TOXICOLOGICAL PROFILE FOR 

IODINE 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES 

Public Health Service 

Agency for Toxic Substances and Disease Registry
 

April 2004 
IODINE 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. 
IODINE iii 

UPDATE STATEMENT 

A Toxicological Profile for Iodine, Draft for Public Comment was released in September 2001. This 

edition supersedes any previously released draft or final profile. 

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

status of previously released profiles, contact ATSDR at: 

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology/Toxicology Information Branch 

1600 Clifton Road NE, 

Mailstop F-32 

Atlanta, Georgia 30333 


vi 

Background Information 

The toxicological profiles are developed by ATSDR pursuant to Section 104(i) (3) and (5) of the 

Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA or 

Superfund) for hazardous substances found at Department of Energy (DOE) waste sites. CERCLA 

directs ATSDR to prepare toxicological profiles for hazardous substances most commonly found at 

facilities on the CERCLA National Priorities List (NPL) and that pose the most significant potential threat 

to human health, as determined by ATSDR and the EPA. ATSDR and DOE entered into a Memorandum 

of Understanding on November 4, 1992 which provided that ATSDR would prepare toxicological profiles 

for hazardous substances based upon ATSDR=s or DOE=s identification of need. The current ATSDR 

priority list of hazardous substances at DOE NPL sites was announced in the Federal Register on July 24, 

1996 (61 FR 38451). 
 

 

 

 

 

IODINE vii 

QUICK REFERENCE FOR HEALTH CARE PROVIDERS 

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

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

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

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

answers to often-asked questions. 

Primary Chapters/Sections of Interest 

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

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

properties in a nontechnical, question-and-answer format, and it includes a review of the general health 

effects observed following exposure. 

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

and assesses the significance of toxicity data to human health. 

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

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

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

this section. 

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

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

observed following exposure. 

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

issues: 

Section 1.6 How Can (Chemical X) Affect Children? 

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

Section 3.8 Children's Susceptibility 

Section 6.6 Exposures of Children 

Other Sections of Interest: 

Section 3.9 Biomarkers of Exposure and Effect 

Section 3.12 Methods for Reducing Toxic Effects 

ATSDR Information Center 

Phone: 1-888-42-ATSDR or (404) 498-0110 Fax: (770) 488-4178 

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

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

 

 

IODINE viii 

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. 

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 
 

 

 

IODINE ix 

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/. 

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, 55 West Seegers Road, Arlington Heights, IL 

60005 Phone: 847-818-1800 FAX: 847-818-9266. 

IODINE xi 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHORS(S): 

John Risher. Ph.D 

ATSDR, Division of Toxicology, Atlanta, GA 

Gary Diamond, Ph.D. 

Steven G. Swarts, Ph.D. 

Richard Amata, Ph.D. 

Syracuse Research Corporation, 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 Research Implementation Branch reviews data needs sections to assure 

consistency across profiles and adherence to instructions in the Guidance. 

 

 

 

IODINE	 xiii 

PEER REVIEW 

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

1.	 Dr. Lewis E. Braverman, Section Chief, Endocrinology, Diabetes, and Nutrition, Boston Medical 

Center, 88 East Newton Street, Evans 201, Boston, MA 02118; 

2. Dr. Richard Leggett, Life Sciences Division, Oak Ridge National Laboratory, 11401 Glen Iris 

Lane, Knoxville, TN 37922-1744; 

3. Dr. Ray Lloyd, Research Professor of Radiobiology, University of Utah School of Medicine, 

6588 South Gold Medal Drive, Taylorsville, UT 84084-6964; 

4. Dr. Marvin Rallison, Professor Emeritus of Pediatric Endocrinology and Metabolism, University 

of Utah School of Medicine, 1706 Oakridge Dr., Salt Lake City, UT 84106; 

5.	 Dr. Elaine Ron, Senior Investigator, National Cancer Institute, Division of Cancer Epidemiology 

and Genetics, Radiation Epidemiology Branch, 6120 Executive Boulevard, EPS/7084, Rockville, 

MD 20852; 

6. Dr. Kiyohiko Mabichi, National Cancer Institute, 6120 Executive Boulevard, Rockville, MD 

20852; 

7.	 Dr. Noel R. Rose, Professor of Molecular Medicine, Johns Hopkins University, 615 North Wolfe 

St., Baltimore, MD 21205; and 

8. Dr. Roy E. Shore, Professor and Director, Division of Epidemiology and Biostatistics, New York 

University School of Medicine, 650 First Ave., New York, NY 10016-3240. 

These experts collectively have knowledge of iodine'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. A list of databases reviewed and 

a list of unpublished documents cited are also included in the administrative record. 

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. 

 

 

 

 

 

 

 

IODINE	 xv 

CONTENTS 

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

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

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

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

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

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

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

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

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

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

1.1 WHAT IS IODINE?......................................................................................................................2 

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

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

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

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

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

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO IODINE? ..........................6 

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

IODINE?...............................................................................................................6 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH?..............................................................................................................7 

1.10 WHERE CAN I GET MORE INFORMATION? .........................................................................8 

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

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO IODINE IN THE 

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

2.2 SUMMARY OF HEALTH EFFECTS.......................................................................................12 

2.3 MINIMAL RISK LEVELS........................................................................................................29 

3. HEALTH EFFECTS................................................................................................33 

3.1 INTRODUCTION.......................................................................................................................33 

3.2 DISCUSSION OF HEALTH EFFECTS FOR STABLE IODINE BY ROUTE OF 

EXPOSURE ................................................................................................................................35 

3.2.1 Inhalation Exposure ............................................................................................................37 

3.2.1.1 Death ............................................................................................................................37 

3.2.1.2 Systemic Effects...........................................................................................................37 

3.2.1.3 Immunological and Lymphoreticular Effects...............................................................37 

3.2.1.4 Neurological Effects.....................................................................................................37 

3.2.1.5 Reproductive Effects....................................................................................................37 

3.2.1.6 Developmental Effects .................................................................................................37 

3.2.1.7 Cancer...........................................................................................................................37 

3.2.2 Oral Exposure .....................................................................................................................37 

3.2.2.1 Death ............................................................................................................................39 

3.2.2.2 Systemic Effects...........................................................................................................40 

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

3.2.2.4 Neurological Effects.....................................................................................................70 

3.2.2.5 Reproductive Effects....................................................................................................70 
 

 

 

IODINE	 xvi 

3.2.2.6 Developmental Effects .................................................................................................71 

3.2.2.7 Cancer...........................................................................................................................71 

3.2.3 Dermal Exposure.................................................................................................................75 

3.2.3.1 Death ............................................................................................................................75 

3.2.3.2 Systemic Effects...........................................................................................................75 

3.2.3.3 Immunological and Lymphoreticular Effects...............................................................78 

3.2.3.4 Neurological Effects.....................................................................................................79 

3.2.3.5 Reproductive Effects....................................................................................................79 

3.2.3.6 Developmental Effects .................................................................................................80 

3.2.3.7 Cancer...........................................................................................................................80 

3.2.4 External Exposure ...............................................................................................................80 

3.3 DISCUSSION OF HEALTH EFFECTS FOR RADIOACTIVE IODINE BY ROUTE OF 

EXPOSURE ................................................................................................................................80 

3.3.1 Inhalation Exposure ............................................................................................................81 

3.3.1.1 Death ............................................................................................................................82 

3.3.1.2 Systemic Effects...........................................................................................................82 

3.3.1.3 Immunological and Lymphoreticular Effects...............................................................82 

3.3.1.4 Neurological Effects.....................................................................................................83 

3.3.1.5 Reproductive Effects....................................................................................................83 

3.3.1.6 Developmental Effects .................................................................................................83 

3.3.1.7 Cancer...........................................................................................................................84 

3.3.2 Oral Exposure .....................................................................................................................84 

3.3.2.1 Death ............................................................................................................................88 

3.3.2.2 Systemic Effects...........................................................................................................88 

3.3.2.3 Immunological and Lymphoreticular Effects...............................................................97 

3.3.2.4 Neurological Effects.....................................................................................................99 

3.3.2.5 Reproductive Effects..................................................................................................100 

3.3.2.6 Developmental Effects ...............................................................................................103 

3.3.2.7 Cancer.........................................................................................................................109 

3.3.3 External Exposure .............................................................................................................127 

3.4 GENOTOXICITY.....................................................................................................................127 

3.5 TOXICOKINETICS..................................................................................................................129 

3.5.1 Absorption.........................................................................................................................129 

3.5.1.1 Inhalation Exposure....................................................................................................129 

3.5.1.2 Oral Exposure.............................................................................................................130 

3.5.1.3 Dermal Exposure ........................................................................................................133 

3.5.1.4 Other Routes of Exposure ..........................................................................................136
 

3.5.2 Distribution .......................................................................................................................136 

3.5.2.1 Inhalation Exposure....................................................................................................136 

3.5.2.2 Oral Exposure.............................................................................................................136 

3.5.2.3 Dermal Exposure ........................................................................................................140 

3.5.2.4 Other Routes of Exposure ..........................................................................................140
 

3.5.3 Metabolism .......................................................................................................................141 

3.5.3.1 Inhalation Exposure....................................................................................................141 

3.5.3.2 Oral Exposure.............................................................................................................141 

3.5.3.3 Dermal Exposure ........................................................................................................148 

3.5.4 Elimination and Excretion ................................................................................................148 

3.5.4.1 Inhalation Exposure....................................................................................................148 

3.5.4.2 Oral Exposure.............................................................................................................148 

3.5.4.3 Dermal Exposure ........................................................................................................150 

3.5.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models.........150 
 

 

 

IODINE xvii 

3.6 MECHANISMS OF ACTION..................................................................................................181
 

3.6.1 Pharmacokinetic Mechanisms...........................................................................................181 

3.6.2 Mechanisms of Toxicity....................................................................................................188 

3.6.3 Animal-to-Human Extrapolations.....................................................................................190 

3.7 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS..........................190 

3.8 CHILDREN’S SUSCEPTIBILITY...........................................................................................191 

3.9 BIOMARKERS OF EXPOSURE AND EFFECT....................................................................197 

3.9.1 Biomarkers Used to Identify or Quantify Exposure to Iodine ..........................................198 

3.9.2 Biomarkers Used to Characterize Effects Caused by Iodine ............................................199 

3.10 INTERACTIONS WITH OTHER CHEMICALS ....................................................................201 

3.11 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE............................................205 

3.12 METHODS FOR REDUCING TOXIC EFFECTS ..................................................................206 

3.12.1 Reducing Peak Absorption Following Exposure ..............................................................207 

3.12.2 Reducing Body Burden.....................................................................................................207 

3.12.3 Interfering with the Mechanism of Action for Toxic Effects............................................208 

3.13 ADEQUACY OF THE DATABASE .......................................................................................209 

3.13.1 Existing Information on Health Effects of Iodine.............................................................210 

3.13.2 Identification of Data Needs.............................................................................................210
 

3.13.3 Ongoing Studies................................................................................................................215 

4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION..................................219 

4.1 CHEMICAL IDENTITY ..........................................................................................................219 

4.2 PHYSICAL, CHEMICAL, AND RADIOLOGICAL PROPERTIES ......................................219 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL.............................................227 

5.1 PRODUCTION .........................................................................................................................227 

5.2 IMPORT/EXPORT ...................................................................................................................228 

5.3 USE.........................................................................................................228 

5.4 DISPOSAL................................................................................................................................229 

6. POTENTIAL FOR HUMAN EXPOSURE....................................................................233 

6.1 OVERVIEW..............................................................................................................................233 

6.2 RELEASES TO THE ENVIRONMENT..................................................................................240 

6.2.1 Air.....................................................................................................240 

6.2.2 Water.................................................................................................................................245 

6.2.3 Soil....................................................................................................246 

6.3 ENVIRONMENTAL FATE .....................................................................................................248 

6.3.1 Transport and Partitioning ................................................................................................248 

6.3.2 Transformation and Degradation ......................................................................................252
 

6.3.2.1 Air...............................................................................................................................253 

6.3.2.2 Water ..........................................................................................................................255 

6.3.2.3 Sediment and Soil.......................................................................................................255 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT.................................256 

6.4.1 Air.....................................................................................................256 

6.4.2 Water.................................................................................................................................257 

6.4.3 Sediment and Soil .............................................................................................................260 

6.4.4 Other Environmental Media..............................................................................................263 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE.......................................266 

6.6 EXPOSURES OF CHILDREN.................................................................................................272
 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES .............................................274 

6.8 ADEQUACY OF THE DATABASE .......................................................................................278 
 

 

IODINE xviii 

6.8.1 Identification of Data Needs .............................................................................................278 

6.8.2 Ongoing Studies................................................................................................................281 

7. ANALYTICAL METHODS.....................................................................................283 

7.1 BIOLOGICAL MATERIALS...................................................................................................283 

7.1.1 Internal Iodine Measurements...........................................................................................283 

7.1.2 External Measurements.....................................................................................................289 

7.2 ENVIRONMENTAL SAMPLES .............................................................................................292 

7.2.1 Field Measurements of Iodine...........................................................................................292 

7.2.2 Laboratory Analysis of Environmental Samples ..............................................................293 

7.3 ADEQUACY OF THE DATABASE .......................................................................................305 

7.3.1 Identification of Data Needs .............................................................................................306 

7.3.2 Ongoing Studies................................................................................................................306 

8. REGULATIONS AND ADVISORIES........................................................................309 

9. REFERENCES.....................................................................................................325 

10. GLOSSARY......................................................................................................497 

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

APPENDIX B. USER'S GUIDE....................................................................................B-1 

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

APPENDIX D. OVERVIEW OF BASIC RADIATION PHYSICS, CHEMISTRY, AND 

 BIOLOGY........................................................................................................D-1 

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

 

IODINE xix 

LIST OF FIGURES 

3-1. Levels of Significant Exposure to Iodine—Chemical Toxicity—Oral....................................48 

3-2. Levels of Significant Exposure to Iodine—Radiation Toxicity—Oral..................................106 

3-3. Pathways Uptake and Metabolism of Iodide in the Thyroid Gland..................................................142
 

3-4. Thyroid Hormones and Metabolic Precursors..................................................................................143
 

3-5. Pathways of Metabolism of Iodothyronines.....................................................................................145
 

3-6. Major Deiodination Pathways of Thyroid Hormones in Peripheral Tissues....................................146
 

3-7. Conceptual Representation of a Physiologically Based Pharmacokinetic (PBPK) Model for a
 

Hypothetical Chemical Substance ....................................................................................................152
 

3-8. Compartment Model to Represent Particle Deposition and Time-Dependent Particle Transport 

in the Respiratory Tract ....................................................................................................................154
 

3-9. Reaction of Gases or Vapors at Various Levels of the Gas-Blood Interface....................................157
 

3-10. The Human Respiratory Tract Model: Absorption into Blood.......................................................162
 

3-11. Structure of EPA (2002) PBPK Model of Iodine in Adult Male Humans and Rats.......................166
 

3-12. Berkovski (2002) Metabolic Model for Iodine...............................................................................170
 

3-13. International Commission on Radiological Protection (ICRP) (1989) Metabolic Model for 

Iodine ................................................................................................................................................173
 

3-14. National Radiological Protection Board of the United Kingdom Metabolic Model for Iodine .....176
 

3-15. Johnson (1982) Metabolic Model for Iodine ..................................................................................178
 

3-16. Existing Information on Health Effects of Stable Iodine ...............................................................211
 

3-17. Existing Information on Health Effects of Radioactive Iodine ......................................................212
 

6-1. Frequency of NPL Sites with Iodine Contamination........................................................................234
 

6-2. Frequency of NPL Sites with 129I Contamination.............................................................................235
 

6-3. Frequency of NPL Sites with 131I Contamination.............................................................................236
 

6-4. Geochemical Cycle of Triad Elements (I, Br, Cl) ............................................................................241
 

6-5. An Outline of the Movement of Iodine in the Environment.............................................................242
 
 

 

IODINE	 xx 

6-6. Diagram of the Global Iodine Cycle at Steady State Showing Environmental Compartments, 

Compartment Inventories in Grams (g), Transport Pathways, and Fluxes in Grams per Year 

(g/year)..............................................................................................................................................249
 

6-7. A Simplified Scheme of Iodine Cycling in the Marine Boundary Layer .........................................254
 
IODINE xxi 

LIST OF TABLES 

2-1. Thyroid Doses and Dose Rates for Various Isotopes of Iodinea ........................................................15
 

2-2. Risk Groups for Iodine-induced Hypothyroidism ..............................................................................17
 

2-3. Risk Groups for Iodine-induced Hyperthyroidism.............................................................................19
 

2-4. Releases from Radioiodine-producing Events....................................................................................22
 

3-1. Levels of Significant Exposure to Iodine—Chemical Toxicity—Oral....................................41 

3-2. Levels of Significant Exposure to Iodine—Radiation Toxicity—Oral..........................................104 

3-3. Estimated Thyroid Radiation Doses in Populations Studied for Radioiodine-related Cancers........110
 

3-4. Binding Characteristics of Major Human Thyroid Hormone-Binding Proteins...............................138
 

3-5. Reference Respiratory Values for a General Caucasian Population at Different Levels of 

Activity .............................................................................................................................................156
 

3-6. Reference Values of Parameters for the Compartment Model to Represent Time-dependent 

Particle Transport from the Human Respiratory Tract .....................................................................158
 

3-7. Chemical-specific Parameters for the Adult Male Rat and Human PBPK Models for Iodide.........164
 

3-8. Properties of Human Iodothyronine Selenodeiodinases...................................................................187
 

3-9. Typical Reference Ranges for Serum Thyroid Hormones and TSH in Humans..............................200
 

3-10. Ongoing Studies on Health Effects of Radioactive Iodine .............................................................216
 

4-1. Chemical Identity of Iodine and Iodine Compounds........................................................................220
 

4-2. Physical and Chemical Properties of Iodine and Iodine Compounds...............................................222
 

4-3. Percent Natural Occurrence and Radioactive Properties of Isotopes of Iodine................................225
 

6-1. Approximate Releases of 129I from Atmospheric and High Altitude Nuclear Weapons Tests.........258
 

6-2. Concentration of Iodine, Chloride, and 129I/127I Ratio in Air and Precipitation as a Function of 

Location and Collection Time...........................................................................................................261
 

6-3. Iodine Content in Specific Soil Types..............................................................................................262
 

6-4. Iodine Content in Missouri Soils as a Function of Depth and Parent Material ................................264
 

6-5. Estimated Average Iodine Intake for Adults in the United States....................................................268
 

7-1. Analytical Methods for Determining Iodine in Biological Samples ................................................284
 
IODINE xxii 

7-2. Analytical Methods for Determining Radioiodine in Biological Samples.......................................291
 

7-3. Analytical Methods for Determining Iodine in Environmental Samples .........................................294
 

7-4. Analytical Methods for Determining Radioiodine in Environmental Samples................................299
 

8-1. Regulations and Guidelines Applicable to Stable Iodine .................................................................310
 

8-2. Regulations and Guidelines Applicable to Radioactive Iodine ........................................................313
 

8-3. Dose Coefficientsa

 (e(50)) for Intakes of Iodine Radionuclides.......................................................323
 
IODINE 1 

1. PUBLIC HEALTH STATEMENT 

This public health statement tells you about iodine and the effects of exposure. 

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

the nation. These sites make up the National Priorities List (NPL) and are the sites targeted for 

long-term federal cleanup activities. Iodine has been found in at least 8 sites. Radioactive iodine 

has been found at 9 sites, including iodine-129 (129I) in at least 3 sites, and iodine-131 (131I) in at 

least 6 sites of the 1,636 current or former NPL sites. However, the total number of NPL sites 

evaluated for iodine is not known. As more sites are evaluated, the sites at which iodine is found 

may increase. This information is important because exposure to iodine may harm you and 

because these sites may be sources of exposure. 

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

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

exposure. You are 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. External exposure to 

radiation may occur from natural or man-made sources. Naturally occurring sources of radiation 

are cosmic radiation from space or radioactive materials in soil or building materials. Man-made 

sources of radioactive materials are found in consumer products, industrial equipment, atom 

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

If you are exposed to either radioactive or stable iodine, many factors determine whether you’ll 

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 the other chemicals you’re exposed to and your 

age, sex, diet, family traits, lifestyle, and state of health. 
IODINE 2 

1. PUBLIC HEALTH STATEMENT 

1.1 WHAT IS IODINE? 

Iodine is a naturally occurring element that is essential for the good health of people and animals. 

Iodine is found in small amounts in sea water and in certain rocks and sediments. Iodine occurs 

in many different forms that can be blue, brown, yellow, red, white, or colorless. Most forms of 

iodine easily dissolve in water or alcohol. Iodine has many uses. Its most important use is as a 

disinfectant for cleaning surfaces and storage containers. Iodine is also used in skin soaps and 

bandages, and for purifying water. Iodine is used in medicines. Iodine is added to food, such as 

table salt, to ensure that all people in the United States have enough iodine in their bodies to 

form essential thyroid hormones. Iodine is put into animal feeds for the same reason. Iodine is 

used in the chemical industry for making inks and coloring agents, chemicals used in 

photography, and in making batteries, fuels, and lubricants. Radioactive iodine also occurs 

naturally. Radioactive iodine is used in medical tests and to treat certain diseases, such as overactivity or cancer of the thyroid gland. 

1.2 WHAT HAPPENS TO IODINE WHEN IT ENTERS THE ENVIRONMENT? 

The oceans are the most important source of natural iodine in the air, water, and soil. Iodine in 

the oceans enters the air from sea spray or as iodine gases. Once in the air, iodine can combine 

with water or with particles in the air and can enter the soil and surface water, or land on 

vegetation when these particles fall to the ground or when it rains. Iodine can remain in soil for a 

long time because it combines with organic material in the soil. It can also be taken up by plants 

that grow in the soil. Cows or other animals that eat these plants will take up the iodine in the 

plants. Iodine that enters surface water can reenter the air as iodine gases. Iodine can enter the 

air when coal or fuel oil is burned for energy; however, the amount of iodine that enters the air 

from these activities is very small compared to the amount that comes from the oceans. 

Radioactive iodine also forms naturally from chemical reactions high in the atmosphere. Most 

radioactive forms of iodine change very quickly (seconds to days) to stable elements that are not 

radioactive. However, one form, 129I, changes very slowly (millions of years), and its levels 

build up in the environment. Small amounts of radioactive iodine, including 129I and 131I, can 
IODINE 3 

1. PUBLIC HEALTH STATEMENT 

also enter the air from nuclear power plants, which form radioiodine from uranium and 

plutonium. Larger amounts of radioactive iodine have been released to the air from accidents at 

nuclear power plants and from explosions of nuclear bombs. 

1.3 HOW MIGHT I BE EXPOSED TO IODINE? 

Iodine is a natural and necessary part of the food that you eat and the water that you drink. In the 

United States, most table salt contains iodine. Iodine is put into table salt to make sure that 

everyone has enough iodine in their bodies to form essential thyroid hormones. In the past, 

people in some areas of the United States did not get enough iodine in their diets. Iodine is in 

some breads because it is added to flour to condition bread dough for baking. Iodine is also in 

cow and goat milk. Iodine gets into milk when cows or goats eat iodine that is in their food and 

water. Iodine can also get into milk when iodine is used to clean milking machines and milk 

storage containers, and to clean the animals’ udders at dairy farms and dairies. Iodine is in ocean 

fish, shellfish, and certain plants that grow in the ocean (kelp). This is because there is iodine in 

sea water, and some sea plants and animals concentrate iodine in their tissues. Iodine can also be 

in the air. Iodine is in sea spray and mist, which are tiny drops of sea water. Iodine is in 

cleansers and medicines that are used to clean and bandage skin wounds (tincture of iodine). 

You can be exposed to these if they are placed on your skin. Some medicines have iodine in 

them. Iodine is used to treat water to make it safe for drinking. You can buy iodine water 

purifying tablets that you add directly to water. You can also buy water treatment cartridges for 

your home that have iodine in them. Some iodine will get into the water that you drink if you 

use these tablets or cartridges. 

People are almost never exposed to radioactive iodine, unless they work in a place where 

radioactive iodine is used or if they are given radioactive iodine by their doctors. Radioactive 

iodine is used in certain medical tests and treatments. You might have these tests if your doctor 

needs to look for problems in your thyroid gland or if your doctor needs to treat you for a 

problem with your thyroid gland. In the past, people were exposed to radioactive iodine released 

from nuclear bomb tests, after accidental explosions and fires at nuclear power plants, or from 

facilities that processed or used nuclear fuel for power plants. 
 

IODINE 4 

1. PUBLIC HEALTH STATEMENT 

1.4 HOW CAN IODINE ENTER AND LEAVE MY BODY? 

Most of the iodine that enters your body comes from the food that you eat. A smaller amount 

comes from the water that you drink. Iodine will enter your body if it is in the air that you 

breathe. Some forms of iodine can enter your body when placed on the skin. Iodine can also be 

injected into your blood by your doctor for special medical tests or treatments. Iodine that enters 

your body quickly goes into your thyroid gland, a small important organ in your neck. Iodine is 

used in the thyroid gland to make hormones that are needed for growth and health. Almost all of 

the iodine in your body is in your thyroid gland. Iodine that does not go into your thyroid gland 

leaves the body in your urine in a few weeks to months. Small amounts of iodine can also leave 

your body in sweat or in breast milk. Iodine that leaves your body each day is usually replaced 

by the iodine that you eat in your food, so that the amount of iodine in your body is just enough 

to keep you healthy. 

1.5 HOW CAN IODINE AFFECT MY HEALTH? 

Iodine is needed for your thyroid gland to produce thyroid hormones. You and your thyroid 

gland are healthy when there is just enough iodine in your body, about 10–15 milligrams, so that 

just the right amount of thyroid hormones are produced. This amount would look like much less 

than a pinch of table salt if placed in your hand. This amount of iodine is in most people when 

they eat the foods that people normally eat in the United States. Your thyroid gland can become 

unhealthy if more or less than this amount of iodine is in your body. An unhealthy thyroid gland 

can affect your entire body. If the thyroid gland cannot make enough hormone, then you would 

have to be given thyroid hormone in pills. If your thyroid gland makes too much hormone, then 

you would have to be given drugs to make your thyroid make less hormone. Radioactive iodine 

can also be unhealthy for your thyroid gland. If too much radioactive iodine enters your body, 

the radioactive iodine will destroy your thyroid gland so that the gland will stop making 

hormones. Too much radioactive iodine in your body can also cause thyroid nodules or cancer. 
IODINE 5 

1. PUBLIC HEALTH STATEMENT 

To protect the public from the harmful effects of toxic chemicals and to find ways to treat people 

who have been harmed, scientists use many tests. 

One way to see if a chemical will harm people is to learn how the chemical is absorbed, used, 

and released by the body. In the case of a radioactive chemical, it is also important to gather 

information concerning the radiation dose and the dose rate to the body. For some chemicals, 

animal testing may be necessary. Animal testing may also be used to identify health effects such 

as cancer or birth defects. Without laboratory animals, scientists would lose a basic method to 

get information needed to make wise decisions to protect public health. Scientists have the 

responsibility to treat research animals with care and compassion. Laws today protect the 

welfare of research animals, and scientists must comply with strict animal care guidelines. 

1.6 HOW CAN IODINE AFFECT CHILDREN? 

This section discusses potential health effects from exposures during the period from conception 

to maturity at 18 years of age in humans. 

Babies and children need iodine to form thyroid hormones, which are important for growth and 

health. If infants and children do not have enough iodine in their bodies, their thyroid glands 

will not produce enough thyroid hormone and they will not grow normally. If they have too 

much iodine in their bodies, they may develop an enlarged thyroid gland (goiter), which may not 

produce enough thyroid hormone for normal growth. We also need just the right amount of 

iodine from our mothers before we are born. Too much iodine from the mother can cause a 

baby’s thyroid gland to be so large that it makes breathing difficult or impossible. Not enough 

iodine from the mother can cause a baby to not produce enough thyroid hormone, which can 

affect growth and mental development of the baby. Radioactive iodine in food can be more 

harmful to babies and children than to adults. When radioactive iodine is in the air, it can get 

onto the grass and water that the cows eat and drink. Infants and children drink a lot more milk 

than most adults. If there is radioactive iodine in the milk that a child or infant drinks, more 

iodine will enter the thyroid gland of the child than of an adult who drinks less milk. In addition, 

because the thyroid gland of a child or infant is smaller than that of an adult, a child’s thyroid 
IODINE 6 

1. PUBLIC HEALTH STATEMENT 

gland will receive a higher radiation dose than the an adult. Children are more sensitive to the 

harmful toxic effects of iodine and radioactive iodine than adults because their thyroid glands are 

still growing and the thyroid gland tissues are more easily harmed by radioactive iodine, and 

because children need a healthy thyroid gland for normal growth. 

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

We all are exposed to iodine in the food that we eat and in the water that we drink. Iodine is 

needed for your good health. We do not want to prevent exposure to iodine, but we do want to 

try to prevent exposure to too much iodine. This is not likely to happen from eating a normal 

diet in the United States or from drinking water or breathing air. It could happen if you were 

careless about storing soaps or cleansers or medicines that have iodine in them. For example, a 

child could swallow medicines that contain iodine. People are rarely exposed to radioactive 

iodine, unless they work in a place where radioactive iodine is used or if they are given 

radioactive iodine by their doctors for certain medical tests or treatments. 

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

your children might also be exposed. Your doctor might need to ask your state health 

department to investigate. 

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

EXPOSED TO IODINE? 

Most physicians do not test for iodine in their offices, but can collect samples and send them to 

special laboratories. They can also feel the thyroid for lumps that may have been caused by 

disease or past exposure to radioactive iodine, but the results do not tell the cause. Every 

person’s body contains a small amount of iodine, but normally not radioactive iodine (such as 

131I). Iodine can be measured in the blood, urine, and saliva. The amount is normally measured 

by its mass (in grams). If the iodine is radioactive, it can be measured by its mass or by its 

radiation emissions. These emissions are used to tell the amount of radioactive iodine (in curies 

or becquerels) and the radiation dose it gives to your body (in sieverts or rem). 
IODINE 7 

1. PUBLIC HEALTH STATEMENT 

Radiation detectors can measure radioactive iodine inside your body using the radiation coming 

from the thyroid gland in your neck. This is useful only if you recently inhaled or ingested some, 

or if your physician recently gave you some for medical purposes. Your body quickly eliminates 

iodine and radioactive iodine, so tests should be done shortly after exposure. 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE 

TO PROTECT HUMAN HEALTH? 

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

Regulations can be enforced by law. Federal agencies that develop regulations for toxic 

substances include the Environmental Protection Agency (EPA), the Occupational Safety and 

Health Administration (OSHA), the Food and Drug Administration (FDA), the Department of 

Energy (DOE), and the U.S. Nuclear Regulatory Commission (USNRC). 

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

law. Federal organizations that develop recommendations for toxic substances include the 

Agency for Toxic Substances and Disease Registry (ATSDR), the National Institute for 

Occupational Safety and Health (NIOSH), and the FDA. 

Regulations and recommendations can be expressed in not-to-exceed levels in air, water, soil, or 

food that are usually based on levels that affect animals; then they are adjusted to help protect 

people. Sometimes these not-to-exceed levels differ among federal organizations because of 

different exposure times (an 8-hour workday or a 24-hour day), the use of different animal 

studies, or other factors. 

Recommendations and regulations are also periodically updated 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 iodine include the following: 

The National Research Council has established a Recommended Dietary Allowance for iodine of 

150 micrograms per day (μg/day), with additional allowances of 25 μg/day during pregnancy and 
 

 

 

 

 

 

IODINE 8 

1. PUBLIC HEALTH STATEMENT 

50 μg/day during nursing. The EPA has established regulations that limit releases of certain 

forms of radioactive iodine to the environment and require that industries report releases of 

certain forms of radioactive iodine. NIOSH has established recommendations for limits of 

worker exposures to iodine and radioactive iodine. The Nuclear Regulatory Commission, the 

National Council of Radiation Protection and Measurements (NRCP) and the International 

Commission of Radiological Protection (ICRP) have established recommended limits for worker 

exposures to radioactive iodine and for releases of radioactive iodine to the environment. 

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, your regional Nuclear Regulatory Commission office, 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 resulting 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 ToxProfiles CD-ROM by calling the information and 

technical assistance toll-free number at 1-888-42ATSDR (1-888-422-8737), by email at 

atsdric@cdc.gov, or by writing to: 

Agency for Toxic Substances and Disease Registry 

Division of Toxicology 

1600 Clifton Road NE 

Mailstop F-32 

Atlanta, GA 30333 

Fax: 1-770-488-4178 
 

 

 

 

 

IODINE 9 

1. PUBLIC HEALTH STATEMENT 

For-profit organizations may request a copy of final 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/ 

IODINE	 11 

2. RELEVANCE TO PUBLIC HEALTH 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO IODINE IN THE UNITED 

STATES 

Iodine is an essential nutrient. An adequate intake of iodine is required for the production of thyroid 

hormones. The term iodine excess is used in this profile to refer to increases in intake relative to 

estimated physiological requirements. As a reference point, the chronic dietary intake of iodine in U.S. 

populations has been estimated to range from approximately 150 to 950 μg/day. Estimates for various 

populations have ranged from <50 μg/day in iodine-deficient regions to >10 mg/day in populations that 

regularly ingest seaweeds containing a high iodine content. The National Research Council (NRC) 

Recommended Dietary Allowance (RDA) for iodine is 150 μg/day (2.1 μg/kg/day for a 70-kg adult), with 

additional allowances of 25 and 50 μg/day during pregnancy and lactation, respectively. 

The diet is the major source of iodine intake in the U.S. population. Iodine enters the human diet from a 

variety of natural sources, including mineral dissolution and atmospheric transport and deposition of 

seawater aerosols to surface water, vegetation, and soil. Major food categories that contribute to dietary 

iodine include marine produce (e.g., fish and shellfish) and milk. Cows and goats absorb iodine from 

ingested vegetation and water, when iodine is either deposited on the vegetation or in water or when the 

iodine is taken up by vegetation grown in soils containing iodine. The absorbed iodine is excreted into 

their milk; goat milk typically has higher concentrations of iodine than cow milk for equal deposition on 

feed. Additional sources of iodine in milk derive from the use of iodine disinfectants on cows, milking 

machines, and other milk processing equipment, as well as from supplementation of dairy feed with 

iodine-containing compounds. Breast milk is the primary source of iodine intake in nursing infants. 

Commercial infant formula preparations are fortified with sufficient iodine to support infant health, 

growth, and development. Cow milk is a significant source of iodine intake in children. Iodine is also 

intentionally added to the U.S. diet as iodized table salt and as iodine-containing bread dough oxidizers. 

Other sources of intake derive from the use of iodine-containing topical disinfectants (e.g., povidoneiodine), iodine-containing diagnostic and therapeutic agents, dietary supplements, and water purifiers 

containing iodine. 

Thirty-five isotopes of iodine are recognized (108I through 142I). Only one isotope is stable (127I); the 

remaining are radioactive. Most of these have radioactive half-lives of minutes or less. Twelve have 
 

 

 

IODINE 12 

2. RELEVANCE TO PUBLIC HEALTH 

half-lives that exceed 1 hour, and six have half-lives that exceed 12 hours (123I, 124I, 125I, 126I, 129I, and 131I). 

Four isotopes (123I, 125I, 129I, and 131I) are of particular interest with respect to human exposures because 

123I and 131I are used medically and all four are sufficiently long-lived to be transported to human 

receptors after their release into the environment. The U.S. population has been exposed to radioiodine in 

the general environment as a result of atmospheric fallout of radioiodine released from uncontained 

and/or uncontrolled nuclear reactions. Historically, this has resulted from surface or atmospheric 

detonation of nuclear bombs, from routine and accidental releases from nuclear power plants and nuclear 

fuel reprocessing facilities, and from hospitals and medical research facilities. Estimates have been made 

of radiation doses to the U.S. population attributable to nuclear bomb tests conducted during the 1950s 

and 1960s at the Nevada Test Site; however, dose estimates for global fallout have not been completed. 

Geographic-specific geometric mean lifetime doses are estimated to have ranged from 0.19 to 43 cGy 

(rad) for a hypothetical individual born on January 1, 1952 who consumed milk only from commercial 

retail sources, 0.7–55 cGy (rad) for people who consumed milk only from home-reared cows, and 6.4– 

330 cGy (rad) for people who consumed milk only from home-reared goats. Additional information is 

available on global doses from nuclear bomb tests and doses from nuclear fuel processing and medical 

uses can be found in United Nations Scientific Committee on the Effects of Atomic Radiations. 

Individuals in the United States can also be exposed to radioiodine, primarily 123I and 131I, as a result of 

clinical procedures in which radioiodine compounds are administered to detect abnormalities of the 

thyroid gland or to destroy the thyroid gland to treat thyrotoxicosis or thyroid gland tumors. Diagnostic 

uses of radioiodine typically involve administration, by the oral or intravenous routes, of 0.1–0.4 mCi (4– 

15 MBq) of 123I or 0.005–0.01 mCi (0.2–0.4 MBq) of 131I. These correspond to approximate thyroid 

radiation doses of 1–5 rad (cGy) and 6–13 rad (cGy) for 123I and 131I, respectively. Cytotoxic doses of 131I 

are delivered for ablative treatment of hyperthyroidism or thyrotoxicosis; administered activities typically 

range from 10 to 30 mCi (370–1,110 MBq). Higher activities are administered if complete ablation of the 

thyroid is the objective; this usually requires 100–250 mCi (3,700-9,250 MBq). Thyroid gland doses of 

approximately 10,000–30,000 rad (300 Gy) can completely ablate the thyroid gland. An administered 

activity of 5–15 mCi (185–555 MBq) yields a radiation dose to the thyroid gland of approximately 5,000– 

10,000 rad (50–100 Gy). 

2.2 SUMMARY OF HEALTH EFFECTS 

An extensive amount of literature is available on the effects of iodine on human physiology and health. 

The intense interest in iodine derives from early recognition of the necessity of appropriate amounts of 
IODINE 13 

2. RELEVANCE TO PUBLIC HEALTH 

iodine for maintenance of normal function of the thyroid gland and of awareness of diseases of the 

thyroid gland that are caused or affected by iodine intake. The prevalence of thyrotoxicosis (the clinical 

outcome of uncontrolled hyperthyroidism) has been estimated to be approximately 0.5%, and that of 

hypothyroidism is of a greater magnitude. Research directed at understanding the epidemiology, 

pathophysiology, and therapeutic strategies for these relatively common diseases have given way to a 

fairly comprehensive, although not complete, understanding of the role of iodine in thyroid gland 

physiology and the related health consequences and risks associated with excessive or inadequate iodine 

intake. The use of radioactive iodine (131I) for treating thyrotoxicosis, as well as studies of the thyroid 

gland as a target for internal exposures to atmospheric 131I fallout, have further complemented our 

understanding of iodine toxicity as it relates to exposures to radioactive isotopes of iodine. 

This profile does not attempt to summarize in detail all of the studies relevant to the adverse effects of 

iodine on the thyroid, as to do so would require several volumes. Instead, the focus is on literature that 

identifies the lowest observable iodine exposure levels associated with adverse effects in humans. Where 

applicable, relevant studies in animals are summarized, particularly when such studies have identified 

potential targets of toxicity not already documented in humans or for which adequate dose-response 

information does not exist for humans. This strategy leads to a focus on the thyroid gland as the primary 

and most sensitive target of iodine for both chemical and radiologic toxicity. This is not surprising given 

that avid uptake of absorbed iodine by the thyroid gland results in approximately 90% of the body iodine 

content residing in the thyroid gland (see Section 3.4, Toxicokinetics). Adverse effects on a wide variety 

of other organ systems can result from disorders of the thyroid gland, including disturbances of the skin, 

cardiovascular system, pulmonary system, kidneys, gastrointestinal tract, liver, blood, neuromuscular 

system, central nervous system, skeleton, male and female reproductive systems, and numerous endocrine 

organs, including the pituitary and adrenal glands. Although these secondary effects are noted in the 

profile, they are not discussed in detail and the reader is referred to authoritative references on these 

subjects for further information. 

An important consideration in interpreting the iodine toxicology literature is that the effect of an increase 

in iodine intake will depend, in part, on the preexisting background dietary intake and the associated 

physiological adaptations to background intake. The response to an upward increase in intake may be 

quite different in individuals who have adapted to either low dietary or high dietary intake. Examples of 

this are described in appropriate sections of this report (e.g., Section 3.2.2.2). In this profile, the term 

molecular iodine is used to refer to I2; the term iodide is used to refer to the anion, I-

, the term iodate is 

used to refer to the anion IO3

-

, and the term iodine is used to refer to the element in any form, usually 
IODINE 14 

2. RELEVANCE TO PUBLIC HEALTH 

when the form was not specified in the literature being summarized or when the form is not relevant to 

the discussion. From a physiological perspective, regardless of the form of iodine that is absorbed after 

exposure, iodide is the form of iodine that is taken up into the thyroid gland, and effects from exposures 

to iodine ultimately derive from exposure of the thyroid gland to iodide. A more important toxicological 

distinction is that, unlike iodide, molecular iodine (I2) is a relatively strong oxidizing agent and has the 

potential to produce injuries related to redox reactions with proteins. This is the primary basis for the use 

of I2 as a topical antiseptic and antimicrobial disinfectant for drinking water. 

The health effects of exposure to radioiodine derive from the emission of beta and gamma radiation. 

Radioiodine that is absorbed into the body quickly distributes to the thyroid gland and, as a result, the 

tissues that receive the highest radiation doses are the thyroid gland and surrounding tissues (e.g., 

parathyroid gland). Tissues other than the thyroid gland can accumulate radioiodine, including salivary 

glands, gastric mucosa, choroid plexus, mammary glands, placenta, and sweat gland. Although these 

tissues may also receive a radiation dose from internal radioiodine, the thyroid gland receives a far higher 

radiation dose. The radiation dose to the thyroid gland from absorbed radioiodine varies with isotope and 

its radiation emission properties (e.g., type of radiation, energy of emission, effective radioactive halflife). A comparison of the doses delivered to the thyroid gland from a few of the isotopes of iodine is in 

Table 2-1. The highest total doses are achieved with 131I, whereas the highest dose rates (rad/hour) are 

delivered from 132I. 

Endocrine Effects. The principal direct effects of excessive iodine ingestion on the endocrine system 

are on the thyroid gland and regulation of thyroid hormone production and secretion. Effects of excess 

iodine on the thyroid gland can be classified into three types: hypothyroidism, hyperthyroidism, and 

thyroiditis. Hypothyroidism refers to the diminished production of thyroid hormones leading to clinical 

manifestations of thyroid hormone insufficiency. This can occur with or without goiter, an enlargement 

of the gland that occurs in response to elevated circulating levels of the pituitary hormone, thyroid 

stimulating hormone (TSH), during periods of suppressed thyroid hormone production. A typical 

biomarker of hypothyroidism is a decrease in the circulating levels of thyroxine (T4) and, when thyroid 

failure is far advanced, triiodothyronine (T3). This is always accompanied by an elevation of TSH (also 

known as thyrotropin) above the normal range, unless the cause of the hypothyroidism resides in the 

pituitary-hypothalmus. Hyperthyroidism is an excessive production and/or secretion of thyroid 

hormones. The clinical manifestation of abnormally elevated circulating levels of T4 and/or T3 is 

thyrotoxicosis. Thyroiditis refers to an inflammation of the gland, which is often secondary to thyroid 

gland autoimmunity. The above three types of adverse effects of excess iodine can occur in children and 
 

 

IODINE 15 

2. RELEVANCE TO PUBLIC HEALTH 

Table 2-1. Thyroid Doses and Dose Rates for Various Isotopes of Iodinea 

Isotope 

Percent of 

dose from beta 

radiation 

Effective halflife in the 

thyroid 

(hours) 

Mean range of 

beta-radiation 

in thyroid 

(mm) 

Total dose 

from 1 mCi 

in the 

thyroid 

(rad) 

Average dose 

rate of 10 rad 

from 1 mCi in 

the thyroid 

(rad/hour) 

123I 77 13 0.1 76 3.7 

125I 73 866 0.01 3,747 3.0 

131I 94 177 0.4 5,627 22 

132I 90 2.3 1.7 199 59 

133I 96 20 1.3 1,355 46 

135I 90 6.7 1.1 434 45 

a

from Maxon and Saenger 2000 
IODINE 16 

2. RELEVANCE TO PUBLIC HEALTH 

adults, in fetuses exposed in utero, or in infants exposed during lactation. The primary effect of iodide 

excess in the fetus is goiter formation secondary to a suppression of thyroid hormone production and an 

elevation in TSH levels. 

Measurements of serum levels of thyroid hormones and TSH are often used as biomarkers of 

hypothyroidism and hyperthyroidism in toxicology and epidemiology studies. In interpreting this 

literature in terms of human health risks, a distinction must be made between outcomes that have a high 

potential for producing clinical manifestations and outcomes that may not be clinically significant. In this 

profile, an observed decrease in circulating T4 and/or T3 levels within the normal range and an increase in 

serum TSH level above the normal range is referred to as subclinical hypothyroidism. Similarly, the term 

subclinical hyperthyroidism refers to a condition in which the circulating levels of T4 or T3 are increased 

within their normal ranges and the serum TSH level is suppressed below the normal range. Typical 

normal ranges for these hormone levels are discussed in Section 3.8.2 

An acute iodide load can cause a decrease in thyroid hormone production in the thyroid gland; this is 

referred to as the acute Wolff-Chaikoff effect. In most people, this is followed by a return to normal levels 

of production, referred to as escape from the acute Wolff-Chaikoff effect, without a clinically significant 

change in circulating hormone levels. Escape is thought to be the result of down regulation of the iodine 

transport mechanism in the thyroid gland (see Section 3.4.3.2 for further details on the Wolff-Chaikoff 

effect). An acute or chronic excess of iodide can also decrease circulating T4 and T3 levels and induce a 

hypothyroid state in people who have an underlying thyroid abnormality. These effects result from a 

persistent acute Wolff-Chaikoff effect and a continued inhibition of thyroid hormone synthesis and 

release. Hypothyroidism is thought to occur primarily in susceptible individuals who fail to escape from 

the inhibitory effect of large doses of iodide that produce the Wolff-Chaikoff effect. Susceptible 

individuals includes fetuses and newborn infants, patients who have autoimmune thyroiditis, patients with 

Graves’ disease (Graves’ disease is a hyperthyroid state in which autoantibodies to the TSH receptor are 

produced and act on the TSH receptor to stimulate the gland to produce thyroid hormones) previously 

treated with radioactive iodine or antithyroid drugs, women who have had postpartum thyroiditis, or 

people who have had subacute thyroiditis. A complete list of such susceptible subpopulations is provided 

in Table 2-2. The hypothyroidism resolves when the excess iodine is discontinued. Spontaneous 

recovery usually occurs within 2–3 weeks, although some individuals may develop primary 

hypothyroidism. 
 

 

 

 

IODINE 17 

2. RELEVANCE TO PUBLIC HEALTH 

Table 2-2. Risk Groups for Iodine-induced Hypothyroidism 

No underlying thyroid disease 

Fetus and neonate, mostly preterm 

Secondary to transplacental passage of iodine or exposure of neonate to topical or 

parenteral iodine-rich substances 

Infant 

Occasionally reported in infants drinking iodine-rich water (China) 

Adult 

In Japanese subjects with high iodine intake where Hashimoto’s thyroiditis has been 

excluded 

Elderly 

Reported in elderly subjects with and without possible defective organification and 

autoimmune thyroiditis 

Chronic nonthyroidal illness 

 Cystic fibrosis 

Chronic lung disease (including Hashimoto’s thyroiditis) 

Chronic dialysis treatment

 Thalassemia major 

 Anorexia nervosa 

Underlying thyroid disease 

Hashimoto’s thyroiditis 

Euthyroid patients previously treated for Graves disease with 131I, thyroidectomy, or antithyroid drugs 

Subclinical hypothyroidism, especially in the elderly 

After transient postpartum thyroiditis 

After subacute painful thyroiditis 

After hemithyroidectomy for benign nodules 

Euthyroid patients with a previous episode of amiodarone-induced destructive thyrotoxicosis 

Euthyroid patients with a previous episode of interferon-alpha-induced thyroid disorders 

Patients receiving lithium therapy 

Source: NRC 2004 
IODINE 18 

2. RELEVANCE TO PUBLIC HEALTH 

Several studies have examined the acute and intermediate-duration effects of increased intake of iodine on 

thyroid hormone status in adults. Acute iodine exposures (1,500 μg/day), in subjects who have no 

underlying thyroid disease, have been shown to produce small, reversible changes in serum thyroid 

hormone levels and serum levels of TSH. These effects result from a small iodine-induced decrease in 

thyroid hormone release, which is accompanied by a commensurate rise in serum TSH concentration, to 

maintain normal thyroid function. The results of epidemiological studies suggest that chronic exposure to 

excess iodine can result in or contribute to hypothyroidism in certain susceptible populations of children 

(1,150 μg/day, 29 μg/kg/day) and elderly adults (160–800 μg/day, 4–12 μg/kg/day). Several studies have 

found an increased prevalence of hypothyroidism in residents of areas of Japan where dietary iodine 

intake is extraordinarily high as a result of consumption of seaweeds with a high iodine content 

(13 mg/day, 0.22 mg/kg/day). Populations that are iodine deficient and, in particular, those that include 

people who have goiter, appear to be particularly sensitive to an increase in iodine intake. A more 

complete list of population subgroups at risk to develop iodine-induced hyperthyroidism is provided in 

Table 2-3. 

People who have autoimmune thyroid disease may be at increased risk of developing thyroid dysfunction 

when exposed to excess iodide. Euthyroid patients, in a mildly iodine-deficient area, who were diagnosed 

with Hashimoto’s thyroiditis and who were positive for antithyroid (thyroid peroxidase) antibodies 

developed subclinical hypothyroidism after oral doses of 375 μg/day (5.8 μg/kg/day) for 6 months or 

clinical hypothyroidism after exposures to 180 mg I/day (2.6 mg/kg/day) for 6 weeks, more than 

1,000 times the RDA. Autoimmune thyroiditis in autoimmune-prone individuals can be accelerated by 

iodine excess, whereas thryoiditis can be attenuated by iodine deficiency. 

The clinical case literature demonstrates that doses of iodide exceeding 200 mg/day (2.8 mg/kg/day) 

given to a mother during pregnancy can result in congenital goiter and hypothyroidism in the newborn 

infant. An iodine-deficient status of the mother can also lead to goiter in the fetus and 

neurodevelopmental impairment of the fetus. Adequate iodine supplementation early in pregnancy can 

correct the deficiency and prevent maternal and neonatal goiter formation. Thyroid dysfunction was not 

detected in newborns of mothers who received oral doses of 3–4 μg/kg/day during pregnancy for the 

purpose of correcting or preventing potential iodine deficiency and for the management of Graves’ 

disease during pregnancy. 
IODINE 19 

2. RELEVANCE TO PUBLIC HEALTH 

Table 2-3. Risk Groups for Iodine-induced Hyperthyroidism 

Underlying thyroid disease 

Iodine supplementation for endemic iodine-deficiency goiter 

Iodine administration to patients with euthyroid Graves disease, especially those in 

remission after antithyroid drug therapy 

Nontoxic nodular goiter 

 Autonomous nodules 

Nontoxic diffuse goiter 

No underlying thyroid disease 

Iodine administration to patients with no recognized underlying thyroid disease, especially in 

areas of mild to moderate iodine 

Source: NRC 2004 
 

 

IODINE 20 

2. RELEVANCE TO PUBLIC HEALTH 

Oral exposure to excess iodide can, under certain circumstances, induce hyperthyroidism and 

thyrotoxicosis. The epidemiological and clinical literature suggest that iodide-induced hyperthyroidism 

occurs most often in people who have a previous history of iodine deficiency and goiter, or, rarely, 

Graves’ disease previously treated with anti-thyroid medications. What has been referred to as an 

epidemic of hyperthyroidism occurred in iodine-deficient areas in the midwestern United States between 

the years 1926 and 1928. Clinical records suggest that the incidence of mortality from hyperthyroidism 

increased in Detroit during this period from approximately 2–4 deaths per 100,000 to approximately 

11 deaths per 100,000 at the peak of the epidemic. Although there is considerable debate about the 

origins of the epidemic, the advent of aggressive supplementation of the diet with iodide in midwestern 

iodine-deficient, endemic goiter areas has been implicated as a contributing factor. More recent and more 

rigorous epidemiologic designs have been applied to several populations in which dietary iodide was 

supplemented as a prophylaxis for iodine deficiency and goiter. These studies confirm that iodide 

supplementation of iodide-deficient diets, to achieve intakes in the range of 3–7 μg/kg/day, does indeed 

result in a detectable increase in the incidence of hyperthyroidism. Cases of iodine-induced 

hyperthyroidism in people who were euthyroid and without apparent thyroid disease have also been 

reported; however, only a few have provided dose information, suggesting effects after oral doses of 3– 

1,440 mg/day (0.05–23 mg/kg/day) for 6 months. 

Extensive clinical use of radioiodine, principally 123I and 131I, for diagnostic purposes, and 131I, and rarely 

125I, for treatment of hyperthyroidism has provided a wealth of information on the effects of relatively 

high acute exposures on thyroid gland function. Radioiodine is cytotoxic to the thyroid gland at high 

radiation doses and produces hypothyroidism when doses to the thyroid gland exceed 25 Gy (2,500 rad). 

Thyroid gland doses of approximately 300 Gy (30,000 rad) can completely ablate the thyroid gland and 

result in hypothyroidism. This dose is achieved with an acute exposure of approximately 25–250 mCi 

(0.9–9 GBq). Such high dosages are used to ablate thyroid remnants after surgery for thyroid cancer. 

Although, a rare outcome, cytotoxic doses of 131I can also produce dysfunction of the parathyroid gland, 

which can receive a radiation dose from β emission of 131I in the adjacent thyroid gland. 

Clinical cases have been reported in which congenital hypothyroidism occurred in newborn infants after 

maternal exposures to high doses of 131I for treatment of thyroid cancer during pregnancy. Exposure in 

these cases ranged from 11 to 77 mCi (407–2,850 MBq). Two studies that reviewed the thyroid status of 

larger sets of infants (37 or 73) born to patients who received 131I for ablative treatment of thyroid cancer 

2–10 years (mean, 5.3 years) prior to pregnancy (i.e., exposure occurred before conception and fetal 
 

 

IODINE 21 

2. RELEVANCE TO PUBLIC HEALTH 

development) found no thyroid gland disorders. The maternal 131I exposures ranged from 2 to 17 GBq 

(50–450 mCi); the mean exposure was 4.4 GBq (120 mCi). 

A large amount of epidemiological literature exists on the health outcomes in populations that were 

exposed to environmental releases of radioiodine. These include (1) releases from explosions of nuclear 

bombs such as the Marshall Islands BRAVO test, the largest U.S. detonation (15 megatons), and from the 

Nevada Test Site; (2) releases from nuclear fuel production facilities such as the Hanford Nuclear Site; 

and (3) accidental releases from nuclear power plants such as the Chernobyl explosion and fire 

(Table 2-4). In general, releases of these types result in mixed exposures to a variety of radioisotopes and 

to radiation doses from both external and internal exposure. However, doses from radioiodine that are 

significant to health derive largely from internal exposure as a result of uptake of relatively short-lived 

radioiodine isotopes into the thyroid gland (see Section 3.4.2.2). Thus, effects on the thyroid attributable 

to radioiodine that were subsequently observed, in some cases, years after the event, derived from 

exposures to the relatively high levels of radioiodine found immediately after the event, rather than from 

sustained exposures. The relative contribution of the inhalation and oral pathways can be expected to 

vary depending on the duration of the release and the duration of human contact with the sites of 

contamination. Epidemiological studies of the Nevada Test Site detonations and releases from the 

Hanford Nuclear Site have focused on subjects who were potentially exposed through the dietary pathway 

as a result of repeated releases during periods of 7 or 13 years, respectively. 

In the so-called BRAVO cohort, which has been studied extensively (see Section 3.2.2 for a more detailed 

discussion), inhalation may have been a more significant contributor to the internal radioiodine dose 

because the subjects comprising the cohort were evacuated from the site of major contamination within 

2 days after the release of radioiodine to the atmosphere; this would have limited their dietary exposures. 

Nevertheless, estimates of inhalation intakes of airborne radioactivity amounted to <1% of the total intake 

estimated based on measurements of 131I in urine, suggesting a substantial contribution from other routes. 

In nursing infants, exposure would have continued from ingestion of contaminated breast milk. Radiation 

doses to the thyroid gland (external and internal) in the most highly exposed individuals after the Marshall 

Islands BRAVO test is estimated to have ranged from 0.3 to 20 Gy (30–2,000 rad). External radiation, 

resulting primarily from exposure to gamma-emitting radioisotopes other than iodine isotopes (e.g., 

137Cs), is estimated to have contributed approximately 4–16% or 10–50% of total thyroid dose, depending 

on the location of the individual with respect to the blast. Thyroid gland outcomes have been assessed 

periodically since the BRAVO test in 1954. Cases of thyroid gland disorders began to be detected in the 

exposed population in 1964, 10 years after the BRAVO test, particularly in exposed children; these 
IODINE 22 

2. RELEVANCE TO PUBLIC HEALTH 

Table 2-4. Releases from Radioiodine-producing Events 

Source 131I Released (PBq)a Reference 

All nuclear bomb tests 650,000 Gonzalez 1998 

Nevada Test Site nuclear bomb tests 5,500 NCI 1997 

Chernobyl power plant accident 3,200 UNSCEAR 2000 

Hanford Nuclear Site nuclear fuel processingrelated releases 27 CDC 1999 

Three Mile Island power plant accident 0.0004–0.0011 NRC 1995 

a

1 PBq=27,000 Ci 

USNRC=U.S. National Regulatory Commission; CDC = Centers for Disease Control; NCI = National Cancer 

Institute; UNSCEAR=United Nations Scientific Committee on the Effects of Atomic Radiations 
 

 

IODINE 23 

2. RELEVANCE TO PUBLIC HEALTH 

included cases of apparent growth retardation, myxedema (typical of hypothyroidism), and thyroid gland 

neoplasms. Collectively, the various health assessments and studies of the so-called BRAVO cohort have 

revealed dose-related abnormally high elevations in serum concentrations of TSH, characteristic of 

hypothyroidism. Among exposed children who were 1 year old at the time of the BRAVO test and who 

received an estimated thyroid radiation dose exceeding 1,500 rad (or 15 Gy), 83% had serum 

concentrations of TSH >5 mU/L; thyroid nodularity was found in 77% of the most highly exposed group, 

and thyroid cancer was discovered in 6% of the most highly exposed group. 

The 1986 explosion and fire at the nuclear power plant at Chernobyl in Ukraine resulted in the release of 

airborne radionuclides to the surrounding regions and contamination of soil, food, and surface water. 

Several populations have been characterized that vary considerably in radiation doses received. These 

include emergency response workers who received the highest acute radiation doses, early evacuees from 

areas near the reactor (generally within 30 km of the reactor), and people who continued to inhabit 

contaminated areas outside the evacuation zone. People living in the vicinity of the Chernobyl accident 

had contact with contaminated areas and contaminated foods (e.g., goat and cow milk, and locally 

harvested produce) for weeks to months after the accident. The thyroid radiation doses in this population 

are thought to have been dominated by the oral exposure pathway. The radiation exposures to the general 

population (i.e., evacuees and people who continued to inhabit contaminated areas) were attributed 

largely to isotopes of cesium (e.g., 137Cs), which accounted for approximately 90–98% of the external 

radiation dose. However, radioiodine is estimated to have contributed approximately 50% of the total 

lifetime committed effective radiation dose for children born in the region in 1986, and approximately 

80% of the radiation dose received during the first year after the release. Estimates of thyroid radiation 

doses to the general population are highly uncertain; however, these estimates suggest that doses were 

highest in children who were younger than 1 year of age at the time of the release. The highest estimated 

doses were received within the 30-km evacuation zone; median doses ranged from 2.3 Gy (230 rad) at age 

<1 year to 0.4 Gy (40 rad) in adolescents and adults. Estimated median doses received in populations 

residing 100–200 km from the plant (e.g., Mogilev region) were <0.3 Gy (30 rad) for all age groups. 

Thyroid screening programs, cancer registries, and epidemiological studies conducted after the Chernobyl 

accident have revealed a dose-related elevated prevalence of thyroid nodules and thyroid cancer in 

children of the Belarus and Ukraine regions, apparent approximately 4 years after the Chernobyl accident. 

These effects have been associated with thyroid radiation doses of 0.3–1 Gy (30–100 rad). In both 

Belarus and the Ukraine, the highest rates of childhood thyroid cancer have occurred in areas where 

exposure to other industrial contaminants is likely to have occurred and where there is evidence for 

widespread iodine deficiency. These factors may have affected the early appearance of thyroid cancer 
IODINE 24 

2. RELEVANCE TO PUBLIC HEALTH 

after the accident, when vigorous public health screening programs for thyroid abnormalities were 

initiated. The incidence of thyroid cancer prior to the accident in these areas was poorly documented. 

Immunological and Lymphoreticular Effects. Excess iodide intake may be a contributing factor 

in the development of autoimmune thyroid disease in susceptible individuals, which can result in 

hypothyroidism or hyperthyroidism (associated with Graves’ disease). Autoimmune thyroiditis is an 

inflammation of the thyroid gland that can lead to fibrosis of the gland, follicular degeneration, follicular 

hyperplasia, and hypothyroidism. IgG autoantibodies to thyroglobulin and, more frequently, thyroid 

peroxidase are a consistent feature of the disorder. Iodine appears to play an important role in the 

autoimmune response, as human lymphocytes recognize and proliferate in response to iodinated human 

thyroglobulin, but not iodine-free thyroglobulin. In general, iodine excess accelerates autoimmune 

thyroiditis in autoimmune-prone individuals, whereas iodine deficiency attenuates thyroiditis. Several 

studies have been conducted in people who reside in endemic goiter areas and who received iodide 

supplementation. These studies suggest that iodine intakes of 230–420 μg I/day (3.3–6.0 μg/kg/day total 

intake) for 12 months can induce thyroid autoimmunity. However, other studies have not found increases 

in autoimmunity associated with iodine supplementation at doses of 1,150 μg/day (29 μg/kg/day). 

Studies using rats have shown that doses of 70–95 mg I/kg/day (in drinking water) for 8–12 weeks may 

increase the incidence of autoimmune thyroiditis in inbred strains of rats that develop spontaneous thyroid 

autoimmunity. 

Larger scale assessments of thyroid autoimmunity have been conducted in the Marshall Islands, where 

exposures to 131I occurred as a result of fallout and contamination from test detonations of thermonuclear 

devices during the period 1946–1958. These studies have not revealed an elevated prevalence of thyroid 

autoimmunity relative to other populations. Studies of populations in Belarus and Ukraine suggest a 

possible contribution of radioiodine exposure to an increased prevalence of thyroid autoimmunity 

following the Chernobyl accident. Cases of autoimmune hyperthyroidism, with serum antibodies to the 

TSH receptor, have occurred after exposures to higher levels of 131I for ablative treatment of non-toxic 

nodular goiter. No relationship was found between the prevalence or incidence of autoimmune thyroiditis 

and exposure to lower thyroid doses of radioiodine associated with bomb tests at the Nevada Test Site. 

Oral exposure to excess iodide can produce allergic reactions in sensitive individuals. The reactions 

include urticaria (hives), acneiform skin lesions (ioderma), and fevers. Cases of more serious reactions 

involve angioedema (localized edema), vasculitis, peritonitis and pneumonitis, and complement 

activation. Both humoral and cell-mediated immune responses are thought to contribute to these 
IODINE 25 

2. RELEVANCE TO PUBLIC HEALTH 

reactions. In general, reactions to iodide have occurred in association with repeated oral doses of iodide 

300–1,600 mg I/day (5–23 mg/kg/day). However, in many of these cases, preexisting disease and related 

drug therapy may have contributed to the reaction to the iodine; thus, the dose-response relationship for 

ioderma in healthy people remains highly uncertain. 

Gastrointestinal Effects. Ablative treatment of thyroid cancers with 131I has been associated with 

inflammation of the salivary glands (sialadentitis) in humans. Salivary glands express a transport protein, 

the sodium-iodine symport (NIS), which is present in high concentrations in the thyroid gland, where it 

functions to transport iodide into the gland for hormone synthesis. Salivary glands can accumulate iodide 

in saliva at concentrations considerably above that in serum (see Sections 3.4.2.2 and 3.5.1). Exposures 

in reported cases of 131I-induced sialadentitis ranged from 100 to 300 mCi (3.7–11 GBq). Sialadentitis 

usually occurred within a few days or weeks of exposure and had a duration of several weeks to 2– 

3 years. 

Neurological Effects. Exposure to excess iodine has been shown to produce hypothyroidism in 

certain sensitive individuals. Sensitive populations include fetuses, newborn infants, and euthyroid 

individuals who have thyroiditis or a history of treated Graves’ disease, many of whom have abnormal 

autoimmune disorders (see Section 3.2.2.2, Endocrine Effects). Of these iodine-induced forms of 

hypothyroidism, those occurring in the fetus or newborn infant have the greatest potential for producing 

neurological effects. This is because thyroid hormones are essential to the development of the 

neuromuscular system and brain. An iodine-induced hypothyroid state can result in delayed or deficient 

brain and neuromuscular development of the newborn. Iodine-induced hypothyroidism in an older child 

or adult would be expected to have little or no deleterious effects on the neuromuscular system. Exposure 

of a fetus to large amounts of radioiodine would result in thyroid tissue ablation and in similar delayed 

brain and neuromuscular development, if the hypothyroid state was not corrected (e.g., with hormone 

replacement therapy) after birth. 

Exposure to excess iodine can also produce hyperthyroidism in sensitive individuals (see Section 3.2.2.2, 

Endocrine Effects). These include people who are iodine deficient with goiter, those who have thyroid 

disease previously, including Graves’ disease previously treated with antithyroid drugs, and those who 

have developed thyrotoxicosis from amiodarone or interferon-alpha treatments. Patients who develop 

thyrotoxicosis may experience neuromuscular disorders, including myopathy, periodic paralysis, 

myasthenia gravis, peripheral neuropathy, tremor, and chorea; however, these are not likely to occur in 

iodine-induced hyperthyroidism, except in sensitive groups, already at risk for neurologic problems. 
 

 

 

IODINE 26 

2. RELEVANCE TO PUBLIC HEALTH 

Developmental Effects. Although iodine excess may result in hypothyroidism, iodine deficiency is 

far more likely to cause prenatal and postnatal hypothyroidism and be associated with neurologic injury 

leading to cretinism, a developmental effect (see Section 3.2.2.2, Endocrine Effects). Thyroid hormone 

deficiency from any cause at critical times of development may result in severe mental retardation, 

neurologic abnormalities, growth retardation, or abnormal pubertal development. 

Congenital hypothyroidism secondary to thyroid ablation has been reported subsequent to maternal 

exposure to ablative doses of 131I. In one case, an infant became hypothyroid after his mother received 

99 mCi (3.7 GBq) of 131I during her sixth week of pregnancy. Growth retardation was also observed in 

some children who were exposed to radioiodine in the Marshall Island BRAVO cohort, early after the 

bomb test. Studies are suggestive of possible extra-thyroidal developmental effects of radioiodine 

following maternal exposures to ablative doses of 131I received 2–10 years prior to pregnancy. Doseresponse relationships for these effects were not established in these studies; therefore, the observed 

outcomes may not have been related to the 131I exposures, The observed outcomes include low birth 

weights with subsequent normal growth patterns, tetrology of Fallot (pulmonic stenosis, atrial septal 

defect, and right ventricular hypertrophy), hypoparathyroidism, Down’s syndrome, and cardiac 

anomalies. The maternal 131I exposures ranged from 1 to 17 GBq (27–460 mCi). Studies of pregnancy 

outcomes in Belarus and Ukraine populations after the Chernobyl accident are suggestive of possible 

developmental effects related to radiation exposures. However, interpretation of these results is highly 

uncertain, as factors other than radioiodine could have affected the outcomes, including exposure to other 

forms of radiation, nutrition, or other chemical exposures. 

Exposure to excess iodine can also produce hyperthyroidism in sensitive individuals (see Section 3.2.2.2, 

Endocrine Effects). Growth acceleration occurs in childhood hyperthyroidism, from any cause, which is 

thought to be related to changes in pituitary regulation of growth. 

Reproductive Effects. Exposure to excess iodine may produce hypothyroidism or hyperthyroidism 

(see Section 3.2.2.2, Endocrine Effects) and could cause disruption of reproductive function, secondary to 

thyroid gland dysfunction. Hypothyroidism can produce changes in the menstrual cycle in humans, 

including menorrhagia (excessive uterine bleeding) and anovulation (no ovulation). Spontaneous 

abortions, stillbirths, and premature births have also been associated with hypothyroidism. Reproductive 

impairments associated with hyperthyroidism include amenorrhea and alterations in gonadotropin release 
IODINE 27 

2. RELEVANCE TO PUBLIC HEALTH 

and sex hormone-binding globulin (SHBG), and associated changes in the levels and metabolism of 

steroid hormones in both females and males. 

Clinical follow-up studies of pregnancies in patients who received 131I (1–17 GBq, 27–460 mCi) for 

ablative treatment of thyroid cancer 2–10 years (mean, 5.3 years) prior to pregnancy have not shown 

evidence of effects on reproductive success. However, clinical cases of transient impaired testicular 

function following exposures to 131I for ablative treatment of thyroid cancer in men have been reported. 

Observed effects included low sperm counts, azospermia (absence of spermatozoa), and elevated serum 

concentrations of follicle stimulating hormone (FSH), which persisted for more than 2 years, but were 

usually of much shorter duration. Exposures to radioiodine ranged from 30 to 1,335 mCi (1.1–49.5 GBq). 

In Belarus and Ukraine populations after the Chernobyl accident, pregnant women who resided in heavily 

exposed areas (including exposures to other industrial contaminants) appeared to be at risk for 

development of toxemia, renal insufficiency, and anemia. 

Cancer. The relationship between iodide intake and thyroid cancer has been examined in several 

large-scale epidemiology studies. The results of these studies suggest that increased iodide intake may be 

a risk factor for thyroid cancer in certain populations, particularly in populations in iodine-deficient, 

endemic goiter regions; however, because not all studies have found an increased risk of cancer, the 

relationship between iodine intake and thyroid cancer remains unclear. A recurrent observation is an 

apparent shift in the histopathology toward a higher prevalence of papillary cancer after increased iodine 

intake in otherwise iodine-deficient populations. Two studies found a significant excess of thyroid gland 

cancer in populations from endemic goiter regions whose diets were supplemented to achieve 

approximate iodine intakes of 3.5 μg/kg/day. 

The thyroid gland receives the highest radiation dose of any organ or tissue following internal exposure to 

radioiodine (see Section 3.4.2.2, Toxicokinetics), and therefore, cancer of the thyroid gland is a major 

cancer concern associated with radioiodine exposures. Children are especially vulnerable to radioiodine 

toxicity and related thyroid cancers (see Section 3.7). Cancer morbidity and mortality among populations 

who received exposures to radioiodine have been examined in several epidemiology studies. In general, 

these studies fall into several categories that can be distinguished by the sources of exposure and 

estimated radiation doses to the thyroid gland and include (see Table 3-3): (1) relatively high exposures 

and doses (10–20 mCi, 370–740 MBq; >10,000 rad, >100 Gy) achieved when 131I is administered to treat 

hyperthyroidism (higher exposures are used in treatment of thyroid cancer); (2) moderate exposures and 

doses (40–70 μCi, 1.5–2.6 MBq; 80–130 rad, cGy) associated with clinical administration of 131I for 
IODINE 28 

2. RELEVANCE TO PUBLIC HEALTH 

diagnosis of thyroid gland disorders; (3) low to moderate doses from exposures to fallout from nuclear 

bomb tests (BRAVO test, 300–2,000 rad, cGy; Nevada Test Site, 1–40 rad, cGy); (4) low to moderate 

high doses from exposures to releases from nuclear power plant accidents (Chernobyl, 1–200 rad, cGy); 

and (5) low doses from exposures from operational releases from nuclear fuel processing plants (Hanford 

Nuclear Site, 0.0001–284 rad, cGy). 

The relatively high and acutely cytotoxic radiation doses to the thyroid gland that are achieved in the 

treatment of thyroid gland disorders, and the related outcomes on the thyroid, are virtually irrelevant to 

predicting outcomes from the much lower environmental exposures that occur in most U.S. populations. 

Nevertheless, these studies have revealed that, even at high exposures (3–27 mCi, 111–999 MBq) and 

thyroid gland doses (60 Gy, 6,000 rad), significant risks for cancers in organs other than the thyroid gland 

have not been consistently detected when the study designs control for other treatments administered to 

the patients. However, the data suggest a small increased thyroid cancer risk following 131I treatment for 

hyperthyroidism. Studies of diagnostic doses of radioiodine have not consistently revealed significant 

risks of thyroid or other cancers; those that have, however, found significantly elevated risks only in 

patients who were administered the radioiodine for diagnosing a suspected thyroid gland tumor and the 

cancer may have predated the administration of 131I or the patients may have had previous external 

radiation exposure. However, in general, studies of the outcomes of medical uses of radioiodine involve 

subjects who were exposed as adults. Studies of thyroid cancers and external radiation exposure have 

found a strong age dependence between thyroid radiation dose and thyroid cancer. Risk is substantially 

greater for radiation doses received prior to age 15 years when compared to risks for doses received at 

older ages, although the excess thyroid cancer risk is not limited to that age group. This same general 

trend in age-dependence would be expected for internal exposures to radioiodine; thus, studies of adult 

exposures to radioiodine may not be directly applicable to predicting outcomes from exposures to 

children. Studies of populations potentially exposed to radioiodine (0.09–3.2 Gy, 9–325 rad) as a result 

of nuclear bomb tests at the Nevada Test Site are suggestive, but not conclusive, of a possible association 

between radioiodine exposures and thyroid cancer. The National Research Council concluded that, 

because of uncertainties related to dose reconstruction and epidemiological analyses of the outcomes 

possibly associated with the Nevada Test Site bomb tests, the currently available information is not 

adequate to determine the extent to which the bomb tests in Nevada increased the incidence of thyroid 

cancer. A study of cancer in populations that resided near the Hanford Nuclear Site in southeastern 

Washington during the period 1944–1957 found that incidences of thyroid carcinoma or nodules were 

found to be unrelated to thyroid radioiodine dose. Although numerous studies have attempted to examine 

possible associations between the Chernobyl accident and thyroid cancers in the region, the strongest 
 

 

 

IODINE	 29 

2. RELEVANCE TO PUBLIC HEALTH 

evidence for an association comes from a case-control study of thyroid cancers among children in 

Belarus; this study provides reasonably strong evidence for the contribution of higher-level radioiodine 

exposure and the etiology of thyroid cancers diagnosed after the Chernobyl accident. Ecological studies 

have provided additional evidence for an association between thyroid cancer and exposures to radioiodine 

in the region, during childhood. More data and epidemiological analyses of these data, in the future, 

should improve the estimate of risks related to radioiodine intake. 

Breast cancer is also a concern with exposures to high levels of radioiodine after ablative therapy for 

hyperthyroidism because the breast expresses the sodium-iodide symport (NIS) and can transport and 

accumulate iodide (see Sections 3.5.4.2 and 3.6.1, Distribution). However, the radiation dose to the 

breast following exposure to radioiodine is much lower than that of the thyroid gland. Consistent with 

this, the epidemiological literature to date has not implicated such exposures as a significant risk factor 

for breast cancer. 

2.3 MINIMAL RISK LEVELS 

Minimal Risk Levels (MRLs) described in this section are for stable iodine (127I) and are based on an 

assessment of dose-response relationships for the chemical toxicity of stable iodine. A discussion of 

MRLs for ionizing radiation can be found in the ATSDR Toxicological Profile for Ionizing Radiation 

(1999). The MRL for acute-duration (14 days or less) exposures to ionizing radiation is 0.004 Sv 

(0.4 rem), and for chronic-duration exposures, is 1 mSv/year (100 mrem/year). 

Inhalation MRLs 

An MRL could not be derived for inhalation exposure to iodine because of a lack of information on doseresponse relationships for the inhalation pathway. 

Oral MRLs 

•	 An MRL of 0.01 mg/kg/day has been derived for acute-duration oral exposure (1–14 days) to 

iodine. 

The acute-duration MRL is based on a no-observed-adverse-effect-level (NOAEL) of 0.01 mg/kg/day in 

healthy adult humans (Gardner et al. 1988; Paul et al. 1988). Although the NOAEL is derived from acute 

studies of healthy adults, supporting studies indicate that the NOAEL would also be applicable to children 
IODINE 30 

2. RELEVANCE TO PUBLIC HEALTH 

and elderly adults (Boyages et al. 1989; Chow et al. 1991). On this basis, an uncertainty factor is not 

needed adjust the NOAEL to account for human variability in sensitivity. 

Although there were small increases in the serum concentrations of TSH, as a compensatory response to 

small decreases in the serum concentrations of thyroid hormone (T4 and T3), in healthy adults who had no 

history of thyroid disease or detectable antithyroid antibodies, hormone levels were within the normal 

range for healthy adults. These changes were almost certainly the result of a small decrease in the 

secretion of T4 and T3 from the thyroid as a result of the excess iodine. Furthermore, the hormone levels 

reverted to pretreatment levels when the iodine dosage was withdrawn. 

Healthy euthyroid adults (nine males, nine females) who had no history of thyroid disease or detectable 

antithyroid antibodies received daily oral doses of 250, 500, or 1,500 μg I/day as sodium iodide for 

14 days (Paul et al. 1988). Based on 24-hour urinary excretion of iodide prior to the iodide supplement, 

the background iodine intake was estimated to be approximately 200 μg/day; thus, the total iodide intake 

was approximately 450, 700, or 1,700 μg I/day (approximately 0.0064, 0.01, or 0.024 mg/kg/day, 

respectively, assuming a 70-kg body weight). Subjects who received 1,700 μg/day (0.024 mg/kg/day) 

had significantly decreased (5–10%) serum concentrations of TT4, FT4, and TT3 compared to pretreatment 

levels, and serum TSH concentrations were significantly increased (47%) compared to pretreatment 

values. All hormone levels were within the normal range during treatment. In this same study, the 

subjects who received daily doses of 250 or 500 μg I/day for 14 days (respective total intakes of 

approximately 450 or 700 μg/day; 0.0064 or 0.010 mg/kg/day) had no significant changes in serum 

hormone concentrations. A limitation of this study is that it included a relatively small number of 

subjects, although the exposures to these subjects were controlled and quantified with high certainty. 

In similar type of study, healthy, euthyroid, adult males (n=10) received daily oral doses of 500, 1,500, or 

4,500 μg I/day (as sodium iodide) for 14 days (Gardner et al. 1988). Based on 24-hour urinary excretion 

of iodide prior to the iodide supplement of 250–320 μg/day, the total estimated intakes were 300, 800, 

1,800, or 4,800 μg/day or approximately 0.004, 0.011, 0.026, or 0.069 mg/kg/day. There were no effects 

on serum thyroid hormone or TSH concentrations at the 800 μg/day intake (0.011 mg/kg/day); however, 

intakes of 1,800 or 4,800 μg I/day (0.026 or 0.069 mg/kg/day) produced small (10%) but significant, 

transient decreases in serum TT4 and FT4 concentrations and an increase (48%) in serum TSH 

concentration, relative to the pretreatment values. Similar to the Paul et al. (1988) study, the Gardener et 

al. 1988) study included a relatively small number of subjects, whose exposures were controlled and 

quantified with high certainty. 
IODINE	 31 

2. RELEVANCE TO PUBLIC HEALTH 

Although the acute NOAEL is derived from acute studies of healthy adults, supporting studies indicate 

that the NOAEL would also be applicable to children and elderly adults (Boyages et al. 1989; Chow et al. 

1991; see discussion of chronic-duration MRL for a description of these studies.). On this basis, an 

uncertainty factor is not needed to adjust the NOAEL to account for human variability in sensitivity. In 

one study (Chow et al. 1991), 30 healthy elderly adult females, without evidence of thyroid peroxidase 

antibodies (TPA), received daily doses of 500 μg I/day (as potassium iodide) for 14 or 28 days. Serum 

concentrations of FT4 were significantly decreased and serum TSH concentrations were significantly 

increased in the women who received the iodide supplements, relative to a placebo control group. On 

average, the magnitude of the changes did not produce clinically significant depression in thyroid 

hormone levels; however, five subjects had serum TSH concentrations that exceeded 5 mU/L. The 

subjects had a lower dietary iodine intake than those in the Gardner et al. (1988) study, approximately 72– 

100 μg/day, based on urinary iodide measurements. Therefore, the total iodide intake was approximately 

600 μg/day or 0.0086 mg/kg/day, essentially the same as the acute NOAEL in healthy adults. The second 

study, Boyages et al. (1989), is the primary basis for the chronic-duration MRL (see discussion of 

chronic-duration MRL). 

The acute-duration MRL is higher than the National Research Council RDA of 150 μg/day 

(0.0021 mg/kg/day for a 70-kg adult), 220 μg/day (0.0031 mg/kg/day), and 290 μg/day 

(0.0041 mg/kg/day) during pregnancy and lactation, respectively (NRC 2001). 

•	 An MRL of 0.01 mg/kg/day has been derived for chronic-duration (>365 days) oral exposure to 

iodine. 

The chronic-duration MRL is based on a NOAEL of 0.01 mg/kg/day and a lowest-observed-adverseeffect level (LOAEL) of 0.029 mg/kg/day for subclinical hypothyroidism in healthy human children 

(Boyages et al. 1989; Li et al. 1987). An uncertainty factor is not needed to adjust the NOAEL to account 

for human variability in sensitivity because the NOAEL is based on a sensitive end point in children, a 

sensitive subpopulation. Supporting studies indicate that the NOAEL would be applicable to elderly 

adults who may represent another sensitive subpopulation (Chow et al. 1991; Szabolcs et al. 1997). The 

chronic MRL was based on a chronic human study; however, since the chronic MRL is the same as the 

acute MRL (0.01 mg/kg/day), it is also applicable to intermediate-duration exposures. 

In the studies that form the primary bases for the chronic-duration MRL (Boyages et al. 1989; Li et al. 

1987), although serum concentrations of TSH were elevated, they remained within the normal range for 
 

 

 

IODINE 32 

2. RELEVANCE TO PUBLIC HEALTH 

children. Thyroid gland enlargement, however, was observed in children who had no history of thyroid 

disease or detectable antithyroid antibodies. Hormone levels were within the normal range for healthy 

children; therefore, these dosages did not induce clinical hypothyroidism. The slight thyroid enlargement 

can be considered a less-serious LOAEL, not indicative of functional impairment. Thyroid status was 

compared in groups of children, ages 7–15 years, who resided in two areas of China where iodide 

concentrations in drinking water were either 462 μg/L (n=120) or 54 μg/L (n=51) (Boyages et al. 1989; Li 

et al. 1987). Urinary iodine was 1,236 μg I/g creatinine in the high iodine group and 428 μg I/g creatinine 

in the low iodine group. Assuming a body weight of 40 kg and lean body mass of 85% of body weight, 

the above urinary iodine/creatinine ratios are approximately equivalent to iodine excretion rates, or steady 

state ingestion rates of 1,150 (0.029 mg/kg/day) and 400 μg/day (0.010 mg/kg/day) in the high and low 

iodide groups, respectively. Although the subjects were all euthyroid with normal values for serum 

thyroid hormones and TSH concentrations, TSH concentrations were significantly higher (33%) in the 

high iodine group. The high iodide group had a 65% prevalence of goiter and a 15% prevalence of 

Grade 2 goiter compared to 15% for goiter and 0% for Grade 2 goiter in the low iodine group. 

Although the acute NOAEL is derived from studies of children, supporting studies indicate that the 

NOAEL would be applicable to elderly adults (Chow et al. 1991; Szabolcs et al. 1997). On this basis, an 

uncertainty factor is not needed to adjust the NOAEL to account for human variability in sensitivity. The 

Chow et al. (1991) is described in the discussion of the basis for the acute-duration MRL. Szabolcs et al. 

(1997) studied elderly nursing home residents in the Carpathian Basin and revealed a prevalence of 

hypothyroidism that increased with increasing iodine intake. Subjects were from one of three regions 

where, based on reported urinary iodine levels of 72, 100, or 513 μg I/g creatinine, the iodine intakes were 

approximately 117, 163, or 834 μg/day (0.0017, 0.0023, or 0.012 mg/kg/day for low, n=119; moderate, 

n=135; or high intake, n=92, respectively). The prevalence of elevated serum TSH concentrations, 

together with serum FT4 concentrations below the normal range, was 0.95, 1.5, and 7.6% in the low, 

moderate, and high iodine groups, respectively. If a prevalence of abnormal thyroid hormone levels of 

<5% is considered a NOAEL, then this study supports a NOAEL in elderly adults that is slightly below 

0.012 mg/kg/day. Linear interpolation of the dose-prevalence data reported above yields an estimate of a 

5% prevalence at an iodine intake of approximately 0.008 mg/kg/day. 

The chronic-duration MRL is higher than the National Research Council RDA of iodine of 150 μg/day 

(0.0021 mg/kg/day for a 70-kg adult), 220 μg/day (0.0031 mg/kg/day), and 290 μg/day 

(0.0041 mg/kg/day) during pregnancy and lactation, respectively (NRC 2001). 
 

 

IODINE 33 

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 iodine. 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. 

Section 3.2 contains a discussion of the chemical toxicity of stable iodine; radiation toxicity associated 

with exposure to radioiodine is discussed in Section 3.3. 

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

Health effects of the element iodine are categorized by the chemical nature of stable iodine (127I) and the 

radioactive nature of unstable isotopes (e.g., 131I). Four radioactive isotopes (123I, 125I, 129I, and 131I) are of 

particular interest with respect to human exposures because 125I and 131I are used medically and all four 

isoptopes are sufficiently long-lived to be transported to human receptors after their release into the 

environment. These isotopes of iodine emit, primarily, beta radiation (that travel short distances in 

tissues) and gamma radiation (that can penetrate the entire body). The radiation dose from these 

radionuclides can be classified as either external (if the source is outside the body) or internal (if the 

source is inside the body). 

The external dose from iodine radionuclides arises primarily from the penetrating gamma radiation that 

can travel through air. Beta radiation emitted outside the body is normally of little health concern unless 

the radioactive material contacts the skin. Skin contact can allow the beta radiation to pass through the 

epidermis to live dermal tissue where it can contribute to the radiation dose to the skin. At very high 

external doses, beta (and gamma) radiation (e.g., greater than 3 Gy, 300 rad) can cause such adverse 

effects as skin erythema, ulceration, or necrosis (Agency for Toxic Substances and Disease Registry 

[ATSDR] 1999). 

Once radioactive iodine is internalized, it is absorbed, distributed, and excreted in the same manner as 

stable iodine. The internal radiation dose from radioactive iodine is actually a measure of the amount of 

energy that the beta and gamma emissions deposit in tissue. The short-range beta radiation produces a 
 

 

IODINE 34 

3. HEALTH EFFECTS 

localized dose while the more penetrating gamma radiation contributes to a whole-body dose. Molecular 

damage results from the direct ionization of atoms that are encountered by beta and gamma radiation and 

by interactions of resulting free radicals with nearby atoms. Tissue damage results when the molecular 

damage is extensive and not sufficiently repaired in a timely manner. 

In radiation biology, the term absorbed dose is the amount of energy deposited by radiation per unit mass 

of tissue, expressed in units of gray (Gy) or rad (see Appendix D for a detailed description of principles of 

ionizing radiation). The term dose equivalent refers to the biologically significant dose, which is 

determined by multiplying the absorbed dose by a quality factor for the type and energy of the radiations 

involved. Dose equivalent is expressed in units of sievert (Sv) or rem. The quality factor is considered to 

be unity for the beta and gamma radiation emitted from iodine radionuclides, so for these radionuclides, 

the absorbed dose (in Gray or rad) is numerically identical to the dose equivalent (in rem or sievert). The 

absorbed dose from internalized iodine radionuclides is estimated by taking into account the quantity of 

radionuclides entering the body (via ingestion or inhalation), the biokinetics (retention, distribution, and 

excretion) of the radionuclides, the rate at which the radionuclides decay to stable forms, the energies and 

intensities of the beta and gamma radiation emitted, and the characteristics of tissues that result in the 

energy of the emitted radiation being absorbed by tissues. Each tissue, therefore, can receive a different 

absorbed dose for a given amount of radioactivity that enters the body. The total absorbed dose to the 

body will reflect the integration of the absorbed doses for the all tissues. In summaries of the radioiodine 

toxicology literature provided in this profile, units of activity, absorbed dose, or dose equivalent are cited 

as reported in the literature and the corresponding conventional or SI units are provided in parentheses. 

The EPA has published a set of internal dose conversion factors for standard persons of various ages 

(newborn; 1, 5, 10, or 15 years of age; and adult) in its Federal Guidance Report No. 13 supplemental CD 

(EPA 1999). For example, the EPA has estimated that the dose equivalent following ingestion of 1 Bq of 

131I is 2.2x10-8 Sv (assuming an integration time of 50 years for an adult following the initial exposure). 

Age-specific dose coefficients for inhalation and ingestion of any of the radioactive isotopes of iodine by 

the general public can be found in International Commission on Radiological Protection (ICRP) 

publications 71 (ICRP 1995) and 72 (ICRP 1996), respectively. Dose coefficients for inhalation, 

ingestion, and submersion in a cloud of iodine radionuclides can be found in U.S. EPA Federal Guidance 

Report No. 11 (EPA 1988). Dose coefficients for external exposure to radioisotopes of iodine in air, 

surface water, or soil contaminated to various depths can be found in U.S. EPA Federal Guidance Report 

No. 12 (EPA 1993). 
 

 

IODINE 35 

3. HEALTH EFFECTS 

The ICRP has developed reference values for dose coefficients that relate dose equivalents to a unit of 

activity to which a person might be exposed. For example, the ICRP (1996, 2001) has estimated that the 

dose coefficient for an acute exposure of an adult to 131I is 2.2x10-8 Sv/Bq. Age-specific dose coefficients 

for inhalation and ingestion of any of the radioactive isotopes of iodine can be found in ICRP publications 

71 (ICRP 1995) and 72 (ICRP 1996), respectively. 

3.2 DISCUSSION OF HEALTH EFFECTS FOR STABLE IODINE BY ROUTE OF EXPOSURE 

Section 3.2 discusses the chemical toxicity of iodine. Radiation toxicity resulting from exposure to 

radioiodine is discussed in Section 3.3. 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

effects to human health. 
IODINE 36 

3. HEALTH EFFECTS 

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 citizens alike. 

Levels of exposure associated with carcinogenic effects (Cancer Effect Levels, CELs) of iodine are 

indicated in Tables 3-1 and 3-2 and Figures 3-1 and 3-2. 

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been 

made for iodine. 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 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 these levels (Barnes and Dourson 1988; EPA 1990), 

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. 

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. 
 

 

IODINE 37 

3. HEALTH EFFECTS 

3.2.1 Inhalation Exposure 

Iodine is absorbed in humans when I2 or methyl iodide vapors are inhaled (Black and Hounam 1968; 

Morgan and Morgan 1967; Morgan et al. 1967a, 1967b, 1968). Once absorbed, iodide would be expected 

to exert effects that are similar to that of iodide absorbed after ingestion, including effects on the thyroid 

gland and thyroid hormone status, sensitivity reactions, and cancer (see Section 3.2.2). Iodine (I2) is a 

strong oxidizing agent; therefore, exposure to high air concentrations of I2 vapor could potentially 

produce upper respiratory tract irritation and possibly oxidative injury. No studies were located regarding 

the following health effects in humans or animals after inhalation exposure to stable iodine: 

3.2.1.1 Death 

3.2.1.2 Systemic Effects 

3.2.1.3 Immunological and Lymphoreticular Effects 

3.2.1.4 Neurological Effects 

3.2.1.5 Reproductive Effects 

3.2.1.6 Developmental Effects 

3.2.1.7 Cancer 

3.2.2 Oral Exposure 

The section that follows provides background information relevant to the various study summaries that 

are presented subsequently. A description of the approaches used to calculate doses of stable iodine is 

provided. The actual study summaries follow. 

A large number of human experimental, clinical, and epidemiological studies on the effects of excess 

iodine on human health have been reported. The key studies that provide information on exposures 

associated with effects are summarized in this section of the profile. Oral iodine intakes were not directly 

assessed in many studies with sufficient accuracy to define dose-response relationships; however, 

measurements of urinary iodide provide a basis for estimating intakes in some of the studies (Konno et al. 
 

 

 

IODINE 38 

3. HEALTH EFFECTS 

1993b). Rather than describing the basis for estimating intakes from urinary iodine data in each of the 

study descriptions that follow, the general approach used is described here. If a 24-hour urinary iodide 

measurement was provided that could be regarded as a steady state value (relatively constant intake for at 

least 6 months), the intake was assumed to be equivalent to the 24-hour excretion rate. This assumption 

is consistent with information available on the toxicokinetics of iodide that indicates nearly complete 

absorption of ingested iodide and that urinary excretion accounts for >97% of the absorbed dose (see 

Sections 3.5.1.2 and 3.5.4.2). The assumption is also supported by studies in which 24-hour urinary 

iodide was measured before and after supplementation. For example, 31 patients received oral 

supplements of 382 μg I/day for 6 months. Prior to the supplementation, the mean 24-hour urinary iodide 

excretion rate was 36 μg/day (range, 13–69), whereas after 6 months of iodide supplementation, the mean 

24-hour urinary iodide excretion rate was 415 μg/day (Kahaly et al. 1998). The difference between these 

two values, 379 μg/day, is nearly identical to the supplemental dose of 382 μg/day. 

If a urine iodide concentration was provided for a morning sample that included overnight bladder urine, 

the measured concentration was assumed to represent the 24-hour average concentration and iodide intake 

was calculated as: 

Intake I = UI ⋅ 1.4 Equation (1) 

where UI is the measured urinary iodine concentration and 1.4 is the average volume of urine excreted per 

day (L/day) for a 70-kg adult (ICRP 1981). Equation 1 is in reasonable agreement with observed 

relationships between morning bladder urine iodide concentrations and 24-hour iodide excretion rates 

(Konno et al. 1993b; Nagata et al. 1998). Urine iodide concentration from untimed (spot) samples, other 

than morning samples that included overnight bladder urine, were considered to be potentially too 

uncertain to derive intake estimates, unless paired urinary creatinine concentrations or a urinary 

iodide:creatinine ratio (μg I:g creatinine) was reported. Urinary iodide:creatinine ratios were converted to 

estimated iodide intake as follows, assuming a constant relationship between urinary creatinine excretion 

rate and lean body mass. The rate of creatinine excretion (e.g., ECr , g creatinine/day) was calculated from 

the relationship between lean body mass (LBM) and ECr: 

LBM = 0 0272 ⋅ ECr . + 8 58 . Equation (2) 
 

 

 

IODINE 39 

3. HEALTH EFFECTS 

where the constants 0.0272 and 8.58 are the weighted arithmetic mean of estimates of these variables 

from eight studies reported in Forbes and Bruining (1976). Lean body mass was calculated as follows 

(ICRP 1981): 

LBM = BW ⋅0 . , 88 males Equation (3) 

LBM = BW ⋅ 085 . , females 

where BW is the reported or assumed body weight for males (75 kg) and females (65 kg) (EPA 1997f). A 

mean value of 60 kg (females, 55 kg; males, 65 kg) was assumed for body weights of adult populations of 

the Asian Pacific countries (e.g., Japan, China, Marshall Islands). Iodide intake was calculated as: 

Intake I = U / I Cr ⋅ ECr Equation (4) 

where UI/Cr is the urinary iodide:creatinine ratio (μg I/g creatinine). This approach yields relationships 

between 24-hour urinary iodide excretion rates and the urinary iodide:creatinine ratios that are in 

reasonable agreement with observations (Konno et al. 1993b). 

3.2.2.1 Death 

Two recent reviews of the clinical case literature note that deaths have occurred after ingestion of iodine 

preparations (FDA 1989b; Pennington 1990b). A review of medical records from the New York City 

Medical Examiners Office revealed that, in a period of 6 years, there were 18 deaths from attempted 

suicides in which adults ingested iodine tinctures (Finkelstein and Jacobi 1937). Tinctures of iodine 

contain a mixture of molecular iodine (I2) and sodium triiodide (NaI3) and have iodine concentrations of 

approximately 40 mg/mL. Doses of iodine from ingestion of the tinctures ranged from 1,200 to 9,500 mg 

(17–120 mg/kg), and deaths usually occurred within 48 hours of the dose. In one case, an adult male 

ingested 15 g of iodine as a potassium iodide solution and survived the episode; 18 hours after the dose, 

his serum iodide concentration was 2.95 mg/mL (Tresch et al. 1974). Symptoms of toxicity that have 

been observed in lethal or near-lethal poisonings have included abdominal cramps, bloody diarrhea and 

gastrointestinal ulceration, edema of the face and neck, pneumonitis, hemolytic anemia, metabolic 

acidosis, fatty degeneration of the liver, and renal failure (Clark 1981; Dyck et al. 1979; Finkelstein and 

Jacobi 1937; Tresch et al. 1974). 
IODINE 40 

3. HEALTH EFFECTS 

Two cases of infant deaths were reported in which death was from complications related to compression 

of the trachea by a goiterous thyroid gland; the mothers had ingested potassium iodide during their 

pregnancies at doses of approximately 850 and 1,180 mg I/day (12 and 17 mg/kg/day) (Galina et al. 

1962). 

The LOAEL values in humans for exposures by the oral route are presented in Table 3-1 and plotted in 

Figure 3-1. 

3.2.2.2 Systemic Effects 

Systemic effects of oral stable iodine exposure, other than after massive acute iodine overload such as in 

cases of attempted suicides (see Section 3.2.2.1), are on the thyroid gland and are discussed in the section 

on Endocrine Effects. As noted in the introduction to this chapter of the profile, adverse effects on a wide 

variety of other organ systems can result from iodine-induced disorders of the thyroid gland, including 

disturbances of the skin, cardiovascular system, pulmonary system, kidneys, gastrointestinal tract, liver, 

blood, neuromuscular system, central nervous system, skeleton, male and female reproductive systems, 

and numerous endocrine organs, including the pituitary and adrenal glands. The reader is referred to 

authoritative references on these subjects for further information (Braverman and Utiger 2000). 

Endocrine Effects. The principal direct effects of excessive stable iodine ingestion on the endocrine 

system are on the thyroid gland and regulation of thyroid hormone production and secretion. Adverse 

effects on the pituitary and adrenal glands derive secondarily from disorders of the thyroid gland. Effects 

on the thyroid gland can be classified into three types: hypothyroidism, hyperthyroidism, and thyroiditis. 

Hypothyroidism refers to the diminished production of thyroid hormone leading to clinical manifestations 

of thyroid insufficiency and can occur with or without goiter, a functional hypertrophy of the gland in 

response to suppressed hormone production and elevated serum thyroid stimulating hormone (TSH, also 

known as thyrotropin) concentrations. Typical biomarkers of hypothyroidism are a depression in the 

circulating levels of thyroxine (T4) and/or triiodothyronine (T3) below their normal ranges. This is always 

accompanied by an elevation of the pituitary hormone, TSH, above the normal range. Hyperthyroidism is 

an excessive production and/or secretion of thyroid hormones. The clinical manifestation of abnormally 

elevated circulating levels of T4 and/or T3 is thyrotoxicosis. Thyroiditis refers to an inflammation of the 

gland, which is often secondary to thyroid gland autoimmunity. The above three types of effects can 

occur in children and adults, in fetuses exposed in utero, or in infants during lactation. 
60

17

0.0086

77

3.4

78

0.069

79

0.46

80

0.024

81

LOAEL 

NOAEL Less Serious a 

System 

Key to 

figure 

Table 3-1 Levels of Significant Exposure to Iodine - Chemical Toxicity - Oral 

(mg/kg/day) (mg/kg/day) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) Species (Strain) 

ACUTE EXPOSURE Death 

1 Human 1 d

Systemic 

2 

Endocr 0.0086

14 d (C) 

Human 

Serious 

(mg/kg/day) 

17 (death) 

3 Human 1 d 

(C) 

Endocr 3.4 

4 Human 14 d 

(C) 

Endocr 0.069 

5 Human 7 d 

(W) 

Endocr 0.46 

6 Human 14 d 

(C) 

Endocr 0.024 

b 
1

82

1

8365

20

66

4.3

130

12

131

17

a

Key to 

figure 

Species 

(Strain) 

LOAEL 

NOAEL Less Serious

System 

Table 3-1 Levels of Significant Exposure to Iodine - Chemical Toxicity - Oral 

(mg/kg/day) (mg/kg/day) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

Serious 

(mg/kg/day) 

(continued) 

7 Human 14 d 

(C) 

Endocr 1 

8 Human 14 d 

(C) 

Endocr 1 

9 

Immuno/ Lymphoret 

8 d (C) 

Human 20 (fever) 

10 11 

5 d (C) 

Human 

INTERMEDIATE EXPOSURE Death 

9 mo (C) 

Human 

4.3 (ioderma) 

12 (death from tracheal 

compression by goiter) 

12 Human 9 mo 

(C) 

17 (death from tracheal 

compression by goiter) 
159

23

161

7.3

162

6.4

15

163

0.0039

165

0.46

0.0047

166

a

Key to 

figure 

Species 

(Strain) 

Systemic 

13 Human 

LOAEL 

NOAEL Less Serious

System 

Table 3-1 Levels of Significant Exposure to Iodine - Chemical Toxicity - Oral 

(mg/kg/day) (mg/kg/day) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

Endocr 

4 mo (C) 

Serious 

(continued) 

(mg/kg/day) 

23 (clinical hyperthyroidism with 

thyrotoxicosis) 

14 Human 2 mo 

(C) 

Endocr 7.3 (goiter in neonate) 

15 Human 9 mo 

(C) 

Endocr 6.4 (goiter and hypothyroidism in 

neonate) 

16 Human 11 wk 

(W) 

Endocr 15 

17 Human 90 d 

(C) 

Endocr 0.0039 0.46 (subclinical hypothyroidism with 

gland enlargement) 

18 Human 9 mo 

(C) 

Endocr 0.0047 
167

13

169

0.39

170

5.4

171

6.6

173

0.05

174

2.6

175

4.6

Table 3-1 Levels of Significant Exposure to Iodine - Chemical Toxicity - Oral (continued) 

Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

19 Human 9 mo 

Endocr 13 (goiter, hypothyroidism in (C) neonate) 

20 Human 28 d 

Endocr 0.39 (subclinical hypothyroidism with (C) 

gland enlargement) 

21 Human 3 mo 

Endocr 5.4 (goiter in neonate) (C) 

22 Human 4 mo 

Endocr 6.6 (goiter in neonate) (C) 

23 Human 6 mo 

Endocr 0.05 (clinical hypothyroidism) (C) 

24 Human 7 wk 

Endocr 2.6 (clinical hyperthyroidism with (C) thyrotoxicosis) 

25 Human 9 mo 

Endocr 4.6 (goiter in fetus) (C) 
140

23

141

11

142

8.6

0.01

114

0.029

118

2.9

120

1

a

Key to 

figure 

Species 

(Strain) 

LOAEL 

NOAEL Less Serious

System 

Table 3-1 Levels of Significant Exposure to Iodine - Chemical Toxicity - Oral 

(mg/kg/day) (mg/kg/day) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

Serious 

(mg/kg/day) 

(continued) 

26 

Immuno/ Lymphoret 

NS (C) 

Human 23 (fever) 

27 Human 6 mo 

(C) 

11 (ioderma) 

28 29 

8 mo (C) 

Human 

CHRONIC EXPOSURE Systemic 

11 yr (W) 

Human 

Endocr 0.01 

c

0.029 (subclinical hypothyroidism with 

gland enlargement) 

8.6 (ioderma) 

30 Human 2 yr 

(C) 

Endocr 2.9 (clinical hypothyroidism with 

goiter in neonate) 

31 Human NS 

(W) 

Endocr 1 (goiter with elevated serum 

TSH) 
121

0.22

0.0046

122

0.0039

124

0.0023

125

0.012

107

15

108

14

96

0.0035

Table 3-1 Levels of Significant Exposure to Iodine - Chemical Toxicity - Oral (continued) 

Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

32 Human 46 yr 

Endocr 0.22 (clinical hypothyroidism without (F) autoimmunity) 

33 Human 68 yr 

Endocr 0.0046

(F, W) 

34 Human 16 mo 

Endocr 0.0039

(C) 

35 Human 81 yr 

Endocr 0.0023 0.012 (clinical hypothyroidism without (F, W) autoimmunity; elderly adults) 

Immuno/ Lymphoret 

36 Human 15 yr 

15 (fever) (C) 

37 Human 1 yr 

14 (ioderma) (C) 

Cancer 

38 Human NS 

0.0035 (thyroid cancer; in endemic (F) goiter area) 
98

0.0035

Table 3-1 Levels of Significant Exposure to Iodine - Chemical Toxicity - Oral (continued) 

Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious 

figure (Strain) (Specific Route) System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

39 Human NS 

0.0035 (thyroid cancer; in endemic (F) goiter area) 

a The number corresponds to entries in Figure 3-1.b Used to derive an acute oral MRL based on a no-observed-effect-level (NOEL) of 0.01mg/kg/day in healthy adult humans, for changes in serum thyroid hormno-observed-adverse-effect-level (NOAEL) is 0.024 mg/kg/day.c Used to derive a chronic oral MRL of 0.005 mg/kg/day; dose divided by an uncertainty factor of 2 for human variability.(C) = capsule; d = day(s); Endocr = endocrine; (F) = feed; kg = kilogram(s); LOAEL = lowest-observed-adverse-effect level; mg = milligram(s); mo = month(s); no-observed-adverse-effect level; NA = not specified; TSH = thyroid-stimulating hormone; (W) = drinking water; wk = week(s); yr = year(s) 
100 

Death Endocrine Immuno/Lymphor 

Figure 3-1. Levels of Significant Exposure to Iodine - Chemical Toxicity - Oral 

Acute (≤14 days) 

Systemic 

mg/kg/day 

9
 1
 

10
 

10
 

3
 

1
 7
 8
 

5
 

0.1 

4
 6
 

0.01 MRL 2
 

0.001 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
100 

Death Endocrine Immuno/Lymphor 

Figure 3-1. Levels of Significant Exposure to Iodine - Chemical Toxicity - Oral (Continue

Intermediate (15-364 days) 

Systemic 

mg/kg/day 

13
 26
 

12
 16
 19
 11
 27
 10
 28
 14
 15
 22
 21
 25
 

24
 

1
 

17
 20
 

0.1 

23
 

0.01 

18
 17
 

0.001 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
100 

Endocrine Immuno/Lymphor Cancer * 

Figure 3-1. Levels of Significant Exposure to Iodine - Chemical Toxicity - Oral (Continu

Chronic (≥365 days) 

Systemic 

mg/kg/day 

36
 37
 

10
 

30
 

1 31
 

32
 

0.1 

29
 35
 0.01 29
 33
 34
 38
 39
 

35
 *Doses represent the lowest dose tested per study that produced a tumorigenic 

response and do not imply the existence of a threshold for the cancer endpoint. 

0.001 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
IODINE 51 

3. HEALTH EFFECTS 

Measurements of serum levels of thyroid hormones and TSH are often used as biomarkers of 

hypothyroidism and thyrotoxicosis in toxicology and epidemiology studies. In interpreting this literature 

in terms of human health risks, a distinction must be made between outcomes that have a high potential 

for producing clinical manifestations and outcomes that are not clinically significant. In this profile, an 

observed increase in serum TSH level and normal T4 and T3 levels is referred to as subclinical 

hypothyroidism. Similarly, the term subclinical hyperthyroidism refers to a condition in which the 

circulating levels of T4 or T3 are normal and the serum TSH concentration is suppressed. Typical normal 

ranges for these hormone levels are discussed in Section 3.9.2 

Hypothyroidism 

An acute iodide excess (above the preexisting dietary intake) transiently decreases the production of 

thyroid hormones in the thyroid gland; this is referred to as the acute Wolff-Chaikoff effect (Wolff et al. 

1949). In normal people, this is followed by a return to normal levels of hormone synthesis, referred to as 

escape from the acute Wolff-Chaikoff effect, without a significant change in circulating hormone levels. 

Escape is thought to be the result of down regulation of the sodium-iodide symport (NIS), the iodide 

transporter in the thyroid gland, resulting in a decrease in the intrathyroidal iodine and the resumption of 

normoral hormone synthesis (see Section 3.5.3.2 for further details on the Wolff-Chaikoff effect). An 

acute or chronic excess of iodide can also decrease circulating T4 and T3 levels and induce a hypothyroid 

state in some people who have underlying thyroid disorders. These effects are the result of a failure to 

escape from the acute Wolff-Chaikoff effect. Most people who experience iodine-induced 

hypothyroidism recover when the excess iodine intake is discontinued. Susceptible individuals include 

fetuses and newborn infants, elderly, patients who have underlying thyroid disease, and patients who have 

received treatment with antithyroid medications. A complete list of susceptible groups is presented in 

Table 2-2, recovery occurs when the excess iodine is discontinued. 

Several studies have examined the acute effects of increased intake of iodine on thyroid hormone status in 

adults (Chow et al. 1991; Gardner et al. 1988; Georgitis et al. 1993; Namba et al. 1993; Paul et al. 1988; 

Robison et al. 1998). These effects, in subjects who have no underlying thyroid disease, result from a 

small iodine-induced decrease in thyroid hormone release, which is accompanied by a rise in serum TSH 

concentration, to maintain normal thyroid function. The studies included relatively small numbers of 

subjects (<30) and, therefore, had low statistical power; this complicates the generalization of findings to 

large populations (in particular, findings of no significant effect). However, an important attribute of 

these studies is that iodine intakes were controlled and quantified with high certainty. The results of these 

studies suggest that acute (14 days) increases in iodine intake of 1,500 μg/day (21 μg/kg/day) above the 
IODINE 52 

3. HEALTH EFFECTS 

preexisting dietary intake can be tolerated without producing a clinically adverse change in thyroid 

hormone levels, although such doses may produce a small reversible depression in serum T4 

concentrations and a small rise in serum TSH concentrations, both within the normal range of values for 

healthy individuals. Changes in thyroid hormone levels within normal ranges are not considered to be 

clinically adverse; however, they are indicative of a subtle suppression of thyroid hormone release. The 

above conclusions apply to healthy adults who have no prior history of thyroid disease, no detectable 

antithyroid antibodies, and no prior history of chronic deficiency or excessive iodine intakes (Gardner et 

al. 1988; Paul et al. 1988). One study found that subclinical hypothyroidism was induced by an acute 

increase of 500 μg/day (7 μg/kg/day) in elderly adults (Chow et al. 1991), suggesting the possibility that 

elderly adults may be less tolerant of an iodide excess than younger adults. Based on estimates of the 

background dietary intakes of the subjects in these studies, in most cases estimated from measurements of 

urinary iodide excretion, the total iodide intakes (including background dietary intake) that could produce 

subclinical hypothyroidism were approximately 1,700 μg/day or approximately 24 μg/kg/day (Gardner et 

al. 1988; Paul et al. 1988). Acute intakes of approximately 700 μg/day or approximately 10 μg/kg/day 

had no detectable effect on thyroid status in healthy individuals (Gardner et al. 1988; Paul et al. 1988). 

One study found no evidence for disturbances in thyroid hormone status in healthy adults who received 

doses of 300 μg/kg/day (approximately 20 mg/day) for 14 days (Robison et al. 1998). This suggests that, 

at least under certain conditions, exposure levels >10–24 μg/kg/day may be tolerated in some people. 

Brief summaries of the relevant studies that provide information on oral exposures to iodine that suppress 

the thyroid gland are provided below. 

Healthy euthyroid adults (nine males, nine females) who had no history of thyroid disease or detectable 

antithyroid antibodies received daily oral doses of 1,500 μg I/day as sodium iodide for 14 days (Paul et al. 

1988). Based on 24-hour urinary excretion of iodide prior to the iodide supplement, the background 

iodine intake was estimated to be, approximately, 200 μg/day; thus, the total iodide intake was 

approximately 1,700 μg I/day (approximately 24 μg/kg/day, assuming a 70-kg body weight). Serum 

concentrations of TT4, FT4, and TT3 were significantly depressed (5–10%) compared to pretreatment 

levels and serum TSH concentrations were significantly elevated (47%) compared to pretreatment values. 

Hormone levels were within the normal range during treatment and, therefore, the subjects were not 

hypothyroid. In this same study, nine females received daily doses of 250 or 500 μg I/day for 14 days and 

there were no significant changes in serum hormone concentrations. Total intake was approximately 

450 or 700 μg/day (6 or 10 μg/kg/day). Some of these women participated in the higher dose study 1 year 

earlier. 
 

 

IODINE 53 

3. HEALTH EFFECTS 

In a similar type of study, healthy, euthyroid, adult males (n=10) received daily oral doses of 500 μg I/day 

(as sodium iodide) for 14 days; there were no effects on serum thyroid hormone or TSH concentrations; 

however, dosages of 1,500 or 4,500 μg I/day produced small (10%) but significant, transient decreases in 

serum TT4 and FT4 concentrations and an increase (48%) in serum TSH concentration, relative to the 

pretreatment values (Gardner et al. 1988). Urinary iodide excretion prior to the dose ranged from 250 to 

320 μg/day, suggesting that the background dietary intake was approximately in this same range (see 

Sections 3.5.1.2 and 3.5.4.2). The magnitude of the changes at the higher iodide dosages yielded 

hormone concentrations that were within the normal range and, thus, would not represent a significant 

thyroid suppression. This suggests that an acute oral intake of 500 μg/day above a preexisting dietary 

intake, or approximately 800 μg I/day total (11 μg/kg/day), is tolerated without thyroid gland suppression 

in healthy adult males, and intakes as high as 4,800 μg I/day (69 μg/kg/day) may be tolerated in some 

people without clinically adverse effects. 

Another similar experimental study has been reported in which 30 healthy, elderly adult females, without 

evidence of thyroid peroxidase antibodies (TPA), received daily doses of 500 μg I/day (as potassium 

iodide) for 14 or 28 days (Chow et al. 1991). Serum concentrations of FT4 were significantly decreased 

(change from pretreatment level, approximately -1 pmol/L) and serum TSH concentrations were 

significantly increased (change from pretreatment level approximately +0.6 mU/L) in the women who 

received the iodide supplements, relative to a placebo control group. On average, the magnitude of the 

changes did not produce depression in thyroid hormone levels below the normal range; however, five 

subjects had serum TSH concentrations that exceeded 5 mU/L, considered mildly elevated. The subjects 

had a lower dietary iodine intake than those in the Gardner et al. (1988) study; approximately 72– 

100 μg/day, based on urinary iodide measurements. Therefore, the total iodide intake was approximately 

600 μg/day (9 μg/kg/day). 

Higher acute iodine exposures have been shown to produce reversible thyroid gland hypertrophy, in 

addition to hormone suppression. The effects of tetraglycine hydroperiodide, an iodine compound used to 

purify drinking water, were examined in an acute experimental study (Georgitis et al. 1993). When 

dissolved in water, tetraglycine hydroperiodide releases I2 and iodide (as a reduction product). Seven 

healthy adults, who had no history of thyroid disease, ingested 227 mL (8 ounces) of a flavored drink into 

which tetraglycine hydroperiodide had been dissolved; the dosage was 32 mg/day of iodine for 

7 consecutive days (460 μg/kg/day). Seven age-, weight-, and height-matched controls received water 

without added iodine. A statistically significant decrease in serum concentration of T4 and T3 (14–15%) 

and a significant increase in TSH concentration (50%) occurred in the treatment group during the 
IODINE 54 

3. HEALTH EFFECTS 

treatment, relative to their pretreatment values, whereas no change occurred in the control subjects. Two 

subjects in the treatment group had T4 concentrations below approximately 60 nmol/L, which is slightly 

below normal, and two subjects had TSH concentrations that were between 4.5 and 6 mU/L, which were 

slightly elevated and suggestive of mild thyroid impairment (it is not clear from the report if these were 

the same two subjects). In a more extensive study of similar design, eight healthy euthyroid adults (seven 

males, one female), who were negative for thyroid antimicrosomal antibody, ingested approximately 

32 mg iodine/day (460 μg/kg/day) as tetraglycine hydroperoxide dissolved in juice or water, for 90 days 

(LeMar et al. 1995). The mean pretreatment 24-hour urinary iodide excretion rate was 276 μg/day. 

Thyroid gland volumes, as determined from ultrasound measurements, increased significantly during the 

treatment, with a peak volume 37% above the pretreatment volume and reverted to pretreatment volumes 

7 months after the iodine dosing was discontinued. Serum TSH concentrations increased significantly 

during treatment, with only one subject having a 3-fold increase to a value above normal, 6.1 mU/L; this 

subject also had the highest thyroid volume during the treatment period. None of the subjects developed 

clinical hypothyroidism. 

Daily doses of 27 mg I/day (390 μg/kg/day), as licorice lecithin-bound iodide, given for 28 days to 

10 healthy, euthyroid adult males who were TPA negative resulted in a statistically significant, 15% 

increase in thyroid gland volume, as determined from ultrasound measurements, compared to 

pretreatment values (Namba et al. 1993). Serum concentrations of FT4 and T3 were decreased, and serum 

TSH and thyroglobulin (Tg) concentrations were significantly elevated, although the values were all 

within the normal ranges. All values, including thyroid gland volume returned to normal within 28 days 

after the last iodide supplement. In a clinical study of 22 hypothyroid adults from Japan who consumed 

an estimated 1–43 mg I/day (17–720 μg/kg/day, from consumption of seaweed), 12 patients reverted to a 

euthyroid state after 3 weeks of voluntary dietary iodine restriction (Tajiri et al. 1986). When seven of 

these patients who converted to a euthyroid state after dietary restriction received supplements of 25 mg 

I/day (420 μg/kg/day) as Lugol’s solution (a mixture of 50 mg/mL I2 and 100 mg/mL potassium iodide 

KI) for 2–4 weeks, all reverted to a hypothyroid state (serum TSH concentrations >5 mU/L). In this same 

study, 11 healthy euthyroid adults (8 females, 3 males) received 25 mg I/day for 14 days (420 μg/kg/day). 

The mean serum TSH concentrations significantly increased (40%) during the treatment compared to 

their pretreatment values; however, their TSH concentrations during treatment (3.9 mU/L) did not exceed 

the normal range (<5 mM/L). 

In contrast to the results of the above studies, no clinical abnormalities in thyroid hormone status occurred 

when healthy, euthyroid, adult males (n=6 or 7), who had no history of thyroid-related illness, ingested 
IODINE 55 

3. HEALTH EFFECTS 

daily oral doses of 300 or 1,000 μg I/kg/day as either I2 or sodium iodide for 14 days (Robison et al. 

1998). Based on measurements of urinary iodide excretion rates, the pretreatment iodide intakes were 

approximately 100 μg/day. The high dosage (1,000 μg I/kg/day) produced a small but statistically 

significant increase in serum TSH concentrations compared to a sodium chloride control group; the TSH 

concentrations in the control group did not exceed the normal range (<5 mU/L) and reverted to control 

levels within 10 days after the iodine supplementation was ended. Serum TT4 and TT3 were not 

significantly different in the treatment groups, compared to the control group. As noted previously, 

studies of this size have low statistical power, which complicates the interpretation of findings of no 

significant effect. 

In a more remarkable, intermediate-duration experimental study, four healthy adults (three males, one 

female) received a daily oral dose of approximately 1,000 mg I/day as a saturated solution of potassium 

iodide (30 drops/day, approximately 36 mg I/drop, 15 mg I/kg/day) for 11 weeks (Jubiz et al. 1977). A 

small, statistically significant decrease in the mean serum concentration of T4 occurred (pretreatment, 

8.8 μg/dL; treatment minimum 7.6 g/dL) and an increase in TSH concentration (pretreatment, 7.3 mU/L; 

treatment maximum, 13.5 mU/L). The above changes were no longer evident within 1 week after the 

treatment was discontinued. In a similar study, eight euthyroid adults (seven male, one female), who 

were hepatitis patients, received daily oral doses of approximately 360 mg I/day (5 mg/kg/day) as a 

saturated solution of potassium iodide (10 drops/day, approximately 36 mg I/drop) for 60 days (Minelli et 

al. 1999). A small statistically significant decrease in the mean serum concentration of T4 (pretreatment, 

13.8 pmol/L; treatment minimum 13.2 pmol/L) and an increase in TSH concentration (pretreatment, 

0.6 mU/L; treatment maximum, 1.7 mU/L) occurred. Two patients were reported to have developed 

transient elevated serum TSH concentrations during the iodide treatment, with normal concentrations of 

FT4 and FT3. There were no incidences of clinical hypothyroidism or hyperthyroidism. A nearly 

identical result was reported for eight euthyroid hepatitis patients who had previously received 

recombinant interferon-alpha therapy (but who did not develop thyroid dysfunction during therapy) and 

who subsequently received daily doses of approximately 360 mg I/day (5 mg/kg/day) as a saturated 

solution of potassium iodide for 60 days (Minelli et al. 1997). As part of the study reported by Jubiz et al. 

(1977), 13 patients with obstructive pulmonary disease who were receiving 1,000–2,000 mg I/day (14– 

28 mg/kg/day) as a saturated potassium iodide solution for periods of 1 month to 8 years exhibited 

unambiguous symptoms of hypothyroidism, including thyroid gland enlargement, depressed serum 

concentrations of T4 (mean 2–2.7 μg/dL), and elevated serum TSH concentrations (20–35 mU/L). Serum 

T4 and TSH levels returned to normal in all but one of the patients within 1 month after the iodide dosage 
 

 

IODINE 56 

3. HEALTH EFFECTS 

was discontinued. However, in the Jubiz et al. (1977) study, the presence of chronic thyroiditis was not 

determined. 

The results of several epidemiological studies suggest that chronic exposure to excess iodine can result in 

or contribute to hypothyroidism. Thyroid status was compared in groups of children, ages 7–15 years, 

who resided in two areas of China where drinking water iodide concentrations were either 462 μg/L 

(n=120) or 54 μg/L (n=51) (Boyages et al. 1989; Li et al. 1987). Although the subjects were all euthyroid 

with normal values for serum thyroid hormones and TSH concentrations, TSH concentrations were 

significantly higher in the high iodine group. The prevalence and severity of goiter in the population were 

evaluated, the latter based on a goiter severity classification scale (Grade 0, no visible goiter; Grade 1, 

palpable goiter that is not visible when the neck is not extended; Grade 2, palpable and visible goiter 

when the neck is not extended). The high iodide group had a 65% prevalence of goiter compared to 15% 

in the low iodine group. The prevalence of more severe, Grade 2 goiter, was also higher in the high 

iodide group (15%) compared to the low iodide group (0%). Urinary iodine was 1,236 μg I/g creatinine 

in the high iodine group and 428 μg I/g creatinine in the low iodine group. Assuming a body weight of 

40 kg and lean body mass of 85% of body weight, the above urinary iodine/creatinine ratios are 

approximately equivalent to iodine excretion rates or steady state ingestion rates of 1,150 μg/day 

(29 μg/kg/day) and 400 μg/day (10 μg/kg/day) in the high and low iodide groups, respectively. 

Zhao et al. (2000) compared the prevalence of thyroid enlargement among children 5–15 years of age to 

drinking water and urinary iodine levels in residents of 65 townships in Jiangsu Province, China. This 

area had a high prevalence of childhood goiter, although urinary iodide measurements suggested dietary 

iodine sufficiency. Urinary iodine measurements were obtained for adults who resided in the same 

townships as the children. The prevalences of goiter and abnormal thyroid volume (not defined in the 

report) increased with increasing urine iodine concentration. The prevalences of goiter increased from 

15% (802 μg I/L urine) to 38% (1,961 μg I/L urine). The prevalences of abnormal thyroid volume 

increased from 5 to 17% over this same range of urinary iodine concentrations. Assuming an adult urine 

volume of 1.4 L/day and an adult body weight of 60 kg, the observed range of urinary iodide 

concentrations in adults (520–1,961 μg I/L) corresponded to approximate intakes of 730–2,750 μg/day 

(12–46 μg/kg/day). 

A survey of a group of Peace Corps volunteers revealed a high prevalence of goiter among volunteers 

who drank water from iodine filters (Khan et al. 1998). Of 96 volunteers surveyed, 44 (46%) had 

enlarged thyroid glands, 33 (34%) had elevated serum TSH concentrations ($4.2 mU/L), and 4 (4%) had 
IODINE 57 

3. HEALTH EFFECTS 

depressed serum TSH concentrations (#0.4 mU/L). The mean iodide concentration in filtered drinking 

water was 10 mg I/L, which corresponded to a daily intake of iodide from drinking water of 50–90 mg 

I/day (0.7–1.3 mg/kg/day, based on a reported daily water consumption of 5–9 L/day). This estimate was 

consistent with measured mean urinary iodide concentration of 11 mg/L, which corresponds to 

approximately 55–99 mg I/day excreted or ingested, assuming daily urine volumes similar to water 

consumption. When the excess iodine was removed from the drinking water, all measures of thyroid 

function returned to normal (Pearce et al. 2002). 

In a study of elderly adults, thyroid status was compared in 423 residents (ages 66–70 years) of Jutland, 

Denmark who had iodine intakes of 40–60 μg/day (0.7 μg/kg/day) and 100 residents of Iceland who had 

intakes of 300–350 μg/day (5 μg/kg/day) (Laurberg et al. 1998). Subjects from the high iodine intake 

region had a significantly higher prevalence (18%) of serum TSH levels above the high end of the normal 

range (>4 mU/L) compared to subjects from the low iodine region (3.8%). The prevalence of serum TSH 

concentrations above 10 mU/L was 4.0% in the high iodine region and 0.9% in the low iodine region. 

Females in both regions had a significantly higher prevalence of elevated TSH concentrations than males. 

Serum concentrations of T4 were not depressed, even in subjects with TSH concentrations that exceeded 

10 mU/L. Thus, although the subjects appeared to be euthyroid, the higher iodine intakes were associated 

with a subclinical suppression of the thyroid gland as indicated by a high prevalence of elevated serum 

TSH concentrations. A study of elderly nursing home residents in the Carpathian Basin also revealed a 

prevalence of hypothyroidism that increased with increasing iodine intake (Szabolcs et al. 1997). 

Subjects were from one of three regions where, based on reported urinary iodine levels of 72, 100, or 

513 μg I/g creatinine, the iodine intakes were approximately 117, 163, or 834 μg/day (1.7, 2.3, or 

12 μg/kg/day for low, n=119; moderate, n=135; or high intake, n=92, respectively). The prevalence of 

serum TSH concentrations above the normal range was 4.2, 10.4, and 23.9% in the low, moderate, and 

high iodine groups, respectively. The prevalence of elevated serum TSH concentrations together with 

serum FT4 concentrations below the normal range was 0.95, 1.5, and 7.6% in the low, moderate, and high 

iodine groups, respectively. 

Several studies have found increased prevalence of hypothyroidism in residents of areas of Japan where 

dietary iodine intake is high as a result of consumption of seaweeds containing a high iodine 

concentration. In one study, urinary iodide and serum TSH concentrations were measured in a group of 

1,061 adult residents of five coastal areas of Japan and in 4,100 residents of two inland areas (Konno et al. 

1993a, 1994). The subjects were classified as having high or normal iodine intakes based on whether 

their urinary iodide concentrations were less than or greater than the high end of the normal range, 
 

 

IODINE 58 

3. HEALTH EFFECTS 

75 μmol/L (9,500 μg/L). The urine samples were not timed and urinary creatinine concentrations were 

not reported; therefore, only rough estimates of the rate of urinary excretion of iodide (μg/day) and iodide 

intake can be made. The report indicates that the urine samples were collected in the morning and 

included night urine (i.e., urine voided on awakening). If it is assumed that the concentrations of iodide in 

the morning urine samples reflect the concentration for a 24-hour sample and that the 24-hour urine 

volume is approximately 1.4 L (ICRP 1981), then the 24-hour excretion and intake rates in the high 

iodine group may have been approximately 13.3 mg/day (0.22 mg/kg/day, assuming a body weight of 

60 kg). Even if the morning urine samples were relatively concentrated compared to the 24-hour average, 

the above urine iodide concentrations suggest an iodide intake of several mg/day. This is consistent with 

other reported estimates that range from 1 to 5 mg/day in Japan among consumers of seaweed 

(Pennington 1990b). Examples of much higher intakes (25–40 mg/day, 0.4–0.7 mg/kg/day) have been 

reported in hypothyroid patients who consume seaweed (Tajiri et al. 1986). The prevalences of elevated 

serum TSH concentrations (>5 mU/L) and urine iodide concentrations (>9,500 μg/L) were both 

significantly higher in the costal regions compared to the inland regions (Konno et al. 1994). Serum TSH 

concentrations were positively correlated with the urine iodide concentrations, and the prevalence of 

elevated serum TSH concentrations in the seven areas correlated positively with the prevalence of high 

urinary iodide concentrations. There were no significant correlations or associations with urine iodide 

and suppressed concentrations of serum TSH (<0.15 mU/L) or with the presence of thyroid antibodies. 

A study of iodine supplementation for treatment of endemic goiter related to iodine deficiency provides 

additional evidence that increases in iodine intake can induce thyroid dysfunction, including thyroid 

autoimmunity. Otherwise healthy adults who had goiter but no evidence of clinical hypothyroidism or 

hyperthyroidism or antithyroid antibodies received either a placebo (16 females, 15 males) or 200 μg 

I/day (3 μg/kg/day total intake) (16 females, 15 males) as potassium iodide for 12 months (Kahaly et al. 

1997). A significant decrease in thyroid volume occurred in the treated group relative to the control 

group. Three subjects in the treatment group (9.7%, two females and one male) developed elevated levels 

of thyroglobulin and thyroid microsomal antibodies compared to none in the control group. Two of these 

subjects developed hypothyroidism and one subject developed hyperthyroidism; all three subjects 

reverted to normal thyroid hormone status when the iodide supplementation was discontinued. In a 

similar study, 31 adult euthyroid patients from an endemic goiter region who had goiter received 

500 μg/day potassium iodide (382 μg I/day, 5 mg I/kg/ day based on reported median body weight of 

75 kg) for 6 months, and 31 patients received 0.125 μg T4/day (Kahaly et al. 1998). Based on reported 

measurements of 24-hour urine iodide excretion, the preexisting iodide intake was approximately 

40 μg/day (range, 13–77, 0.6 μg/kg/day); thus, the total intake during treatment was approximately 
IODINE 59 

3. HEALTH EFFECTS 

420 μg I/day (6 μg/kg/day). After 6 months of iodide supplementation, the mean 24-hour urinary iodide 

excretion rate was 415 μg/day, which is consistent with the estimate of a total iodide intake of 

approximately 420 μg/day. Six of the patients who received iodide (19%) developed high titres of 

thyroglobulin and thyroid microsomal antibodies, compared to none in the T4 group. Four of the high 

antibody patients became hypothyroid and two patients became hyperthyroid. The thyroid hormone 

status reverted to normal and antibody titres decreased during a 6-month period following the treatment in 

which the patients received a placebo. 

People who have autoimmune thyroid disease may be at increased risk of developing thyroid dysfunction 

when exposed to excess iodide. Euthyroid patients (37 females, 3 males) from an iodine-deficient region, 

who were diagnosed with Hashimoto’s thyroiditis and who were positive for antithyroid (thyroid 

peroxidase) antibodies, received an oral dose of 250 μg potassium iodide (190 μg I/day) for 4 months; a 

similar group of thyroiditis patients (41 females, 2 males) served as controls (Reinhardt et al. 1998). 

Based on urinary iodide measurements of 72 μg I/g creatinine before the iodide supplementation, the 

preexisting iodide intake was approximately 125 μg/day, for a total iodide dosage of 375 μg/day 

(5.8. μg/kg/day) in the treatment group. Seven patients in the treatment group developed elevated serum 

TSH concentrations (>4 mU/L) and one patient developed overt clinical hypothyroidism with a TSH 

concentration of 43.3 mU/L and a serum FT4 concentration of 7 pmol/L. One patient in the treatment 

group became clinically hyperthyroid with a serum FT4 concentration of 30 pmol/L and TSH 

concentration of <1 mU/L. One patient in the control group developed mild subclinical hypothyroidism. 

After the iodine supplementation was discontinued, three of the seven hypothyroid patients in the 

treatment group reverted to normal thyroid. An additional patient in the treatment group became 

hypothyroid, requiring T4 supplements. The patient who became hyperthyroid while in the treatment 

group reverted to normal thyroid status after the iodide supplements were discontinued. In a smaller 

clinical study of patients from an iodine-deficient region, four of seven euthyroid patients with 

Hashimoto’s thyroiditis who received 180 mg I/day (2.6 mg/kg/day) as a saturated potassium iodide 

solution for 6 weeks developed hypothyroidism, which reverted to normal after the iodide 

supplementation was discontinued (Braverman et al. 1971a). In addition to autoimmune diseases, other 

thyroid disorders predispose people to iodine-induced hypothyroidism (Table 2-2). 

Maternal exposures to excess iodine during pregnancy have been shown to produce goiter and 

hypothyroidism in neonates. In general, clinical cases have involved maternal exposures to several 

hundred mg I/day during pregnancy. For example, in one clinical case, hypothyroidism and lifethreatening goiter occurred in an infant born to a woman who consumed approximately 200 mg I/day 
 

 

 

IODINE 60 

3. HEALTH EFFECTS 

(2.9 mg/kg/day), as sodium iodide, for 2 years, including during pregnancy (Iancu et al. 1974). The infant 

was treated with levothyroxine and reverted to a normal gland and hormone status within 3 weeks after 

birth, without further hormone therapy. In another case, a woman ingested approximately 260–390 mg 

I/day (4.6 mg/kg/day) during pregnancy and her infant developed goiter in utero, which was successfully 

treated in utero with levothyroxine; the thyroid gland and hormone status of the infant was normal at birth 

(Vicens-Colvet et al. 1998). Coakley et al. (1989) reported, as part of the results of a screening program 

for congenital hypothyroidism, two cases in which women ingested iodide during pregnancy and gave 

birth to infants who had a transient goiter. In one case, the estimated total dose iodide dose was 

approximately 38.3 g I, of which approximately 15.3 g was ingested during the last month of pregnancy. 

These doses are equivalent to an average daily total dose of approximately 96 mg I/day during the first 

8 months and 510 mg I/day (7.3 mg/kg/day) during the last month of pregnancy. Penfold et al. (1978) 

reported two cases, one of goiter without hypothyroidism in an infant born to a mother who ingested 

approximately 380 mg I/day (5.4 mg/kg/day) as potassium iodide during the last trimester of pregnancy, 

and the other case of goiter with hypothyroidism in an infant born to a mother who had ingested 

approximately 460 mg I/day (6.6 mg/kg/day) as potassium iodide during the last 4 months of pregnancy. 

In both cases, hypothyroidism and/or goiter were temporary and did not require thyroid hormone therapy. 

