211, 233, 259, 261, 296
 

hematological effects .............................................................................................. 44, 88, 90, 109, 135, 170
 

hematopoietic........................................................................................................................ 88, 98, 103, 177
 

hepatic effects ................................................................................................................. 44, 81, 90, 137, 173
 

hydrolysis..................................................................................................................................................253
 

immune system ............................................................................................................................. 98, 99, 146
 

immunological ........................................................................................................ 39, 98, 99, 147, 169, 248
 

immunological effects........................................................................................................................... 98, 99
 

LD50........................................................................................................................... 108, 109, 147, 157, 158
 

leukemia.............................................................................................................................. 88, 103, 105, 106
 

lymphatic .............................................................................................................................. 88, 98, 103, 206
 

lymphoreticular......................................................................................................................... 146, 169, 248
 

mass spectroscopy.....................................................................................................................................234
 

melanoma..................................................................................................................................................106
 

metabolic effects .......................................................................................................................................145
 

micronuclei ............................................................................................................................... 151, 180, 182
 

milk ................................................................................................................................... 180, 232, 298, 312
 

mucociliary ................................................................................................................................... 12, 81, 218
 

musculoskeletal effects ....................................................................................................... 90, 136, 158, 170
 

neonatal................................................................................. 17, 31, 153, 155, 188, 232, 246, 320, 321, 328
 

neoplastic ..................................................................................................................................................182
 

neurobehavioral................................................................. 5, 16, 33, 147, 149, 175, 176, 229, 231, 247, 248
 

neurological effects......................................................... 15, 33, 99, 100, 101, 147, 149, 169, 174, 242, 248
 

neurotransmitter .................................................................................................................................. 15, 148
 

norepinephrine ..........................................................................................................................................147
 

nuclear........................................................ 2, 11, 12, 18, 34, 38, 83, 98, 100, 105, 138, 141, 142, 146, 253, 

260, 267, 270, 274, 275, 277, 284, 286, 287, 288, 291, 314, 

322, 327, 329, 332, 335, 345, 351, 356, 357, 358, 360, 362
 

ocular effects................................................................................................................................. 81, 96, 109
 

oxidative phosphorylation.........................................................................................................................227
 

pharmacodynamic............................................................................................................................... 29, 202
 

pharmacokinetic.................................................................................... 29, 92, 185, 202, 203, 204, 230, 232
 

placenta ............................................................................................................................................. 190, 232
 

pulmonary fibrosis .................................................................................................................. 15, 19, 82, 227
 

renal effects............................................................ 14, 15, 22, 23, 24, 25, 26, 27, 28, 33, 35, 44, 87, 91, 92,
 

94, 96, 138, 141, 167, 173, 236, 244, 252, 349, 364
 

reproductive effects......................................................................... 16, 17, 33, 101, 150, 152, 169, 240, 245
 

respiratory effects................................................................................................ 25, 39, 81, 82, 85, 109, 225
 

retention ......................................................... 12, 30, 41, 82, 91, 93, 94, 154, 185, 190, 191, 192, 200, 201, 

206, 211, 212, 215, 224, 225, 233, 252, 261, 333, 353, 354
 

sarcoma ............................................................................................................................................. 106, 156
 

solubility ................................................. 12, 21, 92, 185, 186, 187, 188, 189, 191, 200, 206, 260, 261, 293
 

spermatozoa ................................................................................................................................ 16, 150, 245
 

systemic effects....................................................................................................... 44, 81, 97, 109, 158, 240
 

thyroid................................................................................................................. 35, 143, 191, 193, 275, 360
 

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URANIUM E-3
 

APPENDIX E 

thyroxine ...................................................................................................................................................172
 

toxicokinetic.......................................................................................................................................... 21, 37
 

tremors ......................................................................................................................................................147
 

tumors ......................................................................................................................... 18, 100, 103, 106, 178

weanling....................................................................................................................................................252
 

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