Hassan et al. (1968) reported three cases of neonatal goiter and hypothyroidism. In each case, the mother 

had ingested daily doses of potassium iodide during pregnancy; approximate doses were 450, 688, and 

765 mg I/day (6–11 mg/kg/day). The goiter and hypothyroidism reversed with temporary thyroid 

hormone therapy. Bostanci et al. (2001) reported a similar outcome in an infant of a mother who ingested 

130 mg I/day as potassium iodide during the last 4 months of pregnancy. Martin and Rento (1962) 

reported two cases of goiter and severe but reversible hypothyroidism in infants born to mothers who 

ingested potassium iodide during pregnancy; the approximate dosages were 920 and 1,530 mg I/day 

(13 and 22 mg/kg/day). In two cases, infants died with complications related to a goiterous thyroid gland 

compression of the trachea; the mothers had ingested potassium iodide during their pregnancies at doses 

of approximately 850 and 1,180 mg I/day (12 and 17 mg/kg/day) (Galina et al. 1962). 

The above clinical cases demonstrate that doses of iodide exceeding 200 mg/day (2.8 mg/kg/day) during 

pregnancy can result in congenital goiter and hypothyroidism. There is also a large clinical experience 

with the lower doses of iodide supplementation given during pregnancy for the purpose of correcting or 

preventing potential iodine deficiency and for the management of Graves’ disease during pregnancy. In a 

study of 35 women with Graves’ disease who received 6–40 mg iodide (0.1–0.7 mg/kg/day, assuming a 

60-kg body weight) as potassium iodide during pregnancy, 2 of 35 infants had serum TSH concentrations 

above normal at birth (>20 mU/L) and none had FT4 concentrations below normal at birth (<10 pmol/L; 
 

 

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7 ng/L), suggesting that this level of iodide supplementation did not induce a hypothyroid state in the 

newborn, but did produce a subclinical elevation in TSH levels in some infants (Momotani et al. 1992). 

In a study of iodide supplementation during pregnancy in an iodide-deficient area of Denmark, 28 women 

received daily doses of 200 μg I/day from the 17th–18th week of pregnancy through the first 12 months 

after delivery and 26 women received no supplementation (Pedersen et al. 1993). Pretreatment urinary 

iodide levels were 51 and 55 μg/L, respectively, in the two groups, suggesting a preexisting dietary iodine 

intake of approximately 75 μg/day (assuming that the urine iodide concentration reflected the 24-hour 

average and that urine volume was approximately 1.4 L/day) and a total iodide intake of 275 μg/day 

(4 μg/kg/day). There were no statistically significant differences in serum TT4, FT4, T3, or TSH 

concentrations in the infants in the two groups at birth, and there were no abnormal values for the 

hormones in any of the infants. In a similar type of study, 38 pregnant women from a potentially iodinedeficient region of Germany received daily doses of 230 μg I/day as potassium iodide during pregnancy 

and lactation and 70 women received no supplementation. Pretreatment urinary iodide levels were 53 μg 

I/g creatinine (median), suggesting a preexisting iodide intake of approximately 90 μg/day (Liesenkötter 

et al. 1996) and a total intake of 320 μg/day (5 μg/kg/day). Thyroid gland volumes were significantly 

decreased in infants from the supplemented group, compared to the control group (median control, 

1.5 mL; median treated, 0.7 mL). One infant (1/38, 2.6%) from the supplemented group was classified as 

having an enlarged gland (>1.5 mL) compared to 14 (14/70, 20%) from the control group. The report 

indicates that “no hypothyroidism or hyperthyroidism was observed in the mothers or newborns”, 

although the end points evaluated, other than serum TSH, were not indicated. 

In general, the aforementioned clinical case literature demonstrates that doses of iodide exceeding 

200 mg/day (2.8 mg/kg/day) given to a mother during pregnancy can result in congenital goiter and 

hypothyroidism in the newborn infant (Coakley et al. 1989; Galina et al. 1962; Hassan et al. 1968; Iancu 

et al. 1974; Martin and Rento 1962; Penfold et al. 1978; Vicens-Calvet et al. 1998), although this effect 

has not been observed in all studies (Liesenkötter et al. 1996; Pedersen et al. 1993). An iodine-deficient 

status of the mother can also lead to goiter in the fetus and neurodevelopmental impairment of the fetus. 

Adequate iodine supplementation early in pregnancy can correct the deficiency and prevent maternal and 

neonatal goiter formation (Glinoer et al. 2001). 

Iodized oil has been used to supplement intakes in populations that are iodine deficient in areas where 

supplementation with iodized table salt or drinking water is not practical. Iodized oil (ethiodiol) consists 

of a mixture of covalently iodinated fatty acids of poppy seed oil; the iodine content is approximately 

38% by weight. Iodine in iodized oil is taken up in adipose tissue and has a much longer retention time in 
 

 

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the body than iodide salts; thus, epidemiological studies of iodized oil cannot be directly compared to 

those of iodide. Nevertheless, the studies provide some useful information on oral exposures to iodine 

that are tolerated during pregnancy without apparent adverse consequences to the fetal or neonatal 

thyroid. Delange (1996) reviewed epidemiological studies in which iodized oil was administered just 

prior to and/or during pregnancy to prevent maternal and neonatal hypothyroidism. A study of an iodinedeficient population in Algeria (with a 53% prevalence of goiter and 1% prevalence of congenital 

cretinism) compared thyroid status in infants born to mothers who received a placebo or a single oral dose 

of 240 mg I (3.4 mg/kg), as iodized oil, either 1–3 months prior to conception, during the first month of 

pregnancy, or during the third month of pregnancy. Neonatal serum concentrations of TSH were 

significantly lower in the treated groups compared to controls (treated, 4.6–4.9 mU/L; placebo, 

12.4 mU/L) and serum T4 concentrations were significantly higher compared to controls (treated, 10.4– 

11 μg/dL; placebo, 6.7 μg/dL). The incidence of infant hypothyroidism was 0 in 554 infants; the 

incidence in the placebo control was 2 in 982 (0.2%). A similar outcome occurred in a population from 

an iodine-deficient region of Malawi (59% prevalence of goiter, 1% incidence of cretinism), where 

pregnant women received either a placebo or an oral dose of 240 mg I as iodized oil (Delange 1996). 

Hyperthyroidism 

Oral exposure to excess iodide can, under certain circumstances, induce hyperthyroidism and 

thyrotoxicosis. The epidemiological and clinical literature suggests that hyperthyroidism occurs most 

often in people who have a previous history of iodine deficiency, goiter, or thyroid diseases including 

nodular goiter or Graves’ disease (Braverman and Roti 1996; Fradkin and Wolff 1983; Leger et al. 1984; 

Paschke et al. 1994). Cases of iodine-induced hyperthyroidism in people who were euthyroid and without 

apparent thyroid disease have been reported (Rajatanavin et al. 1984; Savoie et al. 1975; Shilo and Hirsch 

1986); however, only a few have provided dose information. In one case, a 72-year-old female without 

apparent preexisting thyroid disease developed clinical hyperthyroidism after ingesting approximately 

2.8–4.2 mg I/day (0.05 mg/kg/day) in the form of sea-kelp tablets; her thyroid status reverted to normal 

within 6 months after she stopped taking the tablets (Shilo and Hirsch 1986). In another case, a 15-yearold male developed hyperthyroidism and thyrotoxicosis after receiving 1,440 mg I/day (23 mg/kg/day) as 

a saturated solution of potassium iodide for 4 months (Ahmed et al. 1974). The thyroid status reverted to 

normal within 6 months after the potassium iodide was discontinued. 

In a clinical study, eight healthy adult euthyroid females, who had nontoxic goiter, received oral doses of 

180 mg I/day (2.6 mg/kg/day) as a saturated potassium iodide solution for 10–18 weeks (Vagenakis et al. 

1972). Four of the eight patients developed clinical hyperthyroidism and thyrotoxicosis. Two patients 
IODINE 63 

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developed thyrotoxicosis within 7–10 weeks after supplementation began, which became more serious 

after supplementation was discontinued. One patient developed clinical hyperthyroidism after 10 weeks 

of supplementation and then became overtly thyrotoxic after the iodide supplementation was stopped. A 

fourth patient developed subclinical hyperthyroidism during iodide treatment and became clinically 

hyperthyroid with thyrotoxicosis after supplementation was stopped. 

What has been referred to as an epidemic of hyperthyroidism occurred in the midwestern United States 

between the years 1926 and 1928 (Kohn 1975, 1976). Clinical records suggest that the incidence of 

mortality from hyperthyroidism increased in Detroit during this period from approximately 2–4 deaths per 

100,000 to approximately 11 deaths per 100,000 at the peak of the epidemic. Although there is 

considerable debate about the origins of the epidemic, the advent of aggressive supplementation of the 

diet with iodide in midwestern endemic goiter areas has been implicated as a contributing factor. More 

recent and more rigorous epidemiologic designs have been applied to several populations in which dietary 

iodide was supplemented as a prophylaxis for iodine deficiency and goiter (Lind et al. 1998; Stanbury et 

al. 1998). These studies confirm that iodide supplementation of iodide-deficient diets does indeed result 

in a detectable increase in incidence of hyperthyroidism. 

In an epidemiology study conducted in Austria, the annual incidence of hyperthyroidism was evaluated in 

patients examined at nuclear medicine centers (where all thyroid examinations are conducted in Austria) 

before and after an upward adjustment was made in the use of iodized table salt in 1991 (Mostbeck et al. 

1998). The mean urinary iodide concentration before the adjustment was 42–78 μg I/g creatinine and 

after the adjustment was 120–140 μg I/g creatinine; these are approximately equivalent to 77–146 μg/day 

(1.1–2.1 μg/kg/day) and 225–263 μg/day (3.2–3.8 μg/kg/day), respectively. The analysis included 

392,820 patients examined between 1987 and 1995 in 19 nuclear medicine centers. A significant relative 

risk of hyperthyroidism, both for Graves’ disease and intrinsic thyroid autonomy, was found when the 

annual incidences of each in the postadjustment period (1991–1995) were compared to the preadjustment 

period (1987–1989). The highest relative risks were for Graves’ disease, which were 2.19 (2.01–2.38, 

95% confidence interval [CI]) for overt clinical disease and 2.47 (2.04–3.00) for subclinical disease. A 

regression analysis of the pre- and postadjustment incidences found a significant increasing trend for 

hyperthyroidism of both types in the postadjustment period and no trend in the preadjustment period. 

When the postadjustment incidence data were stratified by time periods 1990–1992 or 1993–1995, and by 

sex and age, higher relative risks were evident for intrinsic thyroid autonomy among males compared to 

females and in subjects older than 50 years compared to younger than 50 years. The incidence for 
 

 

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hyperthyroidism (all forms of overt or subclinical) was 70.1 per 100,000 in the preadjustment period and 

reached a peak of 108.4 per 100,000 in 1992, after the adjustment. 

Data collected on the incidence of hyperthyroidism in Tasmania also show that a 2–4-fold increase in 

hyperthyroidism cases occurred within a few months after diets were supplemented with iodide for 

preventing endemic goiter from iodide deficiency (Connolly et al. 1970). The approximate supplemental 

dose was 80–200 μg/day from the addition to potassium iodide to bread. Mean 24-hour urinary iodide 

excretion rates suggested a total postsupplementation iodide intake of approximately 230 μg/day 

(3.3 μg/kg/day); range, 94–398 μg/day (1.3 – 5.7 μg/kg/day), some of which may have came from sources 

other than supplemented bread (Connolly 1971a, 1971b). The highest incidence of hyperthyroidism after 

the iodine supplementation began occurred in people over 50 years of age (Stewart 1975; Stewart and 

Vidor 1976). 

A large multinational epidemiological study was conducted in Africa to evaluate the effectiveness and 

possible adverse consequences of the introduction of iodized salt into diets of populations residing in 

iodine-deficient and endemic goiter regions of Africa (Delange et al. 1999). In each study area, urine and 

table salt were collected from a group of 100–400 randomly-selected children, ages 6–14 years. Health 

care facilities were surveyed for information on thyroid disease in each area. In Zimbabwe, the incidence 

of hyperthyroidism increased by a factor of 2.6 within 18 months after the widespread introduction of 

iodized salt into the diet (from 2.8 in 100,000 to 7.4 in 100,000). Females accounted for 90% of the 

cases, with the highest incidence in the age group 60–69 years. The most common disorders were toxic 

nodular goiter (58%) and Graves’ disease (27%) (Todd et al. 1995). Urinary iodide concentration in 

children increased by a factor of 5–10 over this time period. Urine samples were reported as “casual 

samples” and, thus, there is a large uncertainty in translating the concentrations into intakes. Median 

urine iodide concentrations ranged from 290 to 560 μg/L. Reported estimates of iodide intake from salt 

and seafood were 500 μg/day (7.1 μg/kg/day) and 15–100 μg/day (0.2-1.4 μg/kg/day), respectively. 

Increased numbers of cases of thyrotoxicosis along with an increase in urinary iodide levels (from 16 to 

240 μg/L) occurred after iodized salt was introduced into the diet of an iodine-deficient population in the 

Kivu region of Zaire (Bourdoux et al. 1996). 

An epidemiological study in Switzerland examined the incidence of hyperthyroidism before and after the 

iodine content of salt was increased from 7.5 to 15 mg/kg (Baltisberger et al. 1995; Bürgi et al. 1998). 

The study population included 109,000 people. The mean urinary iodide concentration was 90 μg I/g 

creatinine before the supplementation and 150 μg I/g creatinine after the supplementation. This is 
IODINE 65 

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equivalent to an increase in intake from approximately 170 to 280 μg I/day (4 μg/kg/day), assuming a 

body weight of 70 kg. During the first year after supplementation began, the combined annual incidence 

of hyperthyroidism diagnosed as either Graves’ disease or toxic nodular goiter increased by 27% (from 

62.3/100,000 to approximately 80/100,000). Subsequent to this increase, the incidence of 

hyperthyroidism steadily declined to 44% of the presupplementation rates, with most of the decrease 

resulting from a decline in incidence of toxic nodular goiter. 

In an experimental study, adults with goiter who lived in an iodine-deficient region of Sudan received a 

single oral dose of 200, 400, or 800 mg iodine (3–11 mg/kg/day) as iodine oil (37–41 subjects per dose 

group) and their thyroid status was evaluated for a period of 12 months (Elnagar et al. 1995). 

Approximately half of the subjects were clinically hypothyroid with serum T4 concentrations <50 nmol/L 

and TSH concentrations >4 mU/L. One week after the iodine oil was administered, there was a doserelated increase in the incidence of serum TSH concentrations; 1 in 41 (2.5%) in the low-dose group, 3 in 

37 (8.1%) in the middle-dose group, and 10 in 39 (25.6%) in the high-dose group, although the number of 

subjects exceeding 4 mU/L was not dose-related. One subject in the low-dose group and three subjects in 

the high-dose group became hyperthyroid during the observation period. One of the high-dose subjects 

remained hyperthyroid 1 year after the dose of iodine oil. 

3.2.2.3 Immunological and Lymphoreticular Effects 

Information on immunological effects of oral exposure to stable iodine in humans relates to thyroid gland 

autoimmunity or immune reactions (e.g., ioderma). The highest NOAEL values and all reliable LOAEL 

values in each duration category for immunological and lymphoreticular effects from exposures by the 

oral route are presented in Table 3-1 and plotted in Figure 3-1. 

Excess iodide intake may be contributing factor in the development of autoimmune thyroiditis in people 

who are susceptible (Brown and Bagchi 1992; Foley 1992; Rose et al. 1997, 2002; Safran et al. 1987). 

Autoimmune thyroiditis is an inflammation of the thyroid gland that can lead to fibrosis of the gland, 

follicular degeneration, follicular hyperplasia, and hypothyroidism (Weetman 2000). IgG autoantibodies 

to thyroglobulin and thyroid peroxidase are consistent features of the disorder. Iodine appears to play an 

important role in autoimmune response as human lymphocytes recognize and proliferate in response to 

iodinated human thyroglobulin, but not iodine-free thyroglobulin (Rose et al. 1997). Poorly iodinated 

thyroglobulin is also less antigenic than iodine-rich thyroglobulin (Ebner et al. 1992) 
IODINE 66 

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Evidence for iodide inducing autoimmune thyroiditis in humans is incomplete. Autoimmunity, as 

indicated by IgG autoantibodies to thyroglobulin and thyroid peroxidase, has been observed in some 

studies in individuals whose iodide intakes were <500 μg/day (Hall et al. 1966; Kahaly et al. 1997, 1998; 

Koutras et al. 1996), and not in other studies in which intakes were similar or higher (Boyages et al. 1989; 

Li et al. 1987). This variable dose-response relationship suggests that factors other than iodide intake 

play a role in the development of thyroid autoimmunity. Several studies have been conducted of people 

who reside in endemic goiter areas and who received iodide supplementation. In one study, otherwise 

healthy adults who had goiter, but no evidence of clinical hypothyroidism or hyperthyroidism or 

antithyroid antibodies, received either an oral placebo (16 females, 15 males) or 200 μg I/day 

(3 μg/kg/day total intake) (16 females, 15 males) as potassium iodide for 12 months (Kahaly et al. 1997). 

Three subjects in the treatment group (9.7%, two females and one male) developed elevated levels of 

thyroglobulin and thyroid microsomal antibodies compared to none in the control group. Two of these 

subjects developed hypothyroidism and one subject developed hyperthyroidism; all three subjects 

reverted to normal thyroid hormone status when the iodide supplementation was discontinued. In a 

similar study, 31 adult euthyroid patients from an endemic goiter region who had goiter received either 

500 μg/day potassium iodide (382 μg I/day, 5.1 μg I /kg/day based on reported median body weight of 

75 kg) for 6 months, and 31 patients received 0.125 μg T4/day (Kahaly et al. 1998). Based on reported 

measurements of 24-hour urine iodide excretion, the preexisting iodide intake was approximately 

40 μg/day (range, 13–77, 0.6 μg/kg/day); thus, the total intake during treatment was approximately 

420 μg I/day (6 μg/kg/day). After 6 months of iodide supplementation, the mean 24-hour urinary iodide 

excretion rate was 415 μg/day, which is consistent with the estimate of a total iodide intake of 

approximately 420 μg/day. Six of the patients who received iodide (19%) developed high titres of 

thyroglobulin and thyroid microsomal antibodies, compared to none in the T4 group. Four of the high 

antibody patients became hypothyroid and two patients became hyperthyroid. The thyroid hormone 

status reverted to normal and antibody titres decreased during a 6-month period following the treatment in 

which the patients received a placebo. A comparison of autoantibody titres of 27 adult patients who were 

diagnosed with iodide-induced goiter and/or hypothyroidism with 55 healthy adults revealed a 

significantly greater incidence of antibodies to thyroglobulin in the goiter patients (13 of 27, 48%) than in 

the healthy controls (9 of 55, 16%) (Hall et al. 1966). Iodide doses in the goiter group varied from 24 to 

3,728 mg I/day (0.3–53 mg/kg/day). Koutras (1996) reported that 30% of a group of goiter patients 

developed thyroid autoimmunity several weeks after receiving 150 or 300 μg/day potassium iodide 

(115 or 130 μg I/day, 1.6–1.9 μg/kg/day); further details of the study were not provided. A small, but 

significant, rise in thyroid peroxidase antibodies was observed in Peace Corps workers in West Africa 
 

 

IODINE 67 

3. HEALTH EFFECTS 

when they were exposed for months to a greatly increased intake of iodine in their drinking water (Pearce 

et al. 2002). 

Other studies have not found increases in autoimmunity associated with iodine supplementation. For 

example, thyroid status was compared in groups of children, ages 7–15 years, who resided in two areas of 

China where drinking water iodide concentrations were either 462 μg/L (n=120) or 54 μg/L (n=51) 

(Boyages et al. 1989; Li et al. 1987). Although the subjects were all euthyroid with normal values for 

serum thyroid hormones and TSH concentrations, TSH concentrations were significantly higher in the 

high iodine group. The high iodide group had a 65% prevalence of goiter and a 15% prevalence of 

Grade 2 goiter compared to 15% for goiter and 0% for Grade 2 goiter in the low iodine group. There 

were no differences in the serum titres of either thyroglobulin or thyroid peroxidase antibodies between 

the high and low iodine groups. Urinary iodine was 1,236 μg I/g creatinine in the high iodine group and 

428 μg I/g creatinine in the low iodine group. Assuming a body weight of 40 kg and lean body mass of 

85% of body weight, the above urinary iodine/creatinine ratios are approximately equivalent to iodine 

excretion rates, or steady state ingestion rates of 1,150 μg/day (29 μg/kg/day) and 400 μg/day 

(10 μg/kg/day) in the high and low iodide groups, respectively. 

The effects of iodide on the development of autoimmune thyroiditis have been examined in animal 

models. In general, iodine does not induce autoimmune thyroiditis in outbred strains of rats; however, a 

susceptible inbred strain, the BB/Wor rat, has a high incidence of spontaneous autoimmune thyroiditis 

and does respond to iodide with an increased incidence of thyroid autoimmunity (Allen et al. 1986). This 

can be detected histologically as a lymphocytic infiltration of the gland (lymphocytic thyroiditis) 

accompanied by increased serum titres of antibodies to thyroglobulin, and increased serum TSH 

concentrations, indicating thyroid gland suppression (Allen and Braverman 1990). Weanling BB/Wor 

rats that were exposed to 0.05% iodide in drinking water for 8 weeks (approximately 85 mg/kg/day) had a 

significantly higher incidence of lymphocytic thyroiditis (27 of 35, 77%) compared to a control group 

(11 of 36, 30%) that received tap water. Similarly exposed outbred strains did not have an increase in 

lymphocytic thyroiditis. The spontaneous incidence of lymphocytic thyroiditis in the Buffalo strain rat (a 

Sprague-Dawley strain) is increased after neonatal thymectomy (Noble et al. 1976). In thymectomized 

Buffalo rats, 12 weeks of exposure to 0.05% iodide in drinking water (approximately 70 mg/kg/day) 

resulted in a significant increase in the incidence of lymphocytic thyroiditis (73%) compared to a control 

group that received tap water (31%) (Allen and Braverman 1990). The treatment group also had 

significantly higher serum TSH concentrations and significantly higher serum titres of antithyroglobulin 

antibody. In both of the above two studies, intake from food (Purina chow) was approximately 
IODINE 68 

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0.05 mg/kg/day. Obese strains of chickens are also highly susceptible to lymphocytic thyroiditis when 

exposed to excess iodine (Bagchi et al. 1985a). 

Oral exposure to markedly excess iodide can produce allergic reactions in sensitive subjects. The 

reactions include urticaria, acneiform skin lesions, and fevers (Kubota et al. 2000; Kurtz and Aber 1982; 

Rosenberg et al. 1972; Stone 1985). There were also cases of more serious reactions involving 

angioedema (localized edema), vasculitis, peritonitis and pneumonitis, and complement activation (Curd 

et al. 1979; Eeckhout et al. 1987). Both humoral and cell-mediated immune responses are thought to be 

involved (Curd et al. 1979; Rosenberg et al. 1972; Stone 1985). In general, reactions to iodide have 

occurred in association with repeated doses exceeding 300 mg I/day. 

Oral exposure to markedly excess iodide can produce skin lesions, referred to as ioderma, which are 

thought be a form of cell-mediated hypersensitivity and unrelated to thyroid gland function (Rosenberg et 

al. 1972; Stone 1985). Characteristic symptoms include acneiform pustules, which can coalesce to form 

vegetative (proliferating) nodular lesions on the face, extremities, trunk, and mucous membranes. The 

lesions regress and heal when the excess iodide intake is discontinued. The clinical literature includes 

cases of ioderma that occurred subsequent to oral doses of iodide at 300–1,000 mg I/day (5– 

14 mg/kg/day) (Baumgartner 1976; Khan et al. 1973; Kincaid et al. 1981; Kint and Van Herpe 1977; 

PeZa-Penabad et al. 1993; Rosenberg et al. 1972; Shelly 1967; Soria et al. 1990). However, in many of 

these cases, preexisting disease and related drug therapy may have contributed to the reaction to the 

iodine; thus, the dose-response relationship for ioderma in healthy people remains highly uncertain. A 

typical regimen in the case literature was potassium iodide co-administered with theophylline and 

phenobarbital for treatment of obstructive lung disease. In at least two cases, transient dermal lesions 

typical of ioderma were elicited by a single oral dose of 360 or 500 mg iodide (5.1 or 7.1 mg/kg/day), as 

potassium iodide, and similar lesions were induced in these same patients by oral doses of aspirin, 

suggesting a possible cross sensitivity (Shelly 1967). In a more typical case, an adult male developed 

proliferating (vegetative) dermal lesions of the face, scalp, and trunk 5 days after receiving approximately 

300 mg I/day (5.1 mg/kg/day) as potassium iodide (390 mg/day), along with penicillin for an acute 

respiratory tract infection (Soria et al. 1990). The lesions healed within 4 weeks after the potassium 

iodide was discontinued. Another adult male developed a vegetative dermal lesion of the neck and trunk 

after receiving approximately 600 mg I/day (10 mg/kg/day) as potassium iodide (720 mg/day) along with 

theophylline for obstructive pulmonary disease for 8 months (Soria et al. 1990). The lesions regressed 

within 3 weeks after the potassium iodide was discontinued and returned when an oral provocation dose 

of potassium iodide was administered. Another case of ioderma occurred in an adult female who received 
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oral doses of approximately 740 mg I/day (11 mg/kg/day) as potassium iodide (970 mg/day) for 

6 months, as part of a treatment for obstructive lung disease (Kincaid et al. 1981). Other drugs included 

in the patient’s treatment were ephedrine, theophylline, and phenobarbital. The lesions occurred on the 

face and conjunctiva of the eye, and healed several weeks after the potassium iodide was discontinued. A 

similar case occurred in an adult woman, similarly treated for 1 year with 990 mg I/day (14 mg/kg/day) as 

potassium iodide (1,300 mg/day) for asthma (along with ephedrine, theophylline, and phenobarbital) 

(Rosenberg et al. 1972). The vegetative lesions occurred on her face and arms and healed within 3 weeks 

after the potassium iodide was discontinued. In a more complex case, an adult female who was being 

treated for a variety of disorders, including polyarteritis nodosa, for which she was receiving 

cyclophosphamide and prednisone, and pneumonia, for which she was receiving an expectorant 

containing potassium iodide, developed vegetating dermal lesions on her face (Soria et al. 1990). The 

lesions healed within 1 month after the iodide expectorant was discontinued. She received vidarabine 

during this period, as the dermal lesions were, at that time, suspected of being a herpes simplex infection. 

One week after receiving approximately 400 mg I/day (6 mg/kg/day) as potassium iodide (520 mg/day), 

similar lesions of the skin and oral mucosa developed. The lesions healed within 3 weeks after the 

potassium iodide was discontinued. 

Oral exposures to markedly excess iodide can induce fevers that are thought to have an immunological 

basis, and appear to be related to thyroid function (Horn and Kabins 1972; Kurtz and Aber 1982). 

Reported clinical cases have almost always involved a preexisting disease, usually pneumonia or 

obstructive lung disease in which potassium iodide was administered along with other drugs, including 

antibiotics, barbiturates, and methylxanthines; thus, the dose-response relationship for healthy people is 

highly uncertain. In one case, recurrent fevers occurred in an adult male who was receiving oral doses of 

approximately 1,080 mg I/day (15 mg/kg/day) as a potassium iodide solution (assumed, but not specified 

in the case report, to be a saturated solution) for approximately 15 years (Kurtz and Aber 1982). The 

fevers stopped within 2 weeks after the potassium iodide was discontinued. In another case, an adult 

male developed a fever 8 days after the start of a daily regimen of approximately 1,440 mg I/day as a 

saturated solution of potassium iodide for treatment of a respiratory illness; the fever stopped within 

3 days after the potassium iodide was discontinued (Horn and Kabins 1972). In another case, an adult 

female developed a fever after a dosage of approximately 1,620 mg I/day (23 mg/kg/day) as a saturated 

potassium iodide solution along with ampicillin to treat pneumonia (Horn and Kabins 1972). The fever 

stopped within 36 hours after the potassium iodide was discontinued; at the same time, a regimen of 

diazepam, secobarbitol, and glycerol guaiacolate was administered. The fever returned when a challenge 

dose of potassium iodide was administered. A fourth case involved an adult female diabetic patient who 
IODINE 70 

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received 1,080 mg I/day (15 mg/kg/day) as a saturated potassium iodide solution along with antibiotics, 

cortisone, and aminophylline for pneumonia (Horn and Kabins 1972). Four days after the potassium 

iodide treatments began, the patient developed a fever, which stopped when the potassium iodide was 

discontinued. 

3.2.2.4 Neurological Effects 

Exposure to excess stable iodine has been shown to produce subclinical hypothyroidism, and in sensitive 

individuals who have underlying thyroid disease, may take the form of hypothyroidism. Sensitive 

populations include fetuses, newborn infants, and individuals who have thyroiditis or a history of Graves’ 

disease, many of whom have abnormal autoimmune disorders (see Section 3.2.2.2, Endocrine Effects). 

Of these iodine-induced forms of hypothyroidism, that occurring in the fetus or newborn infant has the 

greatest potential for producing neurological effects. This is because thyroid hormones are essential to 

the development of the neuromuscular system and brain. An iodine-induced hypothyroid state can result 

in delayed or deficient brain and neuromuscular development of the newborn (Boyages 2000b). Iodineinduced hypothyroidism in an older child or adult would be expected to have little or no deleterious 

effects on the neuromuscular system. 

Exposure to excess stable iodine can also produce hyperthyroidism in sensitive individuals (see 

Section 3.2.2.2, Endocrine Effects). These include people who are initially iodine deficient, those who 

have thyroid disease, including nodular goiter, Graves’ disease, those who have been previously treated 

with antithyroid drugs, , and those who have developed thyrotoxicosis from amiodarone or interferonalpha treatments (Roti and Uberti 2001). Patients who develop thyrotoxicosis may experience 

neuromuscular disorders, including myopathy, periodic paralysis, myasthenia gravis, peripheral 

neuropathy, tremor, and chorea (Boyages 2000a); however, these are not likely to occur in iodine-induced 

hyperthyroidism, except in sensitive groups, already at risk for neurological problems. 

3.2.2.5 Reproductive Effects 

Oral exposure to excess stable iodine may produce hypothyroidism or hyperthyroidism (see 

Section 3.2.2.2, Endocrine Effects) and may cause disruption of reproductive function secondary to 

thyroid gland dysfunction. Hypothyroidism can produce changes in the menstrual cycle in humans, 

including menorrhagia (excessive uterine bleeding) and anovulation (no ovulation). Abortions, stillbirths, 

and premature births have also been associated with hypothyroidism (Longcope 2000a). Reproductive 
IODINE 71 

3. HEALTH EFFECTS 

impairments associated with hyperthyroidism include amenorrhea, alterations in gonadotropin release and 

sex hormone-binding globulin (SHBG), and changes in the levels and metabolism of steroid hormones in 

both females and males (Longcope 2000b). 

The highest NOAEL values and all reliable LOAEL values in each duration category for reproductive 

effects from exposures by the oral route are presented in Table 3-1 and plotted in Figure 3-1. 

3.2.2.6 Developmental Effects 

Exposure to excess stable iodine may produce hypothyroidism and hyperthyroidism (see Section 3.2.2.2, 

Endocrine Effects), which could give rise to developmental defects secondary to thyroid gland 

dysfunction (Boyages 2000a, 2000b). Hypothyroidism may be associated with impairment in 

neurological development of the fetus or growth retardation (Boyages 2000a, 2000b; Snyder 2000a). 

Martin and Rento (1962) reported two cases of goiter and severe transient hypothyroidism, without 

neurological sequellae in infants born to mothers who ingested potassium iodide during pregnancy; the 

approximate dosages were 920 and 1,530 mg I/day (13 and 22 mg/kg/day). Growth acceleration may 

occur in childhood hyperthyroidism, which is thought to be related to accelerated pituitary growth 

hormone turnover or a direct effect of thyroid hormone on bone maturation and growth (Snyder 2000b). 

The highest NOAEL values and all reliable LOAEL values in each duration category for developmental 

effects from exposures by the oral route are presented in Table 3-1 and plotted in Figure 3-1. 

3.2.2.7 Cancer 

Cancer effect levels (CELs) for stable iodine exposures by the oral route are presented in Table 3-1 and 

plotted in Figure 3-1. 

The relationship between stable iodine intake and thyroid cancer has been examined in several 

epidemiology studies. The results of these studies suggest that increased iodide intake may be a risk 

factor for thyroid cancer in certain populations, in particular, populations residing in iodine-deficient 

(Bacher-Stier et al. 1997; Harach and Williams 1995; Franceschi 1998; Franceschi and Dal Maso 1999). 

Studies of populations in which iodine intakes are sufficient have not found significant associations 

between iodine intake and thyroid cancer (Horn-Ross et al. 2001; Kolonel et al. 1990) however, a 

recurrent observation is an apparent shift in the histopathology towards a higher prevalence of papillary 
IODINE 72 

3. HEALTH EFFECTS 

cancers, relative to follicular cancers, after increased iodine intake (e.g., dietary supplementation) in 

otherwise iodine-deficient populations (Bakiri et al. 1998; Belfiore et al. 1987; Feldt-Rasmussen 2001; 

Kolonel et al. 1990; Pettersson et al. 1991, 1996). 

Two case control studies have been conducted on populations whose iodine intakes are sufficient; both 

found no significant association between iodine intake and thyroid cancer. A case control study of 

women residents of the San Francisco Bay area of the United States examined dietary habits, including 

iodine intake and other variables in 608 cases of thyroid cancer and 558 age- and ethnicity-matched 

controls, diagnosed during the period 1995–1998 (Horn-Ross et al. 2001). Dietary iodine intakes were 

estimated based on the results of a dietary habits questionnaire and published compilations of the iodine 

content of various foods. When cases and controls were classified according to dietary iodine intake 

(quintile), the risk of papillary thyroid cancer was significantly lower in women who consumed >273 μg 

I/day compared to women who consumed <273 μg I/day (<4.2 μg/kg/day); the odds ratio (OR) for the 

highest quintile (>537 μg I/day, >8.3 μg/kg/day) was 0.49 (95% confidence interval [CI] 0.29–0.84). 

When cases and controls were classified according to seafood consumption rates, ORs for papillary 

thyroid cancers were significantly elevated for consumption of >2.0 g/day of fish sauce/dried salted fish 

compared to none (limited to Asian women; OR 2.3, 95% CI 1.3–4.0). ORs for other types of seafood 

consumed were not significant. Other variables for which ORs were statistically significant included 

medical radiation of head or neck (OR 2.7, 95% CI 1.2–6.2), history benign goiter or thyroid nodules 

(OR 4.7, 95% CI 3.1–7.2), and family history of thyroid disease (ORs ranged from 1.5 hyper- or 

hypothyroidism to 6.1 for thyroid cancer). 

Another case control study of residents of Hawaii examined dietary habits, including iodine intake and 

other variables in 191 cases of thyroid cancer and 441 age- and sex-matched controls, diagnosed during 

the period 1980–1987 (Kolonel et al. 1990). Dietary iodine intakes were estimated based on the results of 

a dietary habits questionnaire and published compilations of the iodine content of various foods. Female 

cases had significantly higher dietary iodine intakes than controls, although the group mean differences 

were not substantial; cases, 394 μg I/day (6.1 μg/kg/day); controls, 326 μg I/day (5.0 μg/kg/day). When 

cases and controls were classified according to dietary iodine intake (quartile), the ORs for thyroid cancer 

in females increased with increasing iodine intake; however, ORs were not statistically significant and 

there were no significant trends in the OR with increasing iodine intake. Other variables for which ORs 

were statistically significant included miscarriage (2.4), use of fertility drugs (4.2), and the combination of 

either of the former characteristics with an iodine intake exceeding 300 μg I/day or 4.6 μg/kg/day (4.8 or 

7.3, respectively), or seafood intake exceeding 27 g/day (3.0 or 6.9, respectively). A limitation of this 
IODINE 73 

3. HEALTH EFFECTS 

study is that iodine intakes were estimated from dietary surveys and were not verified by measurements of 

urinary excretion of iodine. 

Several cohort studies conducted on populations residing in iodine-deficient regions have found 

significant associations between thyroid cancer and iodine intake. A cohort study compared thyroid 

cancer rates in iodine-sufficient and iodine-deficient regions of Sweden during the period 1958–1981 

(Pettersson et al. 1991, 1996). Iodine-deficient regions were defined as having had a goiter prevalence 

that was >33% in females and >15% in males, based on a 1930 survey. In Sweden, dietary iodine intake 

has increased over the study period as a result of dietary supplementation, which began in 1936 and was 

subsequently increased in 1966 and 1971 (Pettersson et a. 1996). Thus, iodine deficiency, even in the 

previously deficient regions has diminished. A multivariate model that included sex, age, dates of 

diagnosis, and region (i.e., iodine deficient or sufficient) as variables was applied to a sample of 

5,838 thyroid cancer cases to estimate adjusted RR for thyroid cancer, where RR was the ratio of the 

adjusted cancer incidence rates for iodine-deficient:iodine-sufficient regions. The RR for papillary 

thyroid cancer was 0.8 (95% CI, 0.73–0.88), suggesting lower risk in the iodine-deficient regions, relative 

to the iodine-sufficient regions. The RR for follicular thyroid cancer was 1.98 (1.60–2.4) in males and 

1.17 (1.04–1.32) in females, suggesting a 1.2- to 2-fold higher risk for follicular cancer in populations 

living in the iodine-deficient regions, relative to iodine-sufficient regions. The prevalence of papillary 

cancers was significantly higher, and follicular cancers were significantly lower in the iodine sufficient 

areas. Analysis of incidence of thyroid cancer as a function of dates of diagnosis revealed a significant 

trend for increasing follicular cancers in the iodine-deficient areas, but not in the iodine-sufficient areas. 

A significant trend for increasing papillary cancers was evident in both the iodine-sufficient and iodinedeficient regions. 

Another cohort study examined the prevalence of thyroid cancer during the period 1979–1985 in 

populations living in iodine-deficient and iodine-sufficient areas of Sicily (Belfiore et al. 1987). Mean 

urinary iodine excretion rate in the deficient regions was approximately 19–43 μg I/day (0.3– 

0.6 μg/kg/day) and, in the iodine-sufficient regions, was approximately 114 μg I/day (1.6 μg/kg/day); the 

intakes in the two regions would be expected to be similar to urinary excretion rates. Randomly selected 

subjects from both regions were subjected to radioiodine thyroid scans to determine the presence of cold 

thyroid gland nodules, indicative of a possible tumor with suppressed iodine uptake. The prevalence of 

cold nodules in the iodine deficient region was significantly greater (72 of 1,683, 4.3%) than in the 

iodine-sufficient group (21 of 1,253, 1.7%). In the second phase of this study, all patients who had cold 

nodules in the two study areas, 911 patients from the iodine-deficient region, and 2,537 patients from the 
IODINE 74 

3. HEALTH EFFECTS 

iodine-sufficient region, were biopsied. The prevalence of thyroid cancer among patients who had one or 

more cold nodules was higher in the iodine-sufficient region (5.48%) than in the iodine-deficient region 

(2.96%). The prevalence of papillary tumors, relative to that of follicular tumors, was higher in the 

iodine-sufficient region (3.8) than in the iodine-deficient region (1.0). When the thyroid cancer 

prevalence among patients with cold nodules was adjusted for the estimated prevalence of cold nodules in 

the two regions, the estimated prevalence of thyroid cancer in the iodine-deficient region was 

significantly higher (127 in 100,000) than in the iodine-sufficient region (93 in 100,000). 

The results of several ecological studies suggest that the incidence of thyroid cancer may increase in 

endemic goiter regions after supplementation of the diet with iodine. In Austria, iodized salt was 

introduced into the diet in 1963 and then increased further in 1991. The mean urinary iodide 

concentration before the adjustment was 42–78 μgI/g creatinine and after the adjustment was 120– 

140 μgI/g creatinine; these are approximately equivalent to 77–146 μg/day (1–2 μg/kg/day) and 225– 

263 μg/day (3–4 μg/kg/day), respectively (Bacher-Stier et al. 1997; Mostbeck et al. 1998). A 

retrospective analysis of medical records in the Tyrol region of Austria (1,063,395 inhabitants) concluded 

that the incidence of thyroid cancer increased from 3.1 per 100,000 year for the period 1960–1970 to 

7.8 for the period 1990–1994 (Bacher-Stier et al. 1997). The prevalence of papillary tumors appeared to 

increase relative to that of follicular tumors after supplementation; the ratio of papillary:follicular tumors 

was 0.6 before supplementation and 1.5 after supplementation. Improved diagnosis may have contributed 

to the increased incidence. In support of this, a trend was observed towards increased prevalence of less 

advanced tumor stages in 439 patients for which complete medical records were available. The authors 

reported that “no excessive natural radiation has been found in Tyrol”. 

A retrospective analysis of 1,000 consecutive patient records from endocrine wards in Algiers, recorded 

during the period 1967–1991, revealed significantly greater prevalence of differentiated follicular thyroid 

tumors in patients who resided in an endemic goiter region (53.6%; n=581) than in nonendemic regions 

(44.0%; n=236) (Bakiri et al. 1998). The prevalence of follicular tumors was significantly greater than 

that of papillary tumors in the endemic areas, whereas follicular tumors were less prevalent than papillary 

tumors in the nonendemic region. The ratio of papillary:follicular tumors was 1.2 in the endemic region 

and 0.8 in the nonendemic region. The mean urinary iodide concentration in the goiter endemic area was 

<50 μg I/g creatinine and was >80 μg I/g creatinine in the nonendemic region; these are approximately 

equivalent to <95 μg/day (1.2 μg/kg/day) and >150 μg/day (2.1 μg/kg/day), respectively. 
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3. HEALTH EFFECTS 

A retrospective analysis of 144 cases of thyroid cancer in the Salta region of Argentina, diagnosed during 

the period 1960–1980, found that the prevalence of papillary tumors appeared to increase relative to that 

of follicular tumors after dietary iodine supplementation was initiated as prophylaxis for goiter; the ratio 

of papillary:follicular tumors was 1.8 before supplementation and 3.0 after supplementation (Harach and 

Williams 1995; Harach et al. 1985). The mean urinary iodide concentration before the supplementation 

was 9 μg I/g creatinine and after the supplementation was 110–150 μg I/g creatinine; these are 

approximately equivalent to 17 μg I/day (0.2 μg/kg/day) and 205–280 μg I/day (3–4 μg/kg/day), 

respectively. 

3.2.3 Dermal Exposure 

3.2.3.1 Death 

No information was located on deaths associated with dermal exposure to iodine. 

3.2.3.2 Systemic Effects 

No information was located regarding respiratory, cardiovascular, gastrointestinal, hematological, 

musculoskeletal, hepatic, renal, dermal, ocular, body weight, or other systemic effects of dermal exposure 

to stable iodine. 

Endocrine Effects. Povidone-iodine is a complex of I2 and polyvinyl pyrrolidone and is widely used 

as a topical antiseptic for mouth, skin, and vaginal infections, and surgical procedures. Topical 

preparations of povidone-iodine contain approximately 9–12% iodine, of which a small fraction is in free 

solution (Lawrence 1998; Rodeheaver et al. 1982). Dermal exposure to povidone-iodine has induced 

acute toxicity in humans. In one case, hyperthyroidism and thyrotoxicosis developed in an adult male 

who, for 6 months, received povidone-iodine skin washes to treat dermal ulcers but had no other history 

of excess iodine intake or treatment with iodine-containing drugs (Shetty and Duthie 1990). The patient 

had elevated antithyroglobulin and thyroid peroxidase (thyroid microsomal) antibodies. The disorder 

eventually required therapy with propylthiouracil and radioiodine. It is possible that the povidone-iodine 

exposure may have aggravated a pre-existing autoimmune disorder in the patient rather than having been 

the cause of the thyrotoxicosis. 
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3. HEALTH EFFECTS 

In a study of 27 neurological ward patients who received topical povidone-iodine treatments for various 

procedures and for periods of 3–133 months, serum iodide, T4, and FT4 concentrations were significantly 

higher than a group of 13 patients who did not receive povidone-iodine treatments (Nobukini et al. 1997). 

Eight of the 27 patients who received povidone-iodine treatments were clinically hyperthyroid (serum FT4 

concentration above the normal range) and 3 of 27 patients were suspected of having subclinical 

hypothyroidism (serum TSH concentrations above the normal range). None of these patients had elevated 

antithyroglobulin or thyroid peroxidase antibodies, suggesting that thyroid autoimmunity was not the 

cause of the apparent thyroid hormone disturbances. Serum FT4 concentrations were significantly 

positively correlated with the duration of povidone-iodine exposure. In a similar study, the thyroid 

hormone status of 16 healthy nurses who regularly used povidone-iodine formulations, mainly for handwashing and gargling, was compared to that of 16 hospital workers who had little or no contact with 

povidone-iodine (Nobukini and Kawahara 2002). Mean serum FT4 levels were slightly, but significantly, 

higher in the groups of nurses compared to the comparison group (1.30±0.15 ng/dL, 1.15"0.14, p<0.01); 

however, serum TSH, FT3, and FT4 levels were within the normal range for all study participants. 

Several cases of hypothyroidism induced by topical applications of povidone-iodine to wounds have been 

described. In one case, an adult female was exposed to approximately 22 mg iodine as povidone-iodine, 

3 days/week for 22 months, when an open fistula was swabbed with povidone-iodine and packed with 

iodoform impregnated gauze (Prager and Gardner 1979). The patient developed clinical hypothyroidism 

with thyroid enlargement and became euthyroid within 6 weeks after the iodine treatment of the wound 

was discontinued. Another patient who had a small nodular goiter developed hyperthyroidism following 

betadine irrigation of a mediastinal wound, after cardiac bypass surgery (Rajatanavin et al. 1984). In 

another study, mouth rinsing with iodine-containing mixtures for gingivitis, for 6 months, induced a small 

decrease in serum T4 and a compensatory rise in serum TSH; however, all values were well within the 

normal range (Ader et al. 1988). 

Povidone-iodine gels are used for vaginal lubrication during labor checks prior to delivery. Use of 

povidone-iodine gels has been associated with increased serum iodide concentrations as well as changes 

in thyroid hormone status, indicative of subclinical thyroid gland suppression. In a study of 18 women 

who received intravaginal treatments with povidone-iodine gel during labor checks, serum iodide 

concentrations were significantly higher after the applications than before the applications (Jacobson et al. 

1984). Serum TSH concentrations were significantly elevated (5.9 mU/L) in the povidone-iodine group 

compared to a group of 13 women who received vaginal lubricants that did not contain iodine 

(1.9 mU/L). There were no differences in the levels of T4 or T3 between the iodine and no-iodine groups. 
IODINE 77 

3. HEALTH EFFECTS 

Topical application of povidone-iodine during labor has been found to produce thyroid gland suppression 

in newborns. In a study of 30 women who received topical povidone-iodine in preparation for a cesarean 

section, newborn serum TSH concentrations (cord blood) were significantly higher than in newborns from 

12 mothers who also underwent a cesarean section, but who were not exposed to povidone-iodine 

(Novaes et al. 1994); however, the levels were not above the normal range for newborns (>20 mU/L, de 

Zegher et al. 1994; Momotani et al 1992). Serum concentrations of T4 and T3 were not different in the 

two groups of newborns. In a study of infants delivered by mothers who received intravaginal povidoneiodine during labor checks, serum TSH concentrations were significantly higher and T4 and T3 

concentrations were significantly lower compared to 18 control infants delivered from mothers who were 

not exposed to povidone-iodine during labor (l’Allemand et al. 1983). Twenty percent of the infants from 

the treated mothers had serum TSH concentrations above the normal range for newborn infants 

(>20 mU/L) and serum T4 concentrations below the normal range (<7 μg/dL) and, thus, were 

hypothyroid. All infants were euthyroid at 14 days after birth. 

Daily douching with betadine for 14 days was associated with an increase in serum iodide levels, small 

decreases in T4, small rises in serum TSD, and a decrease in thyroid iodide uptake, All values returned to 

baseline within 2 weeks after the exposure (Safran et al. 1982). 

Use of povidone-iodine for topical disinfection and surgical wound disinfection in infants has been shown 

to induce hypothyroidism and hyperthyroidism. In a prospective study, 17 premature infants (#36 weeks 

gestation), who were euthyroid with no indications of thyroid disorders, received topical povidone-iodine 

applications for various procedures beginning within 24 hours of birth (Brown et al. 1997). Five of 

17 (29%) of the infants had a significant decrease (<50% of pretreatment value) in their serum T4 

concentrations compared to none of 14 control infants who received the same clinical procedures, but 

with topical application of a noniodine disinfectant (chlorhexidine). These five infants had serum T4 

concentrations that were below 40 nmol/L (3.1 μg/dL) 4–6 days after exposure to povidone-iodine, 

indicating mild hypothyroidism (60 nmol/L is low end of normal range), although their serum TSH 

concentrations were not elevated (<20 mU/L, de Zegher et al. 1994; Momotani et al. 1992). Their T4 

status reverted to normal within 10–25 days after treatment. There were no significant differences 

between the treatment and control group mean values for serum T4 or TSH. Iodide concentrations in 

random untimed urine samples were approximately 24 times higher in the treatment group (1,800– 

3,600 μg/L) than in the control group (90–150 μg/L), indicating absorption of some of the topically 

applied iodine. In a study of 30 intensive care ward infants who received frequent topical applications of 
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3. HEALTH EFFECTS 

povidone-iodine for various procedures, five infants (20%) developed clinical hypothyroidism with serum 

T4 and T3 concentrations below the normal range, serum TSH concentrations above the normal range, and 

thyroid gland enlargement (Chabrolle and Rossier 1978a, 1978b). Urinary iodide excretion at the time of 

treatment ranged from 2.9 to 4.8 mg I/day in four of the patients and was 0.14 mg I/day in one of the 

patients, suggesting daily absorbed doses of iodine in this same range. The thyroid hormone status 

reverted to normal after the povidone-iodine treatments were discontinued. A 30% incidence of 

hypothyroidism was reported in 10 intensive care ward newborns who received topical povidone-iodine 

applications for various procedures for >2 days in duration (l’Allemand et al. 1987). A newborn infant 

who received povidone-iodine irrigations of wound drains became clinically hyperthyroid without 

elevated serum titres of antithyroglobulin or thyroid peroxidase (thyroid microsomal) antibodies (Bryant 

and Zimmerman 1995). The patient became euthyroid within 1 month after the povidone-iodine 

irrigations were discontinued. Thyroid status of four infants with spinal bifida who received daily 

povidone-iodine antiseptic dressings were followed; two of the four patients became hypothyroid after 

4 weeks of exposure and required treatment with T4 (Barakat et al. 1994). The patients became euthyroid 

within 9 months after the povidone-iodine applications were discontinued. In a study of 47 neonatal 

intensive care patients who were exposed to topical povidone-iodine for varying lengths of time, no 

evidence of hypothyroidism was found (Gordon et al. 1995). 

3.2.3.3 Immunological and Lymphoreticular Effects 

Dermal exposures to povidone-iodine have produced localized and systemic allergic responses in humans. 

In one case, an adult male developed a reaction to application of povidone-iodine to an arm wound. The 

reaction consisted of itching of the extremities, urticaria, and angioedema (of the face), which were 

ameliorated with antihistamine treatment (López Sáez et al. 1998). A serum specific IgE assay detected 

reactivity in the patient’s serum to various povidone-iodine and various other iodine preparations. 

Several case reports have been published that describe dermatitis in people who have been exposed to 

topical applications of povidone-iodine and subsequently reacted to dermal challenge tests to povidoneiodine (Nishioka et al. 2000; Okano 1989; Tosti et al. 1990). 

Intravaginal applications of povidone-iodine have also induced allergic reactions in humans. In one case, 

an adult woman developed a bronchospastic reaction in response to application of povidone-iodine and an 

iodine-containing contrast medium (Moneret-Vautrin et al. 1989). The patient reacted in a dermal 

challenge test to povidone-iodine, but not the contrast medium, and the patient’s serum tested positive for 

histamine release and basophil degranulation in vitro. In another case, anaphylaxis occurred in a patient 
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3. HEALTH EFFECTS 

after an intravaginal application of povidone-iodine. The patient reacted to povidone-iodine in a dermal 

challenge test (Waran and Munsick 1995). 

Although the above cases appear to implicate povidone-iodine as the causative agent in the allergic 

responses reported, povidone itself, without iodine, has also been shown to produce allergic reactions and 

anaphylaxis in humans and may have contributed to the reactions observed in some of these cases (Garijo 

et al. 1996). 

3.2.3.4 Neurological Effects 

No information was located on neurological effects associated with dermal exposure to iodine. Dermal 

exposure to excess iodine may produce mild transient hypothyroidism and hyperthyroidism (see 

Section 3.2.3.2, Endocrine Effects), which could give rise to neurological manifestations of thyroid gland 

dysfunction including impairments in neurological development and myopathies (Boyages 2000a, 

2000b). However, based on the mild effects that have been observed in association with dermal 

exposures, such severe neurological sequellae are not likely. 

3.2.3.5 Reproductive Effects 

No information was located on reproductive effects associated with dermal exposure to iodine. Dermal 

exposure to excess iodine may produce mild transient hypothyroidism and hyperthyroidism (see 

Section 3.2.3.2, Endocrine Effects). Either could give rise to disruption of reproductive systems 

secondary to thyroid gland dysfunction; however, based on the mild effects that have been observed in 

association with dermal exposures, significant disruptions of reproductive function are not likely. 

Hypothyroidism can produce changes in the menstrual cycle in humans, including menorrhagia 

(excessive uterine bleeding) and anovulation (no ovulation). Abortions, stillbirths, and premature births 

have also been associated with hypothyroidism (Longcope 2000a). Reproductive impairments associated 

with hyperthyroidism include amenorrhea, alterations in gonadotropin release, and sex hormone-binding 

globulin (SHBG), and changes in the levels and metabolism of steroid hormones in both females and 

males (Longcope 2000b). 
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3.2.3.6 Developmental Effects 

No information was located on developmental effects associated with dermal exposure to iodine. Dermal 

exposure to excess iodine may produce mild transient hypothyroidism and hyperthyroidism (see 

Section 3.2.3.2, Endocrine Effects). Use of povidone-iodine for topical disinfection and surgical wound 

disinfection in infants has been shown to induce hypothyroidism and hyperthyroidism, and topical 

application of povidone-iodine during labor has been found to produce transient, mild hypothyroidism in 

newborns (see Section 3.2.3.2, Endocrine Effects). Hypothyroidism or hyperthyroidism could give rise to 

developmental effects secondary to thyroid gland dysfunction (Boyages 2000a, 2000b). Developmental 

effects of hypothyroidism include severe impairment in neurological development of the fetus known as 

cretinism, or growth retardation (Boyages 2000a, 2000b; Snyder 2000a). Severe impairment of 

neurological development or growth retardation are effects only seen with severe, long-standing thyroid 

deficiency, not the transient form that has been associated with dermal iodine-induced hypothyroidism. 

Growth acceleration may occur in childhood hyperthyroidism, which is thought to be related to 

accelerated pituitary growth hormone turnover or a direct effect of thyroid hormone on bone maturation 

and growth (Snyder 2000b). 

3.2.3.7 Cancer 

No information was located on cancer in association with dermal exposure to iodine. 

3.2.4 External Exposure 

No information was located on health effects associated with external exposure to radioiodine. 

3.3 DISCUSSION OF HEALTH EFFECTS FOR RADIOACTIVE IODINE BY ROUTE OF 

EXPOSURE 

Section 3.3 discusses radiation toxicity associated with exposure to radionuclides of iodine and is 

organized in the same manner as that of Section 3.2, first by route of exposure (inhalation, oral, and 

external) 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). 
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3. HEALTH EFFECTS 

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

figures. The points in the figures showing NOAELs or LOAELs reflect the actual dose (levels of 

exposure) used in the studies. Refer to Section 3.2 for detailed discussion of the classification of 

endpoints as a NOAEL, less serious LOAEL, or serious LOAEL. 

Levels of exposure associated with carcinogenic effects (Cancer Effect Levels, CELs) of radioiodine are 

indicated in Tables 3-1, and 3-2 and Figures 3-1 and 3-2. Because cancer effects could occur at lower 

exposure levels, Figures 3-1 and 3-2 also show a range for the upper bound of estimated excess risks, 

ranging from a risk of 1 in 10,000 to 1 in 10,000,000 (10-4 to 10-7), as developed by EPA. 

Refer to Appendix B for a User's Guide, which should aid in the interpretation of the tables and figures 

for Levels of Significant Exposure. 

3.3.1 Inhalation Exposure 

A large amount of epidemiological literature exists on the heath outcomes in populations exposed to 

radioiodine as a result of releases from explosions of nuclear bombs (e.g., Marshall Islands, Nevada Test 

Site), operational releases from nuclear fuel reprocessing facilities (e.g., Hanford Nuclear Site), and 

accidental releases from nuclear power plants (e.g., Chernobyl). Releases of these types resulted in mixed 

exposures to a variety of radioisotopes, and radiation doses from both external and internal exposure. 

However, doses from radioiodine that are significant to health effects derive largely from internal 

exposure to the thyroid gland as a result of absorption and uptake of radioiodine into the thyroid gland 

(see Section 3.5.2.2). Inhalation of airborne radioiodine is likely to have occurred after each of these 

releases and prior to ground deposition of radioiodine. However, the major contributors to thyroid 

radiation dose in each of these incidents are thought to have been from ingestion of milk, grains, 

vegetables, and water contaminated from atmospheric deposition of radioiodine. Ingestion of human 

breast milk is also considered to have been a contributor to doses received in nursing infants. For 

example, it has been estimated that, in seven Ukraine cities following releases of radioiodine from the 

Chernobyl nuclear power plant, inhalation of 131I contributed between 2 and 13% of total absorbed 

radiation dose, whereas the ingestion pathway contributed from 87 to 98% (IAEA 1991). In the Marshall 

Islands, after the BRAVO bomb test, the inhalation pathway is thought to have contributed <1% of the 

absorbed radioiodine, with the ingestion pathway contributing 80–99% (Lessard et al. 1985). Because of 

the more substantial contribution of the oral pathway to the absorbed thyroid radiation doses, health 
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3. HEALTH EFFECTS 

effects studies related to the Chernobyl accident, the Marshall Islands, the Hanford Nuclear Site, and the 

Nevada Test Site are discussed in the oral section of this profile (Section 3.3.2). However, the effects 

observed that have been related to the internal radiation dose to the thyroid gland are also directly relevant 

to inhalation exposures since inhaled radioiodine absorbed from either the respiratory tract or 

gastrointestinal tract would be expected to distribute to the thyroid gland (see Section 3.5.2.1). 

3.3.1.1 Death 

Deaths related to thyroid cancers (or to other cancers or causes) following the Chernobyl accident are 

being studied with well-controlled epidemiological designs and dose reconstruction efforts, and possible 

associations between mortality and radioiodine exposures may become evident once these studies have 

been completed. Thus far, very few deaths have been attributed to thyroid cancer. Although radiationrelated deaths were recorded among emergency response personnel on site during the Chernobyl accident, 

these deaths were associated with external exposure to gamma radiation from molten fuel areas and not 

with exposure to radioiodine. 

3.3.1.2 Systemic Effects 

All of the information on systemic effects of inhaled radioactive iodine in humans relates to endocrine 

effects from exposures to radioiodine following the BRAVO nuclear bomb test in the Marshall Islands, 

the Chernobyl accident, and radioiodine releases from the Hanford Nuclear Site. Because oral ingestion 

of radioiodine is thought to have been the major contributor to exposure, these studies are discussed in 

detail in Section 3.3.2. No information was located regarding respiratory, cardiovascular, gastrointestinal, 

hematological, musculoskeletal, hepatic, renal, dermal, ocular, body weight, or other systemic effects of 

inhalation exposure to radioiodine. However, one epidemiological study examined health outcomes of 

infants of mothers who resided in the Belarus region before or after the Chernobyl accident (Petrova et al. 

1997). The health outcomes observed in this study include respiratory, hematological, renal, and dermal 

effects; however, their association to radioiodine exposure has not been established. This study is 

discussed in greater detail in the sections of reproductive and developmental effects associated with oral 

exposures to radioiodine (Sections 3.3.2.5 and 3.3.2.6). 

3.3.1.3 Immunological and Lymphoreticular Effects 

All of the information on immunological effects of inhaled iodine in humans relates to thyroid gland 

autoimmunity and exposures to radioiodine following the BRAVO nuclear bomb test in the Marshall 
 

 

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3. HEALTH EFFECTS 

Islands, the Chernobyl accident, and releases of radioiodine from the Hanford Nuclear Site. Because 

exposures in these incidents are thought to have been largely from oral ingestion of radioiodine, these 

studies are discussed in detail in Section 3.3.2. 

3.3.1.4 Neurological Effects 

Although not supported by observations, exposure to radioiodine at sufficient doses to produce 

hypothyroidism could potentially give rise to neurological manifestations of thyroid gland dysfunction 

including impairments in neurological development and myopathy (Boyages 2000a, 2000b). Congenital 

hypothyroidism can be associated with a severe impairment in neurological development of the fetus 

termed cretinism, which usually occurs in areas of endemic iodine deficiency. This condition would be 

highly unlikely in iodine-induced hypothyroidism secondary to inhalation of iodine. 

3.3.1.5 Reproductive Effects 

No information was located regarding reproductive effects of inhalation exposure to radioiodine. 

However, a large-scale retrospective analysis was conducted to evaluate pregnancy health and 

reproductive outcomes of women who were exposed to radiation resulting from releases from the 

Chernobyl nuclear power plant, including a major contribution from 131I (Petrova et al. 1997). Although 

inhalation of radioiodine certainly occurred in this population, internal radiation doses resulting from this 

incident are thought to have been largely from oral ingestion of radioiodine (IAEA 1991). The study is 

summarized in greater detail in Section 3.3.2.5, which discusses the reproductive effects of oral exposures 

to radioiodine. 

3.3.1.6 Developmental Effects 

No information was located regarding developmental effects associated with inhalation exposure to 

radioiodine other than those related to the thyroid gland (e.g., Marshall Islands, Section 3.3.2.2). 

However, one epidemiological study examined health outcomes of infants of mothers who resided in the 

Belarus region before or after the Chernobyl accident (Petrova et al. 1997). Exposures resulting from this 

incident are thought to have been largely from oral ingestion of radioiodine (IAEA 1991) and, therefore, a 

summary of this study can be found in Section 3.3.2.6 on the developmental effects of oral exposures to 

radioiodine. 
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3. HEALTH EFFECTS 

3.3.1.7 Cancer 

Thyroid cancers have been associated with exposures to radioiodine following the BRAVO nuclear bomb 

test in the Marshall Islands and the Chernobyl accident. The occurrence of thyroid cancers has also been 

studied in populations exposed to radioiodine released from nuclear bomb tests at the Nevada Test Site 

and from operational releases of radioiodine from the Hanford Nuclear Site. Although the inhalation of 

radioiodine occurred in these incidents, oral ingestion of radioiodine is thought to have been the major 

contributor to thyroid radiation doses. Summaries of these studies can be found in Section 3.3.2.7 on 

cancer effects of oral exposures to radioiodine. 

3.3.2 Oral Exposure 

The section that follows provides background information on the exposure scenarios from the major 

radioiodine-releasing events for which health effects studies have been reported. The actual study 

summaries follow. A discussion of the relevant biokinetics of radioiodine is provided in Section 3.5. 

Marshall Islands BRAVO Test. Several epidemiologic studies have examined thyroid gland disorders in 

residents of the Marshall Islands who were exposed to radioactive isotopes of iodine from atmospheric 

fallout after atmospheric nuclear bomb tests, in particular, the 1954 Castle BRAVO test. Residents of 

islands near and downwind from the test site on Bikini Atoll (e.g., Ailingnae, Rongelap, Utrik) were 

exposed to both internal radionuclides and external gamma radiation from fallout during the 2 days 

following the BRAVO test and prior to their evacuation. The estimated cumulative gamma radiation dose 

on these islands ranged from 69 to 175 rad (0.7–1.75 Gy) or approximately 10–50% of the estimated 

thyroid dose (Conard 1984). Later studies suggest that external radiation contributed approximately 4– 

16% of total thyroid dose (Hamilton et al. 1987). Internal exposures to the thyroid, resulting primarily 

from radioiodines, were much higher. Although inhalation of airborne radioiodine probably occurred 

during the fallout period immediately after the blast, ingestion of deposited radioiodine on locally 

prepared foods and drinking water during the subsequent 2 days prior to evacuation is thought to be the 

major contributor to the internal exposures (Lessard et al. 1985). Nursing infants would also have 

received internal exposures from ingestion of radioiodine in breast milk. Estimated total absorbed doses 

to the thyroid gland (external and internal) were 3.3–20 Gy (330–2,000 rad) on Rongelap (highest doses 

in children), 1.3–4.5 Gy (130–450 rad) on Ailingnae, and 0.3–0.95 Gy (30–95 rad) on Utrik (Conard 

1984). Estimates of the internal radiation dose to the thyroid remain uncertain as they were based 
 

 

IODINE 85 

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primarily on measurements of radioiodine (principally 131I) in a pooled urine sample, collected 16 days 

after exposure, from a subset of exposed people. Although these measurements allowed back 

extrapolation of the initial internal 131I exposures, shorter-lived radioiodine species (132I, 133I, 135I) could 

not be detected in the urine sample. These isotopes are thought to have contributed 2–3 times the thyroid 

radiation dose of 131I (Conard 1984). It is generally agreed that external radiation exposures resulted 

nearly entirely from fallout and deposits of radionuclide-containing materials on the skin, rather than from 

direct photon irradiation from the blast, as the exposed populations were approximately 100–320 miles 

from the detonation site. In this respect, the Marshall Island exposures are very different from the 

Hiroshima and Nagasaki exposures, which were the result of an acute (single dose) exposure to mostly 

gamma radiation (with neutron contribution in Hiroshima). Sixty-six nuclear bomb tests were conducted 

in the Marshall Islands during the period 1946–1958. Comparisons of contemporary measurements 137Cs 

in soils in the Marshall Islands with estimates of global fallout in the mid-Pacific region suggest 

contamination from local fallout occurred over much of the Marshall Islands (i.e., local 137Cs:global 

137Cs ratio>1) with particularly high local:global 137Cs ratios (>10) on the islands of Bikini Atoll (test 

site), Enewatak Atoll (test site), Rongelap Atoll, and Utrik Atoll (Simon and Graham, 1997). The most 

recent epidemiologic study (Takahashi et al. 1997, 2003) investigated 4,762 inhabitants of the islands 

who were alive during the weapons testing years. 

Chernobyl Accident. In 1986, a chemical explosion and fire at the nuclear power plant in Chernobyl in 

the Ukraine was caused by improper, unstable operation of the reactor, which allowed an uncontrollable 

power surge to occur; this resulted in the release of airborne radionuclides to the surrounding regions and 

contamination of soil and locally grown foods. The external radiation exposures were contributed largely 

by isotopes of cesium (e.g., 137Cs), which accounted for approximately 90–98% of the external radiation 

dose accumulated over the subsequent decades of exposure (Mould 2000; UNSCEAR 2000; Vargo 2000). 

Radioiodine is estimated to have contributed approximately 50% of the internal radiation dose for 

children born in 1986 in the region and approximately 80% of the total radiation dose received during the 

first year after the release (Vargo 2000). Estimates of thyroid radiation doses have been derived from 

external thyroid gland scans that measure radiation (mostly gamma) from radioiodine in the thyroid. 

These measurements suggest that radioiodine doses to the thyroid gland were highest in small children at 

the time of the release, and were highest in locations nearest to the nuclear plant where people were not 

evacuated rapidly. The highest estimated doses were received within 30 km of the Chernobyl plant; 

median doses ranged from 2.3 Gy (230 rad) at age <1 year to 0.4 Gy (40 rad) in adolescents and adults 

(UNSCEAR 2000, Annex J, Table 22). Estimated median doses received in populations residing 

approximately 200 km from the plant (e.g., Mogilev region) were <0.3 Gy (30 rad) for all age groups 
 

 

IODINE 86 

3. HEALTH EFFECTS 

(UNSCEAR 2000). Although inhalation of airborne radioiodine is likely to have occurred after the 

accident, the major contributors to the absorbed thyroid radiation dose are thought to have been from 

ingestion of milk and leafy vegetables contaminated from atmospheric deposition of radioiodine. 

Ingestion of human breast milk is also considered to have been a major contributor to doses received by 

nursing infants. For example, it has been estimated that, in seven Ukraine cities, ingestion of 131I 

contributed between 87 and 98% of total absorbed radiation dose (IAEA 1991). Endemic goiter in the 

Belarus population due to iodine deficiency (Gembicki et al. 1997) secondary to differences in the extent 

of use of stable iodine may have also contributed to the differences in the thyroid doses observed in 

Belarus compared to similarly contaminated areas of Finland. 

Thyroid dose estimates, particularly peak dose rates, are largely based on extrapolations from thyroid 

gland 131I measurements made within 1 to several weeks after the major release from the Chernobyl plant 

and ground monitoring of atmospheric deposition of radiocesium. One set of measurements of thyroid 

gland radioactivity came from postmortem measurements of thyroid glands from 416 people collected 

over the period from May 3 (8 days after the initial release) to August 4, 1986 in Bratislava (Beno et al. 

1991). Back extrapolation of thyroid gland activities and consideration of temporal trends in both the 

thyroid gland data and atmospheric deposition allowed the estimation of transfer coefficients relating 

atmospheric deposition of radioiodine (kBq/m2

) and thyroid dose (μSv); the coefficients were 

641 μSv/kBq-m2

 in exposed children and 221 μSv/kBq-m2 in exposed adults (Beno et al. 1992). Based 

on this approach, and radiocesium measurements made in Belarus, thyroid radiation doses received in 

Belarus may have ranged from 0.12 to 24 μSv (12–2,400 rem) in children and from 0.04 to 8 μSv (4– 

800 rem) in adults (Bleuer et al. 1997). In Gomel, where the highest incidence of thyroid cancer in 

children has been reported, estimated doses were 1.2–12.3 Sv (120–1,230 rem) in children 

(Drobyshevskaya et al. 1996). Various other approaches have been used to estimate thyroid doses 

associated with the Chernobyl accident. In Ukraine, most of these rely on exposure estimates based on 

measured or assumed relationships between radioiodine and 137Cs air levels, and models simulating 

pathways to humans, including milk ingestion (IIyin et al. 1990; Likhtarev et al. 1995). Estimates of 

absorbed thyroid doses from 131I based on 137Cs deposition densities in seven Ukraine cities ranged from 

80 to 240 cGy (rad) in infants, 64–190 cGy (rad) in children, and 19–57 cGy (rad) in adults (IAEA 1991). 

Almost all of the internal radiation exposure of the thyroid gland was received in the first 3 months after 

the accident, during which time, the 131I activity decreased to <0.1% of the initial values. The continued 

129I exposure can be considered minimal, although it will persist for several decades for some populations 

because of environmental contamination and its longer decay half-life. 
 

 

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3. HEALTH EFFECTS 

Nevada Test Site. During the period 1951–1958, 97 atmospheric nuclear bomb tests were conducted at 

the Nevada Test Site (NTS) in southern Nevada (NCI 1997). These tests were followed by nine surface 

detonations during the period 1962–1968 and approximately 809 below-ground tests, of which 38 were 

determined to have resulted in off-site releases of radioactive materials. In response to a mandate from 

the U.S. Congress, a dose estimation methodology was developed by the National Cancer Institute (NCI 

1997), which has enabled estimates of population radiation doses to the thyroid gland of representative 

persons in each of the approximately 3,100 counties of the United States, from direct and indirect (e.g., 

ingestion of cow milk) exposures to 131I resulting from the NTS activities, for the purpose of health 

assessments and epidemiologic investigations (Gilbert et al. 1998). The NCI analysis utilized dose 

reconstruction methods developed earlier by the off-site Radiation Exposure Review Board Project 

(ORERP) (Ng et al. 1990). In addition, an epidemiologic study of thyroid disease in a Utah cohort was 

conducted (Kerber et al. 1993) using dosimetric methods described in Simon et al. (1990). Geographicspecific geometric mean lifetime doses are estimated to have ranged from 0.19 to 43 cGy (rad) for a 

hypothetical individual born on January 1, 1952 who consumed milk only from commercial retail 

sources, 0.7–55 cGy (rad) for people who consumed milk only from home-reared cows, and 6.4–330 cGy 

(rad) for people who consumed milk only from home-reared goats (NCI 1997; NRC 1999). The actual 

dose received by any individual depended on age of exposure, location, and milk consumption habits. A 

discussion of the uncertainties and limitations of these population dose estimates for use in epidemiology 

studies and risk assessment can be found in a review of the NCI (1997) dose estimations conducted by the 

Institute of Medicine and the National Research Council (NRC 1999). 

Hanford Nuclear Site. The Hanford Nuclear Site in southeastern Washington reprocessed uranium to 

produce plutonium. Radioiodine was released to the atmosphere during the early years of operation of the 

facility. Approximately 740,000 Ci (27 PBq) of 131I was estimated to have been released to the 

atmosphere during the period 1944–1957 (CDC 2002). Thyroid radiation doses have been estimated 

using a dosimetry model developed in the Hanford Environmental Dose Reconstruction Project (Shipler 

et al. 1996). The estimated mean thyroid radiation dose in a study cohort of 3,191 people who resided 

near the facility was 174 mGy (±224, standard deviation [SD]) (17.4±22.4 rad), with a range of 0.0029– 

2,823 mGy (0.00029–282 rad). Mean thyroid doses in females and males were similar; 177 mGy 

(17.7 rad) and 171 mGy (17.1 rad), respectively. Doses varied geographically, with the highest doses 

received by people who lived near and downwind from the site. 
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3. HEALTH EFFECTS 

3.3.2.1 Death 

Although radiation-related deaths were recorded among emergency response personnel on site during the 

Chernobyl accident, these deaths were associated with exposure to gamma radiation from molten fuel 

areas and not with exposure to radioiodine (see Section 3.2.2 for a more detailed discussion of the 

exposures from Chernobyl accident). Deaths related to thyroid cancers (or to other cancers or causes) 

following the accident continue to be studied and possible associations between mortality and radioiodine 

exposures may eventually become evident. In general, radiation-induced thyroid cancers tend to be 

papillary carcinomas; these types of tumors tend to be non-fatal (30-year mortality was estimated to be 

approximately 8% in adults (Mazafaferri and Jhiang 1994). However, papillary carcinomas that occur in 

young children, the predominant age group for thyroid cancers observed after the Chernobyl accident, are 

more fatal then when they occur in adults (Harach and Williams 1995). 

The LOAEL values in humans for exposures by the oral route are presented in Table 3-1 and plotted in 

Figure 3-1. 

3.3.2.2 Systemic Effects 

The major systemic effects of exposures to radioiodine are on the thyroid gland; however, other systemic 

effects have been observed, including inflammation of the salivary glands (sialadentitis), following 

relatively high exposures to radioiodine such as those used for ablative treatment of thyroid cancers. 

The highest NOAEL values and all reliable LOAEL values in each duration category for systemic 

(endocrine) effects from exposures by the oral route are presented in Table 3-1 and plotted in Figure 3-1. 

Gastrointestinal Effects. The major systemic effects of exposures to radioiodine are on the thyroid 

gland; however, other systemic effects have been observed, including inflammation of the salivary glands 

(sialadentitis), following relatively high exposures to radioiodine such as those used for ablative treatment 

of thyroid cancers. 

The highest NOAEL values and all reliable LOAEL values in each duration category for systemic 

(endocrine) effects from exposures by the oral route are presented in Table 3-1 and plotted in Figure 3-1. 
 

 

 

 

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3. HEALTH EFFECTS 

Endocrine Effects. 

Effects of Radioiodine on Thyroid Gland Function 

Extensive clinical use of radioiodine, principally 123I and 131I, for diagnostic purposes and 131I for 

treatment of thyrotoxicosis has provided a wealth of information on the effects of relatively high acute 

exposures on thyroid gland function. Radioiodine is cytotoxic to the thyroid gland and produces 

hypothyroidism at absorbed effective doses to the thyroid gland exceeding 2,500 rad (25 Gy). Thyroid 

gland doses of approximately 10,000-30,000 rad (300 Gy) can completely ablate the thyroid gland 

(Maxon and Saenger 2000). Cytotoxic doses of 131I are delivered for treatment of hyperthyroidism or 

thyrotoxicosis; administered activities typically range from 10 to 30 mCi (370–1,110 MBq). Higher 

activities are administered if complete ablation of the thyroid is the objective; this usually requires 100– 

250 mCi (3,700–9,250 MBq). An administered activity of 5–15 mCi (185–555 MBq) yields a radiation 

dose to the thyroid gland of approximately 5,000-10,000 rad (50–100 Gy) (Cooper 2000). Current 

diagnostic uses of radioiodine involve much smaller exposures, typically 0.1–0.4 mCi (4–15 MBq) of 123I 

or 0.005–0.01 mCi 131I (0.2–0.4 MBq). These exposures correspond to approximate thyroid radiation 

doses of 1–5 rad (1–5 cGy) and 6–13 rad (6–13 cGy) for 123I and 131I, respectively (McDougall and 

Cavalieri 2000). However, historically, higher doses have been used for diagnostic procedures (e.g., 

Dickman et al. 2003; Hall et al. 1996). 

Several epidemiological studies have examined the relationship between oral exposure to 131I and thyroid 

gland nodularity. Thyroid nodules are irregular growths of the thyroid gland tissue that can be benign or 

cancerous. Nodules can be detected by physical palpation of the gland or by various imaging techniques. 

Palpation detects only larger (>1 cm) nodules, whereas ultrasound can detect nodules that are not palpable 

(e.g., 1 cm or less). The complete description of a study by Rallison (1996) and by Kerber et al. (1993) is 

provided in Section 3.3.2.7, as it primarily relates to thyroid neoplasms. The study reported no difference 

in prevalence of thyroid nodularity detected by physical examination in a cohort living near the NTS 

when compared to a nonexposed cohort living remote from the NTS (Rallison 1996). However, when the 

thyroid radiation dose from 131I was calculated for each subject in each location, there was a correlation 

between radiation dose and formation of neoplasia of the thyroid, but not to nonneoplastic nodules 

(Kerber et al. 1993). 

The Hall et al. (1996a) study evaluated 1,005 women for thyroid nodularity who had been exposed to 

diagnostic levels of 131I during the period 1952–1977 and whose diagnosis for thyroid abnormalities were 

negative. The subjects were evaluated for palpable thyroid nodules during the period 1991–1992. A 
 

 

IODINE 90 

3. HEALTH EFFECTS 

comparison group consisted of 248 women who attended a mammography screening clinic with no prior 

history of exposure to 131I or thyroid disease. The average total administered 131I activity was 0.95 MBq 

(26 μCi). Absorbed radiation doses to the thyroid gland were estimated based on the administered 

activity and dosimetry tables from International Commission on Radiological Protection (ICRP 1988). 

The average dose was 0.54 Gy (54 rad) (10th–90th percentiles, 0.02–1.45 Gy; 2–145 rad). Thyroid 

nodules were detected in 107 of 1,005 (10.6%) exposed women and 29 of 248 (11.7%) nonexposed 

women. The relative risk (RR, based on odds ratios [ORs]) for thyroid nodularity for women exposed to 

131I was 0.9 (95% CI, 0.6–1.4) and was not statistically significant. A linear quadratic excess relative risk 

model revealed a statistically significant dose trend for thyroid nodularity (excess RR, 0.9/Gy). Hall et al. 

(1996a) suggest as an explanation for the lack of a significant RR for thyroid nodularity that the 

nonexposed control group was self-selected (i.e., the subjects voluntarily sought mammographic 

screening) and, therefore, may not have been an appropriate control group for comparison to the group of 

women who received radioiodine. 

Clinical cases have been reported in which congenital hypothyroidism occurred after maternal exposures 

to high doses of 131I during pregnancy for treatment of thyroid gland tumors (Green et al. 1971; Hamill et 

al. 1961; Jafek et al. 1974; Russell et al. 1957). However, the complex clinical picture and 

pharmacotherapy of the mothers for their thyroid condition during pregnancy makes direct associations 

between the radioiodine exposure and the clinical outcomes of the newborns highly uncertain. Exposures 

in these cases ranged from 11 to 77 mCi (0.4–2.8 GBq). Effects on the fetal and newborn thyroid would 

be expected if mothers received ablative doses of 131I during pregnancy after approximately 12 weeks of 

gestation, when the fetal thyroid begins to take up iodide. A study of 73 infants and children born to 

70 patients who received 131I for ablative treatment of thyroid cancer 2–10 years (mean, 5.3 years) prior to 

pregnancy found no thyroid gland disorders (Casara et al. 1993). The maternal 131I exposures ranged 

from 1.85 to 16.55 GBq (50–450 mCi); the mean exposure was 4.40 GBq (120 mCi). A similar finding 

was reported in a study of 37 patients (47 infants) who received 131I, 1–60 months prior to conception 

(mean, 16.5 months); exposures ranged from 1.1 to 13.1 GBq (30–350 mCi), with a mean exposure of 

3.67 GBq (100 mCi) (Lin et al. 1998). 

Marshall Islands. Shortly after the BRAVO test, residents on three of the Marshall Islands were 

identified as having been exposed to external gamma radiation during the 2 days prior to their evacuation 

(Conard 1984): 64 residents of Rongelap (1.90 Gy, 190 rad), 18 residents of Ailingnae (1.10 Gy, 110 rad) 

and 150 residents of Utrik (0.11 Gy, 11 rad) (see Section 3.3.2 for a more detailed discussion of exposures 

from the Marshall Islands BRAVO test). Estimated total absorbed doses to the thyroid gland (external 
 

IODINE 91 

3. HEALTH EFFECTS 

and internal) were 3.3–20 Gy (330–2,000 rad) on Rongelap (highest doses in children), 1.3–4.5 Gy (130– 

450 rad) on Ailingnae, and 0.3–0.95 Gy (30–95 rad) on Utrik (Conard 1984). As part of a medical 

evaluation program, these individuals, the so-called BRAVO cohort, were evaluated periodically for 

health consequences of their exposures. Evidence of acute radiation sickness was prevalent early after 

exposures, including nausea and vomiting, hematological suppression, and dermal radiation burns. Cases 

of thyroid gland disorders began to be detected in the exposed population in 1964, 10 years after the 

exposure, particularly in exposed children; these included cases of apparent growth retardation, 

myxedema, and thyroid gland neoplasms (Conard et al. 1970). In 1981, when the children from Rongelap 

island were screened, it was discovered that 83% of the children who were <1 year of age at the time of 

the BRAVO test were found to have evidence of hypothyroidism (i.e., a serum concentration of TSH 

>5 mU/L). This group of children had received an estimated thyroid dose exceeding 1,500 rad (15 Gy). 

Prevalence of hypothyroidism and thyroid radiation dose decreased with exposure age: 25% for ages 2– 

10 years (800–1,500 rad, 8–15 Gy) and 9% for ages $10 years (335–800 rad, 3.35–8.00 Gy). Prevalences 

in the exposed groups from Ailignae were 8% for exposure ages >10 years (135–190 rad, 1.35–1.90 Gy) 

and 1% on Utrik (30–60 rad, 0.3–0.6 Gy). In an unexposed group (Rongelap residents who were not on 

the island at the time of the BRAVO test), the prevalence was 0.3–0.4% (Conard 1984). At about the 

same time, in 1964, cases of palpable thyroid gland nodules began to be identified in health screening 

programs (Conard 1984). The prevalence of thyroid nodularity had an age/dose profile similar to that of 

thyroid hypofunction (i.e., elevated serum TSH). In 1981, thyroid nodules were found in 77% Rongelap 

residents exposed before the age of 10 years and in 13% of those exposed after 10 years. Prevalence in 

the Ailingnae populations was 29% in the population of children exposed before age 10 years and 33% in 

the population exposed after age 10 years. In the Utrik population, the prevalence of thyroid nodules was 

8% in the population of children exposed before age 10 years and 12% in the population exposed after 

age 10 years. The prevalence of thyroid gland carcinoma, mainly papillary carcinomas, also appeared to 

be elevated in the exposed Rongelap population (6%) compared to the unexposed group (1%). In 1994, 

thyroid ultrasound examinations were performed on 117 of the original exposure group, 47 from 

Rongelap, and 70 for Utrik, and 47 residents of Rongelap who were on Majuro at the time of the BRAVO 

test, approximately 480 miles south of the test site on Bikini Atoll (Howard et al. 1997). Over the period 

1965–1990, the case rate for thyroid nodules was approximately 3–8% per year in the exposed groups and 

approximately 3 times greater in females than in males. However, the 1994 ultrasound evaluations found 

relatively high, but not significantly different, prevalences of thyroid nodules in exposed (12–33%) and 

nonexposed (25%) groups or between males and females (Howard et al. 1997). The differences in the 

outcomes in 1994 and earlier may reflect the age differences at the time of examination, or possibly that 

palpation detects only larger (>1 cm) nodules, whereas ultrasound can detect nodules that are not palpable 
IODINE 92 

3. HEALTH EFFECTS 

(e.g., ≤10 mm). Ultrasound is more likely to detect clinically insignificant nodules that are actually 

normal variants of thyroid tissue. Another possible contributor to the differences between outcomes is 

that earlier studies may have been biased by greater screening/surveillance intensity given to the highdose groups, whereas the Howard et al. (1997) study was a more systematic comparison across the dose 

range and used a more objective ultrasound criteria for diagnosing nodularity. Thyroid nodule incidence 

is highly susceptible to surveillance effects and these studies were not adequately controlled for such 

effects. A possibly related observation is an apparent high prevalence of iodine deficiency in the 

Marshall Islands, which may have contributed to a high background prevalence of nodular goiter (Hermus 

and Huysmans 2000; Takahashi et al. 1999). 

A retrospective cohort study reexamined the prevalence of thyroid gland nodularity reported in the 1980s 

among residents of the Marshall Islands who were potentially exposed to 131I from atmospheric fallout 

from the BRAVO test in 1954 (Hamilton et al. 1987). This study included residents on islands located 

112–589 miles from the test site. The cohort consisted of 7,266 people known to have been residents on 

the islands (or in utero) in 1954 at the time of the BRAVO test. Each subject was examined for palpable 

thyroid nodules during the period 1983–1985. The examiners were blind to the estimated thyroid 

radiation dose received by each subject. Radiation doses to the thyroid gland were estimated to have been 

21 Gy (2,100 rad) for residents of Rongelap (120 miles from the test site) and 2.80 Gy (280 rad) for 

residents of Utrik (321 miles). Residents of 12 other islands, who historically were thought not to have 

received exposures to radioiodine based on location (distance and/or position with respect to prevailing 

winds), were included in the study. The age-adjusted prevalence of thyroid nodularity was 37% among 

residents of Rongelap Island and 10.3% for Utrik Island. Prevalence among residents of the other 

12 islands ranged from 0.8 to 10.2% and there were no statistically significant differences in prevalence 

among these 12 less-exposed islands. A prevalence of 2.45% was assumed for nonexposed populations, 

based on observed prevalence in the two most southern islands (Ebon and Mili), for the purpose of 

calculating ORs. A logistic regression model yielded a statistically significant effect of sex on OR for 

thyroid nodularity, with an OR 3.7 times higher in females. The model also yielded a significant trend for 

decreasing prevalence of thyroid nodularity with both distance and direction from the test site, with 

prevalence decreasing 3-fold per 100 miles (OR, 0.3 per 100 miles) from the site and 2-fold for every 

10 degrees east or west of the site (OR, 0.59 per 10 degrees). The risk estimate for thyroid nodularity 

among the Marshall Islanders was 1,100 excess cases/Gy/year of exposure per 1 million people 

(0.0011/person-Gy/year, 0.000011/person-rad/year). 
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A large-scale screening program for thyroid disease was conducted in the Marshall Islands during the 

period 1993–1997 (Fujimori et al. 1996; Takahashi et al. 1997, 1999, 2003). Results of screening of 

1,322 residents of Ebeye (in the Kwajalein Atoll, approximately 190 miles from Bikini Atoll) are reported 

in Takahashi et al. (1997). Evaluations included neck palpation, thyroid ultrasound, and fine needle 

aspiration biopsy if warranted (results on diagnoses relevant to thyroid cancer are discussed in 

Section 3.3.1.7). The examiners were blind to the estimated thyroid radiation dose received by each 

subject. Among 815 subjects born before 1954, the date of the BRAVO test, 266 (32.6%) were diagnosed 

with thyroid nodules, 132 (16.2%) were palpable. The prevalence of thyroid nodules (palpable and 

detected by ultrasound) was higher in females than males; however, as was observed in the Hamilton et 

al. (1987) study, the difference was significant only for palpable nodules (palpable: females 17.7%, males 

9.3%; total nodules: females 35.9%, males 21.0%). In either case, nodule prevalence was 2–3 times 

higher among groups born during the bomb testing period (before 1958) than after the testing ended. A 

logistic regression model applied to the nodule prevalence data revealed significant effects of sex, age, 

and distance from Bikini Atoll on nodule prevalence (Takahashi et al. 1997). A more recent report on the 

screening program described the results of thyroid palpation and ultrasound (7,721 subjects), tests of 

thyroid hormone (1,050 subjects), and iodine status (urinary iodide, 309 subjects) (Takahashi et al. 1999). 

The study group included 5,263 residents of Majuro (approximately 480 miles from Bikini Atoll), 

1,610 residents from Ebeye Island (192 miles), and 348 residents from Mejit (398 miles). Of the 

7,221 subjects examined in the study (1993–1997), 4,766 (66%) were of an age to have potential 

exposures to radioactive fallout from bomb tests. The prevalence of thyroid nodules (palpable and 

detected by ultrasound) was approximately 3 times higher in females than males; among females, the 

prevalence was highest (13%, 407 of 3,151) among women born before 1959, the date of the last bomb 

tests. Thyroid hormone tests (T4, T3, and TSH) revealed no evidence of an unusual prevalence of thyroid 

gland dysfunction. Measurements of urinary iodide levels suggested mild to severe iodine deficiency in 

the population; approximately 21% of the adult subjects had urinary iodides in the range of 22–45 nmol 

I/mmol creatinine (25–50 μg I/g creatinine). This corresponds to a urinary excretion rate and iodine 

intake rate of approximately 40–80 μg I/day (based on an assumed body weight of 60 kg). Thyroid 

volumes were compared in subjects who had nodules and were iodine deficient with subjects who were 

iodine sufficient and who did not have nodules. Although there was no apparent indication of excessive 

prevalence of thyroid enlargement in either the iodine-deficient or -sufficient groups, subjects who had 

the largest thyroid volumes tended to fall in the deficient-nodular group. Thyroid nodularity occurs in 

populations that have experienced prolonged iodine deficiency, although it is usually associated with 

goiter (Hermus and Huysmans 2000). The observation of a high prevalence of iodine deficiency in the 

Marshall Island population may be an important confounding variable in many of the epidemiology 
IODINE 94 

3. HEALTH EFFECTS 

studies that have attempted to explore relationships between thyroid nodularity and radiation dose in the 

Marshall Island populations. 

Chernobyl Accident. Subsequent to the release of radioactive materials from the Chernobyl power plant 

in 1986, an increased prevalence of thyroid nodules in children of the Belarus region was reported 

(Astakhova et al. 1996) (see Section 3.3.2 for a more detailed discussion of exposures from of the 

Chernobyl accident). An analysis of the results of ultrasound screening of 20,785 people in Belarus 

conducted during the period 1990–1995 revealed a prevalence of thyroid gland nodules that ranged from 

4 to 22 per 1,000. Prevalence was highest (16–22 per 1,000) among residents from districts in which 

thyroid radiation doses were estimated to have been above 1 Gy (1.3–1.6 Gy, 130–160 rad). Verified 

diagnoses from patients who were referred for further examination as a result of ultrasound results 

revealed a prevalence of thyroid cancer of 2.5–6.2 per 1,000, or approximately 13–50% of nodule cases, 

among cases from districts where thyroid radiation doses were estimated to have been above 1 Gy (1.3– 

1.6 Gy, 130–160 rad) (see Section 3.3.1.7 for further discussion of thyroid cancer related to the Chernobyl 

release). Adenoma was diagnosed in 7–12% of thyroid nodule cases, nodular goiter was diagnosed in 5– 

22% of the thyroid nodule cases, and 7–64% of the nodule cases were diagnosed as benign cysts. In 

districts in which thyroid doses were estimated to have been <0.1 Gy, benign cysts predominated the 

diagnoses, with no thyroid cancers; approximately 0–25% were diagnosed as adenomas, 0–8% as nodular 

goiter, and 75–100% as benign cysts (predominantly cystic-dystropic types of goiter). Dietary iodine 

status was assessed from measurements of urinary iodine (Astakhova et al. 1996). Urinary iodide levels 

varied across regions in Belarus. Approximately 30–80% (mean 61%) of children and adolescents had 

overnight urinary iodine concentrations <100 μg/L, 10–50% (mean 26%) had concentrations <50 μg/L, 

and 0–25% (mean 9%) had concentrations <20 μg/L. These results suggest a substantial prevalence (on 

average 26 and 50% in some districts) of dietary iodine intakes below 50–70 μg/day (assuming a daily 

urine output of 1–1.4 L in children and adolescents). More recent measurements (made in 2000) suggest 

that dietary iodide deficiency in Belarus appears to have persisted since the Chernobyl accident (Ishigaki 

et al. 2001). The results of other thyroid screening programs (e.g., the Chernobyl Sasakawa Health and 

Medical Cooperation Project) also suggest a high prevalence of goiter among people born in Belarus 

between the years 1976 and 1986, which would be consistent with a high prevalence of iodine deficiency 

in the population (UNSCEAR 2000). Therefore, iodine deficiency may have contributed to the observed 

thyroid nodularity and also may be a confounding variable in susceptibility to thyroid cancer (Gembicki 

et al. 1997; Robbins et al. 2001). 
 

 

IODINE 95 

3. HEALTH EFFECTS 

Hanford Nuclear Site. The CDC (2002) has conducted a follow-up prevalence study of thyroid disease 

in populations that resided near the Hanford Nuclear Site in southeastern Washington during the period 

1944–1957 (see Section 3.3.2 for a more detailed discussion of releases from the Hanford Nuclear Site). 

The study included 3,441 subjects who were born during the period 1940–1946 in counties surrounding 

the Hanford Nuclear Site. Thyroid disease was assessed from a clinical evaluation of each subject, which 

included assessments of ultrasound or palpable thyroid nodules, thyroid hormone status, thyroid 

autoimmunity, and parathyroid hormone status. Historical information on thyroid disease and 

information on radiation exposures were obtained by interviews and, when possible, review of medical 

records of participants. Thyroid radiation doses were estimated using a dosimetry model developed in the 

Hanford Environmental Dose Reconstruction Project. Information on residence history and relevant food 

consumption patterns (e.g., milk consumption, breast feeding, consumption of locally harvested produce) 

for each study participant was obtained by interview. The estimated mean thyroid radiation dose, based 

on 91 participants, was 174 mGy (±224, standard deviation [SD]) (17.4±22.4 rad), and the range was 

0.0029–2,823 mGy (0.00029–282 rad). An indication that the statistical power of the study was 

appreciably limited by the low distribution of thyroid doses is the fact that only 24 (0.8%) of the study 

population had estimated thyroid doses >1 Gy (100 rad) and only 7 (0.2%) had doses >2 Gy (200 rad). 

Doses varied geographically, with the highest doses received by people who lived near and downwind 

from the site. Health outcomes investigated included thyroid carcinoma, thyroid nodules, 

hypothyroidism, and hyperthyroidism (serum TSH levels), including Graves’ disease, thyroid 

autoimmunity (serum antimicrosomal antibodies and antithyroid peroxidase), goiter, and hyperparathyroidism. Dose-response relationships were assessed using a linear regression model with adjustments 

for the following confounding and effect modifying variables: sex, age of first exposure, age of 

evaluation, ethnicity, smoking, and potential exposures from Nevada Test Site releases. Alternatives to 

the linear model, including linear quadratic and logistic models, were also explored. Incidence of thyroid 

disease was found to be unrelated to thyroid radioiodine dose for all outcomes evaluated (dose 

coefficients not significantly different from zero). Estimated dose coefficients, based on the linear model, 

were: thyroid cancer, 0.002±0.004 per Gy (CI: <-0.001–0.017, p=0.25, 20 cases, 0.6% prevalence); 

thyroid nodules (of any type), -0.007±0.016 per Gy (CI: <-0.023–0.043, p=0.65, 281 cases, 8.2%); 

hypothyroidism, -0.006±0.019 per Gy (CI: -0.016–0.047, p=0.61, 267 cases, 7.8%); hyperthyroidism, 

0.011±0.015 per Gy (CI: <-0.008–0.052, p=0.22, 161 cases, 4.7%); thyroid autoimmunity, 

-0.024±0.027 per Gy (CI:<-0.058–0.048, p=0.8, 659 cases, 19.2%); goiter, -0.001±0.008 (95% upper CL: 

0.012, p=0.74, 14 cases, 0.4%); hyperparathyroidism, -0.000±0.018 per Gy (95% upper CL: 0.013, 

p=0.61, 14 cases, 0.4%). 
IODINE 96 

3. HEALTH EFFECTS 

The CDC (2002) study was reviewed by the National Academy of Sciences (NAS 2000), which identified 

several sources of uncertainty in the study that need to be considered in interpreting the reported results. 

In particular, reliance on modeling thyroid radiation doses, based on environmental transfer coefficients, 

rather than direct measurements (which was not possible) may have introduced substantial uncertainty in 

the risk estimates, that may have been underestimated in the study. In particular, the NAS pointed out 

that the study utilized a transfer coefficient for radioiodine from cows to cow milk that was approximately 

twice that estimated from other studies. This could have contributed to an overestimate of thyroid doses 

in infants and children, and a lower statistical power of the study. Also, the study utilized survey 

information on the sources and amounts of milk consumed that was collected 40–50 years after the period 

of interest. Large uncertainties in estimates of these model parameters may have also decreased the 

statistical power of the study. Loss of power is particularly important in interpreting the generally 

negative findings of the study. 

Effects of Radioiodine on the Parathyroid Gland 

Cases of hypo- and hyperparathyroidism are rare outcomes in patients who receive 131I treatments for 

ablative therapy of thyroid cancer or hyperthyroidism. The parathyroid gland is in close proximity to the 

thyroid gland. Although in most people, the parathyroid and thyroid glands are separated by more than 

1 cm, in approximately 20% of people, the parathyroid gland is located within the thyroid gland capsule 

(Glazebrook 1987). The latter configuration would result in irradiation of the parathyroid gland with 

β emission from 131I concentrated in the thyroid gland; β emission from 131I has a tissue penetration 

distance of approximately 0.5–2 mm (Esselstyn et al. 1982). Cases of parathyroid dysfunction have been 

reported after exposures to 131I ranging from 4 to 30 mCi (0.15–1.1 GBq) (Better et al. 1969; Burch and 

Posillico 1983; Eipe et al. 1968; Esselstyn et al. 1982; Fjälling et al. 1983; Freeman et al. 1969; 

Glazebrook 1987; Jialal et al. 1980; Rosen et al. 1984). A clinical follow-up study evaluated serum 

calcium status of 125 patients (106 females, 19 males) who received 131I for treatment of hyperthyroidism 

during the period 1951–1960. The follow-up assessments occurred 16–26 years (mean, 21 years) after 

exposure to 131I (Fjälling et al. 1983). A group of age- and sex-matched healthy subjects who had no 

history of irradiation to the head or neck region served as a control group. Exposures to 131I ranged from 

75 to 1,400 MBq (2–38 mCi). These corresponded to radiation doses to the parathyroid of 2–5 Gy in 

subjects whose parathyroid gland was 0.2 cm from the surface of the thyroid gland and 3–7.5 Gy in 

subjects whose parathyroid gland was at the surface of the thyroid gland. Two patients and two control 

subjects were found to have hypercalcemia and verified hyperparathyroidism (the exact basis for the 

verification was not reported). The 131I exposures of the two patients were 140 and 450 MBq (3.8 and 

12 mCi), respectively. 
IODINE 97 

3. HEALTH EFFECTS 

Hanford Nuclear Site. Hyperparathyroidism was assessed as part of the CDC (2002) study of health 

outcomes related to radioiodine releases from the Hanford Nuclear Site (see Section 3.3.2 for a more 

detailed discussion of releases from the Hanford Nuclear Site). The study included 3,441 subjects who 

were born during the period 1940–1946 in counties surrounding the site. Parathyroid hormone status was 

assessed from measurements of serum parathyroid hormone. Historical information on parathyroid 

disease was obtained by interviews and, when possible, review of medical records of participants. The 

estimated mean thyroid radiation dose, based on 91 participants, was 174 mGy (±224, standard deviation 

[SD]) (17.4±22.4 rad), and the range was 0.00029–2,823 mGy (0.002.9–282 rad). Dose-response 

relationships were assessed using a linear regression model with adjustments for the following 

confounding and effect modifying variables: sex, age of first exposure, age of evaluation, ethnicity, 

smoking, and potential exposures from Nevada Test Site releases. Incidence of hyperparathyroidism was 

found to be unrelated to thyroid radioiodine dose (dose coefficients were not significantly different from 

zero). Estimated dose coefficients based on the liner model were -0.000±0.018 per Gy (95% upper CL: 

0.013, p=0.61) based on 14 cases (0.4% prevalence). Incidence of hyperparathyroidism was found to be 

unrelated to thyroid radioiodine dose. Uncertainties in the dose estimates for the cases need to be 

considered in interpreting these results. 

Effects of Radioiodine on Testicular Endocrine Function 

High exposures to 131I may affect testicular endocrine function. Studies relevant to these end points 

(Wichers et al. 2000) are described in Section 3.3.2.5 (Reproductive Effects). 

3.3.2.3 Immunological and Lymphoreticular Effects 

Information on immunological effects of oral exposure to radioiodine in humans relates to thyroid gland 

autoimmunity. The highest NOAEL values and all reliable LOAEL values in each duration category for 

immunological and lymphoreticular effects from exposures by the oral route are presented in Table 3-1 

and plotted in Figure 3-1. 

Cases of autoimmune hyperthyroidism after exposures to 131I for ablative treatment of hyperthyroidism 

have been reported. In three cases, thyrotoxicosis developed with serum antibodies to TSH receptor 3– 

6 months after the patients received oral treatments with 40–86 mCi 131I (1.5–3.2 GBq) for reduction of 
IODINE 98 

3. HEALTH EFFECTS 

nontoxic goiter that was compressing the trachea (Huysmans et al. 1997a). Prior to the 131I treatments, the 

patients were euthyroid and had no detectable TSH antibodies. 

Marshall Islands. Large scale assessments of thyroid autoimmunity have been conducted in the Marshall 

Islands, where exposures to 131I occurred as a result of fallout and contamination from test detonations of 

nuclear bombs during the period 1946–1958 (see Section 3.3.1.2, Endocrine, for a more complete 

description of these studies) (see Section 3.3.2 for a more detailed discussion of exposures from the 

Marshall Islands BRAVO test). In a thyroid screening program conducted during the period 1993–1997, 

7,721 subjects were evaluated for various end points of thyroid size, nodularity, and function (Fujimori et 

al. 1996, Takahashi et al. 1997, 1999). Antithyroglobulin antibodies in serum were detected in 67 of 

2,700 (2.5%) subjects examined (Fujimori et al. 1996). Although this prevalence is unremarkable 

compared to that found in other populations (10% in healthy adults) (Marcocci and Chiovata 2000; 

Takahashi et al. 1999), a statistical comparison with an appropriate referent population was not 

conducted. Furthermore, no attempt was made in this study to assess the relationship between antibody 

levels and radioiodine exposure. 

Chernobyl Accident. A study that compared thyroid cancers in Belarus and Ukraine diagnosed after the 

Chernobyl releases with those diagnosed in Italy and France during the same time period found that the 

Belarus-Ukraine cases had a higher incidence of thyroid autoimmunity (i.e., elevated antithyroid 

peroxidase and thyroglobulin antibodies) than the Italy-France cases (Pacini et al. 1997) (see 

Section 3.3.2 for a more detailed discussion of exposures from of the Chernobyl accident). It is unclear to 

what extent the autoimmunity may be related to the exposures to radioiodine. Serum antithyroglobulin 

antibody titres were measured in 53 children ages 7–14 years (in 1993–1994) who received 0.4–3.2 Gy 

(40–320 rad) as a result of the Chernobyl release (Chernyshov et al. 1998). Antibody titres were detected 

in 80.6% of exposed children compared to 16.7% of a reference group that had no estimated exposure to 

131I, and there was a significant positive correlation between antibody titre and estimated thyroid 131I dose. 

These results suggest a possible contribution of thyroid radioiodine exposure to thyroid autoimmunity. 

Other screening programs conducted in Belarus have not found relationships between thyroid 

autoimmunity and radiation exposure, as assessed by 137Cs soil levels or body 137Cs levels (UNSCEAR 

2000). One of the largest programs, the Chernobyl Sasakawa Health and Medical cooperation project 

(1991–1996), conducted thyroid examinations, including serum antithyroperoxidase and 

antithyroglobulin measurements, on approximately 160,000 children who were <10 years old at the time 

of the accident. No association between body or soil 137Cs activity and thyroid antibody levels was 

observed in an analysis of this screening program (UNSCEAR 2000, Annex J). 
IODINE 99 

3. HEALTH EFFECTS 

Hanford Nuclear Site. Thyroid autoimmunity was assessed as part of the CDC (2002) study of health 

outcomes related to radioiodine releases from the Hanford Nuclear Site (see Section 3.3.2 for a more 

detailed discussion of releases from the Hanford Nuclear Site). The study included 3,441 subjects who 

were born during the period 1940–1946 in counties surrounding the site. Thyroid autoimmunity was 

assessed from measurements of serum antimicrosomal antibody and antithyroid peroxidase. Historical 

information on thyroid disease, including autoimmunity and related disorders (e.g., Graves’ disease), was 

obtained by interviews and, when possible, review of medical records of participants. The estimated 

mean thyroid radiation dose in a population of 3,191 people who resided near the facility was 174 mGy 

(±224, standard deviation [SD]) (17.4±22.4 rad), and the range was 0.0029–2,823 mGy (0.00029– 

282 rad). Dose-response relationships were assessed using a linear regression model with adjustments for 

the following confounding and effect modifying variables: sex, age of first exposure, age of evaluation, 

ethnicity, smoking, and potential exposures from Nevada Test Site releases. Incidence of thyroid 

autoimmunity was found to be unrelated to thyroid radioiodine dose (dose coefficients were not 

significantly difference from zero). Estimated dose coefficients, based on the linear model, were 

-0.024±0.027 per Gy (CI: <-0.058–0.048, p=0.8) based on 659 cases (19.2% prevalence). Alternatives to 

the linear model including linear quadratic and logistic models were also explored. 

Uncertainties in the dose estimation methodology used in this study have been discussed in NAS (2000). 

Major sources of uncertainty derived from the reliance on modeling thyroid radiation doses, based on 

environmental transfer coefficients, rather than direct measurements. In particular, the NAS pointed out 

that the study utilized a transfer coefficient for radioiodine from cows to cow milk that was approximately 

twice that estimated from other studies. This could have contributed to an overestimate of thyroid doses 

in infants and children, and a lower statistical power of the study. Also, the study utilized survey 

information on the sources and amounts of milk consumed that was collected 40–50 years after the period 

of interest. Large uncertainties in estimates of these model parameters may have also decreased the 

statistical power of the study. Loss of power is particularly important in interpreting the generally 

negative findings of the study. 

3.3.2.4 Neurological Effects 

Exposure of a fetus to large amounts of radioiodine would result in thyroid tissue ablation and in similar 

delayed brain and neuromuscular development, if the hypothyroid state was not corrected (e.g., with 

hormone replacement therapy) after birth. An example is a case of severe hypothyroidism with 
IODINE 100 

3. HEALTH EFFECTS 

neurological sequellae that developed at age 8 months in an infant whose mother received 99 mCi 

(3.7 GBq) of 131I during her 6th week of pregnancy (Goh 1981). 

3.3.2.5 Reproductive Effects 

A clinical study of the outcomes of 70 pregnancies in patients who received 131I for ablative treatment of 

thyroid cancer 2–10 years (mean, 5.3 years) prior to pregnancy revealed only two spontaneous abortions 

(Casara et al. 1993). The maternal 131I exposures ranged from 1.85 to 16.55 GBq (50–450 mCi); the 

mean exposure was 4.40 GBq (120 mCi). Maternal gonadal radiation doses ranged from 11 to 20 cGy 

(11–20 rad). In a similar study, 37 patients received 131I prior to conception (mean, 16.5 months prior to 

conception; range 1–60 months); at exposures ranging from 1.1 to 13.1 GBq (30–350 mCi) with a mean 

exposure of 3.67 GBq (100 mCi) (Lin et al. 1998); of 58 pregnancies reported, there were 8 spontaneous 

abortions and 2 threatened abortions. In a retrospective review of pregnancy outcomes of 154 women 

who received ablative 131I therapy for thyroid cancer, two cases of infertility occurred in 35 patients who 

attempted to conceive (Smith et al. 1994). The 131I exposure range was 77–250 mCi (2.8–9.2 GBq) with a 

mean exposure of 148 mCi (5.5 GBq). The above studies did not have control comparison groups. 

The ATSDR (2000a) conducted a retrospective analysis of pregnancy outcomes (pre-term birth rates, fetal 

death) and infant deaths among residents who lived near the Hanford Nuclear Site (see Section 3.3.2 for a 

more detailed discussion of releases from the Hanford Nuclear Site). The study reviewed records of 

outcomes of 72,154 births, 1,957 infant deaths, and 1,045 fetal deaths that occurred in Washington 

counties dear the Hanford Nuclear Site during the period 1940–1952. Subjects were assigned to one of 

four exposure categories based on the subject’s address (zip code) at the time of the subject birth or infant 

death, and estimated 131I exposures in 1945 in those areas were obtained from the Hanford Environmental 

Dose Reconstruction (HEDR) project (CDC 2002). The exposure categories were: low, #50th percentile 

of the 1945 HEDR estimate for the entire study area; medium low, >50th percentile and <75th percentile; 

medium high, ≥75th percentile and # 90th percentile; and high, >90th percentile (radioiodine doses 

associated with these percentiles are not reported in CDC 2002). Associations between 131I exposure and 

outcomes were evaluated in a multivariate logistic regression model. Co-variates that were explored 

included sex of infant, age of mother, race of mother, occupation of father, and history of previous 

pregnancies, stillbirths, or infant mortality. Models were evaluated for outcomes recorded for 1945, the 

year in which exposures were estimated to be the highest, and also for the period May 1, 1945–April 30, 

1946, which could have included exposures to the highest levels during early pregnancy. The adjusted 

odds ratios (low-exposure as the reference) for infant death for the high-exposure category were 1.1 
IODINE 101 

3. HEALTH EFFECTS 

(95% CI, 0.7–1.8) for the year 1945 and 1.3 (CI, 0.8–2.1) for the 1945–1946 period. The adjusted ORs 

for fetal death for the high-exposure category were 0.6 (CI, 0.2–1.6) for the year 1945 and 0.7 (CI, 0.3– 

1.7) for the 1945–1946 period. These results suggest that neither infant nor fetal death were significantly 

associated with estimated 131I exposures. The adjusted odds ratios for preterm birth for the high-exposure 

category were 1.6 (CI, 1.0–2.6) for the year 1945 and 1.9 (CI, 1.2–3.0) for the 1945–1946 period, 

suggesting a possible association between preterm birth and 131I exposures. 

An assessment of uncertainties in the CDC (2002) study is provided in NAS (2000). Major sources of 

uncertainty derived from the reliance on modeling thyroid radiation doses, based on environmental 

transfer coefficients, rather than direct measurements, use of a relatively high value for the transfer 

coefficient for radioiodine from cows to cow milk, and reliance on survey information on the sources and 

amounts of milk consumed that was collected 40–50 years after the period of interest. Large uncertainties 

in estimates of these model parameters may have decreased the statistical power of the study. Loss of 

power is particularly important in interpreting the negative findings of the study. 

A retrospective analysis was conducted to evaluate pregnancy health and reproductive outcomes of 

women who were exposed to radiation resulting from releases from the Chernobyl nuclear power plant, 

including a major contribution from 131I (Petrova et al. 1997) (see Section 3.3.2 for a more detailed 

discussion of exposures from the Chernobyl accident). Interpretation of the results of this study, in terms 

of the contribution of radioiodine to the outcomes, is highly uncertain, as other factors could have affected 

the outcomes, including exposure to other forms of radiation, nutrition, or other chemical exposures. 

Nevertheless, because it is one of the only large-scale epidemiological studies that has focused on 

reproductive and developmental outcomes, and because of the substantial contribution that radioiodine 

made to radiation exposures after the Chernobyl releases, a brief description of the study is presented 

here. In the retrospective analysis, clinical records on 755,297 pregnancies that occurred in Belarus 

during the period 1982–1990 were evaluated. Approximately half of the women resided in Gomel and 

Mogilev, two districts that were relatively heavily contaminated with radioiodine and other radionuclides, 

and approximately half of the women lived in two relatively lightly contaminated areas, Brest and 

Vitebsk. Three categories of outcomes were evaluated: pregnancy outcome, including stillbirths, low 

birth weight, and neonatal or postneonatal mortality; maternal morbidity; and infant health, including 

intrauterine hypoxia, perinatal infection, respiratory disorders, and congenital anomalies. Annual 

incidence of maternal anemia, renal insufficiency (elevated serum BUN and creatinine), and toxemia 

appeared to increase more sharply in the heavily contaminated districts after 1986, the year of the 

Chernobyl releases (a statistical analysis of trend was not reported). Incidence of congenital 
 

 

IODINE 102 

3. HEALTH EFFECTS 

abnormalities and neonatal respiratory disorders also appeared to increase more sharply in the heavily 

contaminated districts after 1986 (no statistical analysis of trend was reported). Fetal death rates appeared 

to increase or not decline in contaminated districts to the same extent as in less contaminated districts. 

A cohort study was conducted as part of this retrospective analysis (Petrova et al. 1997). Health records 

on 757 infants and their mothers who resided in radiation-contaminated or relatively uncontaminated 

areas of Belarus were analyzed. The prevalence of maternal toxemia was 4–5 times greater among 

women who resided in contaminated areas (25–30%) compared to women from the control areas. The 

prevalence of atopic dermatitis in infants who resided in contaminated areas was approximately 2 times 

higher (approximately 40%) compared to infants from control areas. The prevalence of anemia (low 

blood hemoglobin levels) was 6–7 times higher in infants from contaminated areas (18–20%). The 

contribution of radioiodine to the observed outcomes is highly uncertain as other factors could have 

affected the outcomes, including exposure to other forms of radiation, nutrition, or other chemical 

exposures. 

Clinical cases of impaired testicular function have been reported following oral exposures to 131I for 

ablative treatment of thyroid cancer (Ahmed and Shalet 1985; Handelsman and Turtle 1983; Pacini et al. 

1994). Effects observed included low sperm counts, azospermia (absence of spermatozoa), and elevated 

serum concentrations of follicle stimulating hormone (FSH), which persisted for more than 2 years of 

follow-up. Exposures to radioiodine ranged from 50 to 540 mCi (1.8–20 GBq). A study of 103 patients 

who received 131I treatments for thyroid cancer found low sperm counts and elevated serum FSH 

concentrations in some patients when examined 10–243 months after treatment (mean, 94 months) (Pacini 

et al. 1994). Exposures to radioiodine ranged from 30 to 1,335 mCi (1.1–49.4 GBq) with a mean 

exposure of 167 mCi (6.2 GBq). 

Wichers et al. (2000) examined testicular endocrine function in 25 patients before and after they received 

131I for ablative treatment of thyroid carcinoma. The mean cumulative exposure was 9.8"0.89 GBq 

(260 mCi). Serum concentrations of follicle stimulating hormone (FSH), luteinising hormone (LH), 

inhibin B, and testosterone were significantly different from pre-exposure levels. Increases in FSH 

(300%) and LH (100%), and decrease in inhibin B concentrations (88%) showed similar temporal 

patterns, with peak responses 3–6 months after exposure and a return to pre-exposure levels within 

18 months following exposure. Peak levels of FSH (21 UU/L) exceeded the upper limit of the normal 

range (1.8–9.2 IU/L) and the lowest post-exposure levels of inhibin B (22 pg/mL) were below the lower 

limit of the normal range (75-350 pg/mL). Serum concentrations of LH remained within the normal 
 

 

IODINE 103 

3. HEALTH EFFECTS 

range (1.6–9.2 IU/L). Serum concentrations of testosterone were significantly higher (50%) than preexposure levels 12 and 18 months after exposure; however, concentrations remained within the normal 

range (10.4–34.7 nmol/L). These results suggest that exposures to high levels of 131I may affect testicular 

endocrine function. A major limitation of this study is the lack of observations in a set of controls who 

underwent thyroidectomy but who were not exposed to 131I. 

The highest NOAEL values and all reliable LOAEL values in each duration category for reproductive 

effects from exposures by the oral route are presented in Table 3-2 and plotted in Figure 3-2. 

3.3.2.6 Developmental Effects 

A clinical study of the outcomes of 70 pregnancies in patients who received 131I for ablative treatment of 

thyroid cancer 2–10 years (mean, 5.3 years) prior to pregnancy revealed only two spontaneous abortions 

(Casara et al. 1993). Of 73 infants born to the patients, one was diagnosed with tetrology of Fallot’s 

(pulmonic stenosis, atrial septal defect, and right ventricular hypertrophy) and the two other infants had 

low birth weights with subsequent normal growth rates. The maternal 131I exposures ranged from 1.85 to 

16.55 GBq (50–450 mCi); the mean exposure was 4.40 GBq (120 mCi). Maternal gonadal radiation 

doses ranged from 11 to 20 cGy (11–20 rad). A similar study was reported of 37 patients who received 

131I 1–60 months prior to conception (mean, 16.5 months); exposures ranged from 1.1 to 13.1 GBq (30– 

350 mCi) with a mean exposure to 3.67 GBq (100 mCi) (Lin et al. 1998); of 58 pregnancies reported, 

there were 8 spontaneous abortions and 2 threatened abortions. Birth weights of newborns of women 

who received 131I were not different from newborns of maternal age-matched controls who did not receive 

131I and who were not thyroid cancer patients. A retrospective review of pregnancy outcomes of women 

who received ablative 131I therapy for thyroid cancer found 3 spontaneous abortions and 4 premature 

deliveries out of 67 pregnancies in 32 patients (Smith et al. 1994). Two infants were born within 1 year 

of the maternal 131I therapy and both died of congenital abnormalities; severe hypoparathyroidism and 

hypothyroidism in one case, and Down’s syndrome and cardiac anomalies in the second case. The 131I 

exposure range was 77–250 mCi (2.8–9.2 GBq) with a mean exposure of 148 mCi (5.5 GBq). Goh 

(1981) reported a case of cretinism that developed at age 8 months in an infant whose mother received 

99 mCi (3.7 GBq) of 131I during her 6th week of pregnancy. 

ATSDR (2000b) conducted a retrospective analysis of pregnancy outcomes (pre-term birth rates, fetal 

death) and infant deaths among residents who lived near the Hanford Nuclear Site (see discussion of 

Reproductive Effects of Radioactive Iodine for a more detailed description of this study and Section 3.3.2 
54

145

55

325

56

2000

53

180

50

30

51

30

57

5

Table 3-2 Levels of Significant Exposure to Iodine - Radiation Toxicity - Oral 

Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain) System (rad) (rad) (rad) 

ACUTE EXPOSURE Systemic 

1 Human 

Endocr 145 (thyroid gland nodularity) 

2 Human 

Endocr 325 (thyroid gland nodularity) 

3 Human 

Endocr 2000 (thyroid gland nodularity) 

4 Human 

Endocr 180 (thyroid gland nodularity) 

Cancer 

5 Human 

30 (thyroid cancer) 

6 Human 

30 (thyroid cancer) 

7 Human (F) 

5 (kidney and liver cancer) 
58

6000

52

20

17

30097

9

99

325

100

25

a

Key to 

figure 

Species 

(Strain) 

LOAEL 

NOAEL Less Serious

System 

Table 3-2 Levels of Significant Exposure to Iodine - Radiation Toxicity - Oral 

(rad) (rad) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

Serious 

(rad) 

(continued) 

8 Human (F) 6000 (thyroid cancer) 

9 Human 20 (thyroid cancer) 

10 

CHRONIC EXPOSURE Systemic 

Human (F) Endocr 17 

11 

Cancer 

Human (F) 9 (thyroid neoplasm) 

12 Human (F) 325 (thyroid neoplasm) 

13 Human (F) 25 (thyroid neoplasm) 

a the number corresponds to entries in Figure 3-2.Endocr = endocrine; (f) = feed; LOAEL = lowest-observed-adverse-effect level
10000 

Endocrine Cancer * 

Figure 3-2. Levels of Significant Exposure to Iodine - Radiation Toxicity - Oral 

Acute (≤14 days) 

Systemic 

mg/kg/day 

8 

3 

1000 

2 4
 1
 

100
 

5 6 

9 

10 

7 

*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. 

1 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
1000 

Endocrine Cancer * 

Figure 3-2. Levels of Significant Exposure to Iodine - Radiation Toxicity - Oral (Continue

Chronic (≥365 days) 

Systemic 

mg/kg/day 

12 

100 

13 

10 

10 11 

*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.

1 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
 

 

 

IODINE 108 

3. HEALTH EFFECTS 

for a more detailed discussion of releases from the Hanford Nuclear Site). The study reviewed records of 

outcomes of 72,154 births, 1,957 infant deaths, and 1,045 fetal deaths that occurred in Washington 

counties dear the Hanford Nuclear Site during the period 1940–1952. Subjects were assigned to one of 

four exposure categories (low, medium low, medium high, high) based on the subject’s address (zip code) 

at the time of the subject birth or infant death, and estimated 131I exposures in 1945 in those areas were 

obtained from the Hanford Environmental Dose Reconstruction (HEDR) project (CDC 2002). 

Associations between 131I exposure and outcomes were evaluated in a multivariate logistic regression 

model. Models were evaluated for outcomes recorded for 1945, the year in which exposures were 

estimated to be the highest, and also for the period May 1, 1945–April 30, 1946, which could have 

included exposures to the highest levels during early pregnancy. The adjusted odds ratios (low-exposure 

as the reference) for infant death for the high-exposure category were 1.1 (95% CI, 0.7–1.8) for the year 

1945 and 1.3 (CI: 0.8–2.1) for the 1945–1946 period. The adjusted odds ratios for fetal death for the 

high-exposure category were 0.6 (CI: 0.2–1.6) for the year 1945 and 0.7 (CI: 0.3–1.7) for the 1945–1946 

period. These results suggest that neither infant nor fetal death were significantly associated with 

estimated 131I exposures. The adjusted odds ratios for preterm birth for the high-exposure category were 

1.6 (1.0–2.6) for the year 1945 and 1.9 (1.2–3.0) for the 1945–1946 period, suggesting a possible 

association between preterm birth and 131I exposures. 

One epidemiological study has examined health outcomes of infants of mothers who resided in the 

Belarus region before or after the Chernobyl accident (Petrova et al. 1997) (see Section 3.3.2 for a more 

detailed discussion of exposures from of the Chernobyl accident). Interpretation of the results of this 

study, in terms of the contribution of radioiodine to the outcomes, is highly uncertain, as other factors 

could have affected the outcomes, including exposure to other forms of radiation, nutrition, or other 

chemical exposures. Nevertheless, because it is the only epidemiological study that has focused on 

reproductive and developmental outcomes, and because of the substantial contribution that radioiodine 

made to radiation exposures after the Chernobyl releases, a brief description of the study is presented 

here. As part of a retrospective cohort study, health records were analyzed on 757 infants and their 

mothers who resided in heavily radiation-contaminated areas of Belarus resulting from radionuclide 

releases from the Chernobyl nuclear power plant or relatively uncontaminated areas (Petrova et al. 1997). 

Prevalence of atopic dermatitis in infants who resided in contaminated areas was approximately 2 times 

higher (approximately 40%) compared to infants from control areas. The prevalence of anemia (low 

blood hemoglobin levels) was 6–7 times higher in infants from contaminated areas (18–20%). 

Interpretation of the results of this study, in terms of the contribution of radioiodine, to the outcomes, is 
IODINE 109 

3. HEALTH EFFECTS 

highly uncertain, as other factors could have affected the outcomes, including exposure to other forms of 

radiation, nutrition, or other chemical exposures. 

The highest NOAEL values and all reliable LOAEL values in each duration category for developmental 

effects from exposures by the oral route are presented in Table 3-2 and plotted in Figure 3-2. 

3.3.2.7 Cancer 

Cancer effect levels (CELs) for iodine exposures by the oral route are presented in Table 3-2 and plotted 

in Figure 3-2. 

The thyroid gland receives the highest radiation dose of any organ or tissue following an internal 

exposure to radioiodine (see Section 3.5, Toxicokinetics) and, therefore, cancer of the thyroid gland is the 

major health concern associated with radioiodine exposures. Children, in particular, are highly vulnerable 

to radioiodine toxicity. Cancer morbidity and mortality among populations that received exposures to 

radioiodine have been examined in several large-scale epidemiology studies. In general, these studies fall 

into several categories that can be distinguished by the sources of exposure and estimated radiation doses 

to the thyroid gland and include (Table 3-3): (1) exposure to high doses (10–20 mCi, 370–740 MBq; 

>10,000 rad, >100 Gy) achieved when 131I is administered to treat hyperthyroidism (even higher doses are 

used to treat thyroid cancer); (2) exposures to moderately high doses (40–70 μCi, 1.5–2.6 MBq; 80– 

130 rad, cGy) associated with clinical administration of 131I for diagnosis of thyroid gland disorders; 

(3) low doses from exposures to fallout from nuclear bomb tests (BRAVO test, 300–2,000 rad, cGy; 

Nevada Test Site, 1–40 rad, cGy); (4) low to high doses from exposures to releases from nuclear power 

plant accidents (Chernobyl, 10–500 rad, cGy); and (5) low to high environmental exposures from 

operational releases from nuclear fuel processing plants (Hanford Nuclear Site, 0.0001–284 rad, cGy). As 

a point of reference, the dose-response relationship for thyroid cancer and external radiation appears to 

extend down to thyroid doses of 0.1 Gy (10 rad) and predicts an excess relative risk (ERR) of 7/Gy for 

ages <15 years at exposure (Ron et al. 1995). Studies of thyroid cancers and external radiation exposure 

have found a strong dependence of thyroid cancer risk on age at exposure. Risk is substantially greater 
 

 

IODINE 110 

3. HEALTH EFFECTS 

Table 3-3. Estimated Thyroid Radiation Doses in Populations Studied for 

Radioiodine-related Cancersa
 

Type of exposure 

Estimated thyroid 

radiation dose (cGy)a Referenceb 

Radioiodine therapy for hyperthyroidism >5,000c Holm et al. 1991; Ron et al. 1998 

Clinical diagnosis of thyroid gland 

disorders 

80–130c Hall et al. 1996b 

Marshall Islands BRAVO test 280–2,100c Hamilton et al. 1987; Lessard 

et al. 1985 

Chernobyl power plant accident <1–200d Astrakova et al. 1998 

Nevada Test Site nuclear bomb tests 1–30c Gilbert et al. 1998; Kerber et al. 

1993; Rallison 1996 

Hanford Nuclear Site releases 17±22 (0.003–282)d CDC 2002 

a

1 cGy=1 rad 

b

See text for additional references 

c

Cohort means 

d

arithmetic mean ± SD (range) 
 

 

IODINE 111 

3. HEALTH EFFECTS 

for radiation doses received prior to age 15 years when compared to risks for doses received at older ages, 

and this increased risk persists, possibly for the lifetime (Ron et al. 1995). This same general trend in 

age-dependence would be expected for internal exposures to radioiodine; thus, studies of adult exposures 

to radioiodine may not be directly applicable to predicting outcomes from exposures to children. The 

relatively high and acutely cytotoxic radiation doses to the thyroid gland that are achieved in the treatment 

of thyroid gland disorders, and outcomes on the thyroid, are not relevant for predicting outcomes from the 

much lower environmental exposures that occur in most U.S. populations; for example, exposures 

received as a result of nuclear bomb testing (Nevada Test Site) or operational releases from nuclear plants 

(Hanford Nuclear Site). This is in part because cell killing effects decrease the number of viable cells that 

might otherwise be transformed by radiation-associated mutagenesis. Uncertainties in estimating thyroid 

doses are also greater in persons who have thyroid abnormalities because of the nonuniform distribution 

of radioiodine in the thyroid gland (NCRP 1985). Nevertheless, high-dose studies are summarized 

because they provide useful information about the magnitude of radioiodine exposures that would present 

an elevated risk for thyroid and extrathyroidal cancers. Although not specified in most of these studies, it 

is likely that radioiodine was administered as a single dose by the oral route as either potassium or sodium 

iodide, as these are the common clinical practices. However, it is also possible, but highly unlikely, that 

some patients received the radioiodine by injection. Since absorption of an oral dose of iodide is nearly 

complete, this is unlikely to be a significant issue in interpreting the outcomes of the studies, except in 

considering the radiation dose to the gastrointestinal tract. 

Breast cancer is also a concern with exposures to high levels of radioiodine after ablative therapy for 

hyperthyroidism because breast expresses NIS and can transport and accumulate iodide (see 

Sections 3.5.4.2 and 3.6.1, Distribution). However, the epidemiological literature to date has not 

implicated such exposures as a significant risk factor for breast cancer (Goldman et al. 1988; Green et al. 

1995). 

Therapeutic Doses of Radioiodine 

Several studies have explored possible associations between radioiodine therapy for thyroid disease and 

cancer incidence or mortality. The Ron et al. (1998) study specifically assessed cancer outcomes in 

patients who received only 131I, and distinguished these patients from those who received other types of 

treatments alone, or in combination with 131I. This is an important design feature, as the study showed 

that other forms of treatment appear to be risk factors for cancer mortality. The Ron et al. (1998) study 

used a retrospective cohort design to examine cancer mortality in 35,593 patients (79% females; mean 

age, 46 years, 3% younger than 20 years) treated for hyperthyroidism (91% Graves’ disease, 8% toxic 
IODINE 112 

3. HEALTH EFFECTS 

nodular goiter) in 25 U.S. hospitals and 1 British hospital (Ron et al. 1998). The mean total activity 

administered was 10.4 mCi (385 MBq; 5th–95th percentile, 3–27 mCi, 111–999 MBq). The mean total 

administered activity was 10.0 mCi (370 MBq) for treatment of Graves’ disease and 17.0 mCi (629 MBq) 

for toxic nodular goiter. Cancers that occurred between the first visit of the patient to the clinic during the 

enrollment period (1946–1964) until either the death of the patient or the end of the calendar year 1990 

were considered in the analysis. Estimates of expected numbers of cancer deaths were based on U.S. 

national mortality rates for the period 1958–1985. Patients were stratified into various categories of 

treatment, distinguishing those who received 131I as the only form of treatment from those who received 

antithyroid drugs or surgical treatments, alone or in combination with 131I. SMRs (observed/expected 

deaths) were calculated for various treatments (131I, surgery, antithyroid drugs, or combinations). This 

design allowed an assessment of the effects of possible associations between 131I exposure and cancer 

outcomes, independent of the potential effect of other treatments. The study identified 2,960 cancer 

deaths, 29 of which were classified as thyroid cancers. Among patients who received 131I as treatment 

alone (only 131I), SMRs were significantly elevated only for thyroid cancer (4.91; 95% CI, 2.45–8.79), but 

not for other cancers, or all cancers. Among all patients treated with 131I, alone or in combination with 

other treatments (any 131I), SMRs were also significantly elevated for thyroid cancer (3.94, 252–5.86), 

only. When stratified by latency (1–4 years, 5–9 years, 10 years or longer), in the latter group (any 131I), 

SMRs for thyroid cancer were highest 1–4 years after treatment (12.32, 6.38–21.61), but remained 

significantly elevated in the 10 years or longer group (2.78, 1.38-4.97). Radiation doses to specific 

organs were estimated for each patient based on the administered activity and dosimetry tables developed 

by the ICRP (1988). The estimated thyroid dose was 50–70 Gy (5,000–7,000 rad). When stratified by 

administered 131I activity (as a surrogate for thyroid dose), the SMRs for thyroid cancer in this group (any 

131I) increased with increasing exposure, suggesting a possible dose effect on thyroid cancer mortality. 

The highest SMRs occurred in the group that received 15 mCi or more (7.05, 3.05–13.95), and in the 

group treated for toxic nodular goiter (18.88, 7.58–38.98), who would have received higher exposures and 

doses than Graves’ disease patients (2.84, 1.62–4.61). SMRs for cancers in other tissues were also 

significantly elevated in the any 131I group; colorectal cancer, 1–4 years after treatment (1.42, 1.04–1.90); 

lung cancer 1–4 years (1.49, 1.01–2.12) and 5-9 years (1.41, 1.02–1.89) after treatment; and for nonchronic lymphatic leukemia, 5–9 years after treatment ( 2.10, 1.14–3.52). However, interpretation of 

these findings, in terms of the potential contribution of 131I to cancer mortality, is complicated by the 

finding of elevated SMRs in extra-thyroidal tissues in the groups that received treatments other than 131I, 

including bucal cavity, lung, breast, and brain. The results of this study indicate that high exposures to 

131I for treatment of hyperthyroidism did not increase overall cancer mortality; however, it did appear to 

increase mortality for thyroid cancer. Interpretation of the effect on thyroid cancer mortality is 
 

 

IODINE 113 

3. HEALTH EFFECTS 

complicated by the potential impact of thyroid cancers that may have existed in these patients, 

undiagnosed, prior to the treatment. The observation that much of the apparent excess risk for thyroid 

cancer deaths occurred during the first 1–4 years after 131I treatment, suggests a remarkably short latency 

for radiation-induced cancer mortality, or possibly other factors contributed to the outcome. Other 

uncertainties in this study include the use of exposure levels (mCi) as a surrogate for absorbed radiation 

dose to the thyroid. The relationship between administered activity and thyroid dose in hyperthyroid 

patients can be complicated by disease-related variation in thyroid gland size and iodide transport activity. 

Also, administered activity can co-vary with the severity of the initial hyperthyroidism; patients who 

received the highest activities tend to have the most severe disease, and disease severity could vary, 

independently with cancer mortality. 

A retrospective cohort study conducted in Sweden examined cancer incidence among 10,552 patients 

(85% females; age 13–74 years) who received 131I therapy for treatment of Graves’ disease (51%) or toxic 

nodular goiter (42%) (Holm et al. 1991). The mean total activity administered was 506 MBq (13.7 mCi); 

however, this varied with the objectives of the therapy; 360 MBq (9.7 mCi) for treatment of Graves’ 

disease and 700 MBq (18.9 mCi) for toxic nodular goiter. The distribution of the administered activity in 

the study population was as follows: 30% <220 MBq (5.9 mCi), mean, 150 MBq (4.1 mCi); 38% 221– 

480 MBq (6–13 mCi), mean 315 MBq (8.5 mCi); and 32% >480 MBq (13 mCi), mean 1,063 MBq 

(28.7 mCi). Cancers that occurred from 1 year after treatment (on or after 1958) until either the death of 

the patient or the end of the calendar year 1985 were considered in the analysis. Expected numbers of 

cancers were estimated from data from the Swedish Cancer Register for the period 1958–1985. Standard 

incidence ratios (SIR, observed/expected cancers) were significantly elevated for cancers of the lung 

(1.32, 95% CI, 1.07–1.59) and kidney (1.39, 95% CI, 1.07–1.76). Among toxic nodular goiter patients, 

who received, on average, twice the dose as Graves’ disease patients, the SIR was also significantly 

elevated for liver cancer (2.14, 1.20–3.52). Among 10-year survivors, significantly elevated SIRs 

included stomach (1.33, 1.01–1.71), kidney (1.51, 1.06–2.08), and brain (1.63, 1.10–2.32). Doses to 

specific organs were estimated for each patient based on the administered activity and dosimetry tables 

developed by the ICRP (1988). Estimated average radiation doses to these tissues were: thyroid gland, 

>10,000 cGy (>10,000 rad); stomach, 25 cGy (25 rad); lung, 7 cGy (7 rad); kidney, 5 cGy (5 rad); liver, 

5 cGy (5 rad); and brain (not reported). There were no significant dose trends. Notably, SIRs for thyroid 

cancer were not significantly elevated (SIR 1.29, 0.76–2.03). Some of the patients in this study received 

treatments other than 131I for thyroid disorders, including antithyroid drugs (14%), surgery (3%), and/or 

thyroid hormone supplements (2%). Cancer mortality was examined in the same cohort (Hall et al. 

1992a). Standard mortality ratios (SMRs) were calculated based on data from the Swedish Cause-of­
 

 

 

 

IODINE 114 

3. HEALTH EFFECTS 

Death Registry. SMRs were significantly elevated for all cancers (1.14, 1.04–1.24), digestive tract 

cancers (1.28, 1.16–1.45), and respiratory tract cancers (1.31, 1.01–1.66) among patients who had greater 

than a 10-year follow up from the date of their exposure to 131I, and for thyroid gland cancer during the 

first year (11.45, 2.8–33.72). There were no significant dose trends, although the SMR for thyroid gland 

cancer was approximately 4 times higher in patents who received >480 MBq (13 mCi) than in patients 

who received <221 MBq (6 mCi). The results of this study suggest that exposure to high levels of 131I for 

treatment of hyperthyroidism increases cancer risk; however, several uncertainties complicate the 

interpretation of results, in terms of the contribution of 131I to the elevated cancer risk. These include the 

lack of a dose trend for increased cancer incidence or mortality, and the potential contribution of 

treatments, other than 131I to cancer incidence and mortality, which were not quantified in this study. 

Surgical treatment and antithyroid drug therapy appear to be cancer risk factors in hyperthyroid patients 

(Ron et al. 1998). 

A retrospective study examined cancer morbidity and mortality in 7,417 patients (83% females; mean 

age, 57 years ± 13, SD) treated for hyperthyroidism in the West Midlands region of the United Kingdom 

during the period 1950–1991(Franklyn et al. 1999). The mean total activity administered was 308 MBq 

(8.3 mCi); 49% received <220 MBq (<6 mCi) and 17% received >481 MBq (>13 mCi). The follow-up 

period ranged from 1 year (74%) to $20 years (18%). Estimates of expected numbers of cancer deaths in 

England and Wales were based on International Agency for Research on Cancer (IARC) and World 

Health Organization (WHO) data. The SIR for all cancer types was 0.83 (95% CI, 0.77–0.90). The SIR 

for thyroid cancer was 3.25 (1.69–6.25) and for cancer of the small bowel, 4.81 (2.16–10.72). SIRs for all 

other cancers were <1. Similarly, SMRs were 0.90 (0.82–0.98) for all cancer types, 2.78 (1.16–6.67) for 

thyroid cancer, and 7.03 (3.16–15.66) for cancer of the small bowel. Significant positive trends for 

increasing incidence with increasing cumulative radiation exposure were observed for bladder cancer and 

uterine cancer, although SIRs and SMRs for these cancers were not significantly greater than 1. The 

results of this study, consistent with those of the Hall et al. (1992a) and Ron et al. (1998), suggest that 

exposure to high levels of 131I for treatment of hyperthyroidism increases the risk of cancer mortality; 

however, similar to the Hall et al. (1992a) study, the potential contribution of treatments other than 131I 

(e.g., surgical treatment and antithyroid drug therapy, Ron et al. 1998), to cancer incidence and mortality, 

were not quantified in this study. Surgical treatment and antithyroid drug therapy appear to be cancer risk 

factors in hyperthyroid patients (Ron et al. 1998). Other potential uncertainties in interpreting the 

Franklyn et al. (1999) study include: (1) thyroid radiation doses were not reported; thus, it is difficult to 

compare the doses received to subjects in this studies with those in the Ron et al. (1998), Holm et al. 

(1991), and Hall et al. (1992a) studies; (2) the Franklyn et al. (1999) study did not stratify the subjects by 
 

 

 

IODINE 115 

3. HEALTH EFFECTS 

radiation exposure or dose, which may have varied depending on the nature of the original diagnosis of 

hyperthyroidism; and (3) the size of the cohort in the Franklyn et al. (1999) study was smaller than the 

other three studies (7,417 compared to 35,593 in Ron et al. 1998 study, and 10,552 in Holm et al. 1991 

study). 

A follow-up cohort study was conducted of cancer morbidity and mortality among 1,762 women who 

received ablative 131I therapy for hyperthyroidism during the period 1946–1964 (Goldman et al. 1988). 

The follow-up period was 17 years. SMRs and SIRs were estimated based on age-, date-, sex-, and racespecific mortality incidence and mortality of the United States or Massachusetts population. The cohort 

was stratified into treatment categories that included only 131I or 131I in addition to other therapies for 

hyperthyroidism. SIRs in the 131I-only group were not significantly elevated for any cancer type or group. 

SMRs in the 131I-only group were significantly elevated for cancers of all causes (SMR, 1.2, 1.1–1.4, 

95% CI, 10 cases). There were no significant radiation dose trends. Exposures ranged from 0.1 to 

>10 mCi (4–370 MBq). Although, like the Ron et al. (1998) study, cancer mortality risk was evaluated in 

patients who received only 131I as treatment, the much smaller size of the Goldman et al. (1988) study 

makes it difficult to interpret comparisons of results to those from the Ron et al. (1998) study. Like the 

Ron et al. (1998) study, Goldman et al (1988) found elevated cancer mortality in patients who received 

treatments other than 131I. 

A follow-up study was conducted of cancer morbidity among 1,771 patients (21% males) who received 

ablative 131I therapy for treatment of thyroid cancer during the period 1950–1990 (de Vathaire et al. 

1997). The follow-up period was 10 years. Excess relative risk (ERR) was modeled using linear models 

(a quadratic model was also explored), taking into account sex, age at time of treatment, and cumulative 

activity of 131I administered as variables. The mean administered activity of 131I was 7.2 GBq (range, 3.8– 

57.6; 195 mCi, range, 103–156 mCi) which corresponded to a mean radiation dose to bone marrow of 

0.34 Sv (range, 0.13–2.8; 34 rem, range, 13–280 rem). Using the cancer outcomes of patients who 

received 1–0.19 GBq of 131I as the reference group, ERRs for colorectal cancer increased with increasing 

administered activity. In the patient group that received >3.7–7.5 GBq (>100–203 mCi) the ERR was 

4.0 (90% CI, 1.3–12.2) and in the group that received >7.5 GBq>(203 mCi), the ERR was 4.9 (1.2–18.5). 

While this is a relatively small study, it supports an outcome of the much larger Ron et al. (1998) study in 

which SMRs for colorectal cancer were elevated among patients who received lower administered 

activities of 131I for treatment of hyperthyroidism (mean 10.4 mCi, 385 MBq). 
IODINE 116 

3. HEALTH EFFECTS 

Diagnostic Doses of Radioiodine 

A retrospective cohort study examined thyroid cancer incidence among 34,104 patients (80% females, 1– 

75 years of age) in Sweden who received 131I for diagnosis of thyroid disorders during the period 1950– 

1969. The follow-up period was from 1958 to 1990 (Hall et al. 1996b). A total of 2,408 patients (7%) 

were exposed before 20 years of age and 316 patients were exposed before 10 years of age (1%). The 

diagnostic test was for a suspected thyroid tumor in 10,785 (32%) patients and for hypothyroidism, 

hyperthyroidism, or other reasons in 23,319 (68%) patients. The follow-up period ranged from 5 to 

39 years after exposure (thyroid cancers detected within 5 years of the diagnostic test were excluded on 

the basis that they may have been related to cancer present at the time of the diagnostic test). The mean 

total activity administered was 2.4 MBq (65 μCi) for patients suspected of having a thyroid gland tumor 

and 1.6 MBq (43 μCi) for other patients. Radiation doses to the thyroid gland were estimated for each 

patient based on the administered activity and dosimetry tables developed by the ICRP (1988). The mean 

absorbed dose was 1.3 Gy (130 rad) for suspected thyroid tumor patients and 0.8 Gy (80 rad) for other 

patients. SIRs were calculated based on sex-, age-, and date-adjusted cancer incidence rates based on the 

Swedish Cancer Registry. Sixty-seven thyroid tumors were identified during the period of the study, of 

which 42 (63%) were in patients who received 131I for diagnosis of a suspected thyroid gland tumor. SIRs 

were significantly elevated only in the latter group (2.86, 95% CI, 2.06–3.86), but not in patients tested 

for other suspected thyroid disorders. There were no significant dose trends for thyroid cancer in either 

group, and the presence of cancer may have predated the exposures to 131I. A subsequent follow-up of 

this same cohort was conducted, which extended the follow-up period an additional 8 years from that 

reported in Hall et al. (1996b) and included thyroid cancers diagnosed as early as 2 years after diagnostic 

administration of 131I, making the follow-up period 2-47 years (Dickman et al. 2003). Patients (1,767) 

who received diagnostic X-rays to the neck, prior to receiving 131I, were also included in the study to 

explore the effects of external radiation on thyroid cancer incidence. Among patients who did not receive 

X-rays to the neck and who were not referred for diagnostic 131I for suspicion of a possible thyroid tumor, 

the SIR for thyroid cancer was 0.91 (95% CI, 0.64–1.26). The estimated dose to the thyroid in this group 

was 0.94 Gy (94 rad). However, among patients who did receive X-rays prior to 131I, the SIR was 

9.8 (6.3–14.6). The results support the previous findings in this cohort (Hall et al. 1996b) that radiation 

doses to the thyroid resulting from diagnostic administration of 131I are not associated with excess risk of 

thyroid cancer. The study also identifies X-ray exposures as an important variable that, if not controlled 

for, could confound studies of cancer outcomes in patients exposed to 131I. 

The incidence of cancer in extrathyroidal organs was examined in this same cohort (Holm et al. 1989). At 

that time, the cohort consisted of 35,074 patients, 31% of whom received 131I for diagnosis of a suspected 
IODINE 117 

3. HEALTH EFFECTS 

thyroid gland tumor, 42% for suspected hyperthyroidism, 16% for suspected hypothyroidism, and 8% for 

other reasons (the basis for the diagnostic procedure could not be determined for 3% of the patients). The 

mean total activity administered was 52 μCi (range 1–960 μCi) (1.9 MBq, 0.04–36 MBq). The mean total 

administered activity was 71 μCi (2.6 MBq) for patients suspected of having a thyroid tumor, 48 μCi 

(1.8 MBq) for diagnostic tests for hyperthyroidism, and 40 μCi (1.5 MBq) for other diagnostic purposes. 

SIRs were significantly elevated for cancers of the endocrine organs other than thyroid gland (1.93, 1.62– 

2.29), lymphomas (1.24, 1.03–1.48), and leukemias (1.34, 1.11–1.60). The SIR for nervous system 

cancers was 1.19 (1.00–1.41). The SIR for thyroid cancer was significantly elevated only in the 5–9-year 

period of follow-up. There were no significant dose trends. In this study, unlike the Hall et al. (1996b) 

study, SIRs were calculated for all patients, regardless of the intended purpose of the diagnostic test, 

including patients who were administered 131I for the diagnosis of suspected thyroid tumors. 

A smaller retrospective cohort study compared thyroid cancer incidence among 789 patients (74% 

females) in Germany who received 131I for diagnosis of thyroid disorders before the age of 18 years with 

1,118 patients who received a diagnostic procedure on the thyroid that did not involve radioiodine (68% 

females) (Hahn et al. 2001). Diagnostic procedures occurred between 1958 and 1978 in the treatment 

group, and between 1959 and 1978 in the control group. The diagnosis made at the initial referral in the 

treatment groups was nodular goiter in 385 (49%) in patients, no evidence of thyroid disease in 199 (25%) 

patients, and hypothyroidism, hyperthyroidism, or other reasons in 205 (26%) patients. In the control 

group, the diagnoses included 600 (54%) cases of goiter, 327 (29%) of no evidence of thyroid disease, 

and 131 (12%) hypothyroidism, hyperthyroidism, or other reasons. Patients who had a history of external 

radiotherapy of the head or neck regions or thyroid cancer were excluded from the study. The follow-up 

period (1989–1997) ranged from 13 to 33 years in the treatment group and 9–33 years in the control 

group. The median total 131I activity administered in the treatment groups was 0.9 MBq (24 μCi). 

Radiation doses to the thyroid gland were estimated for each patient based on the administered activity 

and dosimetry tables developed by the ICRP (1988). The mean absorbed dose was 1.0 Gy (100 rad); 

however, this varied with age of diagnosis; the range was 0.6–1.2 Gy (60–120 rad). SIRs were calculated 

based on sex-, age-, and date-adjusted cancer incidence rates based on the German Democratic Republic 

cancer registry for the period 1980–1989. Three cases of thyroid cancer were identified in the treatment 

group during the study period and two cases in the control group. SIRs were 5.3 (95% CI, 0.5–15.1) in 

the treatment group and 5.3 (1.1–15.3) in the control group. The relative risk (treatment compared to 

control) was 0.9 (0.1–5.1). Risk of thyroid cancer was not significantly associated with exposure to 

diagnostic levels of 131I. A complication in the interpretation of these findings is that the response rate 

was very low: 3 cases in 1,058 patients, 0.28%; 2 in 795 in the treatment group. 
IODINE 118 

3. HEALTH EFFECTS 

A prospective study examined thyroid outcomes of children and adolescents (<20 years old) who received 

diagnostic doses of 131I during the period 1946–1967 (Hamilton et al. 1987). Study groups consisted of 

3,503 subjects who received diagnostic 131I, 2,495 control subjects who did not receive 131I and who were 

matched with the exposed subjects by sex-, age-, and diagnostic-test date, and a group of 1,070 siblings of 

the control group. The follow-up period was from entry into the study until 1986. Participants were 

surveyed with a questionnaire to identify those who had thyroid or neck surgery during the study period, 

and pathology reports and specimens were retrieved and reviewed by a panel of pathologists; neoplasms 

were classified and the results were compared with hospital pathology reports. The dose to the thyroid 

gland was estimated for each exposed subject based on the reported activity administered, percent thyroid 

uptake, and thyroid weight estimated from published thyroid growth tables. The median total absorbed 

dose was 20–40 rad (0.2–0.4 Gy) (95th percentile, 200–330 rads 2–3 Gy). The survey response rate was 

63%. A total of 34 surgeries were reported, of which 19 were on subjects who did not have any thyroid 

disorder diagnosed at the time of entry into the study; 16 of these subjects had confirmed thyroid tumors; 

10 benign, 8 of which occurred in the exposed group, and 6 malignant tumors, 5 of which occurred in the 

exposed group. Although these results are suggestive of a possible effect of 131I exposure on thyroid 

tumor incidence, the differences between the exposed and control groups were not statistically significant. 

Shore (1992) reviewed the results of the Hamilton et al. (1987) study and calculated a relative risk for 

thyroid cancer of 2.9 (90% CI, 0.6–15) based on the internal comparison of the exposed and unexposed 

groups in the Hamilton et al. (1987) study. Based on the Surveillance, Epidemiology and End Results 

(SEER) cancer data for 1973–1981 (U.S. DHHS 1985), 3.7 thyroid cancers would have been expected in 

the Hamilton et al. (1987) study, compared to the 4 observed during the period of 5 or more years after 

the diagnostic test (one of the cancers reported in the Hamilton et al. (1987) study occurred with a latency 

of 2 years), which, according to Shore (1992), indicates an SIR of 1.1 (95% CI, 0.3–2.6). 

Marshall Islands Nuclear Bomb Test BRAVO. Several epidemiological studies have examined thyroid 

gland disorders in residents of the Marshall Islands who were exposed to radioiodine from atmospheric 

fallout resulting from nuclear bomb tests (including the so-called BRAVO test; see Section 3.3.2 for a 

more detailed discussion of exposures from the Marshall Islands BRAVO test). A more complete 

discussion of these studies is presented in Section 3.3.1.2 (Endocrine), as the studies provide doseresponse information on thyroid disorders other than cancer. However, cancer outcomes have been 

examined in what has become known as the BRAVO cohort, as well as in larger samples of the Marshall 

Island population. Almost all that is known about radioiodine doses to the thyroid from the BRAVO test 

exposures derive from a few urinary measurements collected 15 days after the exposures. These have 
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been estimated to have been (external and internal): 3.3–20 Gy (330–2,000 rad) on Rongelap (highest 

doses in children), 1.3–4.5 Gy (130–450 rad) on Ailingnae, and 0.3–0.95 Gy (30–95 rad) on Utrik 

(Conard 1984). The BRAVO test was not the only potential source of radioiodine exposure in the 

Marshall Island population, as numerous bomb tests were conducted in the Marshall Islands during the 

period 1946–1958. 

The strengths of the Marshall Island studies include the relatively high range of thyroid radiation doses 

and the multiple thyroid screenings, which included, in the more recent studies, relatively objective 

assessments of nodularity by ultrasound. Limitations of the studies include: (1) large dose uncertainties 

in terms of total thyroid dose; (2) further dose uncertainties in terms of the fraction of the dose that was 

from 131I rather than from short-lived isotopes of iodine and gamma radiation; (3) no attempt to estimate 

individual thyroid doses; (4) inequities between the exposed and unexposed populations in the intensity of 

thyroid screening; (5) the relatively small number of exposed subjects in the BRAVO cohort; (6) the 

potential confounding effects of prophylactic iodide administration and thyroid surgery in highly exposed 

subjects; and (7) thyroid radiation dose estimates not available for larger scale studies of populations in 

the Marshall Islands. 

Evidence for a higher prevalence of thyroid cancer among the original 250 people known to have been 

heavily exposed as a result of the BRAVO incident has not been established; however, this may reflect 

the small size of the cohort (see section 3.3.2 for a more detailed discussion of exposures from the 

Marshall Islands BRAVO test). In 1982, a review of the diagnoses for thyroid nodules detected in 

250 exposed and 1,303 nonexposed Marshallanese revealed 9 definitive carcinomas (3.6%) and 

7 adenomas (2.8%) in the exposed group, and 6 carcinomas (0.5%) and 14 adenomas (1%) in the 

nonexposed comparison group (Conard 1984). Subsequent reviews of the thyroid pathology more or less 

agree with the conclusions of Conard (1984), although differences in the composition of comparison 

group have contributed to slightly different estimates of prevalence in the nonexposed population. For 

example, Howard et al. (1997) reported four cancers (1.8%) and one adenoma (0.4%) in a nonexposed 

comparison group. Takahashi et al. (1997) reviewed diagnoses of 22 cases of thyroid nodularity 

discovered in 1993 in an ultrasound screening program that evaluated 1,275 Marshall Island residents 

(mainly from Ebeye). The prevalence of thyroid cancer among patients referred for surgery-based thyroid 

gland ultrasound assessments suggested an overall prevalence of thyroid cancer of approximately 1.2% 

(15/1,275) in the population evaluated, or a 12% prevalence (15/123) of thyroid cancer among those who 

had palpable nodules. A follow-up to this study included the results of thyroid disease screening of 

3,709 Marshall Island residents who were born before the BRAVO test and who lived anywhere in the 
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Marshall Islands during the period of bomb testing. The study group included an estimated 60% of the 

still-living population who resided in the Marshall Islands during this period. Combining findings from 

the previous study (Takahashi et al. 1997) and the follow-up, a total of 57 thyroid cancers were identified 

(1.5%), of which 92% were diagnosed as papillary cancers. Several factors confound attempts to 

associate thyroid cancers in the Marshall Islands population with radioiodine exposures, including lack of 

definitive dosimetry, outside of the small BRAVO cohort. Changes occurred in diagnostic techniques 

used to detect thyroid nodules, which would direct further diagnostic attention; in particular, the use of 

ultrasound for detecting small thyroid nodules began only in 1994. More recent studies have also 

suggested a relatively high prevalence of iodine deficiency in the Marshall Islands, which may have 

affected background thyroid cancer prevalence (Takahashi et al. 1999). 

Nevada Test Site Nuclear Bomb Tests. During the period 1951–1958, 119 atmospheric nuclear bomb 

tests were conducted at the Nevada Test Site (NTS) in southern Nevada (NCI 1997). These tests were 

followed by 9 surface detonations during the period 1962–1968 and approximately 809 below-ground 

tests, of which 38 were determined to have resulted in off-site releases of radioactive materials. A dose 

estimation methodology was developed by the National Cancer Institute (NCI 1997), which has enabled 

estimation of population radiation doses to the thyroid gland from direct and indirect (e.g., in utero, 

ingestion of cow milk) exposures to 131I resulting from the NTS activities for the purpose of health 

assessments and epidemiologic investigations (Gilbert et al. 1998; Kerber et al. 1993). A discussion of 

the uncertainties and limitations of these population dose estimates for use in epidemiology studies and 

risk assessment can be found in a review of the NCI (1997) dose estimations conducted by the Institute of 

Medicine and the National Research Council (NRC 1999). 

The strengths of the NTS studies described above include the attempt to develop a systematic sampling 

frame, the careful, multiple thyroid screenings (two or more times), the relatively high follow-up rate, and 

the extensive attempt to characterize individual 131I doses. Limitations of the studies include: (1) the 

substantial dose uncertainties, since no thyroid exposure measurements were available and individual 

milk and vegetable consumption was recalled more than 30 years after the fact; (2) the food-consumption 

and behavioral questionnaire was conducted after subjects knew their thyroid outcomes; (3) the modest 

sample size and, therefore, small number of thyroid neoplasms found, which limited the statistical power 

and precision; (4) the relatively low dose range, which also limited the statistical power and precision; 

(5) the restriction of the thyroid examinations to palpation (no ultrasound); and (6) the fact that the 

thyroid examinations were only partially blinded (i.e., examiners often knew the subject’s geographic 

region). 
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A cohort study examined thyroid nodularity and performed diagnostic follow up in 2,678 adolescents (age 

11–18 years) who resided in Utah or Nevada near the NTS during the early 1950s and in a comparison 

population of 2,132 adolescents who lived in Arizona. Examinations were conducted during the period 

1965–1970 (Rallison et al. 1974). In a follow-up study conducted in 1985–1987, 1,962 of the original 

Utah-Nevada group and 1,160 from the Arizona group were reexamined (Rallison et al. 1990). 

Radioiodine doses were estimated for each Utah-Nevada subject based on histories of residence, local 

milk and leafy vegetable consumption, records of transport and deposition of radionuclides at their town 

and/or county of residence, and age-specific transfer factors relating iodine ingestion with iodine uptake 

in the thyroid gland (Kerber et al. 1993; Simon et al. 1990). Mean thyroid dose estimates were 150 mGy 

(15 rad) (maximum 4.6 Gy, 460 rad) in the Utah group, 50 mGy (5 rad) (maximum 0.84 Gy, 84 rad) in 

the Nevada group, and 13 mGy (1.3 rad) (maximum 0.45 Gy, 45 rad) in the Arizona group (the group 

names refer to cohort designations used in the study, which were based on the place of residence during 

the potential exposure period, and not necessarily where the entire radiation dose for each individual was 

received). In the 1965–1968 examinations, 76 of 4,819 people examined had palpable thyroid gland 

nodules, 22 of which were subsequently diagnosed as adenomas (20) or carcinomas (2). The prevalence 

of nodules was higher in the Utah-Nevada group (19.7/1,000) than in the Arizona group (10.8/1,000). 

Fifteen of the 22 neoplasms were found in the Utah-Nevada group (5.6/1,000) and 7 in the Arizona group 

(3.3/1,000) (Rallison et al. 1974). In 1985–1987, 125 new cases of thyroid nodularity were identified, 

65 of which were diagnosed as neoplasms and 5 of the latter were carcinomas. Five carcinomas were 

reported in the group during the interval between the two examinations. Combining the results of the first 

and second evaluations, including the five carcinomas observed during the interval (a total of 

12 carcinomas), resulted in similar prevalences in the two groups for nodules (Utah-Nevada 48.6/1,000, 

Arizona 36.6/1,000). Prevalence of neoplasms was not disparate: Utah-Nevada, 2.8/1,000 and Arizona, 

4.8/1,000 (Rallison et al. 1990). Thyroid nodules were detected in 56 of 2,473 subjects; 38 of these 

lesions were diagnosed as nonneoplastic (28 were colloid adenomas, the other 10 were miscellaneous 

nonneoplastic lesions), 11 were benign adenomas (of these, 8 were follicular adenomas and there was one 

each of papillary, fetal, and Hurthle cell adenomas), and 8 were papillary carcinomas (Rallison 1996). 

Stratifying the outcomes by estimated thyroid radiation dose revealed a significant dose trend for 

neoplasms, but not for all nodules or for carcinomas alone. The group that received a dose exceeding 

0.25 Gy (25 rad) had a thyroid neoplasm prevalence of 21–24/1,000, whereas groups that received 

<0.25 Gy had a prevalence of 4–5/1,000. The excess relative risk estimates per Gy were: neoplasms, 

7.0 (lower 95% confidence limit [CL], 0.74, p=0.019); nodules, 1.2 (95% CL<0, p=0.16); and 

carcinomas, 7.9 (95% CL<0, p=0.096) (Kerber et al. 1993). 
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In a large scale ecological study, mortality and incidence of thyroid cancer in 3,053 U.S. counties were 

compared to estimated exposures to 131I from releases from the NTS (Gilbert et al. 1998). Thyroid cancer 

mortality data were obtained from the National Center for Health Statistics for 1957–1994 and thyroid 

cancer incidence data from SEER for the period 1973–1994. County-specific or state-specific cumulative 

radiation doses were reconstructed based on NCI (1997) and were as follows (cGy, where 1 cGy = 1 rad): 

in utero, 4.3 cGy; 0–<1 year, 12.6 cGy; 1–4 years, 10.0 cGy; 5–9 years, 6.7 cGy; 10–14 years, 4.4 cGy; 

15–19 years, 3.1 cGy; $20 years, 1.1 cGy. During the study period, there were 12,657 cases of thyroid 

cancer and 4,602 thyroid cancer deaths. Age-, calendar-, sex-, and count-specific mortality and incidence 

rates in the United States were analyzed in relation to 131I dose estimates, taking into consideration 

geographic location, age at exposure, and birth cohort. There were no significant dose-related trends 

(linear excess relative risk model) in either thyroid cancer mortality or incidence when all exposure age 

groups were composited or when exposure age groups 1–5 years or 1–15 years were considered 

separately. However, when the exposure age group <1 year was analyzed, a dose trend was weakly 

suggested by highly positive excess relative risks (ERR) for thyroid cancer deaths when doses were 

county-specific (ERR 10.6 per Gy, 95% CI, -1.1–29, p=0.085) or state-specific (16.6 per Gy, -0.2–43, 

p=0.054), and for thyroid cancer incidence when doses were county-specific (2.4 per Gy, -0.5–5.6). 

These outcomes were strongly influenced by two deaths and nine cases of thyroid cancer that occurred in 

individuals who received estimated cumulative doses exceeding 9 cGy (9 rad) before they were 

12 months of age. 

Chernobyl Nuclear Power Plant Accident. Clinical records and cancer registries from the Republics of 

Belarus and Ukraine show an increase in the incidence of thyroid cancer in children and adolescents, 

which became apparent approximately 4 years after the release of radioactive materials from the 

Chernobyl nuclear power plant in April 1986, but which has not been increasing in recent years, 

especially among those exposed at older ages (Cherstvoy et al. 1996; Drobyshevskaya et al. 1996; 

Prisyazhuik et al. 1991; Tronko et al. 1996) (see Section 3.3.2 for a more detailed discussion of exposures 

from the Chernobyl accident). Belarus recorded an annual incidence of 0.09 cases per 100,000 in 1986 

among children between the ages of 4 and 17 years and 2.46 per 100,000 in 1991, with the highest 

incidence in the Gomel oblast; from 0.24 cases per 100,000 in 1986 to 12.5 per 100,000 in 1991 

(Drobyshevskaya et al. 1996). In the Ukraine, annual incidence of thyroid cancer in children and 

adolescents (under 15 years of age) increased from approximately 0.05 per 100,000 prior to 1986 to 

0.43 per 100,000 in 1992 (Tronko et al. 1996). In 1994, the incidence (per 100,000) was highest in 

regions nearest to Chernobyl: Chernihiv, 3.8; Zhytomyr, 1.6; and Kiev, 1 (Tronko et al. 1996). Jacob et al 
 

 

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(1998) estimated excess absolute risk of thyroid cancers in Belarus and Northern Ukraine for the period 

1991–1995 using the cancer incidence in southern Ukraine as the control. The relationship between 

thyroid cancer risk and the estimated radiation dose to the thyroid was linear, with a slope of 2.3 (95% CI 

1.4–3.8) per 10,000 person-year Gy. Although the available data strongly show that radiation exposure 

from the accident has led to the excess risk of thyroid cancer, especially in persons exposed as children, 

there is also much uncertainty in the radiation dose estimates. The observed trends for increased 

prevalence of thyroid cancer, as well as the magnitude of the thyroid cancer risk associated with 

radioiodine are highly uncertain because of factors that complicate the epidemiological picture, including 

the contribution external exposure, the effect of the intensive screening for thyroid cancer that followed 

the accident (Astakhova et al. 1998) on the baseline incidence of thyroid cancer, and the potential effects 

of iodine deficiency and endemic goiter in the population (Gembicki et al. 1997; Robbins et al. 2001). 

The relationship between childhood thyroid cancer and radiation exposure was examined in a case-control 

study of children from Belarus (Astakhova et al. 1998). Cases included all children under age 15 years at 

the time of the accident who had confirmed pathology diagnoses of thyroid cancer during the period 

1987–1992 and who could participate in the study (107 of 131 applicable cases in Minsk State Medical 

Institute records). Cases were matched with two control groups; one control group (Type 1) was 

randomly selected from an area of Belarus thought to have relatively low or no exposures from the 

Chernobyl accident (Brest, Grodno, and Vitebsk oblasts in north and west Belarus) but was otherwise 

matched with cases for age, sex, and urban/rural residence. A second control group (Type 2) was drawn 

from each Belarus district, including the more heavily exposed oblasts near Chernobyl (Minsk, Mogilev, 

and Gomel), in numbers proportional to the population census and was matched to cases by pathway to 

diagnosis, in addition to age, sex, and urban/rural residence. The objective of matching the pathway to 

diagnosis was to control for screening intensity as a possible contributor to an increased incidence. 

Diagnosis pathways were classified into three elements: (1) systematic endocrine screening; (2) incidental 

finding during physical examination not necessarily related to the Chernobyl releases; or (3) examination 

prompted by referral because of a swelling of the neck or other symptoms of possible thyroid enlargement 

or nodularity. 

Average thyroid radiation doses were reconstructed based on thyroid gland 131I measurements made on 

200,000 residents of Belarus, after the Chernobyl release, and estimates of cow milk contamination and 

consumption for the area of residence of each case or control (vegetable and goat milk consumption was 

not included in the exposure estimates). If no cow milk consumption was thought to have occurred, 

exposure was assumed to have occurred principally from inhalation. Age-group thyroid doses were 
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constructed for each area of residence included in the study. Mean (standard deviation) of thyroid doses 

in the case group and controls were as follows: cases, 535 mGy (848) mGy; Type I controls, 188 mGy 

(386); and Type II controls, 207 mGy (286). For the purpose of estimating odds ratios (ORs), cases and 

controls were stratified into three thyroid dose categories. The resulting estimated dose distributions 

among thyroid cancer cases were 64/107 (59.8%) in the <0.3 Gy dose category, 26/107 (24.3%) in the 

0.3–0.99 Gy dose category, and 17/107 (15.9%) in the $1 Gy dose category. The corresponding 

distributions in Type 1 controls were 88/107 (82.2%) for <0.3 Gy, 15/107 (14.0%) for 0.3–0.99 Gy, and 

4/107 (3.7%) $1 Gy. The corresponding OR for the $0.3 Gy category compared to <0.3 Gy was 

3.11 (95% CI, 1.67–5.81) and for the $1 Gy category compared to <0.3 Gy was 5.84 (1.96–17.3). ORs 

were significant when Type 2 controls were the comparison group (controls for pathway to diagnosis). 

For routine endocrine screening, ORs were 2.08 (1.0–4.3) for comparison of the dose categories $0.3 Gy 

and <0.3 Gy, and 5.04 (1.5–16.7) when the dose category $1 Gy was compared to <0.3 Gy. The OR for 

incidental findings was significant, 8.31 (1.1–58) when the dose category $0.3 Gy was compared to 

<0.3 Gy. These results suggest that, after controlling for the effects of intensive screening for thyroid 

cancer that occurred after the accident, radiation dose to the thyroid gland was a significant contributor to 

thyroid cancers diagnosed in children who lived in Belarus during and after the Chernobyl releases and 

that this contribution is evident at doses exceeding 0.3 Gy. The OR estimates, however, are highly 

uncertain because of the relatively large uncertainties in the dose estimates. 

An analysis of 251 thyroid cancer cases in children (14 years or younger) from Belarus who were 

diagnosed during the period 1986–1993 revealed a dose trend in incidence when the cases were organized 

by districts that reflected their respective mean thyroid doses (Drobyshevskaya et al. 1996). Incidence 

ranged from 81 to 201 per 100,000 where estimated average thyroid doses were above 1 Gy (1.2–1.6 Gy, 

120–160 rad), and 14–55 per 100,000 where doses were between 0.1 and 0.5 Gy (10–50 rad). The 

highest incidence occurred in Bragin where individual thyroid doses were estimated to have ranged from 

0.8 to 20 Gy (560, 80–2,000 rad) (mean, 5.6 Gy, 560 rad). Incidence was 9 per 100,000 in Braslav where 

the lowest measurable thyroid doses were reported (mean, 0.005 Gy, 0.5 rad). Children who were under 

3 years old or in utero at the time of exposure accounted for 53% of thyroid cancer cases. This age-group 

was estimated to have received a thyroid radiation dose that was approximately 2–3 times that for older 

children (approximately 1.4 Gy average dose). However, 52% of the cancers were diagnosed in children 

who received an estimated thyroid dose of <0.3 Gy and 84% in children who received doses <1 Gy. 

Children under 3 years old accounted for 38% of the cancer cases among children exposed to <0.3 Gy. 

These results suggest that young children were particularly susceptible to lower radiation doses. 
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An analysis of 531 thyroid cancer cases in children and adolescents (under 18 years of age) from Ukraine 

who were diagnosed during the period 1986–1994 revealed that 55% of the cases were under age 6 years 

on the date of the Chernobyl release (Tronko et al. 1996). The annual incidence of thyroid cancer in 

children and adolescents (under 19 years of age) increased from approximately 0.05 per 100,000 prior to 

1986 to 0.43 per 100,000 in 1992. In 1994, the incidence (per 100,000) was highest in regions nearest to 

Chernobyl: Chernihiv, 3.8; Zhytomyr, 1.6; and Kiev, 1 (Tronko et al. 1996). Thyroid radiation doses 

were estimated to have ranged from 0.01 to >1.5 Gy in the case group analyzed. Approximately 20% of 

the cases were estimated to have been exposed to 0.01–0.05 Gy (1–5 rad) and 80% to 0.1–0.3 Gy or less 

(10–30 rad). 

A comparison of the demographics and pathology of thyroid cancers in Belarus and Ukraine, following 

the Chernobyl accident, with those diagnosed in Italy and France during the same time period also is 

suggestive of unique causes for the thyroid cancers in Belarus and Ukraine (Pacini et al. 1997). Thyroid 

cancers cases in 472 children and adolescents <21 years of age diagnosed in Belarus and Ukraine during 

the period 1986–1995 were evaluated. These included approximately 98% of all childhood cases reported 

during that period. The comparison group consisted of 369 cases of the same age groups consecutively 

diagnosed at two clinics in Italy (n=219) and France (n=150). The study revealed several differences in 

the Belarus-Ukraine cases when compared with the Italy-France cases. Most of the Belarus-Ukraine 

cases were 5 years of age or less, whereas most of the Italy-France cases occurred after age 14 years. The 

female:male ratio of the Italy-France cases was significantly higher (2.5) than the ratio in the BelarusUkraine cases (1.6). Most (94%) of the Belarus-Ukraine cases were papillary carcinomas with follicular 

carcinomas accounting for only 5% of cases, whereas 82% of the Italy-France cases were papillary and 

15% were follicular carcinomas. Cancers diagnosed in the Belarus-Ukraine group, typical of thyroid 

cancer in early childhood, tended to be more invasive with extrathyroidal involvement more frequently 

than in the Italy-France cases. The Belarus-Ukraine cases also had a higher incidence of thyroid 

autoimmunity (i.e., elevated antithyroid peroxidase and thyroglobulin antibodies) than the Italy-France 

cases. These results suggest different factors contributed to the Belarus-Ukraine and Italy-France cases, 

radiation dose possibly being at least one factor. 

In both Belarus and the Ukraine, the highest rates of childhood thyroid cancer have occurred in areas 

where exposure to other industrial contaminants are likely to have occurred and where there is evidence 

for widespread iodine deficiency. These factors may have affected the early appearance of thyroid cancer 

after the accident, when vigorous public health screening programs for thyroid abnormalities were 
 

 

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initiated. The incidence of thyroid cancer prior to the accident in these areas was poorly documented 

(Nikiforov and Fagin 1998). 

The strengths of the Chernobyl thyroid studies described above include: (1) the large number of children 

who received substantial thyroid doses; (2) the studies included thyroid exposure measurements on more 

than 100,000 children; (3) the generally high level of thyroid surveillance in the population after the 

accident; and (4) that many children were screened with ultrasound, which provides relatively objective 

evidence of thyroid nodularity; one study (Astakhova et al. 1996) attempted to control for the intensity of 

thyroid surveillance. Limitations of these studies include: (1) substantial dose uncertainties and use of 

average doses in many of the studies rather than estimates of individual doses; (2) no thyroid dose 

estimates for many of the thyroid cancer cases; (3) the presence of iodine deficiency in the study 

populations may have affected both the thyroid radiation dose received from 131I as well as the likelihood 

of a thyroid neoplasm; (4) greater intensity of thyroid screening and surveillance in the areas of highest 

exposure than in areas of lower exposure; and (5) lack of rigorous epidemiologic study designs in many 

of the studies (i.e., no systematic sampling design, no blinding of examiners with respect to likely thyroid 

dose, and irregular variations in thyroid screening). Several international efforts are underway to address 

these issues and to provide better information on health risk associated with the exposures that occurred 

following the Chernobyl accident (UNSEAR 2000). 

Hanford Nuclear Site Releases. The CDC (2002) has conducted a follow-up prevalence study of thyroid 

cancer in populations that resided near the Hanford Nuclear Site in southeastern Washington during the 

period 1944–1957. The study included 3,441 subjects who were born during the period 1940–1946 in 

counties surrounding the Hanford Nuclear Site. Thyroid disease was assessed from a clinical evaluation 

of each subject, which included assessments of ultrasound or palpable thyroid nodules. Historical 

information on thyroid disease and information on radiation exposures were obtained by interviews and, 

when possible, review of medical records of participants, including pathology slides to confirm cancer 

diagnosis. Thyroid radiation doses were estimated using a dosimetry model developed in the Hanford 

Environmental Dose Reconstruction Project. Information on residence history and relevant food 

consumption patterns (e.g., milk consumption, breast feeding, consumption of locally harvested produce) 

for each study participant was obtained by interview. The estimated mean thyroid radiation dose, based 

on 91 participants, was 174 mGy (±224, standard deviation [SD]) (17.4±22.4 rad), and the range was 

0.0029–2,823 mGy (0.00029–282 rad). Doses varied geographically, with the highest doses received by 

people who lived near and downwind from the site. Dose-response relationships were assessed using a 

linear regression model with adjustments for the following confounding and effect modifying variables: 
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sex, age of first exposure, age of evaluation, ethnicity, smoking, and potential exposures from Nevada 

Test Site releases. Alternatives to the linear model were also explored including linear quadratic and 

logistic models. Incidences of thyroid carcinoma or nodules were found to be unrelated to thyroid 

radioiodine dose. As noted above, a final report of conclusions has not been published and the study is 

currently under review by the National Research Council. Strengths of the Hanford study include: (1) the 

extremely careful study design and methods; (2) the systematic sampling and high rates of subject 

location and participation; (3) blinded thyroid assessments by multiple examiners, along with ultrasound, 

which is a more objective assessment of thyroid nodularity; and (4) extensive attempts to model thyroid 

radiation doses in various locales, combined with self-reported or parent-reported estimates of milk and 

vegetable consumption to estimate individual thyroid doses. Limitations of the Hanford study include 

substantial individual dose uncertainties, since no thyroid exposure measurements were available and 

individual milk and vegetable consumption estimates were recalled 30–40 years after the exposure period 

studied; and statistical power and precision were limited by the model’s sample size and relatively low 

dose range (0.8% of the study population had estimated thyroid doses >1 Gy [100 rad] and 0.2% had 

doses >2 Gy [200 rad]). 

3.3.3 External Exposure 

No studies were located on the toxicity of external exposures to radioiodine. The four radioactive 

isotopes of iodine that are of particular interest with respect to human exposures (123I, 125I, 129I, and 131I) 

emit, primarily, beta radiation, which would not be expected to produce adverse effects from external 

exposures, other than possibly to the upper layers of the skin. 

3.4 GENOTOXICITY 

Potassium iodide, I2, and povidone iodine (0.1–10 mg/mL) did not show mutagenic effects in L5178Y 

mouse lymphoma cells or in transforming activity in Balb/c 3T3 cells grown in culture (Kessler et al. 

1980; Merkle and Zeller 1979). Potassium iodide and I2 did not produce lethal mutations in Drosophila 

melanogaster when eggs were incubated in 0.38 mg/mL I2 or 0.75 mg/mL potassium iodide (Law 1938). 

I2 did not show mutagenic activity in His+ revertant assay in Saccharomyces cerevisiae (Mehta and von 

Borstel 1982a) Iodide is a free-radical scavenger and has been shown to decrease hydrogen peroxideinduced reversion in strain TA104 of Salmonella typhimurium (Han 1992). 
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Sodium iodate (NaIO3) was not mutagenic when tested in the bacterial Ames assay, mouse bone marrow 

micronucleus test, or recessive lethal test in D. melanogaster (Eckhardt et al. 1982). Sodium iodate has 

radiosensitizing activity and has been shown to increase the number of gamma radiation-induced singlestrand DNA breaks in bacteria (Myers and Chetty 1973). Iodate is a more active radiosensitizing agent 

than is iodide (Kada 1970; Kada et al. 1970; Noguti et al. 1971) 

Chromosome aberrations (breakages, dicentrics, micronuclei) have been found in peripheral blood cells of 

patients who received 131I ablative therapy for hyperthyroidism, in infants born to mothers who received 

such therapy during pregnancy, and in children exposed to radioiodine released from the Chernobyl 

nuclear power plant (Ardito et al. 1987; Ballardin et al. 2002; Baugnet-Mähieu et al. 1994; Boyd et al. 

1974; Catena et al. 1994; Goh 1981; Gutierrez et al. 1999a; Lehmann et al. 1996; Monteiro et al. 2000; 

Ramírez et al. 1997, 2000) (see Section 3.3.2 for a more detailed discussion of exposures from the 

Chernobyl accident). The range of 131I exposures in these cases was 15–200 mCi (0.6–7.4 GBq). 

A significantly higher frequency of chromosome translocations (number of translocations per cell) was 

observed in blood lymphocytes from nine patients who received 131I for ablative treatment of 

multinodular or autonomous goiter (0.55–0.85 GBq, 15–23 mCi) compared to lymphocytes obtained from 

six healthy adults (Lambert et al. 2001). A study of 21 patients who received various exposures to 131I for 

ablative treatment of thyroid carcinoma found a significantly higher frequency of micronuclei in 

peripheral blood cells of patients compared to a group of 93 healthy controls (Catena et al. 1994). A 

significant exposure response relationship was observed at exposures that ranged from 35 to 202 mCi 

(1.3–7.5 GBq). A study of 10 patients who received 131I for ablative treatment of thyroid carcinoma 

compared the outcomes of cytogenetic assessment of peripheral blood lymphocytes before or 1 and 

10 days after their 131I exposures (Baugnet-Mahieu et al. 1994). The patients received two oral doses of 

840 MBq (13.7 mCi) given on 2 consecutive days. A small but statistically significant increase in 

“abnormal cells” (2.69%) and dicentrics (1.91%) occurred after exposure to 131I. The presence of 

micronuclei and binucleated lymphocytes with micronuclei (BNMN) in blood lymphocytes was assessed 

in six patients, before and after they received who received 131I (2.96–5.50 GBq, 80–149 mCi) for 

treatment of thyroid carcinoma (Ballardin et al. 2002). The estimated radiation dose to bone marrow was 

25.5–52.5 cGy (25.5–52.5 rad). BNMN frequency increased after exposure to 131I, reaching a peak 

response (3.6-fold increase above pre-exposure values) 7 days after exposure. Cytogenetic assessments 

of peripheral blood lymphocytes of five patients who received 15–40 mCi (0.6–1.5 GBq) for treatment of 

hyperthyroidism and four control subjects revealed dicentrics and rings in the treated patients, but no such 

abnormalities in the control subjects (Boyd et al. 1974). An increase in the frequency of micronuclei in 
 

 

 

IODINE 129 

3. HEALTH EFFECTS 

peripheral blood lymphocytes was observed of 12 adult women 1 week after they received 100–150 mCi 

131I (3.7–5.6 GBq) for treatment of thyroid cancer (Ramírez et al. 1997). The frequency of chromosome 

translocations in thyroid tumor tissue was compared among groups of patients who had tumors but no 

radiation history (n=24), patients who received 131I or external radiation therapy (n=7), and children 

(n=40) who were residents of the Gomel, Brest, or Minsk regions of Belarus at the time of the Chernobyl 

accident (Lehmann et al. 1996). The frequency of translocations was highest in the patients who received 

radiation therapy and lowest in the patients that had no history of exposure to radiation. Translocation 

frequencies among Belarussian children were lower than in the radiation therapy patients and higher than 

in the patients who had no radiation history. The highest translocation frequencies among Belarussian 

children were observed in children from the Gomel region where 131I exposures and thyroid radiation 

doses are considered to have been the highest of the three regions studied. 

Goh (1981) reported a case of cretinism that developed at age 8 months in an infant whose mother 

received 99 mCi (3.7 GBq) of 131I during her 6th week of pregnancy. The infant was hypothyroid and had 

no detectable thyroid gland function. Cytogenetic studies conducted on peripheral blood lymphocytes 

revealed chromosomal breakages in both the infant and mother. 

3.5 TOXICOKINETICS 

3.5.1 Absorption 

3.5.1.1 Inhalation Exposure 

Molecular iodine (I2) is absorbed when humans are exposed to I2 vapor. In volunteers who inhaled 

radioiodine I2 vapor, essentially all of the inhaled vapor was retained and cleared from the respiratory 

tract with a half-time of approximately 10 minutes (Black and Hounam 1968; Morgan et al. 1968). Much 

of the clearance of the iodine from the respiratory tract was transferred to the gastrointestinal tract, 

suggesting that the initial deposition was primarily in the conducting airways and subject to mucocilliary 

clearance mechanisms. Observations in humans of relatively rapid absorption of inhaled I2 are supported 

by studies in mice, rats, dogs, and sheep (Bair et al. 1963; Willard and Bair 1961). 

Methyl iodide is also inhaled when humans are exposed to methyl iodide vapor. In volunteers who 

inhaled tracer concentrations of [132I]methyl iodide, approximately 70% of the inhaled iodine was retained 

with a half-time in the respiratory tract of approximately 5 seconds, suggesting extremely rapid 

absorption at the alveolar-blood interface (Morgan and Morgan 1967; Morgan et al. 1967a, 1967b). 
IODINE 130 

3. HEALTH EFFECTS 

Studies of the absorption of inhaled inorganic iodide in humans are not available. However, in monkeys 

that inhaled particulate aerosols of radioiodine as sodium iodide (mass median diameter, 

2.32 μm±1.15 SD), inhaled iodide was retained in the respiratory tract with a half-time of approximately 

10 minutes (Perrault et al. 1967; Thieblemont et al. 1965). In dogs and rats that were exposed to cesium 

chloride aerosols containing 131I (mass median aerodynamic diameter, 1.4 μm±1.7 SD), iodine was 

retained and rapidly cleared from the respiratory tract (McClellan and Rupprecht 1968; Thomas et al. 

1970). Retention and relatively rapid absorption of iodine has also been observed in mice and sheep that 

inhaled radioiodine as either sodium iodide or silver iodide particulate aerosols (mean count diameter, 

0.25 μm) (Bair et al. 1963; Willard and Bair 1961). 

3.5.1.2 Oral Exposure 

Gastrointestinal absorption of iodine is generally considered to be approximately 100% after an ingested 

dose of water soluble iodide salts, such as potassium or sodium iodide. This conclusion is based on 

several types of observations made in human subjects who received oral doses of radioiodine compounds 

(the reader should note that where the chemical form of the radioiodine compound was not reported, 

which is the case for most of the radioiodine tracer studies described here, it is likely that it was sodium 

iodide, as this is a common form supplied commercially for pharmaceutical use). Fecal excretion of 131I 

was <1% of the dose in seven euthyroid adult subjects who ingested a single tracer dose of 131I, 

suggesting near complete absorption of the ingested radioiodine (Fisher et al. 1965). In the same study, 

20 euthyroid adults received daily oral doses of potassium iodide for 13 weeks (0.25 or 1.0 mg I/day). 

Daily urinary iodine excretion was approximately 80–90% of the estimated daily intake, also suggesting 

near complete absorption. Similarly, in an acute ingestion study of nine healthy subjects, urinary and 

thyroid radioiodine accounted for 97% (±5, SD) of a single ingested tracer dose of radioiodine (131I or 

132I), suggesting near complete absorption of the tracer dose (Ramsden et al. 1967). In this same study, 

two subjects ingested the tracer dose together with a dose of 5 or 15 mg stable iodide (the chemical form 

of the stable iodide was not specified, but presumably, it was either potassium or sodium iodide) and the 

recoveries of radioiodine in thyroid and urine were 96 and 98%, respectively. In one subject who 

ingested the tracer dose either after a fast (duration not specified) or with a “full stomach”, the recoveries 

of radioiodine in thyroid and urine were 97 and 98%, respectively (Ramsden et al. 1967). 

Measurement of radioiodine uptake in the thyroid gland is also an indicator of absorption, although such 

measurements alone do not allow an accurate quantitative estimate of absorption without other 
IODINE 131 

3. HEALTH EFFECTS 

assumptions about the pharmacokinetics of iodine. Studies of iodine kinetics in subjects who received 

intravenous injections of tracer doses of radioiodine have shown that the fraction of an injected dose that 

accumulates in the thyroid is affected by many variables; however, it does not vary greatly among 

individuals who have the same iodine intake and whose thyroid glands are "normal" (see Section 3.5.2.2). 

This fraction has been shown to be similar (20–35%) when radioiodine (123I, 125I, or 131I) is administered 

to adults by the intravenous or oral routes, suggesting extensive, if not complete, absorption of ingested 

radioiodine (Bernard et al. 1970; Gaffney et al. 1962; Ghahremani et al. 1971; Oddie and Fisher 1967; 

Pittman et al. 1969; Robertson et al. 1975; Sternthal et al. 1980; Van Dilla and Fulwyler 1963). Although 

the fraction of the oral dose of radioiodine taken up by the thyroid 1–2 days after an oral dose may be 

slightly higher in females than males, there is no evidence that this difference results from differences in 

absorption (Ghahremani et al. 1971; Quimby et al. 1950; Robertson et al. 1975). 

Gastrointestinal absorption of iodine appears to be similar in children, adolescents, and adults, as assessed 

from measurements of 24-hour thyroid uptakes of radioiodine administered orally (Cuddihy 1966; Oliner 

et al. 1957; Van Dilla and Fulwyler 1963). Absorption in infants, however, may be lower than in children 

and adults. Evidence for this comes from studies in which thyroid uptake of radioiodine was measured in 

newborns who received tracer doses of radioiodine orally or by injection. In general, injection of the 

radioiodine intramuscularly or intravenously resulted in higher thyroid uptakes than when the radioiodine 

was administered by gastric tube, suggesting incomplete absorption of the oral dose. For example, in 

8 healthy newborn infants (<36 hours postnatal) who each received a tracer dose of 131I by gastric tube, 

the average peak thyroid uptake (30 hours after the dose) was approximately 50% of the dose compared 

to an average of 70% (25 hours after the dose) in 17 infants who received the tracer dose as an 

intramuscular injection (Morrison et al. 1963). The ratio of the thyroid uptakes after the oral and injected 

iodine doses suggests a fractional oral absorption of approximately 70%. In a study involving slightly 

older newborns (72–96 hours old), 15 newborns each received a tracer dose of 131I by gastric tube and the 

average 24-hour uptake of radioiodine in the thyroid was 20% (range, 6–35%) (Ogborn et al. 1960). By 

contrast, in a study of seven healthy infants (<3 days old), the mean thyroid uptake 24 hours after an 

intramuscular tracer dose of 131I was 70% (range, 46–97) (van Middlesworth 1954). In a study of 

26 healthy newborns (<48 hours old) who each received an intravenous tracer dose of 131I, the mean 24­

hour thyroid uptake was 62% (range, 35–88) (Fisher et al. 1962). The rapid changes in iodine status and 

biokinetics in the early weeks of postnatal life make interpretations of comparisons between injection data 

for a few groups of infants with ingestion data for other groups highly uncertainty. Most or all of the 

differences in the thyroid uptakes observed in the above three studies may reflect differences in age and 

iodine status 
IODINE 132 

3. HEALTH EFFECTS 

Iodide incorporated into food appears to be nearly completely absorbed. In a dietary balance study in 

which dietary iodide intakes (170–180 μg/day) and excretion were measured in 12 healthy adult women 

over two 7-day periods, urinary iodide excretion was 96–98% of the daily intake (Jahreis et al. 2001). 

Iodine incorporated into bovine milk appears to be nearly completely absorbed when ingested. Cuddihy 

(1966) measured thyroid uptakes of radioiodine in euthyroid subjects who ingested radioiodinecontaminated cow milk for 14 days. The milk was collected from a cow that was fed 131I in feed 

(endogenously incorporated). Thyroid uptake 24 hours after the last milk dose was approximately 23% of 

the dose. Since this value is within the range of 20–35% observed when a tracer dose of 131I was 

administered orally or intravenously, it suggests that iodine that is endogenously incorporated into cow 

milk is extensively, if not completely, absorbed. A slightly different observation leads to a similar 

conclusion. Comar et al. (1963) compared radioiodine uptakes in each of 11 healthy adults who ingested 

131I in a capsule (containing an aqueous solution of radioiodine) or 131I endogenously incorporated into 

cow milk. The 24-hour thyroid uptakes were nearly identical under each dosing condition (means, 19 and 

20% of the dose) suggesting a similar absorbed fraction of the dose. Pendleton et al. (1963) measured 131I 

in dairy cow milk from farms near the NTS, and in the thyroids or total bodies of families who lived on 

these farms (measured from external thyroid or total body counting). The average uptake of 131I in 

24 individuals was 17% (range, 5–47%) which is similar to that observed after ingestion or injection of 

radioiodine. Assessments of gastrointestinal absorption of iodine in other foods are not available, 

although Wayne et al. (1964) reported that radioiodine incorporated into watercress was completely 

absorbed when ingested by an adult (no details provided). 

Little information is available on the gastrointestinal absorption of forms of iodine other than iodide. 

Iodine compounds, such as I2 and iodates (e.g., NaIO3), may undergo reduction to iodide before being 

absorbed in the small intestine, and absorption may not be complete (Cohn 1932). Iodine from the 

sodium salt of the thyroid hormone thyroxine (T4) is absorbed when T4 is ingested. In two adults who 

each received a single oral dose of 80 μg [131I]-T4, the rate of fecal excretion of radioiodine was similar to 

that observed in three subjects who received the same dose intravenously (10–15% of the dose), 

suggesting substantial absorption from the gastrointestinal tract (Myant and Pochin 1950). In this same 

study, the sum of urinary excretion of radioiodine and thyroid uptake of radioiodine, 24 hours after the 

oral dose of [131I]-T4, was approximately 25% of the dose, compared to an average of 33% (±7) in six 

subjects who received the [131I]-T4 dose intravenously. This observation is also consistent with 

substantial, if not complete, absorption of T4 from the gastrointestinal tract (at least 75% of the dose). 
 

 

IODINE 133 

3. HEALTH EFFECTS 

Observations in humans that indicate extensive absorption of ingested inorganic iodine are supported by 

experiments in animals. Iodine is extensively absorbed in rats when it is ingested as either I2 or NaI. 

When fasted rats were administered oral gavage tracer doses of 131I as either I2 or NaI, 8–9% of the dose 

was excreted in feces in 72 hours and 34–35% of the dose was excreted in the urine (Thrall and Bull 

1990). In the same study, similar results were obtained in rats that were allowed free access to food 

before the oral radioiodine dose; 6–7% of the dose was excreted in feces in 78 hours and 22–29% was 

excreted in urine (22% of the I2 dose and 29% of the NaI dose). These results suggest that tracer doses of 

ingested iodine from NaI and I2 are both nearly completely absorbed from the gastrointestinal tract in rats. 

In cows, tracer doses of 131I ingested in the diet is nearly completely absorbed (Vandecasteele et al. 2000). 

When tracer levels of radioiodine (131I) were administered orally, intravenously, or subcutaneously to four 

sheep, the peak thyroid uptake of radioiodine was similar, 17–19% of the dose (these values are not 

corrected for radioactive decay of the 131I), suggesting extensive absorption from the oral route (Wood et 

al. 1963). 

Povidone-iodine is a complex of I2 and polyvinyl pyrrolidone that is widely used as topical antiseptic. 

Povidone-iodine preparations contain approximately 9–12% iodine, of which only a small fraction is free 

in solution (Lawrence 1998; Rodeheaver et al. 1982). Absorption of iodine ingested as povidone-iodine 

has been studied in rats. Rats that received single gavage doses of 125[I]I-povidone (dose not specified) 

absorbed approximately 3% of the dose, as assessed by measurements of the radioiodine that was retained 

in the gastrointestinal tract 24 hours after the dose (Abdullah and Said 1981). In the same study, 

absorption was approximately 10 or 5% when the povidone-iodine was administered in 10% ethanol 

solution and 5% when administered as a 0.2% solution of benzalkonium chloride. 

3.5.1.3 Dermal Exposure 

Systemic iodine toxicity has occurred following dermal exposures to iodine compounds, suggesting that 

these compounds of iodine are absorbed across the skin of humans (see Section 3.2.3). Harrison (1963) 

attempted to estimate absorption rates for solutions of potassium iodide or iodine (I2), and gaseous I2 in 

humans. Subjects received topical applications of 131I as potassium iodide or iodine (I2) and absorption 

was estimated from measurements of the cumulative urinary excretion of radioactivity and the 24-hour 

activity in the thyroid. Three subjects received a topical application of tracer concentrations of [131I]KI on 

a 12.5 cm2

 area of the forearm. The site was left uncovered and after 2 hours, all of the applied 

radioactivity could be detected on the skin and approximately 90% of the radioactivity could be recovered 

from the skin by washing with soap and water. Absorption was estimated to be approximately 0.1% of 
IODINE 134 

3. HEALTH EFFECTS 

the applied dose (range, 0.09–0.13) based on 3-day cumulative urine radioactivity. Thyroid radioactivity 

24 hours after the topical dose was below the limits of detection. If it was assumed that the 24-hour 

thyroid uptake was 30% of the absorbed dose and that the all of the absorbed activity that was not 

recovered in urine was in the thyroid, absorption was approximately 0.16% in the three subjects (range, 

0.13–0.19). In two subjects in this same study who received a similar topical application of aqueous 

tracer [131I]I2 along with 0.1 mg of [127I]I2 carrier, the absorption was estimated to be 0.06–0.09% of the 

applied dose, with the higher estimate assuming thyroid uptake of 30% of the absorbed dose. This study 

also estimated iodine absorption after dermal exposure to [131I]I2 vapor. When a 12.5 cm2

 area of skin 

was isolated and placed in contact with I2 vapor for 30 minutes or 2 hours, approximately 90% of the total 

iodine content of the vapor was deposited on the skin. Approximately 50% of the deposited dose could 

be washed off with soap and water. Absorption varied depending on the amount of [127I]I2 carrier in the 

vapor (the concentration was not reported). At the lowest carrier amount (approximately 0.8 mg applied 

to the skin), absorption of 131I was 1.2% of the activity that was on the skin at the end of the 2-hour 

exposure. With exposure to 3–5 mg carrier, which produced visible irritation of the skin (reddening or 

blistering), absorption was 27–78%. These observations suggest that exposure to I2 vapors can result in 

deposition of iodine onto the skin and that dermal irritation produced by I2, and possibly other irritants, 

may substantially increase the absorption of iodine after dermal exposure to I2. Dermal absorption of I2 

vapor was indicated in an experimental study in which 131I was detected in the thyroid glands of seven 

male adult volunteers who were exposed, whole body and without respiratory intake, to 131I2 vapor (the 

exposure appears to have been to tracer levels) for up to 4 hours (Gorodinskiy et al. 1979). 

Povidone-iodine, a complex with iodine and polyvinyl-pyrrolidone, and alcohol tinctures of iodine are 

widely used as a topical antiseptic. Iodine is absorbed to some extent when such preparations are applied 

to the skin, although quantitative estimates of the amount absorbed are not available for humans. Urinary 

iodine excretion has been shown to increase following the topical application of povidone-iodine to the 

hands and arms as part of a surgical scrub routine, indicating systemic absorption (Connolly and Shepard 

1972). Increases in iodine concentration in maternal urine and umbilical cord blood have been observed 

in pregnant women who received dermal or vaginal applications of povidone-iodine prior to delivery for 

disinfection of the skin and fetal scalp electrodes, suggesting that absorption of iodine occurs with these 

uses of povidone-iodine as well (l’Allemand et al. 1983; Bachrach et al. 1984). Thyroid enlargement, 

hypothyroidism, and elevated urinary iodine excretion also have been observed in hospitalized infants 

who received frequent topical antiseptic scrubs with iodine-alcohol preparations as part of preparations 

for various clinical procedures (Brown et al. 1997; Chabrolle and Rossier 1978a, 1978b). 
 

 

 

IODINE 135 

3. HEALTH EFFECTS 

Some quantitative information is also available on dermal absorption of iodine in animals. When tracer 

levels of radioiodine (131I) were applied to the shaved skin (50–100 cm2

) of four sheep, the peak thyroid 

uptake of radioiodine was 2–6% of the applied dose compared to 17–19% when the dose was given 

orally, subcutaneously, or intravenously (these values are not corrected for radioactive decay of the 131I) 

(Wood et al. 1963). In a second study, two sheep received a tracer dose of radioiodine as either an oral 

dose or a topical dose; the peak thyroid uptake was 9–14% of the dose at 48–96 hours after the topical 

dose, compared to 30% at 48 hours after the oral dose (both values corrected for radioactive decay). The 

report of these studies does not specify whether the topical applications were occluded or whether the 

animals were restrained in any way from ingesting the topically applied radioiodine (e.g., licking the site 

of application). If ingestion of the radioiodine did not occur, then these studies suggest substantial 

absorption of topically applied iodine since, during the first 1–4 days after topical dosing, thyroid 

radioiodine uptake was approximately 30–50% of that observed after oral dosing, and thyroid uptakes 

after oral and parenteral dosing were similar. 

Additional evidence for dermal absorption of iodine comes from a study of pigs. A solution (solvent not 

specified) containing a mixture of 85% [131I]I2 and 15% [131I]NaI was applied to a 150 cm2

 area of 

abdominal skin on each of four immature pigs and allowed to dry on the skin; the site of application was 

not covered and it is not clear if the site was accessible to licking and ingestion of the applied radioiodine 

(Murray 1969). Approximately 95% of the applied dose was removed from the skin by washing the site 

of application 2 hours after the dosing. Peak thyroid uptake of radioiodine was approximately 0.2% of 

the dose, 1–2 days after dosing (the report does not indicate whether the radioiodine measurements were 

corrected for radioactive decay). In the same study, a 150 cm2

 area of clipped flank skin on each of four 

immature pigs was exposed for 25 minutes to a vapor of 131I containing 85% gaseous 131I, presumably 

[

131I]I2. The exposed areas were not covered or washed subsequent to exposure. Peak thyroid uptake of 

radioiodine was approximately 0.3% of the applied dose 5–7 days after dosing. The lower amount of 

absorption of radioiodine in the pigs compared to the results obtained in sheep (Wood et al. 1963) cannot 

be interpreted with the available information. It may reflect species differences in skin permeability to 

iodine, differences in the chemical form iodine applied to the skin (I2 or I-

), or differences in the amounts 

of topically applied radioiodine that were ingested from licking the site of application. 

Povidone-iodine, an ingredient of some iodine-based topical disinfectants, is absorbed across the skin of 

dogs. Topical application of povidone-iodine in dogs resulted in elevated serum iodide concentrations 

within 2 hours after application; the amount of iodine absorbed was not determined in this study (Moody 

et al. 1988). Evidence for absorption of iodine from topically applied povidone-iodine is also provided by 
IODINE 136 

3. HEALTH EFFECTS 

experiments with rats and mice. Topical application of povidone-iodine to 15–20 mm2 of the shaved skin 

of either rats or mice 2 hours prior to an injection of radioiodine decreased radioiodine uptake in the 

thyroid by 90%, suggesting competition between the absorbed topically applied iodine and the injected 

radioiodine for thyroid uptake (Furudate et al. 1997). 

3.5.1.4 Other Routes of Exposure 

Iodine is absorbed systemically after intravaginal applications of povidone-iodine. Increases in iodine 

concentration in maternal urine, umbilical cord blood, and breast milk, and in infant urine have been 

observed following vaginal applications of povidone-iodine to pregnant women prior to delivery for 

disinfection of fetal scalp electrodes (l’Allemand et al. 1983). Increases in serum iodine concentrations 

have also been observed following irrigation of the lower colon and rectum with povidone-iodine during 

surgical procedures, suggesting absorption from the lower bowel (Tsunoda et al. 2000). 

3.5.2 Distribution 

3.5.2.1 Inhalation Exposure 

The distribution of absorbed iodine is expected to be similar regardless of the route of exposure to 

inorganic iodine. This is supported by studies in which humans were exposed to tracer levels of 

[

132I]CH3I and approximately 20–30% of the iodine retained in the respiratory tract was distributed to the 

thyroid gland and 30–60% was excreted in urine in approximately 10 hours; essentially identical results 

were obtained when a tracer dose of 132[I]NaI was ingested (Morgan et al. 1967a, 1967b). Similar results 

were obtained when volunteers inhaled tracer levels of radioiodine as I2 (Black and Hounam 1968; 

Morgan et al. 1968). The distribution of inhaled particulate aerosols of sodium iodide in monkeys also 

appears to be similar to ingested iodide (Perrault et al. 1967; Thieblemont et al. 1965). A complete 

discussion of the distribution of iodine after oral exposures to inorganic iodine is presented in 

Section 3.5.2.2, and is applicable to inhalation exposures. 

3.5.2.2 Oral Exposure 

The human body contains approximately 10–15 mg of iodine, of which approximately 70–90% is in the 

thyroid gland, which accumulates iodine in producing thyroid hormones for export to the blood and other 

tissues (Cavalieri 1997; Hays 2001; Stather and Greenhalgh 1983). The concentration of iodine in serum 
IODINE 137 

3. HEALTH EFFECTS 

is approximately 50–100 μg/L under normal circumstances (Fisher et al. 1965). Approximately 5% in 

serum is in the inorganic form as iodide; the remaining 95% consists of various organic forms of iodine, 

principally protein complexes of the thyroid hormones T4 and T3 (Fisher et al. 1965; Nagataki et al. 1967; 

Sternthal et al. 1980; Wagner et al. 1961). 

The tissue distribution of iodide and organic iodine are very different and are interrelated by metabolic 

pathways that lead to the iodination and deiodination of proteins and thyroid hormones in the body (see 

Section 3.5.3.2). Iodide is largely confined to the extracellular fluid compartment, with the exception of 

tissues that possess specialized transport mechanisms for accumulating iodide; these include the thyroid, 

salivary glands, gastric mucosa, choroid plexus, mammary glands, placenta, and sweat glands (BrownGrant 1961) (see Section 3.5.1). Serum concentrations of iodide, indicative of extracellular fluid 

concentrations, normally range from 5 to 15 μg/L; this would suggest a total extracellular iodide content 

of the human body of approximately 85–170 μg, assuming an extracellular fluid volume of approximately 

17 L (Cavalieri 1997; Saller et al. 1998). 

Iodide concentrations in the thyroid are usually 20–50 times that of serum (0.2–0.4 mg/dL, 15–30 nM); 

however, concentrations in excess of 100 times that of blood occur when the gland is stimulated by 

thyrotrophin (a TSH) and concentrations in excess of 400 times blood have been observed (Wolff 1964). 

Other tissues that can accumulate iodide to a concentration greater than that of blood or serum include the 

salivary glands, gastric mucosa, choroid plexus, mammary glands, placenta, and sweat glands (BrownGrant 1961). Iodide taken up by the thyroid gland is utilized in the production of thyroid hormones, 

which are stored in the gland (see Section 3.5.3.2). This organic fraction of the thyroid iodine content 

accounts for approximately 90% of the iodine in the thyroid gland and includes iodinated tyrosine and 

tyrosine residues that comprise the thyroid hormones, T4 and T3, and their various synthesis intermediates 

and degradation products. 

The thyroid hormones, T4 and T3, account for approximately 90–95 and 5% of the organic iodine in 

plasma, respectively (Fisher et al. 1965; Sternthal et al. 1980). Nearly all (>99%) of the T4 and T3 in 

plasma is bound to protein. The major binding protein for T4 and T3 is thyroxine-binding globulin (TBG), 

which has a high affinity for both hormones (Table 3-4) (Larsen et al. 1998; Robbins 1996). Other 

proteins that bind thyroid hormones, with lower affinity, include transthyretin (thyroxine-binding 

prealbumin), albumin, and various apoproteins of the high density lipoproteins HDL2 and HDL3 (3–6% of 

plasma hormones). The distribution of protein-bound thyroid hormones is largely confined to the plasma 

space, whereas the free hormones distribute to the intracellular space of a wide variety of tissues where 
 

 

 

IODINE 138 

3. HEALTH EFFECTS 

Table 3-4. Binding Characteristics of Major Human Thyroid 

Hormone-Binding Proteins 

Parameter 

Thyroxine-binding 

globulin Transthyretin Albumin 

Molecular weight of complex (D) 54,000 54,000 (subunit)a 66,000 

Plasma concentration (μmol/L) 0.27 4.6 640 

T4 binding capacity (μg T4/dL) 21 350 50,000 

Association constants (M-1) 

T4 1x1010 7x107 7x105 

T3 5x108 1.4x107 1x105 

Fraction of sites occupied by T4 

b 0.31 0.02 <0.001 

Distribution volume (L) 7 5.7 7.8 

Turnover rate (percent/day) 13 59 5 

Distribution of thyronines 

(percent/protein) 

T4 68 11 20 

T3 80 9 11 

a

Transthyretin consists of four subunits (54 kD) complexed with retinol binding protein b

In euthyroid state 

T3 = 3,5,3N-triiodo-L-thyronine; T4 = 3,5,3N,5N-tetraiodo-L-thyronine (thyroxine) 

Source: Larsen et al. 1998 
 

 

 

IODINE 139 

3. HEALTH EFFECTS 

they exert the metabolic effects attributed to thyroid hormones. TBG and other binding proteins serve as 

reservoirs for circulating thyroid hormones and contribute to the maintenance of relatively constant free 

hormone concentrations in plasma. 

Uptake of T4 and T3 into liver, skeletal muscle, and other tissues occurs by a saturable, energy-dependent 

carrier transport system (see Section 3.6.1). Lipoprotein transport mechanisms may also play a role in the 

uptake of thyroid hormones into certain tissues (Robbins 1996). Intracellular T4 and T3 exist as free 

hormone and are bound to a variety of intracellular proteins. 

Maternal exposure to iodine results in exposure to the fetus (ICRP 2002). Radioiodine accumulation in 

the fetal thyroid commences in humans at approximately 70–80 days of gestation, and precedes the 

development of thyroid follicles and follicle colloid, which are generally detectable at approximately 

100–120 days of gestation (Book and Goldman 1975; Evans et al. 1967). Fetal iodide uptake activity 

increases with the development of the fetal thyroid and reaches its peak at approximately 6 months of 

gestation, at which point, the highest concentrations in thyroid are achieved, approximately 5% of the 

maternal dose/g fetal thyroid (approximately 1% of the maternal dose) (Aboul-Khair et al. 1966; Evans et 

al. 1967). Fetal radioiodine concentrations 1–2 days following a single maternal dose of radioiodine 

generally exceed the concurrent maternal thyroid concentration by a factor of 2–8 with the highest 

fetal/maternal ratios occurring at approximately 6 months of gestation (Book and Goldman 1975; Millard 

et al. 2001). Following long-term exposure, either from ingestion of administered radioiodine or from 

exposure to radioactive fallout, the fetal/maternal ratio for thyroid radioiodine concentration has been 

estimated to be approximately 2–3 (Beierwaltes et al. 1963; Book and Goldman 1975; Eisenbud et al. 

1963). 

Iodine uptake into the thyroid gland is highly sensitive to the iodide intake. At very low intakes, 

representing iodine deficiency (e.g., 20 μg/day), uptake of iodide into the thyroid gland is increased 

(Delange and Ermans 1996). This response is mediated by TSH, which stimulates iodide transport and 

iodothyronine production in the thyroid gland (see Section 3.6.1). At very high intakes of iodine, 

representing an intake excess (e.g., >1 mg/day), iodine uptake into the thyroid gland decreases, primarily 

as a result of decreased iodothyronine synthesis (Wolff-Chaikoff effect) and iodide transport into the 

gland (Nagataki and Yokoyama 1996; Saller et al. 1998). The fraction of an ingested (or injected) tracer 

dose of radioiodide that is present in the thyroid gland 24 hours after the dose has been measured in 

thousands of patients who received radioiodine for treatment of various thyroid disorders or for the 

assessment of thyroid function; these provide a comparative index of effects of various factors on the 
IODINE 140 

3. HEALTH EFFECTS 

distribution of absorbed iodide to the thyroid gland. A single oral dose of 30 mg iodide (as sodium 

iodide) decreases the 24-hour thyroid uptake of radioiodine by approximately 90% in healthy adults 

(Ramsden et al. 1967; Sternthal et al. 1980). The inhibition of uptake was sustained with repeated oral 

doses of sodium iodide for 12 days, with complete recovery to control (presodium iodide) uptake levels 

within 6 weeks after the last sodium iodide dose (Sternthal et al. 1980) or within 8 days after a single dose 

(Ramsden et al. 1967). Repeated oral doses of 1.5–2.0 mg iodide/m2

 of surface area produced an 80% 

decrease in thyroid uptake in children (Saxena et al. 1962). 

The National Cancer Institute (NCI 1997) has analyzed data on 24-hour thyroid uptakes of radioiodine 

reported over the period from 1950 to 1980 and concluded that thyroid uptakes in adults have decreased 

in the United States over time from approximately 20–40% of the dose in the 1950–1960 period to 

approximately 15–20% currently (Cuddihy 1966; Dunning and Schwartz 1981; Kearns and Phillipsborn 

1962; Kereiakes et al. 1972; Oddie and Fisher 1967; Oliner et al. 1957; Pittman et al. 1969; Van Dilla and 

Fulwyler 1963). This decrease appears to be related to a concurrent increase in the average dietary intake 

of iodide in the population from approximately 200 μg/day to approximately 800 μg/day (NCI 1997). 

Twenty-four-hour radioiodine uptakes into the thyroid gland in males and females who experience similar 

iodide intakes are similar, although uptakes in females, as a percentage of the dose, appear to be 10–30% 

higher than in males (Ghahremani et al. 1971; Oddie et al. 1968a, 1970; Quimby et al. 1950; Robertson et 

al. 1975). Thyroid uptakes in newborns are 3–4 times greater during the first 10 days of postnatal life 

than in adults, and decline to adult levels after approximately age 10–14 days (Fisher et al. 1962; Kearns 

and Phillipsborn 1962; Morrison et al. 1963; Ogborn et al. 1960; Van Middlesworth 1954). 

3.5.2.3 Dermal Exposure 

The distribution of absorbed iodine is expected to be similar regardless of the route of exposure to 

inorganic iodine. A complete discussion of the distribution of iodine after oral exposures to inorganic 

iodine is presented in Section 3.5.2.2, and is applicable to inhalation exposures. 

3.5.2.4 Other Routes of Exposure 

The distribution of absorbed iodine is expected to be similar regardless of the route of exposure to 

inorganic iodine. A complete discussion of the distribution of iodine after oral exposures to inorganic 

iodine is presented in Section 3.5.2.2, and is applicable to inhalation exposures. 
 

 

IODINE 141 

3. HEALTH EFFECTS 

3.5.3 Metabolism 

3.5.3.1 Inhalation Exposure 

The metabolism of absorbed iodine is expected to be similar regardless of the route of exposure to 

inorganic iodine. Inhaled methyl iodide and I2 appear to undergo rapid conversion to iodide based on 

nearly identical distribution and excretion kinetics of radioiodine when it is inhaled as either methyl 

iodide or I2, or ingested as sodium iodide (Black and Hounam 1968; Morgan and Morgan 1967; Morgan 

et al. 1967a, 1967b, 1968). A complete discussion of the metabolism of iodine after oral exposures to 

inorganic iodine is presented in Section 3.5.3.2, and is applicable to inhalation exposures. 

3.5.3.2 Oral Exposure 

Iodide in the thyroid gland is incorporated into a protein, thyroglobulin, as covalent complexes with 

tyrosine residues (Figure 3-3). The iodination of thyroglobulin is catalyzed by the enzyme thyroid 

peroxidase, which resides predominantly in the apical membrane of thyroid follicle cells, with the active 

sites of the enzyme facing the follicular lumen (see Section 3.5.1). The iodination reactions occur at the 

follicular cell-lumen interface and consist of the oxidation of iodide to form a reactive intermediate, the 

formation of monoiodotyrosine and diiodotyrosine residues in thyroglobulin, and the coupling of the 

iodinated tyrosine residues to form T4 (coupling of two diiodotyrosine residues) or T3 (coupling of a 

monoiodotyrosine and diiodotyrosine residue) in thyroglobulin (Figure 3-4). The T4/T3 ratio in the 

thyroid is approximately 15:1; however, the relative amounts of T4 and T3 produced depend, in part, on 

the availability of iodide. Low levels of iodide result in a lower T4/T3 synthesis ratio (Taurog 1996). 

Thyroglobulin is stored in the follicular lumen. When the thyroid gland is stimulated to produce and 

release thyroid hormones, thyroglobulin is transported into the follicular cells (Taurog 1996). Uptake of 

thyroglobulin occurs by endocytosis at the apical membrane, which is followed by fusion of endocytotic 

vesicles with lysosomes. Proteolytic enzymes in the lysosomes break down the thyroglobulin into 
 

Plasma Cell Follicle Lumen Fo

I

-

Na+

ATP

ADP

Na+

K+

-DIT-

-MIT-

-DIT-

-MIT-

--T4--

--T3--

TPO + H2O2

TPO +

H2O2 Tg

I

+, HOI

or EOI

I

- I-

MIT

DIT

T3

T4

(a)

(c)

(d)

(e)

(f)

(g)

(h) Apical Membrane

Basolateral Membrane

T4

T3

(j)

ITDH

5’-DI

TSH

(i)

I

-

Na+ 

ATP

ADP

Na+

K+ ATP

ADP

Na+

K+ ATP 

ADP 

Na+ 

K+ 

-DIT­

-MIT­

-DIT­

-MIT­

--T4 -­

--T3 -­

TPO + H2O2 

TPO + 

H2O2 Tg 

I

+, HOI 

or EOI 

I

- I-

MIT 

DIT 

T3 

T4 

(a) 

(c) 

(d)

(e) 

(f) 

(g) 

(h) Apical Membrane 

Basolateral Membrane 

T4 

T3 

(j) 

ITDH 

5’-DI 

TSH 

(i) 

IODINE 142 

3. HEALTH EFFECTS 

Figure 3-3. Pathways Uptake and Metabolism of Iodide in the Thyroid Gland 

METABOLIC STEP INHIBITOR 

a. Iodine uptake CIO4 

-

, SCN-, Ib. Iodine efflux 

c. Iodination PTU, MMI 

d. Coupling PTU, MMI 

e. Colloid resorption Colchicine, Li2+ 

I

-

, Cytoclasin B 

f. Proteolysis I

-

g. Deiodination of DIT Dinitrotyrosine 

and MIT 

h. Deiodination of T4 PTU 

i. Secretion of T3 and T4 

j. TSH receptor binding 
 

5' 6' 5 6 

HO O CH2CHCOOH 

NH2 

3' 2' 3 2 

3,5,3’,5’-Tetraiodothyonine (thyroxine, T4) 3,5,3’-Triiodothyonine (T3) 

I I I 

HO O CH2CHCOOH HO O CH2CHCOOH 

NH2 NH2 I I I I
 

Diiodotyrosine Iodotyrosine
 

I 

HO CH2CHCOOH HO CH2CHCOOH 

NH2 NH2 I

I 

IODINE 143 

3. HEALTH EFFECTS 

Figure 3-4. Thyroid Hormones and Metabolic Precursors 

Thyronine 
IODINE 144 

3. HEALTH EFFECTS 

constituent amino acid residues, including T4, T3, monoiodotyrosine, and diiodotyrosine. T4 and T3 are 

exported to the blood, while monoiodotyrosine and diiodotyrosine residues are retained in the cell and 

deiodinated, and the iodide is recycled into the follicular lumen where it is reincorporated into 

thyroglobulin. Under circumstances of extreme stimulation of the thyroid gland, monoiodotyrosine, 

diiodotyrosine, and iodide can be released into the blood from the gland along with T4 and T3. Although 

the T4/T3 ratio in thyroglobulin is approximately 15:1 in the iodide replete state, the hormone secretion 

ratio is lower, approximately 10:1; thus, some T4 appears to undergo monodeiodination to T3 in the 

thyroid gland. 

All of the major steps of thyroid hormone synthesis and release are stimulated by the pituitary hormone, 

TSH, including uptake of iodine by the thyroid gland, iodination of thyroglobulin, endocytosis of 

thyroglobulin from the follicle lumen, and proteolysis of thyroglobulin to release thyroid hormone for 

export to blood (see Section 3.5.1). Hormone synthesis is also responsive to serum iodide concentration. 

An acute exposure to high oral doses of iodide (e.g., >1 mg) inhibits the production of iodothyronine in 

the thyroid gland; this effect is not dependent on changes in circulating TSH levels, and is referred to as 

the Wolff-Chaikoff effect (Wolff and Chaikoff 1948). The effect is temporary, and with repeated 

exposure to high doses of iodide, the thyroid gland escapes from the Wolff-Chaikoff effect and hormone 

synthesis resumes to normal levels (Wolff et al. 1949). The mechanism for the Wolff-Chaikoff effect 

appears to involve inhibition of both iodide transport and iodination reactions, possibly through an 

inhibition of the expression of NIS and thyroid peroxidase that is mediated by iodide or an iodinated 

metabolic intermediate (Eng et al. 1999; Spitzweg et al. 1999; Uyttersprot et al. 1997). Escape occurs 

when transport of iodide into the thyroid gland and the thyroid iodide concentration are sufficiently 

depressed to release the gland from inhibition of thyroid peroxidase, or other steps in the production of 

iodothyronines (Saller et al. 1998). A variety of chemical inhibitors of iodine thyroid metabolism have 

been described (Figure 3-3, see Section 3.10). 

The major pathways of metabolism of iodine that occur outside of the thyroid gland involve the 

catabolism of T4 and T3, and include deiodination reactions, ether bond cleavage of thyronine, oxidative 

deamination and decarboxylation of the side chain of thyronine, and conjugation of the phenolic hydroxyl 

group on thyronine with glucuronic acid and sulfate (Figure 3-5). Deiodination products formed in 

peripheral tissues are depicted in Figure 3-6. The monodeiodination of T4 to T3 is the major source of 

production of peripheral T3, which has a greater hormonal potency than T4, and together with the 

production of 3,3',5-triiodo-L-thyronine (reverse T3, rT3), account for approximately 80% of total T4 

turnover in humans (Engler and Burger 1984; Visser 1990). The liver and kidney are thought to be major 
 

deiodination 5’(3’)- 5(3)­

I I I I
 

CH2CHCOOH -O3SO CH2CHCOOH 

deiodination 5(3)­ Gluc-O O O

5’(3’)­ NH2 NH2 I
 I I I
 

T4-Glucuronide T4-Sulphate I I
 

conjugation 

I I I
 

ether 

HO CH HO O CH2CHCOOH 2CHCOOH 

NH2

I I I NH2 cleavage 

T4 COOH 

5’(3’)- 5(3)­

DIT 

deiodination 

I
 I
 

HO O CH2CHCOOH O 

NH2 

HO 

I I
 NH2 I deiodination 

T3 rT3

deiodination 

5(3)- 5’(3’)­

Source: Köhrle et al. 1987
 

OH O

I I 

CH2CH2NH2 

O 

I 

OH

I 

I 

I 

CH2

I 

CH2CHCOOH 

decarboxylation 

oxidative deamination 

5’(3’)­ 5(3)-

Tetram 

Tetrac 

IODINE 145 

3. HEALTH EFFECTS 

Figure 3-5. Pathways of Metabolism of Iodothyronines 
 

O 

I* 

OH

I 

CH2CHCOOH 

NH2 T4 I I 

I* I I* I 40% 40% 

HO O R HO O R

T3 I rT3 I 

I 

I* I I* 

HO O R

HO O R HO O R

I 

I 3,5 -T2 '-T2 3',5'-T 3,3 2

I I* 

HO O R HO O R

3-T1 3'-T1 

HO O R

Thyronine 

Source: Engler and Burger 1984 

IODINE 146 

3. HEALTH EFFECTS 

Figure 3-6. Major Deiodination Pathways of Thyroid Hormones 

in Peripheral Tissues 
 

 

 

IODINE 147 

3. HEALTH EFFECTS 

sites of production of T3 in the circulation; however, local tissue production of T3 from T4 is thought to be 

the predominant source of T3 in the brain and pituitary. Iodothyronine deiodinases also catalyze the 

inactivation of T4 and T3. The activities of deiodinases are under feedback control, mediated by T3, 

T4, and reverseT3 (rT3), an inactive deiodination product of T4 (Darras et al. 1999; Peeters et al. 2001).
 

Deiodination of T4 and T3 also functions to deactivate the thyroid hormones. Iodide released from the 

deiodination reactions is either taken up by the thyroid gland or excreted in urine (see Section 3.5.4.2). 

Deiodination is catalyzed by selenium-dependent deiodinase enzymes (selenodiodinases) (see 

Section 3.6.1). 

Oxidative deamination and decarboxylation of the alanine side chain of the iodothyronines represents 

approximately 2 and 14% of total of T4 and T3 turnover, respectively (Braverman et al. 1970; Gavin et al. 

1980; Pittman et al. 1980; Visser 1990). Enzymes that catalyze these reactions have not been well 

characterized. Activity has been demonstrated in homogenates of rat kidney and brain, and the 

metabolites have been detected in a variety of tissues, including kidney, liver, and skeletal muscle (Engler 

and Burger 1984). The products of side chain deamination and decarboxylation, the acetic acid analogues 

of the iodothyronines, undergo deiodination and conjugation with glucuronic acid and sulfate (Engler and 

Burger 1984; Green and Ingbar 1961; Pittman et al. 1972). 

Sulfate conjugation of the phenolic group of iodothyronines occurs in the liver and probably in other 

tissues. In humans, the reaction in liver is catalyzed by phenolic arylsulfotransferase (Young 1990). 

Iodothyronines having one iodine moiety on the phenolic ring are preferentially sulfated (Sekura et al. 

1981; Visser 1994). The sulfated products undergo deiodination. Although a minor metabolite of the 

thyroid hormones under normal conditions, the sulfation pathway becomes more important when Type I 

deiodinase is inhibited; for example, by treatment with propylthiourea (Visser 1994). 

Glucuronide conjugation of the phenolic hydroxyl group of the iodothyronines occurs in the liver and 

probably other tissues. The identity of the glucuronytransferase enzymes that participate in the 

conjugation of iodothyronines has not been determined in humans; however, in rats, the activity has been 

shown to occur for the microsomal bilirubin, p-nitrophenol, and androsterone uridine diphosphate (UDP)­

glucuronyltransferases (Visser et al. 1993). The activity of the pathway is increased by a variety of 

chemicals that induce microsomal enzymes, including benzopyrene, phenobarbital, 3-methylcholanthrene, 

polychlorinated biphenyls (PCBs), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (Visser 1990).
 
IODINE 148 

3. HEALTH EFFECTS 

Ether bond cleavage is a minor pathway of metabolism of iodotyrosines under normal conditions; 

however, it explains the observation of diiodotyrosine in serum of some patients who received high 

dosages of T4 or who had severe bacterial infections (Meinhold et al. 1981, 1987, 1991). The reaction has 

been observed in phagocytosing leukocytes, which would be abundant during bacterial infections 

(Klebanoff and Green 1973). 

3.5.3.3 Dermal Exposure 

The metabolism of absorbed iodine is expected to be similar regardless of the route of exposure to 

inorganic iodine. A complete discussion of the metabolism of iodine after oral exposures to inorganic 

iodine is presented in Section 3.5.3.2, and is applicable to inhalation or dermal exposures. 

3.5.4 Elimination and Excretion 

3.5.4.1 Inhalation Exposure 

The excretion of absorbed iodine is expected to be similar regardless of the route of exposure to inorganic 

iodine. This is supported by studies in which humans were exposed to tracer levels of radioiodine as 

either I2 or methyl iodide, and in studies in which monkeys inhaled particulate aerosols of sodium iodide 

(Black and Hounam 1968; Morgan et al. 1967a, 1967b, 1968; Perrault et al. 1967; Thieblemont et al. 

1965). A complete discussion of the metabolism of iodine after oral exposures to inorganic iodine is 

presented in Section 3.5.3.2, and is applicable to dermal exposures. 

3.5.4.2 Oral Exposure 

Absorbed iodine is excreted primarily in the urine and feces, but is also excreted in breast milk, exhaled 

air, sweat, and tears (Cavalieri 1997). Urinary excretion normally accounts for >97% of the elimination 

of absorbed iodine, while fecal excretion accounts for approximately 1–2% (Hays 2001; Larsen et al. 

1998). The whole-body elimination half-time of absorbed iodine has been estimated to be approximately 

31 days in healthy adult males (Hays 2001); however, there appears to be considerable inter-individual 

variability in the half-time (Van Dilla and Fulwyler 1963). 

The glucuronide and sulfate conjugates of T4, T3, and metabolites are secreted into bile. Estimates of the 

magnitude of the biliary pathway have been obtained from analyses of bile samples collected from 
IODINE 149 

3. HEALTH EFFECTS 

patients who underwent surgical cholecystectomy; the total secretion of T4 and metabolites was 

approximately 10–15% of the daily metabolic clearance of T4 (Langer et al. 1988; Myant 1956). More 

extensive quantitative information is available on the biliary secretion of iodothyronines conjugates in 

experimental animals, although these models may not represent the patterns or amounts of biliary 

secretion that occurs in humans. In rats, approximately 30% of T4 clearance is accounted for by the 

biliary secretion of the glucuronide conjugate and 5% as the sulfate conjugate; once secreted, the 

conjugates undergo extensive hydrolysis with reabsorption of the iodothyronine in the small intestine 

(Visser 1990). 

Iodide is excreted in human breast milk (Dydek and Blue 1988; Hedrick et al. 1986; Lawes 1992; Morita 

et al. 1998; Robinson et al. 1994; Rubow et al. 1994; Spencer et al. 1986). Simon et al. (2002) estimated 

a transfer coefficient for 131I from intake to breast milk (ratio of steady-state 131I concentration in breast 

milk to 131I intake rate) to be approximately 0.12 day/L milk ("1.5 SD). The fraction of the absorbed 

iodide dose excreted in breast milk varies with functional status of the thyroid gland and with iodine 

intake. A larger fraction of the absorbed dose is excreted in breast milk in the hypothyroid state 

compared to the hyperthyroid state. In the hypothyroid state, uptake of absorbed iodide into the thyroid 

and incorporation into iodothyronines is depressed, resulting in greater availability of the absorbed iodide 

for distribution to the mammary gland and breast milk. Several examples of this have been reported in 

the clinical case literature. A woman who was hyperthyroid and received an oral tracer dose of 

radioiodine as [123I]NaI during lactation excreted approximately 2.5% of the dose in breast milk collected 

over a 5.5-day period (Morita et al. 1998). The peak excretion (48.5% of the dose) occurred in the first 

postdosing collection of breast milk, which occurred 7 hours after the dose. A similar result, 

approximately 2.6% of the oral dose excreted in breast milk, was reported by Hedrick et al. (1986) for a 

hyperthyroid patient. By contrast, a hypothyroid patient excreted 25% of an oral dose of radioiodine (as 

[

123I]NaI) in breast milk in 41 hours (Robinson et al. 1994). The fractional transfer of absorbed iodine to 

breast milk in goats and cows decreases with increasing intake rates (Crout et al. 2000; Vandecasteel et al. 

2000). 

Iodide is excreted in human tears. In an adult patient (hypothyroid with thyroid hormone 

supplementation) who received an oral tracer dose of 123I radioiodine, approximately 0.01% of the dose 

was recovered in tears collected over a 4-hour period. The peak activity in tears was observed 1 hour 

after the dose and activity was present in tears 24 hours after the dose (Bakheet et al. 1998). 
IODINE 150 

3. HEALTH EFFECTS 

Iodide is secreted in saliva in humans (Brown-Grant 1961; Mandel and Mandel 2003; Wolff 1983). 

Salivary secretion of iodide may be an important pathway for recycling of iodine (Mandel and Mandel 

2003). The quantitative contribution of the saliva pathway to excretion of iodine has not been reported, 

and is probably minimal, given the relatively small rate of production of saliva under normal 

circumstances, most of which is ingested (Brown-Grant 1961; Wolff 1983). 

Appreciable amounts of iodide can be excreted in sweat, under conditions of strenuous physical activity 

(Mao et al. 2001). 

Iodide appears to be excreted into the intestine by a mechanism other than biliary secretion of 

iodothyronine (and metabolic conjugates). Evidence in support of this comes from observations of 

radioactivity in the colon of patients who have no functioning iodothyronine production and who received 

doses of radioiodine. Kinetic analyses of the fecal excretion of radioiodine in euthyroid subjects also 

supports a direct blood-to-intestine excretion route for iodide (Hays 1993). Further support for a possible 

colonic excretory pathway in humans comes from experimental studies in cats and rats (Hays et al. 1992; 

Pastan 1957). 

3.5.4.3 Dermal Exposure 

The excretion of absorbed iodine is expected to be similar regardless of the route of exposure to inorganic 

iodine. A complete discussion of the metabolism of iodine after oral exposures to inorganic iodine is 

presented in Section 3.5.3.2, and is applicable to dermal exposures. 

3.5.5 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. 
IODINE 151 

3. HEALTH EFFECTS 

PBPK/PD models refine our understanding of complex quantitative dose behaviors by helping to 

delineate and characterize the relationships between: (1) the external/exposure concentration and target 

tissue dose of the toxic moiety, and (2) the target tissue dose and observed responses (Andersen et al. 

1987; Andersen and Krishnan 1994). These models are biologically and mechanistically based and can 

be used to extrapolate the pharmacokinetic behavior of chemical substances from high to low dose, from 

route to route, between species, and between subpopulations within a species. The biological basis of 

PBPK models results in more meaningful extrapolations than those generated with the more conventional 

use of uncertainty factors. 

The PBPK model for a chemical substance is developed in four interconnected steps: (1) model 

representation, (2) model parametrization, (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) is 

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). 

Similar models have been developed for radionuclides. These models provide a scientifically sound 

means to predict the target tissue dose of chemicals and radiation in humans who are exposed to 

environmental levels (for example, levels that might occur at hazardous waste sites) based on the results 

of studies where doses were higher or were administered in different species. Figure 3-7 shows a 

conceptualized representation of a PBPK model. Figures 3-8 through 3-15 show models for radionuclides 
 

 

Inhaled chemical Exhaled chemical 

Ingestion 

A
 

R
 

T
 

E
 

R
 

I
 

A
 Slowly L

perfused 

tissues 

Fat 

Liver 

Lungs 

V 

E 

N 

U 

O 

S 

B 

Tract 

GI Vmax Km 

L
 

O
 Richly

perfused

tissues 

B O L D O 

O 

Feces 

Kidney 

D 

Urine 

Skin 

Chemicals in air 

contacting skin 

IODINE 152 

3. HEALTH EFFECTS 

Figure 3-7. Conceptual Representation of a Physiologically

Based Pharmacokinetic (PBPK) Model for a 

Hypothetical Chemical Substance 

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 et al. 1994 
IODINE 153 

3. HEALTH EFFECTS 

in general or specifically for iodine. The ICRP (1994b, 1996) developed a Human Respiratory Tract 

Model for Radiological Protection, which contains respiratory tract deposition and clearance 

compartmental models for inhalation exposure that may be applied to gases and vapors of iodine 

compounds and particulate aerosols of iodine. The ICRP (1979, 1989) also developed a biokinetic model 

for human oral exposure that applies to iodine. Several other multicompartmental models of iodine 

pharmacokinetics have been described, two of which are also described below because of either their 

extensive history of use in clinical applications of radioiodine (Oddie et al. 1955) or their potential value 

in environmental risk assessment (Stather and Greenhalgh 1983). The EPA (1998) has adopted the ICRP 

(1989, 1994a, 1995) models for assessment of radiologic risks from iodine exposures. The National 

Council on Radiation Protection and Measurements (NCRP) has also developed a respiratory tract model 

for inhaled radionuclides (NCRP 1997). At this time, the NCRP recommends the use of the ICRP model 

for calculating exposures for radiation workers and the general public. Readers interested in this topic are 

referred to NCRP Report No. 125; Deposition, Retention and Dosimetry of Inhaled Radioactive 

Substances (NCRP 1997). In the appendix to the report, NCRP provides the animal testing clearance data 

and equations fitting the data that supported the development of the human model. 

Human Respiratory Tract Model for Radiological Protection (ICRP 1994) 

Deposition. The ICRP (1994b) has developed a deposition model for behavior of aerosols and vapors in 

the respiratory tract. It was developed to estimate the fractions of radioactivity in breathing air that are 

deposited in each anatomical region of the respiratory tract. ICRP (1994b) provides inhalation dose 

coefficients that can be used to estimate the committed equivalent and effective doses to organs and 

tissues throughout the body based on a unit intake of radioactive material. The model applies to three 

levels of particle solubility, and a wide range of particle sizes (approximately 0.0005–100 μm in 

diameter) and parameter values, and can be adjusted for various segments of the population (e.g., sex, 

age, level of physical exertion). This model also allows the evaluation of 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 gases and 

vapors of volatile iodine compounds (e.g., I2 and methyl iodide) and particulate aerosols containing 

iodine, 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 3-8). The model was developed with 5 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 
 

Sequestered in Tissue Surface Transport 

Anterior
 

Nasal
 

Naso-oro-­

pharynx 

Larynx 

0.001

Extrathoracic

ETSEQ

12

LNET

13

Bronchi

bb2

BB2

LNTH bbSEQ

0.03 2

0.01

0.01

8

BBSEQ

9

Thoracic

6 5

10

Al3

0.0001

BB1

bb1

7

4

Al Al2 1

0.001 0.02

3 2 1

GI Tract

Environment

16

ET2

ET1

14

11 15

100

1

Bronchioles

Alveolar 

Interstitium

0.03 10

0.00002

0.001 

Extrathoracic 

ETSEQ

12 

LNET 

13 

Bronchi 

bb2 

BB2 

LNTH bbSEQ

0.03 2 

0.01 

0.01 

8 

BBSEQ

9

SEQ 

9 

Thoracic 

6 5

10 

Al3 

0.0001 

BB1 

bb1 

7 

4 

Al Al2 1

0.001 0.02 

3 2 1

GI Tract 

Environment 

16 

ET2

ET1

14

11

ET2 

ET1 

14 

11 15 

100 

1 

Bronchioles 

Alveolar 

Interstitium 

0.03 10 

0.00002 

IODINE 154 

3. HEALTH EFFECTS 

Figure 3-8. Compartment Model to Represent Particle Deposition and TimeDependent Particle Transport in the Respiratory Tract* 

*Compartment numbers shown in lower right corners are used to define clearance pathways. The clearance rates, 

half-lives, and fractions by compartment, as well as the compartment abbreviations are presented in Table 3-6. 

Source: ICRP 1994b 
 

 

IODINE	 155 

3. HEALTH EFFECTS 

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 of particles, 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. 

Similar to the extrathoracic region, experimental data served as the basis for lung (bronchi, bronchioles, 

and alveoli) aerosol transport and deposition. A theoretical model of gas transport and particle deposition 

was used to interpret data and to predict deposition for compartments and subpopulations other than adult 

males. Table 3-5 provides reference respiratory values for the general Caucasian population under 

several levels of activity. 

Deposition of inhaled gases and vapors is modeled as a partitioning process that depends on the 

physiological parameters noted above as well as the solubility and reactivity of compound in the 

respiratory tract (Figure 3-9). The ICRP (1994b) model defines three categories of solubility and 

reactivity: SR-0, SR-1, and SR-2: 

•	 Type SR-0 compounds include insoluble and nonreactive gases (e.g., inert gases such as H2, He). 

These compounds do not significantly interact with the respiratory tract tissues and essentially all 

compound inhaled is exhaled. Radiation doses from inhalation of SR-0 compounds are assumed 

to result from the irradiation of the respiratory tract from the air spaces. 

•	 Type SR-1 compounds include soluble or reactive gases and vapors that are expected to be taken 

up by the respiratory tract tissues and may deposit in any or all of the regions of the respiratory 

tract, depending on the dynamics of the airways and properties of the surface mucous and airway 

tissues, as well as the solubility and reactivity of the compound. Molecular iodine (I2) and methyl 

iodide are classified as SR-1 compounds (ICRP 1995). Deposition of molecular iodine vapor is 

assumed to occur in ET1 (10%), ET2 (40%), and BB (50%) regions of the respiratory tract, 

whereas 70% of inhaled methyl iodide is assumed to deposit uniformly in ET2 and deeper regions 

of the respiratory tract (ICRP 1995). 

•	 Type SR-2 compounds include soluble and reactive gases and vapors that are completely retained 

in the extrathoracic regions of the respiratory tract. SR-2 compounds include sulfur dioxide 

(SO2) and hydrogen fluoride (HF). 

Mechanical Clearance from the Respiratory. This portion of the model identifies the principal clearance 

pathways within the respiratory tract. The model was developed to predict the retention of various 

radioactive materials. The compartmental model is linked to the deposition model (see Figure 3-8) and to 

reference values presented in Table 3-6. Table 3-6 provides clearance rates and deposition fractions for 

each compartment for insoluble particles. The table provides rates of insoluble particle transport for each 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

IODINE 156 

3. HEALTH EFFECTS 

Table 3-5. Reference Respiratory Values for a General Caucasian Population at 

Different Levels of Activitya
 

3 mo 1 yr 5 yr 

Male 

10 yr 

Female Both 

15 yr 

Male Female 

Adult 

Male Female 

Resting (sleeping); Maximal workload 8% 

Breathing parameters: 

VT(L)b 0.04 0.07 0.17 

B(m3h-1)

b 0.09 0.15 0.24 

fR(min-1)

b 38 34 23 

— 

— 

— 

— 

— 

— 

0.3 

0.31 

17 

0.500 

0.42 

14 

0.417 

0.35 

14 

0.625 

0.45 

12 

0.444 

0.32 

12 

Sitting awake; Maximal workload 12% 

Breathing parameters: 

VT(L) N/A 0.1 

B(m3h-1) N/A 0.22 

fR(min-1) N/A 36 

0.21 

0.32 

25 

— 

— 

— 

— 

— 

— 

0.33 

0.38 

19 

0.533 

0.48 

15 

0.417 

0.40 

16 

0.750 

0.54 

12 

0.464 

0.39 

14 

Light exercise; Maximal workload 32% 

Breathing parameters: 

VT(L) 0.07 0.13 

B(m3h-1) 0.19 0.35 

fR(min-1) 48 46 

0.24 

0.57 

39 

— 

— 

— 

— 

— 

— 

0.58 

1.12 

32 

1.0 

1.38 

23 

0.903 

1.30 

24 

1.25 

1.5 

20 

0.992 

1.25 

21 

Heavy exercise; Maximal workload 64% 

Breathing parameters: 

VT(L) N/A N/A N/A 

B(m3h-1) N/A N/A N/A 

fR(min-1) N/A N/A N/A 

0.841 

2.22 

44 

0.667 

1.84 

46 

— 

— 

— 

1.352 

2.92 

36 

1.127 

2.57 

38 

1.923 

3.0 

26 

1.364 

2.7 

33 

a

See Annex B (ICRP 1994b) for data from which these reference values were derived b

VT = Tidal volume, B = ventilation rate, fR = respiration frequency 

h = hour; L = liter; m = meter; min = minute; mo = months; N/A = not applicable; yr = year(s) 
 

Airway Uptake Gas or Vapor Convection 

Lumen Diffusion 

Blood 

Sb 

Reaction 

Product 

Reaction 

Product 

Bound 

Material 

Gas/Vapor 

Gas/Vapor 

Reaction 

Product Gas/Vapor 

Airway
 

Fluid
 

Tissue 

Blood 

Source: ICRP 1994b 

IODINE 157 

3. HEALTH EFFECTS 

Figure 3-9. Reaction of Gases or Vapors at Various Levels of the Gas-Blood 

Interface 
 

 

IODINE 158 

3. HEALTH EFFECTS 

Table 3-6. 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-timea 

m1,4 AI1 bb1 0.02 35 days 

m2,4 AI2 bb1 0.001 700 days 

m3,4 AI3 bb1 0.0001 7,000 days 

m3,10 AI3 LNTH 0.00002 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 

See next page for Part B 
 

f s = 05. for dae ≤ 25 . ρ χμ / m and

0 63 .( d ρ χ/ −2 5.) ae f s = 05. e for dae > 25 . ρ χμ / m

IODINE	 159 

3. HEALTH EFFECTS 

Table 3-6. Reference Values of Parameters for the Compartment 

Model to Represent Time-dependent Particle Transport 

from the Human Respiratory Tract (continued) 

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-times are approximate since the reference values are specified for the particle transport rates and are rounded in units 

of d-1. A half-time 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-time of compartment Al3 is determined by the sum of the clearance rates from it. b

See paragraph 181, Chapter 5 (ICRP 1994) 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: 

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; d = day(s); 

ET = extrathoracic region; ETseq = compartment representing prolonged retention in airway tissue of small fraction of particles 

deposited in the nasal passages; LNET = lymphatics and lymph nodes that drain the extrathoracic region; LNTH = lymphatics and 

lymph nodes that drain the thoracic region 

Source: ICRP 1994b 
IODINE 160 

3. HEALTH EFFECTS 

of the compartments, expressed as a fraction per day and also as half-time. ICRP (1994b) also developed 

modifying factors for some of the parameters, such as age, smoking, and disease status. Parameters of the 

clearance model are based on human evidence for the most part, although particle retention in airway 

walls is based on experimental data from animal experiments. 

The clearance of particles from the respiratory tract is a dynamic process. The rate of clearance generally 

changes with time from each region and by each route. Following deposition of large numbers of 

particles (acute exposure), transport rates change as particles are cleared from the various regions. 

Physical and chemical properties of deposited material determine the rate of dissolution, and as particles 

dissolve, absorption rates tend to change over time. By creating a model with compartments of different 

clearance rates within each region (e.g., BB1, BB2, BBseq), the ICRP model overcomes problems 

associated with time-dependent functions. Each compartment clears to other compartments by constant 

rates for each pathway. 

Particle transport from all regions is toward both the lymph nodes and the pharynx, and a majority of 

deposited particles ultimately are 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, 

some 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, 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). 
 

 

 

IODINE	 161 

3. HEALTH EFFECTS 

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. 

Particle clearance from the alveolar-interstitial region has been measured in humans. The ICRP model 

uses two half-times 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 2-stage process, as shown in Figure 3-10. 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), S (slow), and V (instantaneous): 

•	 For Type F, there is rapid 100% absorption within 10 minutes of the material deposited in the BB, 

bb, and AI regions, and 50% of material deposited in ET2. Thus, for nose breathing, there is rapid 

absorption of approximately 25% of the deposit in ET and 50% for mouth breathing. Type F 

iodine compounds include molecular iodine (I2) and particulate aerosols of silver iodide and 

sodium iodide. 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. ICRP (1995) does not identify any Type M iodine 

compounds. 

•	 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. ICRP (1995) does not identify any Type S iodine compounds. 

•	 For Type V, complete absorption (100%) is considered to occur instantaneously. Methyl iodide 

is classified as a Type V compound (ICRP 1995). 
 

Dissolution

Uptake

Particulate Material

Bound Material

Dissociated Material

Particulate Material 

Bound Material 

Dissociated Material 

Blood 

Source: ICRP 1994b 

Dissolution 

Uptake 

IODINE 162 

3. HEALTH EFFECTS 

Figure 3-10. The Human Respiratory Tract Model: Absorption into Blood 
IODINE 163 

3. HEALTH EFFECTS 

EPA (2002) Iodine Biokinetics Models 

Description of the models. 

EPA (2002a) developed PBPK models of the kinetics of ingested or injected iodide in rats and humans. 

The models were developed simultaneously with models of perchlorate biokinetics. When combined, the 

iodide and perchlorate models simulate the acute competitive inhibition of iodide transport by perchlorate 

in thyroid and other tissues that have NIS activity. The adult rat model has been extended to include 

pregnancy and maternal-fetal transfer of iodide, and lactation and maternal-pup iodide transfer through 

milk. 

The adult rat and human models have the same structure and differ only in values for physiological and 

some of iodide parameters (Figure 3-11, Table 3-7). Both models simulate eight tissue compartments: 

blood, kidney, liver, skin, stomach, thyroid, fat, other slowly perfused tissues, and other richly perfused 

tissues. Uptakes from blood into the vascular compartments of the tissues are simulated as flow-limited 

processes. Distributions within blood, skin, stomach, and thyroid are simulated as diffusion-limited 

processes with first-order clearance terms. Transport of iodide within tissues that have NIS activity are 

simulated with tissue-specific affinity constants and maximum transport velocities. This includes uptake 

of iodine into thyroid follicle cells and secretion of iodide into the follicle lumen. Active transport of 

iodide into the stomach lumen and in skin is also simulated in the models. Excretion is simulated with a 

first-order clearance term for transfer of iodide from the kidney into urine. 

Extensions of the adult rat model to simulate iodide kinetics during pregnancy include the addition of two 

additional compartments representing the mammary gland and placenta. Uptake of iodide into the 

mammary gland tissue from the mammary tissue vascular space is simulated as an affinity- and capacitylimited transport process, representing the activity of NIS in this tissue. Uptake of iodide into the 

placenta from blood is simulated as a flow-limited process. Exchanges of iodide between the placenta 

and fetus are simulated with first order clearance terms. The fetal model is identical in structure to the 

adult (non-pregnant) model, with adjustments in the physiological and iodide parameters to reflect the 

fetus. 

The lactating rat model includes a milk compartment in mammary tissue and a first-order clearance term 

for describing secretion of iodide form mammary tissue into milk. Transfer of iodide from milk to the 

neonate is simulated as a first-order clearance process. The neonate model is identical in structure to the 
 

 

IODINE 164 

3. HEALTH EFFECTS 

Table 3-7. Chemical-specific Parameters for the Adult Male Rat and Human 

PBPK Models for Iodidea
 

Partition Coefficients (unitless) Rat Human 

Slowly Perfused/Plasma PS_ 0.21 0.21 

Richly Perfused/Plasma PR_ 0.40 0.40 

Fat/Plasma PF_ 0.05 0.05 

Kidney/Plasma PK_ 1.09 0.05 

Liver/Plasma PL_ 0.44 0.44 

Gastric Tissue/Gastric Blood PG_ 1.40 0.50 

Gastric Juice/Gastric Tissue PGJ_ 3.00 3.50 

Skin Tissue/Skin Blood PSk_ 0.70 0.70 

Thyroid Tissue/Thyroid Blood PT_ 0.15 0.15 

Thyroid Lumen/Thyroid Tissue PDT_ 7.00 7.00 

Red Blood Cells/Plasma 1.00 1.00 

Max Capacity, Vmaxc (ng/hr-kg) 

Thyroid Colloid Vmaxc_DT 4.0x10-7 1.0x108 

Thyroid Follicle Vmaxc_T 5.5x104 ~1.5x105 

Skin Vmaxc_S 5.0x10-5 7.0x105 

Gut Vmaxc_G 1.0x106 9.0105 

Plasma Binding Vmaxc_Bp – – 

Affinity Constants, Km (ng/L) 

Thyroid Lumen Km_DT 1.0x109 1.0109 

Thyroid km_T 4.0x106 4.0x106 

Skin Km_S 4.0x106 4.0106 
IODINE 165 

3. HEALTH EFFECTS 

Table 3-7. Chemical-specific Parameters for the Adult Male Rat and Human 

PBPK Models for Iodidea
 

Partition Coefficients (unitless) Rat Human 

Gut Km_G 4.0x106 4.0106 

Plasma BInding km_B – – 

Permeability Area Cross Products (L/hr-kg) 

Gastric Blood to Gastric Tissue 

PAGc_ 

0.10 0.20 

Gastric Tissue to Gastric Juice 

PAGJc_ 

0.10 2.00 

Skin Blood to Skin Tissue 

PASkc_ 

0.10 0.06 

Plasma to Red Blood Cells 

PARBCc_ 

1.00 1.00 

Follicle to Thyroid Follicle 

PATc_ 

1.0x10-4 1.0x10-4 

Lumen to Thyroid Follicle 

PADTc_ 

1.0x10-4 1.0x10-4 

Clearance Values (L/hr-kg) 

Urinary excretion CLUc_ 0.05 0.1 

Plasma unbinding Clunbc_ – – 

a

Source: EPA 2002a 
 

 i.v. Dose 

Oral Dose 

RBCs 

Stomach 

Contents 

Stomach 

Tissue 

Stomach 

Blood 

QC 

QG 

QL 

QR 

QK 

QT 

QSK 

QF 

QS 

Plasma 

QG 

Liver 

Richly

Perfused 

Kidney 

Colloid 

Thyroid

Follicle 

Stroma 

Skin 

Skin Blood 

Fat 

Slowly

Perfused 

Urine 

IODINE 166 

3. HEALTH EFFECTS 

Figure 3-11. Structure of EPA (2002) PBPK Model of Iodine in Adult Male 

Humans and Rats 

Thick arrows within tissue compartments indicate transfers that are affinity- and capacity-limited (e.g., NIS). Thin 

arrows within tissue compartments are diffusion limited transfers. Q indicates flow for flow-limited transfers. 
IODINE 167 

3. HEALTH EFFECTS 

adult (nonpregnant) model, with adjustments to the physiological and iodide parameter values to reflect 

the neonate. 

Validation of the model. 

The rat iodide model has been evaluated for predicting serum and thyroid iodine concentrations in adult 

rats that received acute intravenous injection of radioiodine (EPA 2002a). Model predictions 

corresponded reasonably well with observations. The model also predicted reasonably well the inhibition 

of radioiodine uptake in the thyroid produced by an acute intravenous dose of perchlorate; however, the 

model under-predicted thyroid iodide uptake in rats that received perchlorate in drinking water for 

14 days at doses >1 mg/kg/day. Thus, the model simulated a greater inhibition of thyroid uptake of 

iodide in animals that received repeated doses of perchlorate than was actually observed. The inability of 

the model to accurately predict the effect of repeated exposures to perchlorate on thyroid iodide uptake is 

not surprising, since the model does not simulate the hormonal regulation of NIS activity and 

organification of iodide in the thyroid. In animals that received repeated exposures to perchlorate, 

induction of NIS and thyroid hormone production are likely to have occurred secondary to elevations in 

serum TSH (EPA 2002a; Uyttersprot et al. 1997). Such a response could have partially restored thyroid 

iodide uptake to higher levels than would be predicted if induction is not taken into account. 

The adult human model also predicted reasonably well radioiodine in serum, thyroid, gastric contents, and 

urine in subjects who received an intravenous dose of radioiodine (Hays and Solomon 1965), when model 

parameters were calibrated to achieve good correspondence to the observations. Similarly, model 

predictions of thyroid radioiodine uptake in subjects who received oral doses of perchlorate agreed with 

observations when the kinetic parameters for iodide in the thyroid (i.e., maximum transport into the 

thyroid follicle) were adjusted to achieve good correspondence to the observations (EPA 2002a). When 

the model was calibrated by adjusting the maximum transport rate for iodide into the thyroid follicle, it 

accurately predicted the observed time course for radioiodine uptake in a Graves’ disease patient who 

received a single tracer dose of radioiodine (Stanbury and Wyngaarden 1952); however, the model 

substantially over predicted iodine uptake after the same patient received a dose of perchlorate. Here 

again, the error in predictions of the effect of perchlorate on iodine uptake may reflect humoral regulation 

of iodide transport and organification mechanisms or the response to perchlorate in Graves’ disease 

patients that is not simulated in the model. 

The rat maternal/fetal models were evaluated by comparing predictions of radioiodine concentrations in 

mammary gland and placenta, and maternal and fetal serum and thyroid following single intravenous 
IODINE 168 

3. HEALTH EFFECTS 

injections of radioiodine, with or without concurrent injection of perchlorate or exposure to perchlorate in 

drinking water (EPA 2002a; Versloot et al. 1997). Model predictions were in reasonable agreement with 

observations for rats that received single injections of iodide with or without single injections of 

perchlorate; however, the model under-predicted maternal thyroid iodide levels in animals that received 

repeated oral exposures to perchlorate. 

Similar outcomes occurred in evaluations of the lactating dam/neonate model (EPA 2002a). The model 

accurately predicted serum and thyroid iodine concentrations in the dam and neonate following single 

intravenous injections of radioiodine, with or without concurrent injection of perchlorate. However, the 

model under predicted maternal iodide levels in dams that received repeated exposures to perchlorate in 

drinking water. 

Risk assessment. 

The rat and human models have been used to calculate human equivalent exposure levels for perchlorate 

that would be expected to produce the same degree of inhibition of iodide uptake into the thyroid gland 

(EPA 2002a). These estimates have been used to extrapolate dose-response relationships for perchlorate 

observed in rats to humans. 

Target tissues. 

The models are designed to calculate iodine concentrations in serum and thyroid. 

Species extrapolation. 

The models are designed for applications to rat or human dosimetry and cannot be applied to other 

species without modification. 

Interroute extrapolation. 

The models are designed to simulate intravenous or oral exposures to radioiodine and cannot be applied to 

other routes of exposure without modification. 
 

 

IODINE 169 

3. HEALTH EFFECTS 

Berkovski (2002) Iodine Biokinetics Model 

Description of the model. 

Berkovski (1999a, 1999b) developed compartmental models of the biokinetics of iodine in the pregnant 

and lactating human female (Figure 3-12). The most recent description of the models (Berkovski 2002) is 

the basis for the ICRP (2002) iodine model. The models simulate the transfer of iodine from the pregnant 

woman to the fetus and to breast milk, during lactation. The maternal model simulates the gastrointestinal 

cycling of iodine, including absorption to blood from the stomach (slow) and small intestine (fast), 

secretion into the stomach, secretion into salivary glands (the latter transfers to the stomach), and 

secretion of organic iodine from other tissues into the large intestine (e.g., biliary transfer; the latter 

transfers to feces). Iodide in the central blood compartment distributes to the breasts, kidney (to urinary 

bladder), ovaries, thyroid gland, and other tissues. The model includes pathways for cycling of iodine 

into and out of the organic iodine (e.g., thyroid hormones) pool. This includes the thyroid gland, which 

has subcompartments for iodide and organic iodine (e.g., thyroid hormone and precursors). The thyroidal 

iodide compartment exchanges with the blood compartment; the organic iodine compartment receives 

input from blood and delivers organic iodine to the other tissue compartment. In the other tissue 

compartment, organic iodine is deiodinated and the resulting iodide pool exchanges with the iodide in the 

blood compartment. The model predicts, for a euthyroid adult who ingests 150 μg iodide/day, 

equilibrium contents of approximately 21 μg iodide in blood, 30 μg iodide and 8,000 μg organic iodine in 

the thyroid gland, 57 μg iodide and 1,350 μg organic iodine in other tissues, and 21 μg iodide in blood. 

The resulting ratio of total iodine in thyroid to that in blood is approximately 400. 

The pregnancy model extends the maternal model with additional compartments representing the uterus 

and placenta, amniotic fluid compartment, and fetus. Iodide in the maternal blood compartment 

exchanges with iodide in the placental/uterine and amniotic fluid compartments. Organic iodine in the 

maternal other tissues compartment exchanges with organic iodine in the placental and amniotic fluid 

compartments. The fetal compartment includes three subcompartments representing cycling of fetal 

iodide into thyroid and extra-thyroidal iodine pools. Iodide can enter the fetal compartment from 

exchange with iodide in the placental/uterine compartments or from transfer from the amniotic fluid (i.e., 

fetal ingestion of amniotic fluid). Transfer coefficients vary through gestation to account for changes in 

maternal and fetal iodine biokinetics associated with growth of the placenta and fetus, initiation of fetal 

thyroid iodine accumulation and hormone production (approximately 12 weeks of gestation), and 

increased maternal renal clearance of iodide. 
 

 

IODINE 170 

3. HEALTH EFFECTS 

Figure 3-12. Berkovski (2002) Metabolic Model for Iodine 

Stomach 

127I 150 μg d-1 

I 

Salivary 

glands 

Gastric 

secretory 

cells 

S 

J 

λS St 

λJ Stv 

SI ULI LLI 

λSt SI 

λSI ULI 

λULI LLI 

λLLIF Faeces 

(F) 

λIS 

λSt I 

λIJ 

Mother 

λOI λIO 

Ovaries 

O 

Iodide in 

blood 

I 

λSI I 

Iodide 

30 μg 

g 

Organic

I8,000 μg 

G 

λIg λgI λIG 

Thyroid 

Iodide 

D 

Organic I 

B 

λDI λID 

Other 

λB ULI λGB

Breasts 

Br 

Urinary 

bladder 

UB 

Kidneys 

K 

λK 

Ub 

Milk (M) 

Urine (U) 

λBr M 

λUB U 

UteroPlacental 

Unit 

Iodide 

PI 

Organic I 

P2 

Embryo and 

Fetus 

Fetal 

iodide 

FI 

Fetal 

thyroid 

FG 

Fetal 

organic 1 

FB 

λFG FB 

λFI FGv 

λFB FI 

Iodide 

A1 

Organic I 

A2 

Amniotic fluid 

λAI FIvv λA2 FI 

λFI PI 

λPI FI 

λBP2 λP2B 

λIK 

λI PI 

λPI I 

λI AI 

λAi I λBD 

λB A2 λA2 B 

St 

Adapted from Berkovski 1999a 
IODINE 171 

3. HEALTH EFFECTS 

The lactation model includes an additional compartment for breast milk, which receives iodide from the 

breast compartment. 

Validation of the model. 

Berkovski (1999a, 1999b, 2002) presents comparisons of model predictions and observations made in 

humans. The model predictions agree well with the observed kinetics of elimination of 131I from amniotic 

fluid after intravenous injection of 131I. The model also simulates, with good agreement, observed fetal 

thyroid radioiodine uptakes and elimination at various stages of gestation. 

Risk assessment. 

The Berkovski (2002) model is the basis for the ICRP (2002) model, which is used to establish radiation 

dose equivalents (Sv/Bq) of various ingested radioactive isotopes of iodine. 

Target tissues. 

The model is designed to calculate radioiodine intake limits based on radiation dose to all major organs 

that concentrate iodine (relative to blood), including the thyroid gland, salivary glands, ovaries, and fetus. 

Species extrapolation. 

The model is designed for applications to human dosimetry and cannot be applied to other species without 

modification. 

Interroute extrapolation. 

The model is designed to simulate oral exposures to radioiodine; however, it has been applied to 

simulating the biokinetics of intravenous injections of iodide and could be applied other routes of 

exposure with modification to include simulations of the absorption from these routes to blood. 

ICRP (1989) Iodine Biokinetics Model 

Description of the model. 

ICRP (1989) developed a compartmental model of the kinetics of ingested iodine in humans with 

parameter values that are applicable to infants, children, adolescents, and adults. The model is a 
IODINE 172 

3. HEALTH EFFECTS 

modification and expansion of a similar model described in ICRP (1979; Riggs 1952). Ingested iodine is 

assumed to be completely absorbed. Absorbed iodine is assumed to distribute to three compartments: 

blood, thyroid gland, and extrathyroid tissues (Figure 3-13). Of the iodine entering the transfer 

compartment, 30% is assumed to be transferred to the thyroid gland; the remaining 70% is excreted in 

urine. All iodine eliminated from the thyroid gland is assumed to be transferred to the extrathyroidal 

tissues compartment as organic iodine (e.g., iodothyronines). Twenty percent of the iodine eliminated 

from extrathyroidal tissues is assumed to be excreted in feces; the remaining 80% is transferred to blood. 

Elimination half-times of iodine from thyroid, and extrathyroidal tissues are age-dependent, while that 

from blood is independent of age (Figure 3-13). The modifications made in this model from ICRP (1979) 

include: (1) 20%, rather than 10% of the of iodine eliminated from extrathyroidal tissues is assumed to be 

excreted in feces; (2) age-dependent elimination half-times for iodine, which allows the model to be 

applied to infants, children, adolescents, and adults; and (3) the extrathyroidal iodine pool is assumed to 

be 0.1 of the thyroid pool and the thyroid iodine pool is allowed to be variable, reflecting geographic 

variation or other sources of variation in intake. 

Validation of the model. 

The extent to which the ICRP model has been validated is not described in ICRP (1989). 

Risk assessment. 

The model has been used to establish radiation dose equivalents (Sv/Bq) of ingested various radioactive 

isotopes of iodine (ICRP 1989, 1993). 

Target tissues. 

The model is designed to calculate radioiodine intake limits based on radiation dose to all major organs, 

including the thyroid gland. 

Species extrapolation. 

The model is designed for applications to human dosimetry and cannot be applied to other species without 

modification. 
 

 

Blood 

f 1k 1· (1-e) k · 3 

Extra-thyroidal Thyroid Tissues 

k2 

(1-f 1 k) · 3 

Urine Feces 

 

 

IODINE 173 

3. HEALTH EFFECTS 

Figure 3-13. International Commission on Radiological Protection (ICRP) (1989) 

Metabolic Model for Iodine 

Uptake from
 

Ingestion
 

ICRP (1989) Metabolic Model for Iodine 

Age f1 

Thyroid 

uptake 

(%) 

Fecal 

excretion 

(%) 

Biological half-timea

 (d) 

Apparent 

half-timeb (d) 

Blood 

T1 

Thyroid 

T2 

Extrathyroidal 

T3 Thyroid 

3 months 1 30 20 0.25 11.2 1.12 15 

1 year 1 30 20 0.25 15 1.5 20 

5 years 1 30 20 0.25 23 2.3 30 

10 years 1 30 20 0.25 58 5.8 70 

15 years 1 30 20 0.25 67 6.7 80 

Adult 1 30 20 0.25 80 12 91 

a

ln2/ki b

2–16 days after uptake 
IODINE 174 

3. HEALTH EFFECTS 

Interroute extrapolation. 

The model is designed to simulate oral exposures to radioiodine and cannot be applied to other routes of 

exposure without modification. 

Killough and Eckerman (1986) Iodine Biokinetics Model 

Description of the model. 

Killough and Eckerman (1986) developed a 2-compartment modification of the 3-compartment model as 

described by Riggs (1952, the basis for the ICRP 1979 model). In the Killough and Eckerman (1986) 

model, the compartment representing the extrathyroidal organic iodine pool in Riggs (1952) has been 

eliminated and transfer into the thyroid gland is represented with a first-order rate constant (rather than a 

deposition fraction). This change provides for simulation of the short-term kinetics of uptake of iodine 

into the thyroid (rather then only maximal uptakes), enabling such observations to be incorporated into 

model calibration efforts (Killough and Eckerman 1986). Values for the transfers of iodine into and out 

of the thyroid are age-dependent, which is the basis for age-dependence of the biokinetics simulated in the 

model. 

Validation of the model. 

The extent to which the Killough and Eckerman model has been validated is not described in Killough 

and Eckerman (1986). 

Risk assessment. 

The model has been used to establish radiation doses to the thyroid for 4,216 patients administered 131I for 

clinical diagnostic purposes (Killough and Eckerman 1986). 

Target tissues. 

The model is designed to calculate thyroid gland radiation doses associated with administered activities of 

radioiodine. 
IODINE 175 

3. HEALTH EFFECTS 

Species extrapolation. 

The model is designed for applications to human dosimetry and cannot be applied to other species without 

modification. 

Interroute extrapolation. 

The model is designed to simulate biokinetics of iodine after the delivery of iodine to the central transfer 

compartment (irrespective of the route of absorption). Oral, inhalation, or other routes exposures to 

radioiodine could be simulated with modification to include simulations of the absorption from these 

routes. 

NRPB-UK Model 

Description of the model. 

The National Radiological Protection Board of the United Kingdom (NRPB-UK) developed a 

compartmental model of ingested iodine in human adults and children (Stather and Greenhalgh 1983). 

The model has three compartments representing the thyroid gland, an inorganic iodide pool that includes 

all inorganic iodide in the body with the exception of that in the thyroid gland, and an organic iodine pool, 

exclusive of organic iodine in the thyroid gland (Figure 3-14). Iodide that enters the gastrointestinal tract 

from ingestion is assumed to be completely absorbed into the inorganic iodide pool. Of the iodine 

entering the inorganic iodide pool, 25% is transferred to the thyroid gland where it resides with an 

elimination half-time of 79 days; the rest is excreted in urine. The thyroid gland is assumed to have a 

steady state iodine content of 8 mg. All iodine eliminated from the thyroid gland is assumed to be 

transferred to the organic iodine pool where it resides with an elimination half-time of 8 days. Twenty 

percent of the iodine eliminated from the organic iodine pool is assumed to be excreted in feces; the 

remaining 80% enters the inorganic iodide pool. 

Models for 1-year-old infants and 10-year-old children are also described in Stather and Greenhalgh 

(1983). The models are essentially the same as the adult model with one change; the elimination halftime for iodine in the thyroid gland is assumed to be 17 days for 1-year-old infants and 72 days for 

10-year-old children. 
 

Dose (D) 

f

1 

Inorganic Iodide 

Pool 

56 μg/day 70 μg/day 

Organic Iodine Thyroid 

Pool (800 μg) (8,000 μg) 70 μg/day 

D-14 μg/day 14 μ/day 

Urine Feces

Source: Stather and Greenhalgh 1983 

IODINE 176 

3. HEALTH EFFECTS 

Figure 3-14. National Radiological Protection Board of the United Kingdom 

Metabolic Model for Iodine 
IODINE 177 

3. HEALTH EFFECTS 

Validation of the model. 

The extent to which the NRPB-UK model has been validated is not described in Stather and Greenhalgh 

(1983). 

Risk assessment. 

The model was developed for calculating radiation doses to populations in the United Kingdom following 

release of iodine isotopes into the environment. The extent to which the model has been used for this 

purpose is not described in Stather and Greenhalgh (1983). 

Target tissues. 

The model is designed to calculate intake and exposure limits, based on radiation dose to the NRPB-UK 

model thyroid gland. 

Species extrapolation. 

The model is designed for applications to human dosimetry and cannot be applied to other species without 

modification. 

Interroute extrapolation. 

The model is designed to simulate oral exposures to radioiodine and cannot be applied to other routes of 

exposure without modification. 

Johnson (1982) Model 

Description of the model. 

Johnson (1982, 1986) described a compartmental model of iodine biokinetics in humans that included 

parameters for simulating pregnancy. The structure of the maternal model is similar to the Stather and 

Greenhalgh (1983) model in that it has three compartments representing the thyroid gland, an extrathyroidal inorganic iodide pool, and an organic iodine pool, exclusive of organic iodine in the thyroid 

gland (Figure 3-15). Iodide that enters the gastrointestinal tract from ingestion or the lungs from 

inhalation is assumed to be absorbed into the inorganic iodide pool. From the inorganic iodide pool, 

iodide is transferred to the thyroid gland (at a rate equal to loss of thyroidal iodine to the organic iodine 
 

 

 

 

 

lr (t) 

1 

Mother’s 

Stomach 

or Lungs 

2 

Mother’s and 

Fetus’ Inorganic 

Compartment 

3 

Mother’s 

Thyroid 

r8 s8 r2 s2 

4 

Mother’s 

Organic 

Compartment 

λ3 

λ1 

λ3 

λ10 λ4 

λ6 

5 

Bladder 

Contents 

Gastrointestinal 

Tract 

λ1 

Urine Feces 

1-F1 1-F0 F1 F0 

l

s (t) 

6 

Fetus’ 

Thyroid 

λ9 

7 

Fetus’ 

Organic 

Compartment
 

Adapted from Johnson 1986 

IODINE 178 

3. HEALTH EFFECTS 

Figure 3-15. Johnson (1982) Metabolic Model for Iodine 
IODINE 179 

3. HEALTH EFFECTS 

pool), or is excreted in urine and feces. All iodine eliminated from the thyroid gland is assumed to be 

transferred to the organic iodine pool, from which it can renter the extra-thyroidal inorganic iodine pool. 

Daily thyroid iodide uptakes vary with thyroid gland mass. Thyroid gland growth and mass are age- and 

gender-dependent, which are the bases for age- and gender dependence of the biokinetics in the model. 

The pregnancy model includes fetal thyroid and fetal organic iodine compartments. Iodide cycles from 

the maternal extrathyroidal iodide pool, to the fetal thyroid pool, to the fetal organic iodine pool, from 

where it can return to the maternal extrathyroidal iodide pool. 

Validation of the model. 

The extent to which the Johnson (1982, 1986) model has been validated is not described in either 

publication. 

Risk assessment. 

The model was developed for calculating radiation doses to populations following release of iodine 

isotopes into the environment. The extent to which the model has been used for this purpose is not 

described in Johnson (1982, 1986). 

Target tissues. 

The model is designed to calculate intake and exposure limits, based on radiation dose to the thyroid 

gland. 

Species extrapolation. 

The model is designed for applications to human dosimetry and cannot be applied to other species without 

modification. 

Interroute extrapolation. 

The model is designed to simulate oral and inhalation exposures to radioiodine; however, it could be 

applied to other routes of exposure with modifications to include simulations of the absorption from these 

routes to the extrathyroidal inorganic iodide pool. 
IODINE 180 

3. HEALTH EFFECTS 

Oddie et al. Model 

Description of the model. 

Oddie et al. (1955) described a compartmental model of absorbed iodine human adults and infants (Fisher 

et al. 1962) for predicting 24-hour radioiodine uptake by the thyroid gland in clinical procedures. The 

model has two compartments representing the thyroid gland and a central iodide pool that includes all 

inorganic iodide in the body with the exception of that in the thyroid gland. An organic iodine pool is not 

included in the model. Although this would preclude the model from accurately simulating radioiodide 

levels in extrathyroidal tissues, including blood, it was not considered necessary for simulating the initial 

uptake of iodide by the thyroid following a single dose of radioiodine, prior to significant release of 

organic iodine from the thyroid gland. Iodide that enters the inorganic iodide pool is assumed to be 

transferred either to the thyroid gland, represented as a first order rate constant k1, or to the kidney for 

urinary excretion, represented by a rate constant k2, usually corrected for loss of iodide in sweat, feces, 

and uncollected urine (Oddie and Fisher 1967). In a study of 20 healthy adults, k1 was estimated to be 

60x10-5/minute in subjects who ingested a tracer dose of radioiodine (Fisher et al. 1965). In this same 

study, the value of k1 was 49x10-5 after 13 weeks of daily ingestion of 252 μg iodide/day and 35x10-5, 

after 13 weeks of daily ingestion of 1,000 μg iodide/day. The estimate of k2 from this study was 

300x10-5 minute-1. Values for k1 estimated in various populations have ranged from 67 to 

134x10-5 minute-1 (Oddie and Fisher 1967). The volume of the iodide space was estimated to be 2.1 L 

(Fisher et al. 1965). 

The same model has been used to predict thyroid uptakes of iodine in infants. Values for k1 and k2 were 

estimated from studies in which 24-hour thyroid uptakes of iodine were measured in 26 euthyroid 

newborn infants (Fisher et al. 1962). The values for k1 and k2 were 2.4x10-3 minute-1 and 

1.1x10-3 minute-1, respectively. The iodide space was estimated to be approximately 0.4 L in newborn 

infants. 

Validation of the model. 

The model has been shown to predict 24-hour iodine uptakes in the thyroid in adults who received single 

doses of radioiodine. Predicted 24-hour thyroid uptakes of radioiodine were compared to observed 

estimates in 1,573 euthyroid subjects reported from various studies; the difference between observed and 

predicted estimated for eight studies ranged from 0.7 to 2.1%, with the observed uptakes ranging from 

21 to 37% (Oddie and Fisher 1967). 
IODINE 181 

3. HEALTH EFFECTS 

Risk assessment. 

The model was developed for predicting the 24-hour uptake of radioiodine in the thyroid after single 

doses of radioiodine are given in the clinical setting for assessing thyroid function. It has been evaluated 

in terms of its predictive value in detecting abnormal thyroid conditions that affect iodide uptake into the 

gland (Oddie et al. 1960). The extent to which the model has been used for risk assessment could not be 

ascertained from the available literature. 

Target tissues. 

The model is designed to predict 24-hour uptakes of radioiodine into the thyroid gland. 

Species extrapolation. 

The model is designed for applications to humans and cannot be applied to other species without 

modification. 

Interroute extrapolation. 

The model is designed to simulate oral ingestion or parenteral injection (e.g., intramuscular in infants) of 

radioiodine and cannot be applied to other routes of exposure without modification. 

3.6 MECHANISMS OF ACTION 

3.6.1 Pharmacokinetic Mechanisms 

Absorption. The mechanism(s) by which iodide is absorbed from the gastrointestinal tract is not 

known. Based on the study conducted by Small et al. (1961), absorption appears to occur primarily in the 

small intestine in humans. This study measured iodine in the saliva of healthy human subjects who 

ingested 0.25 g of potassium iodide (0.19 g iodide) together with a radioopaque suspension of barium 

sulfate that allowed the emptying of the stomach to be imaged with a fluoroscope. In five subjects, iodine 

was not detected in saliva until 2–3 minutes after the first appearance of the barium sulfate in the 

duodenum; the actual time of appearance relative to the oral dose of iodide ranged from 15 to 40 minutes. 

An intravenous dose of probanthine, which delays gastric emptying time, given just prior to the oral dose 

of potassium iodide, substantially delayed the time of appearance of iodine in saliva to 114–133 minutes; 
IODINE 182 

3. HEALTH EFFECTS 

however, in each of three subjects, iodine was detected in saliva 3–4 minutes after the first appearance of 

the radioopaque marker in the duodenum. When iodide was instilled directly into the duodenum together 

with the radioopaque marker (two subjects), iodine was detected in saliva 3–4 minutes after the dose was 

administered. These observations suggest that the absorption of iodide in humans occurs primarily in the 

small intestine and that the stomach may play a minor role in iodide absorption. The mechanisms by 

which iodide is transported across the intestinal epithelium are not known. Iodide may be transported by 

mechanisms that also transport chloride such as the Cl-

/HCO3

-

 antiport (Dalmark 1976; Lambert and 

Lowe 1978) or Cl-

 channels (Katayama and Widdicombe 1991). 

While the above studies implicate the small intestine as the major site of absorption of iodide in humans, 

studies in rats and dogs indicate that 14–30% of an oral dose of iodide may be absorbed in the stomach in 

these species (Small et al. 1961; Cohn 1932) 

Distribution. 

Iodide Transport. Uptake of iodide into the thyroid is facilitated by a membrane carrier in the basolateral 

membrane of the thyroid follicle cell (Carrasco 1993; Levy et al. 1998a; Shen et al. 2001). The carrier, or 

NIS, catalyzes the simultaneous transfer Na+

 and I- across the basolateral membrane (Chambard et al. 

1983; Iff and Wilbrandt 1963; Nilsson et al. 1990). The stoichiometry of transfer reaction is (2)Na+

/(1)I-, 

which confers to the NIS a net positive charge and, therefore, a sensitivity to transmembrane voltage 

(Eskandari et al. 1997; O’Neill et al. 1987). In the presence of an inward-directed electrochemical 

gradient for Na+

, the NIS can transfer I- into the cell against a pronounced outward-directed 

electrochemical gradient for I-

 (Takasu et al. 1984; Williams 1969; Woodbury and Woodbury 1963). 

This enables the follicle cell to achieve intracellular/extracellular concentration ratios of 10–50 for iodide 

(Andros and Wollman 1991; Bagchi and Fawcett 1973; Shimura et al. 1997; Vroye et al. 1998; Weiss et 

al. 1984b; Wolff 1964). 

The NIS has been studied extensively in several in vitro preparations, including isolated plasma 

membrane vesicles of mammalian thyroid (O’Neill et al. 1987), FRTL-5 cells, a cell line derived from 

normal rat thyroid (Weiss et al. 1984b), Xenopus lavis oocytes transformed by intracellular injection of 

FRTL-5 RNA to express NIS (Eskandari et al. 1997), and other mammalian cells cultures transformed to 

express NIS (Levy et al. 1997; Nakamura et al. 1990; Smanik et al. 1996; Yoshida et al. 1997). The 

apparent Km for I-

 transport in cell systems is approximately 30–40 μM, which is considerably higher than 

the serum iodide concentration of 0.04–0.08 μM (5–10 μg/L) (Eskandari et al. 1997; Weiss et al. 1984b). 

The relatively high Km enables the iodide transport rate to be highly sensitive to changes in plasma I­
 

 

 

IODINE 183 

3. HEALTH EFFECTS 

concentration. Iodide transport by the NIS is inhibited by other anions, most notably, thiocyanate (SCN-) 

and perchlorate (ClO4

-

) (Carrasco 1993; Wolff 1964). Thiocyanate is one of several anions other than Ithat can be transported by the NIS, including SeCN-

, NO3

-

, ClO3

-

, Br-, BF4

-

, IO4

-

, and BrO3

- (Eskandari et 

al. 1997). Perchlorate, on the other hand, does not appear to be transported by NIS (Eskandari et al. 1997; 

Yoshida et al. 1997). Thus, thiocyanate and perchlorate, which both inhibit iodide uptake in thyroid in 

vivo, do so by different mechanisms; thiocyanate is a competitive substrate for transport, whereas 

perchlorate appears to block I-

 binding to the NIS. 

Synthesis of NIS is regulated by the pituitary hormone, TSH, which stimulates iodide uptake into the 

thyroid. The mechanism involves both increased transcription of the NIS gene and increased translation 

of mRNA for NIS (Kogai et al. 1997; Levy et al. 1997; Ohno et al. 1999; Pekary et al. 1998). Both 

responses to TSH follow binding of TSH to a receptor on the basolateral membrane and activation of the 

enzyme adenylate cyclase by GTP binding protein Gα (Akamizu et al. 1990; Chazenbalk et al. 1990; 

Kogai et al. 1997; Parmentier et al. 1989; Perret et al. 1990; Raspe and Dumont 1995). In FRTL-5 cells 

grown in the absence of TSH, NIS activity declines to a minimum level and can be restored by the 

addition of TSH to the medium or by treating the cells with dibutryl-cAMP or other agents that increase 

the intracellular concentration of cAMP (Pekary et al. 1998; Weiss et al. 1984a, 1984b). Thus, the actions 

of TSH appear to involve the activation of adenylate cyclase and subsequent increase in the intracellular 

concentration of cAMP. TSH also appears to mediate post-transcriptional regulation of NIS, including 

increasing the intracellular elimination half-time of the NIS protein and stimulating the incorporation of 

the NIS protein into the thyrocyte cell membrane (Riedel et al. 2001). 

Synthesis of NIS also appears to be regulated by plasma iodide concentration through a mechanism that 

does not directly involve TSH. In rats exposed to drinking water containing 500 mg/L I as sodium iodide, 

expression of mRNA for the NIS in the thyroid decreased by 45% after 1 day of exposure and 60% after 

6 days of exposure compared to controls that ingested water without added iodide. Serum iodide 

concentrations were 150–200-fold higher in the exposed rats compared to controls, whereas the serum 

TSH concentrations were not different between control and treated groups (Eng et al. 1999). A similar 

observation was made in dogs made hypothyroid by treatment with propylthiouracil (an inhibitor of 

iodination of thyroglobulin) and perchlorate (Uyttersprot et al. 1997). The hypothyroid state elevated 

TSH concentrations in serum; nevertheless, a single injection of 0.3 mg potassium iodide (0.23 mg I) 

resulted in decreased expression of NIS in the thyroid within 24–48 hours after the dose, without a change 

in TSH concentrations in serum. Both iodide and T3 depress the expression of NIS mRNA and iodide 

uptakes in rat thyroid follicle cells grown in culture (Sptizweg et al. 1999). 
IODINE 184 

3. HEALTH EFFECTS 

The exact mechanisms by which the NIS gene transcription is regulated have not been determined. The 

gene in humans and rats has been sequenced, enabling studies of the mechanisms of gene transcription 

regulation (Dai et al. 1996; Smanik et al. 1996). The human gene resides on chromosome 19 (Smanik et 

al. 1997). Mutations in the gene sequence have been associated with hypothyroidism, goiter, and 

abnormally low thyroid uptake of injected iodide (Fujiwara et al. 1997, 1998, 2000; Kosugi et al. 1998, 

2002; Levy et al. 1998c; Pohlenz and Refetoff 1999; Pohlenz et al. 1997). The 5'

-flanking region of the 

rat NIS gene has been shown to contain one or more promoter regions; however, their role in regulation 

of the NIS transcription is not completely understood (Endo et al. 1997; Kogai et al. 2001; Ohno et al. 

1999; Schmitt et al. 2000, 2001; Tong et al. 1997). A promoter region in the rat NIS gene appears to 

respond to a rise in intracellular cAMP, most likely by binding a cAMP-inducible or cAMP-activated 

transcription factor (Chun and Di Lauro 2001; Ohno et al. 1999). NIS expression in FRTL-5 cells is 

increased in response to extracellular adenosine, possibly through a mechanism that is independent of 

cAMP (Harii et al. 1999). A promoter region in the rat NIS gene responsive to thyroid transcription factor 

1 (TTF-1) has also been described (Endo et al. 1997). Tong et al. (1997) found evidence for a promoter 

region in the rat NIS gene that could be suppressed in cell cultures that were transformed with the 

oncogene PTC1. This may provide a mechanism for the decreased expression of the NIS gene in thyroid 

papillary carcinomas and the decreased iodide uptake of some thyroid carcinomas (Smanik et al. 1996, 

1997). 

Several tissues in humans, other than thyroid, actively express NIS and accumulate iodide; these include 

the mammary gland, salivary glands, and gastric mucosa (Brown-Gant 1961; Lacroix et al., 2001; Smanik 

et al. 1997; Spitzweg et al. 1998, 1999; Wolff 1983). These tissues can achieve intracellular/extracellular 

and/or transepithelial concentration ratios for I-

 concentrations of 20–40. Transport of iodide in these 

tissues is inhibited by thiocyanate and perchlorate; however, transport activity is not responsive to TSH. 

Clinical cases of genetic absence or impaired iodide uptake in the thyroid coupled with low uptakes in 

saliva and gastric fluid suggest an involvement of an NIS mechanism in these tissues (Fujiwara et al. 

1997, 1998; Kosugi et al. 1998; Leger et al. 1987; Pohlenz and Refetoff 1999; Pohlenz et al. 1997; Wolff 

1983). Further evidence for extrathyroidal NIS comes from studies of mammary gland. The NIS gene is 

expressed in the mammary gland of the human, rat, and many strains of mice (Levy et al. 1997; Perron et 

al. 2001; Rillema et al. 2000b; Smanik et al. 1997; Spitzweg et al. 1998; Tazebay et al. 2000). In the rat, 

expression of the NIS, or a structurally similar membrane protein, increases during nursing and decreases 

after weaning (Cho et al. 2000; Levy et al. 1998a). In the mouse and rat, the induction of NIS appears to 
 

 

IODINE 185 

3. HEALTH EFFECTS 

be stimulated by prolactin (Cho et al. 2000; Rillema and Rowady 1997; Rillema et al. 2000b). The NIS 

gene is also expressed in human kidney and placenta (Bidart et al. 2000; Spitzweg et al. 2001). 

Studies in animals have revealed other tissues that actively secrete or accumulate iodide transport by a 

mechanism that is inhibited by perchlorate and thiocyanate, suggestive of an active NIS. These include 

choroid plexus, ciliary body of the eye, small intestine (ileum), ovary, placenta, and skin in mammals; and 

avian salt gland in marine birds (Brown-Grant 1961). In humans, the NIS gene is expressed in mammary 

gland, salivary glands, and gastric mucosa (Lacroix et al. 2001; Smanik et al. 1997; Spitzweg et al. 1998). 

An iodide transporter that is distinct from NIS has been characterized in the apical membrane of the 

thyroid follicle cell (Royaux et al. 2000; Taylor et al. 2002; Yoshida et al. 2002). This transporter may 

function in the facilitated transfer of iodide from the follicle cell in the follicle lumen. Mutations in the 

gene coding for the apical transporter occur in Pendred syndrome, an autosomal recessive disorder 

characterized by hearing loss, thyroid iodide organification deficits goiter (Scott et al. 2000). 

Iodothyronine Transport. Uptake of T4 and T3 into tissues occurs by a saturable, energy-dependent 

carrier transport system. Evidence for active transport derives from a variety of observations. The rate of 

uptake of T3 into the perfused rat liver is proportional to the concentration of free T3 in the perfusate and 

is not related to the total concentration or bound concentration (Mendel et al. 1988). The free cytosolic 

concentration of T3 in the in vivo rat liver and heart muscle exceeds that of the simultaneous free 

concentration in plasma, suggesting uptake of T3 into these tissues against a chemical gradient for T3 

(Oppenheimer and Schwartz 1985). T3 uptake into confluent cultures of human or rat hepatoma cells is 

saturable, stereoselective for the active L enantiomer, temperature dependent, and inhibited by metabolic 

and membrane transport inhibitors, including phloretin (Movius et al. 1989; Topliss et al. 1989). 

Saturable, stereoselective, temperature-dependent, and energy-dependent uptake of T3 and T4 has also 

been observed in cultures of human fibroblasts and of T3 in in vitro preparations of rat skeletal muscle 

(Centanni and Robbins 1987; Docter et al. 1987). 

Metabolism. 

Iodination in the Thyroid Gland. Iodination of thyroglobulin is catalyzed by thyroid peroxidase, a 

hemoprotein in the apical (luminal) membrane of thyroid follicle cells (Dunn and Dunn 2001). Thyroid 

peroxidase catalyzes both the iodination of tyrosine residues in thyroglobulin and the coupling of the 

iodinated residues to form the thyroid hormones, T4 and T3, and diiodotyrosine. The iodination reaction 

involves the oxidation of iodide (I-

) to a reactive species having a sufficiently high oxidation potential to 
 

 

IODINE 186 

3. HEALTH EFFECTS 

iodinate the aromatic ring of tyrosine. The oxidizing agent in the reaction is hydrogen peroxide, which is 

generated at the apical membrane of follicle cells by an NADPH oxidase (Deme et al. 1994; Dupuy et al. 

1991). Although the exact mechanism of the iodination reaction is not completely understood, three 

species are suspected as being candidates for the reactive iodinating species: a free radical (I@), iodinium 

(I+

), or an enzyme-bound hypoiodite ([EOI]-) (Taurog 1996). Human thyroglobulin contains 134 tyrosyl 

residues, of which approximately 20 undergo iodination to yield approximately 2–4 molecules of T4 or T3 

per molecule of thyroglobulin. The coupling reaction occurs within thyroglobulin, rather than as a 

reaction between free iodinated tyrosines. In the formation of T4, two molecules of diiodotyrosine are 

coupled, whereas the formation of T3 is a coupling of monoiodotyrosine and diiodotyrosine residues. The 

reaction is catalyzed by thyroid peroxidase with hydrogen peroxide serving as the oxidizing agent in the 

formation of a reactive intermediate of the contributing diiodotyrosine residue, possibly a free radical 

species (Taurog et al. 1994). Specificity of iodination and coupling of tyrosine residues within 

thyroglobulin is conferred, in part, by the specificity of thyroid peroxidase and, in part, by the structure of 

thyroglobulin (Taurog 1996). 

The gene for human thyroid peroxidase has been isolated and sequenced (Kimura et al. 1987; Libert et al. 

1987; Magnusson et al. 1987). Transcription of the gene is stimulated by TSH, possibly through a 

mechanism involving cAMP (McLachlan and Rapoport 1992). 

Deiodination of Iodothyrones in Peripheral Tissues. Deiodination serves both as an important 

mechanism for the production of extrathyroidal T3 and for the deactivation of the thyroid hormones, T4 

and T3. The deiodination reactions are catalyzed by selenium-dependent deiodinase enzymes 

(selenodeiodinases). Three selenodeiodinases have been described that differ in substrate preference, 

reaction products, response to inhibitors (propylthiouracil, gold), and response to T3 (Table 3-8). Full 

activity of each enzyme requires selenocysteine in the amino acid sequence of the active site, which is the 

basis for deiodination activity being responsive to nutritional selenium status (Larsen and Berry 1994; see 

Section 3.10). 

Excretion. 

Urinary Excretion of Iodide. Urinary excretion normally accounts for >97% of the elimination of 

absorbed iodine. The renal plasma clearance of iodine has been measured in human subjects during 

continuous intravenous infusions of radioiodide (Bricker and Hlad 1955). Under these conditions, only a 

negligible amount of radioiodine in the plasma was associated with protein and >98% was ultrafilterable; 

thus, the renal clearance of radioiodine can be assumed to reflect that of radioiodide (Bricker and Hlad 
 

 

 

IODINE 187 

3. HEALTH EFFECTS 

Table 3-8. Properties of Human Iodothyronine Selenodeiodinases 

Parameter Type 1 Type 2 Type 3 

Physiological role Plasma T3 production, 

deactivate T3 and T4, 

degrade rT3 

Plasma and 

intracellular T3 

production 

Deactivate T3 and 

T4 

Tissue location Liver, kidney, thyroid, 

central nervous system, 

pituitary 

Central nervous 

system, pituitary, brown 

fat, placenta, thyroid, 

skeletal muscle, heart 

Central nervous 

system, placenta, 

skin 

Substrate 

preference 

rT3>>T4>T3 T4$rT3 T3>T4 

Molecular weight 

(D)a 

29,000 35,000 31,500 

Apparent Km (M) ~10-7 (rT3) 

~10-6 (T4)

 10-9 (T4) 

~10-8 (rT3) 

~10-9 (T3) 

~10-8 (T4) 

Deiodination site Outer and inner ring Outer ring Inner ring 

Apparent Ki (M) 

Propylthiouracil 2x10-7 4x10-3 10-3 

Gold ~5x10-9 ~2x10-6 5x10-6 

Response to T3 Increase Decrease Increase 

a

Monomer 

T3 = 3,5,3N-triiodo-L-thyronine; T4 = 3,5,3N,5N-tetraiodo-L-thyronine (thyroxine); rT3 = reverse T3 

Source: Larsen et al. 1998 
 

 

 

IODINE 188 

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1955; Walser and Rahill 1965). Under steady-state conditions with respect to the serum radioiodine 

concentration, the renal plasma clearance of radioiodine was approximately 30% of the glomerular 

filtration rate, suggesting that filtered iodide is reabsorbed in the renal tubule (Vadstrup 1993). 

Measurements of the steady-state renal clearance of radioiodide in dogs have provided additional 

evidence for tubular reabsorption of iodide (Beyer et al. 1981; Walser and Rahill 1965). The mechanism 

of renal tubular reabsorption of iodide has not been elucidated, although studies to examine mechanisms 

have been largely limited to clearance studies. NIS mRNA is expressed in human kidney and NIS 

immunoreactivity has been observed in the human kidney proximal and distal tubules; however, its role in 

iodine transport in the kidney has not been elucidated (Spitzweg et al. 2001). In humans, iodide clearance 

as a fraction of the glomerular filtration rate (CI/GFR) increases in response to an acute increase in GFR 

and decreases in response to an acute decrease in GFR; however, CI/GFR is relatively unaffected by large 

acute increases in the plasma concentration of radioiodine at a constant GFR (Bricker and Hlad 1955). 

This suggests a sensitivity of tubular reabsorption to both filtered load of iodide and tubular flow rate. 

CI/GFR can be increased to near unity during mannitol-induced diuresis (Bricker and Hlad 1955). 

Although the inability to detect an apparent saturation of tubular reabsorption at high filtered loads of 

iodide and the sensitivity of tubular reabsorption to tubular flow rate are consistent with a passive, 

paracellular, component to iodide reabsorption, these observations do not rule out the existence of 

facilitated transport of iodide in the nephron. In humans, CI/GFR, whole body clearance of radioiodine is 

increased during diuresis induced by furosemide and hydrochlorothiazide, two clinical diuretics that 

decrease sodium and chloride reabsorption in the in the loop of Henle and distal convoluted tubule, 

suggesting the possibility of reabsorption of iodide in distal segments of the nephron (Seabold et al. 

1993). This observation is further supported by steady-state clearance measurements in dogs, in which 

CI/GFR was found to increase in response to hydrochlorothiazide-induced diuresis, and to be lower, near 

that of CCl/GFR, in dogs that had been maintained on a sodium deprivation diet (Beyer et al. 1981; Walser 

and Rahill 1965). The latter observation would suggest that adaptations to sodium deprivation that result 

in greater reabsorption of sodium in the late distal nephron also give rise to increased reabsorption of 

iodide. 

3.6.2 Mechanisms of Toxicity 

The mechanism by which excess iodide produces hypothyroidism is not completely understood. Iodide 

excess inhibits the iodination of thyroglobulin in the thyroid gland and inhibits the release of T4 and T3 

from the gland (Pisarev and Gärtner 2000). Both effects could contribute to stimulation of release of TSH 

from the pituitary gland and to the increase in serum concentration of TSH and hypertrophy of the thyroid 
 

 

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gland that has been shown to accompany iodide-induced thyroid gland suppression (see Section 3.2.2.2, 

Endocrine). The mechanism by which iodide suppresses iodination and thyroid hormone release appears 

to involve inhibition of adenylate cyclase. The stimulatory actions of TSH on the thyroid gland, which 

include increased iodide transport and increased iodination of thyroglobulin and production and release of 

T4 and T3, occur in response to a rise in intracellular cAMP levels that follow binding of TSH to TSH 

receptors on thyroid gland follicle cells. Iodide inhibits adenylate cyclase in thyroid gland follicle cells 

and decreases the TSH-induced rise in intracellular cAMP. However, the effect of iodide on adenylate 

cyclase can be prevented by inhibitors of iodination, such as propylthiouracil. This has led to the 

suggestion that the ultimate active inhibitor is an endogenous iodinated species that is produced in a 

reaction requiring thyroid peroxidase. Candidates for the endogenous inhibitor are one or more iodinated 

lipids (Filetti and Rapoport 1983; Pereira et al. 1990; Pisarev and Gärtner 2000). The synthesis of NIS 

also appears to be regulated by plasma iodide concentration, through a mechanism that does not directly 

involve TSH. In rats and dogs, expression of mRNA for the NIS in the thyroid decreased when serum 

iodide concentrations were increased by ingestion or injection of iodide, even when serum TSH 

concentrations were unchanged (Eng et al. 1999; Uyttersprot et al. 1997). 

Excess iodide intake may be a contributing factor in the development of autoimmune thyroiditis in people 

who are susceptible (Brown and Bagchi 1992; Foley 1992; Rose et al. 1997; Safran et al. 1987). In 

certain inbred strains of rats and mice, exposure to iodide has been shown to increase the incidence of 

lymphocytic thyroiditis (Allen and Braverman 1990; Allen et al. 1986; Noble et al. 1976; Rasooly et al. 

1996). The mechanism by which iodide stimulates autoimmunity is not completely understood. In the 

inbred mouse strain, NODh2h4, both CD4+

 and CD8+ T cells are required for iodine-induced acceleration 

of autoimmunity (Hutchings et al. 1999). Highly iodinated thyroglobulin may be an antigen in 

susceptible animals (or humans) (Dai et al. 2002; Rose et al. 1997; Saboori et al. 1998a, 1998b, 1999; 

Sundick et al. 1987). Other proposed mechanisms include effects of iodine on the regulation of major 

histocompatibility complex class I and increased expression of thyroid gland TNF-α (Schuppert et al. 

2000; Roti and Vagenakis 2000; Ruwhof and Drexhage 2001; Verma et al. 2000). Thyroid autoimmunity 

may produce hypothyroidism by stimulating thyroid cell apoptosis (Huang and Kukes 1999; Phelps et al. 

2000; Stassi et al. 2000). 

Excess iodide can, under certain circumstances, induce hyperthyroidism and thyrotoxicosis; this has been 

observed most often after iodine supplementation of iodine-deficient populations (Braverman and Roti 

1996; Fradkin and Wolff 1983; Leger et al. 1984; Paschke et al. 1994). The mechanism by which iodide 

induces hyperthyroidism is not completely understood. Chronic iodine deficiency results in thyroid gland 
 

 

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proliferation, which may increase the fixation of mutations in the gland and promote the development of 

autonomous nodules that are less responsive or unresponsive to regulation in response to serum TSH 

concentrations. Iodine excess, under these conditions, could result in increased and unregulated thyroid 

hormone production (Corvilain et al. 1998; Dremier et al. 1996; Roti and Uberti 2001). 

Extremely high acute doses of iodine in the form of tinctures containing iodine and sodium triiodide have 

resulted in deaths (Finkelstein and Jacobi 1937). The mechanism of toxicity is not understood, although 

direct chemical injury to the gastrointestinal tract and related secondary consequences, including fluid and 

electrolyte loss, massive acute extracellular fluid volume contraction, and cardiovascular shock, may 

contribute to the widespread systemic effects that have been observed in lethal or near-lethal poisonings. 

3.6.3 Animal-to-Human Extrapolations 

The principal health effects of iodine in humans have been characterized in experimental, clinical, and 

epidemiological studies of humans. Animal models remain useful for exploring mechanisms, and where 

relevant, these studies have been described; for example, the use of inbred rat strains to study iodineinduced autoimmune thyroiditis (see Section 3.2.2.2, Endocrine). The major features of the toxicokinetics 

of iodine in humans, particularly following oral exposures, have been characterized in experimental and 

clinical studies of humans. A substantial amount of experience exists in the application of biomarkers for 

assessing human exposures to iodine (e.g., urinary iodine excretion and thyroid scintillation scan) and 

health effects in humans (e.g., serum thyroid hormone, TSH, and thyroid antibodies). Thus, the 

assessment of health effects and health risks associated with exposures to iodine or radioiodine can be 

based soundly on human studies rather than on extrapolations from animal studies. 

3.7 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 Colborn and Clement (1992), was also used in 1996 when Congress mandated the 

Environmental Protection Agency (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 
IODINE 191 

3. HEALTH EFFECTS 

Testing Advisory Committee (EDSTAC), which in 1998 completed its deliberations and made 

recommendations to EPA concerning endocrine disruptors. In 1999, the National Academy of Sciences 

released a report that referred to these same types of chemicals as hormonally active agents. The 

terminology endocrine modulators has also been used to convey the fact that effects caused by such 

chemicals may not necessarily be adverse. Many scientists agree that chemicals with the ability to disrupt 

or modulate the endocrine system are a potential threat to the health of humans, aquatic animals, and 

wildlife. However, others think that endocrine-active chemicals do not pose a significant health risk, 

particularly in view of the fact that hormone mimics exist in the natural environment. Examples of 

natural hormone mimics are the isoflavinoid phytoestrogens (Adlercreutz 1995; Livingston 1978; Mayr et 

al. 1992). These chemicals are derived from plants and are similar in structure and action to endogenous 

estrogen. Although the public health significance and descriptive terminology of substances capable of 

affecting the endocrine system remains controversial, scientists agree that these chemicals may affect the 

synthesis, secretion, transport, binding, action, or elimination of natural hormones in the body responsible 

for maintaining homeostasis, reproduction, development, and/or behavior (EPA 1997). Stated differently, 

such compounds may cause toxicities that are mediated through the neuroendocrine axis. As a result, 

these chemicals may play a role in altering, for example, metabolic, sexual, immune, and neurobehavioral 

function. Such chemicals are also thought to be involved in inducing breast, testicular, and prostate 

cancers, as well as endometriosis (Berger 1994; Giwercman et al. 1993; Hoel et al. 1992). 

Iodine is an endocrine disruptor in that the principal direct effects of excessive iodine ingestion are on the 

thyroid gland and on the regulation of thyroid hormone production and secretion. As discussed in 

Section 3.2.2.2, Endocrine Effects, the effects of iodine on the thyroid gland include hypothyroidism, 

hyperthyroidism, and thyroiditis. The above three types of effects can occur in children and adults, and in 

infants exposed in utero or during lactation. Adverse effects on the pituitary and adrenal glands derive 

secondarily from disorders of the thyroid gland. A wide variety of effects on other organ systems can 

result from disorders of the thyroid gland, including disturbances of the skin, cardiovascular system, 

pulmonary system, kidneys, gastrointestinal tract, liver, blood, neuromuscular system, central nervous 

system, skeleton, male and female reproductive systems, and numerous endocrine organs, including the 

pituitary and adrenal glands (Braverman and Utiger 2000). 

3.8 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 
IODINE 192 

3. HEALTH EFFECTS 

effects on offspring resulting from exposures of parental germ cells are considered, as well as any indirect 

effects on the fetus and neonate resulting from maternal exposure during gestation and lactation. 

Relevant animal and in vitro models are also discussed. 

Children are not small adults. They differ from adults in their exposures and may differ in their 

susceptibility to hazardous chemicals. Children’s unique physiology and behavior can influence the 

extent of their exposure. Exposures of children are discussed in Section 6.6 Exposures of Children. 

Children sometimes differ from adults in their susceptibility to hazardous chemicals, but whether there is 

a difference depends on the chemical (Guzelian et al. 1992; NRC 1993). Children may be more or less 

susceptible than adults to health effects, and the relationship may change with developmental age 

(Guzelian et al. 1992; NRC 1993). Vulnerability often depends on developmental stage. There are 

critical periods of structural and functional development during both prenatal and postnatal life and a 

particular structure or function will be most sensitive to disruption during its critical period(s). Damage 

may not be evident until a later stage of development. There are often differences in pharmacokinetics 

and metabolism between children and adults. For example, absorption may be different in neonates 

because of the immaturity of their gastrointestinal tract and their larger skin surface area in proportion to 

body weight (Morselli et al. 1980; NRC 1993); the gastrointestinal absorption of lead is greatest in infants 

and young children (Ziegler et al. 1978). Distribution of xenobiotics may be different; for example, 

infants have a larger proportion of their bodies as extracellular water and their brains and livers are 

proportionately larger (Altman and Dittmer 1974; Fomon 1966; Fomon et al. 1982; Owen and Brozek 

1966; Widdowson and Dickerson 1964). The infant also has an immature blood-brain barrier (Adinolfi 

1985; Johanson 1980) and probably an immature blood-testis barrier (Setchell and Waites 1975). Many 

xenobiotic metabolizing enzymes have distinctive developmental patterns. At various stages of growth 

and development, levels of particular enzymes may be higher or lower than those of adults, and 

sometimes unique enzymes may exist at particular developmental stages (Komori et al. 1990; Leeder and 

Kearns 1997; NRC 1993; Vieira et al. 1996). Whether differences in xenobiotic metabolism make the 

child more or less susceptible also depends on whether the relevant enzymes are involved in activation of 

the parent compound to its toxic form or in detoxification. There may also be differences in excretion, 

particularly in newborns who all have a low glomerular filtration rate and have not developed efficient 

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. 
IODINE 193 

3. HEALTH EFFECTS 

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). 

Children are highly vulnerable to radioiodine toxicity and related thyroid cancers (NRC 1999). 

Radioiodine is secreted into milk in humans, cows, and goats, and infants and children ingest a larger 

amount of milk per unit of body mass than adults; they also absorb ingested iodine as avidly as adults. As 

a result, children exposed to milk that has been contaminated with radioiodine may receive a larger 

internal dose of radioiodine than similarly exposed adults. This larger absorbed iodine dose per unit of 

body mass is concentrated in a smaller thyroid mass in infants and children (Aboul-Khair et al. 1966; Kay 

et al. 1966; Mochizuki et al. 1963), which can result in a higher radiation dose per unit of thyroid mass. 

In addition to a smaller thyroid mass, thyroid iodine uptakes, expressed as a fraction of absorbed dose, are 

3–4 times higher during the first 10 days of postnatal life compared to adult uptakes and decline to adult 

levels after approximately age 10–14 days (Fisher et al. 1962; Kearns and Phillipsborn 1962; Morrison et 

al. 1963; Ogborn et al. 1960; Van Middlesworth 1954). As a result, newborn infants will be particularly 

vulnerable to high radiation doses from internal exposure to radioiodine. NCI (1997) estimated that the 

radiation dose (rad) to the thyroid gland resulting from ingestion of 1 μCi of 131I activity would increase 

with decreasing age in children from approximately 1.5 rad/μCi in adults, to approximately 6.6 rad/μCi at 

5 years, 12 rad at 1 year, and 33 rad in newborn infants. Another important factor that contributes to 

higher vulnerability of children is that children under 15 years of age appear to be more susceptible to 

developing thyroid tumors from thyroid irradiation (Wong et al. 1996). Studies of thyroid cancers and 

external radiation exposure have found a strong age-dependence between thyroid radiation dose and 

thyroid cancer. Risk is substantially greater for radiation doses received prior to age 15 years when 

compared to risks for doses received at older ages (Ron et al. 1995). An age-dependence has been found 

for solid tumors of other organs and external radiation dose (Thompson et al. 1994). This same general 

trend in age-dependence would be expected for internal exposures to radioiodine; thus, studies of adult 

exposures to radioiodine may not be directly applicable to predicting outcomes from exposures to 

children. 
 

 

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3. HEALTH EFFECTS 

Evidence for vulnerability of infants and children to radioiodine toxicity derive from studies of 

populations that have been exposed to radioiodine fall-out as a result of thermonuclear bomb tests and 

nuclear reactor accidents. Several epidemiological studies have examined thyroid gland disorders in 

residents of the Marshall Islands who were exposed to radioiodine from atmospheric fallout after an 

atmospheric nuclear bomb test (so-called BRAVO test, see Section 3.3.2 for a more detailed discussion of 

exposures from the Marshall Islands BRAVO test). The exposures occurred as a result of an unexpected 

change in the wind direction after the bomb detonation. Residents of several islands near and downwind 

from the test site on Bikini Atoll (e.g., Ailingnae, Rongelap, Utrik) were exposed to both internal 

radioiodine and external gamma radiation from fallout during the 2 days prior to their evacuation. The 

estimated gamma radiation dose on these islands ranged from 69 to 175 rad (0.7–1.75 Gy) or 

approximately 10–50% of the estimated thyroid dose (Conard 1984; Hamilton et al. 1987; Howard et al. 

1997; Takahashi et al. 1999). Cases of thyroid gland disorders began to be detected in the exposed 

population in approximately 10 years after the exposure, particularly in persons who were exposed as 

children; these included cases of apparent growth retardation, myxedema, and thyroid gland nodules and 

neoplasms (Conard et al. 1970). In 1981, health screening of children on Rongelap revealed an 83% 

prevalence of elevated serum concentrations of TSH (>5 mU/L) among exposed children who were 

≤1 year old at the time of the BRAVO test and who received an estimated thyroid radiation dose 

exceeding 1,500 rad (15 Gy). Prevalence of elevated serum TSH decreased with exposure age and/or 

thyroid dose: 25% for ages 2–10 years (800–1,500 rad, 8–15 Gy) and 9% for ages $10 years (335– 

800 rad, 3.3–8 Gy). A similar age-related prevalence of thyroid abnormalities occurred after radioiodine 

release from the fire at the Chernobyl nuclear power plant in the Ukraine. Clinical records from the 

Republics of Belarus and Ukraine show an increase in the incidence of thyroid nodules and thyroid 

cancers in children and adolescents, which became apparent approximately 4 years after the release of 

radioactive materials from the Chernobyl nuclear power plant in April 1986 (Astakhova et al. 1998; 

Cherstvoy et al. 1996; Drobyshevskaya et al. 1996; Tronko et al. 1996) (see Section 3.3.2 for a more 

detailed discussion of exposures from the Chernobyl accident). A comparison of thyroid cancers 

diagnosed in children in the Belarus-Ukraine region after the Chernobyl fire with thyroid cancers 

diagnosed in children in France and Italy during the same period revealed a striking age difference (Pacini 

et al. 1997). Most the Belarus-Ukraine cancers were diagnosed at age ≤5 years, whereas most of the 

cases in France and Italy were diagnosed after age 14 years. This observation is consistent with a 

radioiodine contribution to the Belarus-Ukraine cancers and a higher vulnerability of infants to 

radioiodine toxicity. 
 

 

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Nutritional factors can affect the toxicokinetics of iodine in children and adults. The most important 

factor is dietary iodine. Chronic iodine deficiency triggers homeostatic mechanisms to increase iodide 

uptake into the thyroid gland in order to sustain adequate thyroid hormone levels to regulate metabolism 

(Delange and Ermans 1996). These mechanisms include induction of iodide transport activity and 

iodination activity in the thyroid gland, as well as hypertrophy of the gland (i.e., goiter). As a result, 

exposures to radioiodine that occur during a state of deficiency can be expected to result in a larger 

fraction of the radioiodine dose being deposited in the thyroid gland, which could result in a higher 

radiation dose and risk. 

Another nutritional factor that could potentially affect iodine biokinetics in infants and children is 

selenium deficiency. Selenium is a cofactor in the iodothyronine deiodinases that are important for the 

synthesis of the thyroid hormone, T3, in extrathyroidal tissues. Iodine deficiency, in conjunction with 

selenium deficiency, has been associated with goiter and cretinism, a developmental impairment related 

to prenatal hypothyroidism (Goyens et al. 1987; Vanderpas et al. 1990). In this state, in which the thyroid 

gland is responding to a deficiency in T3 production by increasing iodide transport and iodination activity 

in the thyroid gland, infants and children (as well as adults) may experience a higher thyroid uptake of 

absorbed iodine, and possibly a higher radiation dose to the thyroid when exposed to radioiodine. 

As previously discussed in Section 3.5.2.2, exposure to iodine can begin in utero with maternal exposure 

and, as a result, the fetus is vulnerable to the potential toxic effects of maternal iodine exposures that 

occur during pregnancy. Maternal exposures to excess iodine have been shown to produce thyroid 

enlargement and hypothyroidism in neonates (Coakley et al. 1989; Hassan et al. 1968; Iancu et al. 1974; 

Martin and Reno 1962; Penfold et al. 1978; Vicens-Colvet et al. 1998). Deaths have occurred in neonates 

as a result of tracheal compression from thyroid gland enlargement (Galina et al. 1962). The vulnerability 

of the fetal thyroid gland has a toxicokinetic basis. Radioiodine uptake in the fetal thyroid commences in 

humans at approximately 70–80 days of gestation and precedes the development of thyroid follicles and 

follicle colloid, which are generally detectable at approximately 100–120 days of gestation (Book and 

Goldman 1975; Evans et al. 1967). Fetal iodide uptake activity increases with the development of the 

fetal thyroid and reaches its peak at approximately 6 months of gestation, at which point, the highest 

concentrations in the thyroid are achieved, approximately 5% of the maternal dose/g fetal thyroid 

(approximately 1% of the maternal dose) (Aboul-Khair et al. 1966; Evans et al. 1967). Fetal radioiodine 

concentrations 1–2 days following a single oral maternal dose of radioiodine generally exceed the 

concurrent maternal thyroid concentration by a factor of 2–8, with the highest fetal/maternal ratios 

occurring at approximately 6 months of gestation (Book and Goldman 1975). Following exposure to 131I 
 

 

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3. HEALTH EFFECTS 

from maternal ingestion of medically administered radioiodine or from repeated exposure to radioactive 

fallout, the fetal/maternal ratio for thyroid radioiodine concentration has been estimated to be 

approximately 2–3 (Beierwaltes et al. 1963; Book and Goldman 1975; Eisenbud et al. 1963). 

Dermal exposures to iodine, in particular topical antiseptics containing povidone-iodine, can expose the 

fetus to iodine. For example, increases in iodine concentration in maternal urine and umbilical cord blood 

have been observed in pregnant women who received dermal or vaginal applications of povidone-iodine 

prior to delivery for disinfection of the skin and fetal scalp electrodes, suggesting that absorption of iodine 

occurs with these uses of povidone-iodine as well (l’Allemand et al. 1983; Bachrach et al. 1984). 

Consistent with this are observations that topical application of iodine preparations (i.e., povidone-iodine) 

during labor has produced thyroid gland suppression in newborns (l’Allemand et al. 1983; Novaes et al. 

1994). Infants can also absorb iodine when such iodine preparations are applied topically. Use of 

povidone-iodine for topical and surgical wound disinfection in infants has been shown to induce transient 

hypothyroidism or hyperthyroidism (Brown et al. 1997; Chabrolle and Rossier 1978a, 1978b). 

Nursing infants can be exposed to iodine in breast milk (Dydek and Blue 1988; Hedrick et al. 1986; 

Lawes 1992; Morita et al. 1998; Robinson et al. 1994; Rubow et al. 1994; Spencer et al. 1986). The level 

of exposure will depend not only on the maternal exposure, but also on the physiologic status of the 

maternal thyroid. A larger fraction of the absorbed dose is excreted in breast milk in the hypothyroid 

state compared to the hyperthyroid state; in the hypothyroid state, excretion of radioiodine into breast 

milk can be 10 times higher (e.g., 25% of the dose) than in euthyroid or hyperthyroid states (Hedrick et al. 

1986; Morita et al. 1998; Robinson et al. 1994). 

Iodine is not stored in skeletal tissue or fat to any significant degree and thus, mobilization of these tissues 

during pregnancy, for production of the fetal skeleton or breast milk, would not be expected to contribute 

to fetal or infant exposure. There is no evidence that iodine metabolism would be appreciably different in 

children compared to adults. It is possible that the conjugation of iodothyronines with glucuronic acid 

could be limited in newborns as a result of the normal development of glucuronyltransferase activity in 

the newborn and infant; however, there is no evidence for an effect on iodine toxicokinetics. In the Gunn 

rat, which is a strain of rat that is deficient in glucuronyltransferase activity, glucuronic acid conjugates of 

iodothyronines are formed and biliary excretion of iodothyronines is impaired; however, normal 

circulating levels iodothyronine appear to be maintained (Curran and DeGroot 1991). This would suggest 

that the thyroid gland may not increase uptake of iodine in response to an impairment in glucuronyltransferase activity. 
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3. HEALTH EFFECTS 

Models of the biokinetics of iodine in infants, children, adolescents, and adults have been developed by 

ICRP (1989, 1994a, 1995). Models have also been developed that predict, with reasonably high accuracy, 

the accumulation of radioiodide in the thyroid gland of infants and children exposed to single doses of 

radioiodine for clinical procedures (Fisher et al. 1962). 

3.9 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). 

Due to a nascent understanding of the use and interpretation of biomarkers, implementation of biomarkers 

as tools of exposure in the general population is very limited. 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 or 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 iodine 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 

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 
 

 

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3. HEALTH EFFECTS 

adverse, but can indicate potential health impairment (e.g., DNA adducts). Biomarkers of effects caused 

by iodine 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”. 

3.9.1 Biomarkers Used to Identify or Quantify Exposure to Iodine 

Urinary iodine excretion provides a reliable biomarker of steady state iodine intake. Under steady state 

conditions, in which exposure to iodine has been reasonably constant for at least 6 months, daily iodine 

will approximate the 24-hour urinary iodine excretion. The basis for this relationship is that ingested 

iodide is nearly completely absorbed in the gastrointestinal tract and that urine is the principal route of 

excretion of the absorbed iodide (see Sections 3.5.1.2 and 3.5.4.2). The use of urinary iodide as a 

biomarker of iodide exposure is supported by studies in which 24-hour urinary iodide was measured 

before and after supplementation. For example, 31 patients received oral supplements of 382 μg I/day for 

6 months. Prior to the supplementation, the mean 24-hour urinary iodide excretion rate was 36 μg/day 

(range, 13–69), whereas after 6 months of iodide supplementation, the mean 24-hour urinary iodide 

excretion rate was 415 μg/day (Kahaly et al. 1998). The difference between these two values, 

379 μg/day, is nearly identical to the supplemental dose of 382 μg/day. 

Exposure to 123I, 124I, and 131I can be detected directly from external measurements of gamma radiation 

emanating from the thyroid gland. The basis for this is that approximately 90% of the iodine in the body 

is in the thyroid gland and absorbed iodine is rapidly taken up into the thyroid gland. The measurement 

procedure is known as a thyroid scintillation scan. A scintillation detector device usually consists of a 

shielded sodium iodide crystal connected to a collimator and spectrometer. The detector is placed over 

the thyroid gland and the spectrometer is tuned to collect gamma emissions having peak energies of the 

target isotope (e.g., 0.159, 0.511, or 0.364 MeV for 123I, 124I, or 131I, respectively). Events are corrected 

for attenuation by overlying tissue by counting a neck phantom containing a gamma source of known 

activity. Because of the relatively short radioactive decay half-times of 123I (13 hours), 124I (4.2 days), and 

131I (8 days), thyroid scans must be conducted soon after exposure in order to detect the iodine in the 

thyroid gland. 
IODINE 199 

3. HEALTH EFFECTS 

The thyroid scintillation scan is also used in medical practice to identify disease of the thyroid, and can 

reflect either idodie excess or deficiency. 

3.9.2 Biomarkers Used to Characterize Effects Caused by Iodine 

The thyroid gland is the primary and most sensitive target for both chemical and radioiodine toxicity. As 

a result, biomarkers of iodine effects are those that allow the detection of preclinical and clinical 

suppression or stimulation of the thyroid gland. Effects on the thyroid gland can be classified into three 

types: hypothyroidism, hyperthyroidism, and thyroiditis. Hypothyroidism refers to a state of diminished 

production of thyroid hormones leading to clinical manifestations of thyroid insufficiency and can occur 

with or without goiter, a functional hypertrophy of the gland in response to suppressed hormone 

production and elevated serum thyroid stimulating hormone (TSH, also known as thyrotropin) 

concentrations. Typical biomarkers of hypothyroidism are depressions in the circulating levels of 

thyroxine (T4) and/or triiodothyronine (T3) below their normal ranges. This is always accompanied by an 

elevation of the pituitary hormone, TSH, above the normal range. Typical normal ranges are for hormone 

levels are shown in Table 3-9. Hyperthyroidism is an excessive production and/or secretion of thyroid 

hormones. The clinical manifestation of abnormally elevated circulating levels of T4 and/or T3 is 

thyrotoxicosis. Thyroiditis refers to an inflammation of the gland, which is often secondary to thyroid 

gland autoimmunity. Thyroid autoimmunity can be detected as a presence of IgG antibodies to 

thyroglobulin and thyroid peroxidase in serum antibodies (Table 3-9). In addition to the above 

measurements, physical examination, ultrasound and thyroid scintillation scanning can reveal nodules and 

other normal or abnormal variations in thyroid gland structure and function. Examples of the use of these 

measurements in assessing iodine-induced effects on the thyroid gland are presented in Section 3.2 of the 

profile. 
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3. HEALTH EFFECTS 

Table 3-9. Typical Reference Ranges for Serum Thyroid Hormones 

and TSH in Humans 

 Reference range 

Hormone Metric SI unit 

Total T4 4–11 μg/dL 60–140 nMa 

Free T4 0.7–2.1 ng/dL 10–25 pMa 

Total T3 75–175 ng/dL 1.1–2.7 nMa 

Free T3 0.2–0.5 ng/dL 3–8 pM 

Reverse T3 15–45 ng/dL 0.2–0.7 nM 

TSH 0.3–4.0 mU/Lb,c 1–15 pM 

Thyroid peroxidase antibodies (TPA) <10 IU/mL No data 

Thyroglobulin autoantibodies (Tg- <10 IU/mL No data 

ab) 

a

Children may be higher 

b

Assumes a biologic potency of 7–15 mU/mg 

c

Higher in neonates (de Zegher et al. 1994) 

T3 = 3,5,3N-triiodo-L-thyronine; T4 = 3,5,3N,5N-tetraiodo-L-thyronine (thyroxine); TSH = thyroid stimulating hormone 

Source: Stockigt (2000) and Marcocci and Chiovato (2000) 
 

N S 

N 

O 

IODINE 201 

3. HEALTH EFFECTS 

3.10 INTERACTIONS WITH OTHER CHEMICALS 

Thioureylenes and Thionamides. Several of thionamide compounds that contain a thioureylene chemical 

group have been shown to increase the accumulation of iodide in the thyroid gland and to decrease the 

production of iodothyronines (Green 1996): 

H 

CH3CH2CH2

 Propylthiouracil 

These include several drugs used in the treatment of thyrotoxicosis and other hyperthyroid states, 

(carbimazole, methimazole, and propylthiouracil); as well as the antibiotic, ethionamide; the cancer 

chemotherapy agent, 6-mercaptopurine; and goitrin, a natural constituent of the plant genus Brassicae 

(rutabaga, turnip, and cabbage). The thionamides exert their effects by inhibiting the iodination of 

tyrosine and monoiodotyrosine in the thyroid gland and the coupling of iodotyrosines to form 

iodothyronines. The mechanisms for these effects are not completely understood; however, at least two 

mechanisms are needed to explain the reversible and irreversible inhibition of iodothyronine production 

that is characteristic of these agents. Thionamides agents may act reversibly by reducing I+

 or some other 

reactive intermediate of iodine required in the iodination reaction, and also through a mechanism that 

involves a direct, irreversible reaction with thyroid peroxidase. 

Thiouracil and propylthiouracil, and related thioureylenes, are also inhibitors of iodthyronine deoidinase 

(Leonard and Koehrle 1996). The mechanism of inhibition involves the formation of a covalent complex 

with deiodinase enzymes. Inhibitory potency is highest for Type 1 deiodinase (Table 3-8). The result of 

inhibition is a decreased metabolic clearance of iodothyronines. 

Analine Derivatives. As a class, para-substituted aminobenzenes have activity similar to that of the 

thionamides in that they increase the accumulation of iodide in the thyroid gland and decrease production 

of iodothyronines, although possibly not through the same mechanisms (Green 1996). The group 
 

 

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3. HEALTH EFFECTS 

includes several drugs (and drug classes), amphenone B, carbutamide, amino-glutethimide, 

p-aminosalicylic acid, and the sulfonamides. 

Substituted Phenols. Various substituted phenols that have hydroxyl groups in the meta positions have 

been shown to increase thyroid iodide accumulation and to inhibit iodothyronine production in the 

thyroid. These include resorcinol, 2,4-dihydroxybenzoic acid, and 2,4-dihydroxyphenol. These 

compounds exert their activity by producing an irreversible inhibition of thyroid peroxidase (Green 1996). 

Hydroxypyridines. Hydroxypyridines, including 3-hydroxypyridine and 3,4-dihydroxypyridine, have 

been shown to increase thyroid iodide accumulation and to inhibit iodothyronine production in the thyroid 

(Green 1996). 

Perchlorate and Related Complex Anions. A variety of complex inorganic anions have been shown to 

decrease the uptake of iodide in the thyroid gland. When given at high enough dosages, these agents can 

induce hypothyroidism and goiter (Green 1996). The complex anions include, in order of potency: 

perchlorate (ClO4

-

), perrhenate (ReO4

-

), pertechnetate (TcO4

-

), and tetrafluorborate (BF4

-

). The 

mechanism for their activity is competitive inhibition of the NIS (Carrasco 1993; Eskandari et al. 1997; 

Wolf 1964). These agents may also be transported by the NIS to varying degrees. Perchlorate does not 

appear to be transported by NIS (Eskandari et al. 1997; Yoshida et al. 1997). These anions can also affect 

accumulation and/or secretion of iodide in other tissues that have an active iodide transporter, including 

the choroid plexus, gastric mucosa, mammary gland, placenta, salivary gland, and sweat gland (BrownGant 1961). 

Thiocyanate. Thiocyanate (SCN-

) is a potent inhibitor of iodide uptake in the thyroid gland and 

iodination of thyroglobulin. The mechanism for the effect on iodide uptake is primarily related to 

competitive inhibition of iodide transport by the Na+/I-

 symport in thyroid gland; however, thiocyanate 

may also accelerate iodide efflux from the thyroid by being a substrate with iodide for an anion exchange 

mechanism on the basolateral membrane of thyroid follicle cells (Eskandari et al. 1997; Yoshida et al. 

1997). Thiocyanate inhibits iodination, apparently by its actions as a competitive oxidation substrate for 

thyroid peroxidase (Virion et al. 1980). Unlike other complex anion inhibitors of iodide transport, 

thiocyanate is not accumulated in the thyroid gland. 

Thiocyanate is a product of the metabolism of cyanide (ATSDR 1997) to which humans are exposed 

when they smoke cigarettes, which has prompted interest in the potential effects of smoking on thyroid 
IODINE 203 

3. HEALTH EFFECTS 

iodine metabolism and thyroid disease (Bertelsen and Hegedus 1994). Thiocyanate is a metabolite of 

nitroprusside, a drug used in the treatment of acute hypertensive emergencies and cardiac failure. 

Impairment of thyroid function in patients on nitroprusside has been reported (Bodigheimer et al. 1979; 

Nourok et al. 1964). 

Microsomal Enzyme Inducers. Agents that induce hepatic microsomal enzymes increase the activity of 

phenolic glucuronyl transferases that catalyze the conjugation of iodothyronines with glucuronic acid 

(Curran and DeGroot 1991; Visser 1990). Induction of glucuronyltransferase increases the metabolic 

clearance of iodothyronines and, if sufficiently accelerated, can stimulate TSH release and goiter. Such 

effects have been observed in rats and other experimental animal models in response to exposures to 

2,4-benzopyrene, chlordane, DDT and DDD, 3-methylcholanthrene, PCBs, chlorinated dibenzodioxins 

(CDDs), and toxaphene. A variety of drugs have also been shown to exert effects on glucruonide 

conjugation of iodothyronines, including the sedative, phenobarbital; the anticonvulsants, phenytoin and 

carbamazepine; and the antibiotic, rifampin. 

Polychlorinated Biphenyls (PCBs). Depending on dose and duration, PCBs can disrupt the production 

and disposition of thyroid hormones at a variety of levels and thereby may potentially interact with iodine 

in impairing the thyroid gland. The major findings include (1) histological changes in the thyroid gland 

indicative of both stimulation of the gland (e.g., similar to that induced by TSH or a hypothyroid state) 

and disruption of the processing of follicular colloid needed for normal production and secretion thyroid 

hormone; (2) depression of serum T4 and T3 levels, which may effectively create a hypothyroid state (in 

some studies, low doses resulted in elevated serum T4 levels while depressed levels occurred at higher 

PCB doses); (3) increased rates of elimination of T4 and T3 from serum; (4) increased activities of T4­

UDP-glucuronyl transferase (UDP-GT) in liver, which is an important metabolic elimination pathway for 

T4 and T3; (5) decreased activity of iodothyronine sulfotransferases in the liver, which are also important 

in the metabolic elimination of iodothyronines; (6) decreased activity of iodothyronine deiodinases, 

including brain Type-2 deiodinase, which provide the major pathways for the production of the active 

thyroid hormone, T3; and (7) decreased binding of T4 to transthyretin, an important transport protein for 

both T4 and T3 (ATSDR 2000b). 

Selenium. Selenium is essential for the activity of the glutathione peroxidases and iodothyronine 

deiodinases. In humans, concurrent selenium and iodine deficiency have been associated with goiter and 

cretinism, a developmental impairment related to prenatal hypothyroidism (Goyens et al. 1987; 

Vanderpas et al. 1990). Supplementation of individuals deficient in both iodine and selenium with 
 

 

 

IODINE 204 

3. HEALTH EFFECTS 

selenium produces a further decrease in thyroid function, but if selenium supplementation is preceded by 

normalization of iodine levels, then normal thyroid function is restored (Contempré et al. 1991, 1992). 

Selenium intake has been reported to affect thyroid hormone levels in humans; these effects include 

decreases in serum T3 and T4 levels and increases in serum TSH levels, suggesting suppression of 

thyropid hormone production (Brätter and Negretti De Brätter 1996; Duffield et al. 1999; Hagmar et al. 

1998; Hawkes and Keim 1995). In experimental animals, selenium deficiency produces in decreased 

metabolic clearance of iodothyronines and decreased extrathyroidal production of T3, as a result of 

decreased iodothyronine deiodinase activity, which can be restored to normal by selenium repletion 

(Arthur and Beckett 1994; Behne and Kyriakopolous 1993). Selenium deficiency also results in 

decreases in thyroid iodine concentrations. The latter effect is thought to involve direct and indirect 

effects on thyroid hormone production and secretion. The direct effect is thought to result from decreased 

activity of glutathione peroxidase in the thyroid and increased availability of hydrogen peroxide for 

utilization in the production of iodothyronines in the thyroid, which can then be exported from the gland. 

The indirect effect may involve increased release of TSH from the pituitary gland in response to a 

decrease in plasma concentration of T3, resulting from inhibition of deiodination of T4. 

Amiodarone. The more serious side effects of the use of the antiarrythmia drug, amiodarone, are effects 

on the thyroid, including hypothyroidism, hyperthyroidism, and thyroditis (Bogazzi et al. 2001; Meier and 

Burger 1996). Although the exact mechanisms for these effects are not completely understood, 

amiodarone contains a large quantity of iodine and has been shown to inhibit the deiodination of 

iodothyronines; in particular, the production of T3 from T4, most likely as a result of inhibition of Type 1 

deiodinase (Table 3-8). A metabolite of amiodarone, desethyamiodarone, has been shown to inhibit 

binding of T3 to thyroid hormone receptors in a variety of tissues (Green 1996). As a thyroid receptor 

antagonist, amiodarone (or its metabolite) also stimulates the release of TSH from the pituitary gland. 

Lithium. Hypothyroidism and goiter have been associated with chronic therapy with lithium carbonate 

for management of bipolar disease (Green 1996; Spaulding et al. 1972). The mechanism for these effects 

is not understood, although it has been suggested that lithium may inhibit the coupling reaction in the 

synthesis of iodothyronines and may inhibit thyroid hormone secretion. 

Propranolol. Propranolol is a drug used in the treatment of hypertension, angina, and other 

cardiovascular disorders as well as for the symptomatic treatment of thyrotoxicosis. Although the basis 

for its use in treatment of thyrotoxicosis is to counteract the cardiovascular symptoms of the disorder, the 

drug is also an inhibitor of iodothyronine deiodination (Meier and Burger 1996). The effect is unrelated 
 

 

IODINE 205 

3. HEALTH EFFECTS 

to its activity as a β-adrenergic receptor antagonist, as both the L- and D-isomer (devoid of β-receptor 

antagonist activity) inhibit the deiodination of T4. The mechanism for this action is not understood. 

Dexamethasone. Although the corticosteroids exert multiple effects on the physiological regulation of 

thyroid hormone release (e.g., decreased TSH release from the pituitary), these agents also have 

appreciable activity as inhibitors of iodothyronine deiodinase and can decrease the metabolic clearance of 

iodothyronines (Meier and Burger 1996). 

Iodinated Drugs. A variety of iodine-containing drugs have been shown to inhibit iodothyronine 

deiodination and thereby decrease the metabolic clearance of iodothyronines. These include the 

antiarrhythmic agent, amiodarone (previously discussed), and several radiographic contrast agents used 

for cholecystography such as iopanoic acid, sodium ipodae, and tyropanoate (Meier and Burger 1996). 

3.11 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to iodine than will most persons 

exposed to the same level of iodine 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 iodine, or compromised function of organs affected by 

iodine. Populations who are at greater risk due to their unusually high exposure to iodine are discussed in 

Section 6.7, Populations With Potentially High Exposures. 

People who consume diets deficient in iodine may be more vulnerable to the toxic effects of exposure to 

radioiodine. At very low intakes, representing iodine deficiency (e.g., 20 μg/day), uptake of iodide into 

the thyroid gland is increased (Delange and Ermans 1996). This response is mediated by TSH, which 

stimulates iodide transport and iodothyronine production in the thyroid gland (see Section 3.6.1). If 

exposure to radioiodine was to occur in an individual who is iodine-deficient, a larger fraction of the 

absorbed radioiodine may be taken up by the thyroid gland and a larger radiation dose to the thyroid gland 

may be received. Iodine deficiency has been suggested to be a possible contributing factor to the increase 

in thyroid cancer incidence observed in Belarus after the Chernobyl reactor accident (Gembicki et al. 

1997; Robbins et al. 2001). 

People who have multinodular goiter or thyroid gland adenomas can have foci of thyroid gland tissues 

that produce and secrete thyroid hormone autonomously from control of the gland by TSH. The 
IODINE 206 

3. HEALTH EFFECTS 

mechanisms for thyroid tissue autonomy appear to involve clonal expansion of follicle cells that have a 

either a modified TSH receptor or receptor coupling mechanism, or that overexpress growth factors 

(Corvilain et al. 2000; Derwahl and Studer, 2001; Krohn et al. 2000). Autonomous nodules can give rise 

to hyperthyroidism (e.g., toxic nodular goiter, toxic adenoma). Iodine deficiency and goiter appear to be 

risk factors in the development of autonomous nodules (Aghini-Lombardi et al. 1999). People who have 

the autonomous nodules appear to be more vulnerable to iodide-induced hyperthyroidism (Braverman and 

Roti 1996; Ermans and Camus 1972). This may, in part, explain the increased incidence of 

hyperthyroidism that sometimes accompanies the introduction of iodide supplements into the diet of 

iodine-deficient populations (Connolly 1971b; Corvilain et al. 1998; Delange et al. 1999). In 

experimental studies, supplemental doses of 75–150 μg I/day for 1–2 weeks have induced 

hyperthyroidism in euthyroid patients who had autonomous thyroid adenoma (Livadas et al. 1977). 

Patients with certain types of thyroid autoimmunity may be more susceptible to developing 

hyperthyroidism when exposed to excess iodine (Braverman and Roti 1996; Braverman et al. 1971a; Roti 

and Uberti 2001). 

Populations with diets that are deficient in selenium may be more susceptible to iodine toxicity. Selenium 

is a cofactor in the iodothyronine deiodinases that are important for the synthesis of the thyroid hormone, 

T3, in extrathyroidal tissues. Iodine deficiency, in conjunction with selenium deficiency, has been 

associated with goiter and cretinism, a developmental impairment related to prenatal hypothyroidism 

(Goyens et al. 1987; Vanderpas et al. 1990). In this state, in which the thyroid gland is responding to a 

deficiency in T3 production by increasing iodide transport and iodination activity in the thyroid gland, 

infants and children (as well as adults) may experience a higher thyroid uptake of absorbed iodine and 

possibly a higher radiation dose to the thyroid when exposed to radioiodine. 

People who have $-thalassemia, an inherited disorder of hemaglobin production that can lead to anemia, 

may be more sensitive to developing hypothyroidism when exposed to excess iodide (Alezandrides et al. 

2000). 

3.12 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to iodine. 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 iodine. When specific 

exposures have occurred, poison control centers and medical toxicologists should be consulted for 
 

 

IODINE 207 

3. HEALTH EFFECTS 

medical advice. The following text provides specific information about treatment following exposures to 

iodine: 

Braverman LE, Utiger RD. 2000. Werner and Ingbar's The thyroid: A Fundamental and Clinical Text. 

Philadelphia, PA: Lippincott-Raven. 

Treatment of toxicity from exposure to excess iodine is directed at lowering exposure and, if clinical 

hypothyroidism or hyperthyroidism persists, correcting the thyroid dysfunction. Treatment of clinical 

hypothyroidism includes the administration of thyroid hormone. Treatment of hyperthyroidism involves 

administering thyroid hormone synthesis inhibitors. 

Treatment of toxicity from exposure to radioiodine is also directed at lowering thyroid gland uptakes of 

absorbed iodine, for example, by administration of potassium iodide (see Section 3.12.2). If the exposure 

produces persistent hypothyroidism or hyperthyroidism, the treatment strategies for the clinical 

abnormalities are the same as those for exposure for nonradioactive iodine. 

3.12.1 Reducing Peak Absorption Following Exposure 

No information was located on methods to reduce peak absorption following exposure. Mitigation of 

toxic effects following exposure to radioiodine is directed at reducing the uptake of absorbed iodine in the 

thyroid gland (see Section 3.12.2). 

3.12.2 Reducing Body Burden 

Approximately 90% of the iodine in the human body is contained in the thyroid gland. The thyroid gland 

is also the major toxicity target of radioiodine. Therefore, methods for reducing the uptake and 

accumulation of radioiodine in the thyroid gland can reduce the radioiodine body burden, the absorbed 

radiation dose to the thyroid gland and body, and the toxic effects of exposure to radioiodine. Iodine 

uptake into the thyroid gland is highly sensitive to the iodide intake. At very high intakes of iodine, 

representing an intake excess (e.g., >1 mg/day), iodine uptake into the thyroid gland decreases, primarily 

as a result of decreased iodothyronine synthesis (Wolff-Chaikoff effect) and iodide transport into the 

gland (Nagataki and Yokoyama 1996; Saller et al. 1998). A single oral dose of 30 mg iodide (as sodium 

iodide) decreases the 24-hour thyroid uptake of radioiodine by approximately 90% in healthy adults 

(Ramsden et al. 1967; Sternthal et al. 1980). The inhibition of uptake was sustained with repeated oral 
 

 

IODINE 208 

3. HEALTH EFFECTS 

doses of sodium iodide for 12 days, with complete recovery to control (presodium iodide) uptake levels 

within 6 weeks after the last sodium iodide dose (Sternthal et al. 1980), or within 8 days after a single 

dose (Ramsden et al. 1967). Repeated oral doses of 1.5–2.0 mg iodide/m3

 of surface area produced an 

80% decrease in thyroid uptake of radioiodine in children (Saxena et al. 1962). Inhibition of radioiodine 

uptake by the thyroid gland that occurs when large doses of iodide are administered results in more rapid 

urinary excretion of radioiodine and decreased iodine body burden (Ramsden et al. 1967). The 

administration of iodide as prophylaxis for reducing thyroid uptake of radioiodine after accidental 

releases of radioiodine has been recommended by the FDA and NCRP (FDA 1978, 2001b; NCRP 1977). 

Recommendations regarding the distribution and administration of potassium iodide in the event of a 

nulcear accident have been provided by the National Research Council (NRC 2004). Doses of 50 mg 

(infants <1 year of age) or 100 mg (adults) I, as potassium iodide, just before or at the time of exposure, 

have been found to be effective for blocking (>90%) thyroid uptake of radioiodine (Verger et al. 2001). 

The dose of potassium iodide that is effective for achieving this level radioiodine uptake block will 

depend on the time of dosing, relative to the exposure, as well as the dietary iodide status; higher doses of 

potassium iodide may be needed under conditions of low dietary iodide intake (Zanzonico and Becker 

2000). The FDA (2001b) has recommended that potassium iodide be administered at the following doses, 

daily doses, until the risk of exposure from inhalation or ingestion no longer exists: 

Predicted thyroid 

radiation dose Dose (mg Dose (mg 

Receptor (years) (cGy, rad) KI/day) I/day) 

Adults >40 years $500 

Adults >18–40 years $10 130 100 

Pregnant or lactating women $5 

Adolescents >12–18 years* 65 50 Children >3–12 years $5 Infants <1 month–3 years 32 24 

Infants <1 month 16 12 

* Adolescents $70 kg should receive adult dose (130 mg/day) 

3.12.3 Interfering with the Mechanism of Action for Toxic Effects 

The mechanisms of action of excess iodine in producing goiter, hypothyroidism, hyperthyroidism, or 

thyroiditis involve direct interactions between iodide and physiological elements involved in thyroid 

hormone synthesis and release, and iodine transport. Therefore, the principal strategy for reducing toxic 

effects is to decrease iodine intake or uptake into the thyroid gland (see Section 3.12.2). Numerous cases 

of reversal of iodine-induced hypothyroidism or hyperthyroidism after reduction of iodide intake have 

been reported and are described in this profile (see Section 3.2.2.2, Endocrine Effects). The principal 
 

 

IODINE 209 

3. HEALTH EFFECTS 

clinical strategy for managing permanent hypothyroidism is the administration of T4 (Brent and Larsen 

2000). The principal clinical strategies for managing permanent hyperthyroidism is the administration of 

agents that inhibit iodination of thyroglobulin, such as propylthiouracil or methimazole, or that inhibit 

thyroid uptake of iodine, such as perchlorate, or the destruction of the thyroid gland with radiation. The 

latter is usually accomplished by administering a cytotoxic dose of 131I. β-Adrenergic antagonists are also 

used to manage some of the symptoms of thyrotoxicosis (Cooper 2000). Cases of massive acute, nearlethal poisoning from ingestion of tinctures of iodine (mixtures of molecular iodine and sodium triiodide) 

have included fluid and electrolyte replacement to manage cardiovascular shock (Finkelstein and Jacobi 

1937). 

The sulfhydryl compound, amifostine, has been found to reduce the toxic effects of high exposures to 131I 

in patients who undergo ablative therapy with 131I for thyroid cancers (Bohuslavizki et al. 1996, 1998a, 

1998b, 1999). The mechanism for the protective effect appears to be accumulation of amifostine in the 

salivary gland and scavenging of free radicals formed as a result of interactions of ionizing radiation from 

131I with tissues. 

3.13 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 iodine 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 iodine. 

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. 
IODINE 210 

3. HEALTH EFFECTS 

3.13.1 Existing Information on Health Effects of Iodine 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

iodine are summarized in Figures 3-16 and 3-17. The purpose of this figure is to illustrate the existing 

information concerning the health effects of iodine. 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. 

3.13.2 Identification of Data Needs 

Acute-Duration Exposure. The primary effect of acute exposures to excess iodine in humans is 

hypothyroidism. This effect has been studied extensively in experimental studies of humans and is also 

well documented in the clinical case literature. Reported NOAELs for iodine-induced hypothyroidism in 

humans vary widely for reasons that are not completely understood. Acute exposures to excess iodine 

produce allergic reactions in people. The mechanisms for sensitivity and the reactions are not completely 

understood. 

The effects of acute exposures to radioiodine (primarily 131I) have been extensively studied in humans. 

An enormous amount of epidemiological and case literature derives from the clinical use of 131I in 

diagnostic procedures and in treatment of thyroid gland enlargement and thyrotoxicosis. Epidemiology 

studies have also examined health effects resulting from accidental environmental exposures due to 

nuclear bomb detonations (e.g., Marshall Islands) and releases from nuclear power plants (e.g., 

Chernobyl). These studies collectively and convincingly identify the thyroid gland as the primary target 

of radioiodine. Other tissues that are either near the thyroid gland, such as the parathyroid gland, or that 

accumulate iodine, such as the salivary gland, also are affected by exposures to 131I; however, these 

effects occur at absorbed radiation doses that are clearly cytotoxic to the thyroid gland. Breast tissue 

expresses NIS and appears capable of accumulating 131I and transferring it to mammary milk; therefore, it 

is a potential target of 131I. However, epidemiology studies reported to date have not found a significant 

risk of breast cancer even after cytotoxic exposures to 131I. 
 

Existing Studies 

IODINE 211 

3. HEALTH EFFECTS 

Figure 3-16. Existing Information on Health Effects of Stable Iodine 

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 

Inhalation 

Oral 

Dermal 
IODINE 212 

3. HEALTH EFFECTS 

Figure 3-17. Existing Information on Health Effects of Radioactive Iodine 

Inhalation 

Oral 

Dermal 

Death

Acute

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

External 

Human 

Inhalation 

Oral 

Dermal 

External 

Death

A ut

ermediate 

ro

ic 

muno g

/Lymphoretic 

r

r

c

e 

Int

Ch

n

Im

lo

ic

Neu ologic 

Rep oductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

Animal 

Existing Studies 
 

 

 

IODINE 213 

3. HEALTH EFFECTS 

Intermediate-Duration Exposure. The primary effect of intermediate-duration exposures to excess 

iodine in humans is hypothyroidism. This effect has been studied extensively in humans and is well 

documented in the clinical case literature. Reported LOAELs for iodine-induced hypothyroidism in 

euthyroid humans, without goiter, fall within a reasonably narrow range, and are higher than those for 

people who are iodine deficient, suggesting a higher sensitivity in these subjects. The mechanisms for 

this are not completely understood. Intermediate-duration exposure has also been shown to induce 

hyperthyroidism in people who have nontoxic goiter. Here again, the mechanisms are not completely 

understood, although clonal expansion of autonomous follicle cells and autoimmunity are suspected 

contributors. Intermediate-duration exposures to excess iodine produce allergic reactions in people. The 

mechanisms for sensitivity and the reactions are not completely understood. 

Chronic-Duration Exposure and Cancer. Epidemiological studies and clinical case literature 

identify the thyroid gland as the principal target of chronic exposure to excess iodine. Goiter, 

hypothyroidism, hyperthyroidism, and/or thyroid autoimmunity are the main outcomes of chronic 

exposure to excess iodine. Which effect occurs appears to be related to the pre-existing iodine intake 

(e.g., deficient or replete) and the presence or absence of possibly pre-existing autoimmunity and/or 

thyroid gland enlargement (or nodularity). 

Genotoxicity. Stable iodine has been tested for genotoxicity in a variety of eukaryotic cell systems 

and has been found to be without mutagenic activity. The genotoxicity of radioactive iodine (131I) has 

been extensively studied in clinical studies of patients who received 131I for therapy of thyroid cancer and 

thyrotoxicosis and in people who were exposed to radioiodine from nuclear power plant accidents (e.g., 

Chernobyl). 

Reproductive Toxicity. Several studies of reproductive effects of exposures to 131I have been 

reported. These studies indicate that relatively high exposures to radioiodine (i.e., that are cytotoxic to the 

thyroid gland) can produce impairment of testicular function. The mechanism for this is not understood, 

but the observation of these effects suggests a possible exposure of the testes to 131I. The testis is not 

presently known to express NIS; however, studies of the uptake of radioiodine in testes were not located. 

Developmental Toxicity. Developmental toxicity of iodine and radioiodine related to effects on the 

fetal/neonatal thyroid gland has been well documented in the clinical case literature. The primary effect 

is congenital hypothyroidism and associated sequelae. 
IODINE 214 

3. HEALTH EFFECTS 

Immunotoxicity. The epidemiological and clinical case literature has identified thyroid autoimmunity 

and allergic reactions as the primary immunologic effects of exposure to excess iodine. Thyroid 

autoimmunity is an extremely important mechanism of thyroid gland disease. The mechanisms by which 

iodine induces thyroid autoimmunity are not completely understood. The production of antibodies to 

highly iodinated thyroglobulin has been proposed as a possible contributor. 

Neurotoxicity. The primary target of iodine toxicity is the thyroid gland. A large amount of clinical 

literature exists on the neurological sequelae of thyroid gland disorders. 

Epidemiological and Human Dosimetry Studies. The epidemiological literature on iodine- and 

radioiodine-related health effects is very substantial and provides information on exposures associated 

with the primary effect, thyroid gland dysfunction. There remain certain complications in the 

interpretation of the major epidemiology studies of environmental exposures to iodine and radioiodine. 

These relate to the magnitude of the contribution of iodine deficiency and autoimmunity in the observed 

thyroid gland outcomes (e.g., hypothyroidism, hyperthyroidism, thyroid gland nodularity, and cancers). 

Studies of human dosimetry of 131I are extensive, in large part, because of the extensive use of 131I in 

diagnostic and treatment procedures that require highly certain estimates of the radiation dose delivered to 

the thyroid gland. The clinical information has been incorporated into reconstructions of thyroid doses 

experienced by the general public. 

Biomarkers of Exposure and Effect. 

Exposure. The use of urinary iodide for assessing steady state iodine intakes is well substantiated in the 

clinical and epidemiological literature and is supported by toxicokinetics studies in humans. Similarly, 

the use of external scintillation spectrometry to estimate radioiodine doses to the thyroid gland also has a 

substantial clinical history. 

Effect. The clinical literature on thyroid gland disorders extensively documents the major biomarkers of 

thyroid gland dysfunction that are relevant to iodine toxicity. 

Absorption, Distribution, Metabolism, and Excretion. The toxicokinetics of iodine in humans 

has been substantially explored and characterized in experimental studies and clinical cases. Radioiodine 

toxicity is most likely in tissues that can transport and accumulate iodide. Studies of the expression of 
IODINE 215 

3. HEALTH EFFECTS 

NIS and factors that alter expression of NIS can further advance our understanding of which tissues are at 

risk and what factors, including genetic factors, might affect sensitivity to radioiodine in humans. 

Comparative Toxicokinetics. The extensive information on the toxicokinetics of iodine in humans 

makes extrapolations from animals less important in assessing the health effects of iodine in humans. 

Studies of interindividual variability in humans are valuable for identifying sensitive subpopulations. 

Methods for Reducing Toxic Effects. The principal method for preventing the toxic effects of 

radioiodine is dosing with stable iodine, which decreases the thyroid gland uptake of radioiodine and the 

absorbed radiation dose to the gland. The mechanistic basis and effectiveness of this approach is well 

established from experimental and clinical studies. 

Children’s Susceptibility. Higher susceptibility of the fetus and infants to iodine and radioiodine 

toxicity is substantiated by the epidemiological and clinical case studies. The toxicokinetic basis for the 

susceptibility of infants and children to iodine exposure is understood. Uncertainties in assessing the 

potential health effect of iodine exposures are largely related to estimating exposures, in particular, the 

pathways by which environmental releases result in radioiodine uptake into the fetal or infant thyroid 

gland (see Section 6.8.1). 

Child health data needs relating to exposure are discussed in 6.8.1 Identification of Data Needs: 

Exposures of Children. 

3.13.3 Ongoing Studies 

Ongoing studies pertaining to iodine have been identified and are shown in Table 3-10. 
 

 

IODINE	 216 

3. HEALTH EFFECTS 

Table 3-10. Ongoing Studies on Health Effects of Radioactive Iodine 

Investigator Affiliation Title	 Sponsor 

Baker JR	 University of Michigan 

at Ann Arbor 

Brent GA	 University of 

California, Los 

Angeles 

Burek CL	 John Hopkins 

University 

Burek CL John Hopkins 

University 

Carrasco N Yeshiva University 

Degroot LJ	 University of Chicago 

Kong Y-CM	 Wayne State 

University 

Naylor EW	 Neo Gen Screening, 

Inc. 

Refetoff SS	 University of Chicago 

Refetoff SS	 University of Chicago 

Sgouros G Sloan-Kettering 

Institute for Cancer 

St Germain DL Dartmouth College 

St Germain DL	 Dartmouth College 

Characterization of thyroid 

autoantibodies and antigens 

Regulation of the 

sodium/iodine symporter in 

breast 

Immunotoxic effects of iodine 

Nod h2h4 mice as a sentinel 

model for autoimmune thyroid 

Characterization of the thyroid 

Na +/I-symporter 

Pathogenesis and therapy of 

autoimmune thyroid disease 

T cell recognition—repertoire 

in autoimmune thyroiditis 

Simplified population 

screening for adult 

hypothyroidism 

Regulation and mechanisms 

of hormone action 

Screening for inherited thyroid 

defects 

Modeling and dosimetry for 

radiolabeled antibody therapy 

Regulation of thyroid hormone 

metabolism 

The role of the Type 3 

deiodinase in development 

NCRR 

NCI 

NIH—National Institute 

of Diabetes and 

Digestive and Kidney 

Diseases 

NIEHS 

NIH—National Institute 

of Diabetes and 

Digestive and Kidney 

Diseases 

NIH—National Institute 

of Diabetes and 

Digestive and Kidney 

Diseases 

NIH—National Institute 

of Diabetes and 

Digestive and Kidney 

Diseases 

NIH—National Institute 

of Diabetes and 

Digestive and Kidney 

Diseases 

NIH—National Institute 

of Diabetes and 

Digestive and Kidney 

Diseases 

NCRR 

NCI 

NIH—National Institute 

of Diabetes and 

Digestive and Kidney 

Diseases 

NIH—National Institute 

of Diabetes and 

Digestive and Kidney 

Diseases 
IODINE 217 

3. HEALTH EFFECTS 

Table 3-10. Ongoing Studies on Health Effects of Radioactive Iodine 

Investigator Affiliation Title Sponsor 

Weintraub BD University of Structure/function NIH—National Institute 

Maryland, Baltimore relationships of human of Diabetes and 

Professional School thyrotrophin Digestive and Kidney 

Diseases 

NCI = National Cancer Institute; NCRR = National Center for Research Resources; NIEHS = National Institute 

of Environmental Health Sciences; NIH = National Institute of Health/National Institute of General Medical 

Sciences 

Source: CRISP 2001; National Institutes of Health; Central Repository of Incidents, Solutions, and Problems 

 

 

0.28 s 25.0 m

131In 

56 s 131Sb 23.0 m 131I 8.02 d 131Sn 131Te 131Xe 235U + 1

n 

IODINE 219 

4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION 

4.1 CHEMICAL IDENTITY 

Iodine is a nonmetallic element belonging to the halogen family in Group VIIA of the periodic table. 

Iodine is found in nature as iodide (i.e., I-

) in brines or in molecular compounds with other elements (e.g., 

iodate or IO3 

-

). The chemical information for elemental iodine and some of its compounds is listed in 

Table 4-1. Radioactive isotopes of iodine (e.g., see Section 4.2) are an additional cause of concern with 

regard to human health (see Chapter 3). 

4.2 PHYSICAL, CHEMICAL, AND RADIOLOGICAL PROPERTIES 

The physical properties of iodine and selected iodine compounds are listed in Table 4-2. The percent 

occurrence of iodine isotopes and radiological properties of iodine isotopes is listed in Table 4-3. 

Iodine can exist in several oxidation states: -1, 0, +1, +3, +5, and +7. Under normal environmental 

conditions, the -1, 0, and +5 oxidation states are the most important. There are 36 isotopes of iodine 

having masses between 108 and 143 (Chu et al. 1999); 14 of these yield significant radiation. The only 

naturally-occurring isotopes of iodine are 127I and 129I, which are stable and radioactive, respectively. 

Isotopes of mass less than 127 are produced in particle accelerators (common examples are 123I and 125I), 

while those >127 are formed in neutron generators such as nuclear reactors and atomic bombs (common 

examples are 129I and 131I). A total of 72% of uranium fissions and 75% of plutonium fissions leads 

directly or by beta decay of precursors, to iodine isotopes. For example, 2.89% of 235U and 3.86% of 

239Pu fission atoms lead to the formation of a series of isobar 131 isotopes, including 131In, 131Sn, 131Sb, 

131Te, 131I, and 131Xe. Each isotope can be formed as an initial fission product and, once formed, each 

isotope decays by beta-ray emission to the right on the sequence, through 131I, and with stable 131Xe. The 

process can be displayed as: 
 

 

 

 

IODINE 220 

4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION 

Table 4-1. Chemical Identity of Iodine and Iodine Compounds 

Property Iodine 

Hydrogen 

iodide 

Sodium 

iodide 

Potassium 

iodide 

Methyl 

iodide 

Cesium 

iodide 

Chemical 

formula I2 HI NaI KI CH3I CsI 

Chemical I I +
 

structure Na I I
 

H I + H +

Cs I 

H 

K I 

H 

Synonyms Actomar; 

diiodine; eranol; 

Hydroiodic 

acid 

Sodium 

monoiodide; 

Hydroiodic 

acid, 

Monoiodomethane; No data 

iodine-127; 

molecular iodine 

sodium 

Iodine 

potassium 

salt; PIMA; 

iodomethane 

SSK; iodide 

of potash 

Trade names None None None None Halon 10001 No data 

Identification 

numbers 

 CAS registry 

NIOSH RTECS 

7553-56-2 

NN1575000 

10034-85-2 

MW3760000 

7681-82-5 

WB6475000 

7681-11-0 

TT2975000 

74-88-4 

PA9450000 

7789-17-5 

No data 

EPA None None None None U138 None 

hazardous 

waste 

 OHM/TADS None None None None None None

 DOT/UN/NA/ 

IMO shipping 

UN 1759; 

UN 1760 

UN 2197; 

UN 1787 

Corrosive 

None None UN 2644 Poison/ 

IMO 6.1 

None 

material/ 

IMO 8.0; 

IMO 2.0 

HSDB 34 2155 750 5040 1336 None 

NCI 42355 None None 77362 9366 None 

 STCC None None None None None None 
2+ I Ca I

I + O 

O O K + Cu+ I N O I O Na I I

 

 

 

 

IODINE 221 

4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION 

Table 4-1. Chemical Identity of Iodine and Iodine Compounds 

Potassium Sodium Calcium Copper Povidone 

Property iodate periodate iodide (I) iodide iodine 

Chemical 

formula KIO3 NaIO4 CaI2 CuI C6H9I2NO 

Chemical O O

structure 

O 

Synonyms Iodic acid, Sodium Calcium Copper Poly(1-(2-oxo-1-pyrrolidinyl)­

potassium salt metaperiodate diiodide; monoiodide; ethylene)iodine complex; 

calcium natural betadine; efodine; Iodopoly(vinyl 

iodide marshite; pyrrolidinone); isobetadyne; 

hydrate cuprous isodine; poly(vinylpyrrolidinone) 

iodide iodide; ultradine 

Trade names None None None None None 

Identification 

numbers 

CAS registry 7758-05-6 7790-28-5 10102-68-8 7681-65-4 25655-41-8 

NIOSH NN1350000 None None None TR1579600 

RTECS 

EPA None None None None None 

hazardous 

waste 

OHM/TADS None None None None None

 DOT/UN/NA/ None None None None 

IMO shipping

 HSDB 1231 None None 271 6831 

NCI None None None 26245 

STCC None None None None None 

CAS = Chemical Abstracts Services; 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 Commercial Code 

Source: HSDB 2001; Lide 2000 
 

 

 

 

 

IODINE 222 

4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Iodine and Iodine Compoundsa 

Property Iodine Hydrogen iodide Sodium iodide Potassium iodide 

Molecular weight, 

g/mole 

Color 

Physical state 

Melting point 

Boiling point 

Density, g/cm3 

(25 EC) 

Odor 

Odor threshold: 

Water
 

Air
 

Solubility (25 EC): 

Water 

Organic 

solvents(s) 

Partition 

coefficients: 

Log Kow 

Log Koc 

Vapor pressure 

(25 EC) 

Henry’s Law 

constant 

Autoignition 

temperature 

Flashpoint 

Flammability limits 

Explosive limits 

253.809a 

Bluish-blacka 

Solid; scales or 

platesa 

113.60 ECa 

185.24 ECa 

4.93a 

Characteristica 

No data 

No data 

330 mg/La 

141 g/kg 

benzenea 

2.49b 

No data 

0.305 mm Hga 

No data 

No data 

No data 

No data 

No data 

127.91a 

Colorlessa 

Gasa 

-50.8 ECa 

-35.1 ECa 

5.23a 

No data 

No data 

No data 

2,340 g/L (10 EC)a 

Solublea 

No data 

No data 

5,940 mm Hgc 

No data 

No data 

No data 

Non-flammable 

No data 

149.89a 

White 

Solid; crystals or 

granules 

651 ECa 

1,304 ECd 

3.67a 

Odorlessa 

No data 

No data 

2,000 g/La 

500 g/L alcohola 

No data 

No data 

1 mm Hg 

(767 EC)c 

No data 

No data 

No data 

No data 

No data 

166.02a 

Colorless or whitea 

Solid; crystals, granules, 

or powdera 

680 ECa 

1,323 ECd 

3.12a 

No data 

No data 

No data 

1,429 g/La 

13 g/L acetonea 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

No data 
 

 

 

IODINE 223 

4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Iodine and Iodine Compoundsa 

Property 

Molecular weight, 

g/mole 

Color 

Methyl iodide 

141.94a 

Colorlessa 

Cesium iodide 

259.81a 

Colorlessd 

Potassium iodate 

214.02a 

Whitea 

Sodium periodate 

213.892d 

Whited 

Physical state 

Melting point 

Boiling point 

Density, g/cm3

 (25 EC) 

Liquida 

-66.5 ECa 

42.5 ECa 

2.28 (20 EC)a 

Solid; crystals, or 

powdera 

621 ECa 

ca. 1,280 ECa 

4.5a 

Solid, crystalsa 

560 ECa 

No data 

3.98c 

Solid; crystalsd 

Decomposes ~300 EC 

No data 

3.86d 

Odor Pungent, etherlikec No data No data No data 

Odor threshold: 

Water No data No data No data No data 

Air No data No data No data No data 

Solubility (25 EC): 

Water 

Organic solvents(s) 

13.9 g/L 

(20 EC)c 

Misciblea 

Misciblea 

Soluble in 

alcohol; insoluble 

9.16 g/100 gc 

No data 

Solubled 

No data 

in acetonea 

Partition coefficients: 

Log Kow 

Log Koc 

Vapor pressure (25 EC) 

1.51c 

No data 

405 mm Hg 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

Henry’s Law constant 

Autoignition 

0.00526 

atm-cu m/mole 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

temperature 

Flashpoint 

Flammability limits 

Explosive limits 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

No data 
 

 

 

IODINE 224 

4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Iodine and Iodine Compoundsa 

Property Calcium iodide Copper (I) iodide Povidone iodine 

Molecular weight, g/mole 

Color 

293.89a 

Yellowa 190.45a Red-browna 364.95c Yellow-brownc 

Physical state 

Melting point 

Boiling point 

Density, g/cm3

 (25 EC) 

Odor 

Odor threshold: 

Solid; lumps or 

powdera 

740 EC 

1,100 EC 

No data 

Solid; powder or 

crystalsa 

588–606 ECa 

~1,290 ECa 

5.63a 

No data 

Solid; powderc 

300 ECe 

No data 

Slight characteristicc 

Water No data No data No data 

Air No data No data No data 

Solubility (25 EC) 

Water 

Organic solvents(s) 

Very solublea 

Very soluble in 

alcohol, acetonea 

80 mg/L (18 EC)c 

Insolublea 

Solublec 

Insolublec 

Partition coefficients: 

Log Kow 

Log Koc 

Vapor pressure 

Henry’s Law constant 

Autoignition temperature 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

Flashpoint 

Flammability limits 

Explosive limits 

No data 

No data 

No data 

No data 

No data 

No data 

a

Budavari et al. 1998 

b

Hansch and Leo 1995 

c

HSDB 2000 

d

Lide 2000 

Source: Chemfinder 2001, unless otherwise specified 
 

 

IODINE 225 

4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION 

Table 4-3. Percent Natural Occurrence and Radioactive Properties 

of Isotopes of Iodine 

Gamma 

Isotope 

CAS registry 

number 

Natural 

abundance (%) 

Beta energies, 

MeVa

 (intensity) 

energies, 

keVa Half-life 

Activity, 

Ci/gramc 

123I 15715-08-9 No data 1.08 (97.0%) 158.97 13.3 hours 1.92x106 

124I 14158-30-6 No data ECb 602.7 

722.8 

4.18 days 2.52x105 

1691.0 

125I 14158-31-7 No data ECb 35.5 59.4 days 1.76x104 

126I 14158-32-8 No data ECb 388.6 

666.3 

13.11 days 7.91x104 

753.8 

127I 7553-56-2 <100 No data No data Stable No data 

129I 15046-84-1 1x10-13 to 

1x10-10 

0.154 29.5 

29.8 

1.57x107 years 1.77x10-4 

33.6 

131I 10043-66-0 No data 0.334 (7.3%) 

0.606 (89.9%) 

284.3 

364.5 

8.04 daysd 1.24x105 

132I 14683-16-0 No data 0.74 (13.0%) 

0.96 (8.2%) 

1.18 (18.8%) 

1.61 (12.6%) 

2.14 (19.0%) 

667.7 

772.6 

954.6 

2.30 hours 1.03x107 

133I 14834-67-4 No data 0.54 (87.0%) 

0.88 (4.5%) 

529.9 

875.3 

20.8 hours 1.13x106 

134I 14914-27-3 No data 1.31 (30.4%) 

1.59 (16.2%) 

1.82 (11.0%) 

2.44 (12.5%) 

847.0 

884.1 

52.5 minutes 2.67x107 

135I 14834-68-5 No data 679.7 (8.0%) 

856.8 (8.8%) 

969.9 (21.9%) 

1,082.7 (8.0%) 

1,387.6 (23.8%) 

546.6 

836.8 

1,038.8 

1,131.5 

6.57 hours 3.53x106 

a

Not all gamma and beta energies are included in summary; see Chu et al. (1999) for a complete listing 

b

EC = electron capture decay 

c

Activity = (NA ln2)/(Mw t1⁄2) d

Lide 2000 

Source: Chu et al. 1999 
 

 

131I 131Xe (stable) + β− (0.61 MeV; 85.3%) + γ (0.36 MeV) 

+ β− (0.61 MeV; 5.1%) + γ (0.284 MeV) + γ (0.080 MeV) 

+ β− (0.81 MeV; 0.6%) + γ (0.16 MeV) 

+ β− (0.47 MeV; 0.3%) + γ (0.50 MeV) 

+ β− (0.47 MeV; 0.2%) + γ (0.33 MeV) + γ (0.2 MeV) 

+ β− (0.33 MeV; 6.9%) + γ (0.64 MeV) 

+ β− (0.25 MeV; 1.6%) + γ (0.72 MeV) 

IODINE 226 

4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION 

The same process occurs for 129I (t1⁄2=1.6x107 years) and includes mass 129 isobars beginning with 129Cd 

and ending with 129Xe. Iodine isotopes above 127I decay by emitting beta and gamma radiation, whose 

combined energies are unique to each iodine isotope. 131I, for example, decays by beta particle emission, 

and 0.96 MeV of energy is shared between the beta particle and the gamma ray. At least seven possible 

beta/gamma combinations occur. In 90.4% of the decays, a 0.61 MeV beta particle is emitted. The 

remaining excess energy is emitted as either a 0.364 MeV gamma ray for 85.3% of the time, or a pair of 

0.284 and 0.080 MeV gamma rays for the other 5.1% of the time. The following is the decay scheme for 

131I (Cember 1996): 

Isotopic masses of iodine <127 can be produced using a beam of high energy protons generated using a 

linear accelerator. Proton beams tuned at fixed energies up to 30 MeV produce isotopes, such as 123I, by 

interaction of the proton beam with a target of high atomic mass. 
 

 

 

IODINE 227 

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

5.1 PRODUCTION 

Iodine, a halogen, occurs in low concentrations in nature in the form of iodides mainly in sea water, 

although there are a number of major sources iodine including the underground waters from certain deepwell boring and mineral springs (i.e., brines) and natural deposits of sodium nitrate ore (i.e., caliche) 

found in the northern part of Chile. Only a few marine organisms contain iodine in relatively large 

quantities including seaweeds, sponges, and corals. The different production processes for recovering 

iodine are based on the raw materials used. Approximately 54% of the iodine consumed in the world is 

obtained from Chile as a coproduct from surface mineral deposits used to produce nitrate fertilizers 

(USGS 2002). About 43% of the iodine consumed in the world comes from brines processed in Japan, 

the United States, and the former Soviet Union. The primary production process for recovery of iodine 

from brines is the blow-out process. The blow-out process for brines can be divided into brine clean-up, 

iodide oxidation followed by air blowing and recovery, and iodine finishing. In 2001, iodine was 

recovered from brines by the blow-out process by three companies operating in Oklahoma, which 

accounted for 100% of the U.S. elemental iodine production. These three companies are IOCHEM 

Corporation (Dewey County, Oklahoma), North American Brine Resources (Dover, Oklahoma), and 

Woodward Iodine Corporation (Woodward County, Oklahoma). Production of iodine in the United 

States has remained steady ranging from 1,270 to 1,620 metric tons between the years 1996 and 2000 

(Lauterbach and Ober 1995; USGS 1998, 2002). 

After World War II, the U.S. government began stockpiling iodine for defense applications. By 1968, the 

DOD had acquired 3,700 metric tons of iodine. In 1992, Congress determined that the stockpile was 

unnecessary, reduced the stockpile goal to zero, and authorized the sale of all excess material. As of 

September 30, 2001, the uncommitted inventory of stockpile-grade iodine was 1,629 metric tons (USGS 

1998, 2002). 

The only naturally occurring isotopes of iodine are 127I and 129I, which are stable and radioactive, 

respectively. Other radioactive iodine isotopes (e.g., 131I) do not occur in nature; they are the direct result 

of anthropogenic activity. As discussed in Chapter 4, 129I and 131I are produced by nuclear fission. Nearly 

all of the 129I and 131I generated in the United States is present in spent nuclear reactor fuel rods. These 

fuel rods are currently located at commercial reactor facilities or at Department of Energy (DOE) 
IODINE 228 

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

facilities across the United States. The cumulative yield of 129I is about 1% of all fission products. Thus, 

129I represents only a very small fraction of the total fission product inventory in the nuclear fuel cycle. A 

limited amount of 123I, 125I, and 131I will be produced for industrial, scientific, and medicinal applications 

by International Isotopes Inc. (Denton, Texas) using a linear accelerator (DOE 1996d; International 

Isotopes 2001; USGS 1998). 

5.2 IMPORT/EXPORT 

In 2000, 77% of the apparent consumption of iodine in the United States (6,320 metric tons) was 

imported. Of the 4,790 metric tons of iodine imported in 2000, approximately 67% was imported from 

Chile, 21% from Japan, and 11% from Russia. Exports of iodine have decreased from 2,410, 2,760, and 

2,790 metric tons in 1996, 1997, and 1998, respectively, to 1,130 and 900 metric tons in 1999 and 2000, 

respectively (USGS 1998, 2002). 

5.3 USE 

End uses for iodine in 1999 were estimated from a United States Geological Survey (USGS) canvass of 

consumers as follows (by percentage): sanitation (45%); animal feed (27%); pharmaceutical (10%); heat 

catalyst (8%); stabilizers (5%); and other (5%) (USGS 1999). Other smaller uses included inks and 

colorants, photographic chemicals, laboratory reagents, production of batteries, high-purity metals, motor 

fuels, and lubricants. Hydrogen iodide (i.e., HI) is used in the manufacture of hydroiodic acid and organic 

iodo compounds, and to remove iodine from iodo compounds. Potassium iodide (i.e., KI) is used in 

animal feeds, catalysts, photographic chemicals, for sanitation, and for treatment of radioiodine poisoning 

resulting from nuclear accidents. Sodium iodide (i.e., NaI) is used in photography and for the production 

of organic chemicals. Methyl iodide (i.e., CH3I) is used as a methylation agent in organic synthesis, in 

microscopy, as an embedding material for examining diatoms, and in testing for pyridine. Potassium 

iodate (i.e., KIO3) is used in salt iodization, as an oxidizing agent in analytical chemistry, and as a 

maturing agent and dough conditioner (Lauterbach and Ober 1995; USGS 1998). 

Radioactive iodine has been used successfully for the treatment of cancer of the thyroid. The radioactive 

isotope 123I is considered the agent of choice for brain, thyroid, and renal imaging and uptake 

measurements. 125I is used as a cancer therapeutic, and as a brain, blood, and metabolic function 

diagnostic. 131I is used as a brain, pulmonary, and thyroid diagnostic (Lauterbach and Ober 1995; USGS 

1998). 
IODINE 229 

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

5.4 DISPOSAL 

Most nonradioactive iodine minerals, iodine compounds, and iodine-containing materials do not require 

special disposal or handling requirements. However, some chemical forms may be classified as 

hazardous materials if the compound is chemically reactive, flammable, or toxic. Care should be taken to 

read and understand all of the hazards, precautions, and safety procedures for each specific chemical 

form. In addition, all federal, state, and local laws and regulations should be investigated and 

subsequently followed with regard to disposal and handling of the specific chemical form of the iodine 

compound or material. 

Radioactive iodine does require special disposal and handling requirements and is regulated by the 

Nuclear Regulatory Commission. Radioactive waste-containing radioactive iodine can be grouped into 

three categories: low-level waste (LLW); high-level waste (HLW) and spent nuclear fuel; and mixed 

waste. As defined by the Nuclear Waste Policy Act, high-level radioactive waste is “the highly 

radioactive material resulting from the reprocessing of spent nuclear fuel, including liquid waste produced 

directly in reprocessing and any solid material derived from such liquid waste that contains fission 

products in sufficient concentration.” However, most classifications of HLW also include spent nuclear 

fuel. Most HLW was generated from the production of plutonium. A small fraction is related to the 

recovery of enriched uranium from naval reactor fuel. This waste typically contains highly radioactive, 

short-lived high activity fission by-products as well as other long-lived isotopes, hazardous chemicals, 

and toxic heavy metals. Radioiodine contamination is only a small fraction of the activity of HLW. 

Liquid HLW is typically stored in large underground tanks of either stainless steel or carbon steel 

depending on whether they are acid or alkaline solutions. There are about 100 million gallons of highlevel liquid waste stored in underground tanks in Washington, South Carolina, Idaho, and New York. 

These tanks contain a variety of radioactive liquids, solids, and sludges. Some of the liquid wastes have 

been solidified into glass, ceramic slag, salt cakes, and sludges (DOE 1996a; Murray 1994). 

Spent nuclear fuels, such as fuel elements and irradiated targets used in nuclear reactors, are currently 

disposed of at the commercial nuclear power plants and DOE facilities where they were produced. Spent 

fuel is highly radioactive due to the large concentration of fission products and must be stored in special 

water-cooled pools that shield and cool the material. Most of the radioactive iodine remains trapped in 

the spent fuel rod matrix and is never released. Roughly all DOE spent fuel, about 3,000 metric tons, is 

stored at four sites: Hanford, Savannah River, Idaho National Engineering and Environmental Laboratory 
IODINE 230 

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

(INEEL), and West Valley, New York. Commercial reactors have generated more than 30,000 metric 

tons of spent fuel. The spent fuel from these facilities is stored at the more than 100 commercial nuclear 

reactor sites around the United States. Since spent commercial nuclear reactor fuel is placed in on-site 

storage while awaiting off-site disposal, the only isotope of iodine remaining in the fuel matrix when it 

leaves the generating facility will be 129I. The establishment of an HLW and spent fuel repository for both 

DOE and commercial waste is currently under construction at Yucca Flats, Nevada. It is not projected to 

be in operation until after the year 2010 (DOE 1996b, 2001d; Eisenbud 1987; Murray 1994). A 

temporary storage site for spent fuel rods has been proposed on the Goshute Indian Reservation in the 

Skull Valley of Utah (MHR 2001; NCSL 2002). However, as of 2003, the U.S. Nuclear Regulatory 

Commission (USNRC) as blocked the issuance of a license for the project (USNRC 2003). 

Mixed waste contains both radioactive and chemically hazardous materials such as toxic, corrosive, 

flammable, or explosive materials. The radioactive component may be either HLW or LLW. All liquid 

HLW is mixed waste, usually in the presence of organic solvents or heavy metals in addition to 

radioactive components. Disposal of mixed wastes is regulated by the EPA under the Resource 

Conservation and Recovery Act (RCRA) and by the USNRC under the Atomic Energy Act. The EPA 

and the USNRC have developed special procedures on how to handle and dispose of this special category. 

The DOE operates an incinerator in Oak Ridge, Tennessee, which burns mixed hazardous radioactive 

wastes (DOE 1996a). 

Low-level waste is all radioactive waste that cannot be classified as HLW, spent fuel, or mixed waste. 

Low-level does not necessarily mean low radioactivity or low environmental hazards. However, the bulk 

of LLW has relatively little radioactivity and practically no transuranic elements. Thus, LLW usually 

does not require shielding from radioactivity or heat removal equipment. Most LLW is acceptable for 

near surface land disposal. LLW types that may be contaminated with 129I include both wet and dry 

wastes. Examples of the physical form of LLW are spent ion exchange resins, filter sludges, filter 

cartridges, evaporator bottoms, compactible trash, noncompactible trash, irradiated components, ashes 

produced from the incineration of combustible material, contaminated detergents or solvents, organic 

liquids, and discarded contaminated equipment or tools. Of the LLW generated today, approximately 

64% of the volume and 70% of the radioactivity are generated as a result of nuclear power plant activities 

or supporting fuel cycle operations. Other sources of LLW are industrial, academic, government, and 

medical. Radioiodine contamination accounts for only a small fraction of the activity of LLW. LLW 

typically is packaged in drums or boxes and buried in shallow pits or trenches. Approximately 3 million 

cubic meters of LLW generated in the United States have been disposed of this way. LLW from DOE 
IODINE 231 

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

sources is currently disposed of at several DOE facilities across the United States. Only three sites accept 

non-DOE LLW, Barnwell, South Carolina; Richland, Washington; and Envirocare of Utah, Inc. (Clive, 

Utah). Over half of the LLW in the eastern United States is disposed of at the Barnwell site. As required 

by the Federal LLRW (Low Level Radioactive Waste) Policy Act in 1980 and the 1985 amendments, 

states or interstate compacts are required to build facilities to contain LLW generated from sources within 

their boundaries. However, other than Barnwell, South Carolina; Richland, Washington; and Clive, Utah 

sites, no other facility in the United States is currently accepting LLW from non-DOE sources. Currently, 

many generators store LLW on-site until additional facilities can be constructed in the future (DOE 

1996a; Eisenbud 1987; Envirocare 2001; Murray 1994). 

Decay on-site is one method chosen in the medical community to handle their low level radioiodine 

waste. Contaminated clothing, food trays, linen, materials used to clean patients’ rooms, furniture, and 

telephones are quarantined until levels of radioiodine are sufficiently low. A period of 10 half-lives may 

be adequate to reduce the radioactivity to safe levels to permit reuse of the materials without controls. 

 

 

IODINE 233 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.1 OVERVIEW 

The stable isotope of iodine, 127I, and two of its radioactive isotopes, 129I and 131I, have been identified in 

at least 8, 3, and 6, respectively, of the 1,636 hazardous waste sites that have been proposed for inclusion 

on the EPA National Priorities List (NPL) (HazDat 2004). However, the number of sites evaluated for 

iodine is not known. The frequency of these sites can be seen in Figures 6-1, 6-2, and 6-3. All of these 

sites are located within the United States. 

Iodine is a naturally occurring constituent of the earth’s crust and is the least abundant of the halogen 

elements (Straub et al. 1966). The stable isotope iodine, 127I, is ubiquitous throughout the earth’s surface. 

The concentration of 127I in the earth’s crust is approximately 0.5 ppm; in the oceans, the concentration is 

45–60 μg/L, and in the atmosphere, the concentration ranges from 10 to 20 ng/m3

. Concentrations of 

iodine in the environment throughout the United States vary depending on the proximity to the seacoast 

and the soil type. The concentration of iodine in bedrock varies between 0.5 and 380 ppm, depending on 

whether the rock is igneous or sedimentary. 

Iodine exists in many chemical forms (e.g., molecular iodine, iodide, iodate, periodate) and can undergo 

oxidation-reduction as well as microbial alkylation (mostly methyl iodide). Iodine has nine radioisotopes, 

of which 123I, 125I, 129I, and 131I are commonly encountered in acute or chronic exposures to human 

populations, due either to the life-times of the radioisotope in the environment, their production, and/or 

their use in industry, medicine, and research. 

129I is the only naturally occurring iodine radioisotope. It is produced as a fission product of uranium and 

thorium in soils and oceans, and is also formed in reactions of xenon with high energy particles in the 

upper atmosphere and reactions of neutrons with 128Te and 130Te (Soldat 1976). 129I has a half-life of 

1.6x107 years and decays through β emission; 129I has a mass/decay rate equivalency of 1 g 129I=6.55 MBq 

(177 μCi) (Robkin and Shleien 1995). 129I/127I ratios from natural production of 129I should be 3x10-14 in 

the environment, but with the introduction of 129I from nuclear weapons testing and nuclear energy 

activities, the ratio is now 10-8 (Ballad et al. 1978). The estimated global inventory of 129I is 

approximately 9,600 Ci (0.36 PBq or 5.4x107

 g 129I), of which 9,200 Ci (0.34 PBq or 5.2x107 g 129I) is 

associated with igneous activity (DOE 1994). 
 

 

IODINE 234 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-1. Frequency of NPL Sites with Iodine Contamination 

1 

3 

Frequency of

NPL S ites 

D erived from HazDat 2004 
 

 

IODINE 235 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-2. Frequency of NPL Sites with 129I Contamination 

1 

Frequency of

NPL S ites 

D erived from HazDat 2004 
 

 

IODINE 236 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-3. Frequency of NPL Sites with 131I Contamination 

1 

3 

Frequency of

NPL S ites 

D erived from HazDat 2004 
IODINE 237 

6. POTENTIAL FOR HUMAN EXPOSURE 

125I and 131I are produced in the fission of uranium and plutonium by neutron bombardment in reactors 

and/or heavy nuclei particles in accelerators. 125I has a half-life of 60 days and decays through electron 

capture (EC) emitting a 35.5 keV gamma-ray and K-shell x-rays (27.4 keV, 112%; 31.4 keV, 24%). The 

specific activity of 125I is 67.7 TBq/g or 18,277 Ci/g. 131I has a half-life of 8.04 days and decays through 

β emission; 131I has a specific activity of 457 TBq/g or 123,429 Ci/g. Unlike 129I, 125I and 131I do not have 

long residency times in the environment due to their short half-lives and, thus, do not pose risks 

associated with an accumulation in the environment. However, in acute exposures to 125I and 131I, there is 

the potential for significant radiation exposure to the thyroid. 

Releases of iodine into the environment occur from both natural sources and human activity. The natural 

sources include volatilization of iodine from the oceans, weathering of rock, and volcanic activity (Cohen 

1985; Whitehead 1984). Sources of iodine from human activities include release of radioiodine from 

nuclear weapons testing and nuclear fuel reprocessing, waste stream effluent from municipal plants, and 

combustion of waste and fossil fuels (Likhtarev et al. 1993; Moran et al. 1999; NAS 1974; NCRP 1983; 

Stetar et al. 1993). 

Iodine enters the atmosphere mainly through volatilization of methyl iodide and, to a lesser extent, 

molecular iodine from the ocean surface. 129I is introduced naturally through the conversion of 129Xe 

(xenon-129) to 129I through the interaction with high energy particles in the upper atmosphere. 131I was 

released through weapons production/utilization, nuclear fuel reprocessing, and energy production (AEC 

1974; Likhtarev et al. 1993; Marter 1993; Moran et al. 1999; NCRP 1983; Robkin and Sheien 1995). In 

the atmosphere, iodine undergoes extensive photochemical changes and can exist as gaseous inorganic, 

gaseous organic, or particulate forms. These forms have an average residency time in the atmosphere of 

10, 18, and 14 days, respectively (Whitehead 1984). 

The gaseous inorganic and particulate forms of iodine are precipitated from the atmosphere through wet 

(rain, sleet, and snow) and dry (gravitational settling and wind turbulence) deposition processes 

(Whitehead 1984). Alkyl iodides, such as methyl iodide, have a low susceptibility to both wet and dry 

deposition. The deposition of iodine will depend on particle size and concentration, wind turbulence, and 

the chemical form of iodine. If precipitation occurs over land, iodine will be deposited onto plant 

surfaces or soil surfaces, or into surface waters. The average retention time of iodine on plant surfaces is 

7.5–14 days due to weathering (AEC 1974; Heinemann and Vogt 1980; Kirchner 1994). Retention of 

iodine in the soil is influenced by a number of factors, including soil pH, soil moistness, porosity of soil, 
IODINE 238 

6. POTENTIAL FOR HUMAN EXPOSURE 

and composition of organic and inorganic (e.g., aluminum and iron oxides) components (Sheppard et al. 

1995; Whitehead 1984). Approximately 1% of iodine received through atmosphere-to-soil deposition is 

returned through volatilization of molecular iodine and methyl iodide; the remaining iodine is eventually 

returned to the oceans through surface water and groundwater (USNRC 1979; Whitehead 1984). The 

average residency time of iodine in the soil at 0.3- and 1-meter depths has been suggested to be 80 and 

800 years, with only 1–3% of deposited iodine migrating to the 1-meter depth (DOE 1986). 

Transport of iodine through surface water and groundwater is not greatly retarded by the soil, rock, and 

sediments over or through which these waters flow (USNRC 1981). The concentration of iodine in river 

water ranges between 0.1 and 18 μg/L, which parallels the concentration of iodine in rainwater of 0.1– 

15 μg/L (USNRC 1979). In groundwater, the mean concentration is 1 μg/L (Yuita 1994a). The 

concentration of iodine in river water often increases downstream of urban areas due to the discharge of 

waste streams from municipal treatment facilities. This is especially true for 131I that enters sewage 

streams from patients undergoing radioiodine therapies (Tubiana 1982; UNSCEAR 2000). Slightly 

elevated concentrations of 129I have been observed in surface water and groundwater near nuclear fuel 

reprocessing facilities (Beals and Hayes 1995; DOE 1994). 

Iodine has been shown to bioaccumulate in many seawater and freshwater aquatic plants (Poston 1986). 

Freshwater plants (e.g., algae) contain 10-5% by weight of iodine, whereas marine plants (algae) contain 

10-3% by weight (NCRP 1983). In freshwater fish, iodine concentrations in tissues range from 0.003 to 

0.81 ppm, which gives concentration ratios (fish/water) of 0.9–810. In marine fish, the iodine 

concentrations range between 0.023 and 0.11 ppm, yielding concentration ratios of between 10 and 

20 (Poston 1986). In terrestrial plants, iodine can be taken up through the roots, mainly as iodide and to a 

lesser extent, as iodate or iodine (Burte et al. 1991; Whitehead 1984). The average iodine concentration 

in terrestrial plants is 0.42 μg/g. The uptake is dependent on soil conditions and the use of fertilizers 

(Moiseyev et al. 1984). Distribution of iodine and iodide varies throughout the plant (Voigt et al. 1988). 

The uptake of iodine into terrestrial plants in combination with deposition of iodine onto the surfaces of 

plants plays an important role in the transfer of iodine through the soil-plant-cow-milk pathway. The 

efficiency through which iodine is transferred through this pathway is important in ascertaining the risk of 

radioiodine exposures in the general human population from continuous or accidental releases of 131I and 

129I, especially in children (AEC 1974; Soldat 1976; Tubiana 1982; Voigt et al. 1989). 

The iodine content of food has been studied extensively, with intakes of iodine typically ranging from 

0.064 to 0.379 mg/day (FDA 1974; Pennington et al. 1984, 1986). The major sources of iodine intake 
IODINE 239 

6. POTENTIAL FOR HUMAN EXPOSURE 

from food in a typical U.S. diet are added salt and food additives, followed by meat and meat products, 

milk and milk products, and green/yellow vegetables (FDA 1974). Other foods that can provide a high 

amount of iodine in the diet include seaweed, marine shellfish, and marine fish. 

It is estimated that the intake of iodine through inhalation is 4x10-5 g/year (USNRC 1979). The average 

intake of iodine from drinking water, assuming an average iodine concentration of 3 μg/L, is estimated to 

be 1.5x10-3 g/year (USNRC 1979). If the average intake of iodine from food is assumed to be the 

recommended dietary allowance (RDA) for iodine of 150 mg/day, then the yearly intake of iodine would 

be approximately 55 g. Thus, the largest source of iodine in the average U.S. diet comes from food 

intake. The intake of iodine through food consumption can be increased greatly in diets high in marine 

fish (-800 μg/kg wet weight), shellfish (-800 μg/kg), and seaweed-based products (0.8–4.5 g/kg dry 

weight) (FDA 1974). Other sources of iodine intake are alternative medicines and nutritional 

supplements which, depending on the specific iodine content and dosage, can approach toxic levels (e.g., 

>6 g/day) (Cassileth 1999). 

Currently, the intake of 129I and 131I by the general population through inhalation, drinking water, and food 

intake does not pose any significant risk, due to the extremely low levels of 129I and 131I in the general 

environment. However, there are certain populations of individuals who are at risk to potential exposures 

to high levels of iodine or acute/chronic levels of radioiodine. Individuals undergoing specific diagnostic 

or therapeutic procedures or receiving certain types of medications can significantly increase whole-body 

and thyroid burdens of iodine and 131I (FDA 1989b; Tubiana 1982). Family members, especially 

children, of patients undergoing 131I therapies can experience exposure to both the radioisotope and the 

radiation emitted from 131I (Barrington et al. 1999; Jacobson et al. 1978). Likewise, medical personnel 

working with, or in proximity to, 131I can also have elevated whole-body and thyroid burdens of this 

radioisotope and are at risk to exposure to the photon radiation emitted from 131I (Blum and Liuzzi 1967; 

Mountford and O’Doherty 1999; Tubiana 1982). Workers in nuclear power plants or nuclear fuel 

reprocessing facilities are at risk for potentially high acute exposures of 129I and 131I (Bhat et al. 1973; 

Raghavendran et al. 1978). Laboratory workers who are involved in the iodination of chemicals or 

biologics with 125I/131I or the use of these radioiodinated materials also show increased thyroid burdens of 

these radioisotopes (Bogdanove and Strash 1975; de Groot 1979; Dunn and Dunscombe 1981; Jönsson 

and Mattsson 1998; Kivinitty et al. 1984; Krzesniak et al. 1979; Kwok and Hilditch 1982; Pomroy 1979). 
IODINE 240 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.2 RELEASES TO THE ENVIRONMENT 

The stable isotope of iodine, 127I, and two of its radioactive isotopes, 129I and 131I, have been identified in 

8, 3, and 6, respectively, of 1,636 current or former NPL hazardous waste sites within a variety of 

environmental media (air, leachate, and groundwater) collected at these sites (HazDat 2004). 

Releases of iodine and its radioisotopes into the environment occur from natural sources and from human 

activity (Figures 6-4 and 6-5). The emphasis of the discussion of iodine release into the atmosphere will 

focus on atmospheric (air), water (marine and surface waters), and soils, which are major compartments 

in the geochemical cycling of iodine (Figures 6-4 and 6-5). Throughout this chapter, the units used to 

express concentration or intake of iodine and its radioisotopes are the same units reported by the authors. 

In some cases, values are expressed in mass units, while in other cases, the values are expressed as 

activities (either in Bq or Ci). For 129I, the mass/decay rate equivalencies is 1 g 129I = 6.55 MBq (177 μCi) 

(Robkin and Shleien 1995). For 131I, the specific activity of this radioisotope is 457 TBq/g or 

123,429 Ci/g. For 125I, the specific activity is 67.7 TBq/g or 18,277 Ci/g. 

6.2.1 Air 

Iodine (127I), 129I, and 131I have been identified in 2, 1, and 5 air samples, respectively, collected from the 

1,636 NPL hazardous waste sites where they were detected in some environmental media (HazDat 2004). 

The introduction of iodine into the atmosphere is derived from both natural and human activities 

(Figures 6-4 and 6-5), amounting to approximately 4x107

 kg within the total global atmosphere at an 

average concentration of 10–20 ng/m3

 (Whitehead 1984). The predominant source of iodine in the 

atmosphere is obtained from the transfer of iodine from the ocean to the surrounding atmosphere (FDA 

1974). Evaporation of sea spray is one pathway through which iodine can enter the atmosphere. 

However, a high ratio (ca. 1,000) of iodine to chlorine measured in the atmosphere and rainwater in 

comparison to that found for seawater strongly suggests that other, more important pathways are 

responsible for the transfer of iodine from oceans and the surrounding atmosphere. These could include 

the photochemical or ozone-induced oxidation of iodide to elemental iodine (NCRP 1983; Whitehead 

1984). Indeed, the concentration of ozone near the ocean surface could account for upwards of 6– 

12x107

 kg of iodine released yearly into the atmosphere from the world’s oceans. Yet, the concentration 

of iodine at the ocean’s surface is too low to support this iodide oxidation mechanism as a major 
 

 

IODINE 241 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-4. Geochemical Cycle of Triad Elements (I, Br, Cl) 

Sunlight 

Photolysis of the 

triad compounds

(CH3+hvÿCH3+I, etc.) Clouds Precipitation 

(rain, snow) 

Wet fallout 

(Triad elements 

in rain drops) 

Wind (Transport of the triad compounds) 

Gaseous triad 

Dry fallout

(Gaseous and

particulate 

triad) 

Particulate triad 

Adsorbed by aerosol (Sea salt particulate+dust) 

Inland surface water 

River 

water 

Plant 

Surface sea water Production of CH3I. I2 

(CH3Br), (CH3Cl) by marine

algae, phytoplankton, and 

photochemical oxidation 

Sea water 

(I-, IO3 

-

, Br-, Cl-) 

Spray of sea water

(I-

, IO3 

-

, Br-, Cl-) 

Volatilization 

Gaseous CH3I, I2, (CH3Br), (CH3Cl) 

Source: Yuita 1994a 
IODINE 242 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-5. An Outline of the Movement of Iodine in the Environment* 

Sea Inland 

surface 

water 

Soil 

solution 

Soil 

solid 

material 

12 13 14 

Plants 

Coal 

oil 

17 

Atmosphere 

Gaseous 

iodine 

Particulate 

iodine 

1 1 2 2 3 4 1 2 3 1 2 3 5 

6 10 

11 Animals 

and 

Humans 

8 

7 

9 

Iodised 

salt 

Iodine 

containing

drugs and

sterilants 

Fertilizers 

Herbicides 

Insecticides 

Fungicides 

Groundwater 

15 

Marine 

organisms 

Slurry

Sewage 

Rock 

16 Marine 

sediments 

Lake 

sediments 

Iodophor

detergents

and sterilants 

*1 = deposition in rainfall; 2 = dry deposition (including absorption by plant leaves); 3 = volatilization; 4 = suspension 

of dust; 5 = suspension of marine aerosols; 6 = uptake by plant roots; 7 = decomposition of plant residues; 

8 = consumption of food; 9 = decomposition of animal excreta and residues; 10 = run-off; 11 = irrigation; 

12 = non-specific adsorption/desorption; 14 = immobilization/mineralisation involving soil organic matter; 

15 = leaching; 16 = weathering; 17 = combustion of fossil fuels 

Source: Whitehead 1984 
IODINE 243 

6. POTENTIAL FOR HUMAN EXPOSURE 

contributor to the transfer of iodine into the atmosphere. Instead, it has been suggested that the formation 

of methyl iodide and other alkyl iodides from the biological metabolism of iodine/iodide may, in fact, 

play a major role in the annual transfer of approximately 1.3–2.0x109

 kg of iodine from the ocean into the 

atmosphere (Rasmussen et al. 1982; USNRC 1981; Whitehead 1984). Under this mechanism, the methyl 

iodide that is transferred into the atmosphere can undergo photolytic dissociation into methyl and 

I radicals, with the resultant formation of elemental iodine and other forms of inorganic iodine (HI, HOI, 

INO2, IONO2, OIO, etc.) (Chameides and Davis 1980; Cox et al. 1999; Vogt et al. 1999). Other sources 

of iodine introduction into the atmosphere from the ocean include the release of particulate forms of 

iodine (IO3

-

), iodine-bearing particulates, and/or organically-bound iodine into the marine atmosphere 

with an airborne concentration ranging from 2 to 4 ng/m3

 (NCRP 1983; Vogt et al. 1999; Whitehead 

1984). 

The transfer of iodine from land surface(s) into the atmosphere also occurs, but to a much lesser extent 

than what is observed for the transfer of iodine between the ocean and atmospheric compartments 

(Figures 6-4 and 6-5). It is estimated that 1.6x106

 kg/year of iodine is transferred into the atmosphere 

from surface soils and from the terrestrial biosphere, with an average airborne concentration of iodine 

ranging from 3 to 49 ng/m3

 as both the gaseous and particulate forms of organic and inorganic iodine 

(USNRC 1981; Whitehead 1984). Iodine is transferred into the atmosphere from land sources through 

processes such as volatilization of iodine from soil and suspension of soil. For example, it is estimated 

that approximately 2x1010 g of iodine (as methyl iodide) volatilizes from rice fields worldwide 

(Muramatsu and Yoshida 1995). Like the atmosphere over the ocean compartment, iodine is found in the 

gaseous form ranging from 3 to 45 ng/m3

 versus 0.5–6.9 ng/m3 bound to particulates (Whitehead 1984). 

The ratios of gaseous to particulate forms of iodine (2–5) and inorganic to organic forms of iodine (0.1–2) 

vary, depending on location (Whitehead 1984). 

A natural radioisotope of iodine, 129I, is also introduced into the atmosphere. Sources of 129I include 

interaction of 129Xe with high energy particles in the upper atmosphere and, to a lesser extent, 

spontaneous fission and the reaction of neutrons with 128Te (tellurium-128) and 130Te (tellurium-130) 

(NCRP 1983). This leads to a natural abundance of 129I that varies between 10-12 and 10-15 atoms per atom 

of the stable isotope of iodine, 127I (Soldat 1976). This amounts to approximately 80 kg of 129I in the 

surface environment (e.g., oceans, atmosphere, land) with 5x10-4 kg in the atmosphere (Moran et al. 

1999). Because 129I has a half-life of 1.6x107 years, the introduction of this radioisotope into the 

atmosphere, and the environment as a whole, is cumulative from the standpoint of assessing human 

exposures. 
 

 

IODINE 244 

6. POTENTIAL FOR HUMAN EXPOSURE 

Introduction of iodine and its radioisotopes can occur as a consequence of energy production, nuclear 

weapons production/use, and agricultural and medicinal/research uses. For the stable form of iodine 

(

127I), the introduction of iodine from these manufactured sources is much smaller than that observed for 

the introduction of iodine into the atmosphere from natural sources. However, the introduction of the 

radioisotopes of iodine (i.e., 123I, 125I, and 131I) into the atmosphere, and the environment as a whole, is 

derived mainly from human activities. 

Combustion of fossil fuels also leads to the introduction of iodine from land-based sources (Figure 6-5). 

The average iodine content of coal is reported to be approximately 4 mg/kg, whereas petroleum contains 

iodine at an average concentration of 1 mg/kg (Chameides and Davis 1980). Based on fossil fuel (e.g., 

coal and petroleum) consumption estimates for 1971 of approximately 2,500 million tons of oil equivalent 

per year (Mtoe) per year, this would amount to approximately 4x105

 kg of iodine introduced into the 

atmosphere for that year (0.1% of the total iodine transferred to and from the atmosphere) (Bertine and 

Goldberg 1971; Whitehead 1984). At the current rate of global coal and petroleum consumption of 

approximately 3,000 Mtoe/year, the introduction of iodine into the atmosphere from this source for the 

year 2001 would be 5x105 kg per year (IEA 2000; Whitehead 1984). 

The production and use of nuclear materials for the generation of electrical energy has also contributed to 

the release of iodine and its radioisotopes. 129I is formed in nuclear fission reactions of 235U and 239Pu 

with an atomic yield of 0.12% from uranium and 0.5% from plutonium. The yields of 129I from the 

fission of 235U and 238Pu are 0.9 and 1.7%, respectively (AEC 1974). This gives an approximate ratio of 

4 for 129I/127I in the fission of 235U and 238Pu. Since the nuclear fuel elements are contained in a metal 

cladding, the release of 127I and 129I that is produced in the fission reactions does not occur until the fuel is 

reprocessed. For example, it is estimated that the DOE Savannah River fuel reprocessing plant released 

approximately 2.8 kg/year of 129I during 1964–1965, but has now fallen below 0.7 kg/year since the 

1970s. This amounts to a total of 5.7 Ci (210 GBq or 32 kg) of 129I released during the 1954–1989 

operating history of the plant (DOE 1998; Marter 1993). In 1999, the release into air of 7.27 mCi 

(0.269 GBq or 41 g) of 129I and 10.1 μCi (0.374 MBq or 0.0818 ng) of 131I was reported at the Savannah 

River site (DOE 1999). Releases of 129I from the Hanford Reservation between 1944 and 1995 are 

estimated to be 1,900 GBq (51 Ci or 290 kg 129I) (Robkin and Sheien 1995). The releases of another 

iodine radioisotope, 131I, during the years 1966–1972 was estimated to be 3x105

 Bq (8x10-6 Ci)/MW(e)y 

from fuel reprocessing. From the Savannah site, an estimated 2,520 Ci (93.2 TBq or 20.4 mg) of 131I was 

released from 1954 to 1989 (DOE 1998; Marter 1993). The average releases of 131I from boiling water 
IODINE 245 

6. POTENTIAL FOR HUMAN EXPOSURE 

reactors (BWR) ranges between 2x10-3 Ci (7x107 Bq) and 5x10-3 Ci (2x108 Bq) per MW(e)y, and for 

pressurized water reactors (PWR), the values range from 5x10-5 Ci (2x106 Bq) to 50x10-5 Ci (2x107

 Bq) 

per MW(e)y (NRCC 1980). 

Surface testing of nuclear weapons release of 129I into the environment from nuclear explosions of 235U 

and 239Pu amounted to approximately 30 and 50 μCi (1.1 and 1.9 MBq) per kiloton, respectively. Thus, it 

is estimated that atmospheric testing of nuclear weapons has released approximately 50 kg of 129I into the 

atmosphere. The transport and diffusion of this radioisotope depended on initial height of the nuclear 

cloud and meteorological conditions; residency times were <0.5 years in the lower stratosphere and 

approximately 2 years at medium altitudes. Diffusion of radioisotopes from higher to lower altitudes then 

deposited through either precipitation or dry deposition (NCRP 1983); dry deposition could be as 

important as precipitation in surface deposition of iodine (Machta 1963; Straub et al. 1966). Release of 

131I also occurred during these surface tests of nuclear weapons; however, the 131I that was released into 

the environment from these tests has decayed (half-life of 8.04 days) to levels that are no longer of 

concern in the environment. 

Accidental releases of iodine and its radioisotopes are also sources of iodine introduction into the 

atmosphere. The 1986 Chernobyl reactor accident has released an estimated 1.3 kg of 129I and 1,200– 

1,700 PBq (2.6–3.7 kg) of 131I into the atmosphere (Balonov et al. 1999; Likhtarev et al. 1993; Moran et 

al. 1999; Mould 2000). Other notable accidental releases of 131I include the 1957 Windscale, United 

Kingdom, radiochemical plant fire and the Three Mile Island accident that released approximately 

700 TBq (2 kCi or 2 g) and 0.6 TBq (2 Ci or 1 mg) of 131I, respectively (Likhtarev et al. 1993) 

6.2.2 Water 

Iodine (127I), 129I, and 131I have been identified in 1, 2, and 1 groundwater samples, respectively, and 

no surface water samples collected from the 1,636 NPL hazardous waste sites, where they were detected 

in some environmental media (HazDat 2004). 

Introduction of iodine into surface waters and groundwater occurs predominately through rainwater for 

noncoastal land regions and the combination of rainwater and ocean spray in coastal regions (Figures 6-4 

and 6-5). It is estimated that 1.0x1011 g/year of iodine is deposited onto land surfaces, of which 

8.1x1010 g/year enters surface waters and 1.5x1010 enters groundwater (USNRC 1981). The iodine in 

rainwater is derived from the transfer of iodine from the oceans to the atmosphere (FDA 1974). 
 

 

 

IODINE 246 

6. POTENTIAL FOR HUMAN EXPOSURE 

Other natural releases of iodine into surface waters and groundwater include the leaching of iodine from 

the weathering of rock and volcanic activity (Figure 6-5). It is estimated that rocks contribute between 

1x109

 and 1.6x1010 g/year depending on the iodine content of the rock (0.5–8.8 ppm) (Cohen 1985). 

Volcanic activity can add an estimated 1.2x109 g of iodine per year to the surface environment, where the 

greatest contribution to the oceans is due to undersea volcanic activity (Miyake and Tsunogai 1963; 

USNRC 1979). 

Municipal waste water treatment plants introduce iodine and 131I into surface waters, predominantly 

derived from human waste and the use of 131I in medical treatments. Iodine is poorly captured within 

sludge (2–25%), with the remainder released into surface waters (1.0–16 μg/L) in the waste water stream 

(NAS 1974; Stetar et al. 1993). 

Release of radioiodine has occurred as a result of the reprocessing of nuclear fuel. Release of 129I from 

waste water generated by the Idaho National Engineering Laboratory into Snake River Plain aquifer 

through deep disposal wells (before February 1984) and unlined disposal ponds (1984–1990) amounted to 

approximately 0.56–1.18 Ci (21–44 GBq or 3.2–6.7 kg of 129I) (DOE 1994). This release in both shallow 

and deep groundwater horizons has been minimized through the recycling of the waste stream and storage 

of this stream with high-level radioactive waste. Release of 131I into streams on the DOE Savannah River 

site between 1957 and 1978 totaled 300 Ci (11.1 TBq or 2.43 mg 131I) (DOE 1998). In 1999, 0.0782 Ci 

(2.89 GBq or 441 g) of 129I was released into surface waters at the DOE Savannah River site (DOE 1999). 

The Sellafield (United Kingdom) and Cape de la Hague (France) reprocessing facilities have 

cumulatively released 1,440 kg of 129I directly into ocean waters since operations began in the 1960s; 

direct releases into the ocean amount to 200 kg/year since 1994 and have been increasing (Moran et al. 

1999). 

6.2.3 Soil 

Iodine (127I), 129I, and 131I have not been identified in soil or sediment samples collected from the 

1,636 NPL hazardous waste sites (HazDat 2004). 

The contribution of iodine to soils is derived from natural sources, such as the weathering of rock, decay 

of vegetation, iodine received from rainfall, and from human activities (Figures 6-4 and 6-5). Most soils 

contain, on average, approximately 5 mg/kg of iodine worldwide (Whitehead 1984). It is thought that 
IODINE 247 

6. POTENTIAL FOR HUMAN EXPOSURE 

only a small proportion of this iodine is derived from the weathering of rock (Fuge 1987; Goldschmidt 

1958; Whitehead 1984), although there is some argument to the contrary (Cohen 1985). The natural 

content of iodine in natural geologic materials is (in ppm): ultramafic igneous (0.06–0.3), basaltic igneous 

(0.5), granitic igneous (0.5), shales/clays (212–380), deep sea clays (11–50), limestones (0.4–29), 

sandstones (1.7), and coals/ash (1–11) (NAS 1974). It is expected that the contribution of iodine to soils 

in regions where the bedrock is composed primarily of igneous rock will be much less than that for 

regions where the underlying bedrock is composed of sedimentary rock, which has a higher iodine 

content (Cohen 1985; NAS 1974; Whitehead 1984). 

Wet deposition of iodine from the atmosphere in rain or snowfall contains an average of 2.0 μg iodine/L. 

Assuming an average precipitation rate of 800 mm (32 in) per year, the wet deposition of iodine would 

amount to the addition of 16 g iodine/ha"year (Whitehead 1984). Dry deposition of iodine in a particulate 

form or bound to a particulate carrier can add an estimated 9.6 g iodine/ha"year, assuming a deposition 

rate of 0.2 cm/second and an average concentration of 15 ng/m3

 of particulate iodine (Whitehead 1984). 

However, the iodine that is derived from both the wet and dry deposition will only increase the content of 

the soil (to a 15 cm depth) approximately 0.7 ng/g if all of the iodine is effectively trapped in the soil 

(Whitehead 1984). 

Agricultural activities increase iodine in soils through animal excrement and the use of 

fertilizers/pesticides (Figure 6-5). Animal feces can contain up to 10 mg/kg iodine, and urine can contain 

up to 4 mg/L iodine. The iodine in sewage sludges and fertilizers used in agriculture can vary between 

0.5 and 30 mg/kg. Most inorganic fertilizers contain <0.5 μg/g iodine, except fertilizers containing 

Chilean nitrate, which can provide upwards of 80 μg/g iodine. Superphosphate and compound fertilizers 

derived from rock phosphate can contain up to 26 μg/g iodine (Whitehead 1979). The use of fertilizers, 

however, will not result in an appreciable increase in the iodine content of soil (Whitehead 1984). Yet, 

the use of iodine-containing herbicides, such as ioxynil/ioxynil octanoate (recommended application of 

0.5 kg/ha) and the fungicide benodanil (recommended application of 1.1 kg/ha), can increase iodine 

content of soil about 0.17 and 0.21 μg/g to a depth of 15 cm, respectively (Whitehead 1979, 1984). 

Combustion of coal and petroleum is another source of iodine in soils. In the combustion of coal and 

petroleum, the iodine is introduced to the atmosphere through the flue gases. A large proportion (-80%) 

of the iodine released through the flue gases is deposited onto the surrounding soils by both wet and dry 

deposition, adding approximately 4x105 kg iodine/year to soils globally. 
 

 

IODINE 248 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.3 ENVIRONMENTAL FATE 

6.3.1 Transport and Partitioning 

It is estimated that the earth’s surface contains 6.3x1018 g of iodine. The majority of this iodine is in the 

earth’s crust (3.4x1018 g) and in sedimentary rock (2.9x1018 g). However, this iodine is inaccessible, 

except for the small portion that is liberated through weathering processes (≈109 g/year) and eventually 

enters into the oceans. The ocean, on the other hand, is the largest compartment of accessible iodine that 

can be transferred to other environmental compartments. The earth’s oceans contain 8.1x1016 g of iodine 

(Figure 6-6) at an average concentration of between 45 and 60 μg/L. Other environmental compartments 

with steady-state levels of iodine include atmosphere (8.8x1010 g), surface soil (4.1x1014 g), subsurface 

region (2.5x1013 g), and terrestrial biosphere (3.0x1011 g). The iodine in the ocean is in equilibrium with 

the iodine in ocean sediments (8.0x1017 g), with a net flux of 1.8x1011 g/year. A net transfer of iodine 

also occurs between the ocean surface and the global atmosphere at an average rate of 2.0x1012 g/year, of 

which 1.9x1012 g/year returns to the ocean through wet/dry deposition processes, and 1.2x1011 g/year is 

deposited onto land surfaces. Of the iodine that is deposited on land, 7.7x1010 g/year is returned to the 

ocean through groundwater and river effluents, and 1.6x1010 g/year enters into the terrestrial biosphere, of 

which 1.4x1010 g/year returns to the soil surface through weathering and decay of vegetation (USNRC 

1979). 

The transfer of iodine between the ocean compartment, atmosphere, and land surfaces is due to the 

volatility of iodine in its molecular (I2) and organic (most methyl iodide) forms. The extent to which 

iodine partitions into these compartments, and its residency time, will depend on the chemical form of the 

iodine as it enters into a specific compartment, any chemical alterations that the iodine undergoes in that 

particular compartment, and the solubility/uptake/retention of the various chemical forms of iodine in the 

compartment. The formation of alkyl iodides (predominantly methyl iodide) and, to a lesser extent, 

molecular iodine from biological activity and photochemical reactions on the ocean’s surface, provide for 

the transfer of these iodine species into the ocean atmosphere, where they undergo further photochemical 

conversions into other gaseous and particulate forms of iodine (Cox et al. 1999; Filistovic and 

Nedveckait 1998; Vogt et al. 1999; Whitehead 1984). The relative proportions of iodine as inorganic 

particulates and organic gaseous forms are on average 25% for particulates and 40–80% for organic forms 

as methyl iodide (Moran et al. 1999). The residence times for iodine in the atmosphere are 14 days for 

particulates, 10 days for inorganic gases (i.e., I2), and 18 days for organic gases (compared to a 9-day 
 

Ocean 

atmosphere 

8.3x1010 g 

1.9x1012 2.0x1012 

g/year g/year 

Ocean 

75 m mixed layer 

1.4x1015 g 

7.2x1013 7.2x1013 

g/year g/year 

Deep ocean 3,725 m 8.1x1016 g 

1.8x1011 1.8x1011 

g/year g/year 

Ocean 

sediments 

8.0x1017 g 

Hydrosphere 

Source: Kocher 1981 

1.2x1011 

1 g/year 2 

Land 

2.0x1010 atmosphere

g/year 5.7x109 g 

6.2x1010 

3 g/year 4 

1.6x109 

g/year 5 

Terrestrial 1.6x1010 

g/year biosphere 

3.0x1011 g 

1.4x1010 

g/year 

6 

7 

Surface soil
 

region
 

4.1x1014 g
 

1.5x1010 1.5x1010
 

g/year
 g/year 

8 Shallow
 

subsurface
 2.9x108 

g/year region
 

1.4x1013 g
 

2.9x108 

g/year 

9 Deep 

subsurface 

region 

1.1x1013 g 

Lithosphere 

IODINE 249 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-6. Diagram of the Global Iodine Cycle at Steady State Showing 

Environmental Compartments, Compartment Inventories in Grams (g), 

Transport Pathways, and Fluxes in Grams per Year (g/year) 
 

 

 

IODINE 250 

6. POTENTIAL FOR HUMAN EXPOSURE 

residency time for water vapor), providing for extended global transport and substantial mixing (Moran et 

al. 1999). 

The gaseous and particulate forms of iodine in the atmosphere are deposited onto ocean or land surfaces 

through wet and dry deposition. Gaseous elemental iodine and particulate forms of iodine are susceptible 

to wet deposition, whereas methyl iodide has a low susceptibility. Accordingly, gaseous molecular iodine 

and particulate forms of iodine are susceptible to dry deposition; methyl iodide has a low susceptibility 

(Whitehead 1984). 

The dry deposition rate is dependent on particle size, wind speed, and turbulence. Iodine will settle onto 

soil and plant surfaces. Direct deposition of iodine onto plant surfaces is limited to 7.5–14 days, where 

particulate iodine is removed from plant surfaces through weathering processes (AEC 1974; Heinemann 

and Vogt 1980; Kirchner 1994). Dry deposition onto plant surfaces is affected by the moistness of the 

surface; deposition is approximately 2-fold greater on moist plant surfaces versus dry surfaces 

(Heinemann and Vogt 1980). Also, dry deposition onto plants is affected by the surface area of the plant, 

as is evident from the 2-fold increase in iodine deposited on clover versus grasses (Heinemann and Vogt 

1980). 

The wet deposition of iodine will be predominantly deposited into soil. The relative amounts of iodine 

initially depositing onto the soil will greatly depend on the density and type of plant cover over the soil. 

Upwards of 90% of elemental iodine vapor can be intercepted by a dense cover of grassland herbage, but 

40–70% can typically be expected to be intercepted by a more average density of plant cover (Whitehead 

1984). 

Evaporation of iodine from the land surface to the atmosphere is only about 1% of the flux of iodine from 

the atmosphere to the land surface (USNRC 1979) and iodine is cycled back to the ocean through 

groundwater and river effluent (USNRC 1979; Whitehead 1984). However, the overall content of iodine 

in a soil is determined by the inputs of iodine into the soil and the ability of the soil to retain iodine 

(versus leaching and volatilization), where the main input is from atmospheric deposition, both wet and 

dry, followed by degradation of plant material (mostly from adsorbed iodine) (Whitehead 1984). 

The low flux of iodine from land surfaces to the atmosphere is due to the retention of iodine within 

surface soils, especially in soils rich in organic matter and iron/aluminum oxides (Sheppard et al. 1995). 

When the various chemical forms of iodine enter into the soil, these species are initially retained by their 
 

 

 

 

IODINE 251 

6. POTENTIAL FOR HUMAN EXPOSURE 

absorbance onto soil components in equilibrium with their solubility in soil solution. Isotopic exchange 

studies indicate that between 5 and 30% of iodine is exchangeable (Whitehead 1984). Retention of 

inorganic and organic iodine will depend on both nonspecific and specific sorption onto soil components. 

Nonspecific ion-exchange interactions of iodide and iodate anions occur on free hydrous oxides of iron 

and aluminum; such exchanges involve electrostatic attractions and are dependent on pH and the 

concentration of other anions (Sheppard et al. 1995). Retention of molecular iodine in soil is thought to 

be mediated through the interaction of iodine with thiols and polyphenols present in the organic 

components of soils (Fawcett and Kirkwood 1953; Jirousek and Pritchard 1971; Whitehead 1984) and 

may also involve the oxidation/reduction of iodide and free radical reactions (Huang and Lu 1991). 

Methyl iodide is sorbed by soils to a lesser extent than inorganic iodide, but the factors that determine this 

sorption of methyl iodide to soils are unclear (Whitehead 1984). 

Transport of iodine to lower soil depths is dependent on the porosity and saturation of the soil. 

Macropores formed from roots and earthworm channels allow for rapid transport of iodine into the soil. 

Mobility of iodine into the soil is greatest when the soil is saturated with water. The drier the soil, the 

thinner the water films within the soil, thus limiting the flow rate of water through the soil (Whitehead 

1984. 

In addition to the aforementioned direct deposition of particulate deposition of iodine onto plant surfaces, 

there is also evidence of the uptake of inorganic iodine into the plant through the roots and gaseous iodine 

through the leaves (Whitehead 1984). Iodide is more readily taken up into plant roots than is iodate or 

iodine (Burte et al. 1991; Whitehead 1984); the uptake is dependent on the concentration of iodine in the 

soil, the properties of the soil, and the use of fertilizers (Moiseyev et al. 1984; Shinonaga et al. 2001). 

Soil-to-plant transfer factors (TF), which are defined as the grams iodine per kilogram wet or dry weight 

of plant material divided by the grams of iodine per kilograms dry soil, typically range between 0.001 and 

1.5 for plants of agricultural importance (Shinonaga et al. 2001). Molecular iodine can be absorbed 

through the stomata in the leaves, whereas methyl iodide and hypoiodous acid are not as readily absorbed 

through this route (Whitehead 1984). 

Both the deposition of particulate iodine onto plant surfaces and the direct uptake of iodine into the plant 

factor into the transfer of iodine through the soil-plant-cow-milk pathway. The level of iodine in feed has 

a direct relationship with the level of iodine measured in milk (Tracy et al. 1989; Voigt et al. 1989) and is 

dependent on the season, nutritive quality of pastureland, and ambient temperature (Ekman et al. 1967; 

Lengemann and Wentworth 1979; Pennington 1990a). The transfer coefficient for iodine through the 
 

 

IODINE 252 

6. POTENTIAL FOR HUMAN EXPOSURE 

total pathway is approximately 0.003–0.01 for cow and 0.2 for goat, expressed as the fraction of daily 

intake per liter milk (d/L) (AEC 1974; Kirchner 1994; Voigt et al. 1988, 1989). 

Transfer of iodine in the feed-meat pathway has also been determined in various animals and tissues. 

Transfer factors in whole animals (expressed as the fraction of daily intake per kg [d/kg]) are 0.02 (beef), 

0.09 (pork), and 0.004 (chicken). The thyroid is the organ with the greatest uptake of iodine (AEC 1974). 

Individual tissue measurements have transfer factors range from 10-4 (kidney) to 10-3 (liver) to 

10-2 (muscle) (Handl and Pfau 1989; Handl et al. 1990). Transfer factors have also been determined for 

feed-chicken eggs (0.03) (AEC 1974). 

Iodine can also bioaccumulate to varying extents in aquatic organisms. Aquatic bioaccumulation factors 

for iodine in fresh water are 40 (algae), 5 (invertebrates), and 15 (fish); in salt water, these factors are 

4,000–10,000 (algae), 50–100 (invertebrates), and 10–20 (fish) (AEC 1974). Certain seaweeds and algae 

can concentrate iodine to levels as high as 0.8–4.5 g/kg of dried material; these high levels are usually 

associated with the relatively high levels of iodine in seawater (50 μg/kg) (FDA 1974). 

6.3.2 Transformation and Degradation 

Iodine consists of one stable isotope (127I) and a number of radioisotopes, of which 123I, 125I, 129I and 131I 

are the most common in environmental and occupational exposures. The radioisotopes 129I and 131I decay 

by β-emission to form 129Xe and 131Xe, respectively, whereas 125I decays by electron capture, emitting 

gamma and Te x-rays. 125I and 131I disappear rapidly from the environment due to their short half-lives of 

60 and 8.04 days, respectively, and do not undergo long-term accumulation in the environment. 

However, the long physical half-life of 129I (1.57x107 years) means that any release of this radioisotope 

into the environment is essentially a permanent addition to the total inventory of iodine in the 

environment from the standpoint of assessing human exposures (NCRP 1983). 

The chemical reactions of iodine and its radioisotopes within the environment are the same, but the ratios 

of the isotopes in these reactions may differ, depending on the relative concentrations of the isotopes in a 

particular environment. 127I and its radioisotopes can exist in many forms and oxidation states (iodides 

[-1], molecular iodine [0], iodohalides [+1], iodates [+5], and periodates [+7]) (Holland 1963); organic 

forms of iodine include methyl iodide, ethyl iodide, isopropyl iodide, and methylene iodide (Vogt et al. 

1999). Thus, “iodine” in the discussion of the chemical reactions of iodine in the environment will be 

used to refer to both iodine and its radioisotopes, unless indicated otherwise. 
 

 

IODINE 253 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.3.2.1 Air 

The major source of iodine in air is from the evaporation of alkyl iodides (mostly methyl iodide) and, to a 

lesser extent, molecular iodine from ocean surfaces (Figures 6-4 and 6-7). At ordinary pressures and 

temperature, methyl iodide and iodine have high vapor pressures and will exist predominately in a free 

gaseous form in air. Both iodine and methyl iodide undergo photochemical reactions to form iodine 

radicals (IC), which can then go on to form a number of other iodine species through a complex series of 

reaction pathways (Cox et al. 1999; Filistovic and Nedveckait 1998; Vogt et al. 1999); some of these are 

shown below and in Figure 6-4. 

I2 ÷ 2 IC

 CH3I ÷ CH3C + IC

 IC + HO2C ÷ HI + O2

 IC + NO ÷ INOC

 IC + NO2 ÷ INO2C

 IC + O3 ÷ IOC + O2

 IOC + NO2 ÷ IONO2C

 2IOC ÷ I2O2

 2IOC ÷ OIOC + IC

The overall photochemical dissociation of CH3I and I2 in the atmosphere results in the steady-state 

formation of inorganic iodine species consisting mostly of IONO2C (75%), IOC (15%), and 

HI+HOI (10%) during the daytime. Only minor changes in these percentages are observed during the 

night-time, IONO2C (75%), IOC (7%), and HI+HOI (18%) (Filistovic and Nedveckait 1998). 

Some of these iodine species (e.g., IOC, I2O2) can then go on to react in aerosols or water droplets to form 

IO2

- and IO3-

(Figure 6-7). Gaseous iodine can also dissolve in water droplets to form iodide or 

hypoiodate ions, especially in the presence of alkaline impurities. Iodine is readily reduced to iodide by 

hydrogen sulfide and can be oxidized to free iodine by ozone, hydrogen peroxide, or possibly air and 

sunlight. If the iodine is acidified sufficiently, gaseous hydrogen iodide is liberated (Straub et al. 1966). 

Conversely, HI formed in air can dissolve in water droplets, forming iodide anions that can be oxidized to 

molecular iodine. 
IODINE 254 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-7. A Simplified Scheme of Iodine Cycling in the Marine Boundary Layer* 

ICI 

IO 

I 

HOI 

IONO2 

IBr 

INO2 

I2 

HI 

I2O2 

CH3I CH2I2 C3H7I CH2CII 

hv hv hv hv 

hv 

hv 

-NO 

+IO 

+BrO 

+CIO 

+DMS 

+O3 

+HO7 

+NO2 

a

ICI IBr 

I2 

I

­

HOI 

Aerosol 

+IO 

+Br +I 

+HOI 

IOaq 

IO2 

-

+Cl 

+IO2 

IO3 

-

Ocean 

*Organic iodine compounds are shown in rectangular boxes; temporary iodine reservoir species in the gas and in the 

aerosol phase are shown in octagons 

Source: Vogt et al. 1999 
 

 

 

IODINE 255 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.3.2.2 Water 

Iodine in water exists as iodide and iodate. In rainwater, the relative proportion of iodide to iodate is 

55:45. In surface waters, the proportion of iodide to iodate will vary depending on microbial activity and 

the release of iodine species from terrestrial sources (De Luca Rebello et al. 1990). Iodide is also 

converted in the surface layer of seawater to hypoiodous acid (HOI) by photochemically generated ozone 

(Bichsel and von Gunten 1999). Microbial action converts iodide to organic forms of iodine, primarily 

methyl iodide (iodomethane). The low vapor pressure and limited solubility in water promote the 

volatilization of methyl iodide from surface waters to the surrounding atmosphere. Likewise, microbial 

activity and photochemical reactions, including photolysis of biogenic iodine, can lead to the formation of 

iodine from iodide or iodate; iodine can evaporate into the atmosphere due to its low vapor pressure (Xie 

et al. 1999). In marine waters, up to 40% of iodine can be found as dissolved organic iodine (DOI), with 

the remainder as iodide (Wong and Cheng 1998). 

Disinfection of natural waters results in the oxidation of iodide to hypoiodous acid (HOI) (Bichsel and 

von Gunten 1999). Ozone, chlorine, and monochloramine easily oxidize iodide to HOI. Ozone, at 

concentrations used in the disinfection of water, rapidly oxidizes HOI and hypoiodate (OI-

) to iodinate 

(IO3

-

), whereas chlorine oxidizes HOI in a slower, more complex reaction mechanism. Monochloramine 

was unable to oxidize HOI. As a consequence, the formation of iodoorganics (e.g., iodoform or CH3I), 

which results from the reaction of HOI with organics in natural waters and often causes a problems with 

the taste and odor of drinking water, is much more prevalent when chlorine and chloramines are used as 

oxidants in the disinfection process. 

6.3.2.3 Sediment and Soil 

Iodine can enter sediments through accumulation of plant matter or fixation of iodide in water to humic 

substances in the sediments through microbial action (R@dlinger and Heumann 2000). Weaker and 

reversible binding of iodide to inorganic components in sediments has also been shown to occur, with 

affinities measured as partition coefficients [Kds] ranging from -0.22 mL/g for chlorite minerals to 

15.14 mL/g for illite minerals (Kaplan et al. 2000). Iodine can enter soil as I2, iodide, iodate, or methyl 

iodide through wet or dry deposition. Molecular iodine dissolves in soil water to form iodide or is 

oxidized to iodate. Conversely, chemical, and to a lesser extent, microbial, reduction of iodide or iodate 
 

 

IODINE 256 

6. POTENTIAL FOR HUMAN EXPOSURE 

forms molecular iodine that can evaporate from the soil water into the atmosphere. Iodine can react with 

organic components of soil, such as humic substances, undergoing iodination reactions with polyphenols 

and tyrosine residues (Fawcett and Kirkwood 1953; Jirousek and Pritchard 1971; Whitehead 1984), 

which may involve the oxidation/reduction of iodide and free radical reactions (Huang and Lu 1991). 

Decreases in pH can alter the proportion of iodide to iodate in soil and water due to the protonation of 

iodide to form HI, which can volatilize into the atmosphere. The relative proportions of iodine species 

can also differ in soils under flooded and nonflooded conditions. The proportions of I2:I-

:IO3

-

:organic 

iodine change from 0.045:0.065:0.89:0.016 under the oxidizing nonflooded conditions to 

0.007:0.90:0.097:0 under the reducing flooded conditions (Yuita 1994a). 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

6.4.1 Air 

The average global air iodine concentration ranges between 10 and 20 ng/m3

 with gaseous iodine usually 

exceeding particulate iodine by a factor of 2–6 (Whitehead 1984). Atmospheric concentrations over land 

range from 2 to 14 ng/m3

, while atmospheric levels over oceans average between 17 and 52 ng/m3 

(USNRC 1979). In an urban air environment, iodine content in air over San Francisco in 1970 ranged 

between 4.7 and 10 ng/m3 over nine monitoring stations (John et al. 1973). In remote air environments, 

for example the arctic, the iodine concentrations fall dramatically. Iodine in the arctic stratosphere is 

0.27 ng/m3

, and is 0.33 ng/m3 at the marine boundary layer (Sheridan and Zoller 1989). The annual 

average concentration of iodine in Canadian arctic air ranges between 0.43 and 0.96 ng/m3

 (Barrie and 

Hoff 1985) 

Iodine introduction in the form of methyl iodide emission from a municipal waste incineration plant has 

been measured at an average of 0.50 μg/m3

 in Karlsruhe, Germany (Stieglitz 1995). 

Radioiodine releases from nuclear fuel reprocessing facilities have been well documented. Discharges of 

129I from the Hanford Reservation between 1983 and 1992 ranged from 0.02 to 0.6 Ci/year, with a 

maximum output of 0.5–0.6 between 1986 and 1988 (DOE 1993). The average airborne concentrations 

of 129I onsite ranged from 69–2,000 to 2.2–60 attoCi/m3

 (atto=10-18) along the perimeter to 0.13– 

2.4 attoCi/m3

 at distant monitoring sites (DOE 1993). At the Savannah River site, 129I and 131I releases 

between 1954 and 1989 totaled 5.67 and 2.52 Ci, respectively (DOE 1990). Discharges of 129I into the air 

from the Sellafield (United Kingdom) and La Hague (France) nuclear processing facilities is thought to 
 

 

 

IODINE 257 

6. POTENTIAL FOR HUMAN EXPOSURE 

contribute to the 4–40x108 atoms 129I/L (15–150 attoCi/L or 0.086–0.86 ng/L) measured in rain and snow 

over Sweden between 1998 and 1999, although it is not clear how much of these releases contributed to 

the total concentration of 129I in precipitation (Buraglio et al. 2001). Strong seasonal variations in the 

concentration of 129I in precipitation are observed, due to such factors as seasonal changes in the 

volatilization of CH3

129I from soils and decaying plant matter, and seasonal changes in weather patterns 

that determine the source and availability of moisture in the Baltic region. 

The release of radioiodine into the atmosphere from nuclear weapons testing and its deposition onto 

distant targets has been measured. 131I that was produced in the above-ground nuclear Test Harry and 

deposited (wet) on select New England monitoring sites ranged from 0.2x109

 Bq/km in Buffalo to 

3.4x109

 Bq/km in Pittsburgh to 6.1x109 Bq/km in Binghamton (Hoecker and Machta 1990). The 

emissions of radioiodine are often associated with particulates. The amount of 131I associated with 

particulates increases with the distance from the source of release. Upwards of 60% of 131I released into 

atmosphere is associated with particulates, based on ground-level measurements. It is assumed that 80– 

85% of the fallout of 131I is in the reduced state, 15–20% is present as IO3

-

, and a few percent or more is 

- present as IO4 (Perkins 1963; Straub et al. 1966). The cumulative release of 129I (expressed as Ci) in 

nuclear weapons testing beginning in 1945 and ending in 1975 has been estimated and is shown in 

Table 6-1 (NCRP 1983). 

6.4.2 Water 

The average iodine content in seawater is 40–65 μg/L (USNRC 1979). The iodine content in rainwater 

averages between 0.1 and 15 μg/L, and in rainwater over oceans, the iodine content is 1–15 μg/L 

(USNRC 1979). The iodine content in river water averages between 0.1 and 18 μg/L (USNRC 1979). 

The concentration of iodine in river water will be locally influenced by municipal waste water streams. 

The average iodine content in municipal waste water effluent is 4.0 μg/L (range 1.0–16 μg/L) (NAS 

1974). In groundwater, the average iodine concentration is 1 μg/L (Yuita 1994a). 

The concentration of 129I in ocean surface waters averages between 107

 and 108 atoms 129I per kg (Cooper 

et al. 2001). Some examples reported by Cooper et al. (2001) are 0.18–0.82x108

 atoms 129I/kg in the 

Bering, East, and Chukchi Seas, with several concentrations as high as 9.60x108

 and 16.7x108 atoms 

129I/kg in the Chirikov and Chukchi benthic zones, respectively. Cooper et al. (2001) also showed that the 

concentration of 129I in ocean waters varies as a function of depth of the water column. In the East Sea 
IODINE 258 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Approximate Releases of 129I from Atmospheric and High Altitude

Nuclear Weapons Tests 

Year Cumulative 129I Released (Ci) 

1945–1951 0.04 

1952–1954 2 

1955–1956 3 

1957–1958 5 

1959–1961 6 

1962–1963 10 

1963–1975 10 

Source: NCRP 1983 
IODINE 259 

6. POTENTIAL FOR HUMAN EXPOSURE 

 (Sea of Japan), the concentration of 129I decreased from approximately 0.35x108 atoms 129I/kg in surfaces 

water to 0.05x108

 atoms/kg at a depth of 2,000 meters, but increased again to 0.15x108 atoms/kg at a 

depth of 2,800 meters near the sea floor (3,000 meters). It is suspected that the increase in 129I 

concentration near the sea floor is due to a flux of iodine from sediments (129I concentrations in sediments 

were 168–902x108

 atoms/kg), although this could not be confirmed in their study. 

The iodine content in drinking water typically varies between 0 and 8 μg/kg, with a more nominal range 

averaging between 2 and 4 μg/kg. Concentrations of iodine in drinking water approaching or exceeding 

8 μg/kg are usually associated with water that is directly contaminated with sewage or effluent from 

sewage discharge sites or from urban run-off (FDA 1974). For example, the concentration of iodine in 

the Potomac River was 4.0 μg/L upstream of Alexandria, but increased to 8.0 μg/L downstream. Sewage 

effluent from Alexandria was believed to be the cause. Some effluent streams can have iodine 

concentrations as high as 1,910 μg/L (FDA 1974). 

Seasonal variations in iodine have been measured in Rhode Island precipitation. The volume-weighted 

mean concentration in annual precipitation is 1.71 μg/L, with a concentration range of 0.04–11.3 μg/L. 

The seasonal variations in volume-weighted iodine concentration were 2.14 μg/L during the warm season 

and 1.35 μg/L during the cold season (Heaton et al. 1990). 

Radioiodine is released into surface waters through the effluent of municipal sewage treatment plants. On 

an average working day, approximately 24 mCi (0.89 GBq) of 131I is released into the Ohio River, 

resulting in a concentration of 0.3 pCi (11 mBq) 131I/L downstream from the treatment plant (Sodd et al. 

1975). The concentration of 131I in water downstream from other municipal treatment plants throughout 

the United States has also been determined, ranging from 0 to 83 pCi (0 –3.1 Bq) 131I/L (Prichard et al. 

1981). The 131I that has been measured in these waters is due to the introduction of 131I into the sewer 

systems of cities from the excrement of patients undergoing treatments with this radioisotope. 

The release of 129I into surface waters has also been measured. It has been estimated that the aboveground total fission yield of a 207 megaton equivalent of plutonium fission devices contributed 

approximately 10 Ci (370 GBq) of 129I to the environment (NCRP 1983). Reprocessing of spent fuel 

could release additional amounts of 129I into the environment (at most 2 Ci or 70 GBq) depending on the 

amount of fuel that is reprocessed and the efficiency of gaseous effluent decontamination equipment. 

This has resulted in an increase in the ratio of 129I/127I, which has been changing since 1945 due to the 

release of 129I into environment from nuclear weapon explosions and nuclear facilities. These releases 
IODINE 260 

6. POTENTIAL FOR HUMAN EXPOSURE 

range from 10-8–10-7 in the ambient environment to 10-4–10-3 near some nuclear facilities, as measured in 

thyroid tissues (NCRP 1983). The release of 129I has also resulted in a steady-state inventory of 

8.7x1026 atoms (31 Ci or 1.8x105

 g) of 129I in the oceans (AEC 1966). Slow releases of 129I from
 

radioactive waste dump sites in the North Atlantic and Pacific Oceans, Arctic Ocean, Sea of Japan, and 

Sea of Okhotsk are also contributing to increased inventories of 129I in ocean waters (Povinec et al. 2000). 

The concentrations of 129I can vary significantly. 

The average content of 127I and 129I in air over the United States varies between 0.6 and 12.1 ppb 

(Table 6–2). These 129I concentrations did not appear to differ greatly between coastal (e.g., Galveston, 

Texas) and interior (e.g., Lafayette, Indiana) measurement sites (Moran et al. 1999). The measured ratios 

of 129I to 127I in air and in precipitation was found to vary, ranging between 2.03 and 27.90 (x10-12) in air 

and between 755 and 12,390 (x10-12) in precipitation (Moran et al. 1999). These variations in the ratios of 

129I to 127I may reflect the distances of the various collection sites from the sources of these isotopes (e.g., 

distance from coastal regions for 127I and distance from nuclear fuel reprocessing facilities for 129I) 

(Moran et al. 1999). 

The effect of 129I release from nuclear fuel reprocessing facilities on surface water and groundwater has 

been measured. In 1990–1991, 129I concentrations in the Snake River aquifer at and near the Idaho 

National Engineering Laboratory range between 0.6 aCi/L (22 nBq/L) and 3.82 pCi/L (0.141 Bq/L), with 

a mean of 0.81 pCi/L (30 mBq/L), which is a change from 1.30 pCi/L (48.1 mBq/L) measured in 1986. 

This change reflects a decrease in the amount of 129I disposal and changes in disposal techniques (DOE 

1994). Between January 1993 and June 1994, 129I concentrations measured at 29 sites in and around the 

Savannah River site in surface waters ranged between 0.027 and 3.2 pCi/L (1.0 and 120 mBq/L) and are 

primarily derived from continued discharges of 129I from the facility (Beals and Hayes 1995).
 

6.4.3 Sediment and Soil 

The natural occurrence of iodine in igneous and sedimentary rock is approximately 0.2–5.8 ppm and it is 

5–10 times higher in shales rich in organic matter, in soils, and in coals (NAS 1974). Some references 

indicate that these estimates may be low, suggesting instead an average soil content for iodine as high as 

5.85 ppm (range: 1.5–13.5 ppm) (NAS 1974). Indeed, in one survey of iodine content in soils 

(Table 6-3), the iodine concentration in common soil types is consistent with the mean of 5.85 ppm 

(Whitehead 1979). This survey also shows the large variation in iodine concentrations as a function of 

soil type (Whitehead 1979, Table 6-3). In a study of the iodine concentration of soils in the contiguous 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

IODINE 261 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-2. Concentration of Iodine, Chloride, and 129I/127I Ratio in Air and 

Precipitation as a Function of Location and Collection Time 

Air Rain/Snow 

Locationa I (ppb) 129I/127I (10-12) 129I/127I (10-12) 129I atoms/L (107

) Cl­(ppm) I/Cl 

WL 12/95-2 1.4 12.03 5,756 3.7 

WL 12/95-3 0.9 12.45 8,327 3.7 0.2 0.0045 

WL 12/95-4 0.6 13.85 12,390 3.7 

B 11/95 1.2 7.38 2,027 1.1 1.6 0.0008 

CS 8/22/96 6.6 10.39 755 2.3 

CS 9/1/96–9/15/96 1.9 4.17 913 2.4 0.3 0.0061 

CS 9/15/96–10/15/96 2.5 

CS 10/20/96–10/26/96 2.0 1.2 0.0017 

CS 10/26/96–11/24/96 1.7 2.03 893 0.7 1.1 0.0015 

CS 11/24/96–11/30/96 3.3 1.6 0.0021 

CS 12/21/96–1/16/97 2.9 26.80 3,408 4.5 

CS 1/20/97–1/30/97 2.5 7.60 2,121 2.5 

CS 2/20/97–2/26/97 1.8 5.30 975 0.9 

CS 3/18/97-1 1.4 

CS 3/18/97-2 1.3 

CS 3/18/97-3 0.6 

CS 3/18/97-4 0.8 

CS 3/18/97-5 0.7 

G 1/96–10/96 1.9 9.44 1,735 1.6 

G 11/96 12.1 27.90 1,064 6.0 46.5 0.0003 

G 12/6/96–1/6/97 1.7 4.9 0.0003 

G 1/7/97–1/16/97 1.2 14.87 3,946 2.3 

Ohio snow 1/14/97 0.7 11.10 9,150 3.0 

a

WL = West Lafayette, IN; B = Bryan, TX; CS = College Station, TX; G = Galveston, TX 

Source: Moran et al. 1999 
IODINE 262 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-3. Iodine Content in Specific Soil Types 

Soil Concentration of iodine (μg/g dry soil) 

Acid igneous rocks and associated till 10.4 (4.4–15.7)a 

Till associated with basic igneous rocks 10.9 (3.4–16.3) 

Slate, shale, and associated till 9.8 (4.4–27.6) 

Sand and sandstone 3.7 (1.7–5.4) 

Chalk and limestone 12.3 (7.9–21.8) 

Clay 5.2 (2.1–8.9) 

River and river terrace, alluvium 3.8 (0.5–7.1) 

Marine and estuarine alluvium 19.6 (8.8–36.9) 

Peat 46.8 (18.7–46.8) 

a

Average iodine concentration with the range of measurements given in the parentheses 

Source: Whitehead 1979 
 

 

IODINE 263 

6. POTENTIAL FOR HUMAN EXPOSURE 

United States, the average iodine concentration in soils was 1.2 μg/g. This average does not differ 

between soils measured in the western United States (west of 96th meridian) (1.2 μg/g) or the eastern 

United States (1.2 μg/g) (USGS 1984). Iodine concentration in soils has also been measured as a function 

of soil depth (Table 6-4), showing minimal variation in iodine concentration to depths of 12–24 inches 

(Fuge 1987). The data in Table 6-4 also show that soil concentrations were typically higher than the 

concentration of iodine in the underlying bedrock. 

The iodine content in sewage sludges ranges between 1.0 and 17.1 μg/g dry weight; these values are 

similar to those found in soils, with the mean for iodine in sludges generally being lower. Iodine content 

of sludges was not related to size or degree of industrialization of a particular city or town. 

Measurements of iodine in sludge indicate that iodine does not partition strongly into sludges (Whitehead 

1979). 131I content in sludge generated from the Oak Ridge municipal waste water plant averages 

0.16 nCi/L (5.9 Bq/L or 1.3 fg/L). The background concentration of 131I content in sludge generated at a 

municipal sewage treatment in Ann Arbor, Michigan, was reported to be 1.4 pCi/L (52 mBq/L or 

0.011 fg/L), but could rise as high as 15 pCi/L (0.55 Bq/L or 0.12 fg/L) (Fenner and Martin 1997). These 

concentrations of 131I in sewage sludge are due to the introduction of 131I into city sewer systems from the 

excrement from patients who are undergoing treatment therapies that utilize 131I (Stetar et al. 1993) 

The soil content of 129I has been compared to 127I and has been found to be generally higher near nuclear 

fuel reprocessing facilities than elsewhere. The 129I/127I ratios near facilities range between 10-4 and 10-3, 

whereas more remote locations yield ratios between 10-9 and 10-8 (Robens and Aumann 1988). 

6.4.4 Other Environmental Media 

Iodine content of aquatic plants varies, depending on whether they are fresh or salt water. Freshwater 

algae contain 10-5% by weight of iodine, whereas marine algae contain 10-3% by weight (NCRP 1983). 

For example, concentrations of iodine have been measured in edible marine algae obtained from the St. 

Lawrence River, which vary as a function of species. Enteromorpha and Porphyra had the lowest 

average concentrations of iodine of 22.7 and 31.7 μg/g (dry weight) in contrast to Ascophyllum nodosum 

and Laminaria longicruris, which contained the highest average iodine concentrations of 482 and 

763 μg/g (dry weight) (Phaneuf et al. 1999). 

Epiphytes (plants that have no root systems and acquire their nutrients from the air), such as Spanish 

moss in the southern United States, are used to measure long-term exposures of airborne trace elements. 
IODINE 264 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. Iodine Content in Missouri Soils as a Function of Depth and 

Parent Material 

Bedrock Soil depth (inches) Iodine concentration (μg/g) 

Sandstone 0–5 0.80 

5–8 0.78 

8–12 1.05 

Bedrock <0.04 

Dolomite 0–4 0.89 

4–8 0.85 

8–12 1.13 

12–18 1.08 

18–24 1.28 

Bedrock <0.04 

Alluvium-river valley 0–3 

3–6 

0.91 

0.65 

6–12 0.72 

12–18 0.91 

Limestone (thin soil) 0–3 5.98 

Shale 0–6 1.02 

6–12 1.03 

12–18 1.13 

Bedrock 0.37 

Granite 0–5 2.90 

5–10 5.00 

10–15 7.21 

Bedrock <0.04 

Glacial material 0–5 0.12 

5–10 0.31 

10–15 0.68 

15–20 0.28 

20–24 0.53 

Source: Fuge 1987 
IODINE 265 

6. POTENTIAL FOR HUMAN EXPOSURE 

The concentration of 129I in Spanish moss varies between 0.4 and 4.9 ppm and roughly correlates with 

estimated airborne concentrations of 129I (Moran et al. 1999). In Norway, the iodine in moss averages 

3.3 ppm (Schaug et al. 1990). 

The average content of iodine in terrestrial plants has been reported to be 0.42 mg/kg worldwide (Yuita 

1994a). In some specific examples, iodine content (mg/kg) has been measured at 0.60–2.6 in beet root 

flesh; 0.1–2.4 in cabbage head; and 0.30–1.1 in corn kernel (Sheppard et al. 1993). The iodine content in 

hay has been measured at 0.08 μg/g fresh weight feed (Voigt et al. 1988). The distributions of I2 in 

plants, such as wheat, can vary over the various parts of the plant. In wheat, iodine concentrations 

(μg/mg) change between shoots (0.136), roots (0.206), and total plant (0.153). For iodide, the distribution 

throughout the plant differs as well. In wheat, the iodide concentrations (μg/mg) are 0.645 in shoots, 

0.100 in roots, and 0.261 in plant (Voigt et al. 1988). 

The 129I content in deer thyroids has been assessed as a function of proximity to a nuclear fuel processing 

facility. The 129I thyroid concentrations were highest in deer captured near the nuclear fuel reprocessing 

plant at the Savannah River Site, South Carolina (1–102 Bq/g or 0.03–2.8 nCi/g thyroid in 6.8% of deer) 

and Oak Ridge, Tennessee (0.01–1.0 Bq/g or 0.3–27 pCi/g thyroid in 38% of deer). However, no 

thyroids from deer in Florida or in west Tennessee, which are distant from nuclear fuel processing 

facilities, contained 129I at concentrations above 4 mBq/g or 0.1 pCi/g thyroid (Van Middlesworth 1993). 

Iodine measurements in milk and milk products have yielded the following results (expressed as 

μg/100 g): low fat milk (24), skim milk (21), buttermilk (24), chocolate milk (25), plain lowfat yogurt 

(33), strawberry lowfat yogurt (17), evaporated milk (37), half-and-half (17), cottage cheese (27), 

American cheese (49), cheddar cheese (47), chocolate fast-food milkshake (55), chocolate ice cream (47), 

vanilla ice milk (30), ice cream sandwich (51), and chocolate instant pudding (36) (Pennington 1990a). 

Measurements of 131I have been monitored in milk through the Environmental Radiation Ambient 

Monitoring System (ERAMS) using gamma spectral analysis of milk samples taken from 65 monitoring 

sites with at least one located in each U.S. state, Puerto Rico, and the Panama Canal Zone. The most 

recent measurements of 131I in milk samples taken from July–September 1993 through July–September 

1997 are below the detection limit at all monitoring sites (see ERD 1993 and ERD 1997 for examples). 
 

 

 

IODINE 266 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

Exposure and uptake of iodine and its radioisotopes can be obtained through several routes including 

inhalation, transepidermal absorption, dietary intake, use of medications, and medical procedures. The 

uptake, distribution, and effect of these exposures vary depending on the iodine isotope and the 

population of interest. These points are discussed below. 

Inhalation Exposures. Inhalation exposure of the general population to iodine through inhalation 

represents an intake pathway. Normal human respiratory exposure to iodine has been estimated to be 

5 μg/day from an atmospheric exposure of 0.7 μg/m3

 (FDA 1974). Uptake of 129I through inhalation is a 

minor pathway for human intake of this radioisotope. It is has been calculated that approximately 

4x10-5 g/year of 129I is taken up by the average individual (USNRC 1979). 

Epidermal Exposures. Iodine vapor can penetrate through the skin. Iodine penetration through the 

epidermis was measured under controlled conditions in which volunteers were exposed to various 

concentrations of 131I in the air (3.1–350x10-10 Ci/L or 11–1,300 Bq/L) (Gorodinskii et al. 1979). Entry of 

131I through inhalation was prevented through the use of a specially designed head mask connected to a 

clean air supply line. Penetration of 131I through the epidermis was monitored by 131I uptake in the thyroid 

(3.1–303x10-10 Ci or 11–1,100 Bq), as measured by a scintillation sensor. K values were calculated to 

compare the uptake of 131I in the thyroid (Am) versus the 131I concentration in the air (C), where K=Am 

(Ci)/C (Ci/L). The K values varied between 0.7 and 2.9, indicating individual variations in iodine 

penetration through the skin and uptake of iodine into the thyroid. The results of this study also suggest 

that the value Am after a 4-hour exposure to iodine vapor can be approximated using the relationship 

Am=3C. A comparison of the penetration of iodine through the skin to the penetration of iodine through 

the lungs in previous work shows that entrance of iodine through the skin is 1–2% of its entrance through 

the lungs. 

Dietary Intake of Iodine. The average daily dietary intake of iodine varies considerably, depending on 

the diet. Vought and London found individual daily intakes of iodine to vary from 15 to as high as 

1,540 μg iodine/day, with mean intakes varying from 64 to 379 μg/day (FDA 1974). The recommended 

dietary allowance for iodine is 0.150 mg/day for adults and adolescents (FDA 1989b). 

Several studies have attempted to describe the daily intake of iodine as a function of diet and age 

grouping. Hospital diets were measured to have mean iodine intakes of 0.533 mg/day (range 0.274– 
 

 

 

IODINE 267 

6. POTENTIAL FOR HUMAN EXPOSURE 

0.842 mg/day), 0.677 mg/day (range 0.595–0.713 mg/day), and 0.377 mg/day (range 0.246– 

0.506 mg/day) (Caplan et al. 1976; Pittman et al. 1969). One nursing home diet had an intake of 

1.531 mg/day (Caplan et al. 1976). The daily iodine intake in children has also been measured: 8– 

15 years old (0.450 mg/day) (Trowbridge et al. 1975), 6-month-old infants (0.359 mg/day, range 0.182– 

0.576), 2-year-old children (0.435 mg/day, range 0.231–0.728), and 15–20-year-old males (0.527 mg/day, 

range 0.319–0.827) (Pennington et al. 1984). 

Dietary iodine intakes have been examined among age groups and were measured to be (in mg/day): 6– 

11 months old (0.200), 2-year-old children (0.460), 14–16-year-old girls (0.420), 14–16-year-old boys 

(0.710), 25–30-year-old women (0.270), 25–30-year-old men (0.520), 60–65-year-old women (0.250), 

and 60–65-year-old men (0.340) (Pennington et al. 1986). The average daily iodine intake partitioned by 

food category (expressed as μg/day) for men and women in the age group 20–34 years old has also been 

reported and is shown in Table 6-5 (FDA 1974) 

Drinking Water/Beverages. Human exposures to iodine through drinking water are typically too low to 

provide for significant uptake of iodine. Surface waters rarely exceed 5.0 μg iodine/L, except where 

waters are polluted with municipal waste stream effluent or urban run-off. In these cases, iodine 

concentrations can be as high as 8.7 μg/L (FDA 1974). Some beverages, such as beer and wine, have 

iodine contents in the ranges of 43–46 and 8–32 μg/kg, respectively, which could provide a significant 

amount of iodine to the diet, depending on the level of daily consumption of these beverages (FDA 1974). 

In emergency, camping, or military uses of iodine to disinfect water supplies, iodine concentrations 

approach 8–16 mg/L (Zemlyn et al. 1981). Use of elemental iodine in the disinfecting of water, when 

improperly used, can lead to acute iodine toxicity. Tetraglycine hydroperoxide is more commonly used at 

a concentration of 8 mg/L to provide more accurate and reliable delivery of iodine to disinfect drinking 

water. Prolonged (>7 days) use of iodine as a water disinfectant can lead to mild impairment of thyroid 

function (Georgitis et al. 1993). 

Food Exposures. The human diet is the major source of exposure to iodine for the general human 

population. Although marine seafoods typically contain the highest amount of iodine (160–3,200 μg/kg 

fresh basis, mean 660±180 μg/kg), they constitute only a small part of the American diet. The largest 

sources of iodine in the human diet come from vegetables (320±100 μg/kg), meat products 

(260±70 μg/kg), eggs (260±80 μg/kg), and diary products (130±10 μg/kg) (FDA 1974). The level of 

iodine in vegetables depends upon the type of plant (e.g., spinach has by far the highest content among 
 

 

 

 

 

 

IODINE 268 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-5. Estimated Average Iodine Intake for Adults in the United States 

Food category Average daily consumption Average daily iodine intake 

Male (g/day) Female (g/day) Male (μg/day) Female (μg/day) 

Milk and milk products 397 269 51.6 35.0 

Eggs 55 31 14.3 8.1 

Meat and meat products 325 192 84.5 49.9 

Seafood 14 9 9.2 5.9 

Legumes 40 24 No data No data 

Grain and cereal products 12 81 12.2 8.1 

Yellow and green vegetables 104 88 33.3 28.2 

Other vegetables and fruits 96 56 3.8 2.2 

Sugar and sweets 44 35 No data No data 

Beverages (excluding milk) 749 739 3.0 3.0 

Estimated salt intake 3.42 3.42 142.0 142.0 

Iodine in food as additives No data No data 100.1 100.1 

Total 454.0 382.5 

Source: FDA 1974 
IODINE 269 

6. POTENTIAL FOR HUMAN EXPOSURE 

the common vegetables) and whether iodine was present in fertilizers. The content of iodine of eggs and 

milk (milk products) depends on the dietary intake of chickens and lactating cows. Eggs accumulate 

systemic iodine; however, systemic levels are controlled by the limit that is placed on the content of 

iodine in feed or water (12.5 mg/kg or liter). Similarly, the content of iodine in milk is dependent upon 

iodine intake, in addition to the seasonal climatological variables, level of milk production, and fullness of 

the mammary gland. One source of iodine in the cow’s diet is the addition of potassium iodide to feed. 

However, the iodine content of milk varied between regions and even between individual farms. These 

variations were found to be caused, in part, by differences in the use of iodized salt blocks, exposures of 

cows to iodine in disinfectants, and the presence of iodine in sanitizers and veterinary medications (FDA 

1974). 

Food sources of iodine that have caused adverse effects in humans include water, seaweed, ground beef 

containing thyroid tissue, foods to which iodine was added as a supplement (iodized water, bread, salt), 

and milk that contained iodine resulting from feed supplements and iodophor disinfectants (FDA 1989b). 

For example, iodine in seaweed-based supplements was found to be 0.045–5.0 mg/dose (Norman et al. 

1988). The value of 5.0 mg/dose is approximately 30 times higher than the RDA for iodine and 5 times 

higher than the value of 1.0 mg/day, where acute and chronic toxicities for iodine intake begin to be seen 

(Pennington 1990a). Outside of these sources of high dietary iodine, the average iodine content in various 

food groups (expressed as μg/kg wet weight) are: seafoods (660±180), vegetables (320±100), meat 

products (260±70), eggs (260±80), dairy products (130±10), bread and cereals (100±20), and fruits 

(40±20) (FDA 1974). 

The iodine contained in milk can be readily transferred to milk products, such as cheeses and ice cream. 

Typically, milk has been shown to contain iodine at concentrations ranging from 0.100 to 0.770 mg/L 

(Pennington 1988). Cheeses containing levels as high as 425 μg/kg have been reported (FDA 1974). The 

high concentrations of iodine in milk and in some milk products are thought to be derived from the use of 

iodophor disinfectants and sanitizers in the practice of dairy farming and the processing of milk. As a 

topical disinfectant, the concentration of iodine in iodophors is 0.5–1.0% by weight. Iodophors with an 

iodine concentration of 0.001–0.0025% have been used to disinfect equipment and used in teat dips and 

udder washings. Teat dipping can increase the iodine content in milk by an average 174 μg/L (range, 55– 

353 μg/L). However, there is evidence that the major contributor to iodine content in milk is feed 

supplementation rather than the use of iodophors (FDA 1974). 
 

 

 

IODINE 270 

6. POTENTIAL FOR HUMAN EXPOSURE 

Processed foods, such as breads, have also been shown to be a source of iodine in the human diet. 

Potassium iodate is used as a conditioner of bread dough by some, but not all, major bakeries. When used 

as a dough conditioner, a concentration of 1–2 μg iodide/g bread is typically obtained. Iodine content of 

fast food, ranging from McDonald’s french fries to a filet-of-fish sandwich, varied between 20 and 

84 μg/100 g total product, respectively (FDA 1974). 

Food additives can also contribute to human iodine intake; table salt contains cuprous iodide and 

potassium iodide, alginic acid, and alginate salts that are used as emulsifiers, and stabilizers and 

thickeners that contain upwards of 9 mg/kg iodine, but may only constitute an average intake of 

1 μg/person/day (FDA 1974). Iodized salt in the United States provides 0.076 mg iodine/g (0.418 mg per 

teaspoon) (FDA 1989b). 

Distribution of Iodine in Human Tissues. Iodine concentrations in nonthyroid tissues of recently 

deceased individuals obtained from a healthy Chinese population have been assessed using neutron 

activation analysis techniques (Hou et al. 1997b). Typical intake of iodine in the Chinese diet averages 

between 94 and 169 μg/person/day (Hou et al. 1997a). The concentrations of iodine in five tissues, plus 

hair, averaged over 9–11 individuals (and expressed as ng/g wet weight tissue±1 SD) were: heart 

(46.6±14.9), liver (170±34), spleen (26±8.6), lung (33.3±10.6), muscle (23.5±14.3), and hair (927±528) 

(Hou et al. 1997b). 

Exposures Through Medications/Medical Uses of Iodine. Human exposures to iodine may come from 

medications and vitamin supplements containing iodine in varying amounts. A survey of various 

pharmaceuticals found that of those tested, eight contained between 0.251 and 0.375 mg iodine per dose, 

with one containing 1.447 mg I/dose (Vought et al. 1972). The variation of iodine content could be 

attributed to the use of erythrosine (2,4,5,7-tetraiodofluorescein) as a red coloration (FDA 1974). 

Erythrosine can be metabolized in the digestive tract to liberate iodide, although the bioavailability of 

iodine from erythrosine may be only 2–5% (FDA 1989b). Some medications directly contain added 

potassium iodide or organic iodine compounds. For example, Lugol’s solution that is used to treat 

thyrotoxicosis is a 5% solution of iodine solubilized in 10% potassium iodide. Other iodine-containing 

drugs (most commonly potassium iodide solutions) have been prescribed for their purported expectorant 

for action in asthma, bronchitis, cystic fibrosis, and chronic pulmonary obstructive disease; also, 

amiodarone is prescribed for heart arrhythmias (FDA 1989b). Topical application of iodine-containing 

medications and dietary supplements can increase iodine in breast milk in lactating women; use of 
 

 

IODINE 271 

6. POTENTIAL FOR HUMAN EXPOSURE 

povidone iodine vaginal gel (50 mg/day for 6 days) increased iodine concentration in breast milk by 3– 

4 times (FDA 1989b). 

Large exposures to iodine can be experienced during certain medical procedures (e.g., through the use of 

iodinated compounds as contrast agents in radiological imaging procedures). Iodine in oil is used in 

bronchograms, lymphangiograms, and for myelograms, and is excreted slowly, thus predisposing an 

individual to imbalances in iodine homoeostasis. 

Radioiodine -131I. The greatest periods of exposure to 131I (and other radioiodine isotopes derived from 

nuclear fission) were during active nuclear testing in the years 1951–1958 and 1961–1962, the large 

quantities of fission products released from nuclear accidents such as Three Mile Island and Chernobyl, 

and the nuclear processing and waste facilities (e.g., Hanford, Washington; Aiken, South Carolina; Idaho 

Falls, Idaho). Human uptake of 131I from environmental sources is largely through ingestion of 

contaminated food, with a smaller proportion obtained through inhalation (Straub et al. 1966; Wehmann 

1963). The distribution of 131I in food depends upon the time the isotope is produced, its presence in the 

environment, and the degree of contamination. Some potential dietary sources of 131I include marine 

animals and plants, milk, and leafy vegetables (Straub et al. 1966). 

The largest source of 131I in the human diet is cow’s milk. Approximately 70% of the 131I that is 

consumed by a cow is absorbed into the thyroid, with about 1% found in milk (milk-to-plasma ratio of 131I 

is 2:3) (Bustad et al. 1964; Lengemann and Comar 1964; Straub et al. 1966). The transfer of iodine is bidirectional, and the iodine appears to freely diffuse between mammary gland and plasma (Miller and 

Swanson 1963; Straub et al. 1966). 131I exists in both the free inorganic form, as iodide, or bound to 

protein in milk. It has been determined that in cow’s milk, 82–91% of the 131I is in the free inorganic 

form, with 4.7–13% bound to protein and <0.1% associated with fat (Glassock 1954; Straub et al. 1966). 

The occurrence and concentration of 131I in milk is highly variable, depending on the locale and daily 

variations within a specific locale (Pennington 1990a). Due to meteorological conditions, a large 

proportion of 131I from fallout is deposited on the ground through dry deposition processes, with a lesser 

amount deposited through wet deposition processes (i.e., precipitation) (Straub et al. 1966). The highest 

concentrations of 131I in milk were observed shortly after atmospheric tests of nuclear weapons and 

accidental releases from nuclear reactors or fuel reprocessing facilities (Anderson et al. 1996a; Black et 

al. 1976; Cohn and Gusmano 1963; Kirchner 1994; Martin and Turner 1964; Tracy et al. 1989; Tubiana 

1982; Voigt et al. 1989). The source of 131I in cow’s milk is derived mainly from the dry and wet 
 

 

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6. POTENTIAL FOR HUMAN EXPOSURE 

deposition (to a lesser extent uptake into plants from the soil) of 131I onto grasses and other plants that are 

then consumed by dairy cows. A concentration of 1 μCi 131I/kg (37 kBq 131I/kg) of 131I in pasture grass 

yields a 131I concentration of 0.07 μCi 131I/L (3 kBq 131I/L) of milk (Voigt et al. 1989). 

In cases of exposure to 131I, the absorbed dose has been estimated in various tissues and whole body for 

the ingestion of 1 mCi (40 MBq) of 131I. The values for the absorbed doses (expressed in cGy and based 

on the assumption of a 25% uptake of ingested 131I into the thyroid) are: 0.48 (liver), 0.14 (ovary), 

0.26 (bone marrow), 1.4 (gastric mucosa), 0.088 (testis), and 1,300 (thyroid), with a mean whole body 

dose of 0.71 cGy (Tubiana 1982). 

The levels of 131I in domestic and imported foods measured between 1987 and 1992 were found to be 

below the detection limit of the gamma-ray spectrometry method (<2 Bq/kg or <5 pCi/kg) (Cunningham 

et al. 1994). Detection and quantitation of 129I is difficult due to the low energy of the beta (maximum 

energy=0.15 MeV) and gamma rays (0.04 MeV) that are emitted from this isotope. Concentration of 129I 

in thyroid tissues increases the ability to detect this isotope, but a further limitation results from the low 

specific activity of the radioisotope (0.17 mCi/g or 6.3 MBq/g) (NCRP 1983). However, due to the 

steady-state levels of 129I in the environment, there is a continual exposure of the general human 

population to this radioisotope through inhalation and intake through the diet. It has been estimated (AEC 

1974) that a dose of approximately 0.2–0.5 mrem/year is delivered to the thyroid of an adult from 129I, 

depending on diet. These estimates include the dose received through the inhalation of 129I. For an infant, 

the doses to the thyroid from 129I intake can vary between 0.15 and 0.4 mrem/year, depending on diet. 

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 3.8 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, 
 

 

 

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6. POTENTIAL FOR HUMAN EXPOSURE 

sometimes eat inappropriate things (such as dirt or paint chips), and spend more time outdoors. Children 

also are closer to the ground, and they do not use the judgment of adults to avoid hazards (NRC 1993). 

Children appear to be more susceptible to the development of thyroid cancers from the irradiation of 

thyroid by 131I. Irradiation of the thyroid from a 1–2 Gy dose in Japanese A-bomb survivors and a 3.3 Gy 

dose in Marshall Islanders exposed to fallout results in a high incidence (factor of 2) of thyroid cancers in 

children under the age of 10 compared the exposed adult population (Tubiana 1982). 

Of the iodine radioisotopes, 129I poses the least risk to children with respect to thyroid irradiation. Even at 

a high thyroid content of 1 mCi (40 MBq) 129I in 1 g of stable iodine, the dose to the thyroid in a 6-monthold infant would be 0.9 nGy/year as compared to a dose of 7.2 nGy/year in an adult thyroid. In 

comparison, 131I can deliver much higher doses to the thyroid at lower environmental concentrations than 

those observed for 129I, due to the higher specific activity of 131I (1.24x105

 Ci/g or 457 TBq/g; beta 

particle energies of 0.334 MeV [7.3%] and 0.606 MeV [89.9%]) versus 129I (177 μCi/g or 6.55 MBq/g; 

beta particle energy of 0.154 MeV) (Chu et al. 1999; Robkin and Shleien 1995). For example, the annual 

consumption of milk containing 131I at a concentration of 1–20 nCi/L (37–740 Bq/L) would result in a 

dose to the thyroid in children of between 0.005 and 0.1 cGy/year (Tubiana 1982). In comparison, similar 

concentrations of 129I in milk would yield a thyroid dose of between 0.014 and 0.28 pGy/year, based on 

the specific activities and beta energies listed above. Breast milk is also a source of 131I uptake in 

children. For example, concentrations of 131I in breast milk measured in women exposed to nuclear 

weapons fallout ranged between 0.050 and 0.100 nCi/L (1.9 and 3.7 Bq/L), when the mean body burden 

of 131I in these women was 0.060 nCi (2.2 Bq) (Cohn and Gusmano 1963). 

Children (both 1 and 10 year olds) appear to have a similar fractional uptake of iodine in the thyroid (i.e., 

approximately 31%) of that found in adults. For newborns, however, the fractional uptake is 

approximately 70% at 2 days after birth, but quickly declines to values accepted for an adult by day 5. 

After the first few weeks, uptake changes very little with age. The estimated dietary intake of iodine in 

1 year olds is 151 μg/day, and for 10 year olds, it is 184 μg/day. The percent turnover rates of iodine in 

the thyroid does change with age (expressed as d-1) are: 0–4 years old (3.4±0.5), 4–8 years old (2.1±0.5), 

and 8–12 years old (0.84±0.36); this corresponds to ‘apparent’ half-lives of 20, 33, and 83 days, 

respectively. Iodine concentration in thyroid increases with age (expressed as μg/g): 1 year old (95), 

2 years old (130), 4 years old (180), 10 years old (260), 16 years old (320), and adult (400) (Stather and 

Greenhalgh 1983). 
 

 

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6. POTENTIAL FOR HUMAN EXPOSURE 

In utero exposures of a human fetus to iodine radioisotopes with high specific activity (e.g., 131I) have 

been assessed based on both the maternal intake of iodine radioisotopes and exposure to external radiation 

generated by these isotopes in the immediate environment. Iodine and its radioisotopes freely diffuse 

across the placenta and, as such, their levels within a fetus and the amniotic fluid will depend greatly on 

the concentration of iodine within the mother (Bašič et al. 1988; Dyer and Brill 1972; Etling et al. 1979; 

von Zallinger and Tempel 1998). Before 11 weeks of gestation, the thyroid is still undeveloped and does 

not actively take up iodine (Dyer and Brill 1972; von Zallinger and Tempel 1998). For example, the 

percent of iodine that is taken up by the thyroid in comparison to that contained in the total fetal tissues is 

quite low at a gestation age of 9–11 weeks (0.0002%), but increases after 11 weeks where the percentage 

becomes 0.001% for gestation ages between 13 and 15 weeks, and increases further to 0.002% between 

gestation ages of 16 and 22 weeks (Dyer and Brill 1972). A difference in placental transfer of iodine 

between the mother and fetus is also noted as a function of gestation time. The percentage of 131I activity 

found in the fetus compared to the total activity within the mother at 11 weeks was 0.23%, but increased 

to 2.96% at 22 weeks due to the fact that the concentration of iodine in the fetal thyroid typically exceeds 

that of the maternal thyroid by 3–10 times (von Zallinger and Tempel 1998). Increases in the 

concentration of iodine in the fetus and amniotic fluid (6- to 90-fold increases) were observed in women 

exposed to topical iodine-containing medications (e.g., vaginal therapy with iodinated polyvinylpyrrolidine) or increased iodine intake in their diets (Etling et al. 1979). However, the uptake of iodine 

(measured by 131I uptake) into the fetal thyroid (1.08 pCi/g or 0.0400 Bq/g) at a gestation time of 

22 weeks is not significantly different from what is observed for the maternal thyroid (0.82 pCi/g or 

0.030 Bq/g) (Beierwaltes et al. 1963). 

Emission of ionizing radiation from iodine radioisotopes can also pose an exposure risk to the human 

fetus and the mother in occupations where the mother comes in contact with these isotopes. For example, 

fetal doses in imaging staff performing a whole body scan and/or therapy procedures for thyroid cancer 

patients using 131I ranged between 6.7 and 9.0 μSv (Mountford and Steele 1995). Thus, restrictions on the 

exposure of pregnant women are 1.3 mSv to the maternal abdominal surface (corresponding to a 1.0 mSv 

dose to the fetus) (Mountford and Steele 1995). 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

Occupational Exposures (Medical Personnel, Laboratory Personnel, Personnel at Nuclear 

Power/Fabrication/Storage Facilities). Occupational exposures to airborne iodine can occur when 

iodine is used in the regular functions of the workplace. OSHA has set a limit for airborne iodine 
 

 

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6. POTENTIAL FOR HUMAN EXPOSURE 

concentrations in the workplace of 0.1 ppm. Exposures of workers to concentrations at or in excess of the 

OSHA limit can often occur. For example, at a plant that processes photo-polymer plates, most workers 

were exposed to an average concentration of iodine of 0.005 ppm, but were exposed to concentrations of 

0.122–0.146 ppm when they were in the immediate proximity of the iodine holding tank or iodine 

applicator (Kim et al. 1981). 

The USNRC has set Annual Limits of Intake (ALIs) for inhalation exposures to radioiodine in the 

workplace as specified in USNRC Regulations (10 CFR) (USNRC 2002). The ALIs are based on the 

annual intake of a particular radioisotope that would result in an effective dose equivalent of 5 mrems to 

an organ or tissue; in the case of radioiodine, the thyroid. For inhalation exposures, the ALI is derived 

from Derived Air Concentrations (DACs) that represent the concentration of radioiodine at which a 

“reference man” working 2,000 hours per year under light working conditions (inhalation rate of 

1.2 m3

/hour) results in the intake of one ALI. The current ALIs for inhalation exposure based on the 

thyroid as the target organ are: 123I, 6,000 μCi (DAC=3x10-6 μCi/mL); 125I, 60 μCi (DAC=3x10-8 

μCi/mL); and 131I, 50 μCi (DAC=3x10-8 μCi/mL). 

Workers in the nuclear industry, especially in nuclear fuel reprocessing facilities, have the potential for 

chronic thyroid burdens of 131I in addition to acute exposures from accidental releases. For example, in 

Indian workers, the doses from chronic 131I exposures were found to be as high as 47.4–68.1 rem for 

thyroid and 0.024–0.047 rem for whole body (Raghavendran et al. 1978). In an acute exposure to 131I in a 

steam leak at a nuclear power plant, the mean thyroid burden of 131I in the exposed workers was 1.32 μCi 

(48.8 kBq) on the third day after the exposure; the 131I burden decreased exponentially, falling below 

0.027 μCi (1.0 kBq) on the 38th day (Bhat et al. 1973). 

Internal contamination of medical personnel by 131I can be a problem, especially under conditions where 

the release of iodine as a vapor can occur (Eadie et al. 1980; Luckett and Stotler 1980). Thyroid burdens 

of 131I in medical personnel can typically average around 2,400 pCi (ranges of 35–18,131 pCi or 1.3– 

671.52 Bq) (Blum and Liuzzi 1967). Personnel working with 131I could potentially receive up to 5 nCi 

(200 Bq) per mCi (40 Bq) handled. This means that persons handling therapeutic doses of 131I could have 

activities of 0.1–1.0 μCi (-4,000–40,000 Bq) in their thyroids (Tubiana 1982). For the application of 131I 

in nuclear medicine, it has been shown that the radiochemists and their support staff have yearly thyroid 

131I burdens of between 0.5–200 nCi (20–7,000 Bq) and 0.03–1.5 nCi (1–56 Bq), respectively (Jönsson 

and Mattsson 1998). 
IODINE 276 

6. POTENTIAL FOR HUMAN EXPOSURE 

External exposures of medical personnel to radiation emitted from radioiodine have been assessed for 

both diagnostic and therapeutic applications of 131I and 125I. The dose rate per unit activity (μSv/h @ MBq) 

of 131I has been determined for thyrotoxicosis, thyroid ablation, and thyroid cancer therapies as a function 

of distance from the patient. The dose rate as a function of distance is approximately the same for all 

three therapy regimens; 1.43 μSv/h @ MBq at 0.1 meter, 0.18 μSv/h @ MBq at 0.5 meter, and 

0.07 μSv/h @ MBq at 1.0 meter (Mountford and O’Doherty 1999). Surgical implants of 125I seeds in 

prostate brachytherapy have the potential for radiation exposures to the radiotherapist. However, in most 

instances when the implant procedure is performed properly, the dose rate is <1 μGy/mCi-hour (Liu and 

Edwards 1979). 

Laboratory workers using 125I are at risk for exposures to gamma- and x-rays to the hand. In a typical 

situation where 20 MBq (5 mCi) of 125I from an unshielded source is used weekly (2 hours/week) 

throughout a year, a worker would receive a dose of approximately 225 mSv (22.5 rem), 3/10 of the 

recommended dose equivalent limit to the hands (de Groot 1979). Uptake of 125I into the thyroid has also 

been shown to occur due to airborne radioiodine released from solutions or spills (Bogdanove and Strash 

1975; Dunn and Dunscombe 1981; Krzesniak et al. 1979; Kwok and Hilditch 1982). Activity levels of 

0.013–0.024 μCi (480–890 Bq) and 0.056–0.56 μCi (2,100–21,000 Bq) have been measured in the 

thyroid of a laboratory worker working with 1 and 5 mCi (40 and 200 MBq) of 125I in the day’s activities, 

respectively (Kivinitty et al. 1984). In a more general survey, it was found that 8% of laboratory 

technicians working with 125I labeled materials had thyroid burdens of 125I within 9–90 nCi (300– 

3,000 Bq). However, 33% of those individuals involved in the direct iodination of biomaterials and 

compounds with 125I had thyroid burdens of 9–90 nCi (300–3,000 Bq) (Pomroy 1979). 

Patients Undergoing Medical Treatment Involving Use of Iodinated Compounds. Patients undergoing 

treatment for hyperthyroidism and thyroid carcinoma typically receive between 10 and 150 mCi (370 and 

5,500 MBq) of 131I (Beierwaltes 1979). In addition to the radiation dose received by the thyroid from 

these loadings of 131I, other tissue sites in the patient also receive a radiation dose, albeit a smaller dose. 

This is especially important when considering the impact that the radiation emitted from 131I can have on 

bone marrow in a patient undergoing 131I therapy to treat thyroid carcinomas. During these 131I therapies, 

the bone marrow can receive a dose of 1–5 Gy (Tubiana 1982). This has been shown to lead to a 1% 

incidence of leukemia in these patients (Tubiana 1982). 

There is also an exposure risk of a patient’s immediate family to both the radiation and elemental 131I that 

is emitted from the patient (Barrington et al. 1999). Patients are allowed to return home after the activity 
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6. POTENTIAL FOR HUMAN EXPOSURE 

of 131I within them falls below 30 mCi (1.1 GBq). Due to differences in the excretion rate of radioiodine 

from patients, it is recommended that both biological clearance and physical decay be used in calculating 

the confinement time of a patient (Kaurin et al. 2000; North et al. 2001). However, the level of 131I 

activity of 30 mCi (1.1 GBq) in a patient can produce an exposure rate to ionizing radiation (emitted in 

the decay of 131I) of approximately 10 μGy/hour at a distance of 1 meter. Thus, family members are also 

at risk to exposures to 131I that is emitted from the patients. The dose that a typical family member 

receives from a patient at home ranges between 0.17 and 126 μGy/day, as compared to the natural 

radiation background of 0.35 μGy/day (Jacobson et al. 1978). This can result in some family members 

exceeding the maximum allowable dose of mSv (1 mrem) per year. In another study, it was found that as 

many as 11% of children exposed to patients undergoing 131I therapy exceeded the 1 mSv limit 

(Barrington et al. 1999). Activities of 131I within the thyroids of family members of patients undergoing 

131I therapy were found to range from the detection limit of the measurement of 92–110,000 pCi, resulting 

in a dose of 4–1,330 mrem to the thyroid. Of special concern is the fact that the 131I activity was highest 

in children (Jacobson et al. 1978). 

A growing number of patients who are undergoing treatment for cancer are using alternative medicines 

and nutritional supplements (Cassileth 1999). It is believed that these alternative medicines and 

supplements will help to prevent the onset of a tumor, alleviate specific symptoms that are experienced as 

a consequence of their disease or treatment, or aid in the eradication of the tumor. The self administration 

of some of these alternative medicines and nutritional supplements can result in the intentional (e.g., 

elevated iodine intake to prevent breast cancer) or unintentional (e.g., when iodine is a natural component 

of a specific alternative medicine) elevation of the daily intake of iodine, especially when patients 

consume alternative medicines that contain salt water plants, such as kelp, or those individuals who take 

megavitamins or participate in orthomolecular therapy (Cassileth 1999). The amount of iodine intake will 

vary depending on the specific content of iodine in the supplement and the dosage, which could result in 

iodine intakes that approach toxic levels (e.g., >6 g/day). For most cancers, it is unclear what benefit 

increased iodine will have for the prognosis of the disease or how it can alter the incidence of a particular 

cancer (Cann et al. 2000; Cassileth 1999; Eskin 1970). However, there is evidence to suggest that 

elevated iodine intake, especially for populations where ambient iodine concentrations are low, can help 

to decrease the incidence of breast cancer and, in some cases, help to interfere with breast tumorogenesis 

(Cann et al. 2000; Eskin 1970). 

Diseases/Predisposition to Iodine Toxicities. An increase in the availability of dietary iodine for a 

population may also cause difficulty in controlling Graves’ disease with antithyroid drugs, decrease the 
 

 

 

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6. POTENTIAL FOR HUMAN EXPOSURE 

remission rates for those on antithyroid medication, and increase the dose of radioiodine required to 

induce euthyroidism (FDA 1989b). In the general population, between 0.2 and 33.3% of individuals 

develop goiter in response to excess iodine consumption, whereas an increase in the incidence of 

sensitivity or acute reactions was observed in <30% of individuals in the general population (FDA 

1989b). 

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 iodine and its radioisotopes 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 iodine and its radioisotopes. 

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. 

6.8.1 Identification of Data Needs 

Physical and Chemical Properties. Adequate pertinent data on the physical and chemical 

properties of iodine and its radioisotopes and compounds are available in the literature. 

Production, Import/Export, Use, Release, and Disposal. Since iodine is not covered under 

Superfund Amendments and Reauthorization Acts (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 iodine. There 

is a relatively good database on the release of radioiodine (Beals and Hayes 1995; DOE 1990, 1994; 

NCRP 1983; Patton and Cooper 1993), but only limited information is available on disposal and 

inventories of radioiodine in the disposal sites (DOE 1994). 
IODINE 279 

6. POTENTIAL FOR HUMAN EXPOSURE 

Environmental Fate. The major source of iodine on terrestrial surfaces originates from the 

volatilization of iodine from the ocean surface. Adequate information is available pertaining to the 

chemical species and reactions that take place at and above the ocean surface that are responsible for the 

production of volatile forms of iodine (Cox et al. 1999; Filistovic and Nedveckait 1998; Vogt et al. 1999; 

Whitehead 1984). Further work is needed to examine the organisms and microbial metabolic processes 

that are responsible to the formation of alkyl iodides, as well as the exact contribution of alkyl iodides, 

molecular iodine, and spray to the introduction of iodine into the atmosphere. There is a good body of 

literature on the photochemical reactions of iodine, both in the gaseous phase and in/on particulates or 

water droplets (Cox et al. 1999; Filistovic and Nedveckait 1998; Moran et al. 1999; Vogt et al. 1999; 

Whitehead 1984). The factors that are responsible for the retention of iodine in soil have also been 

examined extensively (Fawcett and Kirkwood 1953; Jirousek and Pritchard 1971; Sheppard et al. 1995; 

Whitehead 1984). However, more work is needed to characterize the interactions of iodine with organic 

components, especially with respect to the mechanisms of the binding and release of iodine from these 

organic components. The environmental fate of 129I and 131I has been examined extensively (AEC 1974; 

DOE 1978a, 1986; USNRC 1979, 1981). 

Bioavailability from Environmental Media. Adequate pertinent data for intake of iodine and 

radioiodine from inhalation, drinking water, and food intake are available (DOE 1993; NCRP 1983; 

USNRC 1979; Whitehead 1984). 

Food Chain Bioaccumulation. Concentrations of iodine in freshwater and marine fish have been 

determined (Poston 1986). Concentrations of iodine in aquatic plants have also been ascertained (NCRP 

1983). Although aquatic plants and fish concentrate iodine in their tissues, there is little evidence for 

bioaccumulation of iodine in the food chain. Iodine and radioiodine concentrations have been measured 

in foods, especially in the context of milk and the transfer of radioiodine through the soil-plant-cow-milk 

pathway (AEC 1974; Kirchner 1994; Tracy et al. 1989; Voigt et al. 1988, 1989). Although some 

information is available, more information is needed on the uptake of iodine from the soil into plants 

(Burte et al. 1991; Moiseyev et al. 1984; Whitehead 1984). 

Exposure Levels in Environmental Media. Adequate pertinent data are available for current 

exposure of iodine in air, rainwater, surface water, groundwater, and soil (FDA 1974; Moran et al. 1999; 

USNRC 1979; Whitehead 1984; Yuita 1994a). 
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6. POTENTIAL FOR HUMAN EXPOSURE 

Exposure Levels in Humans. A good database exists for exposure levels of the general population 

to iodine and its radioisotopes in various food types and drinking water (Allegrini et al. 1983; Bruhn et al. 

1983; Dellavalle and Barbano 1984; Kidd et al. 1974; Pennington et al. 1986), including exposure levels 

in milk (Pennington 1988). Information for the average daily intakes of iodine based on diet and age 

groupings is available (Caplan et al. 1976; Pennington et al. 1984, 1986). Information on occupational 

exposures is available, especially for exposure of medical personnel to 131I and laboratory workers to 125I 

(Blum and Liuzzi 1967; Bogdanove and Strash 1975; de Groot 1979; Dunn and Dunscombe 1981; 

Krzesniak et al. 1979; Kwok and Hilditch 1982; Mountford and O’Doherty 1999; Pomroy 1979; Tubiana 

1982). However, exposure data are currently not available for individuals who come in contact with, 

work in, or live in the vicinity of, clandestine methamphetamine production laboratories. This 

information is especially needed due to the potential for acute and chronic exposures to iodine. Data exist 

for the distribution of iodine in human and fetal tissues, but more information is needed (Dyer and Brill 

1972; Hou et al. 1997b; von Zallinger and Tempel 1998). 

Exposures of Children. A good database exists for exposure levels of children to iodine and its 

radioisotopes in various environmental exposure pathways, including food types, drinking water, and 

especially milk and milk products (Cohn and Gusmano 1963; FDA 1974, 1989; Soldat 1976; Stather and 

Greenhalgh 1983; Tubiana 1982). Information for the average daily intakes of iodine for children based 

on age groupings is available (Pennington et al. 1984, 1986; Trowbridge et al. 1975). Information on in 

utero exposures to iodine and its radioisotopes is available (Bašič et al. 1988; Beierwaltes et al. 1963; 

Dyer and Brill 1972; Etling et al. 1979; Mountford and Steele 1995; von Zallinger and Tempel 1998). 

There is also some information on the exposure of children to 131I, and the radiation that it emits, that 

occurs when children are in contact with, or in the vicinity of, individuals undergoing 131I treatment 

(Barrington et al. 1999; Jacobson et al. 1978). However, more information is needed to adequately assess 

the risk of children to this exposure. Also, there will be a need to develop biomarkers to assess the low 

level exposures of children to 129I. Improvements in analytical methods have provided an ability to detect 

the low concentrations of 129I in tissues and, thus, given us an opportunity to reliably assess low level 

exposures of 129I in children and adults. Yet, the development of biomarkers, such as the identification of 

DNA mutations that would be specifically formed as a consequence of 129I exposure in a cell to monitor 

the possible biological effects of these low level exposures, have been lacking. 

Child health data needs relating to susceptibility are discussed in Section 3.13.2 Identification of Data 

Needs: Children’s Susceptibility. 
IODINE 281 

6. POTENTIAL FOR HUMAN EXPOSURE 

Exposure Registries. No exposure registries for iodine were located. This substance is not currently 

one of the compounds for which a subregistry has been established in the National Exposure Registry. 

Iodine will be considered in the future when chemical selection is made for subregistries to be 

established. The information that is amassed in the National Exposure Registry facilitates the 

epidemiological research needed to assess adverse health outcomes that may be related to exposure to this 

substance. 

6.8.2 Ongoing Studies 

Two studies are currently underway (FEDRIP 2000) to study the interaction of iodine with differing soil 

components and the effect of iodine intake on the underlying mechanisms contributing to autoimmune 

thyroiditis. In the first study, Dr. R.L. Jones, at the Department of Natural Resources and Environmental 

Sciences, University of Illinois, Urbana, Illinois, is conducting a study of iodine in Illinois soils. The 

objective of this work is to determine the concentrations of iodine in a group of selected surface soils so 

that estimates of iodine concentrations can be made for major soil areas in Illinois. Analysis of soils as a 

function of depth and soil type will identify proportions of iodine in organic matter, and iron and 

aluminum fractions with the objective of identify whether differences occur between soils because of 

differences in soil development and genesis. 

In another study, conducted by Dr. Carol L. Burek at Johns Hopkins University, Baltimore, Maryland, 

work is underway to determine whether increased intake of iodine contributes to an increase in the 

incidence of autoimmune thyroiditis (AT). The researchers intend to show that increases in iodine intake 

lead to an increased level of a highly iodinated form of thyroglobulin protein. It is thought that this 

highly iodinated form of thyroglobulin can act as an auto-immunogen and may be responsible for the 

T-cell mediated auto-immune response that is targeted against the thyroid gland. Using the NOD mouse 

model, the researchers will examine whether increased doses of iodine lead to an increase in the incidence 

of AT in these mice. Once this is established, the researchers will examine whether this increased 

incidence in AT is accompanied by an increase in the levels of highly iodinated thyroglobulin protein and 

increased activity of T-cells against this potential auto-immunogen. 

 

 

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7. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting, 

measuring, and/or monitoring iodine and its radioisotopes, their metabolites, and other biomarkers of 

exposure and effect to iodine and its radioisotopes. 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. 

Entry of iodine and its radioisotopes into the human body can be gained through ingestion, inhalation, or 

penetration through skin (IAEA 1988; NCRP 1985). The quantities of iodine within the body can be 

assessed through the use of bioassays that are comprised of in vivo measurements and/or in vitro 

measurements. In vivo measurements can be obtained through techniques that directly quantify 

internally-deposited iodine using, for example, thyroid or whole body counters. These in vivo 

measurement techniques are commonly used to measure body burdens of iodine radioisotopes, but cannot 

be used to assess the stable isotope of iodine. Instead, in vitro measurements provide an estimate of 

internally deposited iodine (both the stable and radioactive isotopes), utilizing techniques that measure 

iodine in body fluids, feces, or other human samples (Gautier 1983). Examples of these analytical 

techniques are given in NCRP Report No. 87 (1987) and are also listed in Table 7-1. 

7.1 BIOLOGICAL MATERIALS 

7.1.1 Internal Iodine Measurements 

In vivo measurement techniques are the most direct and widely used approach for assessing the burden of 

iodine radioisotopes within the body. The in vivo measurement of these radioisotopes within the body is 

performed with various radiation detectors and associated electronic devices that are collectively known 

as in vivo thyroid monitors or whole body counters, depending on the body site of interest. These 
 

 

IODINE 284 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Iodine in Biological Samples 

Sample 

matrix Preparation method 

Analytical 

method 

Sample 

detection limit Percent recovery Reference 

Urine Sample purified on 

Dowex 1x8 resin 

column; dried resin 

INAA (γ-ray 

spectrometry) 

0.01 μg/L 94% Ohno 1971 

fused with 

NaOH/KNO3, 

dissolved in water; 

dry 0.5 mL aliquot on 

polythene sheet; 

irradiated, dissolved 

in water with iodine 

carrier; extracted with 

trioctylamine/xylene; 

back extracted with 

1 N ammonia, 

precipitate as AgI2 

Urine Sample digested in 

chloric acid; 

arsenious acid added 

and then submitted 

for automated 

analysis 

As-Ce 

catalytic 

spectrophotometry 

Between 

0.01 and 

0.06 μg 

per sample 

(0.02–0.50 mL 

sample volume) 

96–97% Benotti and 

Benotti 

1963; 

Benotti 

et al. 1965 

Thyroid Powdered or fresh 

tissue digested with 

H2SO4; iodide 

converted to Al2I6, 

neutron irradiated; 

Neutron 

activation 

plus mass 

spectrometry 

0.11–2.17 mg/g 

(range of 

measured 

values) 

No data Ballad et al. 

1976, 

Boulos 

et al. 1973, 

Oliver et al. 

iodine precipitated 

with Pd 

1982b 

Adipose 

tissue 

Sample placed into 

polyethylene vials and 

neutron irradiated 

INAA (γ-ray 

spectrometry) 

1.4–8.6 μg/g No data EPA 1986 

Nonthyroid 

tissues 

Tissue samples 

lyophilized, sealed in 

polyethylene film, and 

irradiated with 

epithermal neutrons 

using a boron nitride 

shield 

INAA (γ-ray 

spectrometry) 

9.4–2,880 ng/g 

(range of 

measured 

values) 

No data Hou et al. 

1997b 
 

 

IODINE 285 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Iodine in Biological Samples 

Sample 

matrix Preparation method 

Analytical 

method 

Sample 

detection limit Percent recovery Reference 

Tissues Aqueous NaOH and 

Na2S2O5 added to 

tissue homogenates; 

ashed; residue 

dissolved in water 

HPLC with 

UV detection 

0.07–1,060 μg/g 

(range of 

measured 

values) 

87–97% Andersson 

and 

Forsman 

1997 

and then injected into 

an HPLC for the 

separation of 

components on a twocolumn system 

followed by 

quantitation of iodine 

by UV 

Plasma 

(protein 

bound) 

Protein precipitated 

by Somogyi’s zinc 

sulfate reagent, 

digested in CrO3, 

purified by distillation 

As-Ce 

catalytic 

spectrophotometry 

0.01 μg/mL 75–100% 

(0.01–0.05 μg/mL) 

Barker 

1948 

Feces Dried; pulverized; 

digested in HNO3/HF; 

treated with 

ICP-AES 0.1 μg/mL 88–90% Que Hee 

and Boyle 

1988 

HCl/HNO3 

Feces Dried; pulverized; 

digested in chloric 

acid; arsenious acid 

added and then 

submitted for 

automated analysis 

As-Ce 

catalytic 

spectrophotometry 

Between 

0.01 and 

0.06 μg per 

sample 

(20–30 mg 

sample size) 

97–101% Benotti and 

Benotti 

1963, 

Benotti 

et al. 1965 

Milk, 

serum 

Sample is mixed with 

acteonitrile (1:2), 

centrifuged; 

supernatant dried; 

dissolved in 

HPLC with 

UV detection 

0.5 μg/L 97.6–102.4% Verma 

et al. 1992 

acetonitrile/water and 

a 1 mL aliquot 

derivatized with 

2-iodosobenzoate in 

phosphate buffer 

containing 2,6-dimethylphenol 

Milk, 

yogurt, 

cream 

Sample incubated in 

two parts (v:v) 

methanol; filtered; 

HPLC with 

amperometric 

detection 

25 μg/L 92–114% Chadha 

and 

Lawrence 

4 mL filtrated passed 

through Sep-Pak C18 

cartridge; final 2 mL 

of eluate filtered; 

1990 

100 μL aliquot 

analyzed by HPLC 
 

 

IODINE 286 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Iodine in Biological Samples 

Sample Analytical Sample 

matrix Preparation method method detection limit Percent recovery Reference 

Bread Bread is dried; 

ground; treated with 

2N Na2CO3 plus 1% 

KClO3; dried; 

incinerated; 

As-Ce 

catalytic 

spectrophotometry 

0.05 μg/g No data Sachs et al. 

1972 

dissolved; analyzed 

by the ceric arsenite 

reaction 

As-Ce catalytic spectrophotometry = arsenious-ceric ion catalytic spectrophotometry; HPLC = high performance 

liquid chromatography; ICP-AES = inductively coupled plasma-atomic emission spectrometry; INAA = instrument 

neutron activated analysis; UV = ultraviolet/visible 
IODINE 287 

7. ANALYTICAL METHODS 

radiation detectors commonly utilize sodium iodide (NaI), hyperpure germanium, and organic liquid 

scintillation detectors to measure the gamma rays and x-rays emitted from 125I and 131I. 

The gamma-ray and x-ray photopeaks that are commonly used in the detection and quantification of these 

iodine radioisotopes are the 28 keV (0.0665 photons/transition) gamma-ray and/or the Kα1 (27.5 keV, 

0.739 photons/transition), Kα2 (27.2 keV, 0.397 photons/transition), Kβ1 (31.0 keV, 0.140 photons/ 

transition), and Kβ2 (31.7 keV, 0.043 photons/transition) x-rays for 125I, and the 364 keV gamma-ray for 

131I (Jönsson and Mattsson 1998; Landon et al. 1980; Palmer et al. 1976). The third iodine radioisotope 

that is commonly encountered in the environment, 129I, is difficult to quantify using in vivo monitoring 

and scanning techniques, due to its low specific activity (0.17 mCi/g), low abundance in the environment, 

and low energy β-

 (150 keV) and gamma (40 keV) radiation (NCRP 1983). 

Because approximately 20–30% of the iodine that enters the body is taken up by the thyroid gland, in vivo 

thyroid monitoring is preferably and reliably used for assessing 125I and 131I burdens in exposed 

individuals (Bartolini et al. 1988; Bhat et al. 1973; Blum and Liuzzi 1967; Jacobson et al. 1978; Jönsson 

and Mattsson 1998; Landon et al. 1980; Mandó and Poggi 1988; Nishiyama et al. 1980; Palmer et al. 

1976; Plato et al. 1976; Pomroy 1979). As such, in vivo thyroid scanning techniques are routinely used to 

assess thyroid burdens of 125I and 131I in individuals with occupational exposures to these radioisotopes; 

for example, medical personnel, laboratory technicians, nuclear medicine staff, radiochemists, and 

personnel involved with nuclear fuel processing. The relatively low attenuation of the gamma rays 

emitted from 131I by most tissues allows for whole body and thyroid scanning techniques to be used in 

quantifying this iodine radioisotope within an individual (Berg et al. 1987; Nishiyama et al. 1980). 

Attenuation of lower energy gamma-ray and x-ray emissions for 125I through tissues is greater than what 

is observed for the higher energy 131I gamma-ray. However, the position and close proximity of the 

thyroid at the base and surface of the neck helps to minimize the effect that attenuation can have on the 

detection and quantification of 125I in the thyroid, as compared to deeper tissues. 

Many configurations of the thyroid and whole body counter and scanning methods have been used for 

monitoring and quantifying thyroid iodine radioisotope burdens, ranging from unshielded, single-crystal 

field detectors to shielded, multi-detector scanning detectors (IAEA 1962, 1970, 1972, 1976, 1985; NCRP 

1987; Palmer et al. 1976; Plato et al. 1976). The minimum detectable activity of these devices is typically 

around 30–300 pCi (1–10 Bq) for thyroid monitoring and approximately 2 nCi (70 Bq) for whole body 

scanners (Nishiyama et al. 1980; Palmer et al. 1976; Plato et al. 1976). Where appropriate, shielding of 

the room that houses the thyroid or whole body counter can be used to increase the detection sensitivity of 
IODINE 288 

7. ANALYTICAL METHODS 

the equipment by minimizing background radiation. To further insure that internalized iodine 

radioisotopes are accurately measured, removal of external contamination with radioactive iodine or other 

gamma-emitting radioisotopes on the clothing or skin of the individual to be scanned is recommended 

(Palmer et al. 1976). Also, in vitro measurements of iodine (see Section 7.1.2) can be used in conjunction 

with in vivo thyroid monitoring when assessing individuals working with iodine radioisotopes, especially 

in the assessment of individuals who have experienced accidental or routine exposures to iodine 

radioisotopes (Bhat et al. 1973; Nishiyama et al. 1980). 

Calibration of thyroid and whole body counting is achieved through the use of tissue-equivalent 

phantoms. These phantoms are constructed to mimic the shape and density of the anatomical structure 

using tissue equivalent materials such as water-filled canisters or masonite (Bhat et al. 1973; Jönsson and 

Mattsson 1998; Landon et al. 1980; Nishiyama et al. 1980; Palmer et al. 1976; Plato et al. 1976). An 

example of a neck phantom is a polyethylene or Lucite cylindrical container filled with water to 

approximate the dimensions and density of the neck (Jönsson and Mattsson 1998; Landon et al. 1980; 

Palmer et al. 1976; Plato et al. 1976). Radioiodine standards are measured either as point sources along 

the phantom or, more typically, dissolved within two water-filled polyethylene or glass tubes (1–2.5 cm 

in diameter by 5–7 cm in length) that are set at an appropriate distance apart to approximate the 

positioning of the two lobes of the thyroid glands in the base of the neck. The dimensions of the Lucite 

and polyethylene neck phantoms are varied to more accurately mimic the actual ranges of adult and 

children’s neck sizes (Palmer et al. 1976; Plato et al. 1976; Pomroy 1979). Other types of modified 

thyroid-neck phantom models and whole body phantoms have been used to calibrate radioiodine 

measurements as well (Nishiyama et al. 1980). Comparisons of the actual counting rates obtained from 

the phantom and the known activity of the radioiodine standards are used to determine the efficiency of 

the counting technique and, thus, provide the basis for calibration. 

Assessment of short- and long-term retention of iodine radioisotopes must take into account the turnover 

rate for radioiodine within the human body. For 125I, the mean effective half-life within the body is 37– 

39 days (Bartolini et al. 1988; Landon et al. 1980); for 131I, the mean effective half-life is 5–7.6 days 

(Bhat et al. 1973). These values are much less than the actual biological half-life of iodine (127I) in the 

body of 96–138 days (Bartolini et al. 1988; Landon et al. 1980), due to the relatively short physical halflives of these radioisotopes. For acute and chronic exposures to radioiodine, the estimates of radioiodine 

retention are best calculated from results of multiple thyroid or whole-body measurements. This is 

because of individual variability in thyroid uptake rates, excretion rates, and uncertainties in determining 

uptake of radioiodine through inhalation, ingestion, and the skin (Landon et al. 1980; Mandó and Poggi 
IODINE 289 

7. ANALYTICAL METHODS 

1988). However, direct comparisons between laboratory studies of body burdens and clearance rates for 

specific radioisotopes can be complicated by the differing whole body measurement techniques, 

calibration methods, and methods used to account for normal background radiation counts used within the 

different laboratories. 

7.1.2 External Measurements 

In vitro analyses of iodine are routinely performed in situations where in vivo analyses cannot be obtained 

or in support of an in vivo monitoring program. Urine is the preferred sample for in vitro analyses of 

iodine, although other sample types, such as feces, tissue, blood, serum, and hair, can also be used on a 

more limited basis with good detection sensitivities that are typically on the order of <1 μg per sample 

(NAS 1974). Urine provides for an analysis of soluble iodine, fecal analysis can be used to assess the 

fraction of ingested iodine not absorbed by the gut, and tissue is used to assess whole or regional body 

burdens of iodine (NCRP 1987). 

The in vitro analysis of the stable isotope of iodine, 127I, in commonly acquired human samples (e.g., 

urine, tissue, feces) is performed by a number of methods that have the selectivity and/or sensitivity to 

measure iodine in biological matrices (Table 7-1). These methods include arsenious-ceric ion catalytic 

spectrophotometry, instrumental neutron activation analysis (INAA), inductively coupled plasma atomic 

emission spectrometry (ICP-AES), and high performance liquid chromatography/ultra-violet-visible 

detection techniques (Andersson and Forsman 1997; Barker 1948; Benotti and Benotti 1963; Benotti et al. 

1965; Cornelis et al. 1975; EPA 1986; Hou et al. 1997b; Ohno 1971; Que Hee and Boyle 1988). The 

INAA and ICP-AES methods offer the greatest sensitivity for the detection of iodine in human samples 

(Table 7-1). An example of an application of INAA to the measurement of iodine in urine involves a 

prepurification of the urine sample to remove interfering ions, such as bromide, upon activation by 

neutrons (photopeaks are 0.45 MeV for 128I and 0.55 MeV for 82Br). The urine sample is first passed over 

Dowex 1X8 anion exchange resin, and then followed by the fusion of the washed and dried resin with 

NaOH/HNO3. The fusion residue is dissolved in water with a 0.5 mL aliquot transferred to a 

polyethylene sheet and dried. The sample is then irradiated with neutrons, dissolved in a solution 

containing an iodide carrier, extracted with trioctylamine/xylene, back extracted first with 1 M sodium 

nitrate to remove bromine, and then back extracted into 1 N ammonia. From here, the iodine is 

precipitated as silver iodide, filtered, and analyzed by gamma-ray spectrometry (Ohno 1971). 
 

 

 

 

 

IODINE 290 

7. ANALYTICAL METHODS 

For the in vitro analysis of the iodine radioisotopes, 125I and 131I, in human samples, there are a number of 

the analytical methods that can measure these radioisotopes directly in the samples without the 

requirement for an extensive sample preparation procedure (Table 7-2), as has been demonstrated for 

other radioisotopes (Gautier 1983). In the radiochemical analysis of radioiodine in urine, a 24-hour urine 

collection (approximately 2 L) is obtained followed by the transfer of a 1 L aliquot to a Marinelli beaker 

for counting in a gamma-ray spectrometer. This simple procedure offers high recoveries of 98% and the 

minimum detection sensitivity 100 pCi/L (3.70 Bq/L) that is required to evaluate individuals for 

exposures to 125I and 131I. Similar methods can also used for the analysis of these iodine radioisotopes in 

tissues, feces, blood, milk, and food (AOAC 1984; Baratta and Easterly 1989; Ekman et al. 1967; Gautier 

1983). 

For the quantification of 129I, more sensitive methods are required than those described above for 125I and 

131I (Table 7-2). One approach utilizes the transmutation of the 129I isotope to another isotope that can be 

quantified using mass spectrometric techniques. For example, neutron activation of iodine extracted from 

thyroid tissues, followed by noble gas mass spectrometry analysis of the resulting xenon isotopes, has 

been used to measure 129I and the 129I/127I ratio in these tissues (Boulos et al. 1973). This procedure uses 

the measurement of 126Xe, 128Xe, and 130Xe isotopes that are formed in the decay of the iodine isotopes, 

126I, 128I, and 130I, to determine the amount 129I and 127I in tissue extracts (see below). 

127I(n,γ)128I → 128Xe (β-

, half-life = 25 minutes) 

127I(n,2n)126I → 126Xe (β-

, half-life = 13 days) 

129I(n,γ)130I → 130Xe (β-

, half-life = 12.4 hours) 

127I(n,γ)128I(n,γ)129I(n,γ)130I → 130Xe (β-

, half-life = 12.4 hours) 

Both the ratio of 130Xe/128Xe and 130Xe/126Xe will be proportional to the ratio of 129I/127I in the extract. 

The method is able to provide a detection sensitivity that is sufficient to measure 129I as low as 45 pg/g 

tissue and/or a ratio of 129I/127I of 10-10. In those cases where INAA methods cannot be applied due to a 

large sample set size, availability of an appropriate reactor, the short half-life of the isotope of interest 

(e.g., 130I), or the cost of activation, there are other techniques available to enhance the detection 

sensitivity for the 129I isotope (Gabay et al. 1974). For example, preconcentration of 129I using anion 

exchange methods in addition to purifying the sample of interfering materials has been used successfully 

to analyze samples containing low amounts of 129I (Gabay et al. 1974, Table 7-2). Also, inductively 

coupled plasma-mass spectrometry (ICP-MS) methods have been used to quantify iodine in biological 

samples using differing sample preparation methods, including Schöniger combustion and extraction 
 

 

 

IODINE	 291 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Radioiodine in Biological Samples 

Sample Analytical Sample detection Percent 

matrix Preparation method method limit recovery Reference 

Urine Sample transferred to γ-Spectrometry 100 pCi/L (131I) 98% Gautier 1983 

Marinelli beaker and with NaI 

counted detector 

Thyroid 129I counted directly in X-Ray 0.04 pCi/g (129I) No data Van 

thyroid tissue	 spectrometry Middlesworth 

with HP Ge 1993 

detector 

Thyroid	 Powdered or fresh tissue Neutron 45 pg/g (129I) No data Boulos et al. 

digested with H2SO4; iodide activation and 1973; Oliver 

converted to Al2I6; neutron mass et al. 1982b 

irradiated, and iodine spectrometry 

precipitated with Pd 

Thyroid Tissue sample were INAA with 18–74 fCi/g (129I) 85% Handl et al. 

and other lyophiized and ground; Ge(Li) (thyroid) 1990 

tissues pyrolyzed in O2/N2 stream; γ-spectrometry 50–60% 

iodine absorbed onto (other 

charcoal; iodine liberated tissues) 

from charcoal by heating; 

isolated by distillation on 

cooled glass and then 

neutron irradiated 

Saliva Saliva samples obtained Scintillation 1.26–36.5 nCi/mL No data Nishizawa 

and directly counted counter (range of et al. 1985 

measured values) 

(

125I) 

Feces Sample directly counted in γ-Spectrometry 0.14 nCi/L (131I) No data Lipsztein et al 

detector with NaI 1991 

detector 

Cow’s milk Sample (50–100 mL) γ-Spectrometry 4–100 pCi/L (range No data Ekman et al. 

directly counted in iron with NaI of measured 1967 

shielded gamma detector values) (131I) 

spectrometer 

Cow’s milk Conversion of iodine to Liquid 0.3 pCi/L (129I) 58% raw Gabay et al. 

iodide; concentrated on scintillation milk, 80% 1974 

anion exchange resin; counter pasteurized 

extracted through CCl4, milk; with 

water, then toluene 30 mg 

iodine 

carrier 

Food	 Food samples directly γ-Spectrometry 0.05 pCi/g (131I) No data Cunningham 

counted in gamma-ray with NaI or et al. 1989, 

spectrometer Ge(Li) detector 1994 

HP = high purity; INAA = instrument neutron activation analysis 
IODINE 292 

7. ANALYTICAL METHODS 

methods, providing limits of detection (50 and 0.3 ng/g, respectively) that are appropriate for performing 

trace analysis of iodine in a large number of environmental and biological samples (Gélinas et al. 1998). 

Accuracy of in vivo and in vitro measurements of iodine and its radioisotopes is determined through the 

use of standard, certified solutions or radioactive sources with known concentrations or activities of 

iodine. National Institute of Standards and Technology (NIST) traceable standards for 125I and 127I can be 

obtained through a number of commercial sources. The primary source of certified iodine radioisotope 

standards is the NIST. Standard reference materials (SRM) for 129I (SRM 4401LZ, 30MBq [0.8 mCi]) 

and 131I (SRM 4949C, 17 kBq [0.45 μCi]) are available from NIST. SRMs are also available for 127I 

measurements, including SRM 909 (serum), SRM 1486 (bone meal), SRM 1548 (mixed diet), SRM 1549 

(nonfat milk powder), SRM 1846 (infant formula), and SRM 2383 (baby food). 

7.2 ENVIRONMENTAL SAMPLES 

There are two common approaches for measuring iodine radioisotopes in the environment. Iodine 

radioisotopes can either be measured directly in the field (in situ) using portable survey instruments or 

samples can be procured from the field and returned to the laboratory for quantification of iodine. 

However, quantification of the stable iodine isotope in environmental samples is generally conducted in 

the laboratory. 

7.2.1 Field Measurements of Iodine 

In situ measurement techniques are extremely useful for the rapid characterization of radionuclide 

contamination in the environment, such as soils, sediments, and vegetation, or when monitoring personnel 

for exposure to radionuclides. The measurement of gamma-ray-emitting radionuclides in the 

environment is conducted with portable survey instruments such as Gieger-Mueller detectors, sodium 

iodide scintillation detectors, and gamma-ray spectrometers. However, the use of gamma-spectrometers 

in field survey equipment is preferred for measuring 131I in the field because of their selectivity and 

sensitivity (EML 1997). The energy and penetrance of the gamma-rays that are emitted during the decay 

of 131I provides an advantage for assessing the level of iodine both on and below the surface using 

portable field survey instruments such as the gamma-ray spectrometer (EML 1997). These gamma-ray 

spectrometers are equipped with a high purity germanium detector that is able to resolve the 364 keV 

gamma-ray emitted from 131I from the gamma-rays emitted from other radionuclides; for example, 40K 
IODINE 293 

7. ANALYTICAL METHODS 

(USNRC 1997). The concentration and distribution of 131I that have been detected in the field will need 

to be determined by laboratory-based analyses of soil samples procured from the survey area. 

7.2.2 Laboratory Analysis of Environmental Samples 

Analytical methods for quantifying iodine and iodine radioisotopes in environmental samples (e.g., air, 

water, soil, biota, and food) are summarized in Tables 7-3 (127I) and 7-4 (125I, 129I, and 131I). The methods 

that are commonly used in the analysis of 127I are based on instrument-based analytical techniques, such 

as spectrophotometry, electrochemistry, INAA, mass spectrometry (MS), and some colorimetric 

techniques. The analysis of 125I, 129I, and 131I can be determined either as total mass or total activity, 

depending on the analytical technique that is used. Typically, radiochemical methods of analysis 

employing gamma-ray spectrometry and β-γ coincidence scintillation techniques are used to quantify 125I 

and 131I in environmental samples. However, more sensitive analytical techniques, such as INAA and 

MS, are typically required to analyze 129I in environmental samples (Lindstrom et al. 1991; Stephenson 

and Motycka 1994). Neutron activation and mass spectrometric methods are especially useful, since the 

amount of 129I in a sample is often expressed in proportion to amount of 127I in the same sample 

(Muramatsu et al. 1985). For example, the mass spectrometry techniques that are utilized to measure 

iodine in samples, such as neutron activation-noble gas mass spectrometry or accelerator mass 

spectrometry, provide the ability to resolve the 127I and 129I isotopes in the quantitation step and also have 

the required sensitivity range to measure ratios of 10-10–10-7 for 129I/127I in most environmental and 

biological samples (Gramlich and Murphy 1989; Schmidt et al. 1998). 

The analysis of 127I in air is based on the quantification of this isotope of iodine in its gaseous form (I2) or 

within aerosols or particulates, either separately or combined (Dams et al. 1970; Gäbler and Heumann 

1993; Kim et al. 1981; Sheridan and Zoller 1989; Tsukada et al. 1991). The concentration of gaseous 

iodine in air can be determined by passing a known volume of air through a tube containing activated 

charcoal, followed by extraction of the iodine from the charcoal and analysis by a number of techniques, 

including ion chromatography (Kim et al. 1981). Both the gaseous and particulate forms of iodine can be 

simultaneously assessed by passing a specified volume of air through a filtering device containing a series 

of filters with differing pore sizes and coatings (Gäbler and Heumann 1993; Tsukada et al. 1991). Both 

gaseous and particulate forms of iodine are trapped on the various filter stages, depending on the type of 

coating and pore size of the filter stage after a calibrated amount of air is pulled through the filters. For 

the analysis of 127I on the filters, the filter is solvent extracted and the extracted iodine is analyzed by 

INAA (Sheridan and Zoller 1989; Tsukada et al. 1991), nondestructive neutron activation analysis (Dams 
 

 

 

IODINE	 294 

7. ANALYTICAL METHODS 

Table 7-3. Analytical Methods for Determining Iodine in Environmental Samples 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Aerosol Aerosols collected using an 

(ambient) Anderson cascade impactor; 

iodine separated from filters 

by ignition and adsorbed onto 

charcoal; extracted from 

charcoal using NaOH 

solution; acidified; extracted 

into CCl4 as iodine; back 

extracted into dilute H2SO4 

and precipitated as PdI2, then 

neutron irradiated 

Air (ambient) A known volume of air is 

passed through a multistage 

filter assembly; filters 

extracted in a heated 

NaOH/Na2SO3 solution 

containing 129I

-

 as an internal 

standard; filtered; acidified; 

iodide precipitated as AgI; 

filtered; precipitate dissolved 

in aqueous NH3 and analyzed 

Air A known volume of air is 

(occupational)	 drawn into a glass tube 

containing 150 mg of 

charcoal; iodine extracted into 

0.01 M Na2CO3 using an 

ultrasonic bath; filtered; 

injected into ion 

chromatograph 

Water and CaO added to sample; 

waste water filtered; sodium acetate/acetic 

(EPA Method acid then bromine water 

345.1) added; excess bromine with 

sodium formate removed; KI 

and H2SO4, titrate added with 

phenylarsine oxide or sodium 

thiosulfate using starch 

indicator 

Water Sample acidified with HCl; 

oxidized with H2O2 or KMnO4; 

treated with NaSO3 to remove 

excess oxidant; titrated with 

KIO3 

INAA with Ge 1.68–4.23 ng/m3 

γ-ray detector (range of 

measured 

values) 

IDMS 0.02–0.024 

ng/m3

 (for an 

average air 

volume of 

70 m3

) 

Ion chromato- 0.45 μg/mL 

graphy 

Colorimetric 2–20 mg/L 

(range of 

measured 

values) 

Spectrophoto- 25 μg/L– 

metry 6.35 mg/L 

No data Tsukada et al. 

1991 

97–99% Gäbler and 

Heumann 

1993 

101% Kim et al. 

1981 

80–97% EPA 1983 

(at 4.1– 

21.6 mg/L) 

-100% (at Pesavento 

0.13–6.35 and Profumo 

mg/L) 1985 
IODINE	 295 

7. ANALYTICAL METHODS 

Table 7-3. Analytical Methods for Determining Iodine in Environmental Samples 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Water Sample reacted with acidified 

(iodide) NaNO2; evolved iodine 

extracted into xylene; back 

extracted into 0.5 % aqueous 

ascorbic acid and analyzed at 

the emission intensity for 

iodine of 178.28 nm 

Water (iodine	 Samples divided and spiked 129 species) with IO3

129I-

or -; oxidized 

with UV or HNO3/H2O2 

(total I), or concentrated/ 

purified on an anion 

exchange column (I-

, IO3

-

; 

anionic organoiodine); 

samples are then reduced 

with Na2SO3 and precipitated 

as AgI 

Drinking water Sample separated on a 

Dionex AS12 analytical HPLC 

column; the eluted iodate 

reacted with acidified bromide 

in post-column reaction to 

form tribromide that is 

detected at 267 nm 

Tap water Sample acidified to 0.1 mN 

nitric acid + Hg+2 (as 

Hg(NO3)2) added to 300 μg/L; 

20 μL aliquot injected into 

atomizer 

Fresh water Iodine-iodide is directly 

(total iodine) measured in water sample 

Fresh water Iodine-iodide is removed from 

(iodate)	 sample through extraction 

into chloroform as ion-pair 

with tetraphenylarsonium 

cation 

Fresh water One liter sample is acidified 

with nitric acid; 5 mL sample 

is irradiated, filtered, and 

counted 

Drinking water K2CO3 added to sample; 

(total iodine) centrifuged to remove 

precipitated alkaline earth 

metals; iodine measured by 

addition of nitric acid, NaCl, 

NH4Fe(SO4)2 and KSCN 

ICP-AES 

IDMS 

HPLC with UV 

detection 

Electrothermal 

atomic 

absorption 

spectrometry 

As-Ce 

catalytic 

spectrophotometry 

As-Ce 

catalytic 

spectrophotometry 

INAA using 

Ge(Li) 

γ-spectrometry 

Spectrophotometry 

1.6 μg/L 

0.5 μg/L (I-

) 

0.1 μg/L (IO3

-

) 

0.2 μg/L (anionic 

organoiodine) 

0.05 μg/L (total 

iodine) 

0.05 μg/L 

3.0 μg/L 

0.1 μg/L 

0.1 μg/L 

0.20 μg/L 

0.2 μg/L 

97–102% Miyazaki and 

Bansho 1987 

No data Reifenhäuser 

and Heumann 

1990 

110–111% Weinberg and 

(at 0.5– Yamada 1997 

2.0 μg/L) 

94.8– Bermejo104.4% Barrera et al. 

(at 1994 

5–20 μg/L) 

100% Jones et al. 

1982b 

-100% Jones et al. 

(at 2 μg/L 1982b 

iodate) 

No data Salbu et al. 

1975 

90–108% Moxon 1984 
 

 

 

 

IODINE	 296 

7. ANALYTICAL METHODS 

Table 7-3. Analytical Methods for Determining Iodine in Environmental Samples 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Drinking water 

(free iodide) 

Fresh and sea 

waters 

Sea water and 

river water 

Sea water 

Sea water 

(iodine) 

Sea water 

(iodate) 

K2CO3 added to sample; 

centrifuged to remove 

precipitated alkaline earth 

metals; iodide measured by 

addition of reduced amounts 

of nitric acid, NaCl, 

NH4Fe(SO4)2, and KSCN 

Samples directly injected onto 

a weakly anionic ionexchange column for iodide 

analysis; iodate measured 

through reduction to iodide by 

ascorbic acid 

Sample (neat or diluted) were 

treated with HClO4, acetone, 

and KMnO4; KMnO4 reduced 

with oxalic acid, then treated 

with NaS2O3/chromic acid 

followed by extraction into 

benzene containing 

p-dichlorobenzene as an 

internal standard 

Sample acidified with acetic 

acid; bromine vapor dissolved 

into sample; excess removed 

through volume reduction; 

titrated with iodate 

Iodide in sample precipitated 

with AgNO3; precipitate 

dissolved in acetic acid 

saturated with Br2; filtered; 

filtrate reduced in volume; 

then reacted with starch 

solution and CdI2 

Iodide in sample precipitated 

with AgNO3; iodate in fitrate is 

reduced to iodide with 

NaSO3/H2SO4, acetic acid 

saturated with Br2 added; 

filtered; filtrate reduced in 

volume; reacted with starch 

solution and CdI2 

Spectrophoto- 0.4 μg/L 

metry 

HPLC with 2 μg/L 

ion-selective 

electrode 

detector 

GC-ECD 0.1 μg/L 

Amperometric 5 μg/L 

method 

Spectrophoto- 0.025 μg/L 

metry 

Spectrophoto- 0.025 μg/L 

metry 

89–109% Moxon 1984 

No data Butler and 

Gershey 1984 

No data Maros et al. 

1989 

98–112% Barkley and 

Thompson 

1960 

99% Tsunogai 1971 

(at 10 μg/L 

iodine) 

No data Tsunogai 1971 
IODINE 297 

7. ANALYTICAL METHODS 

Table 7-3. Analytical Methods for Determining Iodine in Environmental Samples 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Sea water 

Sea water and 

brackish water 

Sea water and 

brackish water 

Sea water and 

brackish water 

Brine and 

thermal waters 

Groundwater 

Soil 

Sample filtered and 

concentrated/purified on an 

AG1X4 anion exchange 

column; I-

, IO3

-

, and organic 

iodine were isolated 

preferentially isolated; 

neutron irradiated; iodide 

carrier added; treated with 

NaNO2 in HNO3; extracted 

into CCl4; back extracted into 

a KHSO3 solution and 

counted 

Sample treated with CaO; 

iodide oxidized with Br2 in 

acetate buffer; excess Br2 

removed with sodium 

formate; iodate converted to 

iodine and titrated with 

NaS2O3 using starch indicator 

Sample is acidified with HCl; 

iodide converted to iodine 

with KNO2 and extracted into 

CCl4; absorbance of iodineCCl4 measured at 517 nm 

500 μL of sample diluted to 

50 ml with water plus NaNO2 

solution; measured potential; 

quantitated using standard 

additions 

Sample treated with 14 N 

H2SO4 plus 3 M H2O2; 

extracted with CCl4; back into 

0.1 mM NaS2O3; then 

iodine/methylene blue ion pair 

extracted into 1,2-dichloroethane 

Metals chelated with EDTA 

and iodate is directly 

measured; iodide can be 

indirectly measured through 

conversion to iodate by 

treatment with chlorine water 

Sample dried; sieved (7 mm 

diameter), ground; sieved 

(2 mm diameter); extracted 

with 2 N NaOH; arsenious 

acid added then submitted for 

automated analysis 

INAA using 

Ge(Li) 

γ-spectrometry 

Spectrophotometry 

Spectrophotometry 

Iodide 

selective 

electrode 

Spectrophotometry 

Single-sweep 

polarography 

As-Ce 

catalytic 

spectrophotometry 

0.2 μg/L 

0.2–2,000 mg/L 

(range of 

measured 

values) 

0.2–2,000 mg/L 

(range of 

measured 

values) 

1–2,000 mg/L 

(range of 

measured 

values) 

10 μg/L 

0.005 μg/L 

0.5 μg/g 

99.5% 

(postirradiation 

recovery) 

93.6– 

96.7% 

(at 12.1– 

1,375 mg/ 

L) 

100–108% 

(at 12.1– 

1,375 

mg/L) 

102–109% 

(at 12.1– 

1,375 

mg/L) 

68% 

(at 0.4 mM 

iodine) 

No data 

No data 

Hou et al. 

1999 

ASTM 1995 

ASTM 1995 

ASTM 1995 

Koh et al. 

1988 

Whitnack 1975 

Whitehead 

1979 
IODINE 298 

7. ANALYTICAL METHODS 

Table 7-3. Analytical Methods for Determining Iodine in Environmental Samples 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Soil, sediments, 

rock 

Sample dried and pulverized; 

mixed with V2O5 and 

pyrohydrolyzed; evolved 

iodine dissolved in NaOH 

solution digested with acid 

As-Ce 

catalytic 

spectrophotometry 

0.05 μg/g (0.5 g 

sample size) 

75–90% Rae and Malik 

1996 

Coal and fly 

ash 

<250 mg samples dried; 

irradiated with neutrons and 

then counted 

INAA using 

Ge(Li) 

γ-spectrometry 

0.6–1.8 μg/g 

(range of 

measured 

No data Germani et al. 

1980 

values) 

Vegetation Sample prepared by 

microwave digestion using 

HNO3/H2O2; treated with 

Na2S2O3 or ascorbic acid 

ICP-MS 100 pg/g 96–104% Kerl et al. 

1996 

solution to convert iodate to 

iodide 

As-Ce catalytic spectrophotometry = arsenious-ceric ion catalytic spectrophotometry; GC-ECD = gas chromatographyelectron capture detection; HPLC = high performance liquid chromatography; ICP-AES = inductively coupled plasmaatomic emission spectrometry; ICP-MS = inductively coupled plasma-mass spectrometry; IDMS = isotope dilution mass 

spectrometry; INAA = instrumental neutron activation analysis; UV detection = ultraviolet/visible detection 
 

 

IODINE 299 

7. ANALYTICAL METHODS 

Table 7-4. Analytical Methods for Determining Radioiodine in Environmental 

Samples 

Sample matrix Preparation method 

Analytical 

method 

Sample 

detection limit 

Percent 

recovery Reference 

Air 

(occupational) 

Air samples drawn into a 

regulated, constant-flow 

air sampler for personnel 

monitoring at a flow rate 

off 2 L/minute for several 

periods of 2–7 minutes; 

air-borne iodine was 

Scintillation 

counter with NaI 

detector 

2 fCi/mL (131I) No data Luckett and 

Stotler 

1980 

trapped in a charcoal 

sampling tube, then 

counted 

Aerosols 

(occupational) 

Air drawn through a 

25 mm cellulose 

nitrate/acetate filter at a 

constant flow rate of 

Scintillation 

counter with NaI 

detector 

5 fCi/mL (125I) 

0.3 fCi/mL (131I) 

No data Eadie et al. 

1980 

2 L/minute; filter counted 

Aerosols 

(ambient) 

Aerosols were collected 

using an Anderson 

cascade impactor; filters 

removed from impactor 

and then neutron 

INAA with Ge 

γ-ray detector 

0.24–0.26 aCi/m3 

(range of 

measured 

values) (129I) 

No data Tsukada 

et al. 1991 

irradiated 

Water Add iodide carrier and 

NaOCl to 4 L sample; 

stir; add NH2OH�HCl 

γ-Spectrometry 

with Ge detector 

<1 pCi/L (131I) No data ASTM 

1995 

and NaHSO3; stir; filter; 

extract through anion 

exchange resin; elute 

iodide with NaOCl; treat 

with HNO3; extract with 

toluene and aqueous 

NH2OH�HCl, back 

extract with aqueous 

NaHSO3; precipitate 

iodide as CuI 

Drinking water Iodate carrier added to 

sample and iodate 

reduced to iodide with 

β-γ Coincidence 

scintillation system 

0.1 pCi/L (131I) No data EPA 1976, 

1980 

NaSO3; iodide 

precipitated with AgNO3; 

AgI dissolved and 

purified with Zn powder 

and sulfuric acid; iodide 

reprecipitated as PdI2 
 

 

IODINE	 300 

7. ANALYTICAL METHODS 

Table 7-4. Analytical Methods for Determining Radioiodine in Environmental 

Samples 

Analytical Sample Percent 

Sample matrix Preparation method method detection limit recovery Reference 

Drinking water Iodate carrier and tartaric 

acid are added to 

sample, HNO3 added 

and sample distilled into 

NaOH solution; distillate 

acidified with H2SO4 and 

oxidized with NaNO2; 

extracted into CCl4; back 

extracted into NaHSO3; 

and iodide reprecipitated 

as PdI2 

Fresh water Conversion of iodine to 

iodide; concentrated on 

anion exchange resin; 

extracted with CCl4, 

water, then toluene 

Fresh water Iodide carrier added to 

sample; treated with HCl 

and sodium 

metabisulfite; iodide 

concentrated on a strong 

anion exchange resin 

with iodine carrier; 125I 

directly detected on resin 

River water Sample directly analyzed 

or concentrated on an 

anion exchange resin; 

eluted with nitric acid; 

analyzed, using indium 

as an internal standard 

Aqueous sample Sample concentrated on 

a Dowex 1x8 anion 

exchange resin; resin 

pyrolyzed; iodine 

adsorbed onto activated 

charcoal; iodine removed 

by heating charcoal; 

neutron irradiated; iodine 

carrier added; iodine 

extracted into xylene; 

iodide precipitated with 

silver 

Β-γ Coincidence 0.1 pCi/L (131I) 

scintillation system 

Liquid scintillation 0.3 pCi/L (129I) 

counter 

γ-Spectrometry 30 pCi/L (125I) 

with Ge(Li) 

detector and 

x-ray fluorescence 

for yield correction 

ICP-MS 0.5 pCi/L (129I) 

INAA with Ge(Li) 3.8 fCi/L (129I) 

detector 

No data EPA 1976 

74% with Gabay 

30 mg et al. 1974 

iodine 

carrier 

No data Howe and 

Bowlt 1991 

No data Beals and 

Hayes 

1995; 

Beals et al. 

1992 

50% Anderson 

1978 
 

 

IODINE	 301 

7. ANALYTICAL METHODS 

Table 7-4. Analytical Methods for Determining Radioiodine in Environmental 

Samples 

Analytical Sample Percent 

Sample matrix Preparation method method detection limit recovery Reference 

Water Iodide carrier was added 

to samples; treated with 

sodium hypochlorite, 

purified; reduced to 

isolate iodine and iodine 

precipitated as AgI; AgI 

was mixed with either a 

niobium or ultrapure 

silver metal binder and 

dried onto stainless-steel 

sample holders for 

analysis 

Water and Direct count of sample 

waste water 

Treated sewage Sample directly counted 

effluent in 3.5 L aluminum beaker 

Treated sewage Sample counted directly 

(influent/effluent) or first concentrated on 

anion exchange column 

after reduction of iodine 

to iodide in sample; 

eluted with acid then 

counted 

Soil, sediments, Sample dried; iodine 

vegetation extracted through 

combustion of soil in 

oxygen; iodine trapped 

onto charcoal after 

passage over hydrated 

manganese dioxide 

(HMD); neutron 

irradiated; Br removed 

through passage over 

HMD 

Vegetables Sample lyophilized; 

Na2CO3, NaCl, and 131I 

(internal standard) 

added; dried and ashed; 

treated with MnO2 and 

evolved iodine trapped in 

0.1% NaHSO3 containing 

iodide carrier 

AMS <0.3 pg/g (

129I) 

γ-Spectrometry <2 pCi/L (131I) 

with Ge/Li detector
 

γ-Spectrometry No data (131I) 

with NaI(Tl) 

detector 

γ-Spectrometry 180 pCi/L (direct 

with NaI(Tl) count), 

detector 0.35 pCi/L 

(concentrated) 

(

131I) 

INAA with Ge(Li) 5 aCi/g (129I) 

detector 

ICP-MS 1.4 pg/g 

(0.24 fCi/g) (129I) 

No data DOE 1994; 

Elmore and 

Phillips 

1987; 

Elmore et 

al. 1980 

92–100% at ASTM 

2–94 pCi/L 1998 

No data Sodd et al. 

1975 

No data Prichard 

et al. 1981 

No data Lindstrom 

et al. 1991; 

Lutz et al. 

1984 

88% Cox et al. 

1992 
 

 

IODINE 302 

7. ANALYTICAL METHODS 

Table 7-4. Analytical Methods for Determining Radioiodine in Environmental 

Samples 

Analytical Sample Percent 

Sample matrix Preparation method method detection limit recovery Reference 

Plants Plant samples were 

lyophiized and ground; 

125I added as internal 

INAA with Ge(Li) 

γ-spectrometry 

18–74 fCi/g (129I) 50–60% Handl et al. 

1990 

standard; sample was 

pyrolyzed in O2/N2 

stream; iodine absorbed 

onto charcoal; iodine 

liberated from charcoal 

by heating; isolated by 

distillation on cooled 

glass and then neutron 

irradiated 

AMS = accelerator mass spectrometry; ICP-MS = inductively coupled plasma-mass spectrometry; INAA = instrumental 

neutron activation analysis 
IODINE 303 

7. ANALYTICAL METHODS 

et al. 1970), and isotope dilution mass spectrometry (Gäbler and Heumann 1993). Analysis of airborne 

125I, 129I, and 131I can also be performed using the filtering techniques described above, followed by a 

direct measurement by beta- or gamma-ray counting of these radioisotopes on the filter or within 

activated charcoal (Eadie et al. 1980; Luckett and Stotler 1980) or quantified with more sensitive 

techniques (129I) such as INAA (Tsukada et al. 1991). 

For the analysis of iodine in water, there is a broad array of sample preparation and detection 

methodologies that are available (see Tables 7-3 and 7-4). A number of methods can directly quantify 

iodine or its radioactive isotopes within a water sample using spectrophotometric, ion-selective 

electrodes, INAA, ICP-MS, polarography, or radiochemical techniques with minimal sample preparation 

and good detection sensitivities (0.1–2.0 μg/L for 127I, <2 pCi/L [0.07 Bq/L] for 131I) (ASTM 1995, 1998, 

Beals and Hayes 1995; Beals et al. 1992; Butler and Gershey 1984; Jones et al. 1982b; Prichard et al. 

1981; Salbu et al. 1975; Sodd et al. 1975; Stephenson and Motycka 1994; Whitnack 1975). Some 

analytical methods provide for the analysis of total iodine in the sample as well as the various iodine 

species in water (e.g., I-

, I2, IO3

-

, and organic iodine) (Reifenhäuser and Heumann 1990; Wong and Cheng 

1998). However, poor or inconsistent recovery of some iodine species (e.g., I- and IO3

-

) during the ion 

exchange stage of the sample preparation, which is due to both irreversible binding of these iodine species 

to some ion exchange resins and interference from dissolved organic carbon, often can limit the accuracy 

of these methods for determining iodine species in aqueous samples (Stephenson and Motycka 1994). 

One of the more commonly used assays for analyzing iodine at μg/L concentrations in water can be done 

directly using the catalytic spectrophotometric method. In the assay, iodine acts as a catalyst in the 

reduction of the ceric ions [Ce(IV)] by arsenous ions [As(III)]:

 I2Ce(IV) + As(III) ÷ 2Ce(III) + As(V) 

In the absence of iodine, the reaction is very slow (-35 hours), but is on the order of minutes in the 

presence of iodine. The changes in the reaction rate, as followed by the decay in the Ce(IV) absorbance 

at either 420 or 366 nm, are inversely proportional to the iodine concentration in the sample (Jones et al. 

1982b; Lauber 1975; Truesdale and Smith 1975). This assay has been developed into an automated 

process offering the advantage of large sample batch analyses (Truesdale and Smith 1975). 

However, like many of the methods that are used to quantify iodine, a number of interferences can affect 

the measurement of iodine by the catalytic spectrophotometric method, including background coloration, 
 

 

 

IODINE 304 

7. ANALYTICAL METHODS 

turbidity, and compounds, such as Fe(II), that are capable of reducing Ce(IV) (Jones et al. 1982b; 

Truesdale and Smith 1975). Thus, methods have been developed that purify iodine by first extracting 

iodine into an organic solvent and then back extracting the iodine into an appropriate aqueous solution for 

As–Ce catalytic spectrophotometric analysis (Jones et al. 1982b; Whitehead 1979). Likewise, for most 

methods, there is often a need to preconcentrate, redox convert the various iodine species (e.g., I-

, I2, 

IO3

-

), and/or isolate iodine or its radioisotopes from the sample in order to improve sensitivity or remove 

interfering species, as is illustrated in Tables 7-3 and 7-4. Newer techniques have been developed to 

improve the separate quantification of iodine species. An example is the use of ICP-MS to quantify 

iodide directly in the samples after filtering, whereas iodine is quantified as a vapor that is evolved from 

the sample following treatment of the sample with potassium nitrite in sulfuric acid. This approach 

provides a detection limit of 0.04 μg/mL and recoveries of 86.5–118.6% (Anderson et al. 1996b) 

The quantity of iodine and its radioisotopes in soil, sediments, minerals, vegetation, and biota is 

determined using detection methods similar to those described above (Tables 7-3 and 7-4). Analysis of 

iodine in samples by spectrophotometry, electrochemistry, and MS requires some form of sample 

digestion, either treatment in acid or pyrolysis. For most methods, sample concentration or purification is 

required to remove interfering species and/or improve detection sensitivity. 

In the quantification of 129I in soil, mineral, and biological samples by the INAA method, improvements 

to the INAA method for determining 129I have been developed to minimize the possible interferences that 

can occur from 133Cs(n,α)

130I, 127I(3n,γ)130I, 235U(n,f)129I as well as neutron capture by 128Te and 130Te. 

The presence of bromine within a particular sample also can interfere with the quantification of 129I due to 

the higher activity of 82Br, the small difference in the photopeak maxima for 129I (0.45 MeV) and 82Br 

(0.55 MeV) and chemical similarities for I and Br (Ohno 1971; Rook et al. 1975). Most of these 

interferences have been eliminated through the use of pre-irradiation separation step that involves the 

combustion of iodine from biological materials followed by the collection of iodine on activated charcoal 

(Rook et al. 1975). A post-irradiation step also has been developed using a electromagnetic mass 

separator with a hot cathode arc ion chamber source to separate and collect sample components within a 

specific mass range onto a aluminum foil for subsequent quantification by a β-γ coincidence analysis 

system (Rook et al. 1975). 

The detection limits, accuracy, and precision of any analytical methodology are important parameters in 

determining the appropriateness of a method to quantify a specific analyte at the desired level of 

sensitivity within a particular matrix. The Lower Limit of Detection (LLD) has been adopted to refer to 
 

 

IODINE 305 

7. ANALYTICAL METHODS 

the intrinsic detection capability of a measurement procedure (sampling through data reduction and 

reporting) to aid in determining which method is best suited for the required sample quantification (EML 

1997; USNRC 1984). Several factors influence the LLD, including background counting-rates, size or 

concentration of sample, detector sensitivity, recovery of desired analyte during sample isolation and 

purification, level of interfering contaminants, and, particularly, counting time. Because of these 

variables, the LLDs between laboratories, utilizing the same or similar measurement procedures, will 

vary. 

The accuracy of a measurement technique in determining the quantity of a particular analyte in 

environmental samples is greatly dependent on the reliability of the calibrating technique. Thus, the 

availability of standard, certified radiation sources with known concentrations of iodine and its 

radioisotopes are required in order to insure the reliability of the calibration methods and accuracy of 

iodine measurements in environmental samples. NIST traceable standards for 127I can be obtained 

through a number of commercial sources. The primary source of certified iodine radioisotope standards is 

the NIST. Standard reference materials for 129I (SRM 4401LZ, 30 MBq [0.8 mCi]) and 131I (SRM 4949C, 

17 kBq [0.45 μCi]) are available from NIST. SRMs are also available for 127I measurements, including 

SRM 1515 (apple leaves), SRM 1547 (peach leaves), SRM 1566 (oyster tissue), SRM 1572 (citrus 

leaves), SRM 1573 (tomato leaves), SRM 1575 (pine needles), SRM 1577 (bovine liver), SRM 1632 

(coal), SRM 1633 (fly ash), SRM 1643 (water), SRM 2704 (sediment), and SRM 2709 (soil). 

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 iodine and its radioisotopes 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 iodine and its radioisotopes. 

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. 
IODINE 306 

7. ANALYTICAL METHODS 

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 iodine and its radioisotopes 

in human tissues and body fluids. 

Exposure. Analytical methods with satisfactory sensitivity and precision are available to determine the 

exposure levels of iodine and its radioisotopes in human tissues and body fluids. 

Effect. Analytical methods with satisfactory sensitivity and precision are available to determine the 

levels of effect for iodine and its radioisotopes in human tissues and body fluids. 

Methods for Determining Parent Compounds and Degradation Products in Environmental Media. 

Analytical methods with the required sensitivity and accuracy are available for quantifying iodine, both 

total and isotopic, in environmental matrices (Tables 7-3 and 7-4). Knowledge of the levels of iodine in 

various environmental media, along with appropriate modeling (see Chapters 3 and 6), can be used to 

evaluate potential human exposures through inhalation and ingestion pathways. 

Whether in the environment or in the human body, iodine radioisotopes will undergo radioactive decay to 

form a series of compounds that are also radioactive (see Chapter 3). Current analytical methods, such as 

mass spectrometry, have the necessary resolution and sensitivity to detect and quantify these decay 

products. 

7.3.2 Ongoing Studies 

Current research studies, as provided by a search of the Federal Research in Progress (FEDRIP) database, 

are looking at improvements in the resolution and sensitivity of gamma-ray scintillation spectrometers 

through the development of innovative scintillating materials. In the work proposed in the research grant 

entitled “Ultra-Compact Cesium Iodide - Mercuric Iodide Gamma-Ray Scintillation Spectrometer” (B.E. 

Patti, Principal Investigator), the investigators are working with CsI/HgI scintillation pairs to develop a 

room temperature gamma-spectrometer after having some preliminary success with the detection of the 

660 keV gamma-ray from 137Cs (4.58% FWHM) (FEDRIP 2000). In another study entitled “Bismuth 
IODINE 307 

7. ANALYTICAL METHODS 

Iodide Crystal Growth” (L.A. Boatner, Principal Investigator), the investigators are working on 

developing techniques for growing bismuth iodide crystals for room temperature radiation detectors and 

testing these crystals for their efficiency and energy resolution characteristics (FEDRIP 2000). 

 

 

IODINE 309 

8. REGULATIONS AND ADVISORIES 

The international, national, and state regulations and guidelines regarding stable iodine in air, water, and 

other media are summarized in Table 8-1. The regulations regarding radioactive iodine are summarized 

in Tables 8-2 and 8-3. 

No MRLs were derived for inhalation exposure to stable or radioactive iodine. Oral MRLs of 

0.01 mg/kg/day were derived for both acute- and chronic-duration exposures. No oral MRL was derived 

for intermediate-duration exposure. 

The EPA has not classified iodine for human carcinogenicity, nor has the EPA derived reference 

concentrations (RfCs) or reference doses (RfDs) for stable or radioactive iodine (IRIS 2000). 
 

 

 

IODINE	 310 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Stable Iodine 

Agency Description Information References 

INTERNATIONAL 

Guidelines: 

IARC Carcinogenicity classification 

NATIONAL 

Regulations and 

Guidelines: 

a. Air 

ACGIH STEL (ceiling) 

NIOSH REL (ceiling) 

IDLH 

OSHA PEL (ceiling)—general industry 

PEL (ceiling)—construction industry 

PEL (ceiling)—shipyard industry 

b. Water 

EPA Effluent limitation guidelines; 

inorganic chemicals manufacturing 

point source category for iodine 

production 

c. Food 

FDA Drug products containing certain 

active ingredients offered over-thecounter for certain uses 

Drugs; recommended warning and 

caution statements—iodine and 

iodides (oral)
 

Food additives permitted for direct 

addition to food for human
 

consumption (as potassium iodide) 

Total amount for foods labeled 

without reference to age or 

 physiological state 

Food additives permitted for direct 

addition to food for human 

consumption (as potassium iodide) 

Infants 

Children under 4 years of age 

Adults and children 4 or more 

years of age 

Pregnant or lactating women 

Food labelingCRDI 

No data 

0.1 ppm ACGIH 2000

0.1 ppm NIOSH 2001

2.0 ppm 

0.1 ppm OSHA 2001b 

29CFR1910.1000 

0.1 ppm OSHA 2001a 

29CFR1926.55 

0.1 ppm OSHA 2001c 

29CFR1915.1000 

Effluent reduction EPA 2001b 

attainable by the 40CFR415.432 

application of BPT; no 

discharge of process 

wastewater pollutants 

to navigable waters 

Digestive aid and FDA 2000a 

weight control drug 21CFR310.545 

product 

If a skin rash appears, FDA 2000b 

discontinue use and 21CFR369.20 

consult physician 

FDA 2000c 

21CFR172.375 

225 μg 

FDA 2000c 

21CFR172.375 

45 μg 

105 μg 

225 μg 

300 μg 

150 μg FDA 2001b 

21CFR101.9 
 

 

 

 

 

IODINE 311 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Stable Iodine 

Agency Description Information References 

NATIONAL (cont.) 

FDA Indirect food additives; sanitizing Aqueous solution FDA 2000d 

solutions used on food and 21CFR178.1010 

dairy processing (b)(40) 

equipment and 

utensils 

NutrientsCminimum amount per 5.0 μg FDA 2001a 

100 kilocalories 

Nutrition labeling of dietary FDA 2000e 

supplements 21CFR101.36 

Nutritional quality guidelines FDA 2000f 

RDIa 150 μg 21CFR104.20 

Amount per 100 caloriesb 7.5 μg (d)(3) 

Trace minerals added to animal 

feedsCcalcium iodate, calcium 

iodobehenate, cuprous iodide, 

3,5-diiodosalicylic acid, 

ethylenediamine dihydroiodide, 

potassium iodate, potassium iodide, 

sodium iodate, sodium iodide, and 

thymol iodide 

Recognized as safe 

when added at levels 

consistent with good 

feeding practice 

FDA 2000i 

21CFR582.80 

d. Other 

ATF List of denaturants authorized for ATF 2001a 

denatured spirits 27CFR21.151 

List of products and processes 

using specially denatured alcohol 

and rum, and authorized formula 

 ATF 2001b 

27CFR21.141

 USC List II chemicalCregulated by the 

Attorney General as a chemical 

used in manufacturing a controlled 

substance

 USC 2001 

21USC802 

STATE 

Regulations and 

Guidelines: 

a. Air 

Alaska PEL (ceiling) 0.1 ppm BNA 2001h 

California Airborne contaminant BNA 2001h 

HAP BNA 2001h 

Hawaii Air contaminant BNA 2001h 

Idaho Toxic air pollutants 

OEL 

EL 

AAC (24-hour average) 

0.1 mg/m3 

6.7x10-3 pounds/hour 

5x10-3 mg/m3 

BNA 2001h 

 Michigan Occupational air contaminant; 

maximum allowable concentrations 

0.1 ppm BNA 2001h 

Limits for air contaminants BNA 2001h 

 PEL (ceiling) 0.1 ppm 
 

 

IODINE 

8. REGULATIONS AND ADVISORIES 

312 

Agency 

Table 8-1. Regulations and Guidelines Applicable to Stable Iodine 

Description Information References 

STATE (cont.)

 Montana Occupational air contaminant 

TLV 0.1 ppm 

BNA 2001h 

New Hampshire Regulated toxic air pollutant 

OEL 1 mg/m3 

BNA 2001h 

New Mexico Toxic air pollutant and emissions 

OEL 

 Emissions 

0.1 ppm 

6.67x10-2 pounds/hour 

BNA 2001h 

New York Exposure limits 

 PEL (ceiling) 0.1 ppm 

BNA 2001h 

 Oregon Air contaminant 

 PEL (8-hour TWA) 0.1 ppm 

BNA 2001h 

Texas Airborne contaminant BNA 2001h 

Vermont Hazardous air contaminant BNA 2001h 

Hazardous air contaminants that BNA 2001h 

cause short-term irritant effects

 Annual average 

 Averaging time 

 Action level 

100 μg/m3 

8 hours 

4.2 pounds/8 hours 

Washington Toxic air pollutant and acceptable 

source impact levels 

3.3 μg/m3

 per 24-hour 

average 

BNA 2001h 

b. Water 

Maine Drinking water guidelineCiodide ion 340 μg/L HSDB 2001 

 Rhode Island Water resourcesCtoxic pollutant BNA 2001h 

c. Food No data 

d. Other 

California Hazardous substance list BNA 2001h 

Florida Toxic substance in the workplace BNA 2001h 

Massachusetts Oil and hazardous material list BNA 2001h 

Pennsylvania Worker and Community Right-to­ BNA 2001h 

Know ActChazardous substance 

list 

a

RDI for adults and children 4 or more years of age 

b

100 calories, based on 2,000 calorie intake as a daily standard 

AAC = acceptable ambient concentrations; ACGIH = American Conference of Governmental Industrial Hygienists;
 

ATF = Alcohol, Tobacco, and Firearms; BPT = best practicable control technology; BNA = Bureau of National Affairs;
 

CFR = Code of Federal Regulations; EL = emissions level; EPA = Environmental Protection Agency; FDA = Food 

and Drug Administration; HAP = hazardous air pollutant; HSDB = Hazardous Substances Data Bank;
 

IARC = International Agency for Research on Cancer; IDLH = immediately dangerous to life and health;
 

NIOSH = National Institute of Occupational Safety and Health; OEL = occupational exposure limit;
 

OSHA = Occupational Safety and Health Administration; PEL = permissible exposure limit; RDI = recommended daily 

intake; REL = relative exposure limit; STEL = short term exposure limit; TLV = threshold limit value; TWA = time
 

weighted average; USC = United States Code
 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

IODINE 313 

8. REGULATIONS AND ADVISORIES 

Table 8-2. Regulations and Guidelines Applicable to Radioactive Iodine 

Agency Description Information References 

INTERNATIONAL 

Guidelines: 

IARC Carcinogenicity classification No data 

ICRP Occupational recommended dose 

limitsa;; effective dose 

20 mSv per year, averaged 

over defined period of 

5 yearsb 

ICRP 1991 

Annual equivalent dose 

Lens of the eye 

Skinc 150 mSv 

500 mSv 

Hands and feet 500 mSv 

General population recommended dose 

limitsa

 Effective dose 

Annual equivalent dose 

Lens of the eye 

Skinc 

1.0 mSv per yeard 

15 mSv 

50 mSv 

ICRP 1991 

Hands and feet No data 

NATIONAL 

Regulations and 

Guidelines: 

a. Air 

 ACGIH Effective dose ACGIH 2000 

 Any single year 

Averaged over 5 years 

50 mSv 

20 mSv 

Annual equivalent dose to 

Lens of the eye 

Skin 

150 mSv 

500 mSv 

Hands and feet 500 mSv 

Embryo-fetus exposures once the 

pregnancy is known 

Monthly equivalent dose 

Dose to the surface of women’s 

0.5 mSv 

2 mSv for the remainder of the 

abdomen (lower trunk) 

Intake of radionuclide 

pregnancy 

1/20 ALI

 NIOSH REL No data 

USNRC Occupational values—inhalation 120I 120mI 121I 123I 124I 125I 126I 128I 

ALI (μCi) 

1x104 

2x104 

5x104 

6x103 

3x102 

2x102 

1x102 

1x105 

DACe (μCi/mL) 

4x10-6 

9x10-6 

8x10-6 

3x10-6 

3x10-8 

3x10-8 

1x10-8 

5x10-5 

USNRC 2001a 

10CFR20, 

Appendix B 
 

 

 

 

 

 

 

IODINE 314 

8. REGULATIONS AND ADVISORIES 

Table 8-2. Regulations and Guidelines Applicable to Radioactive Iodine 

Agency Description Information References 

NATIONAL (cont.) 

USNRC (cont.) Occupational values—inhalation 129I 130I 131I 

ALI (μCi) 

3x101 

2x103 

2x102 

DACe

 (μCi/mL) 

4x10-9 

3x10-7 

2x10-8 

USNRC 2001a 

10CFR20, 

Appendix B 

132I 1x104 3x10-6 

 132mI 2x104 4x10-6 

133I 9x102 1x10-7 

134I 5x104 2x10-5 

135I 4x103 7x10-7 

Effluent concentrations (μCi/mL) USNRC 2001a 120I 120mI 121I 

2x10-8 

3x10-8 

7x10-8 

10CFR20, 

Appendix B 

124I 4x10-10 

125I 3x10-10 

126I 2x10-10 

128I 2x10-7 

129I 4x10-11 

130I 3x10-9 

131I 2x10-10 

132I 2x10-8 

 132mI 3x10-8 

133I 1x10-9 

134I 6x10-8 

135I 6x10-9 

OSHA PEL (8-hour TWA) 

b. Water 

No data 

USNRC Effluent concentrations (μCi/mL) USNRC 2001a 120I 120mI 121I 

1x10-4 

2x10-4 

4x10-4 

10CFR20, 

Appendix B 

124I 2x10-6 

125I 2x10-6 

126I 1x10-6 

128I 8x10-4 

129I 2x10-7 

130I 2x10-5 

131I 1x10-6 

132I 1x10-4 

 132mI 1x10-4 

133I 7x10-6 

134I 4x10-4 

135I 3x10-5 

Releases to sewers; monthly average USNRC 2001a 

concentration (μCi/mL) 120I 120mI 

1x10-3 

2x10-3 

10CFR20, 

Appendix B 

121I 4x10-3 

124I 2x10-5 
 

 

 

 

 

 

 

 

 

 

IODINE 315 

8. REGULATIONS AND ADVISORIES 

Table 8-2. Regulations and Guidelines Applicable to Radioactive Iodine 

Agency Description Information 

NATIONAL (cont.) 

References 

USNRC (cont.) Releases to sewers; monthly average USNRC 2001a 

concentration (μCi/mL) 125I 126I 

2x10-5 

1x10-5 

10CFR20, 

Appendix B 

128I 8x10-3 

129I 2x10-6 

130I 2x10-4 

131I 1x10-5 

132I 1x10-3 

 132mI 1x10-3 

133I 7x10-5 

134I 4x10-3 

135I 

 Food 

3x10-4 

c.

FDA Derived intervention levelf (DIL; Bq/kg 

food) for 131I in accidentally167 FDA 1998 

contaminated human food 

Sources of radiation used for food Not more than 2.2 million FDA 2000h 

inspection; sealed units producing 

radiation (125I) 

electron volts 21CFR179.21 

Requirements regarding certain Diagnosis of thyroid functions; FDA 2000g 

radioactive drugs (131I) thyroid scans; treatment of 21CFR310.503 

hyper-thyroidism and/or cardiac 

dysfunction; treatment of 

d. Other 

thyroid carcinoma 

DOE Radiation standards; DACg

 for controlling DOE 2001b 

radiation exposure to workers at DOE 10CFR835, 

facilitiesh

(μCi/mL) 120mI 9x10-6 Appendix A 

120I 4x10-6 

121I 7x10-6 

123I 3x10-6 

124I 3x10-8 

125I 3x10-8 

126I 1x10-8 

128I 5x10-5 

129I 4x10-9 

130I 3x10-7 

131I 2x10-8 

 132mI 4x10-6 

132I 3x10-6 

133I 1x10-7 

134I 2x10-5 

135I 7x10-7 
 

 

 

 

 

 

 

 

 

 

IODINE 316 

8. REGULATIONS AND ADVISORIES 

Table 8-2. Regulations and Guidelines Applicable to Radioactive Iodine 

Agency Description Information References 

NATIONAL (cont.) 

DOE Radiation standards; DACg for workers DOE 2001a 

from external exposure during immersion 10CFR835, 

in contaminated atmospheric cloud 

(Ci/mL) 122I 5x10-6 

Appendix C 

128I 5x10-5 

132I 2x10-6 

134I 1x10-6 

135I 7x10-7 

136I 1x10-6 

Values for establishing sealed 

radioactive source accountability and 

radioactive material posting and labeling 

DOE 2001c 

10CFR835, 

Appendix E 

requirements 125I 3.5x102 

129I 1.8x102 

DOT General requirements for shipments and 

packagings; A1 and A2 values for 

radionuclides 123I 

A1 (Ci) 

6 

A2 (Ci) 

162 

DOT 2001a 

49CFR173.435 

124I 0.9 24.3 125I 2 54.1 126I 0.9 24.3 129I Unlimited Unlimited 131I 0.5 13.5 132I 0.4 10.8 133I 0.5 13.5 134I 0.3 8.11 135I 0.3 13.5 

Hazardous substance and reportable DOT 2001b 

quantity (Ci) 120I 120mI 

10 

100 

49CFR171.101, 

Appendix A 

121I 100 123I 10 124I 0.1 125I 0.01 126I 0.01 128I 129I 

1,000 

0.001 130I 1.0 131I 0.01 132I 10 132mI 10 133I 0.1 134I 100 135I 10 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

IODINE 317 

8. REGULATIONS AND ADVISORIES 

Table 8-2. Regulations and Guidelines Applicable to Radioactive Iodine 

Agency Description Information References 

NATIONAL (cont.) 

EPA Annual possession quantities for 

environmental compliance (Ci/year) 123I 124I 

Gas 

4.9x10-1 

9.3x10-3 

Liquid/ 

Solid 

4.9x105 

9.3x103 

Powder 

4.9x102 

9.3x100 

EPA 2001a 

40CFR61, 

Appendix E 

125I 6.2x10-3 6.2x103 6.2x100 

126I 3.7x10-3 3.7x103 3.7x100 

128I 9.3x100 9.3x106 9.3x103 

129I 2.6x10-4 2.6x102 2.6x10-1 

130I 4.6x10-2 4.6x104 4.6x101 

131I 6.7x10-3 6.7x103 6.7x100 

132I 2.0x10-1 2.0x105 2.0x102 

133I 6.7x10-2 6.7x104 6.7x101 

134I 3.2x10-1 3.2x105 3.2x102 

135I 1.2x10-1 1.2x105 1.2x102 

Release limits for containmenti BNA 2001e 129I 100 Ci 40CFR191, 

Appendix A 

Reportable quantity (Ci) 

 120mI 120I 121I 

100 

10 

100 

BNA 2001f 

40CFR302.4, 

Appendix B 

123I 10 124I 0.1 125I 0.01 126I 0.01 128I 129I 

1,000 

0.001 130I 1.0 131I 0.01 132mI 10 132I 10 133I 0.1 134I 100 135I 10 

Carcinogenicity slope factorsj EPA 2002b 

Ingestion—lifetime excess total cancer 

risk/pCi 

Water 122I No data 123I 6.96x10-13 

125I 2.54x10-11 

126I 8.73x10-11 

129I 1.48x10-10 

130I 6.36x10-12 

131I 4.55x10-11 

132I 8.44x10-13 

133I 1.44x10-11 

134I 2.50x10-13 

135I 3.05x10-12 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

IODINE 318 

8. REGULATIONS AND ADVISORIES 

Table 8-2. Regulations and Guidelines Applicable to Radioactive Iodine 

Agency Description Information References 

NATIONAL (cont.) 

EPA (cont.) Ingestion—lifetime excess total cancer 

risk/pCi 

Food 122I 123I 125I 126I 129I 130I 131I 132I 133I 134I 135I 

Ingestion—lifetime excess total cancer 

risk/pCi 

Soil 122I 123I 125I 126I 129I 130I 131I 132I 133I 134I 135I 

 Inhalationk

—lifetime excess total cancer 

risk/pCi 122I 123I 125I 126I 129I 130I 131I 132I 133I 134I 135I 

 External exposurel

—risk/year per pCi/g 

in soil 122I 123I 125I 126I 129I 130I 

EPA 2002b 

No data 

2.05x10-12 

6.29x10-11 

2.48x10-10 

3.22x10-10 

1.88x10-11 

1.34x10-10 

2.34x10-12 

4.40x10-11 

6.44x10-13 

8.99x10-12 

No data 

1.96x10-12 

5.55x10-11 

2.31x10-10 

2.71x10-10 

1.80x10-11 

1.26x10-10 

2.22x10-12 

4.26x10-11 

5.96x10-13 

8.62x10-12

No data 

3.03x10-13 

1.06x10-11 

3.70x10-11 

6.07x10-11 

2.76x10-12 

1.95x10-11 

3.74x10-13 

6.25x10-12 

1.02x10-13 

1.34x10-12

4.17x10-6 

5.10x10-7 

7.24x10-9 

1.96x10-6 

6.10x10-9 

9.67x10-6 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

IODINE	 319 

8. REGULATIONS AND ADVISORIES 

Table 8-2. Regulations and Guidelines Applicable to Radioactive Iodine 

Agency Description Information References 

NATIONAL (cont.) 

EPA (cont.) External exposurel—risk/year per pCi/g 

in soil 131I 132I 133I 134I 135I 

NCRP Occupational exposuresm 

Effective dose limits 

Annual 

Cumulative 

Equivalent dose annual limits for tissues 

and organs 

Lens of eye 

Skin, hands, and feet 

Public exposures (annual) 

Effective dose limit, continuous 

or frequent exposurem 

Effective dose limit, infrequent

 exposurem 

Equivalent dose limits for tissues and 

organsm 

Lens of eye 

Skin, hands, and feet 

USNRC ALI (μCi)—oral ingestion 120I 120mI 121I 123I 124I 125I 126I 128I 129I 130I 131I 132I 132mI 133I 134I 135I 

Byproduct material listing (Ci)

125I 

126I 129I 131I 132I 133I 134I 135I 

1.59x10-6 

1.06x10-5 

2.72x10-6 

1.24x10-5 

7.83x10-6 

50 mSv 

10 mSv x age 

150 mSv 

500 mSv 

1.0 mSv 

5 mSv 

15 mSv 

50 mSv 

8x103 

1x104 

3x104 

3x103 

2x102 

1x102 

7x101 

6x104 

2x101 

1x103 

9x101 

9x103 

1x104 

5x102 

3x104 

3x103 

Column In 

0.1 

0.1 

0.1 

0.1 

10 

1.0 

10 

1.0 

Column IIo 

0.00 

0.001 

0.01 

0.001 

0.1 

0.01 

0.1 

0.01 

EPA 2002b 

NCRP 1993 

USNRC 2001a 

10CFR20, 

Appendix B 

USNRC 2001b 

10CFR33.100, 

Schedule A 
 

 

 

 

 

 

IODINE	 320 

8. REGULATIONS AND ADVISORIES 

Table 8-2. Regulations and Guidelines Applicable to Radioactive Iodine 

Agency Description Information References 

NATIONAL (cont.) 

USNRC Individual monitoring 131I 

Laboratory testing and use 125I and 131I 

Packaging and transportation of 

radioactive material; determination of A1 

and A2 123I 124I 125I 126I 129I 131I 132I 133I 134I 135I 

Quantities requiring consideration of the 

need for an emergency plan; 125I and 131I 

 Release fraction

 Quantity 

Standards for protection against 

radiation; quantities of licensed material 

requiring labeling (μCi) 120mI 120I 121I 123I 124I 125I 126I 128I 129I 130I 131I 132mI 132I 133I 134I 135I 

 Waste classification 

 Concentration of 129I 

STATE 

Regulations and 

Guidelines: 

a. Air 

b. Water 

Kentucky	 Maximum groundwater contaminant 

level 131I 

c. Food 

1.0 Ci 

≤10 μCi 

A1 (Ci) 

6.0 

0.9 

2.0 

0.9 

Unlimited 

0.5 

0.4 

0.5 

0.3 

0.5 

0.5% 

10 Ci 

1,000 

100 

1,000 

100 

10 

1.0 

1.0 

1,000 

1.0 

10 

1.0 

100 

100 

10 

1,000 

100 

0.08 Ci/m3 

No data 

3 pCi/L 

No data 

A2 (Ci) 

162 

24.3 

54.1 

24.3 

Unlimited 

13.5 

10.8 

13.5 

8.11 

13.5 

Specific 

Activity
 

1.9x106 

2.5x105 

1.7x104 

8.0x104 

1.8x104 

1.2x105 

1.0x107 

1.1x106 

2.7x107 

3.5x106 

BNA 2001a 

10CFR20.2206 

BNA 2001b 

10CFR32.71 

USNRC 2001c 

10CFR71, 

Appendix A 

BNA 2001c 

10CFR30.72, 

Schedule C 

BNA 2001d 

10CFR20, 

Appendix C 

USNRC 2001d 

10CFR61.55 

BNA 2001h 
 

 

 

 

 

 

 

 

 

 

IODINE 321 

8. REGULATIONS AND ADVISORIES 

Table 8-2. Regulations and Guidelines Applicable to Radioactive Iodine 

Agency Description Information 

d. Other 

References 

Arkansas Licensing of radioactive materials; BNA 2001h 

exempt concentrations (Ci/mL, solids are Column 1n Column 2o 

Ci/g) 126I 3x10-9 6x10-4 

131I 2x10-5 1x10-8 

132I 3x10-9 7x10-5 

133I 2x10-5 2x10-7 

134I 8x10-8 1x10-3 

California Licensing of radioactive materials; Column 1n Column 2o BNA 2001h 

Schedule C (μCi/mL) 126I 3x10-9 2x10-5 

131I 3x10-9 2x10-3 

132I 8x10-8 6x10-4 

133I 1x10-8 7x10-3 

134I 2x10-7 1x10-3 

Florida Quantities requiring consideration of the 

need for an emergency plan; 125I and 131I 

BNA 2001h 

 Release fraction

 Quantity 0.5% 

10 Ci 

Indiana Licensing of radioactive materials; BNA 2001h 

Schedule A; exempt concentrations Column 1n Column 2o 

(μCi/mL)

126I 3x10-9 2x10-5 

131I 3x10-9 2x10-3 

132I 8x10-8 6x10-4 

133I 1x10-8 7x10-3 

134I 2x10-7 1x10-3 

Kansas Licensing of sources of radiation; 

Schedule B; exempt quantities of 

BNA 2001h 

radioactive material (μCi) 123I 100 125I 1.0 126I 1.0 129I 0.1 131I 1.0 132I 10 133I 1.0 134I 10 135I 10 

Louisiana Standards for protection against 

radiation 

BNA 2001h 

 120mI 100 120I 10 121I 100 
 

 

 

 

 

IODINE 322 

8. REGULATIONS AND ADVISORIES 

Table 8-2. Regulations and Guidelines Applicable to Radioactive Iodine 

Agency Description Information References 

STATE (cont.)

 Louisiana 

(cont.) 

Standards for protection against 

radiation 123I 10 

BNA 2001h 

124I 0.1 125I 0.01 126I 0.01 128I 129I 

1,000 

0.001 130I 1.0 131I 0.01 132mI 10 132I 10 

a

The limits apply to the sum of the relevant doses from external exposure in the specified period and the 50-year 

committed dose (to age 70 years for children) from intakes in the same period.

b

With the further provision that the effective dose should not exceed 50 mSv in any single year. Additional restrictions 

apply to the occupational exposure of pregnant women.

c

The limitation on the effective dose provides sufficient protection for the skin against stochastic effects. An additional 

limit is needed for localized exposures in order to prevent deterministic effects.

d

In special circumstances, a higher value of effective dose could be allowed in a single year, provided that the average 

over 5 years does not exceed 1.0 mSv per year.

e

DAC is the concentration of radioactive material in air and the time of exposure to that radionuclide, in hours. An 

NRC licensee may take 2,000 hours to represent one ALI, equivalent to a committed effective dose equivalent of 

5 rems (0.05 sievert).

f

The FDA-recommended Derived Intervention Level (DIL) for radionuclides of 131I, is defined as the DIL for the most 

sensitive age group (1 year) that was calculated from the most limiting Protective Action Goal (PAG; 50 mSv 

committed dose equivalent to the thyroid).

g

DAC for the radionuclides listed in Appendix A of 10CFR835, the airborne concentration that equals ALI divided by 

the volume of air breathed by an average worker for a working year of 2,000 hours (assuming a breathing volume of 

2,400 m3

). For the radionuclides listed in Appendix C of 10CFR835, the air immersion DACs were calculated for a 

continuous, non-shielded exposure via immersion in a semi-infinite atmospheric cloud.

h

Class D: approximate length of retention in the pulmonary region is less than 10 days. 

i

Release limit per 1,000 metric tons of heavy metal or other unit of waste.

j

Radioactive slope factors calculated by EPA’s Office of Radiation and Indoor Air (ORIA). Slope factors are central 

estimates in a linear model of the age-averaged, lifetime attributable radiation cancer incidence (fatal and nonfatal 

cancer) risk per unit of activity ingested, expressed as risk per picocurie (pCi).

k

Inhalation slope factors are central estimates in a linear model of the age-average, lifetime attributable radiation 

cancer incidence (fatal and nonfatal cancer) risk per unit of activity inhaled, expressed as risk per picocurie (pCi).

l

External slope factors are central estimates of the lifetime attributable radiation cancer incidence risk for each year of 

exposure to external radiation from photon-emitting radionuclides distributed uniformly in a thick layer of soil, 

expressed as risk/year per pCi per gram of soil.

mSum of external and internal exposures but excluding doses from natural sources. 

n

Column 1: gas concentration 

o

Column 2: liquid and solid concentration 

ACGIH = American Conference of Governmental Industrial Hygienists; ALI = annual limits on intake; BNA = Bureau of 

National Affairs; CFR = Code of Federal Regulations; DAC = derived air concentrations; DOE = Department of 

Energy; DOT = Department of Transportation; EPA = Environmental Protection Agency; FDA = Food and Drug 

Administration; IARC = International Agency for Research on Cancer; ICRP = International Commission on 

Radiological Protection; mSv = millisievert; NIOSH = National Institute of Occupational Safety and Health; 

NCRP = National Council on Radiation Protection; USNRC = U.S. Nuclear Regulatory Commission; 

OSHA = Occupational Safety and Health Administration; PAG = protective action guide; PEL = permissible exposure 

limit; REL = relative exposure limit; TLV = threshold limit value; TWA = time-weighted average 
 

 

 

IODINE 323 

8. REGULATIONS AND ADVISORIES 

Table 8-3. Dose Coefficientsa (e(50)) for Intakes of Iodine Radionuclides 

Inhalation, Inhalation, 

1μm AMADb 5μm AMAD Ingestion 

Radionuclide Half-life f1c e(50) e(50) e(50) 

120I 1.35/hour 1.0 1.0x10-10 1.9x10-10 3.4x10-10 

120mI 0.883/hour 1.0 8.7x10-11 1.4x10-10 2.1x10-10 

121I 2.12/hour 1.0 2.8x10-11 3.9x10-11 8.2x10-11 

123I 13.2/hour 1.0 7.6x10-11 1.1x10-10 2.1x10-10 

124I 4.18/day 1.0 4.5x10-9 6.3x10-9 1.3x10-8 

125I 60.1/day 1.0 5.3x10-9 7.3x10-9 1.5x10-8 

126I 13.0/day 1.0 1.0x10-8 1.4x10-8 2.9x10-8 

128I 0.416/hour 1.0 1.4x10-11 2.2x10-11 4.6x10-11 

129I 1.57x107

/year 1.0 3.7x10-8 5.1x10-8 1.1x10-7 

130I 12.4/hour 1.0 6.9x10-10 9.6x10-10 2.0x10-9 

131I 8.04/day 1.0 7.6x10-9 1.1x10-8 2.2x10-8 

132I 2.30/hour 1.0 9.6x10-11 2.0x10-10 2.9x10-10 

132mI 1.39/hour 1.0 8.1x10-11 1.1x10-10 2.2x10-10 

133I 20.8/hour 1.0 1.5x10-9 2.1x10-9 4.3x10-9 

134I 0.876/hour 1.0 4.8x10-11 7.9x10-11 1.1x10-10 

135I 6.61/hour 1.0 3.3x10-10 4.6x10-10 9.3x10-10 

a

ICRP (1994a)

b

ICRP (1994a) calculated inhalation dose coefficients for particles with AMAD of 1 or 5 μm. c

Fractional absorption factor used by ICRP (1994, Annexes E and F) to calculate effective dose coefficients.
 

ALI = annual limits on intake; AMAD = activity median average diameters; Ci = curies 

 

 

 

_________ 

IODINE 325 

9. REFERENCES 

Abbott A, Barker S. 1996. Chernobyl damage 'underestimated'. Nature 380:658. 

Abdel-Nabi H, Ortman JA. 1983. Radiobiological effects of 131I and 125I on the DNA of the rat thyroid: 

I. Comparative study with emphasis on the post radiation hypothyroidism occurrence. Radiat Res 

93:525-533. 

*Abdullah ME, Said SA. 1981. Release and organ distribution of 125I from povidone-iodine under the 

influence of certain additives. Arzneim Forsch 31(1):59-61. 

Abel MS, Blume AJ, Garrett KM. 1989. Differential effects of iodide and chloride on allosteric 

interactions of the GABAA receptor. J Neurochem 53:940-945. 

*Aboul-Khair SA, Buchanan TJ, Crooks J, et al. 1966. Structural and functional development of the 

human foetal thyroid. Clin Sci 31:415-424. 

Aboul-Khair SA, Crooks J, Turnbull AC, et al. 1964. The physiological changes in thyroid function 

during pregnancy. Clin Sci 27:195-207. 

Absil AC, Buxeraud J, Raby C. 1984. [Charge-transfer complexation of chlorpromazine in the presence 

of iodine; thyroid side effect of this molecule.] Can J Chem 62(9):1807-1811. (French) 

ACGIH. 1992. Iodine. In: Documentation of the threshold limit values and biological exposure indices. 

Sixth Edition. Volume II. American Conference of Governmental Industrial Hygienists Inc. Cincinnati, 

OH. 

*ACGIH. 2000. Threshold limit values for chemical substances and physical agents and biological 

exposure indices. American Conference of Governmental Industrial Hygienists Inc. Cincinnati, OH. 

Adamson AS, Gardham JRC. 1991. Post 131I carcinoma of the thyroid. Postgrad Med J 67:289-290. 

*Ader AW, Paul TL, Reinhardt W, et al. 1988. Effect of mouth rinsing with two polyvinylpyrrolidoneiodine mixtures on iodine absorption and thyroid function. J Clin Endocrinol Metab 66(3):632-635. 

*Adinolfi M. 1985. The development of the human blood-CSF-brain barrier. Dev Med Child Neurol 

27:532-537. 

*Adlercreutz H. 1995. Phytoestrogens: Epidemiology and a possible role in cancer protection. Environ 

Health Perspect Suppl 103(7):103-112. 

Advani SH, Hege UP. 1992. Leukemia after 131I treatment of thyroid cancer-comments on the article 

second cancer following chemotherapy and radiotherapy-an epidemiological perspective by J. Kaldor. 

Acta Oncol 31(1):65. 

*Cited in text 
 

 

 

IODINE 326 

9. REFERENCES 

*AEC. 1966. I-129 as a geochemical and ecological tracer. U.S. Atomic Energy Commission. 

Pittsburgh, PA: Carnegie Institute of Technology. Report No. NYO-3624-1. 

*AEC. 1968. Fission product inhalation program annual report 1967-1968. Lovelace Foundation for 

Medical Education and Research for U.S. Atomic Energy Commission. LF-39, UC-48. 

AEC. 1970. Medical survey of the people of Rongelap and Utirik Islands thirteen, fourteen, and fifteen 

years after exposure to fallout radiation (March 1967, March 1968, and March 1969). Brookhaven 

National Laboratory for U.S. Atomic Energy Commission. BNL 50220 (T-562). 

*AEC. 1974. U.S. Atomic Energy Commission. Environmental behavior and radiation doses from 

iodine-129. BNWL-SA-4879. 

AECB. 1986. Transfer of radionuclides from the environment to human milk - A review. Ottawa, 

Canada: Atomic Energy Control Board. INFO-0192. NTIS DE 88705117. 

AECB. 1994. Radioactive emission data from Canadian nuclear generating stations 1972 to 1992. 

Ottawa, Canada: Atomic Energy Control Board. INFO-0210(e) Rev-5. NTIS MIC-95-00188. 

AECL. 1994. Atomic Energy of Canada, Ltd. Review and assessment of methods for the measurement 

and speciation of iodine in fresh water. NTIS PB95-160487. 

Agbunag R. 2001. Preoperative vaginal preparation with povidone-iodine decreases the risk of postcesarean endometritis. Am J Obstet Gynecol 184(1):S182. 

*Agency for Toxic Substances and Disease Registry. 1989. Decision guide for identifying substancespecific data needs related to toxicological profiles; Notice. Federal Register 54(174):37618-37634. 

*Agency for Toxic Substances and Disease Registry. 1990. Biomarkers of organ damage or dysfunction 

for the renal, hepatobiliary, and immune systems. Subcommittee on Biomarkers of Organ Damage and 

Dysfunction, Atlanta, GA. 

*Agency for Toxic Substances and Disease Registry. 1997. Toxicological Profile for Cyanide (Update). 

U.S. Department of Health and Human Services. Public Health Service. 

*Agency for Toxic Substances and Disease Registry. 1999. Toxicological profile for ionizing radiation. 

Atlanta, GA. 

*Agency for Toxic Substances and Disease Registry. 2000a. Hanford infant mortality and fetal death 

analysis 1940-1952. Atlanta, GA: U.S. Department of Health and Human Services. PB2000105892. 

*Agency for Toxic Substances and Disease Registry. 2000b. Toxicological profile for polychlorinated 

biphenyls, Atlanta, GA. 

Agerbaek H. 1974. Weight and iodine content of the thyroid gland in Jutland, Denmark [Letter]. Acta 

Med Scand 196:505. 

Aggett PJ. 1998. Neonatal trace element metabolism. In: Cowett RM, ed. Principles of perinatalneonatal metabolism. New York, NY: Springer, 909-941. 
IODINE 327 

9. REFERENCES 

*Aghini-Lombardi A, Antonangeli L, Martinon E, et al. 1999. The spectrum of thyroid disorders in an 

iodine-deficient community: The Pescopagano survey. J Clin Endocrinol Metab 84:561-566. 

Ahlgren L, Ivarsson S, Johansson L, et al. 1985. Excretion of radionuclides in human breast milk after 

the administration of radiopharmaceuticals. J Nucl Med 26:1085-1090. 

Ahmad AM, Ahmad M, Young ET. 2002. Objective estimates of the probability of developing 

hypothyroidism following radioactive iodine treatment of thyrotoxicosis. Eur J Endocrinol 146(6):767­

775. 

*Ahmed M, Doe RP, Nuttall FQ. 1974. Triiodothyronine thyrotoxicosis following iodide ingestion: A 

case report. J Clin Endocrinol Metab 38:574-576. 

*Ahmed SR, Shalet SM. 1984. Radioactive iodine and testicular damage. N Engl J Med 311:1576. 

*Ahmed SR, Shalet SM. 1985. Gonadal damage due to radioactive iodine (I131) treatment for thyroid 

carcinoma. Postgrad Med J 61:361-362. 

Ahn C-S, Rosenberg IN. 1968. Prompt stimulation of the organic binding of iodine in the thyroid by 

adenosine 3',5'-phosphate in vivo. Proc Natl Acad Sci U S A 60(3):830-835. 

Ahn CS, Rosenberg IN. 1970. Iodine metabolism in thyroid slices: Effects of TSH, dibutyryl cyclic 

3',5'-AMP, NaF and prostaglandin E. Endocrinology 86:396-405. 

Ahnstrom G, Ehrenberg L, Hussain S, et al. 1970. On the killing and mutagenic action in e. coli 

associated with the Auger effect during 125I decay. Mutat Res 10:247-250. 

Ahren B, Rerup C. 1987. Kinetics of radioiodine released from prelabelled thyroid gland in vivo: 

Influence of propylthiouracil. Pharmacol Toxicol 61:69-71. 

Aiba M, Ninomiya J, Furuya K, et al. 1999. Induction of a critical elevation of povidone-iodine 

absorption in the treatment of a burn patient: Report of a case. Jpn J Surg 29:157-159. 

Aii T, Kume A, Takahashi S, et al. 1990. The effect of the radionuclides from Chernobyl on iodine-131 

and cesium-137 contents in milk and pastures in south-western Japan. Jpn J Zootech Sci 61(1):47-53. 

Aizawa Y, Yoshida K, Kaise N, et al. 1997. The development of transient hypothyroidism after iodine131 treatment in hyperthyroid patients with Graves' disease: Prevalence, mechanism and prognosis. Clin 

Endocrinol 46:1-5. 

*Akamizu T, Ikuyama S, Saji M, et al. 1990. Cloning, chromosomal assignment, and regulation of the 

rat thyrotropin receptor: Expression of the gene is regulated by thyrotropin, agents that increase cAMP 

levels, and thyroid autoantibodies. Proc Natl Acad Sci U S A 87:5677-5681. 

Akerib M. 1971. Iodine toxic to young animals. Worlds Poult Sci J 27(1):35-37. 

Akleyev AV. 1996. Experience with the studies of medical and biological effects of radiation incidents 

in the south Urals. In: Nagataki S, Yamashita S, eds. Nagasaki symposium radiation and human health: 

Proposal from Nagasaki. Amsterdam, the Netherlands: Elsevier, 117-126. 
IODINE 328 

9. REFERENCES 

Aktay R, Rezai K, Seabold JE, et al. 1996. Four- to twenty-four hour uptake ratio: An index of rapid 

iodine-131 turnover in hyperthyroidism. J Nucl Med 37:1815-1819. 

Albinsson Y, Engkvist I. 1989. Diffusion of americium, plutonium, uranium, neptunium, cesium, iodine 

and technetium in compacted sand-bentonite mixture. Chalmers University of Technology, Department 

of Nuclear Chemistry, Goeteborg, Sweden. SKB Tech. Rep. 89-22. 

Albinsson Y, Engkvist I. 1991. Diffusion of Am, Pu, U, Np, Cs, I and Tc in compacted sand-bentonite 

mixture. Radioact Waste Manage Nucl Fuel Cycle 15(4):221-239. 

Albrecht HH, Creutzig H. 1976. [Salivary gland scintigraphy after radio-iodine therapy. Functional 

scintigraphy of the salivary gland after high dose radio-iodine therapy (author's translation).] Fortschr 

Geb Rontgenstrahlen Nuklearmed Erganzungsbd 125(6):546-551. (German) 

Alexander C, Bader JB, Schaefer A, et al. 1998. Intermediate and long-term side effects of high-dose 

radioiodine therapy for thyroid carcinoma. J Nucl Med 39:1551-1554. 

*Alexandrides T, Georgopoulos N, Yarmenitis S, et al. 2000. Increased sensitivity to the inhibitory 

effect of excess iodide on thyroid function in patients with beta-thalassemia major and iron overload and 

the subsequent development of hypothyroidism. Eur J Endocrinol 143(3):319-325. 

*Allegrini M, Pennington JAT, Tanner JT. 1983. Total diet study: Determination of iodine intake by 

neutron activation analysis. J Amer Diet Assoc 83:18-24. 

Allen EM. 1993. Acute iodine ingestion increases intrathyroidal glutathione. J Endocrinol Invest 

16:265-270. 

*Allen EM, Braverman LE. 1990. The effect of iodine on lymphocytic thyroiditis in the thymectomized 

Buffalo rat. Endocrinology 127(4):1613-1616. 

*Allen EM, Appel MC, Braverman LE. 1986. The effect of iodide ingestion on the development of 

spontaneous lymphocytic thyroiditis in the diabetes-prone BB/W rat. Endocrinology 118(5):1977-1981. 

Allen EM, Appel MC, Braverman LE. 1987. Iodine-induced thyroiditis and hypothyroidism in the 

hemithyroidectomized BB/W rat. Endocrinology 121:481-485. 

*Allweiss P, Braunstein GD, Katz A, et al. 1984. Sialadenitis following I-131 therapy for thyroid 

carcinoma: Concise communication. J Nucl Med 25:755-758. 

Al-Rashood KA, Hagga MEM, Al-Khamees HA, et al. 1995. Differential pulse polarographic and 

spectrophotometric methods for the determination of trace amounts of iodide in Saudi waters. Saudi 

Pharm J 3(4):181-187. 

Als C, Helbling A, Peter K, et al. 2000a Urinary iodine concentration follows a circadian rhythm: A 

study with 3023 spot urine samples in adults and children. J Clin Endocrinol Metab 85(4):1367-1369. 

Als C, Keller A, Minder C, et al. 2000b Age- and gender-dependent urinary iodine concentrations in an 

area-covering population sample from the Bernese region in Switzerland. Eur J Endocrinol 143(5):629­

637. 
IODINE 329 

9. REFERENCES 

*Altman PL, Dittmer DS. 1974. In: Biological handbooks: Biology data book. Vol. III. 2nd ed. 

Bethesda, MD: Federation of American Societies for Experimental Biology, 1987-2008, 2041. 

Alvarez E. 1979. Neutropenia in a burned patient being treated topically with povidone-iodine foam. 

Plast Reconstr Surg 63(6):839-840. 

Amdur MO. 1978. Respiratory response to iodine vapor alone and with sodium chloride aerosol. J 

Toxicol Environ Health 4:619-630. 

Amiro BD, Sheppard SC, Johnston FL, et al. 1996. Burning radionuclide question: What happens to 

iodine, cesium and chlorine in biomass fires? Sci Total Environ 187:93-103. 

Ammerman CB, Miller SM, Fick KR, et al. 1977. Contaminating elements in mineral supplements and 

their potential toxicity: A review. J Anim Sci 44(3):485-538. 

Amphoux-Fazekas T, Samih N, Hovsepian S, et al. 1998. DIDS (4,4'-diisothiocyanatostilbene-2,2'­

disulfonic acid) increases iodide trapping, inhibits thyroperoxidase and antagonizes the TSH-induced 

apical iodide efflux in porcine thyroid cells. Mol Cell Endocrinol 141:129-140. 

Amvrosiev AP, Banetskaya NY. 1992. [Early and long-term effects of the combined action of iodine131 and cesium-137 at low doses on ovaries of animals.] Dokl Akad Nauk Belarusi 36(9-10):855-858. 

(Russian) 

Amvros'ev AP, Vereshchako GG, Redrov AG. 1991. [Analysis of the effect of iodine-131 on the 

cytochemical activity of peripheral blood lymphocyte hydroxyreductases in rats.] Gig Sanit 7:53-55. 

(Russian) 

Anders E. 1962. Minimal dosage of iodide required to suppress uptake of iodine-131 by normal thyroid. 

Science 138:430-433. 

*Andersen ME, Krishnan K. 1994. Relating in vitro to in vivo exposures with physiologically based 

tissue dosimetry and tissue response models. In: Salem H, ed. Animal test alternatives: Refinement, 

reduction, replacement. New York, NY: Marcel Dekker, Inc., 9-25. 

*Andersen ME, Clewell HJ III, Gargas ML, et al. 1987. Physiologically based pharmacokinetics and the 

risk assessment process for methylene chloride. Toxicol Appl Pharmacol 87:185-205. 

Andersen S, Pedersen KM, Pedersen IB, et al. 2001. Variations in urinary iodine excretion and thyroid 

function. A 1-year study in health men. Eur J Endocrinol 144(5):461-465. 

Anderson DM, Marsh TL, Deonigi DA. 1996a. Developing historical food production and consumption 

data for 131I dose estimates: The Hanford experience. Health Phys 71(4):578-587. 

Anderson GS, Bird T. 1961. Congenital iodide goitre in twins. Lancet 2:742-743. 

*Anderson KA, Casey B, Diaz E, et al. 1996b. Speciation and determination of dissolved iodide and 

iodine in environmental aqueous samples by inductively coupled plasma atomic emission spectrometry. J 

AOAC Int 79(3):751-756. 

Anderson LL, Lau CC, Gracely EJ, et al. 1997. Enhancement of 131I-mediated cytotoxicity by caffeine. 

Gynecol Oncol 65:253-257. 
IODINE 330 

9. REFERENCES 

*Anderson TJ. 1978. Methodology for the determination of environmental 129I and 99Tc. Savannah River 

Laboratory, Aiken, SC. NTIS: DP-MS-77-75 (Conf 780719-2). 

*Andersson S, Forsman U. 1997. Determination of total iodine in biological material by alkaline ashing 

and column-switching ion-pair liquid chromatography. J Chromatogr B Biomed Appl 692:53-59. 

Andreyeva LP, Shvedov VL. 1977. [Changes in the rat hemopoietic system when exposed to Strontium 

89 and Iodine 131 simultaneously.] Radiobiologia 17(5):752-757. (Russian) 

*Andros G, Wollman SH. 1991. Kinetics of equilibration of radionuclide in individual mouse thyroid 

follices in vivo. Am J Physiol 261(24):E529-E538. 

Anno Y, Sasaki T, Takeshita A, et al. 1975. Incidence of hypothyroidism after radioiodine treatment of 

hyperthyroidism: A report of the radioiodine therapy follow-up study. Nippon Igaku Hoshasen Gakkai 

Zasshi 35(7):545-555. 

Anokhin IN, Norets TA. 1986. [Disorders of immunologic homeostasis as affected by radioactive iodine 

preparation.] Med Radiol 31(11):55-58. (Russian) 

Anonymous. 1980. Radioactive iodine and the risk of malignant thyroid tumour. N Z Med J 92:386­

387. 

Anonymous. 1987. Studies evaluate medical responses to nuclear accidents, question use of potassium 

iodide. Am J Hosp Pharm 44:2651-2652. 

Anonymous. 1991. Nuclear accident countermeasures: Iodine prophylaxsis. Rep Health Soc Subj 

(Lond) 39:1-63. 

Anonymous. 1994. Comparison of radionuclide levels in soil, sagebrush, plant litter, cryptogams, and 

small mammals. Westinghourse Hanford Co., Richland, WA. NTIS DE95001629. 

Anonymous. 1997. Chemical mixture. Environ Health Perspect Suppl 105(1):371-372. 

Ansell JE. 1996a. The blood in hypothyroidism. In: Braverman LE, Utiger RD, eds. Werner and 

Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 821-825. 

Ansell JE. 1996b. The blood in thyrotoxicosis. In: Braverman LE, Utiger RD, eds. Werner and 

Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 637-644. 

Antonangeli L, Maccherini D, Cavaliere R, et al. 2002. Comparison of two different doses of iodine in 

the prevention of gestational goiter in marginal iodine deficiency: A longitudinal study. Eur J Endocrinol 

147(1):29-34. 

*AOAC. 1984. Official methods of analysis, 14th ed. Association of Official Analytical Chemists. 

Arlington, VA. 

APHS. 1998. Standard methods for the examination of water and waste water, 20th ed. American Public 

Health Association. Washington, DC. 
 

 

IODINE 331 

9. REFERENCES 

Appell R, Tsangaris N, Spiegel J. 1978. Radioiodine treated hyperthyroidism and thyroid carcinoma. 

Am Surg 44:537-540. 

Ardawi MSM, Nasrat HA, Mustafa BE. 2002. Urinary iodine excretion and maternal thyroid function. 

Saudi Medicine 23(4):413-422. 

*Ardito G, Lamberti L, Bigatti P, et al. 1987. Comparison of chromosome aberration frequency before 

and after administration of 131I in two groups of thyroid cancer patients. Tumori 73:257-262. 

Ardito G, Lamberti L, Bigatti MP. 1988. Chromosome studies on human lymphocytes following 

treatment with radioactive iodine in vitro. Boll Soc Ital Biol Sper 2(LXIV):131-138. 

Ardito G, Lamberti L, Cottino F, et al. 1983. Analysis of cell kinetics, chromosome aberration frequency
 

and sister chromatid exchanges in lymphocyte "in vitro" cultures of patients irradiated by 131I. 

Preliminary note. Boll Soc Ital Biol Sper 59(2):135-141. 

Arena Ansotegui J, Emparanza Knorr JI, San Millan Vege MJ, et al. 1989. [Iodine overload in newborn 

infants caused by the use of PVP-iodine for perineal preparation of the mother in vaginal delivery.] An 

Esp Pediatr 30(1):23-26. (Spanish) 

Arndt D, Mehnert WH, Franke W-G, et al. 1994. Radioiodine therapy during an unknown remained 

pregnancy and radiation exposure of the fetus. Strahlenther Onkol 170(7):408-414. 

Arrington LR, Taylor RN, Ammerman CB, et al. 1965. Effects of excess dietary iodine upon rabbits, 

hamsters, rats and swine. J Nutr 87:394-398. 

Arslan NC, Geard CR, Hall EJ. 1986. Low dose-rate effects of cesium-137 and iodine-125 on cell 

survival, cell progression, and chromosomal alterations. Am J Clin Oncol 9(2):114-115. 

Artemova EP, Nikolaev AI. 1976. [Congenital disorders of the thyroid gland in experimental litters 

obtained from mothers subjected to immunization and the action of I-131.] Probl Endokrinol (Mosk) 

22(2):66-70. (Russian) 

Arthur JR. 1999. Functional indicators of iodine and selenium status. Proc Nutr Soc 58:507-512. 

*Arthur JR, Beckett GF. 1994. Roles of selenium in Type I iodothyronine 5'-deiodinase and in thyroid 

hormone and iodine metabolism. In: Burk RF, ed. Selenium in biology and human health. New York, 

NY: Springer-Verlag, 94-115. 

Arthur JR, Nicol F, Beckett GJ. 1992a. The role of selenium in thyroid hormone metabolism and effects 

of selenium deficiency on thyroid hormone and iodine metabolism. Biol Trace Elem Res 34:321-325. 

Arthur JR, Nicol F, Beckett GJ. 1992b. The role of selenium in thyroid hormone metabolism and effects 

of selenium on thyroid hormone and iodine metabolism. Biol Trace Elem Res 33:37-42. 

Asmis LM, Gerber H, Kaempf J, et al. 1995. Epidermal growth factor stimulates cell proliferation and 

inhibits iodide uptake of FRTL-5 cells in vitro. J Endocrinol 145:513-520. 

Assimakopoulos PA, Ioannides KG, Pakou AA, et al. 1987. Transport of the radioisotopes iodine-131, 

cesium-134, and cesium-137 from the fallout following the accident at the Chernobyl nuclear reactor into 

cheese and other cheesemaking products. J Dairy Sci 70:1338-1343. 
 

 

IODINE 332 

9. REFERENCES 

Assimakopoulos PA, Ioannides KG, Pakou AA. 1988. The environmental behavior of 131I in 

northwestern Greece following the nuclear reactor accident at Chernobyl. Health Phys 55(5):783-791. 

Assimakopoulos PA, Ioannides KG, Pakou AA. 1989. The propagation of the Chernobyl 131I impulse 

through the air-grass-animal-milk pathway in northwestern Greece. Sci Total Environ 85:295-305. 

*Astakhova LN, Anspaugh LR, Beebe GW, et al. 1998. Chernobyl-related thyroid cancer in children in
 

Belarus: A case-control study. Rad Res 150:349-356. 

*Astakhova LN, Mityukova TA, Kobzev VF. 1996. Endemic goiter in Belarus following the accident at 

the Chernobyl nuclear power plant. In: Nagataki S, Yamashita S, eds. Nagasaki symposium radiation 

and human health: Proposal from Nagasaki. Amsterdam, the Netherlands: Elsevier, 67-95. 

*ASTM. 1995. Annual book of ASTM Standards. Vol. 11.02. American Society for Testing of 

Materials. Philadelphia, PA. 

*ASTM. 1998. American Society for Testing and Materials. Standard test methods for iodide and 

bromide ions in brackish water, seawater, and brines. NTIS ASTM-D 3869-95, 338-344. 

ASTM. 1999. Annual book of ASTM standards, vol. 11.02. American Society for Testing of Materials. 

Philadelphia, PA: ASTM, 290-300. 

*ATF. 2001a. Denaturants authorized for denatured spirits. U.S. Bureau of Alcohol, Tobacco, and 

Firearms. Code of Federal Regulations. 27 CFR 21.151. http://frwebgate.access.gpo.gov/cgi. 

May 16, 2001. 

*ATF. 2001b. Uses of specially denatured alcohol and specially denatured rum. U.S. Bureau of 

Alcohol, Tobacco, and Firearms. Code of Federal Regulations. 27 CFR 21.141. 

http://frwebgate.access.gpo.gov/cgi-bin. May 16, 2001. 

Aungst BJ, Vesell ES, Shapiro JR. 1979. Unusual characteristics of the dose-dependent uptake of 

propylthiouracil by thyroid gland in vivo: Effects of thyrotropin, iodide or phenobarbital pretreatment. 

Biochem Pharmacol 28:1479-1484. 

Austin AR, Whitehead DC, Le Du YLP, et al. 1980. The influence of dietary iodine on iodine in the 

blood serum of cows and calves in the perinatal period. Res Vet Sci 28:128-130. 

Ayala C, Navarro E, Rodriguez JR, et al. 1998. Conception after iodine-131 therapy for differentiated 

thyroid cancer. Thyroid 8(11):1009-1011. 

Ayromlooi J. 1972. Congenital goiter due to maternal ingestion of iodides. Obstet Gynecol 39(6):818­

822. 

Babu S, Shenolikar I. 1992. Thiocyanate ingestion through milk and its effects on serum 

triiodothyronine (T3) and thyroxine (T4) levels in monkeys fed low iodine diet. Indian J Dairy Sci 

45(6):326-329. 

*Bacher-Stier C, Riccabona G, Totsch M, et al. 1997. Incidence and clinical characteristics of thyroid 

carcinoma after iodine prophylaxis in an endemic goiter country. Thyroid 7(5):733-741. 
 

 

IODINE 333 

9. REFERENCES 

*Bachrach LK, Burrow GN, Gare DJ. 1984. Maternal-fetal absorption of povidone-iodine. J Pediatr 

104(1):158-159. 

Backer H, Hollowell J. 2000. Use of iodine for water disinfection: Iodine toxicity and maximum 

recommended dose. Environ Health Perspect 108(8):679-684. 

Bagchi N, Brown TR. 1986. Adaptation of male and female rats to iodine deficiency. Horm Metab Res 

18:811-813. 

*Bagchi N, Fawcett DM. 1973. Role of sodium ion in active transport of iodide by cultured thyroid 

cells. Biochim Biophys Acta 318:235-251. 

*Bagchi N, Brown TR, Urdanivia E, et al. 1985a. Induction of autoimmune thyroiditis in chickens by 

dietary iodine. Science 230:325-327. 

Bagchi N, Shivers B, Brown TR. 1985b. Studies on the mechanism of acute inhibition of thyroglobulin 

hydrolysis by iodine. Acta Endocrinol 108:511-517. 

*Bair WJ, Snyder MD, Walters RA, et al. 1963. Effect of I127 on thyroid uptake of inhaled I131 . Health 

Phys 9:1399-1410. 

Bairakova A, Nikolova M, Kiradzhiev G. 1990. [Side-effects of iodine prophylaxis in pregnancy.] 

Rentgenol Radiol 29(2):46-50. (Russian) 

Baker HJ, Lindsey JR. 1968. Equine goiter due to excess dietary iodide. J Am Vet Med Assoc 

153(12):1618-1630. 

*Bakheet SMB, Hammami MM, Hemidan A, et al. 1998. Radioiodine secretion in tears. J Nucl Med 

39(8):1452-1454. 

Bakheet SMB, Hammami MM, Powe J. 1996. False-positive radioiodine uptake in the abdomen and the 

pelvis: Radioiodine retention in the kidneys and review of the literature. Clin Nucl Med 21(12):932-937. 

*Bakiri F, Djemli FK, Mokrane LA, et al. 1998. The relative roles of endemic goiter and socioeconomic 

developmental status in the prognosis of thyroid carcinoma. Cancer 82:1146-1153. 

Bal CS, Padhy AK, Jana S, et al. 1994. Comparison of low and high dose I-131 ablation of remnant in 

differentiated thyroid cancer patients. In: Proceedings of the XVI International Cancer Congress: Free 

papers and posters: New Delhi (India), October 30-November 5, 1994. Bologna, Italy: Monduzzi 

Editore, 1059-1063. 

Bal CS, Padhy AK, Jana S, et al. 1996. Prospective randomized clinical trial to evaluate the optimal dose 

of 131I for remnant ablation in patients with differentiated thyroid carcinoma. Cancer 77:2574-2580. 

Ball DW, Baylin SB, de Bustros AC. 1996. Medullary thyroid carcinoma. In: Braverman LE, Utiger 

RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: 

Lippincott-Raven, 946-960. 

*Ballad RV, Holman DW, Hennecke EW, et al. 1976. Iodine-129 in thyroids of grazing animals. Health 

Phys 30:345-350. 
 

 

IODINE 334 

9. REFERENCES 

*Ballad RV, Tan SH, Johnson JE, et al. 1978. Iodine-129 in man, cow and deer. Health Phys 34:691­

696. 

*Ballardin M, Gemignani F, Bodei L, et al. 2002. Formation of micronuclei and of clastogenic factor(s) 

in patients receiving therapeutic doses of iodine-131. Mutat Res 514(1-2):77-85. 

*Balonov MI, Krisyuk EM, Ramel C. 1999. Environmental radioactivity, population exposure and 

related health risks in the east Baltic region. Scand J Work Environ Health 25:17-32. 

Balsam A, Sexton F, Borges M, et al. 1983. Formation of diiodotyrosine from thyroxine. J Clin Invest 

72:1234-1245. 

Balter M. 1995. Chernobyl's thyroid cancer toll. Science 270:1758-1759. 

*Baltisberger BL, Minder CE, Burgi H. 1995. Decrease of incidence of toxic nodular goitre in a region 

of Switzerland after full correction of mild iodine deficiency. Eur J Endocrinol 132:546-549. 

Baltrukiewicz Z, Derecki J, Pogorzelska-Lis M. 1973. Transfer of selected radionuclides from the 

organism of pregnant and feeding female rat to the offsprings. Acta Physiol Pol 24:437-444. 

Banerjee R, Gopinath G, Gopinath PG. 1988. Vascular changes in the brain following internally 

administered radioiosotope131-I in rats during postnatal period. Indian J Med Res 87:484-493. 

Banfield WG, Grimley PM, Hammond WG, et al. 1971. Electron probe analysis for iodine in human 

thyroid and parathyroid glands, normal and neoplastic. J Natl Cancer Inst 46:269-273. 

Bangming R, Jianguo L, Xianyu C, et al. 1996. [Study of thyroglobulin gene activity in thyroid disease.]
 

Zhonghua Heyixue Zazhi 16(4):250-252. (Chinese) 

*Barakat M, Carson D, Hetherton AM, et al. 1994. Hypothyroidism secondary to topical iodine 

treatment in infants with spina bifida. Acta Paediatr 83:741-743. 

Baran DT. 1996a. The skeletal system in hypothyroidism. In: Braverman LE, Utiger RD, eds. Werner 

and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 853-857. 

Baran DT. 1996b. The skeletal system in thyrotoxicosis. In: Braverman LE, Utiger RD, eds. Werner 

and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 678-686. 

*Baratta EJ, Esterly DG. 1989. Gamma-ray spectroscopic determination of iodine-131 and cesium-137 

in foods: Two collaborative studies. J Assoc Off Anal Chem 72(4):667-669. 

*Barker SB. 1948. Determination of protein-bound iodine. J Biol Chem 173:715-724. 

*Barkley RA, Thompson TG. 1960. Determination of chemically combined iodine in sea water by 

amperometric and catalytic methods. Anal Chem 32:154-158l. 

*Barnes DG, Dourson M. 1988. Reference dose (RfD): Description and use in health risk assessments. 

Regul Toxicol Pharmacol 8:471-486. 

Barnes ND, O'Connell EJ, Cloutier MD. 1975. Iodide-induced (SSKI) hypothyroidism in infancy. Ann 

Allergy 35:305-308. 
IODINE 335 

9. REFERENCES 

*Barrie LA, Hoff RM. 1985. Five years of air chemistry observations in the Canadian Arctic. Atmos 

Environ 19:1995-2010. 

Barrington SF, Kettle AG, O'Doherty MJ, et al. 1996. Radiation dose rates from patients receiving 

iodine-131 therapy for carcinoma of the thyroid. Eur J Nucl Med 23(2):123-130. 

*Barrington SF, O'Doherty MJ, Kettle AG, et al. 1999. Radiation exposure of the families of outpatients 

treated with radioiodine (iodine-131) for hyperthyroidism. Eur J Nucl Med 26(7):686-692. 

Barsano CP. 1996. Other forms of hypothyroidism. In: Braverman LE, Utiger RD, eds. Werner and 

Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 768-778. 

Bartalena L, Bogazzi F, Martino E. 1996. Adverse effects of thyroid hormone preparations and 

antithyroid drugs. Drug Saf 15:53-63. 

Bartalena L, Marcocci C, Bogazzi F, et al. 1989. Use of corticosteroids to prevent progression of Graves' 

ophthalmopathy after radioiodine therapy for hyperthyroidism. N Engl J Med 321(20):1349-1352. 

Bartalena L, Marcocci C, Bogazzi F, et al. 1998. Relation between therapy for hyperthyroidism and the 

course of Graves' ophthalmopathy. N Engl J Med 338(2):73-78. 

*Bartolini P, Ribela MTCP, Araujo EA. 1988. Results of a thyroid monitoring survey carried out on 

workers exposed to 125I in Sao Paulo, Brazil. Health Phys 55(3):511-515. 

*Bašič M, Kasal B, Simonovic I, et al. 1988. 131I dose to the human fetal thyroid in the Zagreb district, 

Yugoslavia, from the Chernobyl accident. Int J Radiat Biol 54(2):167-177. 

Bastiani P, Papandreou J, Blanck O, et al. 1995. On the relationship between completion of Nacetyllactosamine oligosassharide units and iodine content of thyroglobulin: A reinvestigation. 

Endocrinology 136(10):4204-4209. 

*Baugnet-Mahieu L, Lemaire M, Leonard ED, et al. 1994. Chromosome aberrations after treatment with 

radioactive iodine for thyroid cancer. Radiat Res 140:429-431. 

*Baumgartner TG. 1976. Potassium iodide and iododerma. Am J Hosp Pharm 33:601-603. 

Bautista A, Barker PA, Dunn JT, et al. 1982. The effects of oral iodized oil on intelligence, thyroid 

status, and somatic growth in school-age children from an area of endemic goiter. Am J Clin Nutr 

35:127-134. 

Baverstock KF. 1993. Thyroid cancer in children in Belarus after Chernobyl. World Health Stat Q 

46:204-208. 

Bayliff CD, Sibbald WJ, Mills DG, et al. 1981. Electrolyte abnormalities following povidone-iodine 

topical therapy. Drug Intell Clin Pharm 15(10):801-802. 

Bazyltchik SV, Astakhova LN. 1996. Mental development of children exposed to ionizing radiation in 

utero and in infancy. In: Nagataki S, Yamashita S, eds. Nagasaki symposium radiation and human 

health: Proposal from Nagasaki. Amsterdam, the Netherlands: Elsevier, 97-102. 
 

 

 

IODINE 336 

9. REFERENCES 

Beach SA, Dolphin GW. 1962. A study of the relationship between x-ray dose delivered to the thyroids 

of children and the subsequent development of malignant tumours. Phys Med Biol 6:583-598. 

*Beals DM, Hayes DW. 1995. Technetium-99, iodine-129 and tritium in the waters of the Savannah 

river site. Sci Total Environ 173/174:101-115. 

*Beals DM, Chastagner P, Turner P. 1992. Analysis of iodine-129 in aqueous samples by inductively 

coupled plasma-mass spectrometry. Westinghouse Savannah River Company, Aiken, SC. NTIS 

DE93002694. 

Beaugelin-Seiller K, Baudin JP, Brottet D. 1994. Use of aquatic mosses for monitoring artificial 

radionuclides downstream of the nuclear power plant of Bugey (River Rhone, France). J Environ 

Radioact 24:217-223. 

Becciolini A, Porciani S, Lanini A, et al. 1994. Serum amylase and tissue polypeptide antigen as 

biochemical indicators of salivary gland injury during iodine-131 therapy. Eur J Nucl Med 21:1121­

1125. 

Bech K. 1988. Importance of cytolytic activity and dietary iodine in the pathogenesis of postpartum 

thyroiditis. Allergy 43:161-166. 

Becker BA. 1961. Iodide transport by the rabbit eye. Am J Physiol 200(4):804-806. 

Becker BA, Fenves AZ, Breslau NA. 1999. Membranous glomerulonephritis associated with Grave's 

disease. Am J Kidney Dis 33(2):369-373. 

Becker DV. 1979. The role of radioiodine treatment in childhood hyperthyroidism. J Nucl Med 

20(8):890-894. 

Becker DV. 1983. Physiological basis for the use of potassium iodide as a thyroid blocking agent 

logistic issues in its distribution. Bull N Y Acad Med 59(10):1003-1008. 

Becker DV. 1987. Reactor accidents: Public health strategies and their medical implications. JAMA 

258:649-654. 

Becker DV, Zanzonico P. 1997. Potassium iodide for thyroid blockade in a reactor accident: 

Administrative policies that govern its use. Thyroid 7(2):193-197. 

Becker DV, Braverman LE, Dunn JT, et al. 1984. The use of iodine as a thyroidal blocking agent in the 

event of a reactor accident: Report of the Environmental Hazards Committee of the American Thyroid 

Association. JAMA 252(5):659-661. 

Becker PC, Ibanez CA, Aguayo JB, et al. 1986. [Absence of foetal hypothyroidism despite treatment 

with 131I during gestation.] Rev Med Chil 114:343-345. (Spanish) 

Becker W, Borner W, Reiners C, et al. 1988. [Radioiodine therapy for immune hyperthyroidism 

depending on age. A tenable risk even for younger patients?]. Dtsch Med Wochenschr 113(23):954-961. 

(German) 

Beckham W, Ralson A. 1991. Letters to the editor. Australas Phys Eng Sci Med 14(3):173. 
IODINE 337 

9. REFERENCES 

Becks GP, Eggo MC, Burrow GN. 1987. Regulation of differentiated thyroid function by iodide: 

Preferential inhibitory effect of excess iodide on thyroid hormone secretion in sheep thyroid cell cultures. 

Endocrinology 120(6):2569-2575. 

Bednar J, Nemec J, Soutorova M, et al. 1980. Composition of circulating iodoproteins following 

therapeutic application of 131I for thyroid carcinoma. Radiochem Radioanal Lett 45(6):377-386. 

Bednarczuk T, Kennerdell JS, Wall JR. 1997. Thyroid-associated ophthalmopathy: Etiology and 

pathogenesis. In: Falk SA, ed. Thyroid disease: Endocrinology, surgery, nuclear medicine, and 

radiotherapy. Philadelphia, PA: Lippincott-Raven Publishers, 341-357. 

Beekhuis H, Piers DA. 1983. Radiation risk of thyroid scintigraphy in newborns. Eur J Nucl Med 

8:348-350. 

Beere HM, Bidey SP, Tomlinson S. 1989. Cytotoxicity of high iodide levels for porcine thyroid cells in 

primary culture is relieved by methimazole or stable cylic AMP analogues. J Endocrinol 121(Suppl):No 

pagination. 

Beere HM, Cowin AJ, Soden J, et al. 1995. Iodide-dependent regulation of thyroid follicular cell 

proliferation: A mediating role of autocrine insulin-like growth factor-I. Growth Regul 5:203-209. 

Beere HM, Tomlinson S, Bidey SP. 1990. Iodide autoregulation of functional and morphological 

differentiation events in the FRTL-5 rat thyroid cell strain. J Endocrinol 124:19-25. 

Beeson KC, Forbes AL, Horvath DJ, et al. 1978. Plants and foods of plant origin. In: Geochemistry and 

the environment. Vol. III. Distribution of trace elements related to the occurrence of certain cancers, 

cardiovascular diseases and urolithiasis. Washington, DC: National Academy of Sciences, 59-78. 

Beeson PB. 1994. Effects of iodides on inflammatory processes. Perspect Biol Med 37(2):173-181. 

Begishev A. 1975. [Data on the toxicity characteristics of iodine vapors under conditions of increased air 

temperature (experimental data).] Gig Tr Prof Zabol 6:38-41. (Russian) 

*Behne D, Kyriakopoulos A. 1993. Effects of dietary selenium on the tissue concentrations of type I 

iodothyronine 5'-deiodinase and other selenoproteins. Am J Clin Nutr Suppl 57:310S-312S. 

*Beierwaltes WH. 1979. The history of the use of radioactive iodine. Semin Nucl Med IX(3):151-155. 

Beierwaltes WH, Crane HR, Wegst A, et al. 1960. Radioactive iodine concentration in the fetal human 

thyroid gland from fall-out. JAMA 173(17):1895-1902. 

*Beierwaltes WH, Hilger MTJ, Wegst A. 1963. Radioiodine concentration in fetal human thyroid from 

fallout. Health Phys 9:1263-1266. 

BEIR V. 1990. Health effects of exposure to low levels of ionizing radiation. Biological Effects of 

Ionizing Radiations. Washington, DC: National Academy Press. 

*Belfiore A, La Rosa GL, Padova G, et al. 1987. The frequency of cold thyroid nodules and thyroid 

malignancies in patients from an iodine-deficient area. Cancer 60:3096-3102. 
IODINE 338 

9. REFERENCES 

Bellisola G, Bratter P, Cinque G, et al. 1998. The TSH-dependent variation of the essential elements 

iodine, selenium and zinc within human thyroid tissues. J Trace Elem Med Biol 12:177-182. 

*Beno M, Hrabovcova A, Piknova D, et al. 1991. Human postmortem thyroid 131I content and risk 

estimates in Bratislava, Czechoslovakia following the Chernobyl accident. Health Phys 60(2):203-208. 

*Beno M, Mikulecky M, Hrabina J. 1992. Transfer factor of 131I from the fallout to human thyroid dose 

equivalent after the Chernobyl accident. Radiat Environ Biophys 31:133-139. 

*Benotti J, Benotti N. 1963. Protein-bound iodine, total iodine and butanol-extractable iodine by partial 

automation. Clin Chem 9:408-416. 

*Benotti J, Benotti N, Pino S, et al. 1965. Determination of total iodine in urine, stool, diets and tissues. 

Clin Chem 11:932-936. 

Benson SG. 1969. Kinetics of I 131 uptake and release in the rat thyroid gland. Ph.D. Dissertation, The 

University of Nebraska, 70. 

Bercz JP. 1991. Endocrine toxicity of drinking water disinfectants. I. In vivo dehalogenation and 

clearance of iodinated nutrients. J Am Coll Toxicol 10(5):525-532. 

Bercz JP, Jones LL, Harrington RM, et al. 1986. Mechanistic aspects of ingested chlorine dioxide on 

thyroid function: Impact of oxidants on iodide metabolism. Environ Health Perspect 69:249-255. 

Berenbaum MC. 1974. The production of pulmonary oedema in mice by cyclophosphamide and iodide. 

Agents Actions 4(1):7-14. 

Beresford NA, Mayes RW, Barnett CL, et al. 1997. The effectiveness of oral administration of 

potassium iodide to lactating goats in reducing the transfer of radioiodine to milk. J Environ Radioact 

35(2):115-128. 

*Berg D, Kollmer WE, Kriegel H, et al. 1987. Radioactive iodine and cesium in Bavarian citizens after 

the nuclear reactor accident in Chernobyl. Trace Subst Environ Health 21:219-225. 

Berg GEB, Michanek AMK, Holmberg ECV, et al. 1996. Iodine-131 treatment of hyperthyroidism: 

Significance of effective half-life measurements. J Nucl Med 37(2):229-232. 

Berg GEB, Nystrom EH, Jacobsson L, et al. 1998. Radioiodine treatment of hyperthyroidism in a 

pregnant woman. J Nucl Med 39:357-361. 

Berg JN, Padgitt D. 1985. Iodine concentrations in milk from iodophor test dips. J Dairy Sci 68:457­

461. 

*Berger GS. 1994. Epidemiology of endometriosis. In: Berger GS, ed. Endometriosis: Advanced 

management and surgical techniques. New York, NY: Springer-Verlag. 

*Berkovski V. 1999a. Radioiodine biokinetics. Part 1. Pregnant woman. In: Radiation and thyroid 

cancer. National Research Council, Canada, 319-325. 

*Berkovski V. 1999b. Radiation biokinetics in the mother and fetus. Part 2. Fetus. In: Radiation and 

thyroid cancer. National Research Council, Canada, 327-332. 
 

 

 

IODINE 339 

9. REFERENCES 

*Berkovski V. 2002. New iodine models family for simulation of short-term biokinetics processes, 

pregnancy and lactation. Food and Nutrition Bulletin 23(3):87-94. 

*Bermejo-Barrera P, Moreda-Pineiro A, Aboal-Somoza M, et al. 1994. Indirect determination of iodide, 

as an HgxIx complex, by electrothermal atomic absorption spectrometry. J Anal Atom Spectrom 9:483­

487. 

*Bernard JD, McDonald RA, Nesmith JA. 1970. New normal ranges for the radioiodine uptake study. J 

Nucl Med 11:449-451. 

Bernhard JD, Freedberg IM, Vogel LN. 1996a. The skin in hypothyroidism. In: Braverman LE, Utiger 

RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: 

Lippincott-Raven, 792-795. 

Bernhard JD, Freedberg IM, Vogel LN. 1996b. The skin in thyrotoxicosis. In: Braverman LE, Utiger 

RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: 

Lippincott-Raven, 595-597. 

*Bertelsen JB, Hegedus L. 1994. Cigarette smoking and the thyroid. Thyroid 4:327. 

Berthezene F, Greer MA. 1974. Studies on the composition of the thyroid psammoma bodies of 

chronically iodine-deficient rats. Endocrinology 95:651-659. 

Berthezene F, Mornex R. 1971. Variations chez le rat de la clearance thyroidienne de l'iode (CIT), du 

taux d'iodure plasmatique (PII) et de la captation absolue de l'iode stable (AUI) apres l'arret d'un 

traitement par le methylthiouracil (MTU). Pathol Biol 23-24:1075-1079. 

Berthier C, Lemarchand-Beraud T. 1976. Thyroid cAMP and iodine, plasma and pituitary TSH during 

goiter development in rats. Excerpta Medica 378:485-489. 

Berthier C, Lemarchand-Beraud T. 1978. Importance of thyroid iodine and cyclic AMP and TSH 

concentrations on goitre formation in rats. Acta Endocrinol 89:567-579. 

Bertin M, Lallemand J, Hubert D. 1994. [Health consequences of a Chernobyl accident. An assessment 

eight years later.] Lyon Pharm 45(1):9-16. (French) 

*Bertine KK, Goldberg ED. 1971. Fossil fuel combustion and the major sedimentary cycle. Science 

173:233-235. 

Best JD, Chan V, Khoo R, et al. 1981. Incidence of hypothyroidism after radioactive iodine therapy for 

thyrotoxicosis in Hong Kong Chinese. Clin Radiol 32:57-61. 

Bestano M, Pagliaini R, Maira G, et al. 1993. Mediastinal uptake of 131-I in patients with thyroid 

cancer: May it be referred to normal thymus? Eur J Nucl Med 20:648. 

Bethell MF. 1970. Toxic psychosis caused by radioactive iodine [Letter]. Br J Psychiatry 117:473-479. 

*Better OS, Garty J, Brautbar N, et al. 1969. Diminished functional parathyroid reserver following I131 

treatment for hyperthyroidism. Isr J Med Sci 5(3):419-422. 
IODINE 340 

9. REFERENCES 

*Beyer KH, Fehr DM, Gelarden RT, et al. 1981. Hydrochlorothiazide-induced 131I excretion facilitated 

by salt and water. J Clin Pharmacol 21(5-6):201-212. 

Beyssen ML, Lagorce JF, Cledat D, et al. 1999. Influence of dietary iodine on drug-induced 

hypothyroidism in the rat. J Pharm Pharmacol 51:745-750. 

Bhat IS, Kamath PR. 1969. Goat thyroids as indicators for routine environmental monitoring of 

radioiodine. Health Phys 16:65-67. 

*Bhat IS, Hedge AG, Chandramouli S, et al. 1973. Evaluation of internal exposure to radionuclides of I, 

Cs, and Co during maintenance operations on primary steam leak in a nuclear power station. Health 

Physics 25:135-139. 

Bhatt H. 1977. Effect of calcium intake on thyroid and renal clearance of iodine in goiter. J Physiol 

269:64-65. 

Bhatta KM, Evenstad KL. 1994. Use of potassium iodide for the treatment of symptomatic benign 

hyperplasia. (to Upsher-Smith Laboratories) Application: USA WO 94/25040, 10 Nov 1994. USA 

Patent WO 94/25040, issued 10 Nov 1994. 

Bianco AC, Nunes MT, Martins EJ, et al. 1981. Possible mechanism of action of cholesterol enriched 

diet on the thyroid. Endocrinol Exp 15:277-285. 

*Bichsel Y, Vongunten U. 1999. Oxidation of iodine and hypoiodous acid in the disinfection of natural 

waters. Environ Sci Technol 33:4040-4045. 

*Bidart JM, Lacroix L, Evain-Brion D, et al. 2000. Expression of Na+

/I- symporter and Pendred 

syndrome genes in trophoblast cells. J Clin Endocrinol Metab 85(11):4367-4372. 

Birnbaum DA. 1978. Febrile response to whirlpool bath treatments [Letter]. JAMA 239(12):1133. 

Bishop ME, Garcia RL. 1978. Iododerma from wound irrigation with povidone-iodine. JAMA 

240(3):249-250. 

Bitton R, Sachmechi I, Benegalro Y, et al. 1993. Leukemia after a small dose of radioiodine for 

metastatic thyroid cancer. J Clin Endocrinol Metab 77(5):1423-1426. 

*Black A, Hounam RF. 1968. Penetration of iodine vapour through the nose and mouth and the 

clearance and metabolism of the deposited iodine. Ann Occup Hyg 11:209-225. 

Black JA. 1963. Neonatal goitre and mental deficiency: The role of iodides taken during pregnancy. 

Arch Dis Child 38:526-529. 

*Black SC, Douglas RL, Barth DS. 1976. Gaseous radioiodine transport in the air-forage-cow-milk 

system. US Environmental Protection Agency, Las Vegas, NV. Report No. EMLS-LV-539-1, 1-25. 

Blackwell N, Stevenson AC, Wiernik G. 1974. Chromosomal findings in patients treated with small 

doses of iodine-131. Mutat Res 25:397-402. 

Blahos J, Soumar J. 1973. [Increased frequency of hypothyroidism after iodine 131. Longitudinal 

study.] Probl Acutels Endocrinol Nutr 17:95-103. (French) 
 

 

 

IODINE 341 

9. REFERENCES 

Blahos J, Soumar J. 1975. The role of age in the development of hypothyroidism after treatment with 

radioiodine. Endokrinologie 64(2):196-200. 

*Bleuer JP, Averkin YI, Abelin T. 1997. Chernobyl-related thyroid cancer: What evidence for role of 

short-lived iodines? Environ Health Perspect Suppl 105(6):1483-1486. 

Blincoe C, Bohman VR. 1991. Fallout 131I in western Nevada cattle thyroid glands: 1962-Early 1969. 

Bull Environ Contam Toxicol 47:485-490. 

Blomgren H, Wasserman J, Petrini B, et al. 1991. Blood lymphocyte population following 131I treatment 

for hyperthyroid. Acta Endocrinol 124:152-158. 

Bloomer WD, Adelstein SJ. 1981. Iodine-125 cytotoxicity: Implications for therapy and estimation of 

radiation risk. Int J Nucl Med Biol 8:171-178. 

Bloomer WD, McLaughlin WH, Adelstein SJ. 1982. Therapeutic implications of iodine-125 

cytotoxicity. Int J Radiat Oncol Biol Phys 8:1903-1908. 

*Blum M, Liuzzi A. 1967. Thyroid 131I burdens in medical and paramedical personnel. JAMA 

200(11):184-186. 

Blumenthal RD, Alisauskas R, Lew W, et al. 1998. Myelosuppressive changes from single or repeated 

doses of radioantibody therapy: effect of bone marrow transplantation, cytokines, and hematopoietic 

suppression. Exp Hematol 26:859-868. 

Blumenthal RD, Sharkey RM, Quinn LM, et al. 1990. Use of hematopoietic growth factors to control 

myelosuppression caused by radioimmunotherapy. Cancer Res Suppl(50):1003s-1007s. 

*BNA. 2001a. Reports of individual monitoring. The Bureau of National Affairs, Inc. 

http://www.bna.com. February 22, 2001. 

*BNA. 2001b. General license for use of byproduct material for certain in vitro clinical or laboratory 

testing. The Bureau of National Affairs, Inc. http://www.bna.com. February 22, 2001. 

*BNA. 2001c. Quantities of radioactive materials requiring consideration of the need for an emergency 

plan for responding to a release. The Bureau of National Affairs, Inc. http://www.bna.com. February 22, 

2001. 

*BNA. 2001d. Quantities of licensed material requiring labeling. The Bureau of National Affairs, Inc. 

http://www.bna.com. February 22, 2001. 

*BNA. 2001e. Release limits for containment requirements. The Bureau of National Affairs, Inc. 

http://www.bna.com. February 22, 2001. 

*BNA. 2001f. Designation, reportable quantities, and notification. The Bureau of National Affairs, Inc. 

http://www.bna.com. February 22, 2001. 

*BNA. 2001h. Environment and safety library: States and territories. The Bureau of National Affairs, 

Inc. http://www.bna.com. February 13, 2001. 
 

 

IODINE 342 

9. REFERENCES 

Bo G, Guishan Y. 1997. [Effects of high-dose iodine on brain development in mice.] Chin J Prev Med 

31(3):134-136. (Chinese) 

Bobechko WP. 1989. Iodine in the diet. Can Med Assoc J 140:1431. 

Bocanera LV, Krawiec L, Nocetti G, et al. 2001. The protein kinase C pathway inhibits iodide uptake by 

calf thyroid cells via sodium potassium-adenosine triphosphate. Thyroid 11(9):813-817. 

Bocanera LV, Krawiec L, Silberschmidt D, et al. 1997. Role of cyclic 3'5'guanosine monophosphate and 

nitric oxide in the regulation of iodide. J Endocrinol 155:451-457. 

Bockisch A, Jamitzky T, Derwanz R, et al. 1993. Optimized dose planning of radioiodine therapy of 

benign thyroidal diseases. J Nucl Med 34(10):1632-1638. 

Bodansky HJ. 1986. Thyroid cancer after 131I treatment. Lancet 2(8509):755-756. 

*Bodigheimer K, Nowak F, Schoenborn W. 1979. Pharmacokinetics and thyrotoxicity of the sodium 

nitroprusside metabolite of thiocyanate. Dtsc Med Wochenschr 104:939-943. 

Body JJ, Demeester-Mirkine N, Corvilain J. 1988. Calcitonin deficiency after radioactive iodine 

treatment. Ann Intern Med 109(7):590-591. 

Boeynaems J-M, Van Sande J, Dumont JE. 1995. Which iodolipids are involved in thyroid 

autoregulation: Iodolactones or iodoaldehydes? Eur J Endocrinol 132:733-734. 

Bogazzi F, Bartalena L, Brogioni S, et al. 1999. Comparison of radioiodine with radioiodine plus lithium 

in the treatment of Graves' hyperthyroidism. J Clin Endocrinol Metab 84(2):499-503. 

*Bogazzi F, Bartalena L, Gasperi M, et al. 2001. The various effects of amiodarone on thyroid function. 

Thyroid 11(5):511-519. 

*Bogdanove EM, Strash AM. 1975. Radioiodine escape is an unexpected source of radioummunoassay 

error and chronic low level environmental contamination. Nature 257:426-427. 

*Bohuslavizki KH, Brenner W, Klutmann S, et al. 1998a. Radioprotection of salivary glands by 

amifostine in high-dose radioiodine therapy. J Nucl Med 39:1237-1242. 

*Bohuslavizki KH, Brenner W, Lassmann S, et al. 1996. Quantitative salivary gland scintigraphy in the 

diagnosis of parenchymal damage after treatment with radioiodine. Nucl Med Commun 17:681-686. 

*Bohuslavizki KH, Klutmann S, Bleckmann C, et al. 1999. Salivary gland protection by amifostine in 

high-dose radioiodine therapy by differentiated thyroid cancer. Strahlenther Onkol 175:57-61. 

*Bohuslavizki KH, Klutmann S, Brenner W, et al. 1998b. Salivary gland protection by amifostine in 

high-dose radioiodine treatment: Results of a double-blind placebo-controlled study. J Clin Oncol 

16(11):3542-3549. 

Boice JD, Engholm G, Kleinerman RA, et al. 1988. Radiation dose and second cancer risk in patients 

treated for cancer of the cervix. Radiat Res 116:3-55. 
IODINE 343 

9. REFERENCES 

Bolster AA, Hilditch TE. 1996. The radiation dose to the urinary bladder in radio-iodine therapy. Phys
 

Med Biol 41:1993-2008. 

Bonnema SJ, Bertelsen H, Mortensen J, et al. 1999. The feasibility of high dose iodine 131 treatment as 

an alternative to surgery in patients with a very large goiter: Effect on thyroid function and size and 

pulmonary function. J Clin Endocrinol Metab 84(10):3636-3641. 

Book DA, McNeill DA, Parks NJ, et al. 1980. Comparative effects of iodine-132 and iodine-131 in rat 

thyroid glands. Radiat Res 81:246-253. 

Book SA. 1977a. 131I uptake and retention in fetal guinea pigs. Health Phys 32:149-154. 

Book SA. 1977b. Iodine-129: Limits to radiologic dose. Health Phys 32(4):321-324. 

Book SA. 1983. Iodine-129 uptake and effects of lifetime feeding in rats. Health Phys 45(1):61-66. 

*Book SA, Goldman M. 1975. Thyroidal radioiodine exposure of the fetus. Health Phys 29:874-877. 

Book SA, McNeill DA, Spangler WL. 1980. Age and its influence on effects of iodine-131 in guinea pig 

thyroid glands. Radiat Res 81:254-261. 

Book SA, Wolf HG, Parker HR, et al. 1974. The exchange of radioiodine in pregnant and fetal sheep. 

Health Phys 26:533-539. 

Booz J, Smith T. 1977. Local distribution of energy deposition in and around the follicles of a 125I 

contaminated thyroid. Curr Top Radiat Res Q 12:12-32. 

Bordell FL, Sayeg JA, Wald N, et al. 1972. In vivo measured effective half-life of 125I in human thyroids. 

Phys Med Biol 17(3):365-373. 

Bors J, Martens R, Kuhn W. 1984. [Effect of microorganisms on the adsorption and translocation of 

radioiodine in soil.] Atomkernerg Kerntech 44(1):87-88. (German) 

Borys RD, Duce RA. 1979. Relationships among lead, iodine, trace metals and ice nuclei in a coastal 

urban atmosphere. J Appl Meteorol 18(11):1490-1494. 

*Bostanci I, Sarioglu A, Ergin H, et al. 2001. Neonatal goiter caused by expectorant usage. Journal of 

Pediatric Endocrinology & Metabolism 14(8):1161-1162. 

Boudewyns A, Claes J. 2001. Acute cochleovestibular toxicity due to topical application of potassium 

iodide. Eur Arch Oto-rhino-laryngol 258(3):109-111. 

*Boulos MS, Becker VJ, Manuel OK. 1973. Iodine-129 in thyroid glands. Health Phys 24:375-378. 

Bourdoux P, Ermans A, Mukalay A, et al. 1995. Recommendations concerning iodine prophylaxis. Eur 

J Endocrinol 133:764. 

*Bourdoux PP, Ermans AM, Mukalay A, et al. 1996. Iodine-induced thyrotoxicosis in Kivu, Zaire. 

Lancet 347:552-553. 
IODINE 344 

9. REFERENCES 

Bourke JR, Murdoch S, Manley SW, et al. 1991. Epidermal growth factor (EGF) inhibits the 

secretomotor response of the thyroid: effects of EGF on radioiodine turnover and fluid transport in 

cultured porcine thyroid cells. J Endocrinol 128:213-218. 

Bourrinet P, Dencausse A, Cochet P, et al. 1997. Secretion in milk and transplacental transfer of two 

iodized oils, Lipiodol UF and Oriodol, in rabbits. Biol Neonate 71:395-402. 

Bouville A. 1977. [Estimation of the doses of iodine-129 effluents from nuclear installations-local and 

regional scales.] In: Iodine-129: Proceedings of an NEA specialist meeting. Paris, France: 

Organisation for Economic Co-Operation and Development, 53-68. (French) 

Bouville A, Dreicer M, Beck HL, et al. 1990. Models of radioiodine transport to populations within the 

continental U.S. Health Phys 59(5):659-668. 

Bowlt C, Howe JR. 1992a. Measured human thyroid 125I activities deriving from waste discharges in the 

Thames Valley area, UK. J Radiol Prot 12(2):59-65. 

Bowlt C, Howe JR. 1992b. The self-defining critical group and its application to a measured check of 

the derived limit for 125I in drinking water. Health Phys 63(6):686-691. 

Bowlt C, Tiplady P. 1989. Radioiodine in human thyroid glands and incidence of thyroid cancer in 

Cumbria. Br Med J 299:301-302. 

Bowman JC. 1975. Iodide mumps. J Tenn Dent Assoc 55(4):212-213. 

Bowman KO, Shenton LR, Bernard SR. 1985. Study of age dependent half-life of iodine in man: A 

reinforcement-depletion urn model. Bull Math Biol 47(2):205-213. 

*Boyages SC. 2000a. The neuromuscular system and brain in hypothyroidism. In: Braverman LE, 

Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 8th ed. Philadelphia, 

PA: Lippincott-Raven, 803-810. 

*Boyages SC. 2000b. The neuromuscular system and brain in thyrotoxicosis. In: Braverman LE, Utiger 

RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 8th ed. Philadelphia, PA: 

Lippincott-Raven, 631-633. 

*Boyages SC, Bloot AM, Maberly GF, et al. 1989. Thyroid autoimmunity in endemic goitre caused by 

excessive iodine intake. Clin Endocrinol 31:452-465. 

*Boyd E, Ferguson-Smith MA, McDougall IR, et al. 1974. Chromosome breakage in human peripheral 

lymphocytes after radioactive iodine (125I) treatment. Radiat Res 57:482-487. 

Brabant G, Bergmann P, Kirsch CM, et al. 1992. Early adaptation of thyrotropin and thyroglobulin 

secretion to experimentally decreased iodine supply in man. Metabolism 41:1093-1096. 

Branemark PI, Albrektsson B, Lindstrom J, et al. 1966. Local tissue effects of wound disinfectants. 

Acta Chir Scand Suppl 357:166-176. 

*Brätter P, Negretti de Bratter VEN. 1996. Influence of high dietary selenium intake on the thyroid 

hormone level in human serum. J Trace Elements Med Biol 10:163-166. 
IODINE 345 

9. REFERENCES 

Braverman LE. 1990. Effects of iodine on thyroid function in man. Trans Am Clin Climatol Assoc 

102:143-151. 

Braverman LE. 1994a. Deiodination of thyroid hormones: A 30 year perspective. Exp Clin Endocrinol 

102:355-363. 

Braverman LE. 1994b. Iodine and the thryoid: 33 years of study. Thyroid 4(3):351-356. 

*Braverman LE, Roti E. 1996a Effects of iodine on thyroid function. Acta Med Austriaca 23:4-9. 

Braverman LE, Utiger RD. 1996b Introduction to hypothyroidism. In: Braverman LE, Utiger RD, eds. 

Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 

736-737. 

Braverman LE, Utiger RD. 1996c Introduction to thyrotoxicosis. In: Braverman LE, Utiger RD, eds. 

Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 

522-524. 

*Braverman LE, Utiger RD, eds. 2000. Werner and Ingbar’s: The thyroid: A fundamental and cliical 

text. 8th ed. New York, NY: Lippincott Williams and Wilkins. 

*Braverman LE, Ingbar SH, Sterling K. 1970. Conversion of thyroxine (T4) to triiodothyronine (T3) in 

athyreotic human subjects. J Clin Invest 49:855-864. 

*Braverman LE, Ingbar SH, Vagenakis AG, et al. 1971a. Enhanced susceptibility to iodide myxedema 

in patients with Hashimoto's disease. J Clin Endocrinol 32:515-521. 

Braverman LE, Paul T, Reinhardt W, et al. 1987. Effect of iodine intake and methimazole on 

lymphocytic thyroiditis in the BB/W rat. Acta Endocrinol 281:70-76. 

Braverman LE, Vagenakis AG, Wang C-A, et al. 1971b. Studies on the pathogenesis of iodide 

myxedema. Trans Assoc Am Physicians 84:130-138. 

Braverman LE, Woeber KA, Ingbar SH. 1969. Induction of myxedema by iodide in patients euthyroid 

after radioiodine or surgical treatment of diffuse toxic goiter. N Engl J Med 281(15):816-821. 

Bremner VF, Kennedy JS. 1978. Radiation effects of iodine-125 and iodine-131 on the overactive rat 

thyroid. Strahlentherapie 154:413-418. 

*Brent GA, Larsen PR. 2000. Treatment of hypothyroidism. In: Braverman LE, Utiger RD, eds. 

Werner and Ingbar's the thyroid: A fundamental and clinical text. 8th ed. Philadelphia, PA: LippincottRaven, 851-858. 

Briancon C, Halpern S, Jeusset J, et al. 1992. Acute effects of various doses of iodide on thyroid iodine 

autoregulation. Biol Trace Elem Res 32:267-273. 

Briancon C, Halpern S, Telenczak P, et al. 1990. Changes in 127I mice thyroid follicle studied by 

analytical ion microscopy: A key of the comprehension of amiodarone-induced thyroid diseases. 

Endocrinology 127(1):1502-1509. 
 

 

IODINE 346 

9. REFERENCES 

*Bricker NS, Hlad CJ. 1955. Observations on the mechanism of the renal clearance of I131 . J Clin Invest 

34:1057-1072. 

Brincker H, Hansen HS, Andersen AP. 1973. Induction of leukemia by 131I treatment of thyroid 

carcinoma. Br J Cancer 28:232. 

Brown AS, Susser ES, Butler PD, et al. 1996. Neurobiological plausibility of prenatal nutritional 

deprivation as a risk factor for schizophrenia. J Nerv Ment Dis 184(2):71-85. 

Brown J. 1956. Extra-thyroidal iodide metabolism in the rat. Endocrinology 58:68-78. 

*Brown RS, Bloomfield S, Bednarek FJ, et al. 1997. Routine skin cleansing with povidone-iodine is not 

a common cause of transient neonatal hypothyroidism in North America: A prospective controlled study. 

Thyroid 7(3):395-400. 

*Brown TR, Bagchi N. 1992. The role of iodine in the development of autoimmune thyroiditis. Int Rev 

Immunol 9:167-182. 

*Brown-Grant K. 1961. Extrathyroidal iodide concentrating mechanisms. Physiol Rev 41:189-213. 

Brown-Grant K. 1967. A quantitative study of the effects of progesterone and related steroids on the 

uterus: Plasma concentration ratio for radioactive iodide in the rat. J Endocrinol 38:145-161. 

Brown-Grant K, Sherwood MR. 1971. Viability of the rat blastocyst following the oral administration of 

potassium perchlorate or potassium iodide to the mother. J Reprod Fertil 27:265-267. 

Brown-Grant K, John PN, Rogers AW. 1972. Analysis of the effects of progesterone on the synthesis of 

RNA and protein in the uterus of the ovariectomized rat and on the development of an iodide 

concentrating mechanism. J Endocrinol 53:363-374. 

*Bruhn JC, Franke AA, Bushnell RB, et al. 1983. Sources and content of iodine in California milk and 

dairy products. J Food Prot 46(1):41-46. 

*Bryant WP, Zimmerman D. 1995. Iodine-induced hyperthyroidism in a newborn. Pediatrics 95(3):434­

436. 

Brzezinski J, Lewinski A, Karbownik M, et al. 1997. Effects of insulin-like growth factor I, epidermal 

growth factor and kalium iodide on thymidine kinase activity in homogenates of rat thyroid lobes 

incubated in vitro. Biomed Lett 55:153-167. 

Bubenhofer R, Hedinger C. 1977. Schilddrusenmalignome vor und nach einfuhrung der 

jodsalzprophylaxe. Schweiz Med Wochenschr 107:733-741. 

Bucher H, Torresani T, Sobradillo B, et al. 1983. [Does PVP-iodine disinfection of newborn infants 

cause transient hypothyroidism? Report on 6 cases and prospective study of 19 early operated infants 

using T4 and TSH determinations of dried blood samples.] Schweiz Med Wochenschr 113(18):671-679. 

(German) 

Buczek A. 1993. Influence of iodine compounds on embryogenesis of argas (A.) reflexus (Fabricius, 

1794) (Acari, Ixodida, Argasidae). Acta Parasitol 38(1):41-43. 
 

 

IODINE 347 

9. REFERENCES 

*Budavari S, O’Neil MJ, Smith A, et al., eds. 1998. The Merck index: An encyclopedia of chemicals, 

drugs, and biologicals. Whitehouse Station, NJ: Merck and Co., Inc. 

Budyka AK, Ogorodnkiov BI. 1993a. [Calculation of gaseous fallout of Chernobyl accident by 

calculation of inhaled radiation dose.] Radiats Biol Radioecol 33(5):611-619. (Russian) 

Budyka AK, Ogorodnikov BI. 1993b. [Gaseous forms and aerosol particle sizes of iodine-131 products 

of Chernobyl accident during determination of inhaled dose radiaton.] Radiats Biol Radioecol 33(2):611­

619. (Russian) 

Bundi RS, Scott JS, Halnan KE. 1977. Chronic myeloid leukemia following radioiodine therapy for 

carcinoma thyroid. Br J Radiol 50:61-64. 

Bunzl K, Schimmack W. 1989. Associations between the fluctuations of the distribution coefficients of 

Cs, Zn, Sr, Co, Cd, Ce, Ru, Tc and I in the upper two horizons of a podzol forest soil. Chemosphere 

18(11/12):2109-2120. 

*Buraglio N, Aldahan A, Possnert G, et al. 2001. 129I from the nuclear reprocessing facilities traced in 

precipitation and runoff in Northern Europe. Environ Sci Technol 35:1579-1586. 

Burakov VS, Isaevich AV, Misakov PY, et al. 1993. Intracavity laser spectroscopic method for 

determining trace amounts of iodine and barium in water and biological samples. J Anal Atom Spectrom 

0:307-309. 

Burch HB, Gorman CA, Bahn RS, et al. 1996. Ophthalmopathy. In: Braverman LE, Utiger RD, eds. 

Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 

536-553. 

*Burch WM, Posillico JT. 1983. Hypoparathyroidism after I-131 therapy with subsequent return of 

parathyroid function. J Clin Endocrinol Metab 57(2):398-401. 

Burek CL, Talor M, Santana C, et al. 1998. Thyroiditis in NOD-H2 h4 mice born and reared in 

conventional housing and ingesting different dose of iodine. FASEB J 12(5):A1097. 

Burger AG, Engler D, Buergi U, et al. 1983. Ether link cleavage is the major pathway of iodothyronine 

metabolism in the phagocytosing human leukocyte and also occurs in vivo in the rat. J Clin Invest 

71:935-949. 

Burgess JR, Dwyer T, McArdle K, et al. 2000. The changing incidence and spectrum of thyroid 

carcinoma in Tasmania (1978-1998) during a transition from iodine sufficiency in iodine deficiency. J 

Clin Endocrinol Metab 85(4):1513-1517. 

Bürgi H, Andersen MC, Schwander J, et al. 1973. Secretion of thyroxine and non-thyroxine iodine by 

the normal human thyroid gland. Influence of carbimazole and pharmacological doses of iodide. Eur J 

Clin Invest 3:142-150. 

Bürgi H, Baumbartner H, Steiger G. 1982. [Is there an upper limit of tolerance for dietary iodine 

administration?] Schweiz Med Wochenschr 112:2-7. (German) 

*Bürgi H, Kohler M, Morselli B. 1998. Thyrotoxicosis incidence in Switzerland and benefit of improved 

iodine supply. Lancet 352:1034. 
 

 

IODINE 348 

9. REFERENCES 

Bürgi H, Radvila A, Kohler H, et al. 1974. Effects of pharmacological doses of iodide on the 

hyperplastic rat thyroid gland. Roles of intrathyroid iodide, thyrotropin and thyroglobulin in the WolffChaikoff phenomenon. Endocrinology 95:388-396. 

Bürgi H, Schaffner T, Seiler JP. 2001. The toxicology of iodate: A review of the literature. Thyroid 

11(5):449-456. 

Burke G, Kowalski K. 1971. Comparative effects of thyrotropin and long-acting thyroid stimulator on 

iodide trapping isolated thyroid cells. Acta Endocrinol 68:645-656. 

Burke G, Silverstein GE. 1969. Hypothyroidism after treatment with sodium iodide I 131. JAMA 

210(6):1051-1058. 

Burki HJ, Koch C, Wolff S. 1977. Molecular suicide studies of 125I and 3

H disintegration in the DNA of 

Chinese hamster cells. Curr Top Radiat Res Q 12:408-425. 

Burman KD, Smallridge RC, Burge JR, et al. 1987. Iodide administration enhances thyrotropin 

responsivenesss to thyrotrophin-releasing hormone during fasting: Evidence for normal pituitary 

feedback regulation. Clin Endocrinol 26:9-15. 

Burmeister LA, Beatty RL, Wall JR. 1999. Malignant ophthalmopathy presenting one week after 

radioiodine treatment of hyperthyroidism. Thyroid 9(2):189-192. 

Burmeister LA, de Cret RP, Mariash CN. 1991. Local reactions to radioiodine in the treatment of 

thyroid cancer. Am J Med 90:217-222. 

Burnett JW. 1989. Iodides and bromides. Cutis 43(2):130. 

Burns PA, Peggie JR. 1979. Thyroid measurements of iodine-125 workers. Australian Radiation 

Laboratory, Yallambie, Victoria, Australia. NTIS ARLTR008. 

Burrow GN. 1965. Neonatal goiter after maternal propylthiouracil therapy. J Clin Endocrinol Metab 

25:403-408. 

*Burte PP, Nair AGC, Manohar SB, et al. 1991. Iodide and iodine uptake in plants. J Radioanal Nucl 

Chem 155(6):391-402. 

Bushnell DL, Boles MA, Kaufman GE, et al. 1992. Complications, sequela and dosimetry of iodine-131 

therapy for thyroid carcinoma. J Nucl Med 33(12):2214-2221. 

*Bustad LK. 1964. Biology of radioiodine. Oxford, England: Pergamon Press. 

Buthieau A-M, Autissier N. 1977. [The effect of Mn2+ on thyroid iodine metabolism in rats.] C R 

Seances Soc Biol Fil 171(5):1024-1028. (French) 

*Butler EC, Gershey RM. 1984. Application of ion-exchange chromatography with an ion-selective 

electrode detector to iodine determination in natural waters. Anal Chim Acta 164:154-161. 

Buxeraud J, Absil AC, Raby C. 1984. Secondary antithyroid action of drugs in relation to structure. J 

Pharm Sci 73(12):1687-1690. 
IODINE 349 

9. REFERENCES 

Buxeraud J, Lagorce JF, Comby F, et al. 1992. Interaction between tetrahydro-3,5 dimethyl-2H-1,3,5 

thiazidine-2-thione (MDTT or DAZOMET) and molecular iodine: Possible role in thyroid toxicity. Int J 

Environ Stud 42:177-186. 

Cabanillas AM, Masini-Repiso AM, Coleoni AH. 1991. Rat thyroid monoamine oxidase (MAO) is 

regulated by thyrotropin: evidence that the main form of the enzyme (MAO-A) is not directly involved in 

iodide organification. J Endocrinol 131:25-31. 

Cailleux A-F, Schlumberger MJ. 1998. The role of iodine-131 scanning and serum thyroglobulin in 

follow-up of differentiated thyroid carcinoma after total ablation. Curr Opin Endocrinol Diabetes 5:307­

313. 

*Cann SA, van Netten JP, van Netten C. 2000. Hypothesis: Iodine, selenium and the development of 

breast cancer. Cancer Causes Control 11:121-127. 

Cann SAH, van Netten JP, van Netten C. 2001. Iodized salt and hypertension. Arch Intern Med 

161(4):505-506. 

Canning JF, Stacey TE, Ward RHT, et al. 1986. Radioiodide transfer across sheep placenta. Am J 

Physiol 250(19):R112-R119. 

Cantin M. 1967a. Skeletal muscle lesions in iodide-treated rats. Arch Pathol 83:500-506. 

Cantin M. 1967b. Study of a generalized erythema induced by iodide. J Invest Dermatol 48(6):560-566. 

Cao X-Y, Jiang X-M, Dou Z-H, et al. 1994. Timing of vulnerability of the brain to iodine deficiency in 

endemic cretinism. N Engl J Med 331:1739-1744. 

*Capar SG, Cunningham WC. 2000. Element and radionuclide concentrations in food: FDA total diet 

study 1991-1996. J AOAC Int 83(1):157-177. 

Caplan RH, Kujak R. 1971. Thyroid uptake of radioactive iodine. JAMA 215(6):916-918.
 

*Caplan RH, Kujak R, Murvich S, et al. 1976. Current status of the radioactive 131I uptake test. Minn.
 

Med. 59:530-535. 

Carey JE, Swanson DP. 1979. Thyroid contamination from airborne I-131. J Nucl Med 20:362. 

*Carrasco N. 1993. Iodide transport in the thyroid gland. Biochim Biophys Acta 1154:65-82. 

Carroll KK. 1975. Experimental evidence of dietary factors and hormone-dependent cancers. Cancer 

Res 35:3374-3383. 

Carswell F, Kerr MM, Hutchinson JH. 1970. Congenital goitre and hypothyroidism produced by
 

maternal ingestion of iodides. Lancet 1(7659):1241-1243. 

*Casara D, Rubello D, Saladini G, et al. 1993. Pregnancy after high therapeutic doses of iodine-131 in
 

differentiated thyroid cancer: Potential risks and recommendations. Eur J Nucl Med 20:192-194. 

*Cassileth BR. 1999. Complementary and alternative cancer medicine. J Clin Oncol 17(11):44-52. 
 

 

 

 

 

IODINE 350 

9. REFERENCES 

Cassorla FG, Finegold DN, Parks JS, et al. 1983. Vasculitis, pulmonary cavitation, and anemia during 

antithyroid drug therapy. Am J Dis Child 137:118-122. 

Castaing H, Fournet JP, Leger FA, et al. 1979. [The thyroid gland of the newborn infant and postnatal 

iodine overload.] Arch Fr Pediatr 36(4):356-368. (French) 

Castronovo FP. 1986. Iodine-131 thyroid burdens of European travelers returning to Boston after the 

Chernobyl accident. N Engl J Med 315:1679-1680. 

Castronovo FP. 1987. Iodine-131 thyroid uptake results in travelers returning from Europe after the 

Chernobyl accident. J Nucl Med 28:535-541. 

Castronovo FP. 1999. Teratogen update: Radiation and Chernobyl. Teratology 60(2):100-106. 

Catena C, Conti D, Trenta G, et al. 2000. Micronucleus yield and colorimetric test as indicators of 

damage in patients' lymphocytes after 131I therapy. J Nucl Med 41(9):1522-1524. 

*Catena C, Villani P, Nastasi R, et al. 1994. Micronuclei and 3AB-index in patients receiving iodine131 therapy. J Nucl Biol Med 38:586-593. 

Caturegli P, Hejazi M, Suzuki K, et al. 2000. Hypothyroidism in transgenic mice expressing IFN-gamma 

in the thyroid. Proc Natl Acad Sci USA 97(4):1719-1724. 

Caughey JE. 1970. Effects of iodation of bread. Lancet 1(7651):847. 

Cavalieri RR. 1996. Nuclear imaging in the management of thyroid carcinoma. Thyroid 6(5):485-492. 

*Cavalieri RR. 1997. Iodine metabolism and thyroid physiology: Current concepts. Thyroid 7(2):177­

181. 

CDC. 1993. Hanford thyroid disease study: Study protocol. Atlanta, GA: Centers for Disease Control. 

Prepared under CDC Contract Number 200-89-0716, 1-13, 68. 

CDC. 1994. Radionuclide releases to the atmosphere from Hanford Operations, 1944-1972: Hanford 

environmental dose reconstruction project. Centers for Disease Control. PNWD-2222 HEDR UC-000. 

NTIS DE94 013 713. 

*CDC. 1999. Hanford thyroid disease study. Centers for Disease Control, Atlanta, GA. 

http://www.fhcrc.org/science/phs/htds/. 

*CDC. 2002. Hanford thyroid disease study. Final report. Centers for Disease Control. Fred 

Hutchinson Cancer Research Center. 

Cebulska-Wasilewska A. 1989. Comparison of ambient air mutagenicity detected with tradescantia 

stamen hairs after Chernobyl accident and one year later. Environ Mol Mutagen 14(Suppl 15):35. 

Celani VJ, Gee W, Kaupp HA, et al. 1989. Unusual symmetric common carotid lesions and oral iodine 

131 for hyperthyroidism. Vascular Surgery 9(6):833-834. 

*Cember H. 1996. In: Introduction to Health Physics. 3rd ed. New York, NY: McGraw-Hill, 66. 
IODINE 351 

9. REFERENCES 

*Centanni M, Robbins J. 1987. Role of sodium in thyroid hormone uptake by rat skeletal muscle. J Clin 

Invest 80:1068-1972. 

Cevallos JL, Hagen GA, Maloof F, et al. 1974. Low-dosage 131I therapy of thyrotoxicosis (diffuse 

goiters). N Engl J Med 290:141-143. 

*Chabrolle JP, Rossier A. 1978a. Danger of iodine skin absorption in the neonate [Letter]. J Pediatr 

93(1):158-159. 

*Chabrolle JP, Rossier A. 1978b. Goitre and hypothyroidism in the newborn after cutaneous absorption 

of iodine. Arch Dis Child 53:495-498. 

*Chadha RK, Lawrence JF. 1990. Determination of iodide in dairy products and table salt by ion 

chromatography with electrochemical detection. J Chromatogr 518:268-272. 

*Chambard M, Verrier B, Gabrion J, et al. 1983. Polarization of thyroid cells in culture: Evidence for 

the basolateral localization of the iodide "pump" and of the thyroid-stimulating hormone receptor-adenyl 

cyclase complex. J Cell Biol 96:1172-1177. 

*Chameides WL, Davis DD. 1980. Iodine, its possible role in tropospheric photochemistry. Journal of 

Geophysical Research 85:7383-7398. 

Chan PC, Lisco E, Lisco H, et al. 1976. Radiotoxicity of intracellular 3

H, 125I and 131I: A comparative 

study on cell survival and cytogenetic responses. Radiat Res 67:633. 

Chan PC, Lisco E, Lisco H, et al. 1977. Cell survival and cytogenetic responses to 125I-UdR in cultured 

mammalians cells. Curr Top Radiat Res Q 12:426-435. 

Chan T, Scheier NW, O'Connor PA. 1997. A numerical study of the effects of a discrete fracture and an 

excavation damage zone on 129I transport through the geosphere. At Energy Can Ltd, [Rep] AECL 

11587:1-53. 

Chang J-K, Chen Y-C, Liu C-H, et al. 1984. A case of chronic myelogenous leukemia following 131I 

therapy for metastatic thyroid carcinoma. J Formosan Med Assoc 83:730-735. 

Chang T-C, Chang C-C, Chen F-W, et al. 1986. Long-term effect of radioiodine therapy on the thyroid 

antibodies in the patients of Graves' disease with postirradiation hypothyroidism. J Formosan Med Assoc 

85:1177-1182. 

Chang Y-O. 1969. Effect of iodinated casein on production of vitamin B12 and folic acid deficiency in 

rats. Am J Physiol 216(1):11-15. 

Chang-Chien Y, Liaw K-Y, Wang D-J, et al. 1977. Thyroid cancer after irradiation. Int Surg 62(2):112­

114. 

Chanoine JP, Toppet V, Bourdoux P, et al. 1991. Smoking during pregnancy: A significant cause of 

neonatal thyroid enlargement. Br J Obstet Gynaecol 98:65-68. 

Chapman EM, Corner GW, Robinson D, et al. 1948. The collection of radioactive iodine by the human 

fetal thyroid. J Clin Endocrinol Metab 8:717-720. 
 

 

IODINE 352 

9. REFERENCES 

Chapman RS, Main RA. 1967. Diffuse thinning of hair in iodide-induced hypothyroidism. Br J 

Dermatol 79(2):103-105. 

Chapman WH. 1968. The changing frequency of thyroid carcinoma and Hashimoto’s thyroiditis as 

related to diagnostic criteria, iodized salt, and radiation. Lawrence Radiation Laboratory, University of 

California at Livermore, Bio-Medical Division. California. TID-4500, UC-48. 

Chas J, Marciniak M, Baltrukiewicz Z. 1990. Retention of iodine upon intravenous or oral 

administration of Na131I and the absorbed doses of radiation derived from iodine radioisotopes 

incorporated into mature rats and sucklings. Nucleonika 35(7-9):195-211. 

*Chazenbalk GD, Nagayama Y, Kaufman KD, et al. 1990. The functional expression of recombinant 

human thyrotropin receptors in nonthyroidal eukaryotic cells provides evidence that homologous 

desensitization to thyrotropin stimulation requires a cell-specific factor. Endocrinology 127(3):1240­

1244. 

Chazenbalk GD, Valsecchi RM, Krawiec L, et al. 1988. Thyroid autoregulation, inhibitory effects of 

iodinated derivatives of arachidonic acid on iodine metabolism. Prostaglandins 36(2):163-172. 

Chegrinets G. 1992. [The iodine level of the environment and the risk of developing thyroid diseases.] 

Lik Sprava 4:16-19. (Russian) 

*Chemfinder. 2001. Iodine. Chemfinder.com: Database and internet searching. 

http://www.chemfinder.com. 

Chen J-Y, Huang H-S, Huang M-J, et al. 1990. Outcome following radioactive iodine therapy in Graves' 

disease. Chang Keng I Hsueh Tsa Chih 13(4):258-267. 

Chen S-H, Wu S-M, Kou H-S, et al. 1994. Electron-capture gas chromatographic determination of 

cyanide, iodide, nitrite, sulfide, and thiocyanate anions by phase-transfer-catalyzed derivatization with 

pentafluorobenzyl bromide. J Anal Toxicol 18:81-85. 

*Chernyshov VP, Vykhovanets EV, Slukvin II, et al. 1998. Effect of iodine isotope on the pituitarythyroid and immune systems of children living on the territories polluted by radionuclides. Bull Exp Biol 

Med 126(8):835-838. 

*Cherstvoy ED, Nerovnya AM, Pozharskaya VP, et al. 1996. Thyroid carcinomas in children of the 

Republic of Belarus. In: Nagataki S, Yamashita S, eds. Nagasaki symposium radiation and human 

health: Proposal from Nagasaki. Amsterdam, The Netherlands: Elsevier, 43-48. 

Chester HA, Pisarev MA, Juvenal GJ, et al. 1990. Further studies on iodide uptake autoregulation in calf 

thyroid slices. Acta Physiol Pharmacol Latinoam 40:149-154. 

Chiacchierini RP. 1990. Iodine-131 exposures and neoplasia. Radiat Res 124(3):359-360. 

Chin HS, Chin DKH, Morgenthaler NG, et al. 2000. Rarity of anti- Na+

/I-- symporter (NIS) antibody 

with iodide uptake inhibiting activity in autoimmune thyroid diseases (AITD). J Clin Endocrinol Metab 

85(10):3937-3940. 
IODINE 353 

9. REFERENCES 

Ching M. 1981. Dose-related effect of growth hormone on thyroidal radioiodine uptake. Horm Res 

14:234-242. 

Chiovato L, Fiore E, Vitti P, et al. 1998. Outcome of thyroid function in Graves' patients treated with 

radioiodine: Role of thyroid-stimulating and thyrotropin-blocking antibodies and of radioiodine-induced 

thyroid damage. J Clin Endocrinol Metab 83(1):40-46. 

Chiovato L, Santini F, Vitti P, et al. 1994. Appearance of thyroid stimulating antibody and Graves' 

disease after radioiodine therapy for toxic nodular goitre. Clin Endocrinol 40:803-806. 

Chisholm JC. 1981. Hypothyroidism: A rare cause of the bilateral carpal tunnel syndrome-a case report 

and a review of the literature. J Natl Med Assoc 73(11):1082-1085. 

Chiu AC, Sherman SI. 1997. Clinical manifestations and differential diagnosis of hypothyroidism. In: 

Falk SA, ed. Thyroid disease: Endocrinology, surgery, nuclear medicine, and radiotherapy. 

Philadelphia, PA: Lippincott-Raven Publishers, 379-391. 

*Cho JY, Leveille R, Kao R, et al. 2000. Hormonal regulation of radionuclide uptake activity and Na+/Isymporter expression in mammary glands. J Clin Endocrinol Metab 85(8):2936-2943. 

Choe SY, Yen-Chow YC, Woodbury DM. 1982. Effects of thyrotropin, acetazolamide, 4-acetamido-4'­

isothiocyanostilbene-2,2'-disulfonic acid, perchlorate, and ouabin on the distribution of iodide ions in 

cells and luminal fluid of turtle thyroid. Endocrinology 110(1):121-125. 

Chopra IJ. 1996. Nature, source, and relative significance of circulating thyroid hormones. In: 

Braverman LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 

Philadelphia, PA: Lippincott-Raven, 111-124. 

*Chow CC, Phillips DIW, Lazarus JH, et al. 1991. Effect of low dose iodide supplementation on thyroid 

function in potentially susceptible subjects: Are dietary iodide levels in Britain acceptable? Clin 

Endocrinol 34:413-416. 

Chow SY, Kemp JW, Woodbury DM. 1983. Effects of acetazolamide on iodide transport, electrolyte 

distribution and activities of carbonic anhydrase, Na+

, K+-ATPase and HCO3

-

-ATPase in mouse, rat and 

turtle thyroid gland. J Endocrinol 97:167-174. 

Christensen VL, Ort JF. 1991. Iodine toxicity in large white turkey breeder hens. Poult Sci 70:2402­

2410. 

Christiansen C, Pichler WJ, Skotland T. 2000. Delayed allergy-like reactions to X-ray contrast media: 

Mechanistic considerations. Eur Radiol 10(12):1965-1975. 

Christov K. 1978. Radiation-induced thyroid tumors in infant rats. Radiat Res 73:330-339. 

Christov K, Raichev R. 1972. Thryoid carcinogenesis in hamsters after treatment with 131-iodine and 

methylthiouracil. Z Krebsforsch 77:171-179. 

Christov K, Raichev R. 1973. Proliferative and neoplastic changes in the ovaries of hamsters treated 

with 131-iodine and methylthiouracil. Neoplasma 20(5):511-516. 
 

 

IODINE 354 

9. REFERENCES 

*Chu SYF, Ekstrom LP, Firestone RB. 1999. Isotope explorer: WWW table of radioactive isotopes. 

http://nucleardata.nuclear.lu.se/nucleardata/toi/listnuc.asp? 

*Chun JT, Di Lauro R. 2001. Characterization of the upstream enhancer of the rat sodium/iodide 

symporter gene. Exp Clin Endocrinol Diabetes 109(1):23-26. 

Clairand I, Bouchet LG, Ricard M. 2000. Improvement of internal dose calculations using mathematical 

models of different adult heights. Phys Med Biol 45(10):2771-2785. 

Clark DE. 1955. Association of irradiation with cancer of the thyroid in children and adolescents. 

JAMA 159(10):1007-1009. 

*Clark MN. 1981. A fatal case of iodine poisoning. Clin Toxicol 18(7):807-811. 

Clark WE, Thompson CT. 1977. Immobilization of iodine in concrete. (to The United States of America 

as represented by the United States Energy Research and Development Administration) Application: 

United States 4,017,417, 12 Apr 1977. United States Patent 4,017,417, issued 12 Apr 1977. 

Clayson DB. 1975. Nutrition and experimental carcinogenesis: A review. Cancer Res 35:3292-3300. 

Clayton CG. 1953. Irregularities of iodine assimilation by the follicles of the rat thyroid. Br J Radiol 

26:99-101. 

Clemens PC, Neumann RSJ. 1989a. The Wolff-Chaikoff effect: Hypothyroidism due to iodine 

application [Letter]. Arch Dermatol 125(5):705. 

Clemens PC, Neumann S. 1989b. Transient primary hypothyroidism in the neonate. Clin Pediatr 

28(7):335. 

*Clewell HJ III, Andersen ME. 1985. Risk assessment extrapolations and physiological modeling. 

Toxicol Ind Health 1(4):111-131. 

Coakley FV, Panicek DM. 1997. Iodine allergy: An oyster without a pearl? Am J Roentgenol 

169(4):951-952. 

Coakley FV, Panicek DM. 1998. Reply [Letter]. Am J Roentgenol 171(2):518-519. 

*Coakley JC, Francis I, Gold H, et al. 1989. Transient primary hypothyroidism in the newborn: 

Experience of the Victorian Neonatal Thyroid Screening Programme. Aust Paediatr J 25:25-30.
 

Cobb LM, Harrison A, Dudley NE, et al. 1989. Relative concentration of astatine-211 and iodine-125 by 

human fetal thyroid and carcinoma of the thyroid in nude mice. Radiother Oncol 13:203-209. 

Codaccioni J-L, Valery-Milhaud F, Ochi C. 1987. [Carbimazole administered alone can be effective in 

the treatment of hyperthyroidism induced by iodine.] Presse Med 16(6):312. (French) 

Cody V. 1996. Thyroid hormone structure-function relationships. In: Braverman LE, Utiger RD, eds. 

Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 

185-189. 

*Cohen BI. 1985. The origin of I in soil and the 129I problem. Health Phys 49(2):279-285.
 
IODINE 355 

9. REFERENCES 

Cohen J, Gierlowski TC, Schneider AB. 1990. A prospective study of hyperparathyroidism in 

individuals exposed to radiation in childhood. JAMA 264(5):581-584. 

Cohen JC, Roxe DM, Said R, et al. 1980. Iodide mumps after repeated exposure to iodinated contrast 

media. Lancet 1:762-763. 

Cohen SB, Weetman AP. 1988. The effect of iodide depletion and supplementation in the Buffalo strain 

rat. J Endocrinol Invest 11:625-627. 

*Cohn BNE. 1932. Absorption of compound solution of iodine from the gastro-intestinal tract. Arch 

Intern Med 49:950-956. 

*Cohn SH, Gusmano EA. 1963. Uptake and transfer of fallout i131 in pregnant women. Health Phys 

9:1267-1269. 

Colin IM, Selvais PL, Rebai T, et al. 1994. Expression of the endothelin-1 gene in the rat thyroid gland 

and changes in its peptide and mRNA levels in goiter formation and iodide-induced involution. J 

Endocrinol 143:65-74. 

Collins SL. 1997. Thyroid cancer: Controversies and etiopathogenesis. In: Falk SA, ed. Thyroid 

disease: Endocrinology, surgery, nuclear medicine, and radiotherapy. Philadelphia, PA: LippincottRaven Publishers, 495-564. 

Collins WT, Capen CC. 1980a. Biliary excretion of 125I-thyroxine and fine structural alterations in the 

thyroid glands of Gunn rats fed polychlorinated biphenyls (PCB). Lab Invest 43:158-164. 

Collins WT, Capen CC. 1980b. Ultrastructural and functional alterations of the rat thyroid gland 

produced by polychlorinated biphenyls compared with iodide excess and deficiency, and thyrotropin and 

thyroxine administration. Virchows Arch B 33:213-231. 

*Comar CL, Wentworth RA, Georgi JR. 1963. Thyroidal deposition in man, rat and dog of radioiodine 

from milk and non-milk sources. Health Phys 9:1249-1252. 

*Conard RA. 1984. Late radiation effects in Marshall Islanders exposed to fallout 28 years ago. In: 

Boice KD, Fraument JF, eds. Radiation carcinogenesis: Epidemiology and biological significance. New 

York, NY: Raven Press, 57-71. 

*Conard RA, Dobyns BM, Sutow WW. 1970. Thyroid neoplasia as late effect of exposure to radioactive 

iodine in fallout. JAMA 214(2):316-324. 

Connell JMC, Hilditch TE, McCruden DC, et al. 1983. Transient hypothyroidism following radioiodine 

therapy for thyrotoxicosis. Br J Radiol 56:309-313. 

Connolly KJ, Pharoah POD, Hetzel BS. 1979. Fetal iodine deficiency and motor performance during 

childhood. Lancet 2:1149-1151. 

*Connolly RJ. 1971a. The changing iodine environment of Tasmania. Med J Aust 2:1191-1193. 

*Connolly RJ. 1971b. An increase in thyrotoxicosis in southern Tasmania after an increase in dietary 

iodine. Med J Aust 1(24):1268-1271. 
IODINE 356 

9. REFERENCES 

*Connolly RJ, Shepherd JJ. 1972. The effect of preoperative surgical scrubbing with providone iodine 

on urinary iodine levels. Aust N Z J Surg 42(1):94-95. 

*Connolly RJ, Vidor GI, Stewart JC. 1970. Increase in thyrotoxicosis in endemic goitre area after 

iodation of bread. Lancet 1(7645):500-502. 

Conrad LM, Hemken RW. 1978. Milk iodine as influenced by an iodophor teat dip. J Dairy Sci 61:776­

780. 

*Contempré B, Duale NL, Dumont JE, et al. 1992. Effect of selenium supplementation on thyroid 

hormone metabolism in an iodine and selenium deficient population. Clin Endocrinol 36:579-583. 

*Contempré B, Dumont JE, Ngo B, et al. 1991. Effect of selenium supplementation in hypothyroid 

subjects of an iodine and selenium deficient area: The possible danger of indiscriminate supplementation 

of iodine-deficient subjects with selenium. J Clin Endocrinol Metab 73(1):213-215. 

Convey EM, Chapin L, Kesner JS, et al. 1979. Serum thyrotropin and thyroxine after thyrotropin 

releasing hormone in dairy cows fed varying amounts of iodine. J Dairy Sci 60(6):975-980. 

Cooper DS. 1998. Radioiodine for hyperthyroidism: Where do we stand after 50 years? JAMA 

280(4):375-376. 

*Cooper DS. 2000. Treatment of thyrotoxicosis. In: Braverman LE, Utiger RD, eds. Werner and 

Ingbar's the thyroid: A fundamental and clinical text. 8th ed. Philadelphia, PA: Lippincott-Raven, 691­

715. 

*Cooper LW, Hong GH, Beasley TM, et al. 2001. Iodine-129 concentrations in marginal seas of the 

North Pacific and Pacific-influenced waters of the Arctic Ocean. Mar Pollut Bull 42(12):1347-1356. 

Cooper RM. 1988. Potassium iodide for radiation exposure. Drug Intell Clin Pharm 22:33-34. 

Coover LR. 1999. Vocal cord paralysis after 131I therapy for solitary toxic nodule. J Nucl Med 40:505. 

Coppa A, Mincione G, Mammarella S, et al. 1995. Epithelial rat thyroid cell clones, escaping from 

transforming growth factor beta negative growth control, are still inhibited by this factor in the ability to 

trap iodide. Cell Growth Differ 6:281-290. 

Coppola M, Vulpis N, Bertoncello G. 1984. Enhancement of chromosomal damage in human 

lymphocytes irradiated with x rays in the presence of iodine. Radiat Prot Dosim 9(2):99-104. 

Corah LR, Ives S. 1991. The effect of essential trace minerals on reproduction in beef cattle. Vet Clin 

North Am 7(1):41-57. 

Corda D, Kohn LD. 1986. Role of pertussis toxin sensitive G proteins in the alpha1 adrenergic receptor 

but not in the thyrotropin receptor mediated activation of membrane phospholipases and iodide fluxes in 

FRTL-5 thyroid cells. Biochem Biophys Res Commun 141(3):1000-1006. 

Corda D, Marcocci C, Kohn LD, et al. 1985. Association of the changes in cystolic Ca 2+ and iodide 

efflux induced by thyrotropin and by the stimulation of alpha1-adrenerigic receptors in cultured rat thyroid 

cells. J Biol Chem 260(16):9230-9236. 
IODINE 357 

9. REFERENCES 

*Cornelis R, Speecke A, Hoste J. 1975. Neutron activation analysis for bulk and trace elements in urine. 

Anal Chim Acta 78:317-327. 

*Corvilain B, Dumont JE, Vassart G. 2000. Toxic adenoma and toxic multinodular goiter. In: 

Braverman LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 8th ed. 

Philadelphia, PA: Lippincott-Raven, 564-572. 

Corvilain B, Laurent E, Lecomte M, et al. 1994. Role of the cyclic adenosine 3',5'-monophosphate and 

the phosphatidylinositol-Ca 2+ cascades in mediating the effects of thyrotropin and iodide on hormone 

synthesis and secretion in human thyroid slices. J Clin Endocrinol Metab 79(1):152-159. 

Corvilain B, Van Sande J, Dumont JE. 1988. Inhibition of iodide by iodide binding to proteins: The 

"Wolff-Chaikoff" effect is caused by inhibition of H2O2 generation. Biochem Biophys Res Commun 

154(3):1287-1292. 

*Corvilain B, Van Sande J, Dumont JE, et al. 1998. Autonomy in endemic goiter. Thyroid 8(1):107­

113. 

Cosmetic Ingredient Review Expert Panel. 1995. Final report on the safety assessment of sodium iodate. 

J Am Coll Toxicol 14(3):231-239. 

Coughtrey PJ, Jackson D, Thorne MC. 1983. Iodine. In: Radionuclide distribution and transport in 

terrestrial and aquatic ecosystems: A critical review of data. Rotterdam: A.A. Balkema, 322-372. 

Cowin AJ, Bidey SP. 1995. Porcine thyroid follicular cells in monolayer culture activate the iodideresponsive precursor form of transforming growth factor-beta1. J Endocrinol 144:67-73. 

*Cox RA, Bloss WJ, Jones RL, et al. 1999. OIO and the atmospheric cycle of iodine. Geophys Res Lett 

26(13):1857-1860. 

*Cox RJ, Pickford CJ, Thompson M. 1992. Determination of iodine-129 in vegetable samples in 

inductively coupled plasma mass spectrometry. J Anal Atom Spectrom 7:635-640. 

Craswell PWT. 1972. Vocal cord paresis following radioactive iodine therapy. Br J Clin Pract 

26(12):571-572. 

Creutzig H, Hundeshagen H. 1977. [Thyroid cancer risk from Iodine-131 treatment.] Med Klin 

72(19):855-857. (German) 

Crile GJ, Esselstyn CBJ, Cook SA. 1979. Cancer of the thyroid appearing after (but probably not caused 

by) treatment with radioactive iodine. Cleve Clin Q 46(4):159-162. 

*CRISP. 2001. CRISP Database. Computer Retrieval of Information on Scientific Projects. 

Crocker DG. 1984. Nuclear reactor accidents-the use of KI as a blocking agent against radioiodine 

uptake in the thyroid-a review. Health Phys 46(6):1265-1279. 

Croughs W, Visser HKA. 1965. Familial iodide-induced goiter. Evidence for an abnormality in the 

pituitary-thyroid homeostatic control. J Pediatr 67:353-362. 
IODINE 358 

9. REFERENCES 

*Crout NMJ, Beresford NA, Mayes RW, et al. 2000. A model of radioiodine transfer to goat milk 

incorporating the influence of stable iodine. Radiat Environ Biophys 39(1):59-65. 

*Cuddihy RG. 1966. Thyroidal iodine-131 uptake, turnover and blocking in adults and adolescents. 

Health Phys 12:1021-1025. 

Culpepper RM, Hirsch JI, Fratkin MJ. 1992. Clearance of 131I by hemodialysis. Clin Nephrol 

28(2):110-114. 

Cundiff JG, Portugal L, Sarne DH. 2001. Parathyroid adenoma after radioactive iodine therapy for 

multinodular goiter. Am J Otolaryngol 22(5):374-375. 

Cunnien AJ, Hay ID, Gorman CA, et al. 1982. Radioiodine-induced hypothyroidism in Graves' disease: 

Factors associated with the increasing incidence. J Nucl Med 23:978-983. 

*Cunningham WC, Anderson DL, Baratta EJ. 1994. Radionuclides in domestic and imported foods in 

the United States, 1987-1992. J AOAC Int 77(6):1422-1427. 

*Cunningham WC, Stroube WB, Baratta EJ. 1989. Radionuclides in domestic and imported foods in the 

United States, 1983-1986. J Assoc Off Anal Chem 72(1):15-18. 

*Curd JG, Milgrom H, Stevenson DD, et al. 1979. Potassium iodide sensitivity in four patients with 

hypocomplementemic vasculitis. Ann Intern Med 91:853-857. 

*Curran PG, DeGroot LJ. 1991. The effect of hepatic enzyme-inducing drugs on thyroid hormones and 

the thyroid gland. Endocrine Rev 12(2):135-150. 

Cvejic D, Savin S, Sinadinovic J. 1997. Effects of thyrotropin and insulin-like growth factor I (IGF-I) on 

3

H-thymidine incorporation and iodine metabolism in cultured porcine thryoid follicles. Iugosl Physiol 

Pharmacol Acta 33:33-43. 

*Dai G, Levy O, Carrasco N. 1996. Cloning and characterization of the thyroid iodide transporter. 

Nature 379:458-460. 

*Dai YD, Rao VP, Carayanniotis G. 2002. Enhanced iodination of thyroglobulin facilitates processing 

and presentation of a cryptic pathogenic peptide. J Immunol 168(11):5907-5911. 

*Dalmark M. 1976. Effects of halides and bicarbonate on chloride transport in human red blood cells. J 

Gen Physiol 67:223-234. 

*Dams R, Robbins JA, Rahn KA, et al. 1970. Nondestructive neutron activation analysis of air 

particulates. Anal Chem 42:861-867. 

Daniels AL, Everson GJ. 1935. The relation of manganese to congenital debility. J Nutr 9(2):191-203. 

*Darras VM, Hume R, Visser TJ. 1999. Regulation of thyroid hormone metabolism during fetal 

development. Mol Cell Endocrinol 151:37-47. 

Das SC, Isichei UP. 1993. The "feto-maternal" thyroid function interrelationships in an iodine-deficient 

region in Africa-the role of T3 in possible fetal defence. Acta Endocrinol 128:116-119. 
IODINE 359 

9. REFERENCES 

Datz FL. 1986. Cerebral edema following iodine-131 therapy for thyroid carcinoma metastatic to the 

brain. J Nucl Med 27:637-640. 

Daunt N. 1998. Iodine allergy. [Letter]. Am J Roentgenol 171(2):518. See also Coakley & Panicek, 

1998. 

Davidovich D, Stigliano H, Garcis JRAR, et al. 1970. [Study of thyroid function in 20 inhabitants of a 

zone with an excess of iodine in the drinking water.] Rev Argent Endocrinol Metab 16(3):75-79. 

(Spanish) 

Davidson DC, Ford JA, Fox EG. 1974. Iodide sialadenitis in childhood. Arch Dis Child 49(1):67-68. 

Davies TF. 1996. Graves' disease: The pathogenesis of Graves' disease. In: Braverman LE, Utiger RD, 

eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: LippincottRaven, 525-536. 

Davies TF, Yang C, Platzer M. 1989. The influence of antithyroid drugs and iodine on thyroid cell MHC 

class II antigen expression. Clin Endocrinol 31:125-135. 

Davis RJ. 1980. To the editor. Ann Intern Med 92(5):712-713. 

Dawson CA, Skebba SC, Linehan JH, et al. 1985. Influence of pulmonary embolism on absorption of 

inhaled iodide-125. J Appl Physiol 58(4):1061-1068. 

Dawson KP. 1970. Congenital goitrous cretinism due to iodide. Br Med J 2(701):112-113. 

De SK, Ganguly CK, Chakraborty TK, et al. 1985. Endocrine control of extrathyroidal peroxidases and 

iodide metabolism. Acta Endocrinol 110:383-387. 

De Braekeleer M, Mayer G, Chaventre A. 1998. Genetic factors in iodine deficiency disorders: A 

general review. Coll Antropol 1:9-15. 

*DeCheke ME. 1989. Chemical analysis of water and wastewater. Inorganics. Journal WCPF 

61(6):727-755. 

de Groot LJ. 1997. Radioiodine and the immune system. Thyroid 7(2):259-264.
 

de Groot LJ, Reilly M. 1982. Comparison of 30- and 50-mCi doses of iodine-131 for thyroid ablation. 

Ann Intern Med 96:51-53. 

de Groot LJ, Reilly M, Pinnameneni K, et al. 1983. Retrospective and prospective study of radiationinduced thyroid disease. Am J Med 74:852-862. 

*de Groot R. 1979. The hazards of iodine-125 labeling-a recommended code of practice. Australas 

Phys Sci Med 2(7):386-393. 

*Delange F. 1990. Iodine nutrition and risk of thyroid irradiation from nuclear accidents. In: Rubery E, 

Smales E, eds. Iodine prophylaxis following nuclear accidents. Oxford, UK: Pergamon Press, 45-54. 

*Delange F. 1996. Administration of iodized oil during pregnancy: A summary of the published 

evidence. Bull W H O 74(1):101-108. 
 

 

 

 

IODINE 360 

9. REFERENCES 

Delange F. 1998a. Screening for congenital hypothyroidism used as an indicator of the degree of iodine 

deficiency and of its control. Thyroid 8(12):1185-1192. 

Delange F. 1998b. Search for effective immunomodulating strategies against sepsis. Lancet 351:922­

923. 

*Delange FM, Ermans A-M. 1996. Iodine deficiency. In: Braverman LE, Utiger RD, eds. Werner and 

Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 296-316. 

Delange F, Lecomte P. 2000. Iodine supplementation. Benefits outweigh risks. Drug Saf 22(2):89-95. 

Delange F, Chanoine JP, Abrassari C, et al. 1988. Topical iodine, breastfeeding, and neonatal 

hypothyroidism [Letter]. Arch Dis Child 63(1):106-107. 

*Delange F, de Benoist B, Alnwick D. 1999. Risks of iodine-induced hyperthyroidism after correction 

of iodine deficiency by iodized salt. Thyroid 9(6):545-556. 

Delange F, de Benoist B, Burgi H, et al. 2002. Determining median urinary iodine concentration that 

indicates adequate iodine intake at population level. Bull World Health Organ 80(8):633-636. 

Delange F, Van Minh N, Vanderlinden L, et al. 1980. Influence of goitrogens in pregnant and lactating 

rats on thyroid function in the pups. In: Ermans AM, Mbulamoko NM, Delange F, et al., eds. Role of 

cassava in the etiology of endemic goitre and cretinism, 167-182. 

Delange F, Wolff P, Gnat D, et al. 2001. Iodine deficiency during infancy and early childhood in 

Belgium: Does it pose a risk to brain development? Eur J Pediatr 160(4):251-254. 

*Dellavalle ME, Barbano DM. 1984. Iodine content of milk and other foods. J Food Prot 47:678-684. 

Deleu S, Allory Y, Radulescu A, et al. 2000. Characterization of autonomous thyroid adenoma: 

Metabolism, gene expression, and pathology. Thyroid 10(2):131-140. 

DeLong GR. 1996. 'Iodine and brain development' [Letter]. Dev Med Child Neurol 38:278-282. 

*De Luca Rebello A, Herms FW, Wagener K. 1990. The cycling of iodine as iodate and iodide in a 

tropical estuarine system. Marine Chemistry 29:77-93. 

Demangeat K-L, Lautier F, Demangeat C, et al. 1982. [Consequences of the chronic cutaneous 

application of iodinated antiseptics on the thyroid function in the guinea-pig.] Zentralbl Bakteriol [B]
 

176:277-290. (German) 

*Deme D, Doussuere J, de Sandro V et al. 1994. The Ca2+/NADPH-dependent H2O2 generator in thyroid 

plasma membrane: Inhibition by diphenyleneiodium. 

Demir M, Kabasakal L, Onsel C. 1996. Evaluation of external radiation exposure rate from radioiodinetreated hyperthyroid patients and radiation safety considerations. Nucl Med Commun 17:692-695. 

Denef J-F, Many M-C, van den Hove MF. 1996. Iodine-induced thyroid inhibition and cell necrosis: 

Two consequences of the same free-radical mediated mechanism? Mol Cell Endocrinol 121:101-103. 
 

 

IODINE 361 

9. REFERENCES 

Denham MJ, Himsworth RL. 1974. Hyperthyroidism induced by potassium iodide given in the course of 

125I-fibrinogen test. Age Ageing 3:221-225. 

De Prospo N, De Martino LJ, McGuinness ET. 1968. Melatonin's effect on 131I uptake by the thyroid 

glands in normal and ovariectomized rats. Life Sci 7:183-188. 

*Derwahl M, Studer H. 2001. Nodular goiter and goiter nodules: Where iodine deficiency falls short of 

explaining the facts. Exp Clin Endocrinol Diabetes 109(5):250-260. 

Derwahl M, Manole D, Sobke A, et al. 1998. Pathogenesis of toxic thyroid adenomas and nodules: 

Relevance of activating mutations in the TSH-receptor and Gs-alpha gene, the possible role of iodine 

deficiency and secondary and TSH-independent molecular mechanisms. Exp Clin Endocrinol Diabetes 

106(Suppl 4):S6-S9. 

De Sandro V, Catinot R, Kriszt W, et al. 1992. Male rat hepatic UDP-glucuronosyltransferase activity 

toward thyroxine: Activation and induction properties-relation with thyroxine plasma disappearance rate. 

Biochem Pharmacol 43(7):1563-1569. 

DeSantis DM, Chabot GE. 2001. An alternative method for the release criteria and calculation of the 

total dose equivalent to another individual from a patient treated with a therapeutic dose of 131I. Health 

Phys 81(1):15-26. 

De Vathaire F, Fragu P, Francois P, et al. 1993. Long-term effects on the thyroid of irradiation for skin 

angiomas in childhood. Radiat Res 133:381-386. 

De Vathaire F, Le Vu B, Challeton-De Vathaire C. 2000. Thyroid cancer in French Polynesia between 

1985 and 1995: Influence of atmospheric nuclear bomb tests performed at Mururoa and Fangataufa 

between 1966 and 1974. Cancer Causes Control 11(1):59-63. 

*De Vathaire F, Schlumberger M, Delisle MJ, et al. 1997. Leukemia and cancers following iodine-131 

administration for thyroid cancer. Br J Cancer 75(5):734-739. 

Deves JR, Tonkin JP. 1980. Vocal cord paralysis in benign thyroid disease before operation. Med J 

Aust 2(11):632. 

de Vijlder JJM, Vulsma T. 1996. Hereditary metabolic disorders causing hypothyroidism. In: 

Braverman LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 

Philadelphia, PA: Lippincott-Raven, 749-755. 

DeWitte M, Eberhart RJ, Griel LCJ. 1980. Mastitis caused by teat-dipping error. Vet Med Small Anim 

Clin 75(10):1613-1616. 

*de Zegher F, Vanhole C, Van den Berghe G, et al. 1994. Properties of thyroid-stimulating hormone and 

cortisol secretion by the human newborn on the day of birth. J Clin Endocrinol Metab 79:576-581. 

Diamond ML, Mackay D, Cornett RJ, et al. 1990. A model of the exchange of inorganic chemicals 

between water and sediments. Environ Sci Technol 24:713-722. 

*Dickman PW, Holm LE, Lundell G, et al. 2003. Thyroid cancer risk after thyroid examination with 

131I: a population-based study. Int J Cancer 10(106):580-587. 
 

 

IODINE 362 

9. REFERENCES 

Dienhart KJ. 1974. Suppurative ulcerating iododerma [Letter]. N Engl J Med 290(9):521. 

Dietlein M, Dederichs B, Weigand A, et al. 1999. Radioiodine therapy and thyroid-associated 

orbitopathy: Risk factors and preventive effects of glucocoticoids. Exp Clin Endocrinol Diabetes 

107:S190-S194. 

*Dietrich AM, Costa WFD. 1997. Measurement and monitoring of pollutants. Chemical species. Water 

Environ Res 69(4):391-403. 

Di Girolamo M, D'Arcangelo D, Bizzarri C, et al. 1991. Muscarinic regulation of phospholipase A2 and 

iodide fluxes in FRTL-5 thyroid cells. Acta Endocrinol 125:192-200. 

Di Lauro E. 1966. [Ludwig's pseudoangina due to iodism.] Ann Laringol Otol Rinol Faringol 

65(2):261-263. (Italian) 

Dixon GW. 1996. Processed product for skin and hair treatment. Application: USA 5,554,361, 10 Sep 

1996. USA Patent 5,554,361, issued 10 Sep 1996. 

Dluhy RG. 1996a. The adrenal cortex in hypothyroidism. In: Braverman LE, Utiger RD, eds. Werner 

and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 841-844. 

Dluhy RG. 1996b. The adrenal cortex in thyrotoxicosis. In: Braverman LE, Utiger RD, eds. Werner 

and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 656-660. 

Dmitrev AI, Istomina GN. 1978. [Long term changes in the endurance of rats after combined external 

gamma irradiation and contamination with radioactive iodine.] Radiobiologiia 18(5):777-779. (Russian) 

DNA. 1992. Evaluation of residual radioactivity in human tissues associated with weapons testing at the 

Nevada test site. Alexandria, VA: Defense Nuclear Agency. DNA-TR-91-166. 

Dobyns BM. 1975. Radiation effects of radioiodine on the thyroid: Effects vary with dosage and 

sensitivity of the gland to radiation. R I Med J 58(3):94-97. 

Dobyns BM, Sheline GE, Workman JB, et al. 1974. Malignant and benign neoplasms of the thyroid in 

patients treated for hyperthyroidism: A report of the cooperative thyrotoxicosis therapy follow-up study. 

J Clin Endocrinol 38:976-998. 

*Docter R, Krenning EP, Bernard HF, et al. 1987. Active transport of iodothyronines into human 

cultured fibroblasts. J Clin Endocrinol Metab 65(4):624-628. 

*DOE. 1954. Thyroid absorbed dose for people at Rongelap, Utirik, and Sifo on March 1, 1954. U.S. 

Department of Energy. BNL 51882. 

*DOE. 1978a. Iodine-129: A review of its potential impact on the environment. U.S. Department of 

Energy. NTIS Y/OWI/Sub-7278/1. 

*DOE. 1978b. Methodology for the determination of environmental exp 129 U and exp 99 TC. U.S. 

Department of Energy. NTIS DPMS7775. 

DOE. 1980. Measurements of deposition and biological half-life of iodine on vegetation. 

Washington, DC: U.S. Department of Energy. NTIS DE83000759. 
 

 

 

 

IODINE 363 

9. REFERENCES 

DOE. 1985. Volatilization of iodine from soils and plants. Washington, DC: U.S. Department of 

Energy. NTIS DE85018226. 

*DOE. 1986. U.S. Department of Energy. A literature review of the concentration ratios of selected 

radionuclides in freshwater and marine fish. NTIS DE86 015820. 1021, 82-87, 243-272. 

*DOE. 1990. U.S. Department of Energy. Savannah River site radionuclide atmospheric releases and 

offsite maximum doses. NTIS DE93 004259. 

DOE. 1992a. Analysis of iodine-129 in aqueous samples by inductively coupled plasma-mass 

spectrometry. Washington, DC: U.S. Department of Energy. NTIS DE93002694. 

DOE. 1992b. Chemical contaminants on DOE lands and selection of contaminant mixtures for 

subsurface science research. Washington, DC: U.S. Department of Energy. NTIS DE92-014826. 

DOE. 1992c. External radiation doses in a household from a patient receiving a therapeutic amount of 

131I. New York, NY: U.S. Department of Energy, Environmental Measurements Laboratory. EML-547. 

DOE. 1992d. National low-level waste management program radionuclide report series: Volume 4: 

Iodine-129. Idaho: U.S. Department of Energy, Office of Environmental Restoration and Waste 

Management, Idaho Field Office. NTIS DE93 007049. 

*DOE. 1993. U.S. Department of Energy. Air pathway effects of nuclear materials production at the 

Hanford site, 1983 to 1992. NTIS DE94002708. 

*DOE. 1994. U.S. Department of Energy. Iodine-129 in the Snake River plain aquifer at and near the 

Idaho National Engineering Laboratory, Idaho, 1990-91. NTIS DE95001913. 

DOE. 1995. U.S. Department of Energy. Technetium-99, iodine-129 and tritium in the waters of the 

Savannah River site. NTIS DE95004803. 

*DOE. 1996a. Closing the circle on the splitting of the atom: The environmental legacy of nuclear 

weapons production in the United States and what the department of energy is doing about it. 

Washington, DC: Office of Environmental Management, U.S. Department of Energy. DOE/EM-0266. 

*DOE. 1996b. Selected radionuclides important to low-level radioactive waste management: National 

low-level waste management program. U.S. Department of Energy. DOE/LLW-238. 

DOE. 1996c. Radiological effluents released from U.S. continental tests 1961 through 1992. Nevada: 

U.S. Department of Energy, Nevada Operations Office. NTIS DOE/NV-317. 

*DOE. 1996d. High-level waste inventory, characteristics, generation, and facility assessment for 

treatment, storage, and disposal alternatives considered in the U.S. Department of Energy. 

*DOE. 1998. Assessment of radionuclides in the Savannah River Site. Environmental summary. Oak 

Ridge TN: US Department of Energy. Office of Scientific and Technical Information. DE-AC09­

96SR18500. 
 

 

 

 

IODINE 364 

9. REFERENCES 

*DOE. 1999. In: Arnett MW, Mamatey AR, eds. Savannah River site environmental data for 1999. 

Oak Ridge TN: U.S. Department of Energy Office of Scientific and Technical Information. DE-AC09­

96SR18500. 

*DOE. 2001a. Derived air concentrations (DAC) for workers from external exposure during immersion 

in a contaminated atmospheric cloud. U.S. Department of Energy. Code of Federal Regulations. 10 

CFR 835, Appendix C. http://ecfrback.access.gpo.gov/otcgi/otfilter.cgi.. 

..cgi...d&QUERY=159004&RGN=BAPPCT&SUBSET=SUBSET &FROM=1&ITEM-1. May 16, 2001. 

*DOE. 2001b. Derived air concentrations (DAC) for controlling radiation exposure to workers at DOE 

facilities. U.S. Department of Energy. Code of Federal Regulations. 10 CFR 835, Appendix A. 

http://ecfrback.access.gpo.gov/otcgi/otilter.cgi...d&QUERY=22008*RGN=BAPPCT&SUBSET=SUBSE 

T&FROM=1&ITEM=1. May 16, 2001. 

*DOE. 2001c. Values for establishing sealed radioactive source accountability and radioactive material 

posting and labeling requirements. U.S. Department of Energy. Code of Federal Regulations. 10 CFR 

835, Appendix E. http://ecfrback.access.gpo.gov/otcgi/. May 16, 2001. 

*DOE. 2001d. Timeline/Milestones for the Yucca Mountain Project. 

http://www.ymp.gov/timeline/index.htm. May 10, 2001. 

Doniach I. 1956. Comparison of the carcinogenic effect of x-irradiation with radioactive iodine on the 

rat's thyroid. Br J Cancer XI:67-76. 

Doniach I. 1963. Effects including carcinogenesis of I131 and x-rays on the thyroid of experimental 

animals: A review. Health Phys 9:1357-1362. 

Donaich I. 1974. Carcinogenic effect of 100, 250 and 500 rad x-rays on the rat thyroid gland. Br J 

Cancer 30:487-495. 

Doniach I, Logothetopoulos JH. 1955. Effects of radioactive iodine on the rat thyroid's function, 

regeneration and response to goitrogens. Br J Cancer IX:117-127. 

Doniach I, Shale DJ. 1976. Biological effects of 131I and 125I isotopes of iodine in the rat. J Endocrinol 

71:109-114. 

Donaich I, Williams ED. 1986. Biologic effects of radiation on the thyroid. In: Braverman LE, Utiger 

RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia,PA: 

Lippincott, 432-444. 

Donovan JW, Adelstein AM. 1974. Mutiple-cause analysis of deaths of patients treated with radioiodine. Br J Prev Soc Med 28:69. 

Doshi GR, Joshi SN, Pillai KC. 1991. 129I in soil and grass samples around a nuclear reprocessing plant. 

J Radioanal Nucl Chem 155(2):115-127. 

*DOT. 2001a. Shippers-general requirements for shipments and packagings. Table of A1 and A2 values 

for radionuclides. U.S. Department of Transportation. Code of Federal Regulations. 49 CFR 173.435. 

http://ecfrback.access.gpo.gov/otcgi/cfr/ May 16, 2001. 
 

 

IODINE 365 

9. REFERENCES 

*DOT. 2001b. List of hazardous substances and reportable quantities. U.S. Department of 

Transportation. Code of Federal Regulations. 49 CFR 172.101, Appendix A. 

http://ecfrback.access.gpo.gov/. May 16, 2001. 

Dottorini ME. 1996. Genetic risk assessment after iodine-131 exposure: An opportunity and obligation 

for nuclear medicine. J Nucl Med 37(4):612-615. 

Dottorini ME, Lomuscio G, Mazzucchelli L, et al. 1995. Assessment of female fertility and 

carcinogenesis after iodine-131 therapy for differentiated thyroid carcinoma. J Nucl Med 36:21-27. 

Douglas WS, Alexander JOD. 1975. Dermatitis herpetiformis, iodine compounds and thyrotoxicosis 

[Letter]. Br J Dermatol 92(5):596-598. 

Downie SE, Wasnidge C, Floto F, et al. 1977. Lithium-induced inhibition of 125I accumulation by 

thyroids and growing oocytes of Japanese quail. Poult Sci 56:1254-1258. 

Draper A, Lewis J, Malhotra N, et al. 1993. The energy and nutrient intakes of different types of 

vegetarian: A case for supplements. Br J Nutr 69:3-19. 

Dreicer M, Bouville A. 1989. Variability of I-131 thyroid doses from Nevada weapons testing: 

Discussion of the most sensitive parameters. Health Phys 56(Suppl 1):S51. 

Dreicer M, Bouville A, Wachholz BW. 1990. Pasture practices, milk distribution, and consumption in 

the continental U.S. in the 1950's. Health Phys 59(5):627-636. 

*Dremier S, Coppee F, Delange F, et al. 1996. Clinical review 84: Thyroid autonomy: Mechanism and 

clinical effects. J Clin Endocrinol Metab 81(12):4187-4193. 

Drew B, Barber WP, Williams DG. 1975. The effect of excess dietary iodine on pregnancy mares and 

foals. Vet Rec 97:93-95. 

Driscoll J, Hintz HF, Schryver HF. 1978. Goiter in foals caused by excessive iodine. J Am Vet Med 

Assoc 173:858-859. 

*Drobyshevskaya IM, Astakhova LN, Nalivko AS, et al. 1996. Thyroid cancer in children of Belarus 

following the Chernobyl accident. In: Nagataki S, Yamashita S, eds. Nagasaki symposium radiation and 

human health: Proposal from Nagasaki. Amsterdam, the Netherlands: Elsevier, 49-65. 

Duan SB, Wu HW, Luo JA, et al. 1999. Assessment of renal function in the early stages of 

nephrotoxicity induced by iodinated contrast media. Nephron 83:122-125. 

Duan Y, Zhang H, Jiang X, et al. 1995. A simple, innovative method for the determination of iodide by 

using gas-phase molecular absorption spectrometry after volatile species evolution. J Environ Sci Health 

Part A 30(7):1577-1593. 

Duffy BJ, Fitzgerald PJ. 1950. Cancer of the thyroid in children: A report of 28 cases. J Clin 

Endocrinol Metab 10:1296-1308. 

*Duffield AJ, Thomson CD, Hill KE, et al. 1999. An estimation of selenium requirements for New 

Zealanders. Am J Clin Nutr 70:896-903. 
IODINE 366 

9. REFERENCES 

Dugrillon A. 1996. Iodolactones and iodoaldehydes-mediators of iodine in thyroid autoregulation. Exp 

Clin Endocrinol Diabetes 104(Suppl 4):41-45. 

Dugrillon A, Gartner R. 1992. The role of iodine and thyroid cell growth. Thyroidology 4:31-36. 

Dugrillon A, Gartner R. 1995. Gamma-iodolactones decrease epidermal growth factor-induced 

proliferation and inositol-1,4,5-triphosphate generation in porcine thyroid follicles-a possible mechanism 

of growth inhibition by iodide. Eur J Endocrinol 132:735-743. 

Dugrillon A, Bechtner G, Uedelhoven WM, et al. 1990. Evidence that an iodolactone mediates the 

inhibitory effect of iodide on thyroid cell proliferation but not on adenosine 3',5'-monophosphate 

formation. Endocrinology 127(1):337-343. 

Dugrillon A, Uedelhoven WM, Pisarev MA, et al. 1994. Identification of gamma-iodolactone in iodide 

treated human goiter and its inhibitory effect on proliferation of human thyroid follicles. Horm Metab 

Res 26:465-469. 

Dumas D, Guibout M. 1978. Effect of catecholamines on iodide transport in isolated thyroid cells. 

FEBS Lett 88(2):287-291. 

Dumont JE. 1991. Iodine supply in diet in various European regions and risks of iodine prophylaxis. In: 

Gerber G, ed. Improvement of practical countermeasures: Preventive medication. Commission of the 

European Communities. EUR 12256:19-34. 

Dumont JE, Corvilain B, Contempre B. 1994. The biochemistry of endemic cretinism: Roles of iodine 

and selenium deficiency and goitrogens. Mol Cell Endocrinol 100:163-166. 

Dunn AD. 1996. Thyroglobulin retrieval and the endocytic pathway. In: Braverman LW, Utiger RD, 

eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: LippincottRaven, 81-84. 

Dunn JT. 1993. Iodine supplementation and the prevention of cretinism. Ann N Y Acad Sci 678:158­

168. 

Dunn JT. 1996. Thyroglobulin: Chemistry and biosynthesis. In: Braverman LE, Utiger RD, eds. 

Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 

85-95. 

Dunn JT, Dunn AD. 2001. Update in intrathyroidal iodine metabolism. Thyroid 11(5):407-414. 

Dunn JT, Semigran MJ, Delange F. 1998. The prevention and management of iodine-induced 

hyperthyroidism and its cardiac features. Thyroid 8(1):101-106. 

*Dunn MJ, Dunscombe PB. 1981. Levels of airborne 125I during protein labeling. Radiat Prot Dosim 

1(2):143-146. 

*Dunning DE, Schwarz G. 1981. Variability of human thyroid characteristics and estimates of dose from 

ingested 131I. Health Phys 40:661-675. 

Dunscombe PB, Dunn MJ, Bhattacharyya AK. 1980. Activated carbon badges as detectors of airborne 

125I. Health Phys 39:717-721. 
 

 

IODINE 367 

9. REFERENCES 

*Dupuy C, Virion A, de Sandro V et al. 1991. Mechanism of hydrogen peroxide formation catalyzed by 

NADPH oxidase in thyroid plasma membrane. J Biol Chem 266:3739-3743. 

Dussault JH. 1990. Thyroid antibodies in congenital hypothyroidism. In:, ed. Transplacental disorders: 

Perinatal detecion, treatment and management (including pediatric AIDS). Alan R. Liss, Inc., 77-83. 

DuVaull GE, Dunn WE, Ljegren JC, et al. 1989. Field measurement and model evaluation program for 

assessment of the environmental effects of military smokes: Analysis methods and results of 

hexachloroethane smoke dispersion experiments conducted as part of Atterbury-87 field studies. Fort 

Detrick, Frederick, MD: U.S. Army Medical Research and Development Command. AD A 216 048. 

Dwivdei R, Skierczynski P, Park H-M. 2002. Thymus gland uptake of radioactive iodine. Thyroid 

12(2):179-180. 

Dybing E, Sanner T. 1999. Species differences in chemical carcinogenesis of the thyroid gland, kidney 

and urinary bladder. In: Capen CC, Dybing E, Rice JM, et al., eds. Species differences in thyroid, 

kidney and urinary bladder carcinogenesis. Lyon, France: International Agency for Research on Cancer, 

15-32. 

*Dyck RF, Bear RA, Goldstein MB, et al. 1979. Iodine/iodide toxic reaction: Case report with emphasis 

on the nature of the metabolic acidosis. Can Med Assoc J 120:704-706. 

*Dydek GJ, Blue PW. 1988. Human breast milk excretion of iodine-131 following diagnostic and 

therapeutic administration to a lactating patient with Graves' disease. J Nucl Med 29:407-410. 

*Dyer NC, Brill AB. 1972. Maternal-fetal transport of iron and iodine in human subjects. Adv Exp Med 

Biol 27:351-366. 

*Eadie AS, Horton PW, Hilditch TE. 1980. Monitoring of airborne contamination during the handling of 

technetium-99m and radioiodine. Phys Med Biol 25(6):1079-1087. 

*Ebner SA, Lueprasitsakul W, Fang AS, et al. 1992. Iodine content of rat thyroglobin affects its 

antigenicity in inducing lymphocytic thyroiditis in the BB/Wor rat. Autoimmunity 13(3):209-214. 

*Eckhardt K, Gocke E, King M-T, et al. 1982. Mutagenic activity of chlorate, bromate, and iodate. 

Mutat Res 97:185. 

Edington GM. 1976. Dietary iodine and risk of breast, endometrial, and ovarian cancer. Lancet 

1(7974):1413-1414. 

Edmonds CJ, Smith T. 1986. The long-term hazards of the treatment of thyroid cancer with radioiodine. 

Br J Radiol 59:45-51. 

*Eeckhout E, Willemsen M, Deconinck A, et al. 1987. Granulomatous vasculitis as a complication of 

potassium iodide treatment for Sweet's syndrome. Acta Derm Venereol (Stockh) 67(4):362-364. 

Egan RW, Gale PH, Beveridge GC, et al. 1978. Radical scavenging as the mechanism for stimulation of 

prostaglandin cyclooxygenase and depression of inflammation by lipioc acid and sodium iodide. 

Prostaglandins 16(6):861-869. 
IODINE 368 

9. REFERENCES 

Ehrfeld A, Planas-Bohne F, Lucke-Huhle C. 1986. Amplification of oncogenes and integrated SV40 

sequences in mammalian cells by the decay of incorporated iodine-125. Radiat Res 108:43-51. 

Einhorn N, Wasserman J, Packalen T. 1970. Cellular autoimmune reactions following radioiodine 

treatment for hyperthyroidism. Acta Radiol Ther Phys Biol 9:225-232. 

*Eipe J, Johnson SA, Kiamko RT, et al. 1968. Hypoparathyroidism following 131I therapy for 

hyperthyroidism. Arch Intern Med 121:270-272. 

*Eisenbud M, ed. 1987. Environmental radioactivity: From natural, industrial, and military sources. 

New York, NY: Academic Press, Inc. 

*Eisenbud M, Mochizuki Y, Laurer G. 1963. 131 dose to human thyroids in New York City from nuclear 

tests in 1962. Health Phys 9:1291-1298. 

Ekholm R. 1981. Iodination of thyroglobulin: An intracellular or extracellular process? Mol Cell 

Endocrinol 24:141-163. 

*Ekman L, Eriksson A, Fredriksson L, et al. 1967. Studies on the relationship between iodine-131 

deposited on pasture and its concentration in milk. Health Phys 13:701-706. 

Ellingsen DG, Efskind J, Haug E, et al. 2000. Effects of low mercury vapour exposure on the thyroid 

function in Chloralkali workers. J Appl Toxicol 20(6):483-489. 

Elliott JE, Scheuhammer AM. 1997. Heavy metal and metallothionein concentrations in seabirds from 

the Pacific coast of Canada. Mar Pollut Bull 34(10):794-801. 

Elmalak O, Lovich MA, Edelman E. 2000. Correlation of transarterial transport of various dextrans with 

their physicochemical properties. Biomaterials 21(22):2263-2272. 

*Elmore D, Phillips FM. 1987. Accelerator mass spectrometry for measurement of long-lived 

radioisotopes. Science 236:543-550. 

*Elmore D, Gove HE, Ferraro R, et al. 1980. Determination of 129I using tandem accelerator mass 

spectrometry. Nature 286:138-140. 

*Elnagar B, Eltom M, Karlsson FA, et al. 1995. The effects of different doses of oral iodized oil on 

goiter size, urinary iodine, and thyroid-related hormones, J Clin Endocrinol Metab 80(3):891-897. 

Elnour A, Hambraeus L, Elton M, et al. 2000. Endemic goiter with iodine sufficiency: A possible role 

for the consumption of pearl millet in the etioloy of endemic goiter. Am J Clin Nutr 71(1):59-66. 

Elstner EF, Adamczyk R, Kroner R, et al. 1985. [Uptake and biochemical activity of potassium iodide in 

isolated rabbit eyes.] Ophthalmologica 191:122-126. (German) 

Eltom A, Elnagar B, Gebre-Medhin M. 1999. Thyroid hormones and iodine status in Sudanese pregnant 

women with goitre. Int J Food Sci Nutr 50:105-109. 

Eltom A, Eltom M, Elnagar B, et al. 2000. Changes in iodine metabolism during late pregnancy and 

lactation: A longitudinal study among Sudanese women. Eur J Clin Nutr 54(5):429-433. 
 

 

IODINE 369 

9. REFERENCES 

Eltom A, Eltom M, Idris M, et al. 2001. Thyroid function in the newborn in relation to maternal thyroid 

status during labour in a mild iodine deficiency endemic area in Sudan. Clin Endocrinol 2001(55):485­

490. 

Emerson CH. 1996. Thyroid disease during and after pregnancy. In: Braverman LE, Utiger RD, eds. 

Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 

1021-1031. 

EML. 1992. EML Procedures Manual, 27th ed, Vol 1, February 1992. Environmental Measurements 

Laboratory, U.S. Department of Energy. 

*EML. 1997. EML Procedures Manual, HASL-300, 28th ed, Vol 1, February 1997. Environmental 

Measurements Laboratory, U.S. Department of Energy. 

Emrich D. 1977. [Effect of etiroxate hydrochloride on iodine metabolism in man.] Arzneim Forsch 

27(2):422-426. (German) 

Emrich D, Schicha H, Facorro U, et al. 1980. Correlation of iodine excretion to hormone concentrations 

in different states of thyroid function. J Mol Med 4:183-189. 

*Endo T, Kaneshige M, Nakazato M, et al. 1997. Thyroid transcription factor-1 activated the promoter 

activity of rat thyroid Na+

/I- symporter gene. Mol Endocrinol 11:1747-1755. 

*Eng PHK, Cardona GR, Fang S-L, et al. 1999. Escape from the acute Wolff-Chaikoff effect is 

associated with a decrease in thyroid sodium/iodide symporter messenger ribonucleic acid and protein. 

Endocrinology 140:3404-3410. 

*Engler D, Burger AG. 1984. The deiodination of the iodothyronines and of their derivatives in man. 

Endocrine Rev 5(2):151-184. 

Engler H, Taurog A, Luthy C, et al. 1983. Reversible and irreversible inhibition of thyroid peroxidasecatalyzed iodination by thioureylene drugs. Endocrinology 112(1):86-95. 

*Environcare. 2001. Envirocare receives first low-level shipments from LEHR. 

http://www.envirocareutah.com. May 22, 2001. 

EPA. 1974. The behavior of 131I in an artificial rumen and in the stimulated fluids of the abomasum and 

intestine. Las Vegas, NV: U.S. Environmental Protection Agency. NERC-LV-539-32. 

EPA. 1975. 131I levels in cow’s milk following ingestion of contaminated alfalfa or sudan grass. Las 

Vegas, NV: U.S. Environmental Protection Agency, Environmental Monitoring and Support Laboratory, 

Monitoring Systems Research and Development Division. EMSL-LV-539-1. 

*EPA. 1976. Interim radiochemical methodology for drinking water. Cincinnati, OH. U.S. 

Environmental Protection Agency. Environmental Monitoring and Support Laboratory. EPA 600/4-75­

008. 

EPA. 1978. Follow-up of patients receiving diagnostic doses of 131 iodine during childhood. Research 

Triangle Park, NC: U.S. Environmental Protection Agency, Office of Research and Development, Health 

Effects Research Laboratory. EPA-600/1-78-059. 
IODINE 370 

9. REFERENCES 

*EPA. 1980. Method 902.0. Prescribed procedures for measurement of radioactivity in drinking water. 

Cincinnati, OH. U.S. Environmental Protection Agency, Environmental Monitoring and Support 

Laboratory. EPA-600/4-80-032. 

*EPA. 1983. Method 345.1. Methods for chemical analysis of water and wastes. Cincinnati, OH: U.S 

Environmental Protection Agency, Environmental Monitoring and Support Laboratory. EPA-600/4-79­

020. 

*EPA. 1986. Iodination of nutrients in the presence of chlorine based disinfectants used in drinking 

water treatment. Research Triangle Park, NC: U.S. Environmental Protection Agency, Office of 

Research and Development, Health Effects Research Laboratory. NTIS PB87180683. 

*EPA. 1988. Limiting values of radionuclide intake and air concentration and dose conversion factors 

for inhalation, submersion, and ingestion. Federal Guidance Report No. 11. Office of Radiation and 

Indoor Air. U.S. Environmental Protection Agency. EPA-520/1-88-020. 

EPA. 1990. 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. EPA 600/8-90/066A. 

*EPA. 1993. External exposure to radionuclides in air, water, and soil. Federal Guidance Report No. 12. 

Office of Radiation and Indoor Air. U.S. Environmental Protection Agency. EPA-402-R-93-081. 

EPA. 1994. Estimating radiogenic cancer risks. Washington, DC: U.S. Environmental Protection 

Agency, Office of Radiation and Indoor Air. EPA 402-R-93-076. NTIS PB96-139860. 

EPA. 1997a. Environmental radiation data report 79: July - September 1994. Montgomery, AL: U.S. 

Environmental Protection Agency, National Air and Radiation Environmental Laboratory. NTIS EPA402-R-97-002. 

EPA. 1997b. Environmental radiation data report 80: October-December 1994. Montgomery, AL: U.S. 

Environmental Protection Agency, National Air and Radiation Environmental Laboratory. NTIS EPA402-R-97-003. 

EPA. 1997c. Environmental radiation data report 81: January - March 1995. Montgomery, AL: U.S. 

Environmental Protection Agency, National Air and Radiation Environmental Laboratory. NTIS EPA402-R-97-004. 

EPA. 1997d. Environmental radiation data report 82: April-June 1995. Montgomery, AL: U.S. 

Environmental Protection Agency, National Air and Radiation Environmental Laboratory. NTIS EPA402-R-97-005. 

EPA. 1997e. U.S. Environmental Protection Agency. National primary drinking water regulations: 

Analytical methods for radionuclides; Final Rule and Proposed Rule. Fed Reg 62(43):10167-10174. 

*EPA. 1997f. Exposure factors handbook. Vol 1. General factors. Washington, DC: U.S. 

Environmental Protection Agency. EPA/600/P-95/002Fa. 

*EPA. 1997g. Health Effects Assessment Summary Tables. FY-1997 Update. Office of Research and 

Development, Office of Emergency and Remedial Response. Washington, DC: U.S. Environmental 

Protection Agency. EPA/540/R-97/036. NTIS PB 97-921199. 
 

 

 

 

 

 

 

IODINE 371 

9. REFERENCES 

*EPA. 1998. United States Environmental Protection Agency. Health risks from low-level 

environmental exposure to radionuclides. Office of Radiation and Indoor Air. EPA 402-R-97-014. 

*EPA. 1999. Cancer risk coefficients for environmental exposure to radionuclides. Federal Guidance 

Report No. 13. Office of Radiation and Indoor Air. U.S. Environmental Protection Agency. EPA402-R99-001. 

*EPA. 2001a. Annual possession quantities for environmental compliance. U.S. Environmental 

Protection Agency. Code of Federal Regulations. 40 CFR 61, Appendix E, Table 1. 

http://ecfrback.access.gpo.gov/otcgi/. May 16, 2001. 

*EPA. 2001b. Iodine production subcategory. U.S. Environmental Protection Agency. Code of Federal 

Regulations. 40 CFR 415, Subpart AQ. 

http://ecfrback.access.gpo.gov/otcgi/cfr...1&RGN=BAPPCT&SUBSET=SUBSET&FROM=1&ITEM=1. 

May 16, 2001. 

*EPA. 2002a. Perchlorate environmental contamination: Toxicological review and risk characterization. 

U.S. Environmental Protection Agency. Office of Research and Development. NCEA-1-0503. 

*EPA. 2002b. Radionuclide carcinogenicity slope factors. U.S. Environmental Protection Agency. 

Washington, DC. http://www.epa.gov/radiation/heast/docs/heast2_table_4-d2_0401.pdf. November 1, 

2002. 

*ERD 1993. Environmental Radiation Data Report 75, July-September 1993. Environmental Protection 

Agency http://www.epa.gov/narel/erdonline.htm. 

*ERD 1997. Environmental Radiation Data Report 91, July-September 1997. Environmental Protection 

Agency http://www.epa.gov/narel/erdonline.htm. 

ERDA. 1978. Iodine-129 in thyroids and tellurium isotopes in meteorites by neutron activation analysis. 

U.S. Energy Research and Development Administration. NTIS COO24501. 

Ericson LE, Nilsson M. 1996. Effects of insulin-like growth factor I on growth, epithelial barrier and 

iodide transport in polarized pig thyrocyte monolayers. Eur J Endocrinol 135:118-127. 

*Ermans AM, Camus M. 1972. Modifications of thyroid function induced by chronic administration of 

iodide in the presence of >>autonomous<< thyroid tissue. Acta Endocrinol 70:463-475. 

*Eskandari S, Loo DD, Dai G, et al. 1997. Thyroid Na+/I- symporter: Mechanism, stoichiometry, and 

specificity. J Biol Chem 272(43):27230-27238. 

*Eskin BA. 1970. Iodine metabolism and breast cancer. Trans N Y Acad Sci 32(8):911-947. 

Eskin BA. 1976. Dietary iodine and cancer risk [Letter]. Lancet 2(7989):807. 

Eskin BA. 1977. Iodine and mammary cancer. Adv Exp Med Biol 91:293-304. 

Eskin BA, Merion JA, Stamieszkin I. 1976. Estrogen-iodine interaction in breast dysplasia. [Abstract]. 

Proc Am Assoc Cancer Res 17:169. 
 

 

 

 

IODINE 372 

9. REFERENCES 

Eskin BA, Shuman R, Krouse T, et al. 1975. Rat mammary gland atypia produced by iodine blockade 

with perchlorate. Cancer Res 35:2332-2339. 

*Esselstyn CB, Schumacher OP, Eversman J, et al. 1982. Hyperparathyroidism after radioactive iodine 

therapy for Graves disease. Surgery 92:811-813. 

Eszlinger M, Krohn K, Kratzsch J. 2001. Growth factor expression in cold and hot thyroid nodules. 

Thyroid 11(2):125-135. 

Etling N, Gehin-Fouque F. 1984. Iodinated compounds and thyroxine binding to albumin in human 

breast milk. Pediatr Res 18(9):901-903. 

*Etling N, Vielh JP. 1979. [Iodine overloads in amniotic fluids.] Nouv Presse Med 8:1647-1648. 

(French) 

*Etling N, Gehin-Fouque F, Vielh JP, et al. 1979. The iodine content of amniotic fluid and placental 

transfer of iodinated drugs. Obstet Gynecol 53(3):376-380. 

*Etling N, Padovani E, Gehin-Fouque F, et al. 1983. Iodine and thyroid hormone levels in serum and 

urine of full term newborn infants. Helv Paediatr Acta 38:117-122. 

Evans PMS, Webster J, Evans WD, et al. 1998. Radioiodine treatment in unsuspected pregnancy. Clin 

Endocrinol 48:281-283. 

*Evans TC, Kretzschmar RM, Hodges RE, et al. 1967. Radioiodine uptake studies of the human fetal 

thyroid. J Nucl Med 8:157-165. 

Exss R, Graewe B. 1974. Congenital athyroidism in the newborn infant from intra-uterine radioiodine 

action. Biol Neonate 24:289-291. 

Fagin JA. 1996. Molecular pathogenesis. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's the 

thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 909-916. 

Fanelli A, Berlin WK, Grollman EF. 1995. Inhibition of iodide transport in rat thryoid cells using Nsubstituted anthranilic acid derivatives. Thyroid 5(3):223-230. 

Farris WT, Napier BA, Ikenberry TA, et al. 1996. Radiation doses from Hanford site releases to the 

atmosphere and the Columbia river. Health Phys 71:588-601. 

Fatourechi V. 1996. Localized myxedema and thyroid acropachy. In: Braverman LE, Utiger RD, eds. 

Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 

553-558. 

*Fawcett DM, Kirkwood S. 1953. The mechanism of the antithyroid action of the iodide ion and of the 

“aromatic” thyroid inhibitors. Journal of Biological Chemistry 204:787-796. 

FDA. 1973. Scientific literature reviews on generally recognized as safe (GRAS) food ingredients - 

Iodine and iodine salts. Washington, DC: U.S. Food and Drug Administration. PB 223 849. 
 

 

IODINE 373 

9. REFERENCES 

*FDA. 1974. Iodine in foods: Chemical methodology and sources of iodine in the human diet. 

Washington, DC: U.S. Food and Drug Administration, Bureau of Foods, Division of Nutrition. PB-233­

559. 

*FDA. 1978. Potassium iodide as a thyroid-blocking agent in a radiation emergency. U.S. Food and 

Drug Administration. Federal Register 43:58798-800. 

FDA. 1989a. A follow-up study of persons who had iodine-131 and other diagnostic procedures during 

childhood and adolescence. Rockville, MD: U.S. Food and Drug Administration, Public Health Service, 

Center for Devices and Radiological Health. FDA 89-8276. 

*FDA. 1989b. Iodine toxicity. Washington, DC: U.S. Food and Drug Administration, Center for Food 

Safety and Applied Nutrition. NTIS PB89 183016. 

*FDA. 1998. Accidental radioactive contamination of human food and animals feeds: 

Recommendations for state and local agencies. U.S. Department of Health and Human Services. Food 

and Drug Administration. Center for Devices and Radiological health. Rockville, MD 20850. August 

13, 1998. 

*FDA. 2000a. Drug products containing certain active ingredients offered over-the-counter (OTC) for 

certain uses. U.S. Food and Drug Administration. Code of Federal Regulations. 21 CFR 310.545. 

http://frewebgate.access.gpo.gov/. May 16, 2001. 

*FDA. 2000b. Drugs; recommended warning and caution statements. U.S. Food and Drug 

Administration. Code of Federal Regulations. 21 CFR 369.20. http://frewebgate.access.gpo.gov/. May 

16, 2001. 

*FDA. 2000c. Food additives permitted for direct addition to food for human consumption. U.S. Food 

and Drug Administration. Code of Federal Regulations. 21 CFR 172.375. 

http://frwebgate.access.gpo.gov/. March 06, 2001. 

*FDA. 2000d. Indirect food additives: Adjuvants, production aids, and sanitizers. Sanitizing solutions. 

U.S. Food and Drug Administration. Code of Federal Regulations. 21 CFR 178.1010. 

http://frewebgate.access.gpo.gov/. May 16, 2001. 

*FDA. 2000e. Nutritional labeling of dietary supplements. U.S. Food and Drug Administration. Code 

of Federal Regulations. 21 CFR 101.36. http://frewebgate.access.gpo.gov/. May 16, 2001. 

*FDA. 2000f. Nutritional quality guidelines for foods. U.S. Food and Drug Administration. Code of 

Federal Regulations. 21 CFR 104.20. http://frewebgate.access.gpo.gov/. May 16, 2001. 

*FDA. 2000g. Requirements regarding certain radioactive drugs. U.S. Food and Drug Administration. 

Code of Federal Regulations. 21 CFR 310.503. http://ecfrback.access.gpo.gov/otcgi/. May 16, 2001. 

*FDA. 2000h. Sources of radiation used for inspection of food,for inspection of packaged food, and for 

controlling food processing. U.S. Food and Drug Administration. Code of Federal Regulations. 21 CFR 

179.21. http://ecfrback.access.gpo.gov/otcgi/. May 16, 2001. 

*FDA. 2000i. Trace minerals added to animal feed. U.S. Food and Drug Administration. Code of 

Federal Regulations. 21 CFR 582.80. http://frewebgate.access.gpo.gov/cgi-bin/... 

&PART=582&SECTION=80&YEAR=2000&TYPE=TEXT. May 16, 2001. 
 

 

IODINE 374 

9. REFERENCES 

*FDA. 2001a. Nutrients. U.S. Food and Drug Administration. 

http://www.verity.fda.gov/opacom/laws/fdrgact.htm. March 6, 2001. 

*FDA. 2001b. U.S. Food and Drug Administration. Code of Federal Regulations. 21CFR101.9. 

*FEDRIP. 2000. Federal Research in Progress. Dialog Information Services, Inc. Palo Alto, CA. 

Feek CM, Sawers JS, Irvine WJ, et al. 1980. Combination of potassium iodide and propanolol in 

preparation of patients with Graves' disease for thyroid surgery. N Engl J Med 302:883-885. 

Feinendegen LE, Henneberg P, Tisljar-Lentulis G. 1977. DNA strand breakage and repair in human 

kidney cells after exposure to incorporated iodine-125 and cobalt-60 gamma rays. Curr Top Radiat Res Q 

12:436-452. 

Feldkamp J, Pascher E, Perniok A, et al. 1999. Fas-mediated apoptosis is inhibited by TSH and iodine in 

moderate concentrations in primary human thyrocytes in vitro. Horm Metab Res 31:355-358. 

*Feldt-Rasmussen U. 2001. Iodine and cancer. Thyroid 11(5):483-486. 

*Fenner FD, Martin JE. 1997. Behavior of Na131I and meta(131I) iodobenzylguanidine (MIBG) in 

municipal sewerage. Health Phys 73:333-339. 

Ferguson MM, Alexander WD, Connell JMC, et al. 1984. Peroxidase activity in relation to iodide. 

17beta-oestradiol and thioreylene drug uptake in human polymorphoneutrophils. Biochem Pharmacol 

33(5):757-762. 

Ferriols Lisart F, Rodilla Calvelo F, Ciges Sanmartin E, et al. 1995. [Use of Lugol to protect thyroid 

from a radiologic exposure.] Farm Clin 12:683-685. (Spanish) 

Field JB, Dekker A, Titus G, et al. 1979. In vitro and in vivo refractoriness to thyrotropin stimulation of 

iodine organification and thyroid hormone secretion. J Clin Invest 64:265-271. 

Fike JR, Gobbel GT, Marton LJ, et al. 1994. Radiation brain injury is reduced by the polyamine 

inhibitor alpha-difluoromethylornithine. Radiat Res 138:99-106. 

*Filetti S, Rapoport B. 1983. Evidence that an organic iodine attenuates the adenosine 3'5' 

monophosphate response to thyrotropin stimulation in thyroid tissue by an action at or near the sdenylate 

cyclase catalytic unit. Endocrinology 113:1608. 

Filetti S, Bidart J-M, Arturi F, et al. 1999. Sodium/iodide symporter: A key transport system in thyroid 

cancer cell metabolism. Eur J Endocrinol 141(5):443-457. 

*Filistovic V, Nedveckaite T. 1998. Reaction pathways involving 127I and 131I in the atmospheric air. 

Environ Phys 20(2):5-12. 

*Finkelstein R, Jacobi M. 1937. Fatal iodine poisoning: A clinico-pathologic and experimental study. 

Adv Intern Med 60:1283-1296. 

Fischer PWF, Giroux A. 1993. Iodine content of Canadian retail milk samples II. After the 

ethylenediamine dihydroiodide ban. Food Res Int 26:277-281. 
 

 

IODINE 375 

9. REFERENCES 

Fischer PWF, Campbell JS, Giroux A. 1989. Effect of dietary iodine on autoimmune thyroiditis in the 

BB Wistar rat. J Nutr 119:502-507. 

Fischman RA, Fairclough GF, Cheigh JS. 1978. Iodide and negative anion gap [Letter]. N Engl J Med 

298(18):1035-1036. 

Fish RE, Swanson EW. 1982. Effects of excessive intakes of iodine upon growth and thyroid function of 

growing Holstein heifers. J Dairy Sci 65:605-610. 

Fisher DA. 1989. Upper limit of iodine in infant formulas. J Nutr 119:1865-1868. 

Fisher DA. 1996. Thyroid physiology in the perinatal period and during childhood. In: Braverman LE, 

Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: 

Lippincott-Raven, 974-983. 

*Fisher DA, Oddie TH, Burroughs JC. 1962. Thyroidal radioiodine uptake rate measurement in infants. 

Am J Dis Child 103:738-749. 

*Fisher DA, Oddie TH, Epperson D. 1965. Effect of increased dietary iodide on thyroid accumulation 

and secretion in eurthyroid Arkansas subjects. J Clin Endocrinol 25:1580-1590. 

Fisher NS, Fowler SW, Boisson F, et al. 1999. Radionuclide bioconcentration factors and sediment 

partition coefficients in Arctic seas subject to contamination from dumped nuclear wastes. Environ Sci 

Technol 33:1979-1982. 

Fisher WD, Voorhess ML, Gardner LI. 1965. Congenital hypothyroidism in infant following maternal 

I

131 therapy: With a review of hazards of environmental radioiosotope contamination. J Pediatr 62:132­

146. 

Fisherman EW, Cohen GN. 1977. A vascular test to detect iodide hypersensitivity (intolerance). Ann 

Allergy 38:163-168. 

*Fjälling M, Dackenberg A, Hedman I, et al. 1983. An evaluation of the risk of developing 

hyperparathyroidim after 131I treatment for thyrotoxicosis. Acta Chir Scand Suppl 149:681-686. 

Floyer C, Wilkinson JD. 1988. Treatment of venous leg ulcers with cadexomer iodine with particular 

reference to iodine sensitivity. Acta Chir Scand Suppl 544:60-61. 

Folb PI, Graham Dukes MN. 1990. Thyroid and antithyroid drugs. In: Drug safety in pregnancy. Cape 

Town, South Africa: University of Cape Town, 305-314. 

Foley TP. 1991. Maternally transferred thyroid disease in the infant: Recognition and treatment. In: 

Bercu BB, Shulman DI, eds. Advances in perinatal thyroidology. New York, NY: Plenum Press, 209­

226. 

*Foley TP. 1992. The relationship between autoimmune thyroid disease and iodine intake: A review. 

Endokrynol Pol 43 (Suppl 1):53-69. 

Foley TPJ. 1996. Congenital hypothyroidism. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's 

the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 988-994. 
 

 

 

IODINE 376 

9. REFERENCES 

Foley TP, Charron M. 1997. Radioiodine treatment of juvenile Graves disease. Exp Clin Endocrinol 

Diabetes 105(Suppl 4):61-65. 

*Fomon SJ. 1966. Body composition of the infant: Part I: The male “reference infant”. In: Falkner F, 

ed. Human development. Philadelphia, PA: WB Saunders, 239-246. 

*Fomon SJ, Haschke F, Ziegler EE, et al. 1982. Body composition of reference children from birth to 

age 10 years. Am J Clin Nutr 35:1169-1175. 

Fontana B, Curti G, Biggi A, et al. 1980. The incidence of hypothyroidism after radioactive iodine (131I) 

therapy for autonomous hyperfunctioning thyroid nodule evaluated by means of life-table method. J Nucl 

Med Allied Sci 24(1-2):85-91. 

*Forbes. GB, Bruining GJ. 1976. Urinary creatinine excretion and lean body mass. Am J Clin Nutr 

29:1359-1366. 

Foster HD. 1987. Disease family trees: The possible roles of iodine in goitre, cretinism, multiple 

sclerosis, amyotrophic lateral sclerosis, Alzheimer's and Parkinson's diseases and cancer of the thyroid, 

nervous system and skin. Med Hypotheses 24:249-263. 

Foster HD. 1993. The iodine-selenium connection: Its possible roles in intelligence, cretinism, sudden 

infant death syndrome, breast cancer and multiple sclerosis. Med Hypotheses 40:61-65. 

*Fradkin JE, Wolff J. 1983. Iodide-induced thryotoxicosis. Medicine 62(1):1-20. 

Fragu P, Othman SB, Nataf BM. 1979. Effect of PTU added to a low iodine diet on peroxidase activity 

and other parameters of thyroid function in rats. Acta Endocrinol 91:462-472. 

*Franceschi S. 1998. Iodine intake and thyroid carcinoma-a potential risk factor. Exp Clin Endocrinol 

Diabetes 106(Suppl 3):S38-S44. 

*Franceschi S, Dal Maso L. 1999. Hormonal imbalances and thyroid cancers in humans. In: Capen CC, 

Dybing E, Rice JM, et al., eds. Species differences in thyroid, kidney and urinary bladder carcinogenesis. 

Lyon, France: International Agency for Research on Cancer, 33-43. 

Franceschi S, Levi F, Negri E, et al. 1991. Diet and thyroid cancer: A pooled analysis of four European 

case-control studies. Indian J Cancer 48:395-398. 

Franceschi S, Talamini R, Fassina A, et al. 1990. Diet and epithelial cancer of the thyroid gland. Tumori 

76:331-338. 

Francis AR, Shetty TK, Bhattacharya RK. 1988. Modifying role of dietary factors on the mutagenicity 

of aflatoxin B1: In vitro effect of trace elements. Mutat Res 199:85-93. 

Francois PJ, Szmigielski M, De Rouck A, et al. 1966. [Electrophysiologic and histologic study of 

experimental tapeto-retinal degeneration evoked by sodium iodide. I. Electrophysiologic study.] 

Ophthalmologica 152:131-148. (French) 

Franklyn J, Sheppard M. 1992. Radioiodine for hyperthyroidism: Perhaps the best option. Br Med J 

305:727-728. 
IODINE 377 

9. REFERENCES 

Franklyn JA, Daykin J, Holder R, et al. 1995. Radioiodine therapy compared in patients with toxic 

nodular or Graves' hyperthyroidism. Q J Med 88:175-180. 

Franklyn JA, Maisonneuve P, Sheppard MC, et al. 1998. Mortality after the treatment of 

hyperthyroidism with radioactive iodine. N Engl J Med 338:712-718. 

*Franklyn JA, Maisonneuve P, Sheppard M, et al. 1999. Cancer incidence and mortality after 

radioiodine treatment for hyperthyroidism: A population-based cohort study. Lancet 353:2111-2115. 

*Freeman M, Guiliani M, Schwartz E, et al. 1969. Acute thyroiditis, thyroid crisis, and hypocalcemia 

following radioactive iodine therapy. N Y State J Med 69(14):2036-2041. 

Fregly MJ, McCarthy JS. 1973. Effect of diuretics on renal iodide excretion by humans. Toxicol Appl 

Pharmacol 25:289-298. 

Freidman NB, Catz B. 1996. The reactions of euthyroid and hyperthyroid glands to radioactive iodine. 

Arch Pathol Lab Med 120:660-661. 

Freitas JE, Swanson DP, Gross MD, et al. 1979. Iodine-131: Optimal therapy for hyperthyroidism in 

children and adolescents? J Nucl Med 20:847-850. 

Fritzsche H, Benzer W, Furlan W, et al. 1993. [Prophylaxis of iodine-induced thyrotoxicosis after 

coronary angiography.] Acta Med Austriaca 20:13-17. (German) 

Frohmberg E, Goble R, Sanchez V, et al. 2000. The assessment of radiation exposures in Native 

American communities from nuclear weapons testing in Nevada. Risk Anal 20(1):101-111. 

From E, Thomsen K. 1974. Dermatitis herpetiformis: A case provoked by iodine. Br J Dermatol 

91(2):221-224. 

From GLA, Lawson VG. 1997. Solitary thyroid nodule: Concepts in diagnosis and treatment. In: Falk 

SA, ed. Thyroid disease: Endocrinology, surgery, nuclear medicine, and radiotherapy. Philadelphia, PA: 

Lippincott-Raven Publishers, 411-429. 

*Fuge R. 1987. Iodine in the environment: Its distribution and relationship to human health. In: 

Hemphill DD, ed. Trace substances in environmental health. Columbia, Mo: Curators of the University 

of Missouri, 74-87. 

*Fujimori K, Takahashi T, Ohtomo H, et al. 1996. Preliminary medical findings of the Marshall Islands 

nationwide thyroid study. In: Nagataki S, Yamashita S, eds. Nagasaki symposium radiation and human 

health: Proposal from Nagasaki. Amsterdam, The Netherlands: Elseiver, 167-173. 

*Fujiwara H, Tatsumi K, Miki K, et al. 1997. Congenital hypothyroidism caused by a mutation in the 

Na+

/I- symporter. Nat Genet 16:124-125. 

­ *Fujiwara H, Tatsumi K-I, Miki K, et al. 1998. Recurrent T354P mutation of the Na +/I symporter in 

patients with iodide transport defect. J Clin Endocrinol Metab 83(8):2940-2943. 

*Fujiwara H, Tatsumi K, Tanaka S, et al. 2000. A novel V59E missense mutation in the sodium iodide 

symporter gene in a family with iodide transport defect. Thyroid 10(6):471-474. 
 

 

IODINE 378 

9. REFERENCES 

Fujiwara S, Ezaki H, Sposto R, et al. 1990. Hyperparathyroidism among atomic bomb survivors in 

Hiroshima, 1986-88. DCBN 22-0058403 (Upstate) TR 8-90:1-12. 

Fukuda H, Yasuda N, Greer MA. 1975. Acute effects of thyroxine, triiodothyronine, and iodide on 

thyrotropin secretion. Endocrinology 97:924-931. 

Fukui M, Fujikawa Y, Satta N. 1996. Factors affecting interaction of radioiodine and iodate species with 

soil. J Environ Radioact 31(2):199-216. 

Fulop M. 1971. Hypoparathyroidism after 131I therapy. Ann Intern Med 75(5):808. 

Furr AK, Parkinson TF, Heffron CL, et al. 1978. Elemental content of tissues and excreta of lambs, 

goats, and kids fed white sweet clover growing on fly ash. J Agric Food Chem 26:847-851. 

Furrer J, Dillman H-G (1986): Apparatus for detecting iodine isotopes. (to Kernforschungszentrum 

Karlsrube G.m.b.H.) Application: Germany 4,626,692, 2 Dec 1986. United States Patent 4,626,692, 

issued 2 Dec 1986. 

*Furudate S, Nishimaki T, Muto T. 1997. 125I uptake competing with iodine absorption by the thyroid 

gland following povidone-iodine skin application. Exp Anim 46(3):197-202. 

*Gabay JJ, Paperiello CJ, Goodyear S, et al. 1974. A method for determining iodine-129 in milk and 

water. Health Phys 26:89-96. 

*Gäbler H-E, Heumann KG. 1993. Determination of atmospheric iodine species using a system of 

specifically prepared filters and IDMS. Fresenius J Anal Chem 345:53-59. 

Gadzhiev KM. 1990. [A case of anaphylactic shock in response to the topical application of 5 percent 

alcohol tincture of iodine.] Azerb Med Zh 4:56-57. (Azerbaijani) 

*Gaffney GW, Gregerman RI, Shock NW. 1962. Relationship to age to the thyroidal accumulation, 

renal excretion and distribution of radioiodide in euthyroid man. J Clin Endocrinol Metab 22:784-794. 

Gaitan E, Cooksey RC, Meydrech EF, et al. 1989. Thyroid function in neonates from goitrous and 

nongoitrous iodine-sufficient areas. J Clin Endocrinol Metab 69(2):359-363. 

*Galina MP, Avnet NL, Einhorn A. 1962. Iodides during pregnancy: An apparent cause of neonatal 

death. N Engl J Med 267:1124-1127. 

Galla JH, Kotchen TA, Luke RG. 1977. Failure of sodium iodide loading to inhibit renin in the rat. Proc 

Soc Exp Biol Med 154:30-32. 

Gambal D, Quackenbush FW. 1968. Essential fatty acids, plasma protein bound iodine, and the thyroid 

gland. Proc Soc Exp Biol Med 127(4):1137-1138. 

Gambert SR. 1996. Intrinsic and extrinsic variables. In: Braverman LE, Utiger RD, eds. Werner and 

Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 254-259. 

Gao F, Fu C, Zhang C, et al. 1992. [Further studies on the carcinogenic effects of radioiodine in rats.] 

Zhong Fan Yixue Yu Fanghu Zazhi 12(4):249-252. (Chinese) 
IODINE 379 

9. REFERENCES 

Garcia-Mayor RV, Rios M, Fluiters E. 1999. Effect of iodine supplementation on a pediatric population 

with mild iodine deficiency. Thyroid 9(11):1089-1093. 

Garcia Pascual L, Simo R, Mesa J, et al. 1992. [Myelodysplastic syndrome following radioiodine 

treatment of differentiated carcinoma of the thyroid [Letter]. Rev Clin Esp 191(3):169-170. (Spanish) 

*Gardner DF, Centor RM, Utiger RD. 1988. Effects of low dose oral iodide supplementation on thyroid 

function in normal men. Clin Endocrinol 28:283-288. 

Gardner DF, Mars DR, Thomas RG, et al. 1986. Iodine retention and thyroid dysfunction in patients on 

hemodialysis and continuous ambulatory peritoneal dialysis. Am J Kidney Dis VII(6):471-476. 

Gardner DF, Rothman J, Utiger RD. 1979. Serum thyroglobulin in normal subjects and patients with 

hyperthyroidism due to Graves' disease: Effects of T3, iodide, 131I and antithyroid drugs. Clin Endocrinol 

11:585-594. 

*Garijo MAG, Quintana JAD, Gonzalez PB, et al. 1996. Anaphylactic shock following povidone. Ann 

Pharmacother 30:37-40. 

Gartner R, Dugrillon A, Bechtner G. 1996. Evidence that iodolactones are the mediators of growth 

inhibition by iodine on the thyroid. Acta Med Austriaca 23:47-51. 

Gartner R, Greil W, Demharter R, et al. 1985. Involvement of cyclic AMP, iodide and metabolites of 

arachidonic acid in the regulation of cell proliferation of isolated porcine thyroid follicles. Mol Cell 

Endocrinol 42:145-155. 

*Gautier MA. 1983. Manual of Analytical methods for radiobioassay, DOE Report No. LA-9763-M 

(National Technical Information Services), Springfield, VA. 

*Gavin LA, Livermore BM, Cavalieri RR, et al. 1980. Serum concentration, metabolic clearance, and 

production rates of 3,5,3'-triiodothyroacetic acid in normal and athyreotic man. J Clin Endocrinol Metab 

51(3):529-534. 

Gedik O, Ozdemir T, Akalin S. 1991. Discordant hypothyroxinemia and hypertriiodothyroninemia in 

treated patients with hyperthyroid Graves' disease and toxic multinodular goiter. Isr J Med Sci 27:361­

364. 

Geisthovel W. 1984. [Hyperthyroidism after administration iodine-containing eyedrops.] Dtsch Med 

Wochenschr 109(34):1304-1305. (German) 

*Gélinas Y, Iyengar GV, Barnes RM. 1998. Total iodine in nutritional and biological reference materials 

using neutron activation analysis and inductively coupled plasma mass spectrometry. Fresenius J Anal 

Chem 362:483-488. 

Gembicki M. 1996. Physiological basis of iodine prophylaxis in case of a nuclear accident. In: 

Radiodosimetry and preventative measures in the event of a nuclear accident. Austria: International 

Atomic Energy Agency, 87-100. IAEA-TECDOC-893. 
IODINE 380 

9. REFERENCES 

*Gembicki M, Stozharov AN, Arinchin AN, et al. 1997. Iodine deficiency in Belarusian children as a 

possible factor stimulating the irradiation of the thyroid gland during the Chernobyl catastrophe. Environ 

Health Perspect Suppl 105(6):1487-1490. 

*Georgitis WJ, McDermott MT, Kidd GS. 1993. An iodine load from water-purification tablets alters 

thyroid function in humans. Mil Med 158:794-797. 

Germani MS, Zoller WH. 1988. Vapor-phase concentrations of arsenic, selenium, bromine, iodine, and 

mercury in the stack of a coal-fired power plant. Environ Sci Technol 22:1079-1085. 

*Germani MS, Gokmen I, Sigleo AC, et al. 1980. Concentrations of elements in the antional bureau of 

standards’ bituminous and subbituminous coal standard reference materials. Anal Chem 52:240-245. 

Geselowitz DA, McManaway MM, Hofer KG, et al. 1995. Low-let radiotoxicity from incorporated 3

H 

or 125I during the cell cycle: Implications for mechanisms of high-let damage. In: Fuciarelli AF, 

Zimbrick JD, eds. Radiation damage in DNA: Structure/function relationships at early times. 

Columbus,OH: Battelle Press, 223-230. 

*Ghahremani GG, Hoffer PB, Oppenheim BE, et al. 1971. New normal values for thyroid uptake of 

radioactive iodine. JAMA 217(3):337-339. 

Gibberd M, McMillan M, Staffurth JS. 1974. Thyrotropin (T.S.H.) after iodine-131 therapy. Lancet 

1(7865):1048. 

Gibbs RA, Camakaris J, Hodgson GS, et al. 1987. Molecular characterization of 125I decay and x-rayinduced HPRT mutants in CHO cells. Int J Radiat Biol 51(2):193-199. 

*Gilbert ES, Tarone R, Bouville A, et al. 1998. Thyroid cancer rates and 131I doses from Nevada 

atmospheric nuclear bomb tests. J Natl Cancer Inst 90(21):1654-1660. 

Gilbert-Dreyfus Z, Gali P. 1958. Cataracte tetanique apres IRA-therapie. Sem Hop 34:1301-1304. 

Gilchrist B. 1997. Should iodine be reconsidered in wound management? J Wound Care 6(3):148-150. 

Gillespie FC, Orr JS, Greig WR. 1970. Microscopic dose distribution from 125I in the toxic thyroid gland 

and its relation to therapy. Br J Radiol 43:40-47. 

Gimeno EJ, Walinder G, Feinstein RE, et al. 1986. Effect of high 131I doses to the thyroid gland on 

tumorigenicity of 90Sr and 90Y in mice. Acta Radiol Oncol 25:4-6. 

Ginsberg J, Murray PG. 1991. Stimulation of TSH-mediated iodide organification in porcine thyroid 

cells following protein kinase C inhibition. In: Gordon A, Gross J, Hennemann G, eds. Progress in 

thyroid research. Rotterdam, the Netherlands: Balkema, 599-602. 

Ginsberg J, Matowe W, Murray PG. 1993. Enhancement of thyrotropin-stimulated iodide organification 

in porcine thyroid cells after protein kinase-C inhibition. Endocrinology 132(4):1815-1819. 

Gittoes NJL, Franklyn JA. 1995. Drug-induced thyroid disorders. Drug Saf 13(1):46-55. 

Gittoes NJL, Franklyn JA. 1998. Hyperthyroidism: Current treatment guidelines. Drugs 55(4):543-553. 
 

 

IODINE 381 

9. REFERENCES 

*Giwercman A, Carlsen E, Keiding N, et al. 1993. Evidence for increasing incidence of abnormalities of 

the human testis: A review. Environ Health Perspect Suppl 101(2):65-71. 

Glanzmann C, Horst W. 1979. [Treatment of thyrotoxicosis with 125-iodine: Results in 93 patients 3 to 

5 years after treatment, and comparison with 131-iodine therapy.] Strahlentherapie 155:1-5. (German) 

Glanzmann C, Horst W. 1980. Iodine-125 and iodine-131 in the treatment of hyperthyroidism. Clin 

Nucl Med 5(7):325-333. 

*Glassock RF. 1954. The secretion of a single tracer dose of labeled iodine in the milk of the lactating 

cow. J Dairy Res 21:318. 

*Glazebrook GA. 1987. Effect of decicurie doses of radioactive iodine 131 on parathyroid function. Am
 

J Surg 154:368-373. 

Glennon JA, Gordon ES, Sawin CT. 1972. Hypothyroidism after low-dose 131I treatment of 

hyperthyroidism. Ann Intern Med 76:721-723. 

Glick PL, Guglielmo BJ, Winter ME, et al. 1990. Iodine toxicity secondary to continuous povidoneiodine mediastinal irrigation in dogs. J Surg Res 49:428-434. 

Glinoer D. 1999. What happens to the normal thyroid during pregnancy? Thyroid 9(7):631-635. 

*Glinoer D. 2001. Pregnancy and iodine. Thyroid 11(5):139-149.
 

Globel B, Globel H, Andres C. 1985. The risk of hyperthyroidism following an increase in the supply of
 

iodine. J Hosp Infect 6(Supplement):201-204. 

Gluzman BE, Coleoni AH, Targovnik HM, et al. 1977. Effects of amiodarone on thyroid iodine 

metabolism in vitro. Acta Endocrinol 85:781-790. 

Gobbel GT, Marton LJ, Lamborn K, et al. 1991. Modification of radiation-induced brain injury by
 

alpha-difluoromethylornithine. Radiat Res 128:306-315. 

*Goh K. 1981. Radioiodine treatment during pregnancy: Chromosomal aberrations and cretinsim
 

associated with maternal iodine-131 treatment. J Am Med Womens Assoc 36(8):262-265. 

Goldberg RC, Chaikoff IL. 1951. Development of thyroid neoplasms in the rat following a single 

injection of radioactive iodine. Proc Soc Exp Biol Med 76:563-566. 

Goldberg REA, Miraldi F. 1987. Radionuclide imaging of potassium iodide-induced sialadenitis. Clin 

Nucl Med 12:370-372. 

Golden MHN. 1982. Trace elements in human nutrition. Hum Nutr Clin Nutr 36C:185-202. 

Goldman M, Grau TJ. 1974. A comparative study on the influence of dimethyl sulfoxide on iodine 

metabolism in male Long-Evans rats and male CF1 mice. Toxicol Appl Pharmacol 29:340-347. 

Goldman M, Landry D. 1976. The effect of povidone-iodine on thyroid function in rats. Toxicol Appl 

Pharmacol 35:341-346. 
IODINE 382 

9. REFERENCES 

*Goldman MB, Maloof F, Monson RR, et al. 1988. Radioactive iodine therapy and breast cancer: A 

follow-up study of hyperthyroid women. Am J Epidemiol 127(5):969-980. 

*Goldschmidt VM. 1958. Geochemistry. Oxford University Press, London, pp.602-620. 

Goldsmith JR, Grossman CM, Morton WE, et al. 1999. Juvenile hypothyroidism among two populations 

exposed to radioiodine. Environ Health Perspect 107(4):303-308. 

Goldstein R, Hart IR. 1983. Follow-up of solitary autonomous thyroid nodules treated with 131I. N Engl 

J Med 309(24):1473-1476. 

Golstein J, Dumont JE. 1996. Cytotoxic effects of iodide on thyroid cells: Difference between rat 

thyroid FRTL-5 cell and primary dog thyrocyte responsiveness. J Endocrinol Invest 19:119-126. 

Golstein P, Abramow M, Dumont JE, et al. 1992. The iodide channel of the thyroid: A plasma 

membrane vesicle study. Am J Physiol 263(32):C590-C597. 

Gomez JM, Virgili N, Soler J, et al. 1989. Transient hypothyroidism after iodine-131 treatment of 

Graves' disease. Thyroidology 3:149-152. 

Gomez N, Gomez JM, Orti A, et al. 1995. Transient hypothyroidism after iodine-131 therapy for Grave's 

disease. J Nucl Med 36:1539-1542. 

Gomez N, Gomez JM, Villabona C, et al. 1998. Transient hypothyroidism after iodine-131 therapy for 

Graves' disease. Clin Endocrinol 48:526-527. 

Goncharov AT, Ametov AS. 1977. [The effect of chrome on the thyroid in rats kept on an iodinedeficient diet.] Probl Endokrinol (Mosk) 23(6):59-61. (Russian) 

*Gonzalez AJ. 1998. Radioactive residues of the cold war period. A radiological legacy. IAEA Bulletin 

40(4):2-11. 

Goolden AWG, Stewart JSW. 1986. Long-term results from graded low dose radioactive iodine therapy 

for thyrotoxicosis. Clin Endocrinol 24:217-222. 

Goolden AWG, Kam KC, Fitzpatrick ML, et al. 1986. Oedema of the neck after ablation of the thyroid 

with radioactive iodine. Br J Radiol 59:583-586. 

*Gordon CM, Rowitch DH, Mitchell ML, et al. 1995. Topical iodine and neonatal hypothyroidism. 

Arch Pediatr Adolesc Med 149:1336-1339. 

Gorman CA. 1995. Radioiodine therapy does not aggravate Graves' ophtalmopathy. J Clin Endocrinol 

Metab 80:340-342. 

Gorman CA. 1999. Radioiodine and pregnancy. Thyroid 9(7):721-726. 

*Gorodinskiy SM, Yes’kova-Soskovets LS, Rokhlin MI, et al. 1979. Penetration of gaseous I131 

through human skin. Ohio: Foreign Technology Division, Wright-Patterson Air Force Base. NTIS 

ADA087882. 
IODINE 383 

9. REFERENCES 

Gorowski T, Gabryelewicz MB, Jastrzebska H. 1992. [Anaplastic thyroid carcinoma developed after 

treatment of "hot" thyroid nodule with radioiodine.] Endokrynol Pol 43(3):308-313. (Russian) 

Gossage AAR, Neal FE, Ross CMD, et al. 1984. Cases of carcinoma of thyroid following iodine-131 

therapy for hyperthyroidism. Oncology 41:8-12. 

Gotoh T, Ito A, Yamada K, et al. 1996a. [Occurrence of time and dose-dependent rat thyroid tumors 

induced by radioiodine (131I) and fission neutron (252Cf).] Nagasaki Igakkai Zasshi 71:375-379. 

(Japanese) 

Gotoh T, Watanabe H, Tanizaki M, et al. 1996b. Promotion of thyroid tumors in F344 male rats given a 

low iodine diet after treatment with n-methyl-n-nitrosourea in their drinking water. J Toxicol Pathol 

9:191-197. 

*Goyens P, Golstein J, Nsombola B et al. 1987. Selenium deficiency as a possible factor in the 

pathogenesis of myxoedamatous cretinism. Acta Endocrinol 114:497-502. 

Graham GD, Burman KD. 1986. Radioiodine treatment of Graves' disease. Ann Intern Med 105:900­

905. 

*Gramlich JW, Murphy TJ. 1989. Determination of trace level iodine in biological and botanical 

reference materials by isotope dilution mass spectrometry. J Res Nat Inst Stand Technol 94(4):215-220. 

Granter SR, Cibas ES. 1997. Cytologic findings in thyroid nodules after 131I treatment of 

hyperthyroidism. Am J Clin Pathol 107:20-25. 

Gray B, Galton VA. 1974. The transplacental passage of thyroxine and foetal thyroid function in the rat. 

Acta Endocrinol 75:725-733. 

Gray HW, McKillop JH, McGurk FM, et al. 1982. Carcinoma of trachea following iodine-125 therapy 

for thyrotoxicosis. Lancet 1:688. 

*Green DM, Edge SB, Penetrante RB, et al. 1995. In situ breast carcinoma after treatment during 

adolescence for thyroid cancer with radioiodine. Med Pediatr Oncol 24:82-86. 

*Green HG, Gareis FJ, Shepard TH, et al. 1971. Cretinism associated with maternal sodium iodide I 131 

therapy during pregnancy. Am J Dis Child 122:247-249. 

Green WL. 1970. Relationships between the effects of iodide, methimazole and thyrotropin on the 

intermediary metabolism of bovine thyroid slices. Endocrinology 86:708-712. 

*Green WL. 1996. Antithyroid compounds. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's 

the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 266-276. 

*Green WL, Ingbar SH. 1961. The peripheral metabolism of tri- and tetraiodothyroacetic acids in man. 

J Clin Endocrinol Metab 21:1548-1565. 

Greer MA. 1996. Thyrotoxicosis of extrathyroid origin. In: Braverman LE, Utiger RD, eds. Werner 

and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 592-594. 
IODINE 384 

9. REFERENCES 

Greig WR, Smith JFB, Gillespie FC, et al. 1969. Iodine-125 treatment for thyrotoxicosis. Lancet 1:755­

757. 

Greig WR, Smith JFB, Orr JS, et al. 1970. Comparative survivals of rat thyroid cells in vivo after 131I, 

125I and X irradiations. Br J Radiol 43:542-548. 

Gresham DG, Wool MS. 1984. Hypoparathyroidism after radioiodine therapy for Graves' disease: Is its 

incidence increasing? Postgrad Med 75(4):299-305. 

Griem ML, Malkinson FD. 1967. Some studies on the effects of radiation and radiation modifiers on 

growing hair. Radiat Res 30:431-443. 

Gross MD, Shapiro B, Sisson JC. 1999. Radioiodine therapy for thyrotoxicosis. Rays 24(2):334-347. 

Grossman CM, Nussbaum RH, Morton WE. 1996. Hypothyroidism and spontaneous abortions among 

Hanford, Washington, downwinders. Arch Environ Health 51(3):175-176. 

Grossman CM, Nussbaum RH, Nussbaum FD. 2002. Thyrotoxicosis among Hanford, Washington, 

downwinders: A community-based health survey. Arch Environ Health 57(1):9-15. 

Gruffat D, Gonzalvez S, Mauchamp J, et al. 1991. Phenol red: An inhibitor of thyroglobulin iodination 

in cultured porcine thyroid cells. Mol Cell Endocrinol 81:195-203. 

Gruffat D, Venot N, Marriq C, et al. 1992. Thyroid hormone synthesis in thyroglobulin secreted by 

porcine thyroid cells cultured on porous bottom chambers: Effect of iodide. Endocrinology 131(6):2921­

2927. 

Grumbach MM, Werner SC. 1956. Transfer of thyroid hormone across the human placenta at term. J 

Clin Endocrinol Metab 16:1392-1395. 

Grunditz T, Sundler F. 1996. Autonomic nervous control: Adrenergic, cholinergic, and peptidergic 

regulation. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and 

clinical text. Philadelphia, PA: Lippincott-Raven, 247-253. 

Grunwald F, Palmedo H, Biersack HJ. 1995. Unilateral iodine-131 uptake in the lactating breast. J Nucl 

Med 36(9):1724-1725. 

Gu Y, Ciu Y, Liu X. 1984. Changes in peripheral T and B lymphocytes of rat after intravenous injection 

of 131I. Chin Med J 97(10):773-776. 

Gumarnik S. 1988. Skin preparation and spinal headache. Anaesthesia 43(12):1057-1058. 

Gupta GS, Chopra VK. 1977. Biological damage in testis by iodine-125 in partially blocked thyriod of 

rats. Radiat Environ Biophys 14:147-152. 

Gupta GS, Chopra VK. 1980. Biological damage in spleen by iodine-125 in potassium perchlorate 

blocked thyroid of rats. Strahlentherapie 156:579-582. 

Gupta SM, Goyal PK, Dev PK. 1981. Weight changes in mice after intrauterine treatment with MPG (2­

mercaptopropionylglycine) against I131 irradiation. Experientia 37:898-899. 
IODINE 385 

9. REFERENCES 

Gutiérrez S, Carbonell E, Galofre P, et al. 1995. A cytogenetic follow-up study of thyroid cancer 

patients treated with 131I. Cancer Lett 91:199-204. 

*Gutiérrez S, Carbonell E, Galofre P, et al. 1998a. The alkaline single-cell gel electrophoresis (SCGE) 

assay applied to the anaylsis of radiation-induced DNA damage in thyroid cancer patients treated with 

131I. Mutat Res 413:111-119. 

Gutierrez S, Carbonell E, Galofre P, et al. 1998b. Application of the single cell gel electrophoresis 

(SCGE) assay to the detection of DNA damage induced by 131I treatment in hyperthyroidism patients. 

Mutagenesis 13(1):95-98. 

*Gutierrez S, Carbonell E, Galofre P, et al. 1999a. Cytogenic damage after 131-iodine treatment for 

hypothyroidism and thyroid cancer. Eur J Nucl Med 26(12):1589-1596. 

Gutierrez S, Carbonell E, Galofre P, et al. 1999b. Low sensitivity of the sister chromatid exchange assay 

to detect the genotoxic effects of radioiodine therapy. Mutagenesis 14(2):221-226. 

*Guzelian PS, Henry CJ, Olin SS, eds. 1992. Similarities and differences between children and adults: 

Implications for risk assessment. Washington, DC: International Life Sciences Institute Press. 

Haddow J, Hermos R, Mitchell M, et al. 1998. Maternal hypothyroidism and child development. Horm 

Res 50:18. 

Haffenden GP, Blenkinsopp.WK, Ring NP, et al. 1980. The potassium iodide patch test in dermatitis 

herpetiformis in relation to treatment with a gluten-free diet and dapsone. Br J Dermatol 102:313-317. 

*Hagmar L, Persson-Moschos M, Akesson B, et al. 1998. Plasma levels of selenium, selenoprotein P 

and glutathione peroxidase and their correlations to fish intake and serum levels of thyrotropin and 

thyroid hormones: A study on Latvian fish consumers. Eur J Clin Nutr 52:796-800. 

Haggard DL, Stowe HD, Conner GH, et al. 1980. Immunologic effects of experimental iodine toxicosis 

in young cattle. Am J Vet Res 41(4):539-543. 

*Hahn K, Schrell-Inderst P, Grosche B, et al. 2001. Thyroid cancer after diagnostic administration of 

iodine-131 in childhood. Radiat Res 156(1):61-70. 

Halford DK, Markham OD. 1984. Iodine-129 in waterfowl muscle from a radioactive leaching pond 

complex in southeastern Idaho. Health Phys 46(6):1259-1263. 

Hall MT. 1973. Chemical antagonism by iodine of the pharmacological activity of sympathomimetic 

amines. J Pharm Pharmacol 25(11):923-925. 

*Hall PE, Holm LE. 1996. Thyroid cancer incidence among Swedish patients exposed to diagnostic 

doses of iodine-131: A preliminary report. In: Radiodosimetry and preventative measures in the event of 

a nuclear accident. Austria: International Atomic Energy Agency, 55-63. IAEA-TECDOC-893. 

Hall PFL. 1991. Cancer risks in humans after iodine-131 exposure. Diss Abstr Int C 53-03C:458. 

Hall P, Holm L-E. 1995a. Cancer in iodine-131 exposed patients. J Endocrinol Invest 18:147-149. 
 

 

IODINE 386 

9. REFERENCES 

Hall P, Holm L-E. 1995b. Cancer incidence and mortality after iodine-131 therapy for hyperthyroidism. 

Adv Chem Ser 243:103-112. 

Hall P, Holm L-E. 1997. Late consequences of radioiodine for diagnosis and therapy in Sweden. 

Thyroid 7(2):205-208. 

*Hall P, Berg G, Bjelkengren G, et al. 1992a. Cancer mortality after iodine-131 therapy for 

hyperthyroidism. Int J Cancer 50:886-890. 

Hall P, Boice JDJ, Berg G, et al. 1992b. Leukemia incidence after iodine-131 exposure. Lancet 

340(8810):1-4. 

Hall P, Holm L-E, Lundell G, et al. 1991. Cancer risks in thyroid cancer patients. Br J Cancer 64:159­

163. 

Hall P, Holm L-E, Lundell G, et al. 1992c. Tumors after radiotherapy for thyroid cancer. Acta Oncol 

31(4):403-407. 

Hall P, Lundell G, Holm L-E. 1993. Mortality in patients treated for hyperthyroidism with iodine-131. 

Acta Endocrinol 128:230-234. 

*Hall P, Furst CJ, Mattsson A, et al. 1996a. Thyroid nodularity after diagnostic administration of iodine131. Radiat Res 146:673-682. 

*Hall P, Mattsson A, Boice JDJ. 1996b. Thyroid cancer after diagnostic administration of iodine-131. 

Radiat Res 145:86-92. 

*Hall R, Turner-Warwick M, Doniach D. 1966. Autoantibodies in iodide goitre and asthma. Clin Exp
 

Immunol 1:285-296. 

Halmi NS. 1961. Thyroidal iodide transport. Vitam Horm 19:133-163. 

Halmi NS, Gifford TH, Glesne RE. 1967. Further observations concerning the effect of actinomycin D 

on thyroidal iodide transport in rats. Endocrinology 81:893-898. 

Halmi NS, King LT, Widner RR, et al. 1958. Renal excretion of radioiodide in rats. Am J Physiol 

193:379-385. 

Halmi NS, Nissen WM, Scranton JR. 1969. The kinetics of the enhancement of thyroidal iodide 

accumulation after actinomycin D administration. Endocrinology 84:943-945. 

Halnan KE. 1958. The radioiodine uptake of the human thyroid in pregnancy. Clin Sci 17:281-290. 

Halnan KE. 1983. Risks from radioiodine treatment of thyrotoxicosis. Br Med J 287:1821-1822. 

Halnan KE. 1992. Leukemia after iodine-131 exposure [Letter]. Lancet 340:437. 

Halpern S, Alazraki N, Littenberg R, et al. 1973. 131I thyroid uptakes: Capsule versus liquid. J Nucl 

Med 14(7):507-510. 
IODINE 387 

9. REFERENCES 

Hamby DM, Benke RR. 1999. Uncertainty of the iodine-131 ingestion dose conversion factor. Radiat 

Prot Dosim 82(4):245-256. 

*Hamill GC, Jarman JA, Wynne MD. 1961. Fetal effects of radioactive iodine therapy in a pregnant 

woman with thyroid cancer. Am J Obstet Gynecol 81(3):1018-1023. 

*Hamilton TE, van Belle G, LoGerfo JP. 1987. Thyroid neoplasia in Marshall Islanders exposed to 

nuclear fallout. JAMA 258(5):629-636. 

Hampel R, Grodalla A, Zollner H, et al. 2000. Continuous rise of urinary iodine excretion and drop in 

thyroid gland size among adolescents in Mecklenburg-West-Pomerania from 1993 to 1997. Exp Clin 

Endocrinol Diabetes 108:197-201. 

*Han JS. 1992. Effects of various chemical compounds on spontaneous and hydrogen peroxide-induced 

reversion in strain TA104 of salmonella typhimurium. Mutat Res 266(2):77-84. 

Hanauer G, Schroth HJ. 1990. [Estimation of the radioiodine dose necessary for complete ablation of the 

thyroid gland in male Wistar rats.] Zentralbl Veterinarmed A 37:747-751. (German) 

*Handelsman DJ, Turtle JR. 1983. Testicular damage after radioactive iodine (I-131) therapy for thyroid 

cancer. Clin Endocrinol 18:465-472. 

Handelsman DJ, Conway AJ, Donnelly PE, et al. 1980. Azoospermia after iodine-131 treatment of 

thryoid carcinoma. Br Med J 281:1527. 

*Handl J, Pfau A. 1989. Long-term transfer of I-129 into the food chain. Sci Total Environ 85:245-252. 

*Handl J, Pfau A, Huth FW. 1990. Measurements of 129I in human and bovine thyroids in EuropeTransfer of 129I into the food chain. Health Phys 58(5):609-618. 

Hang J, Rillema JA. 1998. Possible involvement of PI3K in prolactin-stimulated milk product formation 

and iodide transport in mouse mammary explants. Proc Soc Exp Biol Med 219:154-159. 

*Hansch C, Leo A, eds. 1995. Exploring QSAR: Fundamentals and applications in chemistry and 

biology. Washington, DC: American Chemical Society. 

*Harach HR, Williams ED. 1995. Thyroid cancer and thyroiditis in the goitrous region of Salta, 

Argentina, before and after iodine prophylaxis. Clin Endocrinol 43:701-706. 

*Harach HR, Escalante DA, Onativia A, et al. 1985. Thyroid carcinoma and thyroiditis in an endemic 

goitre region before and after iodine prophylaxis. Acta Endocrinol 108:55-60. 

Harapanhalli RS, Narra VR, Yaghmai V, et al. 1994. Vitamins as radioprotectors in vivo II. Protection 

by vitamin A and soybean oil against radiation damage caused by internal radionuclides. Radiat Res 

139:115-122. 

Harden RM, Alexander WD, Chisholm CJS, et al. 1968. The salivary iodide trap in nontoxic goiter. J 

Clin Endocrinol Metab 28:117-120. 

Harden RM, Harrison MT, Alexander WD. 1963. Phosphate excretion and parathyroid function after 

radioiodine therapy and thyroidectomy. Clin Sci 25:27-36. 
IODINE 388 

9. REFERENCES 

*Harii N, Endo T, Ohmori M, et al. 1999. Extracellular adenosine increases Na+

/I- symporter gene 

expression in rat thyroid FRTL-5 cells. Mol Cell Endocrinol 157(1-2):31-39. 

Harley NH, Harley JH. 1986. Fallout inhalation [Letter]. Health Phys 50(3):422. 

Harrington RM, Shertzer HG, Bercz JP. 1985. Effects of ClO2 on the absorption and distribution of 

dietary iodide in the rat. Fundam Appl Toxicol 5:672-678. 

Harris PF, Sanchez JF, Mode DG. 1970. Iodide mumps [Letter]. JAMA 213(13):2271-2272. 

Harris SJ, Gilmore A. 1980. Penetration of protective gloves as a route of intake for tritiated water and 

125I-labeled sodium iodide solution. Phys Med Biol 25(6):1089-1094. 

*Harrison J. 1963. The fate of radioiodine applied to human skin. Health Phys 9:993-1000. 

Harrison LC, Buckley JD, Martin FIR. 1977. Use of a computer-based postal questionnaire for the 

detection of hypothyroidism following radioiodine therapy for thyrotoxicosis. Aust N Z J Med 7:27-32. 

Harrop JS, Hopton MR, Lazarus JH. 1981. Concentration of serum thyroid hormone binding proteins 

after 131I treatment of hyperthyroidism. Ann Clin Biochem 18:211-214. 

Hartman PE, Morgan RW. 1982. Nitrate/nitrite/iodide/ascorbate ingestion and gastric/esophageal cancer 

mortality. Environ Mutagen 4(3):339-340. 

Harvey RD, Metcalfe RA, Morteo C, et al. 1995. Acute pre-tibial myxodema following radioiodine 

therapy for thyrotoxic Graves' disease. Clin Endocrinol 42:657-660. 

Hasan SS, Mazumdar S, Prasad GC, et al. 1984. The effect of radioactive iodine on brain acetylcholine 

and serotonin in normal and stress subjected rats. Folia Biol 32(3):201-208. 

Hashizume K, Akasu F, Takazawa K, et al. 1976. The inhibitory effect of acute administration of excess 

iodide on the formation of adenosine 3',5'-monophosphate induced by thyrotropin in mouse thyroid lobes. 

Endocrinology 99:1463-1468. 

Hashizume K, Ichikawa K, Komiya I, et al. 1984. Thyrotropin-induced acceleration of calcium efflux 

from mouse thyroid: Evidence for inhibition by excess iodide. Endocrinology 114:1672-1677. 

*Hassan AI, Aref GH, Kassem AS. 1968. Congenital iodide-induced goitre with hypothyroidism. Arch 

Dis Child 43:702-704. 

Hauben M. 1993. Seizures after povidone-iodine mediastinal irrigation [Letter]. N Engl J Med 

328(5):355. 

Hawe P, Francis HH. 1962. Pregnancy and thyrotoxicosis. Br Med J 2:817-822. 

*Hawkes WC, Keim NL. 1995. The effect of selenium (Se) on triiodothyronine (T3) and weight changes 

in healthy men in a metabolic research unit. FASEB J 9(5):A160. 
IODINE 389 

9. REFERENCES 

Hay ID, Morris JC. 1996. Toxic adenoma and toxic multinodular goiter. In: Braverman LE, Utiger RD, 

eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: LippincottRaven, 566-572. 

Hayek A. 1978. Thyroid storm following radioiodine for thyrotoxicosis. J Pediatr 93(6):978-980. 

Hayek A, Brooks M. 1975. Neonatal hyperthyroidism following intrauterine hypothyroidism. J Pediatr 

87(3):446-448. 

Hayek A, Chapman EM, Crawford JD. 1970. Long-term results of treatment of thyrotoxicosis in 

children and adolescents with radioactive iodine. N Engl J Med 283(18):949-953. 

*Hays MT. 2001. Estimation of total body iodine content in normal young men. Thyroid 11(7):671-675. 

Hays MT. 1979. Kinetics of the human thyroid trap: Effects of iodide, thyrotropin, and propylthiouracil. 

J Nucl Med 20:944-949. 

Hays MT. 1982. Hypothyroidism following iodine-131 therapy. J Nucl Med 23(2):176-179. 

Hays MT. 1984. Compartmental models for human iodine metabolism. Math Biosci 72:317-335. 

*Hays MT. 1993. Colonic excretion of iodide in normal human subjects. Thyroid 3(1):31-35. 

*Hays MT, Solomon DH. 1965. Influence of the gastrointestinal iodide cycle on the early distribution of 

radioactive iodide in man. J Clin Invest 44:117-127. 

- Hays MT, Wesselossky B. 1973. Simultaneous measurement of thyroidal trapping (99mTcO4 and binding 

131I-

: Clinical and experimental studies in man. J Nucl Med 14(11):785-792. 

Hays MT, Carr LJ, Turrel JM. 1987. Effect of sampling site on early kinetics of blood radioiodide and 

pertechnetate. Am J Physiol 253(16):E691-E700. 

*Hays MT, Hsu L, Kohatsu S. 1992. Transport of the thyroid hormones across the feline gut wall. 

Thyroid 2:45-56. 

*HazDat. 2004. Agency of Toxic Substances and Disease Registry (ATSDR), Atlanta, GA. June 2003. 

Heath CW, Fullerton HW. 1935. The rate of absorption of iodide and glycine from the gastrointestinal 

tract in normal persons and in disease conditions. J Clin Invest 14:475-481. 

*Heaton RW, Rahn KA, Lowenthal DH. 1990. Determination of trace elements, including regional 

tracers, in Rhode Island precipitation. Atmos Environ 24A(1):147-153. 

*Hedrick WR, DiSimone RN, Keen RL. 1986. Radiation dosimetry from breast milk excretion of 

radioiodine and pertechnetate. J Nucl Med 27:1569-1571. 

Hegedus L, Perrild H, Poulsen LR, et al. 1983. The determination of thyroid volume by ultrasound and 

its relationship to body weight, age, and sex in normal subjects. J Clin Endocrinol Metab 56(2):260-263. 

Heidenreich WF, Kayro I, Jacob P, et al. 2001. Age- and sex-specific relative thyroid radiation exposure 

to 131I in Ukraine after the Chernobyl accident. Health Phys 80(3):242-250. 
IODINE 390 

9. REFERENCES 

*Heinemann K, Vogt KJ. 1980. Measurements of the deposition of iodine onto vegetation and of the 

biological half-life of iodine on vegetation. Health Phys 39:463-474. 

Held KR, Cruz ME, Moncayo F. 1990. Clinical pattern and the genetics of the fetal iodine deficiency 

disorder (endemic cretinism): Results of a field study in highland Ecuador. Am J Med Genet 35:85-90. 

Helds A, Lehrs E, Bolshevica J, et al. 1980. Function of thyroid and hypotalamic-pituitary-thyroid axis 

in radioiodine treated thyrotoxic patients. Endokrinologie 76(3):345-350. 

Hemken RW. 1980. Estimates of human iodine consumption and implications for human health. Annual 

meeting of the National Mastitis Council, Vol. 19, 81-86. 

Hempelmann LH, Hall WJ, Phillips M, et al. 1975. Neoplasms in persons treated with x-rays in infancy: 

Fourth survey in 20 years. J Natl Cancer Inst 55(3):519-530. 

Hendrich CE, Jackson WJ, Porterfield SP. 1984. Behavioral testing of progenies of Tx (hypothyroid) 

and growth hormone-treated Tx rats: An animal model for mental retardation. Neuroendocrinology 

38:429-437. 

Hengstler JG, Bockisch A, Fuchs J, et al. 1997. Increase in DNA single-strand break rejoining by 

continuous exposure of human mononuclear blood cells to radioiodine (131I) in vitro. Int J Radiat Biol 

72(5):607-613. 

Henrichs K, Mueller-Brunecker G, Paretzke HG. 1983. [Radiation exposure of the thyroid on 

incorporation of iodine isotopes: Age dependence and reliability of dose factors.] GSF-Ber S 960:1-56. 

(German) 

Henzen C, Buess M, Brander L. 1999. [Iodine-induced thyrotoxicosis)"fodbasedow"): An up-to-date 

clinical picture.] Schweiz Med Wochenschr 129(17):658-664. (German) 

*Hermus AR, Huysmans DA. 2000. The epidemiology of thyroid diseases. In: Braverman LE, Utiger 

RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 8th ed. Philadelphia, PA: 

Lippincott-Raven, 474-482. 

Hernberg S, Kurppa K, Ojajarvi J, et al. 1983. Congenital malformations and occupational exposure to 

disinfectants: A case-referent study. Scand J Work Environ Health 9:55. 

Herrera E, Escobar del Rey F, Morreale de Escobar G. 1968. Mechanism of goitrogenesis by very low 

doses of propylthiouracil and the role of iodine intake. Acta Endocrinol 59:529-544. 

Hershman JM. 1996. Trophoblastic tumors. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's 

the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 573-576. 

Hershman JM, Lee H-Y, Sugawara M, et al. 1988. Human chorionic gonadotropin stimulates iodide 

uptake, adenylate cyclase, and deoxribonucleic acid synthesis in cultured rat thyroid cells. J Clin 

Endocrinol Metab 67:74-79. 

Hetzel BS. 1994. Iodine deficiency and fetal brain damage. N Engl J Med 331(26):1770-1771. 
 

 

IODINE 391 

9. REFERENCES 

Heufelder AE, Hofbauer LC. 1996. How iodide gets access to thyrocytes: Molecular details on the 

thyroid iodide transporter. Eur J Endocrinol 135:34-36. 

Heymann WR. 2000. Potassium iodide and the Wolff-Chaikoff effect: relevance for the dermatologist. J 

Am Acad Dermatol 42(3):490-492. 

Hiasa Y, Kitahori Y, Kato Y, et al. 1987. Potassium parchlorate, potassium iodide, and propylthiouracil: 

Promoting effect on the development of thyroid tumors in rats treated with n-bis(2-hydroxypropyl)­

nitrosamine. Jpn J Cancer Res 78:1335-1440. 

Hildebrandt JD, Halmi NS. 1981. Intrathyroidally generated iodine: The role of transport in its 

utilization. Endocrinology 106(3):842-849. 

Hillman D. 1980. Chronic iodide toxicity in dairy herds. J Dairy Sci 63(Suppl 1):67-68. 

Hillman D, Curtis AR. 1980. Chronic iodine toxicity in dairy cattle: Blood chemistry, leukocytes, and 

milk iodide. J Dairy Sci 63:55-63. 

Himsworth RL. 1985. Hyperthyroidism with a low iodine uptake. Clin Endocrinol Metab 14(2):397­

415. 

Hindie E, Bourahla K, Petiet A, et al. 1997. Microscopic distribution of radioactive iodine, and sideeffects of thyroid protection in iodine-deficient new-born rats: Insights into the aftermath of the 

Chernobyl accident. J Trace Microprobe Tech 15(4):701-705. 

Hintze G, Emrich D, Richter K, et al. 1988. Effect of voluntary intake of iodinated salt on prevalence of 

goitre in children. Acta Endocrinol 117:333-338. 

Hnilica P, Langer P. 1983. Incidence of malignity in cystic nontoxic nodular goitre. Acta Endocrinol 

Suppl 252:14-15. 

Hobel M, Asmar F, Kruger FW, et al. 1967. Uber die ausscheidung von 131J- in das bronchotrachaelsekret von laboratoriums-tieren und deren beeinflussung durch pharmaka (II). Arch Int 

Pharmacodyn 168(1):116-140. 

Hodges RE, Evans TC, Bradbury JT, et al. 1955. The accumulation of radioactive iodine by human fetal 

thyroids. J Clin Endocrinol Metab 15(6):661-667. 

Hodgson-Jones IS. 1970. Clioquinol and iodine metabolism. Trans St Johns Hosp Dermatol Soc 

56(1):51-53. 

*Hoecker WH, Machta L. 1990. Meteorological modeling of radioiodine transport and deposition within 

the continental United States. Health Phys 59(5):603-617. 

*Hoel DG, Davis DL, Miller AB, et al. 1992. Trends in cancer mortality in 15 industrialized countries, 

1969-1986. J Natl Cancer Inst 84(5):313-320. 

Hofbauer LC, Rafferzeder M, Janssen OE, et al. 1995. Insulin-like growth factor I messenger 

ribonucleic acid expression in porcine thyroid follicles is regulated by throtropin and iodine. Eur J 

Endocrinol 132:605-610. 
 

 

IODINE 392 

9. REFERENCES 

Hofer KC, Keough G, Smith JM. 1977. Biological toxicity of auger emitters: Molecular fragmentation 

versus electron irradiation. Curr Top Radiat Res Q 12:335-354. 

Hofer KG, Van Loon N, Schneiderman MH, et al. 1992. The paradoxical nature of DNA damage and 

cell death induced by 125I decay. Radiat Res 130:121-124. 

Hofer KG, van Loon N, Schneiderman MH, et al. 1993. Targets for radiation-induced cell death: Target 

replication during the cell cycle evaluated in cells exposed to X-rays or 125I decays. Int J Radiat Biol 

64(2):205-216. 

Hoffman DA. 1976. Delayed effects of therapeutic levels of iodine-131 mortality experience in patients 

treated with hyper thyroidism. Radiat Res 67(3):556. 

Hoffman DA, McConahey WM. 1983. Breast cancer following iodine-131 therapy for hyperthroidism. 

J Natl Cancer Inst 70(1):63-67. 

Hoffman DA, McConahey WM, Diamong EL, et al. 1982a. Mortality in women treated for 

hyperthyroidism. Am J Epidemiol 115(2):243-254. 

Hoffman DA, McConahey WM, Fraumeni JFJ, et al. 1982b. Cancer incidence following treatment of 

hyperthyroidism. Int J Epidemiol 11(3):218-224. 

Hoffman FO. 1978. A review of measured values of the milk transfer coefficient (fm) for iodine. Health 

Phys 35(2):413-416. 

Hoffman FO, Dunning DEJ. 1979. Some uncertainties associated with parameter values and models in 

U.S. NRC regulatory guide 1. 109: Prediction of the 131I thyroid dose to children via the grass-cow-milk 

pathway [Abstract]. Health Phys 37(6):848-849. 

Hoffman L, De Luise M, Martin FIR. 1981. Falliblity of postal questionnaire follow-up for detection of 

hypothyroidism after iodine-131 therapy. Med J Aust 1:303-304. 

Hohenwald H, Ramm C. 1970. [Iodide sialadenitis and lipids in guinea pigs.] Acta Histochem Bd 

36(2):414-416. (German) 

Holbreich M. 1982. Asthma and other allergic disorders in pregnancy. Am Fam Physician 25(3):187­

192. 

*Holland JZ. 1963. Physical origin and dispersion of radioiodine. Health Physics 9:1095. 

Hollingsworth DR, Austin E. 1969. Observations following I131 for Graves disease during first trimester 

of pregnancy. South Med J 62:1555-1556. 

Hollowell JG, Hannon WH. 1997. Teratogen update: Iodine deficiency, a community teratogen. 

Teratology 55:389-405. 

*Hollowell JG, Staehling NW, Flanders WD, et al. 2002. Serum TSH, T4, and thyroid antibodies in the 

United States population (1998 to 1994): National Health and Nutrition Examination Survey (NHANES 

III). J Clin Endocrinol Metab 87(2):486-488. 
 

 

IODINE 393 

9. REFERENCES 

Holm J-E, Lundell G, Wallnder G. 1980. Incidence of malignant thyroid tumors in humans after 

exposure to diagnostic doses of iodine-131. I. Retrospective cohort study. J Natl Cancer Inst 

64(5):1055-1059. 

Holm L-E. 1980. Thyroid treatment and its possible influence on occurrence of malignant tumors after 

diagnostic 131I. Acta Radiol Oncol 19:455-459. 

Holm LE. 1982a. Carcinogenic and genetic risks of ionizing radiation with special reference to 

radioiodines. In: Thyroid disease. France: Pergamon Press, 159-186. 

Holm L-E. 1982b. Changing annual incidence of hypothyroidism after iodine-131 therapy for 

hyperthyroidism, 1951-1975. J Nucl Med 23:108-112. 

Holm LE. 1984. Malignant disease following iodine-131 therapy in Sweden. In: Boice JDJ, Fraumeni 

JFJ, eds. Radiation carcinogenesis: Epidemiology and biological significance. New York, NY: Raven 

Press, 263-271. 

Holm L-E. 1985. Thyroid cancer after exposure to radioiodine. Strahlenschutz ForschPrax 25:36-56. 

*Holm L-E. 1991. Cancer risks after diagnostic doses of 131I with special reference to thyroid cancer. 

Cancer Detect Prev 15(1):27-30. 

Holm L-E, Hall PFL. 1993. Swedish iodine-131 study. Radiat Res 133(1):134-135. 

Holm LE, Dahlqvist I, Israelsson A, et al. 1980a. Malignant thyroid tumors after iodine-131 therapy. N 

Engl J Med 303(4):188-191. 

Holm LE, Eklund G, Lundell G. 1980b. Incidence of malignant thyroid tumors in humans after exposure 

to diagnostic doses of iodine-131. II. Estimation of thyroid gland size, thyroid radiation dose, and 

predicted versus observed number of malignant thyroid tumors. J Natl Cancer Inst 63(6):1221-1224. 

*Holm L-E, Hall P, Wiklund K, et al. 1991. Cancer risk after iodine-131 therapy for hyperthyroidism. J 

Natl Cancer Inst 83:1072-1077. 

Holm L-E, Lundell G, Israelsson A, et al. 1982. Incidence of hypothyroidism occurring long after 

iodine-131 therapy for hyperthyroidism. J Nucl Med 23:103-107. 

Holm LE, Lundell G, Walinder G. 1980c. Incidence of malignant thyroid tumors in humans after 

exposure to diagnositc doses of iodine-131. I. Retrospective cohort study. J Natl Cancer Inst 

64(5):1055-1059. 

Holm L-E, Wiklund KE, Lundell GE, et al. 1988. Thyroid cancer after diagnostic doses of iodine-131: 

A retrospective cohort study. J Natl Cancer Inst 80:1132-1138. 

*Holm L-E, Wiklund DE, Lundell GE, et al. 1989. Cancer risk in population examined with diagnostic 

doses of 131I. J Natl Cancer Inst 81:302-306. 

Hooper PL, Turner JR, Conway MJ, et al. 1980. Thyroid uptake of 123I in a normal population. Arch 

Intern Med 140:757-758. 

*Horn B, Kabins SA. 1972. Iodide fever. Am J Med Sci 264(6):467-471. 
IODINE 394 

9. REFERENCES 

*Horn-Ross PL, Morris JS, Lee M, et al. 2001. Iodine and thyroid cancer risk among women in a 

multiethnic population: the Bay Area Thyroid Cancer Study. Cancer Epidemiol Biomarkers Prev 

10(9):979-985. 

Hoshi M, Takada J, Oka T, et al. 1996. A possible explanation for the DS86 discrepancy between the 

data and calculation in Hiroshima. In: Nagataki S, Yamashita S, eds. Nagasaki symposium radiation and 

human health: Proposal from Nagasaki. Amsterdam, The Netherlands: Elsevier, 175-191. 

Hoshi M, Yamamoto M, Kawamura H, et al. 1994. Fallout radioactivity in soil and food samples in the 

Ukraine: Measurements of iodine, plutonium, cesium, and strontium isotopes. Health Phys 67(2):187­

191. 

Hoskin PJ, Spathis GS, McCready VR, et al. 1985. Low-dose radiation given six-monthly in Graves' 

disease. J R Soc Med 78:893-898. 

*Hou X, Chai C, Qian Q, et al. 1997a. The study of iodine in Chinese total diets. Sci Total Environ 

193:161-167. 

*Hou X, Chai X, Qian Q, et al. 1997b. Determination of bromine and iodine in normal tissues from 

Beijing health adults. Biol Trace Elem Res 56:225-230. 

*Hou X, Dahlgaard H, Rietz B, et al. 1999. Determination of chemical species of iodine in seawater by 

radiochemical neutron activation analysis combined with ion-exchange preseparation. Anal Chem 

71:2745-2750. 

Houssay AB, Gamper GH, Arias NH, et al. 1978. Effects of indomethacin upon 131I uptake by thyroid 

and submaxillary glands in mice. J Dent Res 57(1):83-86. 

*Howard JE, Vaswani A, Heotis P. 1997. Thyroid disease among the Rongelap and Utirik population-an 

update. Health Phys 73(1):190-198. 

Howarth DM, Epstein MT, Thomas PA, et al. 1997. Outpatient management of patients with large 

multinodular goitres treated with fractionated radioiodine. Eur J Nucl Med 24(12):1465-1469. 

*Howe JR. Bowlt C. 1991. A rapid method for estimating iodine-125 in water samples using x-ray 

fluorescence for yield correction. J radioanal Nucl Chem 152:347-357. 

*HSDB. 2000. Hazardous Substances Data Bank. National Library of Medicine, National Toxicology 

Program, Bethesda, MD. July 2000. 

*HSDB. 2001. Hazardous Substances Data Bank. National Library of Medicine, National Toxicology 

Program, Bethesda, MD. July 2001. 

*Huang W, Kukes, GD. 1999. Hashimoto’s thyroiditis: An organ-specific autoimmune disease - 

pathogenesis and recent developments. Lab. Invest. 79(10): 1175-1180. 

*Huang T-S, Lu F-J. 1991. Iodide binding by humic acid. Environ Toxicol Chem 10:179-184. 

Hughes WL, Weinblatt AC, Prensky W. 1977. Chromosome damage in Chinese hamster cells produced 

by 125I-UdR at the site of its incorporation. Curr Top Radiat Res Q 12:453-471. 
 

 

IODINE 395 

9. REFERENCES 

Hugo AC, Pisarev MA, Juvenal GJ, et al. 1990. Further studies on iodide uptake autoregulation in calf 

thyroid slices. 40:149-154. 

Hunermann B. 1976. [Iodine-131 treatment of hyperthyroidism.] Therapiewoche 26(2):129-133. 

(German) 

Hurley JR. 1994. Orbitopathy after treatment of Graves' disease. J Nucl Med 35(5):918-920. 

Hurley LS. 1980. Trace elements I: Iron, copper, iodine. In: Developmental nutrition. Englewood 

Cliffs, NJ: Prentice-Hall, 183-197. 

Hurrell RF. 1997. Bioavailability of iodine. Eur J Clin Nutr 51(Suppl 1):S9-S12. 

*Hutchings PR, Verma S, Phillips JM, et al. 1999. Both CD4(+) T cells and CD8(+) T cells are required 

for iodine accelerated thyroiditis in NOD mice. Cell Immunol 192(2):113-121. 

Huysmans DAKC, Buijs WCAM, van de Ven MTP, et al. 1996. Dosimetry and risk estimates of 

radioiodine therapy for large, multinodular goiters. J Nucl Med 37(12):2072-2079. 

*Huysmans DAKC, Hermus ARMM, Edelbroek MAL, et al. 1997a. Autoimmune hyperthyroidism 

occurring late after radioiodine treatment for volume reduction of large multinodular goiters. Thyroid 

7(4):535-539. 

Huysmans D, Hermus A, Edelbroek M, et al. 1997b. Radioiodine for nontoxic multinodular goiter. 

Thyroid 7(2):235-239. 

*IAEA. 1962. Whole-body counting. International Atomic Energy Agency. Vienna: IAEA Publication 

No. STI/PUB/47. 

*IAEA. 1970. Directory of whole-body radioactivity monitors. International Atomic Energy Agency. 

Vienna: IAEA Publication No. STI/PUB/213. 

*IAEA. 1972. Assessment of radioactive contamination in man. International Atomic Energy Agency. 

Vienna: IAEA Publication No. STI/PUB/290. 

*IAEA. 1976. Diagnosis and treatment of incorporated radionuclides. International Atomic Energy 

Agency. Vienna: IAEA Publication No. STI/PUB/411. 

*IAEA. 1985. Assessment of radioactive contamination in man. International Atomic Energy Agency. 

Vienna: IAEA Publication No. STI/PUB/674. 

*IAEA. 1988. The radiological accident in Goiania. International Atomic Energy Agency. Vienna: 

IAEA Publication No. STI/PUB/815. 

IAEA. 1989. Measurement of radionuclides in food and the environment. International Atomic Energy 

Agency. Vienna: IAEA Publication No. STI/DOC/10/295. 

*IAEA. 1991. The international Chernobyl project. Technical Report. Assessment of radiological 

consequences and evaluation of protective measures. International Atomic Energy Agency. Vienna. 
 

 

 

IODINE 396 

9. REFERENCES 

*Iancu T, Boyanower Y, Laurian N. 1974. Congenital goiter due to maternal ingestion of iodide. Am J 

Dis Child 128:528-530. 

IARC. 1977. IARC monographs on the evaluation of the carcinogenic risk of chemicals to man: Some 

fumigants, the herbicides 2,5-D and 2,4,5-T, chlorinated dibenzodioxins and miscellaneous industrial 

chemicals. Lyon, France: International Agency for Research on Cancer. 

Ichikawa R. 1978. A comment on the paper "Thyroidal burdens of 129I from various dietary sources" by 

S.A. Book et al. Health Phys 34:277-278. 

*ICRP. 1979. Limits for intakes of radionuclides by workers. ICRP Publication 30, Part 1. International 

Commission on Radiological Protection. Pergamon Press, Oxford, 88-90. 

*ICRP. 1981. Report of the task group on reference man. The International Commission on 

Radiological Protection. Pergamon Press. IRCP Publ No. 23. 

*ICRP. 1988. Radiation dose to patients from radiopharmaceuticals. International Commission on 

Radiological Protection. Pergamon Press, Oxford. ICRP publ No. 53, 259-277. 

*ICRP. 1989. Age-dependent doses to members of the public from intake of radionuclides: Part 1. 

International Commission on Radiological Protection. Pergamon Press, Oxford. P.45-51. 

*ICRP. 1991. 1990 Recommendations of the International Commission on Radiological Protection, 

ICRP Publication 60. Oxford: Pergamon Press, 46. 

*ICRP. 1993. Age dependent doses to members of the public from intake of radionuclides: Part 2 

ingestion dose coefficients. International Commission on Radiological Protection. Annals of the ICRP. 

Vol. 23(3/4). ICRP publication 67. 

*ICRP. 1994a. Dose coefficients for intakes of radionuclides by workers. International Commission on 

Radiological Protection. Annals of the ICRP. Vol. 24(4). ICRP publication 68. 

*ICRP. 1994b. Human respiratory tract model for radiological protection. International Commission on 

Radiological Protection. Pergamon Press, Oxford. 

*ICRP. 1995. Age-dependent doses to members of the public from intake of radionuclides: Part 4. 

Inhalation dose coefficients. International Commission on Radiological Protection. Pergamon Press, 

Oxford, 195-232. 

*ICRP. 1996. Age-dependent doses to members of the public from intake of radionuclides: Part 5. 

Compilation of ingestion and inhalation dose coefficients. Ann ICRP 26(1):60-61. 

*ICRP. 2001. The ICRP database of dose coefficients: Workers and members of the public. Version 

2.01. Elsevier Science Ltd. International Commission on Radiological Protection. 

Idee JM, Beaufils H, Bonnemain B. 1994. Iodinated contrast media-induced nephropathy: 

Pathophysiology, clinical aspects and prevention. Fundam Clin Pharmacol 8:193-206. 

*IEA 2000. Key world energy statistics from the IEA, 2000 Web edition 

(http://www.iea.org/statist/index.htm. International Energy Agency, Paris, France. 
IODINE 397 

9. REFERENCES 

*Iff HW, Wilbrandt W. 1963. [The dependency of iodine accumulation in thyroid slices on the ional 

composition of the incubation medium; influence of heart glycosides.] Biochim Biophys Acta 70:711­

752. (German) 

Igumnov S, Drozdovitch V. 2000. The intellectual development, mental and behavioural disorders in 

children from Belarus exposed in utero following the Chernobyl accident. Eur Psychiatry 15(4):244-253. 

*Iiyin LA, Balonov MI, Buldakov LA, et al. 1990. Radiocontamination patterns and possible health 

consequences of the accidents at the Chernobyl nuclear power station. J Radiol Prot 10(13):3-29. 

Ilundain A, Larralde J, Toval M. 1987. Iodide transport in rat small intestine: Dependence on calcium. 

J Physiol 393:19-27. 

Ingbar DH. 1996a. The respiratory system in hypothyroidism. In: Braverman LE, Utiger RD, eds. 

Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 

805-810. 

Ingbar DH. 1996b. The respiratory system in thyrotoxicosis. In: Braverman LE, Utiger RD, eds. 

Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 

616-627. 

Inman P. 1974. Iododerma. Br J Dermatol 91(6):709-711. 

*International Isotopes. 2001. International Isotopes Inc achieves beam in CP-42 MeV accelerator. 

http://www.nuclear-medicine.com. May 22, 2001. 

*IRIS. 2001. Integrated Risk Information System. U.S. Environmental Protection Agency. 

http://www.epa.gov/iris/subst/index.htm. 

Isaacs GH, Rosenberg IN. 1967. Effect of thyrotropin on thyroid clearance of iodide and pertechnetate: 

Comparative observations at normal and high plasma iodide concentrations. Endocrinology 81:981-992. 

*Ishigaki K, Namba H, Takamura N. 2001. Urinary iodine levels and thyroid diseases in children; 

comparison between Nagasaki and Chernobyl. Endocr J (Tokyo) 48(5):591-595. 

Ishikawa M, Izawa G, Omori T, et al. 1985. Application of proton induced x-ray emission to the 

qualitative and quantitative analysis of iodine in biological samples. J Radioanal Nucl Chem 91(1):163­

171. 

Ishizuki Y, Hirooka Y, Tanigawa S, et al. 1996. Confirmation of the safety of iodine-overloaded women 

during lactation. Nippon Naibunpi Gakkai Zasshi 72(3):523-532. 

Isozaki O, Emoto N, Tsushima T, et al. 1992. Opposite regulation of deoxyribonucleic acid synthesis 

and iodide uptake in rat thyroid cells by basic fibroblast growth factor: Correlation with opposite 

regulation of c- fos and thyrotropin receptor gene expression. Endocrinology 131(6):2723-2732. 

Itikawa A, Kawada J, Ito Y. 1967. Iodide goiter in the mouse. Endocrinol Jpn 14(4):333-341. 

Ito K. 1999. Semi-micro ion chromatography of iodide in seawater. J Chromatogr 830:211-217. 
 

 

IODINE 398 

9. REFERENCES 

Ito K, Tsuchiya T, Sugino K, et al. 1996. [An evaluation of the incidence of hyperparathyroidism after 

131I treatment for Basedow disease (Part II).] Kaku Igaku 33(7):737-742. (Japanese) 

Ivanov VK, Gorsky AI, Tsyb AF, et al. 1999. Dynamics of thyroid cancer incidence in Russia following 

the Chernobyl accident. J Radiol Prot 19(4):305-318. 

Ivanov VK, Tsyb AF. 1996. Chernobyl radiation risks: Assessments of morbidity, mortality and 

disability rates according to the data of the National Radiation and Epidemiological Registry, 1995. In: 

Nagataki S, Yamashita S, eds. Nagasaki symposium radiation and human health: Proposal from 

Nagasaki. Amsterdam, the Netherlands: Elsevier, 31-42. 

Izembart M, Chavaudra J, Aubert B, et al. 1992. Retrospective evaluation of the dose received by the 

ovary after radioactive iodine therapy for thyroid cancer. Eur J Nucl Med 19:243-247. 

Jackson GL, Flickinger FW, Graham WP, et al. 1979. Thymus accumulation of radioactive iodine. Pa 

Med 82(11):37-38. 

Jackson HJ, Sutherland RM. 1981. Effect of povidone-iodine on neonatal thyroid function [Letter]. 

Lancet 2(8253):992. 

*Jacob P, Goulko G, Heidenreich WF, et al. 1998. Thyroid cancer risk to children calculated. Nature 

392(6671):31-32. 

*Jacobson AP, Plato PA, Toeroek D. 1978. Contamination of the home environment by patients treated 

with iodine-131: Initial results. Am J Public Health 68(3):225-230. 

Jacobson JM, Hankins GV, Murray JM, et al. 1981. Self-limited hyperthyroidism following intravaginal 

iodine administration. Am J Obstet Gynecol 140(4):472-473. 

*Jacobson JM, Hankins GV, Young RL, et al. 1984. Changes in thyroid function and serum iodine 

levels after prepartum use of a povidone-iodine vaginal lubricant. J Reprod Med 29(2):98-100. 

*Jafek BW, Small R, Lillian DL. 1974. Congenital radioactive iodine-induced stridor and 

hypothroidism. Arch Otolaryngol 99:369-371. 

Jagetia GC, Gupta SM, Kumar S, et al. 1982. Response of peripheral blood to 131I treatment by Swiss 

albino mice. Radiobiol Radiother 23:187-190. 

*Jahreis G, Hausmann W, Kiessling G, et al. 2001. Bioavailability of iodine from normal diets rich in 

dairy products-results of balance studies in women. Exp Clin Endocrinol Diabetes 109(3):163-167. 

Jahreis G, Hesse V, Plenert W, et al. 1985. Influence of phytogenic substances with thyreostatic effects 

in combination with iodine on the thyroid hormones and somatomedin level in pigs. Exp Clin Endocrinol 

85(2):183-190. 

Jambut-Absil AC, Buxeraud J, Lagorce JF, et al. 1987. Charge transfer complexes of drugs with iodine 

investigation by UV/visible spectroscopy. Int J Pharm 35:129-137. 

James RA 1964. Calculation of radioactive iodine concentrations in milk and human thyroid as a result 

of nuclear explosions. Lawrence Radiation Laboratory, University of California at Livermore. 

Livermore, California. UCRL-7716. 
 

 

IODINE 399 

9. REFERENCES 

Jay K, Stieglitz L. 1995. Identification and quantification of volatile organic components in emissions of 

waste incineration plants. Chemosphere 30(7):1249-1260. 

Jefferies AL, Coates G, Webber CE, et al. 1984. Measurement of pulmonary clearance of radioaerosol 

using a portable sodium iodide probe. J Appl Physiol 57(6):1908-1912. 

Jelovsek FR, Mattison DR, Chen JJ. 1989. Prediction of risk for human developmental toxicity: How 

important are animal studies for hazard identification? Obstet Gynecol 74:624-636. 

Jendrasiak GL, Estep TN. 1977. The inhibition of iodide uptake in the thyroid gland by the fluorescent 

dye, ANS. Life Sci 21:149-158. 

Jenkins KJ, Hidiroglou M. 1990. Effects of elevated iodine in milk replacer on calf performance. J 

Dairy Sci 73:804-807. 

Jensen RH, Reynolds JC, Robbins J, et al. 1997. Glycophorin A as a biological dosimeter for radiation 

dose to the bone marrow from iodine-131. Radiat Res 147:747-752. 

*Jialal I, Pillay NL, Asmal AC. 1980. Radio-iodine-induced hypoparathyroidism. S Afr Med J 58:939­

940. 

*Jirousek L, Pritchard ET. 1971. On the chemical iodination of tyrosine with protein sulfenyl iodide and 

sulfenyl periodide derivatives: The behavior of thiol protein-iodine systems. Biochemica Biophysica 

Acta 243:230-238. 

Jirousek L, Soodak M. 1974. Studies of positive iodine compounds as models of the thyroidal "active 

iodine": Reaction of N-iodosuccinimide and of N-iodophtalimide with thiocarbamide goitrogens. J 

Pharmacol Exp Ther 191(2):341-348. 

Joesfsson M, Grunditz T, Ohlsson T, et al. 2002. Sodium/iodide-symporter: Distribution in different 

mammals and role in entero-thyroid circulation of iodide. Acta Physiol Scand 175(2):129-137. 

*Johanson CE. 1980. Permeability and vascularity of the developing brain: Cerebellum vs cerebral 

cortex. Brain Res 190:3-16. 

Johansson H, Nylander G. 1968. Effect of iodine and thyroxine on the thyroid in thiouracil-treated rats. 

Acta Soc Med Ups 74:151-160. 

*John W, Kaifer R, Rahn K, et al. 1973. Trace element concentrations in aerosols from the San 

Francisco bay area. Atmos Environ 7:107-118. 

Johnson CE, Cohen IA. 1988. Theophylline toxicity after iodine 131 treatment for hyperthyroidism. 

Clin Pharm 7:620-622. 

Johnson JK. 1993. Outcome of treating thyrotoxic patients with a standard dose of radioactive iodine. 

Scott Med J 38:142-144. 

Johnson JR. 1978. Summary of bioassay and thyroid monitoring results following an accidental 

exposure to 125I. Health Phys 34:106-107. 
 

 

IODINE 400 

9. REFERENCES 

*Johnson JR. 1982. Fetal thyroid dose from intakes of radioiodine by the mother. Health Phys 

43(4):573-582. 

*Johnson JR. 1986. A review of age dependent radioiodine dosimetry. In: Gerber, GB, Metivier H, 

Smith H, eds. Workshop on age, related factors in radionuclide metabolism and dosimetry. Angers, 

France, 249-260. 

Johnson JR, Lamothe ES. 1987. Dose to the basal layer of the skin grom 125I skin contamination. Radiat 

Prot Dosim 20(4):253-256. 

Johnson TM, Rapini RP. 1988. The Wolff-Chaikoff effect: Hypothyroidism due to potassium iodide 

[Letter]. Arch Dermatol 124:1184-1185. 

Jonadet M, Chopineau J, Bastide P. 1982. [Optotoxic effects of sodium iodate on several enzymatic 

activities of the retina (glycolysis, Krebs cycle, pentose cycle.] Ann Pharm Fr 40(3):281-289. (French) 

Jonckheer MH, Velkeniers B, Vanhaelst L, et al. 1992. Further characterization of iodide-induced 

hyperthyroidism based on the direct measurement of intrathyroidal iodine stores. Nucl Med Commun 

13:114-118. 

Jones AR, Edwards K. 1973. Alkylating esters VII. The metabolism of iso-propyl methanesulphonate 

and iso-propyl iodide in the rat. Experientia 29(5):538-539. 

*Jones RE, Aulerich RJ, Ringer RK. 1982a. Feeding supplemental iodine to mink: Reproductive and 

histopathologic effects. J Toxicol Environ Health 10:459-471. 

*Jones SD, Spencer CP, Truesdale VW. 1982b. Determination of total iodine and iodate-iodine in 

natural freshwater. Analyst 107:1417-1424. 

*Jönsson H, Mattsson S. 1998. Thyroid burdens of 125I in hospital laboratory workers during a 20-y 

period. Health Phys 75(5):475-478. 

Jooste PL, Weight MJ, Lombard CJ. 2000. Short-term effectiveness of mandatory iodization of table 

salt, at an elevated iodine concentration, on the iodine and goiter status of schoolchildren with endemic 

goiter. Am J Clin Nutr 71(1):75-80. 

Jorgensen JV, Brandrup F, Schroll M. 1973. Possible synergism between iodine and lithium carbonate. 

JAMA 223(2):192-193. 

Joseph K, Mahlstedt J, Welcke U. 1980. [Early recognition of autonomous thyroid tissue by a 

combination of quantitative thyroid pertechnetate scintigraphy with the free T4 equivalent.] 

Nuklearmedizin 19(2):54-63. (German) 

Joshi P. 1989. A complication of povidone-iodine. Anaesthesia 44(8):692. 

Jost DT, Gaggeler HW, Baltensperger U, et al. 1986. Chernobyl fallout in size-fractionated aerosol 

[Letter]. Nature 324(6092):22-23. 

Joyce WT, Cowan RJ. 1995. A potential false-positive posttherapy radioiodine scan secondary to I-131 

excretion in perspiration. Clin Nucl Med 20:368-369. 
IODINE 401 

9. REFERENCES 

*Jubiz W, Carlile S, Lagerquist LD. 1977. Serum thyrotropin and thyroid hormone levels in humans 

receiving chronic potassium iodide. J Clin Endocrinol Metab 44:379-382. 

Juhasz F, Stenszky V, Bartha I, et al. 1983. A complex clinical and genetic analysis of patients with 

medullary thyroid carcinoma. Acta Endocrinol Suppl 252:16-17. 

Juvenal GJ, Pregliasco LB, Krawiec L, et al. 1997. Long-term effect of norepinephrine on iodide uptake 

in FRTL-5 cells. Thyroid 7(5):795-800. 

*Kada T. 1970. Radio-sensitization with iodine compounds: II. Studies on mutant strains of 

Escherichia coli K12 resistant to radiation-induced toxic products from iodoacetic acid, potassium iodide 

or potassium iodate. Int J Radiat Biol 17(5):419-430. 

*Kada T, Noguti T, Namiki M. 1970. Radio-sensitization with iodine compounds: I. Examination of 

damage in deoxyribonucleic acid with Bacillus subtilis transformation system by irradiation in the 

presence of potassium iodide. Int J Radiat Biol 17(5):407-418. 

Kader A, Ahmad S, El-Gendy AE, et al. 1994. Spectrophotometric studies on molecular interactions I. 

Complexation of iodine with polyvinylpyrrolidone polymer and with the monomer n-methyl-2­

pyrrolidone. Bull Fac Pharm (Cairo Univ) 32(1):17-23. 

Kagan RJ, Miller RW, Wagner WM. 1976. Radioiodine breathing zone monitor efficiency as a function 

of radioiodine concentration and sampling rate. Health Phys 31(6):555-556. 

*Kahaly G, Dienes HP, Beyer J, et al. 1997. Randomized, double blind, placebo-controlled trial of low 

dose iodide in endemic goiter. J Clin Endocrinol Metab 82(12):4049-4053. 

*Kahaly GJ, Dienes HP, Beyer J, et al. 1998. Iodide induced thyroid autoimmunity in patients with 

endemic goitre: A randomised, double-blind, placebo-controlled trial. Eur J Endocrinol 139:290-297. 

Kalaria VG, Porsche R, Ong LS. 2001. Iodine mumps: Acute sialadenitis after contrast administration 

for angioplasty. Circulation 104(19):2384. 

Kalk WJ, Durbach D, Kantor S, et al. 1980. Very low doses of radio-iodine for hyperthyroidism: 

Failure to prevent a high incidence of early hypothyroidism. S Afr Med J 57:479-482. 

Kanda T, Ghidoni JJ. 1970. Light and electron microscopic observations on iodide-induced sialoadenitis 

of hamster submaxillary glands. Laryngoscope 80(3):455-466. 

Kang Z, Zhou Q, Liu S. 1995. [The early development of hypothyroidism after 131I treatment for 

hyperthyroid Graves' disease.] Zhonghua Heyixue Zazhi 15(1):26-28. (Chinese) 

Kanno J, Onodera H, Furuta K, et al. 1992. Tumor-promoting effects of both iodine deficiency and 

iodine excess in the rat thyroid. Toxicol Pathol 20(2):226-235. 

Kapitola J, Kuechel O, Schreiberova O, et al. 1968. Decreased thyroid radioiodine uptake after 

diazoxide in rats. Experientia 24(1):50-51. 

Kapitola J, Schullerova M, Schreiberova O. 1970. Blood flow and radioiodine uptake in the thyroid 

gland of rats after administration and discontinuation of methylthiouracil. Acta Endocrinol 65:435-441. 
IODINE 402 

9. REFERENCES 

*Kaplan DI, Serne RJ, Parker KE, et al. 2000. Iodide sorption to subscribe sediments and illitic 

minerals. Environ Sci Technol 34:399-405. 

Kaplan MM, Garnick MB, Gelber R, et al. 1983. Risk factors for thyroid abnormalities after neck 

irradiation for childhood cancer. Am J Med 74:272-280. 

Kaplan MM, Meier DA, Dworkin HJ. 1998. Treatment of hyperthyroidism with radioactive iodine. 

Endocrinol Metab Clin North Am 27(1):205-223. 

Kapuscinski W, Bacin F, Kantelip B, et al. 1979. [Experimental retinopathy induced by sodium iodate: 

Comparison with human retinitis pigmentosa.] Bull Soc Ophtalmol Fr 79(3):231-238. (French) 

Kargacin B, Kostial K. 1985. Reduction of 85Sr, 137Cs, 131I and 141Ce retention in rats by simultaneous 

oral administration of calcium alginate, ferrihexacyanoferrate(II), KI and Zn-DTPA. Health Phys 49:858­

864. 

Karlan MS, Pollock WF, Snyder WH. 1964. Carcinoma of the thyroid following treatment of 

hyperthyroidism with radioactive iodine. Calif Med 101(3):196-199. 

Kasatkina EP, Shilin DE, Matkovskaya AN, et al. 1995. [Radiation-induced pathomorphism of endemic 

goiter in children and adolescents in a focus of iodine deficiency (initial manifestations of remote effects 

of the Chernobyl accident).] Probl Endokrinol (Mosk) 41(3):17-23. (Russian) 

Kassis AI, Fayad F, Kinsey BM, et al. 1987a. Radiotoxicity of 125I in mammalian cells. Radiat Res 

111:305-318. 

Kassis AI, Sastry KSR, Adelstein SJ. 1987b. Kinetics of uptake, retention, and radiotoxicity of 125IUdR 

in mammalian cells: Implications of localized energy deposition by auger processes. Radiat Res 109:78­

89. 

Katagiri K, Shimizue T, Akatsu Y, et al. 1997. Study on the behavior of 129I in the terrestrial 

environment. J Radioanal Nucl Chem 226(1-2):23-27. 

*Katayama Y, Widdicombe JH. 1991. Halide transport in xenopus oocytes. J Physiol 443:587-599. 

Kato GT (1981): A comparison study between I-123 and I-131 in thyroid uptakes in adults. Master of 

Science in Medical Physics Thesis, University of California, Los Angeles, p. 38. 

Kaul A, Roedler HD. 1980. Radioiodine: Biokinetics, mean dose and dose distribution. Radiat Environ 

Biophys 18:185-195. 

*Kaurin DGL, Carsten AL, Baum JW. 2000. Effective half-lives for patients administered radiolabeled 

antibodies and calculated dose to the public in close proximity to patients. Health Phys 78(2):215-221. 

*Kay C, Abrahams S, McClain P. 1966. The weight of normal thyroid glands in children. Arch Pathol 

82:349-352. 

Kay TWH, Heyma P, Harrison LC, et al. 1987. Graves disease induced by radioactive iodine. Ann 

Intern Med 107(6):857-858. 
 

 

IODINE 403 

9. REFERENCES 

*Kearns JE, Philipsborn HF. 1962. Values for thyroid uptake of I131 and protein-bound iodine in 

"normal" individuals from birth to twenty years. Q Bull Northwest Univ Med Sch 36:47-50. 

Keating FR, Albert A. 1949. The metabolism of iodine in man as disclosed with the use of radioiodine. 

Recent Prog Horm Res IV:429-481. 

Keith RL, McGuinness SJ, Gandolfi AJ, et al. 1995. Interaction of metals during their uptake and 

accumulation in rabbit renal cortical slices. Environ Health Perspect Suppl 103(1):77-80. 

Keldsen N, Mortensen BT, Hansen HS. 1990. Hematological effects from radioiodine treatment of 

thyroid carcinoma. Acta Oncol 29:1035-1039. 

Kellen JA. 1973. Induction of rat mammary tumours in altered iodine metabolism. Oncology 28:269­

273. 

Kelly GN. 1977. Global circulation of iodine 129. In:, ed. Iodine 129: Proceedings of an NEA 

specialist meeting. Paris, France: Organisation for Economic Co-Operation and Development, 40-42. 

Kemp WN. 1939. Iodine deficiency in relation to the stillbirth problem. Can Med Assoc J 41:356-361. 

Kendall-Taylor P, Keir MJ, Ross WM. 1984. Ablative radioiodine therapy for hyperthyroidism: Long 

term follow up study. Br Med J 289:361-363. 

Kennedy JS, Thomson JA. 1974. The changes in the thyroid gland after irradiation with 131I or partial 

thyroidectomy for thyrotoxicosis. J Pathol 112:65-81. 

Kennish MJ. 1998. Trace metal-sediment dynamics in estuaries: Pollution assessment. Rev Environ 

Contam Toxicol 155:69-110. 

*Kerber RA, Till JE, Simon SL, et al. 1993. A cohort study of thyroid disease in relation to fallout from 

nuclear weapons testing. JAMA 270:2076-2082. 

*Kereiakes JG, Wellman HN, Simmons G, et al. 1972. Radiopharmaceutical dosimetry in pediatrics. 

Semin Nucl Med 2(4):316-327. 

*Kerl W, Becker JS, Dietze H-J, et al. 1996. Determination of iodine using a special sample introduction 

system coupled to a double-focusing sector field inductively coupled plasma mass spectrometer. J Anal 

Atom Spectrom 11:723-726. 

*Kessler FK, Laskin DL, Borzelleca JF, et al. 1980. Assessment of somatogenotoxicity of povidoneiodine using two in vitro assays. J Environ Pathol Toxicol 4(2-3):327-335. 

*Khan F, Einbinder JM, Seriff NS. 1973. Suppurative ulcerating iododerma-a rare manifestation of 

inorganic iodide hypersensitivity. N Engl J Med 289:1018-1020. 

*Khan LK, Ruowel LI, Gootnick D, et al. 1998. Thyroid abnormalities related to iodine excess from 

water purification units. Lancet 352:1519. 

Khanna CM, Jain SK, Walia RP. 1994. Thyrotoxicosis-treatment by 131I therapy and early prediction of 

hypothyroidism following this therapy. J Assoc Physicians India 42(1):36-38. 
 

 

IODINE 404 

9. REFERENCES 

*Kidd PS, Trowbridge FL, Goldsby JB, et al. 1974. Sources of dietary iodine. Journal of the American 

Dietary Association 65:420-422. 

Kilbane MT, Ajjan RA, Weetman AP, et al. 2000. Tissue iodine content and serum-mediated 125I 

uptake-blocking activity in breast cancer. J Clin Endocrinol Metab 85(3):1245-1250. 

*Killough GG, Eckerman KF. 1986. Age- and sex-specific estimation of dose to a normal thyroid from 

clinicacal adminstration of iodine-131. Oak Ridge, Tennessee: Oak Ridge National Laboratory, 1-29. 

*Kim WS, McGlothlin JD, Kupel RE. 1981. Sampling and analysis of iodine in the industrial 

atmosphere. Am Ind Hyg Assoc J 42(3):187-190. 

*Kimura S, Kotani T, McBride OW et al. 1987. Human thyroid peroxidase: Complete cDNA and 

protein sequence, chromosome mapping and identification of two alternately spliced mRNAs. Proc Natl 

Acad Sci USA 84:5555-5559. 

*Kincaid MC, Green WR, Hoover RE, et al. 1981. Iododerma of the conjunctiva and skin. 

Ophthalmology 88:1216-1220. 

*Kint A, Van Herpe L. 1977. Iododerma. Dermatologica 155(3):171-173. 

Kinuya S, Hwang E-H, Ikeda E, et al. 1997. Mallory-Weiss syndrome caused by iodine-131 therapy for 

metastatic thyroid carcinoma. J Nucl Med 38(11):1831. 

*Kirchner G. 1994. Transport of iodine and cesium via the grass-cow-milk pathway after the Chernobyl 

accident. Health Phys 66(6):653-665. 

*Kiviniitty K, Nasman P, Leppaluoto J. 1984. Accumulation of 125I in the thyroid glands of laboratory 

workers. Health Phys 46(1):234-236. 

*Klebanoff SJ, Green WL. 1973. Degradation of thyroid hormones by phagocytosing human leukocytes. 

J Clin Invest 52:60-72. 

Kleiman de Pisarev DL, Pisarev MA, Juvenal GJ. 1978. Action of KI and several iodocompounds on 

[

3

H]uridine incorporation into thyroid RNA. Acta Endocrinol 89:316-322. 

Klein E. 1972. [Thyroid hormones following iodine isotope therapy.] Dtsch Med Wochenschr 97:42. 

(German) 

Klein I, Levey GS. 1983. Iodide excess and thyroid function. Ann Intern Med 98(3):406-407. 

Klein I, Levey GS. 1996. The cardiovascular system in thyrotoxicosis. In: Braverman LE, Utiger RD, 

eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: LippincottRaven, 607-615. 

Klein I, Ojamaa K. 1996. The cardiovascular system in hypothyroidism. In: Braverman LE, Utiger RD, 

eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: LippincottRaven, 799-804. 
IODINE 405 

9. REFERENCES 

Klein RZ, Mitchell ML. 1996. Hypothyroidism in infants and children. In: Braverman LE, Utiger RD, 

eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: LippincottRaven, 984-988. 

Klett M, Ohlig M, Manz F, et al. 1999. Effect of iodine supply on neonatal thyroid volume and TSH. 

Acta Paediatr Suppl 432:18-20. 

Klett M, Ohlig M, Troger F, et al. 2001. Newborn thyroid volume reflects maternal iodine supply and 

smoking habit. Pediatr Res 49(2):300. 

Klonecke A, Peterson MM, McDougall IR. 1990. Thyrotoxicosis with low thyroidal uptake of 

radioiodine. Semin Nucl Med XX(4):364-366. 

Knudsen N, Bulow I, Jorgensen T, et al. 2000a. Comparative study of thyroid function and types of 

thyroid dysfunction in two areas in Denmark with slightly different iodine status. Eur J Endocrinol 

143(4):485-491. 

Knudsen N, Bulow I, Jorgensen T, et al. 2000b. Goitre prevalence and thyroid abnormalities at 

ultrasonography: A comparative epidemiological study in two regions with slightly different iodine 

status. Clin Endocrinol 53(4):479-485. 

Knudsen N, Christiansen E, Brandt-Christiansen M, et al. 2000c. Age- and sex-adjusted 

iodine/creatinine ratio. A new standard in epidemiological surveys? Evaluation of three different 

estimates of iodine excretion based on casual urine samples and comparison to 24h values. Eur J Clin 

Nutr 54(4):361-363. 

Knudsen N, Perrild H, Christiansen E, et al. 2000d. Thyroid structure and size and two-year follow-up of 

solitary cold thyroid nodules in an unselected population with borderline iodine deficiency. Eur J 

Endocrinol 142(3):224-230. 

Ko YI, Kim SS, Han SK. 1995. Transdermal permeation-enhancing activities of some inorganic anions. 

Arch Pharmacal Res 18(4):231-236. 

Kobberling J, Hintze G, Becker HD. 1985. Iodine-induced thyrotoxicosis- A case for subtotal 

thyroidectomy in severely ill patients. Klin Wochenschr 63:1-7. 

*Kocher DC. 1981. On the long-term behavior of 129I in the terrestrial environment. International 

Symposium on Migration in the Terrestrial Environment of Long-Lived Radionuclides from the Nuclear 

Fuel Cycle. IAEA-SM-257/56. 

Kocher DC. 1991. A validation test of a model for long-term retention of 129I in surface soils. Health 

Phys 60(4):523-531. 

*Kogai T, Endo T, Saito T, et al. 1997. Regulation by thyroid-stimulating hormone of sodium/iodide 

symporter gene expression and protein levels in FRTL-5 cells. Endocrinology 138(6):2227-2232. 

*Kogai T, Hershman JM, Motomura K, et al. 2001. Differential regulation of the human sodium/iodide 

symporter gene promoter in papillary thyroid carcinoma cell lines and normal thyroid cells. 

Endocrinology 142(8):3369-3379. 
IODINE 406 

9. REFERENCES 

Kogai T, Schultz JJ, Johnson LS, et al. 2000. Retinoic acid induces sodium/iodide symporter gene 

expression and radioiodide uptake in the MCF-7 breast cancer cell line. Proc Natl Acad Sci USA 

91(15):8519-8524. 

*Koh T, Ono M, Makino I. 1988. Spectrophotometric determination of iodide at the 10-6 mol 1-1 level by 

solvent extraction with methylene blue. Analyst 113:945-948. 

Kohan SL, Guillen CE, Pardes EM, et al. 1992. Effects of keotconazole on the iodide uptake by FRTL-5 

cells. Acta Endocrinol 127:449-453. 

*Kohn LA. 1975. A look at iodine-induced hyperthyroidism: Recognition. Bull N Y Acad Med 

51(8):959-966. 

*Kohn LA. 1976. The midwestern American "epidemic" of iodine-induced hyperthyroidism in the 

1920s. Bull N Y Acad Med 52(7):770-781. 

Kohn LD, Suzuki K, Nakazato M, et al. 2001. Effects of thyroglobulin and pendrin on iodide flux 

through the thyrocyte. Trends in Endocrinology & Metabolism 12(1):10-16. 

*Köhrle J. 1994. Thyroid hormone deiodination in target tissues-a regulatory role for the trace element 

selenium. Exp Clin Endocrinol 102:63-89. 

*Kolonel LN, Hankin JH, Wilkens LR, et al. 1990. An epidemiologic study of thyroid cancer in Hawaii. 

Cancer Causes Control 1:223-234. 

*Komori M, Nishio K, Kitada M, et al. 1990. Fetus-specific expression of a form of cytochrome P-450 

in human livers. Biochemistry 29:4430-4433. 

Kondo H, Fukuda H, Ono H, et al. 2001. Sodium thiosulfate solution spray for relief of irritation caused 

by Lugol's stain in chromoendoscopy. Gastrointest Endosc 53(2):199-202. 

Konermann G. 1992. Biokinetics of radioiodine (125I) during pre and post-natal development and the 

interference with the induction of developmental effects in the mouse brain. Radiat Prot Dosim 41:157­

162. 

*Konno N, Makita H, Yuri K, et al. 1994. Association between dietary iodine intake and prevalence of 

subclinical hypothyroidism in the coastal regions of Japan. J Clin Endocrinol Metab 78(2):393-397. 

*Konno N, Taguchi H, Miura K, et al. 1993a. Serum thyrotropin concentration in apparently healthy 

adults, in relation to urinary iodide concentration. Clin Chem 39(1):174-175. 

*Konno N, Yuri K, Miura K, et al. 1993b. Clinical evaluation of the iodide/creatine ratio of casual urine 

samples as an index of daily iodine excretion in a population study. Endocrine Journal 40(1):163-169. 

Konoplya EF, Fil'chenkov GN, Popov EG, et al. 1992. [Effect of iodine-131 on sex and thyroid hormone 

binding to blood plasma proteins in children with functional lesions of the thyroid gland as a result of 

Chernobyl disaster.] Radiobiologiia 32(4):488-492. (Russian) 

Konukoglu D, Hatemi HH, Arikan S, et al. 1998. Radioiodine treatment and oxidative stress in 

thyroidectomised patients for differentiated thyroid cancers. Pharmacol Res 38(4):311-315. 
IODINE 407 

9. REFERENCES 

Koong S-S, Reynolds JC, Movius EG, et al. 1999. Lithium as a potential adjuvant to 131I therapy of 

metastatic, well differentiated thyroid carcinoma. J Clin Endocrinol Metab 84(3):912-916. 

Korolev GK. 1970. [Metabolism of iodine-131 in relation to the path of entry and the toxic action 

following entry into the respiratory system.] In: Raspredel kinet obmena biol diestvie radioactiv izotop 

ioda, 36-45. (Russian) 

Korsager S, Kristensen HPO. 1979. Iodine-induced hypothyroidism and its effect on the severity of 

asthma. Acta Med Scand 205:115-117. 

Kostial K, Kargacin B, Rabar I, et al. 1981. Simultaneous reduction of radioactive strontium, caesium 

and iodine retention by single treatment in rats. Sci Total Environ 22:1-10. 

Kostial K, Vnucec M, Tominac C, et al. 1980. A method for a simultaneous decrease of strontium, 

caesium and iodine retention after oral exposure in rats. Int J Radiat Biol 37(3):347-350. 

*Kosugi S, Inoue S, Matsuda A, et al. 1998. Novel, missense and loss-of-function mutations in the 

sodium/iodide symporter gene causing iodide transport defect in three Japanese patients. J Clin 

Endocrinol Metab 83(9):3373-3376. 

*Kosugi S, Okamoto H, Tamada A, et al. 2002. A novel peculiar mutation in the sodium/iodide 

symporter gene in Spanish siblings with iodide transport defect. J Clin Endocrinol Metab 87(8):3830­

3836. 

Kotajima A, Miyamoto Y, Tsuruo M, et al. 1995. Effects of activin A on deoxyribonucleic acid 

synthesis, iodine metabolism, and cyclic adenosine monophosphate accumulation in porcine thyroid cells. 

Endocrinology 136(3):1214-1218. 

Kotz D. 2000. Hanford: Study leaves questions about increased thyroid cancer rates unanswered. J Nucl 

Med 41(4):17N-18N, 21N, 25N. 

*Koutras DA. 1996. Control of efficiency and results, and adverse effects of excess iodine 

administration on thyroid function. Ann Endocrinol (Paris) 57:463-469. 

Koutras DA. 2000. Circulating iodide concentrations during and after pregnancy. J Clin Endocrinol 

Metab 85(3):1345. 

Koyanagi T, Hirano S, Matsuba M. 1985. The transfer of radioiodine in different chemical forms 

through food chain. J Radiat Res 26(1):83. 

Kraiem Z, Sadeh O, Blithe DL, et al. 1994. Human chorionic gonadotropin stimulates thyroid hormone 

secretion, iodide uptake, organification, and adenosine 3',5'-monophosphate formation in cultured human 

thyrocytes. J Clin Endocrinol Metab 79(2):595-599. 

Kraiem Z, Sadeh O, Yosef M. 1991. Iodide uptake and organification, tri-iodothyronine secretion, cyclic 

AMP accumulation and cell proliferation in an optimized system of human thyroid follicles cultured in 

collagen gel suspended in serum-free medium. J Endocrinol 131:499-506. 

Krari N, Berre S, Allain P. 1992. Effects of thyroparathyroidectomy on the distribution of bromine and 

iodine in rat tissues. Biol Trace Elem Res 32:275-279. 
 

 

IODINE 408 

9. REFERENCES 

Krawiec L, Ryder E, Campos G. 1981. Excessive ingestions of iodide by the rat during pregnancy and 

lactation. Effects on ribonucleic acid transcription in the pups brain. Acta Physiol Latinoam 31:241-247. 

Kreps EM, Kreps SM, Kreps SI. 1973. Treatment of hyperthyroidism with sodium iodide I 131: 

Carcinoma of the thyroid after 20 years. JAMA 226(7):774-775. 

Krisch RE, Sauri CJ. 1977. DNA breakage, repair, and lethality accompanying 125I decay in 

microorganisms. Curr Top Radiat Res Q 12:355-368. 

*Krishnan K, Andersen ME. 1994. Physiologically based pharmacokinetic modeling in toxicology. In: 

Hayes AW, ed. Principles and methods of toxicology. 3rd ed. New York, NY: Raven Press, Ltd., 149­

188. 

*Krishnan K, Andersen ME, Clewell HJ III, et al. 1994. Physiologically based pharmacokinetic 

modeling of chemical mixtures. In: Yang RSH, ed. Toxicology of chemical mixtures: Case studies, 

mechanisms, and novel approaches. San Diego, CA: Academic Press, 399-437. 

Krishnan U, Que Hee SS. 1992. Ear wax: A new biological monitoring medium for metals. Bull 

Environ Contam Toxicol 48:481-486. 

Krohn K, Paschke R. 2002. Somatic mutations in thyroid nodular disease. Molecular Genetics and 

Metabolism75(3):202-208. 

*Krohn K, Wohlegemuth S, Gerber H, et al. 2000. Hot microscopic areas of iodine-deficient euthyroid 

goitres contain constitutively activating TSH receptor mutations. J Pathol 192(1):37-42. 

Krouse TB, Eskin BA, Mobini J. 1979. Age-related changes resembling fibrocystic disease in iodineblocked rat breasts. Arch Pathol Lab Med 103:631-634. 

*Krzesniak JA, Chomicki OA, Czerminksa M, et al. 1979. Airborne radioiodine contamination caused 

by 131I treatment. Nuklearmedizin 18(5):246-251. 

Krzesniak JW. 1978. A laboratory for investigating and monitoring the contamination of air with 

radioactive iodine. Postepy Fiz Med 13(1):53-65. 

Krzesniak JW, Porstendorfer J. 1978. Diffusion coefficients of airborne radioactive iodine and methyl 

iodide. Health Phys 35:417-421. 

Krzesniak JW, Chomicki OA, Krajewski P, et al. 1983. Radiation hazards from inhaled airborne 

radioiodine in a nuclear medicine unit. In: Nuclear medicine and biology advances: Proceedings of the 

third World Congress of Nulcear Medicine and Biology, August 29 to September 2, 1982, Paris, France. 

Oxford, England: Pergamon Press, 2985-2988. 

Krzesniak JW, Krajewski P, Emrich D, et al. 1986. Personnel inhalation hazard during "In-Vitro" and 

"In-Vivo" work with 125I and 131I [Abstract]. Nuklearmedizin 25(4):A74. 

Krzesniak JW, Schuernbrand P, Porstenduerfer J, et al. 1984. Levels of airborne contamination while 

handling 125I and 131I and 99mTc unsealed sources in medical diagnostic procedures. In: Radiat. Risk. 

Prot., Int. Congr., 6th., 833-836. 
 

 

 

 

IODINE 409 

9. REFERENCES 

*Kubota Y, Koga T, Nakayama J. 2000. Iodine allergy induced by consumption of iodine-containing 

food. Contact Dermatitis 42(5):286-287. 

Kuleff I, Zotschev S, Stefanov G. 1986. Determination of the 129I content of the primary coolant nuclear 

power reactors. J Radioanal Nucl Chem 97(1):73-79. 

Kumamoto T, Toyooka K, Nishida M, et al. 1990. Effect of 2,4-dihydro-3H-1,2,4-trizole-3-thiones and 

thiosemicarbazones on iodide uptake by the mouse thyroid: The relationship between their structure and 

anti-thyroid activity. Chem Pharm Bull 38(9):2595-2596. 

Kung AWC, Yau CC, Cheng A. 1994. The incidence of ophthalmopathy after radioiodine therapy for 

Graves' disease: Prognostic factors and the role of methimazole. J Clin Endocrinol Metab 79:542-546. 

Kung AW, Yau C-C, Cheng AC. 1995. The action of methimazole and L-thyroxine in radioiodine 

therapy: A prospective study on the incidence of hypothyroidism. Thyroid 5(1):7-12. 

Kunze J, Kaiser HJ, Petres J. 1983. [Relevance of a iodine-allergy to commercialized povidone-iodinepreparations.] Z Hautkr 58(4):255-261. (German) 

*Kurtz SC, Aber RC. 1982. Potassium iodide as a cause of prolonged fever. Arch Intern Med 142:1543­

1544. 

*Kwok CS, Hilditch TE. 1982. Airborne iodine-125 arising from surface contamination. Phys Med Biol 

27(1):149-151. 

Labbe E, Peyroux T. 1984. Mechanisms of adverse reactions to iodinated contrast material. Radiat Med 

2(2):93-100. 

Labmann M, Hanscheid H, Schelper L-F, et al. 1998. [Measurement of incorporation in family members 

of patients with benign thyroid disease after radioiodine therapy.] Nuklearmedizin 37:120-123. 

(German) 

Lachapelle JM. 1984. Occupational allergic contact dermatitis to povidone-iodine. Contact Dermatitis 

11(3):189-190. 

*Lacroix L, Mian C, Cailou B, et al. 2001. Na+

/I- symporter and Pendred syndrome gene and protein 

expressions in human extra-thyroidal tissues. Eur J Endocrinol 144(3):297-302. 

Ladenson PW. 1996a. Diagnosis of hypothyroidism. In: Braverman LE, Utiger RD, eds. Werner and 

Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 878-882. 

Ladenson PW. 1996b. Diagnosis of thyrotoxicosis. In: Braverman LE, Utiger RD, eds. Werner and 

Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 708-712. 

LaFranchi S, Mandel SH. 1996. Graves' disease in the neonatal period and childhood. In: Braverman 

LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: 

Lippincott-Raven, 1000-1008. 

Laing RW, Saunders MI. 1992. A case of lung carcinoma induced by radioactive iodine given for 

disseminated thyroid carcinoma. Clin Oncol 4:394-395. 
 

 

IODINE 410 

9. REFERENCES 

*l'Allemand D, Gruters A, Beyers P, et al. 1987. Iodine in contrast agents and skin disinfectants is the 

major cause for hypothyroidism in premature infants during intensive care. Horm Res 28:42-49. 

*l'Allemand D, Gruters A, Heidemann P, et al. 1983. Iodine-induced alterations of thyroid function in 

newborn infants after prenatal and perinatal exposure to povidone iodine. J Pediatr 102(6):935-938. 

Lamberg-Allardt C, Valtonen E, Polojarvi M, et al. 1991. Characterization of 1,25-dihydroxy-vitamin D3 

receptor in FRTL-5 cells. Evidence for an inhibitory effect of 1,25-dihydroxy-vitamin D3 on thyrotropininduced iodide uptake. Mol Cell Endocrinol 81:25-31. 

*Lambert A, Lowe AG. 1978. Chloride/bicarbonate exchange in human erythrocytes. J Physiol 275:51­

63. 

Lambert JP. 1981. Report of a minor 125I exposure in a research laboratory. Health Phys 40:746-748. 

*Lambert V, Thierens H, Monsieurs M. 2001. Translocation frequencies measured in patients one year 

after radioactive iodine therapy for thyrotoxins. Int J Radiat Biol 77(6):679-685. 

*Landon S, Smith PG, Staniek SP, et al. 1980. Advantages of using thin sodium iodide detectors for 

thyroid monitoring of personnel working with 125I. Clin Chem 26(1):18-21. 

Lang JCT, Lees JFH, Alexander WD, et al. 1983a. Effect of variations in acute and chronic iodine intake 

on the accumulation and metabolism of [35S]methimazole by the rat thyroid gland: Differences from 

[

35S]propylthiouracil. Biochem Pharmacol 32(2):241-247. 

Lang JCT, Lees JFH, Alexander WD, et al. 1983b. Effect of variations in acute and chronic iodine 

uptake on the accumulation and metabolism of [34S]propylthiouracil by the rat thyroid gland. Biochem 

Pharmacol 32(2):233-240. 

*Langer P, Moravec R, Ohradka B, Foldes O. 1988. Iodothyronines in human bile. Endocrinol Exp 

22:35-39. 

Laroche D, Namour F, Lefrancois C, et al. 1999. Anaphylactoid and anaphylactic reactions to iodinated 

contrast material. Allergy 54:13-16. 

*Larsen PR, Berry MJ. 1994. Type I iodothyronine deiodinase: Unexpected complexities in a simple 

deiodination reaction. Thyroid 4(3):357-362. 

Larsen PR, Wolff J. 1967. Iodide transport: Inhibition by agents reacting at the membrane. Science 

155:335-336. 

*Larsen PR, Davies TF, Hay ID. 1998. The thyroid gland. In: Wilson JD, Foster DW, Kronenberg HM, 

et al., eds. Williams textbook of endocrinolgy. Philadelphia, PA: W.B. Saunders Company, 390-515. 

*Lauber K. 1975. Iodine determination in biological material. Kinetic measurement of the catalytic 

activity of iodide. Anal Chem 47:769-771. 

Laurberg P, Bulow Pedersen I, Pedersen KM, et al. 1999. Low incidence of rate of overt hypothyroidism 

compared with hyperthyroidism in an area with moderately low iodine intake. Thyroid 9(1):33-38. 
 

 

IODINE 411 

9. REFERENCES 

Laurberg P, Bulow Pedersen I, Knudsen N, et al. 2001. Environmental iodine intake affects the type of 

nonmalignant thyroid disease. Thyroid 11(5):457-469. 

*Laurberg P, Pedersen KM, Hreidarsson A, et al. 1998. Iodine intake and the pattern of thyroid 

disorders: A comparative epidemiological study of thyroid abnormalities in the elderly in Iceland and in 

Jutland, Denmark. J Clin Endocrinol Metab 83(3):765-769. 

Laurent E, Mockel J, Takazawa K, et al. 1989. Stimulation of generation of inostiol phosphates by 

carbamoylcholine and its inhibition by phorbol esters and iodide in dog thyroid cells. Biochem J 

263:795-801. 

Laurenti L, Salutari P, Sica S, et al. 1998. Acute myeloid leukemia after iodine-131 treatment for thyroid 

disorders. Ann Hematol 76:271-272. 

Laurie AJ, Lyon SG, Lasser EC. 1992. Contrast material iodides: Potential effects on radioactive iodine 

thyroid uptake. J Nucl Med 33:237-238. 

*Lauterbach A, Ober G. 1995. Iodine and iodine compounds. In: Kirk-Othmer encyclopedia of 

chemical technology. 4th ed. Vol. 14. New York, NY: John Wiley and Sons, 709-737. 

Lavelle KF, Doedens DJ, Kleit SA, et al. 1975. Toxicity of sodium iodide in the rabbit: Effects on 

hydrogen ion homeostasis, hepatic and renal functions. Toxicol Appl Pharmacol 33:52-61. 

Laverock MJ, Stephenson M, Macdonald CR. 1995. Toxicity of iodine, iodide, and iodate to Daphnia 

magna and rainbow trout (Oncorhynchus mykiss). Arch Environ Contam Toxicol 29:344-350. 

Lavu S, Reddy PP, Reddi OS. 1985a. Chromosomal abnormalities induced by iodine-125 in mouse germ 

cells. Int J Radiat Biol 48(4):603-607. 

Lavu S, Reddy PP, Reddi OS. 1985b. Iodine-125 induced micronuclei and sperm head abnormalities in 

mice. Int J Radiat Biol 47(3):249-253. 

*Law LW. 1938. The effects of chemicals on the lethal mutation rate in drosophilia melanogaster. Proc 

Natl Acad Sci U S A 24:546-550. 

*Lawes SC. 1992. 123I excretion in breast milk - additional data. Nucl Med Commun 13:570-572. 

*Lawrence JC. 1998. The use of iodine as an antiseptic agent. J Wound Care 7(8):421-425. 

Lawrence JE, Lamm SH, Braverman LE. 1999. The use of perchlorate for the prevention of 

thyrotoxicosis in patients given iodine rich contrast agents. J Endocrinol Invest 22:405-407. 

Lazarus JH. 1994. Thyroxine excess and pregnancy. Acta Med Austriaca 21:53-56. 

Lazarus JH. 1996. Silent thyroiditis and subacute thyroiditis. In: Braverman LE, Utiger RD, eds. 

Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 

577-591. 

Lazarus JH. 1999. Thyroid hormone and intellectual development: A clinician's view. Thyroid 

9(7):659-660. 
IODINE 412 

9. REFERENCES 

Lazarus JH, Muston HL. 1978. The effect of lithium on the iodide concentrating mechanism in mouse 

salivary gland. Acta Pharmacol Toxicol (Copenh) 43:55-58. 

Lazjuk GI, Nikolaev DI, Khmel RD. 2000. Epidemiology of congenital malformations in Belarus and 

Chernobyl accident. Am J Hum Genet 67:214. 

Lecos C. 1983. Tracking trace minerals. FDA Consum 17:16-21. 

Lee JY, Sawada S, Satow Y. 1990. Toxicity of iodic kalium to the rat embryos. J Radiat Res 31(1):79. 

Lee JY, Shoju S, Satow Y. 1989. Developmental toxicity of potassium iodide in rats. Teratology 

40(6):676-677. 

Lee K, Bradley R, Dwyer J, et al. 1999. Too much versus too little: The implications of current iodine 

intake in the United States. Nutr Rev 57(6):177-181. 

Lee TC, Habert JC, Dejter SW, et al. 1985. Vocal cord paralysis following I-131 ablation of a 

postthyroidectomy remnant. J Nucl Med 26:49-50. 

Lee W-NP, Mpanias PD, Wimmer RJ, et al. 1978. Use of I-123 in early radioiodide uptake and its 

suppression in children and adolescents with hyperthyroidism. J Nucl Med 19:985-993. 

Lee W, Chiacchierini RP, Shleien B, et al. 1981. Dose responses in thyroid tumor inductions from 

iodine-131 and localized thyroid and pituitary irradiations in rats. Radiat Res 87(2):452. 

Lee W, Chiacchierini RP, Shleien B, et al. 1982. Thyroid tumors following 131I or localized X irradiation 

to the thyroid and pituitary glands in rats. Radiat Res 92:307-319. 

Lee W, Shleien B, Telles NC, et al. 1979. An accurate method of 131I dosimetry in the rat thyroid. 

Radiat Res 79:55-62. 

*Leeder JS, Kearns GL. 1997. Pharmcogenetics in pediatrics: Implications for practice. Pediatr Clin 

North Am 44(1):55-77. 

*Leger AF, Massin JP, Laurent MF, et al. 1984. Iodine-induced thyrotoxicosis: Analysis of eighty-five 

consecutive cases. Eur J Clin Invest 14:449-455. 

*Leger FA, Doumith R, Courpotin C, et al. 1987. Complete iodide trapping defect in two cases with 

congenital hypothyroidism: Adaptation of thyroid to huge iodide supplementation. Eur J Clin Invest 

17:249-255. 

Le Guen B, Malarbet JL, Roy M, et al. 1998. Methodology for 129I dose calculations, in the case of 

potential exposure from nuclear waste in France. Radiat Prot Dosim 79(1-4):211-214. 

*Lehmann L, Zitzelsberger H, Kellerer AM. 1996. Chromosome translocations in thyroid tissues from 

Belarussian children exposed to radioiodine from the Chernobyl accident, measured by FISH-painting. 

Int J Radiat Biol 70(5):513-516. 

*LeMar HJ, Georgotis WJ, McDermott MT. 1995. Thyroid adaptation to chronic tetraglycine 

hydroperiodide water purification tablet use. J Clin Endocrinol Metab 80:220-223. 
 

 

IODINE 413 

9. REFERENCES 

Lengemann FW. 1966. Reduction of iodine transfer to milk of cows after perchlorate ingestion. J Dairy 

Sci 56:753-756. 

Lengemann FW. 1979. Effects of low and high ambient temperatures on metabolism of radioiodine by 

the lactating goat. J Dairy Sci 62:412-415. 

*Lengemann FW, Comar CL. 1964. Metabolism of 131I by dairy cows during long term daily 

administration of the radioscope. Health Phys 10:55-59. 

*Lengemann FW, Wentworth RA. 1979. Extremes of environmental temperature and the transfer of 

radioiodide into milk. Health Phys 36:267-271. 

*Leonard JL, Koehrle J. 1996. Intracellular pathways of iodothyronine metabolism. In: Braverman LE, 

Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: 

Lippincott-Raven, 125-161. 

Lequesne M. 1967. [Alsodystrophy of chemotherapeutic origin. Pseudorheumatism due to isoniazid, 

ethionamide, phenobarbital and radioactive iodine.] Sem Hop 43(42):2581-2595. (French) 

*Lessard ET, Miltenberger RP, Conard RA, et al. 1985. Thyroid absorbed dose for people at Rongelap 

Uterik and Sifo on March 1, 1954. Brookhaven National Library. BNL 51882. 

Leszynsky HE, Gross-Kielselstein EG, Abrahamov A. 1971. Hyperthyroidism in a 3-month-old baby. 

Pediatrics 47:1069-1083. 

*Leung H-W. 1993. Physiologically-based pharmacokinetic modelling. In: Ballentine B, Marro T, 

Turner P, eds. General and applied toxicology. Vol. 1. New York, NY: Stockton Press, 153-164. 

Leung PMK, Nikolic M. 1998. Disposal of therapeutic 131I waste using a multiple holding tank system. 

Health Phys 75(3):315-321. 

LeValley MJ. 1982. Acute toxicity of iodine to channel catfish (Ictalurus punctatus). Bull Environ 

Contam Toxicol 29:7-11. 

Levenson D, Gulec S, Sonenberg M, et al. 1994. Peripheral facial nerve palsy after high-dose 

radioiodine therapy in patients with papillary thyroid carcinoma. Ann Intern Med 120(7):576-578. 

*Levy O, Dai G, Riedel C, et al. 1997. Characterization of the thyroid Na+

/I- symporter with an antiCOOH terminus antibody. Proc Natl Acad Sci U S A 94:5568-5573. 

*Levy O, De la Vieja A, Carrasco N. 1998a. The Na+

/I- symporter (NIS): Recent advances. J Bioenerg 

Biomembr 30(2):195-206. 

Levy O, De la Vieja A, Ginter CS, et al. 1998b. N-linked glycosylation of the thyroid Na+

/I- symporter 

(NIS). J Biol Chem 273(35):22657-22663. 

*Levy O, Ginter CS, De la Viega A, et al. 1998c. Identification of a structural requirement for thyroid 

Na+

/I- symporter (NIS) function from analysis of a mutation that causes human congenital 

hypothyroidism. FEBS Lett 429:36-40. 

Lewitus Z. 1983. Thyroid carcinoma in Israel. Acta Endocrinol Suppl 252:15. 
IODINE 414 

9. REFERENCES 

Lewitus Z, Lubin E, Rechnic J, et al. 1971. The problem of iodine-125 for treatment of thyrotoxicosis. 

Hormones 2:115-128. 

*Li M, Boyages SC. 1994. Iodide induced lymphocytic thyroiditis in the BB/W rat: Evidence of direct 

toxic effects of iodide on thyroid subcellular structure. Autoimmunity 18:31-40. 

Li M, Eastman CJ, Boyages SC. 1993. Iodine induced lymphocytic thyroiditis in the BB/W rat: Early 

and late imuune phenomena. Autoimmunity 14:181-187. 

*Li W, Qu C, Jia G, et al. 1987. Endemic goitre in Central China caused by excessive iodine intake. 

Lancet, August 1:257-258. 

Li W, Xiong JQ, Cohen BS. 1998. The deposition of unattached radon progeny in a tracheobronchial 

cast as measured with iodine vapor. Aerosol Sci Technol 28:502-510. 

*Libert F, Lefort A, Gerard C, et al. 1989. Cloning, sequencing and expression of the human thyrotropin 

(TSH) receptor: Evidence for binding of autoantibodies. Biochem Biophys Res Commun 165(3):1250­

1255. 

*Libert F, Ruel J, Ludgate M et al. 1987. Complete nucleotide sequence pf the human thyroperoxidasemicrosomal antigen cDNA. Nucleic Acids Res 15:6735. 

*Lide DR, ed. 2000. CRC handbook of chemistry and physics. 81st ed. Boca Raton, FL: CRC Press. 

*Liesenkötter KP, Gopel W, Bogner U, et al. 1996. Earliest prevention of endemic goiter by iodine 

supplementation during pregnancy. Eur J Endocrinol 134:443-448. 

Lightner ES, Fismer DA, Giles H, et al. 1977. Intra-amniotic injection of thyroxine (T4) to a human 

fetus: Evidence for conversion o fT4 to reverse T3. Am J Obstet Gynecol 127:487-490. 

Lightowler HJ, Davies GJ, Trevan MD. 1996. Iodine in the diet: Perspectives for vegans. J R Soc 

Health 116:14-20. 

Likhtarev IA, Gulko GM, Kairo IA, et al. 1994. Thyroid doses resulting from the Ukraine Chernobyl 

accident-Part I: Dose estimates for the population of Kiev. Health Phys 66(2):137-146. 

Likhtarev IA, Kairo I, Tronko ND, et al. 1998. Thyroid cancer risk to children calculated. Nature 

392:31-32. 

*Likhtarev IA, Shandala NK, Gulko GM, et al. 1993. Ukranian thyroid doses after the Chernobyl 

accident. Health Phys 64(6):594-599. 

*Likhtarev IA, Sobolev BG, Kairo IA, et al. 1995. Thyroid cancer in the Ukraine. Nature 375:365. 

Lim C-F, Bernard BF, de Jong M, et al. 1993. A furan fatty acid and indoxyl sulfate are the putative 

inhibitors of thyroxine hepatocyte transport in uremia. J Clin Endocrinol Metab 76(2):318-324. 

Lima FRS, Gervais A, Colin C, et al. 2001. Regulation of microglial development: A novel role for 

thyroid hormone. J Neurosci 21(6):2028-2038. 
 

 

IODINE 415 

9. REFERENCES 

*Lin JD, Wang HS, Weng HF, et al. 1998. Outcome of pregnancy after radioactive iodine treatment for 

well differentiated thyroid carcinomas. J Endocrinol Invest 21:662-667. 

Lin TJ, Tanaka Y, Aznar R, et al. 1973. Contraceptive effect of intrauterine application of Lugol's 

solution. Am J Obstet Gynecol 116(2):167-174. 

Lin W-Y, Shen Y-Y, Wang S-J. 1996. Short-term hazards of low-dose radioiodine ablation therapy in 

postsurgical thyroid cancer patients. Clin Nucl Med 21(10):780-782. 

*Lind P, Langsteger W, Molnar M, et al. 1998. Epidemiology of thyroid diseases in iodine sufficiency. 

Thyroid 8(12):1179-1183. 

Linder N, Davidovitch N, Reichman B, et al. 1997a. Topical iodine-containing antiseptics and 

subclinical hypothyroidism in preterm infants. J Pediatr 131:434-439. 

Linder N, Sela B, German B, et al. 1997b. Iodine and hypothyroidism in neonates with congenital heart 

disease. Arch Dis Child 77:F239-F240. 

Lindsay S, Nichols CWJ, Chaikoff IL. 1968. Carcinogenic effect of irradiation: Low doses of 

radioactive iodine on the thyroid gland of the rat and mouse. Arch Pathol 85:487-492. 

Lindsay S, Potter GD, Chaikoff IL. 1963. Radioiodine-induced thyroid carcinomas in female rats. Arch 

Pathol 75:20-24. 

*Lindstrom RM, Lutz GJ, Norman BR. 1991. High-sensitivity determination of iodine isotopic ratios by 

thermal and fast neutron activation. J Trace Microprobe Tech 9(1):21-32. 

Ling CC, Li WX, Anderson LL. 1995. The relative biological effectiveness of I-125 and Pd-103. Int J 

Radiat Oncol Biol Phys 32(2):373-378. 

Links JM. 1996. Radiation physics. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's the 

thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 330-341. 

Linsley GS. 1977. Criteria for safe working with iodine-125. Radiography 43(508):91-93. 

Lione A. 1988. Nonprescription drugs as a source of aluminum, bismuth, and iodine during pregnancy. 

Reprod Toxicol 1:243-252. 

*Lipsztein JL, Bertilli L, Melo DR, et al. 1991. Application of in-vitro bioassy for 137Cs during the 

emergency phase of the Goiania accident. Health Physics 60:43-49. 

Little JR, Murray PR, Traynor PS, et al. 1999. A randomized trial of povidone-iodine compared with 

iodine tincture for venipuncture site disinfection: Effects on rats of blood culture contamination. Am J 

Med 107:119-125. 

Liu J, Liu Y, Barter RA, et al. 1995. Alteration of thyroid homeostasis by UDP-glucuronosyltransferase 

inducers in rats: A dose-response study. J Pharmacol Exp Ther 273:977-985. 

*Liu K, Edwards FM. 1979. Radiation exposure to medical personnel during iodine-125 seed 

implantation of the prostate. Radiology 132:748-749. 
 

 

IODINE 416 

9. REFERENCES 

Liu Z, Fu C, Li C, et al. 1982. 131I and 132I carcinogenic effects in rat thyroid glands. Chin Med J 

95(9):641-648. 

Liu Z, Fu C, Li Z, et al. 1986. Study on late effects of radioiodine on rats. Sci Sin [B] XXIX(10):1039­

1053. 

Liu Z, Fu C, Li Z, et al. 1987. Carcinogenic effects of 131I, 132I and 125I on rat thyroids. Chin Med J 

100(2):92-96. 

*Livadas DP, Koutras DA, Souvatzoglou A, et al. 1977. The toxic effects of small iodine supplements in 

patients with autonomous thyroid nodules. Clin Endocrinol 7:121-127. 

*Livingston, AL. 1978. Forage plant estrogens. J Toxicol Environ Health 4:301-324. 

LiVolsi VA. 1996. Pathology. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A 

fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 497-520. 

LiVolsi VA. 1997. Pathology of thyroid disease. In: Falk SA, ed. Thyroid disease: Endocrinology, 

surgery, nuclear medicine, and radiotherapy. Philadelphia, PA: Lippincott-Raven Publishers, 65-104. 

Lloyd DC, Purrott RJ, Dolphin GW, et al. 1976. A comparison of physical and cytogenetic estimates of 

radiation dose in patients treated with iodine-131 for thyroid carcinoma. Int J Radiat Biol 30(5):473-485. 

Lloyd RD, Tripp DA, Kerber RA. 1996. Limits of fetal thyroid risk from radioiodine exposure. Health 

Phys 70(4):559-562. 

Lloyd WE. 1982. Toxicology of ethylenediamine dihydriodide [Letter]. J Am Vet Med Assoc 

180(5):476,478. 

Lo MT, Hill DC. 1971. Effect of dietary rapeseed meal on the serum proteins of rats. Can J Physiol 

Pharmacol 49:1100-1105. 

Loeb JN. 1996a. Metabolic changes in hypothyroidism. In: Braverman LE, Utiger RD, eds. Werner 

and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 858-862. 

Loeb JN. 1996b. Metabolic changes in thyrotoxicosis. In: Braverman LE, Utiger RD, eds. Werner and 

Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 687-693. 

Long Y, France J-L, Giraud A. 1990. Inhibition of N-glycan processing affects iodide organification in 

porcine thyroid cells. Mol Cell Endocrinol 73:217-224. 

*Longcope C. 2000a. The male and female reproductive systems in hypothyroidism. In: Braverman 

LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 8th Philadelphia, 

PA: Lippincott-Raven, 824-827. 

*Longcope C. 2000b. The male and female reproductive systems in thyrotoxicosis. In: Braverman LE, 

Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 8th Philadelphia, PA: 

Lippincott-Raven, 653-658. 

*Lopez Saez MP, de Barrio M, Zubeldia JM, et al. 1998. Acute IgE-mediated generalized urticariaangioedema after topical application of povidone-iodine. Allergol Immunopathol (Madr) 26(1):23-26. 
 

 

IODINE 417 

9. REFERENCES 

LoPresti JS, Singer PA. 1997. Physiology of thyroid hormone synthesis, secretion, and transport. In: 

Falk SA, ed. Thyroid disease: Endocrinology, surgery, nuclear medicine, and radiotherapy. 

Philadelphia, PA: Lippincott-Raven Publishers, 29-40. 

Loran M, Kleinmann K. 1975. Semiquantitative test of iodine vapor above complexed iodine solutions. 

Am J Hosp Pharm 32:431-432. 

Lowdell CP, Dobbs HJ, Spathis GS, et al. 1985. Low-dose 131I in treatment of Graves' disease. J R Soc 

Med 78:197-202. 

*Luckett LW, Stotler RE. 1980. Radioiodine volatilization from reformulated sodium iodide I-131 oral 

solution. J Nucl Med 21:477-479. 

Lueprasitsakul W, Abend S, Alex S, et al. 1990. Effect of thalidomide on the incidence of iodineinduced and spontaneous lymphocytic thyroiditis and spontaneous diabetes mellitus in the BB/Wor rat. 

Acta Endocrinol 123:79-83. 

Lundell G, Holm L-E. 1980. Hypothyroidism following 131I therapy for hyperthyroidism in relation to 

immunologic parameters. Acta Radiol Oncol 19:449-454. 

Lundell G, Jonsson J. 1973. Thyroid antibodies and hypothyroidism in 131I therapy for hyperthyroidism. 

Acta Radiol Ther Phys Biol 12(5):443-453. 

Lundell G, Holm L-E, Ljunggren J-G, et al. 1981. Incidence of hypothyroidism after 131I therapy for 

hyperthyroidism. Acta Radiol Oncol 20(4):225-230. 

Lupulescu A, Petrovici A. 1964. The fine structure of thyroid tumours induced by low iodine diet in rats. 

Acta Anat 57:294-305. 

Lupulescu A, Stebner F. 1974. Effect of synthetic salmon calcitonin in iodine metabolism in rabbits. 

Proc Soc Exp Biol Med 146:56-58. 

Luther GW, Swartz CB, Ullman WJ. 1988. Direct determination of iodide in seawater by cathodic 

stripping square wave volammetry. Anal Chem 60:1721-1724. 

*Lutz GJ, Rook HL, Lindstrom RM. 1984. Determination of I-129 at natural levels by thermal neutron 

activation analysis. J Trace Microprobe Tech 2(1):33-51. 

Lybeck H, Leppaluoto J, Virkkunen P, et al. 1973. Suppression of TRH-mediated thyroidal release of 

131I by a synthetic analog. Neuroendocrinology 12:366-370. 

Maas LC, Gelzayd EA. 1978. Endoscopic removal of an ulcerated appendiceal stump. JAMA 

240(3):248-249. 

Maayan ML. 1977. TSH and catecholamines: Independent effects on active transport and iodine 

organification in isolated thyroid cells. Acta Endocrinol 86:763-767. 

Maayan ML, Ingbar SH. 1968. Epinephrine: Effect on uptake of iodine by dispersed cells of calf thyroid 

gland. Science 162:124-125. 
IODINE 418 

9. REFERENCES 

Maayan ML, Miller SL, Ingbar SH. 1971. Effects of serotonin on iodide and intermediary metabolism in 

isolated thyroid cells. Endocrinology 88:620-626. 

Maayan ML, Shapiro R, Ingbar SH. 1973. Epinephrine precursors: Effects on the iodine and 

intermediary metabolism of isolated calf thyroid cells. Endocrinology 92:912-916. 

Maayan ML, Volpert EM, From A. 1981. Norepinephrine and thyrotropin effects on the thyroid in vitro: 

Simultaneous stimulation of iodide organification and antagonism of thyroxine release. Endocrinology 

109:930-934. 

Macaron C. 1996. An epidemic of hyperthyroidism following salt iodination in Lebanon. J Med Liban 

44(4):200-202. 

*Machta L. 1963. Metereological processes in the transport of weapon radionuclides. Health Physics 

9:43. 

Madaoui S, Rappaport L, Nunez J. 1974. Prostaglandins and in vitro TSH-dependent iodide binding by 

rat thyroid glands. Biochimie 56:109-113. 

Maekoshi H, Orito T, Nishizawa K, et al. 1979. [Measurement of 131I concentration in saliva of a 

patient and monitoring of exposure and contamination in a ward.] Radioisotopes 28(3):180-183. 

(Chinese) 

*Magnusson RP, Chazenbalk GD, Gestautas J et al. 1987. Molecular cloning of the complementary 

deoxyribonucleic acid from human thyroid peroxidase. Mol Endocrinol 1:856. 

Mahillon I, Peers W, Bourdoux P, et al. 1989. Effect of vaginal douching with povidone-iodine during 

early pregnancy on the iodine supply to mother and fetus. Biol Neonate 56:210-217. 

Mahn DC, Vallet JL. 1997. Vitamin and mineral transfer during fetal development and the early 

postnatal period in pigs. J Anim Sci 75:2731-2738. 

Maienchenko AF, Seregin VV, Kuz'mina TS. 1976. [Effect of uranium on the metabolism of radioactive 

and stable iodine in the thyroid gland.]. Dokl Akad Nauk SSSR 20(4):373-376. 

Maier H, Bihl H. 1987. Effect of radioactive iodine therapy on parotid gland function. Acta Otolaryngol 

(Stockh) 103:318-324. 

Maillie HD. 1986. Should the annual limit on intake for 125I and 131I be lowered? [Letter]. Health Phys 

50(3):425. 

Makhon'ko KP, Kim VM. 1997. Calculation of the dose load to the thyroid gland from consumption of 

milk after the Chernobyl accident. At Energ (English) 83(1):534-537. Translation from Atomnaya 

Energiya, 83(1):57-60. 

Malarbet JL, Aurengo A, Roy M, et al. 1998. [Dose coefficients from incorporated iodine-129. 

Influence of dietary intake.] Radioprotection 33(1):15-33. (French) 

Malcolm RL. 1989. The relative importance of pH, charge, and water solubility on the movement of 

organic solutes in soils and ground water. Ecol Stud 73:288-301. 
 

 

 

IODINE 419 

9. REFERENCES 

Malinauskas AP, Bell JT. 1987. The chemistry of fission-product iodine under nuclear reactor accident 

conditions. Nuclear Safety 28(4):505-514. 

Malone JF. 1993. Consequences of iodine fall out: Dosimetric and radiobiological considerations. In: 

Delange F et al, ed. Iodine deficiency in Europe. New York, NY: Plenum Press, 229-235. 

Malone JF, Cullen MJ. 1976. Two mechanisms for hypothyroidism after 131I therapy. Lancet 

2(7976):73-75. 

Malone JF, Cullen MJ. 1977. Hypothyroidism after 125I therapy [Letter]. Ann Intern Med 86(6):823. 

Maloof F, Dobyns BM, Vickery AL. 1952. The effect of various doses of radioactive iodine on the 

function and structure of the thyroid of the rat. Endocrinology 50(6):612-638. 

Malpani BL, Samuel AM, Jasiwar RK. 1998. Salivary gland scintigraphy after radioiodine therapy. 

Nucl Med Commun 19:183-184. 

*Mandel SJ, Mandel L. 1999. Persistent sialadenitis after radioactive iodine therapy: Report of two 

cases. J Oral Maxillofac Surg 57:738-741. 

*Mandel SJ, Mandel L. 2003. Radioactive iodine and the salivary glands. Thyroid 13:265-271. 

Mandell RB, Mandell LZ, Link CJJ. 1999. Radioisotope concentrator gene therapy using the 

sodium/iodide symporter gene. Cancer Res 59:661-668. 

Mandell R, McCann L, Link CJ. 1997. Gene therapy of cancer by retroviral transfer and expression of 

the rat sodium/iodide symporter (NIS) [Abstract]. Proc Am Assoc Cancer Res 38:381. 

*Mand\ PA, Poggi G. 1988. In vivo measurements of 131I build-up in human thyroids after the 

Chernobyl reactor accident. Health Phys 54(2):207-209. 

Mangkoewidjojo S. 1979. I. Pathologic effects of polybrominated biphenyls in rats fed a diet containing 

excessive iodine. II. Pathologic changes in calves after oral administration of excessive iodine for six 

months. Ph.D. Dissertation, Michigan State University, p. 193. 

Mangkoewidjojo S, Sleight SD, Convey EM. 1980. Pathologic features of iodide toxicosis in calves. 

Am J Vet Res 41(7):1057-1061. 

Manley SW, Bourke JR, Huxham GJ. 1987. Ionic mechanisms regulating thyroidal secretion: Effects of 

ouabain and medium sodium concentration on radioiodine release from cultured porcine thyroid cells. J 

Endocrinol 112:399-405. 

Manley SW, Huxham GJ, Bourke JR. 1986. Role of sodium influx in thyrotrophin action: Effects of the 

sodium channel agonist veratridine and thyrotropin on radioiodine turnover and membrane potential in 

cultured porcine thyroid cells. J Endocrinol 110:459-466. 

Mano MT, Potter BJ, Belling GB, et al. 1989. The effect of thyroxine, 3,5-dimethyl-3'-isopropyl-Lthyronine and iodized oil on fetal brain development in the iodine-deficient sheep. Acta Endocrinol 

121:7-15. 
 

 

 

IODINE 420 

9. REFERENCES 

Manso PG, Fulanetto RP, Wolosker AMB, et al. 1998. Prospective and controlled study of 

ophthalmopathy after radioiodine therapy for Graves' hyperthyroidism. Thyroid 8(1):49-52. 

Many MC, Denef JF. 1992. Iodine and goiter involution. Thyroidology 4:23-26. 

Many M-C, Denef JS, Hamudi S, et al. 1986. Effects of iodide and thyroxine on iodine-deficient mouse 

thyroid: A morphological and functional study. J Endocrinol 110:203-210. 

Many M-C, Denef J-F, Haumont S, et al. 1985. Morphological and functional changes during thyroid 

hyperplasia and involution in C3H mice: Effects of iodine and 3,5,3'-triiodothyronine during involution. 

Endocrinology 116:798-806. 

Many M-C, Maniratunga S, Varis I, et al. 1995. Two-step development of Hashimoto-like thyroiditis in 

genetically autoimmune prone non-obese diabetic mice: effects of iodine-induced cell necrosis. J 

Endocrinol 147:311-320. 

Many M-C, Papadopoulos J, Martin C, et al. 1991. Iodine induced cell damage in mouse hyperplastic 

thyroid is associated to lipid peroxidation. In: Gordon A, Gross J, Hennemann G, eds. Progress in 

thyroid research. Rotterdam, The Netherlands: Balkema, 635-638. 

Manz F, van't Hof MA, Haschke F, et al. 2000. Iodine supply in children from different European areas: 

The Euro-growth study. J Pediatr Gastroenterol Nutr 31:S72-S75. 

*Mao IF, Chen ML, Ko YC. 2001. Electrolyte loss in sweat and iodine deficiency in a hot environment. 

Arch Environ Health 56(3):271-277. 

*Marcocci C, Chiovato L. 2000a. The epidemiology of thyroid diseases. In: Braverman LE, Utiger RD, 

eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 8th ed. Philadelphia, PA: 

Lippincott-Raven, 474-482. 

*Marcocci C, Chiovato L. 2000b. Thyroid-directed antibodies. In: Braverman LE, Utiger RD, eds. 

Werner and Ingbar's the thyroid: A fundamental and clinical text. 8th ed. Philadelphia, PA: LippincottRaven, 414-431. 

Marcocci C, Cohen JL, Grollman EF. 1984. Effect of actinomycin D on iodide transport in FRTL-5 

thyroid cells. Endocrinology 115:2123-2132. 

Marcocci C, Luini A, Santisteban P, et al. 1987. Norepinephrine and thyrotropin stimulation of iodide 

efflux in FRTL-5 thyroid cells involves metabolits of arachidonic acid and is associated with the 

iodination of thyroglobulin. Endocrinology 120:1127-1133. 

Margulies K, Schirger J, Burnett JJ. 1991. Radiocontrast-induced nephropathy: Current status and 

future prospects. Int Angiol 11:20-25. 

Marine D, Feiss HO. 1915. The absorption of potassium iodide by perfused thyroid glands and some of 

the factors modifying it. J Pharmacol Exp Ther 7:557-576. 

Mariotti S, Martino E, Francesconi M, et al. 1986. Serum thyroid autoantibodies as a risk factor for 

development of hypoparathyroidism after radioactive iodine therapy for single thyroid 'hot' nodule. Acta 

Endocrinol 113:500-507. 
 

 

IODINE 421 

9. REFERENCES 

*Markou K, Georgopopoulos, Kyriazopoulou V, et al. 2001. Iodine-indiced hypothyroidism. Thyroid 

11(5): 501-510. 

*Maros L, Káldy M, Igaz S. 1989. Simultaneous determination of bromide and iodide as acetone 

derivatives by gas chromatography and electron capture detection in natural waters and biological fluids. 

Anal Chem 61:733-735. 

*MARSSIM. 1997. Multi-agency radiation survey and site investigation manual. Nuclear Regulatory 

Commission, Energy Department, Environmental Protection Agency, and Defense Department. 660p. 

NUREG 1575, EPA 402 R 97 016. 

*Marter WL. 1993. Savannah River site radioiodine atmospheric releases and offsite maximum doses 

(U). Westinghouse Savannah River Company, Savannah River Laboratory, SRL-ETS-900317 

(NTIS/DE93004259), pp. 1-35. 

Martin ES, Godley PJ. 1993. Letter to the editor. N Engl J Med 328(5):355-356. 

Martin JE, Fenner FD. 1997. Radioactivity in municipal sewage and sludge. Public Health Reports 

112:308-316. 

Martin MM, Matus RN. 1966. Neonatal exophthalmos with maternal thyrotoxicosis. Am J Dis Child 

111:545-547. 

*Martin MM, Rento RD. 1962. Iodide goiter with hypothyroidism in 2 newborn infants. J Pediatr 

61:94-99. 

Martin RF, Haseltine WA. 1981. Range of radiochemical damage to DNA with decay of iodine-125. 

Science 213:896-898. 

*Martin WE, Turner FB. 1964. Project Sedan. Food-chain relationships of iodine-131 in Nevada 

following the Sedan test of July 1962. NTIS AD-A076 363/1 (AEC-PNE-236F), 5-58. 

Martinez-Galan JR, Pedraza P, Santacana M, et al. 1997. Early iodine deficiency on radial glial cells of 

the hippocampus of the rat fetus. J Clin Invest 99:2701-2709. 

Martino E, Bartalena L, Faglia G, et al. 1996. Central hypothyroidism. In: Braverman LE, Utiger RD, 

eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: LippincottRaven, 779-791. 

Martino E, Bartalena L, Mariotti S, et al. 1988. Radioactive iodine thyroid uptake in patients with 

amiodarone-iodine-induced thyroid dysfunction. Acta Endocrinol 119:167-173. 

Martins MC, Lima N, Knobel M, et al. 1989. Natural course of iodine-induced thyrotoxicosis 

(jodbasedow) in endemic goiter area: A 5 year follow-up. J Endocrinol Invest 12:239-244. 

Martmer EE, Corrigan KE, Charbeneau HP, et al. 1956. A study of the uptake of iodine (I-131) by the 

thyroid of premature infants. Pediatrics 17:503-509. 

Maruyama H, Yamamoto I. 1992. Suppression of 125I-uptake in mouse thyroid by seaweed feeding: 

Possible preventative effect of dietary seaweed on internal radiation injury of the thyroid by radioactive 

iodine. Kitasato Arch Exp Med 65(4):206-216. 
 

 

IODINE 422 

9. REFERENCES 

Mashita K, Kawamura S, Kishino B, et al. 1982. Effects of iodide and propyltiouracil on the release of 

3,5,3'-triiodothyronine and of cyclic adenosine 3',5'-monophosphate from perifused rat thyroids. 

Endocrinology 110:1023-1029. 

Masri MT, Menne M, Rooney BL, et al. 1995. A simplified method for treating Graves' disease with 

radioactive 131I. Wis Med J 94(1):21-25. 

Mathieu I, Caussin J, Smeesters P, et al. 1997. Doses in family members after 131I treatment. Lancet 

350(9084):1074-1075. 

Matovinovic J, Nishiyama RH, Hill HC, et al. 1969. The role of sex and iodine deficiency in the growth 

and function of the rat thyroid transplantable tumor. Cancer Res 29:1398-1406. 

Matsumoto T, Itoh H, Akiba Y. 1969. Effect of (-)-5-vinyl-2-oxazolidinethione on the radioiodine 

metabolism in growing chicks. Poult Sci 48(3):1061-1069. 

Matsunaga E, Shiota K. 1980. Search for maternal factors associated with malformed human embryos: 

A prospective study. Teratology 21:323-331. 

*Maxon HR, Saenger EL. 1996. Biologic effects of radioiodines on the human thyroid gland. In: 

Braverman LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 

Philadelphia, PA: Lippincott-Raven, 342-351. 

*Maxon HR, Saenger EL. 2000. Biologic effects of radioiodines on the human thyroid gland. In: 

Braverman LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 

Philadelphia, PA: Lippincott-Raven, 345-354. 

Maxon HR, Saenger EL, Thomas SR, et al. 1980. Clinically important radiation-associated thyroid 

disease: A controlled study. JAMA 244(16):1802-1805. 

Maxon HR, Thomas SR, Hertzberg VS, et al. 1983. Relation between effective radiation dose and 

outcome of radioiodine therapy for thyroid cancer. N Engl J Med 309(16):937-941. 

Maxon HR, Thomas SR, Saenger EL, et al. 1977. Ionizing irradiation and the induction of clinically 

significant disease in the human thyroid gland. Am J Med 63:967-978. 

Maxon R, Thomas SR, Maxon H. 1987. Effect of gut retention on the effective body half-time of iodine131 in thyroid cancer patients. J Nucl Med Technol 15:13-15. 

May W, Wu D, Eastman C, et al. 1990. Evaluation of automated urinary iodine methods: Problems of 

interfering substances identified. Clin Chem 36:865-869. 

*Mayr U, Butsch A, Schneider S. 1992. Validation of two in vitro test systems for estrogenic activities 

with zearalenone, phytoestrogens and cereal extracts. Toxicology 74:135-149. 

Mazzaferri E. 1996a. Radioiodine and other treatments and outcomes. In: Braverman LE, Utiger RD, 

eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: LippincottRaven, 937-938. 
 

 

IODINE 423 

9. REFERENCES 

Mazzaferri EL. 1996b. Radioiodine and other treatments and outcomes. In: Braverman LE, Utiger RD, 

eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: LippincottRaven, 922-945. 

*Mazzaferri EL, Jhiang SM. 1994. Long-term impact of initial surgical and medical therapy on 

papillary and follicular thyroid cancer. Am J Med 97:418. 

Mazzaferri Z. 1996. Radioiodine and other treatments and outcomes. In: Braverman LE, Utiger RD, 

eds. Werner and Ingbar's the thyroid. Philadelphia, PA: Lippincott Raven, 937-939. 

McAlexander RA, Stevenson JK, Olch PD, et al. 1962. Accelerated mammary tumor development in 

C3H mice fed an iodine-deficient diet. Surg Forum 13:105-106. 

McBride JA. 1964. Acute leukaemia after treatment for hyperthyroidism with radioactive iodine. Br 

Med J 2:736. 

McCarthy JS, Fregly MJ, Nechay BR. 1967. Effect of diuretics on renal iodide excretion by rats and 

dogs. J Pharmacol Exp Ther 158(2):294-304. 

McCauley EH, Linn JG, Goodrich RD. 1973. Experimentally induced iodide toxicosis in lambs. Am J 

Vet Res 34(1):65-70. 

McClain RM. 1989. The significance of hepatic microsomal enzyme induction and altered thyroid 

function in rats: Implications for thyroid gland neoplasia. Toxicol Pathol 17(2):294-306. 

McClain RM. 1992. Thyroid gland neoplasia: Non-genotoxic mechanisms. Toxicol Lett 64/65:397­

408. 

McClain RM, Rice JM. 1999. A mechanistic relationship between thyroid follicular cell tumours and 

hepatocellular neoplasms in rodents. In: Capen CC, Dybing E, Rice JM, et al., eds. Species differences 

in thyroid, kidney and urinary bladder carcinogenesis. Lyon, France: International Agency for Research 

on Cancer, 61-68. 

*McClellan RO, Rupprecht FC, eds. 1968. Radioiodine metabolism in the beagle dog - the importance 

of age and mode of 131I exposure. Fission product inhalation program annual report 1967-1968. 

Albuquerque, NM: Lovelace Foundation for Medical Education and Research, 122-127. 

McClintock JT. 1974. Thyroid cancer after radioactive iodine therapy [Letter]. JAMA 228(3):290. 

McComb DE, Whittum JA. 1973. Chick-embryo deaths traced to tincture of iodine. J Infect Dis 

127(5):581. 

McCruden DC, Hilditch TE, Connell JMC, et al. 1985. Kinetics of [123I]iodide uptake and discharge by 

perchlorate in studies of inhibition of iodide binding by antithyroid drugs. Acta Endocrinol 110:499-504. 

McCullagh FP, Jelden GL, Rodriguez-Antunez A. 1976. Incidence of hypothyroidism following small 

doses of 131I in the treatment of Graves' disease. Ohio State Med J 72(9):538-540. 

McDermott MT. 1997. Oncogenes and thyroid cancer. In: Falk SA, ed. Thyroid disease: 

Endocrinology, surgery, nuclear medicine, and radiotherapy. Philadelphia, PA: Lippinocott-Raven 

Publishers, 231-239. 
 

 

 

 

IODINE 424 

9. REFERENCES 

McDermott MT, Kidd GS, Dodson LE, et al. 1983. Radioiodine-induced thyroid storm. Am J Med 

75:353-359. 

McDougall IR. 1974. Thyroid cancer after iodine-131 therapy [Letter]. JAMA 227(4):438. 

McDougall IR. 1977. In comment: [Letter]. Ann Intern Med 86(6):823-824. 

McDougall IR. 1993. Does radioiodine cause the ophthalmopathy of Graves' disease? Nucl Med 

Commun 14:79-81. 

McDougall IR. 1997. 74 MBq radioiodine 131I does not prevent uptake of therapeutic doses of 131I (i.e. it 

does not cause stunning) in differentiated thyroid cancer. Nucl Med Commun 18:505-512. 

McDougall IR. 1999. Cancer deaths after 131I therapy for thyrotoxicosis. Nucl Med Commun 20:407­

409. 

*McDougall IR, Cavalieri RR. 2000. In vivo radionuclide tests and imaging. In: Braverman LE, Utiger 

RD, eds. Werner and Ingbar’s the thyroid: A fundamental and clinical text. Philadelphia, PA: LippincottRaven, 355-375. 

McDougall IR, Greig WR. 1976. 125I therapy in Graves' disease: Long-term results in 355 patients. Ann 

Intern Med 85:720-723. 

McDougall IR, Greig WR, Gillespie FC. 1971a. Persistence of 125I in thyroid. N Engl J Med 286(3):161. 

See also 79280; Van Middlesworth. 

McDougall IR, Kennedy JS, Thomson JA. 1971b. Thyroid carcinoma following iodine-131 therapy. 

Report of a case and review of the literature. J Clin Endocrinol 33:287-292. 

McDougall IR, Nelsen TS, Kempson RL. 1981. Papillary carcinoma of the thyroid seven years after I131 therapy for Graves' disease. Clin Nucl Med 6(8):368-371. 

McFarlane IA, Shalet SM, Beardwell CG, et al. 1979. Transient hypothyroidism after iodine-131 

treatment for thyrotoxicosis. Br Med J 2:421. 

McGavack TH, Seegers W. 1959. Status of the thyroid gland after age 50. Metabolism 8:136-150. 

McGhee D, John S, Williams JB. 1998. Expression of the sodium-dependent iodide symporter in rat 

organs and identification of a potential isoform generated by alternative mRNA splicing. In: The 

Endocrine Society-annual meeting, program and abstracts. Bethesda, MD: Endocrine Society. 

McGuire RA, Berman M. 1978. Maternal, fetal, and amniotic fluid transport of thyroxine, 

triiodothyronine, and iodide in sheep: A kinetic model. Endocrinology 103(2):567-576. 

McKenzie JM, Zakarija M. 1996. Antibodies in autoimmune thyroid disease. In: Braverman LE, Utiger 

RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: 

Lippincott-Raven, 416-432. 

McKillop JH, Doig JA, Kennedy JS, et al. 1978. Laryngeal malignancy following iodine-125 therapy for 

thyrotoxicosis. Lancet 2(8101):1177-1179. 
IODINE 425 

9. REFERENCES 

*McLachlan SM, Rapaport B. 1992. The molecular biology of thyroid peroxidase: Cloning, expression 

and role as an autoantigen in autoimmune thyroid disease. Endocr Rev 13:192-206. 

*McLachlan SM, Rapoport B. 1996. Genetic factors in thyroid disease. In: Braverman LE, Utiger RD, 

eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: LippincottRaven, 483-496. 

McMonigal KA, Braverman LE, Dunn JT, et al. 2000. Thyroid function changes related to use of 

iodinated water in the U.S. Space Program. Aviat Space Environ Med 71(11):1120-1125. 

Meck RA, Chen MS, Kenny PJ. 1985. Criteria for the administration of KI for thyroid blocking of 

radioiodine. Health Phys 48(2):141-157. 

Medeiros-Neto GA. 1971. Respiration and iodine transport by thyroid slices as influenced by ouabain, 

succinate, alpha-ketoglutarate, sodium and potassium. Acta Physiol Latinoam 21:126-136. 

Medeiros-Neto G. 1994. Letter to the Editor. Clin Endocrinol 40:435. 

Medeiros-Neto GA, Billerbeck AE, Wajchenberg BL, et al. 1993. Defective organification of iodide 

causing hereditary goitrous hypothyroidism. Thyroid 3(2):143-159. 

Medeiros-Neto GA, Hollander CS, Knobel M, et al. 1978. Effects of iodides on the hypothalamicpituitary-thyroid axis in neurological endemic cretinism: Evidence for compensated thyroidal failure in 

adult life. Clin Endocrinol 8:213-218. 

*Mehta RD, von Borstel RC. 1982a. Effect of growth phase and different solvents on the genetic activity 

and cell toxicity of diethylstilbesterol in Saccharomyces cerevisiae. Environ Mutagen 4:417. 

*Mehta RD, von Borstel RC. 1982b. Genetic activty of diethylstilbesterol in Saccharomyces cerevisiae: 

Enhancement of mutagenicity by oxidizing agents. Mutat Res 92:49-61. 

*Meier CA, Burger AG. 1996. Effects of pharmacologic agents on thyroid hormone homeostasis. In: 

Braverman LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 

Philadelphia, PA: Lippincott-Raven, 276-286. 

*Meinhold H, Beckert A, Wenzel KW. 1981. Circulating diiodotyrosine: Studies of its serum 

concentration, source, and turnover using radioimmunoassay after immunoextraction. J Clin Endocrinol 

Metab 53(6):1171-1178. 

*Meinhold H, Gramm HJ, Meissner W, et al. 1991. Elevated serum diiodotyrosine (DIT) in severe 

infections and sepsis: DIT, a possible new marker of leukocyte activity. J Clin Endocrinol Metab 

72:945-953. 

*Meinhold H, Olbricht T, Schwartz-Porsche D. 1987. Turnover and urinary excretion of circulating 

diiodotyrosine. J Clin Endocrinol Metab 64(4):794-800. 

Mello RS, Callisen H, Winter J, et al. 1983. Radiation dose enhancement in tumors with iodine. Med 

Physics 10(1):75-78. 
IODINE 426 

9. REFERENCES 

*Mendel CM, Weisiger RA, Cavalieri RR. 1988. Uptake of 3,5,3'-triiodothyronine by the perfused rat 

liver: Return to the free hormone hypothesis. Endocrinology 123:1817-1824. 

Mendel CM, Weisiger RA, Jones AL, et al. 1987. Thyroid hormone-binding proteins in plasma facilitate 

uniform distribution of thyroxine within tissues: A perfused rat liver study. Endocrinology 120:1742­

1749. 

Mercantini ES. 1970. Iododerma from seafood. Can Med Assoc J 102:759-760. 

*Merkle J, Zeller H. 1979. Absence of povidone-iodine induced mutagenicity in mice and hamsters. J 

Pharm Sci 68:100-102. 

Merwin SE, Balonov MI. 1993. The Chernobyl papers: Vol. I. Doses to the Soviet population and early 

health effects studies. Richland, WA: Research Enterprises. 

Messerli FH, Schmieder RE. 2002. Salt and hypertension. Going to the heart of the matter. Arch Intern 

Med 162(1):104-105. 

Mestdagh C, Many M-C, Halpern S, et al. 1990. Correlated autoradiographic and ion-microscopic study 

of the role of iodine in the formation of "cold" follicles in young and old mice. Cell Tissue Res 260:449­

457. 

Meyer MA. 1994. Re: Cancer risk after iodine-131 therapy for hyperthyroidism [Letter]. J Natl Cancer 

Inst 86(13):1026-1027. 

*MHR. 2001. Nuclear waste dry cask storage. Information brief. St. Paul, Mn: Minnesota House of 

Representatives Research Department. http://www.leg.state.mn.us/hrd/pubs/nucwaste.pdf. 

Michelangeli VP, Poon C, Topliss DJ, et al. 1995. Specific levels of radioiodine treatment on TSAb and 

TBAb levels in patients with Graves' disease. Thyroid 5(3):171-176. 

Mikkonen R. 1998. Incidence and risk factors for delayed allergy-like reactions to x-ray contrast media 

adult and pediatric populations. Pharmacoepidemiol Drug Saf 7:S11-S15. 

Mikulecky M, Beno M, Komornik I. 1993. Time delay of maximal human thyroid 131I uptake after the 

Chernobyl accident. Naturwissenschaften 80:125-127. 

*Millard RK, Saunders M, Palmer AM, et al. 2001. Approximate distribution of dose among foetal 

organs radioiodine uptake via placenta transfer. Phys Med Biol 46(11):2773-2783. 

*Miller JK, Swanson EW. 1963. Some factors affecting iodine secretion in milk. J Dairy Sci 46:927. 

Miller KL, Coen PE, White WJ, et al. 1989. Effectiveness of skin absorption of tincture of I in blocking 

radioiodine from the human thyroid gland. Health Phys 56(6):911-914. 

Miller KL, White WJ, Lang CM, et al. 1985. Skin exposure to I blocks thyroid uptake to 131I. Health 

Phys 49(5):791-794. 

Miller M. 1998. Risk modeling can be key to determining radiation exposures. J Natl Cancer Inst 

90(21):1596-1598. 
IODINE 427 

9. REFERENCES 

Miller WJ. 1975. New concepts and developments in metabolism and homeostasis of inorganic elements 

in dairy cattle. A review. J Dairy Sci 58(10):1549-1560. 

Mills I, Sherwin JR. 1985. A comparison of the mechanisms of alpha-adrenergic inhibition of 

thyrotropin-stimulated adenosine 3',5'-monophosphate in cat, rat, mouse, hamster, beef, and pig tissues 

with the stimulatory effect of epinephrine on beef thyroid iodination: Evidence for multiple, speciesspecific adrenergic mechanisms. Endocrinology 116:1310-1315. 

*Minelli R, Braverman LE, Guiberti T, et al. 1997. Effects of excess iodine administration on thyroid 

function in euthyroid patients with a previous episode of thyroid dysfunction induced by interferon-alpha 

treatment. Clin Endocrinol 47:357-361. 

*Minelli R, Braverman LE, Valli MA, et al. 1999. Recombinant interferon alpha (rIFN-alpha) does not 

potentiate the effect of iodine excess on the development of thyroid abnormalities in patients with HCV 

chronic active hepatitis. Clin Endocrinol 50:95-100. 

Misaki T, Miyamoto S, Alam MS, et al. 1996. Tumoricidal cytokines enhance radioiodine uptake in 

cultured thyroid cancer cells. J Nucl Med 37(4):646-648. 

Mittag TW, Guo W-B, Taniguchi T. 1993. Interaction of vanadate and iodate oxyanions with adenylyl 

cyclase of ciliary processes. Biochem Pharmacol 45(6):1311-1316. 

Mityukova TA, Astakhova LN, Asenchyk LD, et al. 1995. Urinary iodine excretion in Belarus children. 

Eur J Endocrinol 133:216-217. 

Miura S, Hara Y, Iitaka M, et al. 1991. Disturbance of thyroidal iodine metabolism in BB/W rat. 

Endocrinol Jpn 38:647-653. 

*Miyake Y, Tsunogai S. 1963. Evaporation of iodine from the ocean. J Geophys Res 68:3989. 

Miyake Y, Eguchi W, Adachi M, et al. 1979. Effect of carbon dioxide on the absorption rate and 

mechanism of iodine vapor. J Chem Eng Jpn 12(6):436-442. 

*Miyazaki A, Bansho K. 1987. Differential determination of trace amounts of iodide and iodate in water 

by solvent extraction-inductively coupled plasma atomic emission spectrometry. Spectrochim Acta, Part 

B 42B:227-233. 

Mizukami Y, Michigishi T, Nonomura A, et al. 1993. Iodine-induced hypothyroidism: A clinical and 

histological study of 28 patients. J Clin Endocrinol Metab 76(2):466-471. 

M'Kacher R, Legal J-D, Schlumberger M, et al. 1997. Sequential biological dosimetry after a single 

treatment with iodine-131 for differentiated thyroid carcinoma. J Nucl Med 38:377-380. 

M'Kacher R, Schlumberger M, Legal J-D, et al. 1998. Biologic dosimetry in thyroid cancer patients after 

repeated treatments with iodine-131. J Nucl Med 39:825-829. 

*Mochizuki Y, Mowafy R, Pasternack B. 1963. Weights of human thyroids in New York City. Health 

Phys. 9:1299-1301. 
 

 

IODINE 428 

9. REFERENCES 

*Moiseyev IT, Tikhomirov FA, Perevezentsev VM, Rerikh LA. 1984. Role of soil properties, 

interspecific plant differences, and other factors affecting the accumulation of radioactive iodine in crops. 

Soviet Soil Science 16:60-66. 

*Momotani N, Hisaoka T, Noh J, et al. 1992. Effects of iodine on thyroid status of fetus versus mother 

in treatment of Graves' disease complicated by pregnancy. J Clin Endocrinol Metab 75(3):738-744. 

Monakhov AS. 1988. [Cytogenetic and blastomogenic effects of 45Ca and 131I administered to rats.] 

Eksp Onkol 10(4):27-30. (Russian) 

*Moneret-Vautrin DA, Mata E, Gerard H, et al. 1989. Probable allergy to polyvidon, responsible for a 

reaction to iodinated contrast medium: A case of asthma after hysterosalpingography. Allerg Immunol 

21(5): 198-199. (French) 

*Monteiro Gil O, Oliveira NG, Rodrigues AS, et al. 2000. Cytogenic alterations and oxidative stress in 

thyroid cancer patients after iodine-131 therapy. Mutagenesis 15(1):69-75. 

*Moody KD, Miller KL, White WJ, et al. 1988. The effects of topical povidone I solution on serum 

iodide levels and thyroid uptake of 131I in dogs. Health Phys 55(1):9-13. 

Mooij P, De Wit HJ, Bloot AM, et al. 1993a. Iodine deficiency induces thyroid autoimmune reactivity in 

Wistar rats. Endocrinology 133(3):1197-1204. 

Mooij P, De Wit HJ, Drexhage HA. 1993b. An excess of dietary iodine accelerates the development of a 

thyroid-associated lymphoid tissue in autoimmune prone BB rats. Clin Immunol Immunopathol 

69(2):189-198. 

Mooij P, De Wit HJ, Drexhage HA. 1994. A high iodine intake in Wistar rats results in the development 

of a thyroid-associated ectopic thymic tissue and is accompanied by a low thyroid autoimmune reactivity. 

Immunology 81:309-316. 

Moore MJ. 1975. Leukemia incidence in adults not increased after 131I. N Engl J Med 292(25):1353­

1354. 

Morales de Villalobos LM, Campos G, Ryder E. 1986. Effect of chronic ingestion of iodide during 

pregnancy and lactation on rat pup brain enzymes. Enzyme 35:96-101. 

*Moran JE, Oktay S, Santschi PH, et al. 1999. Atmospheric dispersal of 129iodine from nuclear fuel 

reprocessing facilities. Environ Sci Technol 33:2536-2542. 

Moreno AJ, Hartshome MF, Yedinak MA, et al. 1986. Tinea corporis overlying the thyroid gland after 

radioiodine (131I) treatment of Graves' disease. Cutis 37(4):271-273. 

*Morgan A, Morgan DJ, Arkell GM. 1967a. A study of the retention and subsequent metabolism of 

inhaled methyl iodide. In. Davies CN, ed. Inhaled Particles and Vapours II. Pergamon Press, Oxford, 

309-321. 

*Morgan A, Morgan DJ, Black A. 1968. A study on the deposition, translocation and excretion of 

radioiodine inhaled as iodine vapour. Health Phys 15:313-322. 
IODINE 429 

9. REFERENCES 

*Morgan A, Morgan DJ, Evans JC, et al. 1967b. Studies on the retention and metabolism of inhaled 

methyl iodide-II: Metabolism of methyl iodide. Health Phys 13:1067-1074. 

*Morgan DJ, Morgan A. 1967. Studies on the retention and metabolism of inhaled methyl iodide-I: 

Retention of inhaled methyl iodide. Health Phys 13:1055-1065. 

Morgan KG, Entrikin RK, Bryant SH. 1975. Mytonia and block of chloride conductance by iodide in 

avian muscle. Am J Physiol 229(5):1155-1158. 

*Morita S, Umezaki N, Ishibashi M, et al. 1998. Determining the breast-feeding interruption schedule 

after administration of 123I-iodide. Ann Nucl Med 12(5):303-306. 

Morizono T, Sikora MA. 1983. Compound action potential input-output decruitment: Effect of topically 

applied antiseptics. Arch Otolaryngol 109:677-681. 

Morreale de Escobar G, Calvo R, Obregon MJ, et al. 1992. Homeostatis of brain T3 in rat fetuses and 

their mothers: Effects of thyroid status and iodine deficiency. Acta Med Austriaca 19(Suppl 1):110-116. 

Morreale de Escobar G, Obregon MJ, Calvo R, et al. 1991. Maternal thyroid hormones during 

pregnancy: Effects on the fetus in congenital hypothyroidism and in iodine deficiency. In: Bercu BB, 

Shulman DI, eds. Advances in perinatal thyroidology. New York, NY: Plenum Press, 133-156. 

Morreale de Escobar G, Obregon MJ, Calvo R, et al. 1993. Effects of iodine deficiency on thyroid 

hormone metabolism and the brain in fetal rats: The role of the maternal transfer of thyroxin. Am J Clin 

Nutr Suppl(57):280S-285S. 

Morreale de Escobar G, Obregon MJ, Escobar del Rey F. 1987. Fetal and maternal thyroid hormones. 

Horm Res 26:12-27. 

Morrish DW, Jackson FI, Lalani ZH, et al. 1989. Cystic thyroid mass following I-131 treatment of 

papillary thyroid carcinoma: An unusual complication. Clin Nucl Med 14(12):894-896. 

*Morrison RT, Birkbeck JA, Evans TC, et al. 1963. Radioiodine uptake studies in newborn infants. J 

Nucl Med 4:162-166. 

*Morselli PL, Franco-Morselli R, Bossi L. 1980. Clinical pharmacokinetics in newborns and infants: 

Age-related differences and therapeutic implications. Clin Pharmacokin 5:485-527. 

Mortensen JD, Woolner LB, Bennett WA. 1955. Gross and microscopic findings in clinically normal 

thyroid glands. J Clin Endocrinol Metab 15:1270-1280. 

Moschizuki Y, Mowafy R, Pasternack B. 1963. Weights of human thyroids in New York City. Health 

Phys 9:1299-1301. 

Moses AM, Scheinman SJ. 1996a. The kidneys and electrolyte metabolism in hypothyroidism. In: 

Braverman LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 

Philadelphia, PA: Lippincott-Raven, 812-815. 

Moses AM, Scheinman SJ. 1996b. The kidneys and electrolyte metabolism in thyrotoxicosis. In: 

Braverman LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 

Philadelphia, PA: Lippincott-Raven, 628-631. 
 

 

IODINE 430 

9. REFERENCES 

Mosher BW, Winkler P, Jaffrezo J-L. 1993. Seasonal aerosol chemistry at Dye 3, Greenland. Atmos 

Environ 27A(17/18):2761-2772. 

*Mostbeck A, Galvan G, Bauer P, et al. 1998. The incidence of hyperthyroidism in Austria form 1987 to 

1995 before and after an increase in salt iodization in 1990. Eur J Nucl Med 25(4):367-374. 

Mothersill C, Seymour C, Malone JF, et al. 1986. Survival and transformation frequency of 

differentiated sheep thyroid cells exposed to iodine-131 and gamma-irradiation. Int J Radiat Biol 

49(3):524-525. 

Mothersill C, Seymour CB, Moriarty MJ, et al. 1984. Further studies on the transformation of thyroid 

cultures by gamma-irradiation and by iodine-131. Int J Radiat Biol 46(5):648. 

*Mould RF. 2000. Chernobyl record: The definitive history of the Chernobyl catastrophe. Philadelphia, 

PA: Institute of Physics Publishing. 

Mountford PJ, Coakley AJ. 1989. A review of the secretion of radioactivity in human breast milk: Data, 

quantitative analysis and recommendations. Nucl Med Commun 10:15-27. 

*Mountford PJ, O'Doherty MJ. 1999. Exposure of critical groups to nuclear medicine patients. Appl 

Radiat Isot 50:89-111. 

*Mountford PJ, Steele HR. 1995. Fetal dose estimates and the ICRP abdominal dose limit for 

occupational exposures of pregnant staff to technetium-99m and iodine-131 patients. Eur J Nucl Med 

22(10):1173-1179. 

Moura EG, Ramos CF, Nascimento CCA, et al. 1987. Thyroid function in fasting rats: Variations in 131I 

uptake and transient decrease in peroxidase activity. Braz J Med Biol Res 20:407-410. 

*Movius EG, Phyillaier MM, Robbins J. 1989. Phloretin inhibits cellular uptake and nuclear receptor 

binding of triiodothyronine in human hep G2 hepatocarcinoma cells. Endocrinology 124(4):1988-1997. 

*Moxon RE. 1984. Automatic methods for the determination of total inorganic iodine and free iodide in 

waters. Analyst 109:425-430. 

Mu L, Chengyi Q, Qidong Q, et al. 1987. Endemic goitre in central China caused by excessive iodine 

intake. Lancet 2(8553):257-259. 

Mukherjee B. 1983. Inhibition and recovery of the iodine uptake function of rat thyroids after 18 MeV 

proton irradiation in vivo. Br J Radiol 56:67-68. 

Murakami S, Nasu M, Fukayama H, et al. 1993. Propranolol has direct antithyroid activity: Inhibition of 

iodide transport in cultured thyroid follicles. Cell Biochem Funct 11:159-165. 

Muraki T, Tsukahara F, Fujii E, et al. 1991. Alpha1-adrenergic stimulation of iodide organification in 

mouse thyroid-inhibition by protein kinase C inhibitors. Arch Int Pharmacodyn 314:122-132. 

*Muramatsu Y, Yoshida S. 1995. Volatilization of methyl iodide from the soil-plant system. Atmos 

Environ 29(1):21-25. 
IODINE 431 

9. REFERENCES 

Muramatsu Y, Sumiya M, Ohomo Y. 1986. Levels and behavior of 127I and 129I in the environment in 

Japan. In: Spurenelement-Symposium Iodine, 5th ed, 35-41. 

Muramatsu Y, Uchida S, Sriyotha P, et al. 1990. Some considerations on the sorption and desorption 

phenomena of iodide and iodate on soil. Water Air Soil Pollut 49:125-138. 

*Muramatsu Y, Uchida S, Sumiya M, et al. 1985. Iodine separation procedure for the determination of 

129I and 127I in soil by neutron activation analysis. J Radioanal Nucl Chem 94(5):329-338. 

Murphy PC, Burson ZG. 1973. Personnel exposures due to inadequate leak test methods for 125I sources. 

Health Phys 24:443-444. 

*Murray JL. 1969. Thyroid uptake of iodine-131 from skin exposure. Health Phys 17:730-731. 

*Murray RL. 1994. Understanding radioactive waste. 4th ed. Columbus, OH: Battelle Press, 60-193. 

Mutaku JF, Many M-C, Colin I, et al. 1998. Antigoitrogenic effect of combined supplementation with 

dl-alpha-tocopherol, ascorbic acid and beta-carotene and of dl-alpha-tocopherol alone in the rat. J 

Endocrinol 156:551-561. 

*Myant NB. 1956. Enterohepatic circulation of thyroxine in humans. 

*Myant NB. 1958. Passage of thyroxine and tri-iodo-thyronine from mother to foetus in pregnant 

women. Clin Sci 17:75-79. 

*Myant NB, Pochin EE. 1950. The metabolism of radiothyroxine in man. Clin Sci 9:421-440. 

Myers DK. 1971. DNA repair in E. coli B/r after X-irradiation in the presence of iodide or 

iodoacetamide. Int J Radiat Biol 19(3):293-295. 

Myers DK. 1977. Repair of the double-strand breaks produced by 125I disintegrations in the DNA of 

Micrococcus radiodurans. Curr Top Radiat Res Q 12:369-388. 

*Myers DK, Chetty KG. 1973. Effect of radiosensitizing agents on DNA strand breaks and their rapid 

repair during irradiation. Radiat Res 53:307-314. 

Nagata C, Tagashira T, Inomata M, et al. 1971. Effect of iodine on the carcinogenicity of 3,4­

benzopyrene. Jpn J Cancer Res 62:309-314. 

*Nagata K, Takasu N, Akamine H, et al. 1998. Urinary iodine and thyroid antibodies in Okinawa, 

Yamagata, Hyogo, and Nagano, Japan: The differences in iodine intake do not affect thyroid antibody 

positivity. Endocrine Journal 45(6):797-803. 

Nagataki S, Nagayama Y. 1997. Molecular biology of the thyroid stimulating hormone receptor. In: 

Falk SA, ed. Thyroid disease: Endocrinology, surgery, nuclear medicine, and radiotherapy. 

Philadelphia, PA: Lippincott-Raven Publishers, 209-222. 

*Nagataki S, Yokoyama N. 1996. Other factors regulating thyroid function: Autoregulation: Effects of 

iodide. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical 

text. Philadelphia, PA: Lippincott-Raven, 241-247. 
 

 

IODINE 432 

9. REFERENCES 

Nagataki S, Shibata Y, Inoue S, et al. 1994. Thyroid diseases among atomic bomb survivors in 

Nagasaki. JAMA 272:364-370. 

*Nagataki S, Shizume K, Nakao K. 1967. Thyroid function in chronic excess iodide ingestion: 

Comparison of thyroidal absolute iodine uptake and degradation of thyroxine in euthyroid Japanese 

subjects. J Clin Endocrinol 27:638-647. 

Nagataki S, Uchimura H, Masuyama Y, et al. 1973. Is TSH-stimulated thyroid hormone release 

inhibited by iodide? Endocrinology 93:532-539. 

Nair SK, Apostoaei AI, Hoffman FO. 2000. A radioiodine speciation, deposition, and dispersion model 

with uncertainty propagation for the Oak Ridge Dose Reconstruction. Health Phys 78(4):394-413. 

Nakajima H, Sasaki N, Kubimura N, et al. 1974. [Infantile hypothyroidism caused by 131 I in mother's 

milk.] Nippon Rinsho 32(7):2430-2432. (Japanese) 

Nakajima T, Wang R-S, Elovaara E, et al. 1992. A comparative study on the contribution of cytochrome 

P450 isozymes to metabolism of benzene, toluene and trichloroethylene in rat liver. Biochem Pharmacol 

43(2):251-257. 

Nakamoto Y, Saga T, Misaki T, et al. 2000. Establishment and characterization of a breast cancer cell 

line expressing Na+/I- symporters for radioiodide concentrator gene therapy. J Nucl Med 41(11):1898­

1904. 

*Nakamura Y, Kotani T, Ohtaki S. 1990. Transcellular iodide transport and iodination on the apical 

plasma membrane by monolayer porcine thyroid cells cultured on collagen-coated filters. J Endocrinol 

126:275-281. 

Nakane Y, Honda S, Mine M, et al. 1996. The mental health of atomic bomb survivors. In: Nagataki S, 

Yamashita S, eds. Nagasaki symposium radiation and human health: Proposal from Nagasaki. 

Amsterdam, The Netherlands: Elsevier, 239-249. 

Nakayama S. 1970a. [Studies on hematologic changes after administration of therapeutic doses of 

radioactive iodine: I. Statistical studies on the occurrence of leukemia.] Nippon Ketsueki Gakkai Zasshi 

33(5):560-577. (Japanese) 

Nakayama S. 1970b. [Studies on the hematological changes after administration of therapeutic doses of 

radioactive iodine.] Nippon Ketsueki Gakkai Zasshi 33(5):578-597. (Japanese) 

*Namba H, Yamashita S, Kimura H, et al. 1993. Evidence of thyroid volume increase in normal subjects 

receiving excess iodide. J Clin Endocrinol Metab 76(3):605-608. 

Nanping W, Guangjun Y, Zijin T. 1998. Kinetic effect of testosterone of estradiol on iodine absorption 

in castrating rat intestine. Wei Sheng Yen Chiu 27(6):396-399. 

Napier BA, Eslinger PW, Nichols WE, et al. 2001. Improvements in modeling sagebrush concentrations 

of radioiodine released from the Hanford site. J Environ Radioact 54(3):377-389. 

Narra VR, Howell RW, Harapanhalli RS, et al. 1992. Radiotoxicity of some iodine-123, iodine-125 and 

iodine-131-labeled compounds in mouse testes: Implications for radiopharmaceutical design. J Nucl 

Med 33(12):2196-2201. 
 

 

IODINE 433 

9. REFERENCES 

Narra VR, Howell RW, Sastry KSR, et al. 1993. Vitamin C as a radioprotector against iodine-131 in 

vivo. J Nucl Med 34:637-640. 

Narra VR, Howell RW, Thanki KH, et al. 1991. Radiotoxicity of 125I-iodoeoxyuridine in preimplantation mouse embryos. Int J Radiat Biol 60(3):525-532. 

*NAS. 1974. Geochemistry and the environment: Volume I: The relation of selected trace elements to 

health and disease. Washington, DC: National Academy of Sciences. NTIS PB80-135197. 

*NAS/NRC. 1989. Report of the oversight committee. In: Biologic markers in reproductive toxicology. 

Washington, DC: National Academy of Sciences, National Research Council, National Academy Press. 

Nasu M, Sugaware M. 1994. Exogenous free iodotyrosine inhibits iodide transport through the 

sequential intracellular events. Eur J Endocrinol 130:601-607. 

Nauman J, Wolff J. 1993. Iodide prophylaxis in Poland after the Chernobyl reactor accident: Benefits 

and risks. Am J Med 94:524-532. 

*NCI. 1997. Estimated exposures and thyroid doses received by the American people from iodine-131 in 

fallout following Nevada atmospheric nuclear bomb tests. National Cancer Institute. 

http://rex.nci.nih.gov/massmedia/Fallout. 

*NCRP. 1977. Protection of the thyroid gland in the event of releases of radioiodine. Washington, DC: 

National Council on Radiation Protection and Measurements. NCRP Report No. 55, 19-29. 

*NCRP. 1983. Iodine-129: Evaluation of releases from nuclear power generation. Bethesda, MD: 

National Council on Radiation Protection and Management. NCRP Report No. 75. 

*NCRP. 1985. General concepts for the dosimetry of internally deposited radionuclides. National 

Council on Radiation Protection and Measurements. Bethesda, MD: NCRP Report No.84. 

*NCRP. 1987. Use of bioassay procedures for assessment of internal radionuclide deposition. National 

Council on Radiation Protection and Measurements. Bethesda, MD: NCRP Report No. 87. 

*NCRP. 1993. Limitation of exposure to ionizing radiation. National Council on Radiation Protection 

and Measurements. Report No. 116. National Council on Remediation Protection and Measurement. 

NCRP. 1996. A guide for uncertainty analysis in dose and risk assessments related to environmental 

contamination. Bethesda, MD: National Council on Radiation Protection and Management. NCRP 

Commentary No. 14. 

*NCRP. 1997. Deposition, retention and dosimetry of inhaled radioactive substances. National Council 

on Radiation Protection and Measurements. Report No. 125. 

*NCSL. 2002. Radioactive waste news. A quarterly summary of generation, transportation, storage and 

disposal issues. National Conference of Sate Legislatures. Vol. 19(2) 1-8. 

*Negretti de Bratter VE, Bratter P, Tomiak A. 1990. An automated microtechnique for selenium 

determination in human body fluids by flow injection hydride atomic absorption spectrometry (FlHAAS). J Trace Elem Electrolytes Health Dis 4(1):41-48. 
IODINE 434 

9. REFERENCES 

Nelson M, Phillips DIW. 1985. Seasonal variations in dietary iodine intake and thyrotoxicosis. Hum 

Nutr Appl Nutr 39A:213-216. 

Nemec J, Neradilova M, Zamrazil V, et al. 1968. [Hematological changes during treatment of 

thyrotoxicosis and thyroid carcinoma with radioactive iodine 131.] Cas Lek Cesk 107(25):742-748. 

(Czech) 

Nemec J, Soumar J, Zeman V, et al. 1978. Differentiated thyroid cancer following radioiodide 131I 

therapy of hyperthyroidism - a case report. Oncology 35:277-280. 

Netelenbos JC, Lips P. 1981. Hyperparathyroidism after radioactive iodine therapy. Arch Intern Med 

141:1555-1556. 

Neu F, Rebai T, Denef J-F, et al. 1994. Involvement of T cell immunity in the transient thyroid 

inflammation induced by iodide in goitrous BALB/C and nude mice. Autoimmunity 17:209-216. 

Neve P, Starling JR, Golstein J, et al. 1988. Effects of iodine intake on thyroid secondary lysosomes 

after subtotal thyroidectomy. Endocrinology 1988:478-486. 

Newkirk KA, Ringel MD, Wartofsky L, et al. 2000. The role of radioactive iodine in salivary gland 

dysfunction. Ear Nose Throat J 79(6):460-468. 

Newton GL, Clawson AJ. 1974. Iodine toxicity: Physiological effects of elevated dietary iodine on pigs. 

J Anim Sci 39(5):879-884. 

Newton GL, Barrick ER, Harvey RW, et al. 1974. Iodine toxicity. Physiological effects of elevated 

dietary iodine on calves. J Anim Sci 38(2):449-455. 

*Ng YC, Anspaugh LR, Cederwall RT. 1990. ORERP internal dose estimates for individuals. Health 

Phys 59(5):693-713. 

Nicoloff JT, LoPresti JS. 1996. Nonthyroidal illnesses. In: Braverman LE, Utiger RD, eds. Werner and 

Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 286-296. 

*Nikiforov YE, Fagin JA. 1998. Radiation-induced thyroid cancer in children after the Chernobyl 

accident. Thyroid Today: 21(2):1-10. 

Nilsson G. 1973. Self-limiting episodes of Jodbasedow. Acta Endocrinol 74:475-482. 

Nilsson M, Ericson LE. 1994. Effects of epidermal growth factor on basolateral iodide uptake and apical 

iodide permeability in filter-cultured thyroid epithelium. Endocrinology 135(4):1428-1436. 

*Nilsson M, Bjorkman U, Ekholm R, et al. 1990. Iodide transport in primary cultured thyroid follicle 

cells: Evidence of a TSH-regulated channel mediating iodide efflux selectively across the apical domain 

of the plasma membrane. Eur J Cell Biol 52:270-281. 

*NIOSH. 2001. Documentation for immediately dangerous to life or health concentrations. National 

Institute for Occupational Safety and Health. http://www.cdc.gov/niosh/idlh/intridl4.html. 
 

 

 

IODINE 435 

9. REFERENCES 

NIREX. 1987. Radionuclide interactions with marine sediments. Harwell, England: Nuclear Industry 

Radioactive Waste Executive. NTIS DE90630517. 

Nishimaki T, Furudate S. 1997. Effects of stable KI administration on iodine-125 distribution in various 

mouse organs. Radioisotopes 46(10):720-723. 

*Nishioka K, Seguchi T, Yasuno H, et al. 2000. The results of ingredient patch testing in contact 

dermatitis elicited by povidone-iodine preparations. Contact Dermatitis 42(2):90-94. 

*Nishiyama H, Lukes S, Mayfield G, et al. 1980. Internal contamination of laboratory personnel by 131I. 

Radiology 137:767-771. 

*Nishizawa K, Hamada N, Sadayuki S. 1985. In vitro monitoring of salivary 125I. Health Phys 

49(2):290-295. 

*Noble B, Yoshida T, Rose NR, et al. 1976. Thyroid antibodies in spontaneous autoimmune thyroiditis 

in the Buffalo rat. J Immunol 117:1447. 

*Nobukuni K, Kawahara S. 2002. Thyroid function in nurses: The influence of povidone-iodine hand 

washing and gargling. Dermatology 204:99-102. 

*Nobukini K, Hayakawa N, Namba R, et al. 1997. The influence of long-term treatment with providoneiodine on thyroid function. Dermatology 195(Suppl 2):69-72. 

*Noguti T, Sadaie H, Kada T. 1971. Radiosentization with iodine compounds: III. Macromolecular 

synthesis and repair in Bacillus subtilis irradiated in the presence of iodoacetic acid, potassium iodide or 

potassium iodate. Int J Radiat Biol 19(4):305-322. 

Nohr SB, Jorgensen A, Pedersen KM, et al. 2000. Postpartum thyroid dysfunction in pregnant thyroid 

peroxidase antibody-positive women living in an area with mild to moderate iodine deficiency: is iodine 

supplementation safe? J Clin Endocrinol Metab 85(9):3191-3198. 

Nolte W, Mueller R, Huefner M. 1995. [Treatment of iodine induced hyperthyroidism. Possibilities and 

limits of the pharmacotherapy.] Med Klin 90(5):246-253. (German) 

Nomura T, Katagiri H, Kitahara Y, et al. 1980. Methods of I-129 analysis for environmental monitoring. 

In: Ed. Radiation protection: A systematic approach to safety. Oxford, England: Pergamon Press, 935­

938. 

*Nordenson I, Beckman G, Beckman L, et al. 1978. Occupational and environmental risks in and around 

a smelter in northern Sweden: II. Chromosomal aberrations in workers exposed to arsenic. Hereditas 

88:47-50. 

Norfray JF, Quinn JLIII. 1974. Furosemide mediated elevations of thyroid iodide uptake in the rat. Proc 

Soc Exp Biol Med 145:286-288. 

*Norman JA, Pickford CJ, Sanders TW, Waller M. 1988. Human intake of arsenic and iodine from 

seaweed-based supplements and health foods available in the UK. Food Additives and Contaminants 

5:103-109. 
 

 

 

 

 

IODINE 436 

9. REFERENCES 

*North DL, Shearer DR, Hennessey JV, et al. 2001. Effective half-life of 131I in thyroid cancer patients. 

Health Phys 81(3):325-329. 

Noteboom JL, Hummel WA, Broerse JJ, et al. 1997a. Protection of the infant thyroid from radioactive 

contamination by the administration of stable iodide. An experimental evaluation in chimpanzees. Radiat 

Res 147:698-706. 

Noteboom JL, Hummel WA, Broerse JJ, et al. 1997b. Protection of the maternal and fetal thyroid from 

radioactive contamination by the administration of stable iodide during pregnancy. An experimental 

evaluation in chimpanzees. Radiat Res 147:691-697. 

Noteboom JL, Hummell WA, Jansen JTM, et al. 1997c. Simulation of measurements of uptake of 123Iiodide in the thyroid of fetal chimpanzees. Radiat Res 147:686-690. 

*Nourok DS, Gassock RJ Solomon DH, Maxwell MH. 1964. Hypothyroidism following prolonged 

sodium nitroprusside therapy. Am J Med Sci 284:129-138. 

*Novaes M, Biancalana MM, Garcia SA, et al. 1994. Elevation of cord blood TSH concentration in 

newborn infants of mothers exposed to acute povidone iodine during delivery. J Endocrinol Invest 

17:805-808. 

*NRC. 1989. National Research Council. Iodine. In: Recommended dietary allowances. 10th edition. 

Washington, DC: National Academy Press, 213-217. 

*NRC. 1993. Pesticides in the diets of infants and children. National Research Council. Washington, 

DC: National Academy Press. 

*NRC. 1995. Radiation dose reconstruction for epidemiologic uses. Committee on Assessment of CDC 

Radoation Studies, National Research Council. National Academy Press, Washington, 103-111. 

*NRC. 1999. Exposure of the American people to iodine-131 from Nevada nuclear-bomb tests. 

National Research Council. National Academy Press, Washington, DC. 

*NRC. 2000. Review of the Hanford thyroid disease study draft final report. National Reaserch 

Council. National Academy Press, Washington, D.C. 

*NRC. 2004. Distribution and administration of potassium iodide in the event of a nuclear incident. 

National Research Council. National Academy Press, Washington, DC., 28-29. 

*NRCC. 1980. National Research Council of Canada. Radioactivity in the Canadian environment. 

Ottawa, Ontario. NTIS DE82701242. 

Nygaard B, Faber J, Veje A, et al. 1995a. Appearance of Graves'-like disease after radioiodine therapy 

for toxic as well as non-toxic multinodular goitre. Clin Endocrinol 43:129-131. 

Nygaard B, Faber J, Veje A, et al. 1999. Transition of nodular toxic goiter to autoimmune 

hyperthyroidism triggered by 131I therapy. Thyroid 9(5):477-481. 

Nygaard B, Hegedus L, Gervil M, et al. 1993. Radioiodine treatment of multinodular non-toxic goitre. 

Br Med J 307:828-832. 
 

 

IODINE 437 

9. REFERENCES 

Nygaard B, Hegedus L, Gervil M, et al. 1995b. Influence of compensated radioiodine therapy on thyroid 

volume and incidence of hypothyroidism in Graves' disease. J Int Med 238:491-497. 

Nygaard B, Knudsen JH, Hegedus L, et al. 1997. Thyrotropin receptor antibodies and Graves' disease, a 

side-effect of 131I treatment in patients with nontoxic goiter. J Clin Endocrinol Metab 82(9):2926-2930. 

Ober KP, Hennessy JF. 1981. Jodbasedow and thyrotoxic periodic paralysis. Arch Intern Med 

141:1225-1227. 

Oberhausen E. 1990. Side effects of iodine-containing chemical. In: Rubery E, Smales E, eds. Iodine 

prophylaxis following nuclear accidents. Oxford, UK: Pergamon Press, 93-100. 

Oberhausen E. 1991. Risk of thyroid carcinoma after iodine-131 treatment. EUR 12556:111-144. 

O'Connell MEA, Flower MA, Hinton PJ, et al. 1993. Radiation dose assessment in radioiodine therapy. 

Dose-response relationships in differentiated thyroid carcinoma using quantitative scanning and PET. 

Radiother Oncol 28:16-26. 

*Oddie TH, Fisher DA. 1967. Mean euthyroid 24-hour radioiodine uptake as a characteristic of different 

patient populations. J Clin Endocrinol Metab 27:11-14. 

Oddie TH, Fisher DA, Criner G. 1966. Lag time for oral radioiodide tracer doses. J Clin Endocrinol 

Metab 26(5):581-582. 

Oddie TH, Fisher DA, Long JM. 1964. Factors affecting the estimation of iodine entering the normal 

thyroid gland using short-term clearance studies. J Clin Endocrinol 24:924-933. 

*Oddie TH, Fisher DA, McConahey WM, et al. 1970. Iodine intake in the United States: A 

reassessment. J Clin Endocrinol 30:659-665. 

*Oddie TH, Meschan I, Wortham J. 1955. Thyroid function assay with radioiodine. I. Physical basis of 

study of early phase of iodine metabolism and iodine uptake. J Clin Invest 34:95-105. 

*Oddie TH, Myhill J, Pirnique FG, et al. 1968a. Effect of age and sex on the radioiodine uptake in 

euthryoid subjects. J Clin Endocrinol 28:776-782. 

Oddie TH, Pirnique FG, Fisher DA, et al. 1968b. Geographic variation of radioiodine uptake in 

euthyroid subjects. J Clin Endocrinol 28:761-775. 

*Oddie TJ, Thomas ID, Rundle FF, et al. 1960. Diagnostic limits for thyroidal radioiodine uptake rates. 

J Clin Endocrinol Metab 20:389-400. 

O'Doherty MJ, Coakley AJ. 1998. Drug therapy alternatives in the treatment of thyroid cancer. Drugs 

55:801-812. 

O'Doherty MJ, Kettle AG, Eustance CNP, et al. 1993. Radiation dose rates from adult patients receiving 

131I therapy for thyrotoxicosis. Nucl Med Commun 14:160-168. 

O'Doherty MJ, McElhatton PR, Thomas SHL. 1999. Treating thyrotoxicosis in pregnant or potentially 

pregnant women: The risk to the fetus is very low. Br Med J 318:5-6. 
 

 

IODINE 438 

9. REFERENCES 

O'Donnell AL, Spaulding SW. 1997. Hyperthyroidism: Systemic effects and differential diagnosis. In: 

Falk SA, ed. Thyroid disease: Endocrinology, surgery, nuclear medicine, and radiotherapy. 

Philadelphia, PA: Lippincott-Raven Publishers, 241-252. 

O'Donnell E, Duckart EC, Schulz RK. 1993. Anion retention in soil: Possible application to reduce 

migration of buried technetium and iodine-development of a field test. In: Waste management '93: 

Working towards a cleaner environment: Waste processing, transportation, storage and disposal, 

technical programs and public education: Technology and programs for radioactive waste management 

and environmental restoration. Tuscon, AZ: Arizona Board of Regents, 1541-1551. 

O'Donoghue JA, Wheldon TE. 1996. Targeted radiotherapy using Auger electron emitters. Phys Med 

Biol 41:1973-1992. 

*Ogborn RE, Waggener RE, VanHove E. 1960. Radioactive-iodine concentration in thyroid glands of 

newborn infants. Pediatrics :771-776. 

Ogris E. 1997. [Exposure with J-131 during pregnancy: Significance for mother and child.] Acta Med 

Austriaca 24:150-153. (German) 

O'Hare NJ, Gilligan P, Murphy D, et al. 1997. Estimation of foetal brain dose from I-131 in the foetal 

thyroid. Phys Med Biol 42:1717-1726. 

O'Hare NJ, Murphy D, Malone JF. 1998. Thyroid dosimetry of adult European populations. Br J Radiol 

71:535-543. 

O'Hare NJ, Murphy D, Malone JF. 2000. Thyroid dosimetry in Europe following the Chernobyl 

accident. Br J Radiol 73:636-640. 

Ohmomo Y, Nakamura Y, Honma Y, et al. 1978. [Studies on the estimation of radiation dose to thyroid 

gland through foods contaminated by gaseous radioactive iodine.] Hoshasen Igaku Sogo Kenkyusho, 

[Tech Rep] NIRS-R 8:29-35. (Japanese) 

*Ohno S. 1971. Determination of iodine and bromine in biological materials by neutron activation 

analysis. Analyst 96:423-426. 

*Ohno M, Zannini M, Levy O, et al. 1999. The paired-domain transcription factor Pax8 binds to the 

upstream enhancer of the rat sodium/iodide symporter gene and participates in both thyroid-specific and 

cyclic-AMP-dependent transcription. Mol Cell Biol 19(3):2051-2060. 

Ohshima M, Ward JM. 1986. Dietary iodine deficiency as a tumor promoter and carcinogen in male 

F344/NCr rats. Cancer Res 46:877-883. 

Ohtake M, Onaya T, Sato A, et al. 1973. Studies on the mechanism of inhibitory action of excess iodide 

on thyroid hormone secretion. Proc Soc Exp Biol Med 144(2):538-543. 

Ohtaki S, Nakagawa H, Nakamura M, et al. 1996. Thyroid peroxidase: Experimental and clinical 

integration. Endocr J (Tokyo) 43(1):1-14. 

*Okano M. 1989. Irritant contact dermititis caused by the povidone-iodine. J Am Acad Dermatol 

20(5):860. 
IODINE 439 

9. REFERENCES 

Okuno Y, Kunimatsu T, Tanahashi K, et al. 1996. Effect of simultaneous treatment of large amounts of 

vitamin A and thiourea on thyroidal iodine uptake and organification in rats. J Toxicol Pathol 9:385-390. 

*Oliner L, Kohlenbrener RM, Fields T, et al. 1957. Thyroid function studies in children: Normal values 

for thyroidal I131 uptake and PBI131 levels up to the age of 18. J Clin Endocrinol Metab 17:61-75. 

Olinescu R, Bartoc R, Militaru M, et al. 1992. The changes of peroxides and total antioxidant in the 

plasma of patients who received 131I therapeutically. Rev Roum Med Med Interne 30(2):113-117. 

Oliver LL, Ballad RV, Manuel OK. 1982a. Iodine-129 in Missouri rain and milk. J Radioanal Chem 

68(1-2):233-244. 

*Oliver LL, Ballad RV, Manuel OK. 1982b. 129I in Missouri thyroids. Health Phys 42:425-432. 

Olsen KJ, Ehlers N, Schonheyder F. 1979. Studies on the handling of retinotoxic doses of iodate in 

rabbits. Acta Pharmacol Toxicol (Copenh) 44:241-250. 

Olson WG, Stevens JB, Anderson J, et al. 1984. Iodine toxicosis in six herds of dairy cattle. J Am Vet 

Med Assoc 184(2):179-181. 

Olurin E. 1983. Epidemiology of cancer of the thyroid gland in Ibadan (Nigeria). Acta Endocrinol 

Suppl 252:16. 

Ondov JM, Choquette CE, Zoller WH, et al. 1989. Atmospheric behavior of trace elements on particles 

emitted from a coal-fired power plant. Atmos Environ 23(10):2193-2204. 

*O'Neill B, Magnolato D, Semenza G. 1987. The electrogenic, Na +-dependent I-

 transport system in 

plasma membrane vesicles from thyroid glands. Biochim Biophys Acta 896:263-274. 

*Oppenheimer JH, Schwartz HL. 1985. Stereospecific transport of triiodothyronine from plasma to 

cytosol and from cytosol to nucleus in rat liver, kidney, brain, and heart. J Clin Invest 75:147-154. 

Oppenheimer JH, Schwartz HL, Strait KA. 1996. The molecular basis of thyroid hormone actions. In: 

Braverman LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 

Philadelphia, PA: Lippincott-Raven, 162-184. 

Orazio AF, Dunkleberger JD. 1988. New York's development of low-level radioactive waste disposal 

capability. In:, ed. Proceedings of the ACPA annual meeting. Air Pollution and Control Association, 

88-23.10. 

Orme MCL, Connolly ME. 1971. Hypoparathyroidism after iodine-131 treatment of thyrotoxicosis. 

Ann Intern Med 75(1):136-137. 

Orr MM, Tamarind DL, Cook J, et al. 1975. Chronic lesions of rabbit bowel due to contact with 

antiseptic skin preparation. Gut 16(5):401. 

Oscarson DW, Hume HB, Sawatsky NG, et al. 1992. Diffusion of iodide in compacted bentonite. Soil 

Sci Soc Am J 56:1400-1406. 
IODINE 440 

9. REFERENCES 

*OSHA. 2001a. Air contaminants. Shipyards. Occupational Safety and Health Administration. U.S. 

Department of Labor. Code of Federal Regulations. 29 CFR 1915.1000, Table Z. http://www.oshaslc.gov/OshStd_data/1915_1000.html. March 26, 2001. 

*OSHA. 2001b. Limits for air contaminants. Occupational Safety and Health Administration, U.S. 

Department of Labor. http://www.osha-slc.gov/OshStd_data/1910_1000_TABLE_Z-1.html. February 

22, 2001. 

*OSHA. 2001c. Threshold limit values of airborne contaminants for construction. Occupational Safety 

and Health Administration. U.S. Department of Labor. Code of Federal Regulations. 29 CFR 1926.55, 

Appendix A. http://www.osha-slc.gov/OshStd_data/1926_0055_APP_A.html. March 26, 2001. 

Osmanagaoglu K, Foulon W. 1998. Concerns about risks of irradiation during pregnancy. J Nucl Med 

39(12):2194-2195. 

OTA. 1990. Neurotoxicity: Identifying and controlling poisons of the nervous system. Washington, 

DC: Office of Technology Assessment. OTA-BA-438. 

Othman S, Phillips DIW, Lazarus JH, et al. 1992. Iodine metabolism in postpartum thyroiditis. Thyroid 

2(2):107-111. 

Ott RA, Hofmann C, Oslapas R, et al. 1987. Radioidine sensitivity of parafollicular C cells in aged 

Long-Evans rats. Surgery 102(6):1043-1048. 

*Owen GM, Brozek J. 1966. Influence of age, sex and nutrition on body composition during childhood 

and adolescence. In: Falkner F, ed. Human development. Philadelphia, PA: WB Saunders, 222-238. 

Ozakay H, Unak P, Biber Z, et al. 1998. Determination of iodide in drinking water by isotope dilution 

analysis. J Radioanal Nucl Chem 230(1-2):231-233. 

Ozaki O, Ito K, Mimura T, et al. 1994. Thyroid carcinoma after radioactive iodine therapy for Graves' 

disease. World J Surg 18:518-521. 

Ozawa Y, Migita M, Watanabe T, et al. 1994. Development of Graves' ophthalmopathy and uveitis after 

radioiodine therapy for Graves' disease in a patient with HTLV-I associated myelopathy (HAM). Intern 

Med 33:564-568. 

*Pacini F, Gasperi M, Fugazzola L, et al. 1994. Testicular function in patients with differentiated thyroid 

carcinoma treated with radioiodine. J Nucl Med 35(9):1418-1422. 

*Pacini F, Vorontsova T, Demidchik EP, et al. 1997. Post-Chernobyl thyroid carcinoma in Belarus 

children and adolescents: Comparison with naturally occurring thyroid carcinoma in Italy and France. J 

Clin Endocrinol Metab 82(11):3563-3569. 

Pacyna JM. 1995. The origin of Arctic air pollutants: Lessons learned and future research. Sci Total 

Environ 160/161:39-53. 

Pahjua DN, Rajan MGR, Borkar AV, et al. 1993. Potassium iodate and its comparison to potassium 

iodide as a blocker of 131I uptake by the thyroid in rats. Health Phys 65(5):545-549. 
 

 

IODINE 441 

9. REFERENCES 

Pahuja DN, Rajan MGR, Chaudhari PR, et al. 1997. On thyroid protection against radioiodine. Radiat 

Prot Environ 20(2):93-95. 

Paindakhel SM, Begum N, Shah H, et al. 1980. Iodine induced thyrotoxicosis-case reports and review of 

literature. JPMA JPakMedAssoc 30(5):122-124. 

Painter RB, Young BR. 1977. Anomalous effects of 125I after its incorporation into mammalian cell 

DNA. Curr Top Radiat Res Q 12:472-479. 

*Palmer HE, Branson BM, Cohn SH, et al. 1976. Standard field methods for determining 131I in vivo. 

Health Phys 30:113. 

Palms JM, Veluri VR, Boone FW. 1975. The environmental impact 129I released by a nuclear fuelreprocessing plant. Nuclear Safety 16(5):593-602. 

Panariti E. 1995. The secretion of radioactive iodine (131J) into the milk of small ruminants following 

their experimental contamination. DtschTieraerztlWochenshr 102:198-200. 

Panday CS, Kochupillai N. 1982. Iodine prophylaxis and endemic goitre. Indian J Pediatr 49:819-822. 

Papa CM. 1976. Acne and hidden iodides [Letter]. Arch Dermatol 112:555-556. 

Papadopoulos D, Thomas P. 1977. [Ratio of the dose factors of the isotopes of iodine.]
 

Kernforschungszentrum Karlsruhe, [Ber.], KFK 2544, 14 pp. (German) 

Papadopoulos I, Schnapka C, Kelami A. 1986. Examinations of polyvidone-iodine as an irrigation 

solution for spermatic duct occlusions. Andrologia 18(6):649-658.
 

Papas A, Ingalls JR, Campbell LD. 1979. Studies on the effects of rapeseed meal on thyroid status of 

cattle, glucosinolate and iodine content of milk and other parameters. J Nutr 109:1129-1139. 

Park YK, Harland BF, Vanderveen JE, et al. 1981. Estimation of dietary iodine intake of Americans in 

recent years. J Am Diet Assoc 79:17-24. 

*Parmentier M, Libert F, Maenhaut C, et al. 1989. Molecular cloning of the thyrotropin receptor. 

Science 246:1620-1622. 

Parrott MW, Johnston ME, Durbin PW. 1960. The effects of thyroid and parathyroid deficiency on
 

reproduction in the rat. Endocrinology 67:467-483. 

*Paschke R, Vogg M, Winter J, et al. 1994. The influence of iodine on the intensity of the intrathyroidal 

autoimmune process in Graves' disease. Autoimmunity 17:319-325. 

*Pastan I. 1957. Absorption and secretion of iodide by the intestine of the rat. Endocrinol 61:93-97. 

Pasternak FP, Socolow EL, Ingbar SH. 1969. Synergistic interaction of phenazone and iodide on thyroid 

hormone biosynthesis in the rat. Endocrinol 84:769-777. 

Patten JR, Whitford GM, Stringer GI, et al. 1978. Oral absorption of radioactive fluoride and iodide in
 

rats. Arch Oral Biol 23:215-217. 
IODINE 442 

9. REFERENCES 

*Patton GW, Cooper AT. 1993. Air pathway effects of nuclear materials production at the Hanford site, 

1983 to 1992. Battelle Pacific Northwest Laboratories, Richland WA. NTIS:DE94002708. 

*Paul T, Meyers B, Witorsch RJ, et al. 1988. The effect of small increases in dietary iodine on thyroid 

function in euthyroid subjects. Metabolism 37(2):121-124. 

Pavlovic-Hournac M, Delbauffe D. 1977. Discontinuity of thyroid gland response to hormonal 

stimulation: Effect of TSH and cAMP on iodide organification. Mol Cell Endocrinol 8:157-173. 

Pawels EK, Thompson WH, Blokland JAK, et al. 1999. Aspects of fetal thyroid dose following iodine131 administration during early stages of pregnancy in patients suffering from benign thyroid disorders. 

Eur J Nucl Med 26(11):1453-1457. 

*Pearce EN, Gerber AR, Gootnick DB, et al. 2002. Effect of chronic iodine excess in a cohort of longterm American workers in West Africa. J Clin Endocrinol Metab 87(12):5499-5502. 

Peden NR, Hart IR. 1984. The early development of transient and permanent hypothyroidism following 

radioiodine therapy for hyperthyroid Graves' disease. Can Med Assoc J 130:1141-1144. 

*Pedersen KM, Laurberg P, Iverson E, et al. 1993. Amelioration of some pregnancy-associated 

variations in thyroid function by iodine supplementation. J Clin Endocrinol Metab 77(4):1078-1083. 

*Peeters R, Fekete C, Goncalves C, et al. 2001. Regional physiological adaptation of the central nervous 

system deiodinases to iodine deficiency. Am J Physiol Endocrinol Metab 281(1):E54-E61. 

*Pekary AE, Hershman JM, Berg L. 1998. Tumor necrosis factor, ceramide, transforming growth factor­ ­ beta1, and aging reduce Na +/I symporter messenger ribonucleic acid levels in FRTL-5 cells. 

Endocrinology 139(2):703-712. 

*Peňa-Penabad C, De Unamuno P, Garcis-Silva J, et al. 1993. Vegetating iododerman and conjunctival 

involvement. EJD Eur J Dermatol 3:671-673. 

Pendergrast WJ, Milmore BK, Marcus SC. 1961. Thyroid cancer and thyrotoxicosis in the United States: 

Their relation to endemic goiter. J Chronic Dis 13:22-38. 

*Pendleton RC, Lloyd RD, Mays CW, Lloyd RD. 1963. Iodine-131 in Utah during July and August 

1962. Science 141(3581):640-642. 

*Pendleton RC, Mays CW, Lloyd RD. 1963. Differential accumulation of 131I from local fallout in 

people and milk. Health Phys 19:1253-1262. 

*Penfold JL, Pearson CC, Savage JP, et al. 1978. Iodide induced goitre and hypothyroidism in infancy 

and childhood. Aust Paediatr J 14:69-73. 

Pennington JS, Martin FIR. 1967. Hypothyroidism following treatment of thyrotoxicosis with 

radioiodine. Med J Aust 2(14):641-643. 

*Pennington JT. 1988. Iodine. In: Smith KT, ed. Handbook on Trace Minerals in Foods: Their 

Relationship to Health and Nutrition. New York, NY: Marcel Dekker. 
 

 

 

IODINE 443 

9. REFERENCES 

*Pennington JT. 1990a. Iodine concentrations in US milk: Variation due to time, season, and region. J 

Dairy Sci 73:3421-3427. 

*Pennington JT. 1990b. A review of iodine toxicity reports. J Am Diet Assoc 90:1571-1581. 

*Pennington JT, Young BE, Wilson DB, et al. 1986. Mineral content of foods and total diets: The 

selected minerals in foods survery, 1982-1984. J Am Diet Assoc 86:876-891. 

*Pennington JT, Wilson, Harland BF, et al. 1984. Selected minerals in foods surveys, 1974 to 1981/82. 

J Amer Diet Assoc 84:771-780. 

Pepe F, Calvo G, Chirico E, et al. 1993. [Obstetric and perinatal implications of thyroid pathology in 

pregnancy. Review of the literature.] Minerva Ginecol 45(11):565-585. (Italian) 

*Pereira A, Braekman JC, Dumont JE, et al. 1990. Identification of a major iodoloipid form horse 

thyroid gland as 2-iodohexadecanol. J Biol Chem 271:23006. 

*Perkins 1963. Physical and chemical form of I131 in fallout. Health Physics 9:1113. 

Perlman JA, Sternthal PM. 1983. Effect of 131I on the anemia of hyperthyroidism. J Chronic Dis 

36(5):405-412. 

*Perrault G, Thieblemont P, Pasquier C, et al. 1967. Cinetique du passage du radioide soluble a travers 

les epitheliums respiratoires, apres inhalation. Health Phys 13:707-718. 

*Perret J, Ludgate M, Libert F, et al. 1990. Stable expression of the human TSH receptor in CHO cells 

and characterization of differentially expressing clones. Biochem Biophys Res Commun 171(3):1044­

1050. 

*Perron B, Rodriguez A-M, Leblanc G, et al. 2001. Cloning of the mouse sodium iodide symporter and 

its expression in the mammary gland and other tissues. J Endocrinol 170:185-196. 

*Pesavento M, Profumo A. 1985. General procedure for the determination of trace amounts of iodine in 

natural water samples of unknown composition by spectrophotometric titration. Analyst 110:181-183. 

Peter HJ, Burgi U, Gerber H. 1996. Pathogenesis of nontoxic diffuse and nodular goiter. In: Braverman 

LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: 

Lippincott-Raven, 890-895. 

Peters J, O'Reilly S, Barragry JM. 1993. Anaplastic carcinoma of the thyroid following radio-iodine 

therapy. Isr J Med Sci 162(1):3-4. 

Petersen RB, Goren H, Cohen M, et al. 1997. Transthyretin amyloidosis: A new mutation associated 

with dementia. Ann Neurol 41:307-313. 

*Petrova A, Gnedko T, Maistrova I, et al. 1997. Morbidity in a large cohort study of children born to 

mothers exposed to radiation from Chernobyl. Stem Cells 15(Suppl 2):141-150. 

*Pettersson B, Adami H-O, Wilander E, et al. 1991. Trends in thyroid cancer incidence in Sweden, 

1958-1981, by histopathologic type. Indian J Cancer 48:28-33. 
IODINE 444 

9. REFERENCES 

*Pettersson B, Coleman MP, Ron E, et al. 1996. Iodine supplementation in Sweden and regional trends 

in thyroid cancer incidence by histopathologic type. Indian J Cancer 65:13-19. 

Petty CS, DiBenedetto RL. 1957. Goiter of the newborn. N Engl J Med 256:1103-1105. 

*Phaneuf D, Cote I, Dumas P, et al. 1999. Evaluation of the contamination of marine algae (seaweed) 

from the St. Lawrence river and likely to be consumed by humans. Environ Res 80:S175-S182. 

Pharoah POD. 1996. 'Iodine and brain development' [Letter]. Dev Med Child Neurol 38:278-282. 

Pharoah POD, Connolly KJ. 1991. Effects of maternal iodine supplementation during pregnancy. Arch 

Dis Child 66(1):145-147. 

Pharoah POD, Connolly KJ. 1995. Iodine and brain development. Dev Med Child Neurol 37(8):744­

748. 

Pharoah POD, Buttfield IH, Hetzel BS. 1971. Neurological damage to the fetus resulting from severe 

iodine deficiency during pregnancy. Lancet 1:308-310. 

Pharoah POD, Buttfield IH, Hetzel BS. 1972. The effect of iodine prophylaxis on the incidence of 

endemic cretinism. Adv Exp Med Biol 30:201-221. 

*Phelps E, Wu P, Bretz J, et al. 2000. Thyroid cell apoptosis. Autoimmune Thyroid Disease 29(2)375­

388. 

Phillips DIW, Lazarus JH, Hall R. 1988a. Iodine metabolism and the thyroid. J Endocrinol 119:361­

363. 

Phillips DIW, Nelson M, Barker DJP, et al. 1988b. Iodine in milk and the incidence of thyrotoxicosis in 

England. Clin Endocrinol 28:61-66. 

Pic P, Michel-Bechet M, Bottini J. 1984. TSH stimulation of iodine organification in early foetal rat 

thyroid in vitro. Biol Cell 51:105-108. 

Piermattei A, Arcovito G, Azario L. 1990. Assessment of 125I clinical dose specification from recent 

dose rate evaluations. Med Physics 17(5):934-936. 

Piers DA, Janssen S, Oosten HR, et al. 1988. Mediastinal hemorrhage after treatment of thyrotoxicosis 

using radioiodine. Clin Nucl Med 13(8):574-576. 

Pietrzyk Z, Michalkiewicz M, Huffman LJ, et al. 1992. Vasoactive intestinal peptide enhances thyroidal 

iodide uptake during dietary iodine deficiency. Endocr Res 18(3):213-228. 

Pietsch J, Meakins JL. 1976. Complications of povidone-iodine absorption in topically treated burn 

patients. Lancet 1(7954):280-282. 

Pilch BZ, Kahn CR, Ketcham AS, et al. 1973. Thyroid cancer after radioactive iodine diagnostic 

procedures in childhood. Pediatrics 51(5):898-902. 

Piletta P, Rieckhoff L, Saurat JH. 1994. Triggering of bullous pemphigoid by iodine [Letter]. Br J 

Dermatol 131(1):145-147. 
IODINE 445 

9. REFERENCES 

Pinchera A, Bartalena L, Marcocci C. 1995. Radioiodine may be bad for Graves' ophthalmopathy, but... 

J Clin Endocrinol Metab 80(2):342-345. 

Pinchera A, Fenzi GF, Mariotti S, et al. 1990. Iodine and autoimmune thyroid disease. In: Rubery E, 

Smales E, eds. Iodine prophylaxis following nuclear accidents. Oxford, UK: Pergamon Press, 39-44. 

Pisarev MA. 1985. Thyroid autoregulation. J Endocrinol Invest 8:475-484. 

Pisarev MA, Aiello LO. 1976. Studies on the mechanism of action of potassium iodide on thyroid 

protein biosynthesis. Acta Endocrinol 82:298-305. 

Pisarev MA, Altschuler N. 1973. Action of potassium iodide on thyroid acid protease. Acta Endocrinol 

74:703-710. 

*Pisarev MA, Gärtner R. 2000. Autoregulatory actions of iodine. In: Braverman LE, Utiger RD, eds. 

Werner and Ingbar's the thyroid: A fundamental and clinical text. 8th ed. Philadelphia, PA: LippincottWilliams and Wilkins, 85-90. 

Pisarev MA, Itoiz ME. 1972. Action of KI on stimulated thyroid protein biosynthesis. Endocrinol 

90:1409-1412. 

Pisarev MA, Aiello LO, Kleiman de Pisarev DL. 1976. Action of KI, thyroxine and cyclic AMP on 

[

3

H]uridine incorporation into the RNA of thyroid slices. Acta Endocrinol 83:313-320. 

Pisarev MA, DeGroot LJ, Hati R. 1971. KI and imidazole inhibition of TSH and c-AMP induced 

thyroidal iodine secretion. Endocrinology 88:1217-1221. 

Pitslavas V, Smerdely P, Li M, et al. 1997. Amiodarone induces a different pattern of ultrastructural 

change in the thyroid to iodine excess alone in both the BB/W rat and the Wistar rat. Eur J Endocrinol 

137:89-98. 

*Pittman CS, Buck ME, Chambers JB. 1972. Urinary metabolites of 14C-labeled thyroxine in man. J 

Clin Invest 51:1759-1766. 

*Pittman CS, Shimizu T, Burger A, et al. 1980. The nondeiodinative pathways of thyroxine metabolism: 

3,5,3',5'-tetraiodothyroacetic acid turnover in normal and fasting human subjects. J Clin Endocrinol 

Metab 50(4):712-716. 

*Pittman JA, Dailey GE, Beschi RJ. 1969. Changing normal values for thyroidal radioiodine uptake. N 

Engl J Med 280(26):1431-1434. 

Pizzulli A, Ranjbar A. 2000. Selenium deficiency and hypothyroidism. A new etiology in the 

differential diagnosis of hypothyroidism in children. Biol Trace Elem Res 77(3):199-208. 

*Plato P, Jacobson AP, Homann S. 1976. In vivo thyroid monitoring for iodine-131 in the environment. 

Int J Appl Radiat Isot 27:539-545. 

Ploth DW, Fitz A, Schnetzler D, et al. 1978. Thyroglobulin-anti-thyroglobulin immune complex 

glomerulonephritis complicating radioiodine therapy. Clin Immunol Immunopathol 9:327-334. 
IODINE 446 

9. REFERENCES 

Pochin EE. 1952. The iodine uptake of the human thyroid throughout the menstrual cycle and in 

pregnancy. Clin Sci 11:441-445. 

*Pohlenz J, Refetoff S. 1999. Mutations in the sodium/iodide symporter (NIS) gene as a cause for iodide 

transport defects and congenital hypothyroidism. Biochimie 81:469-476. 

*Pohlenz J, Medeiros-Neto G, Gross JL, et al. 1997. Hypothyroidism in a Brazilian kindred due to 

iodide trapping defect caused by a homozygous mutation in the sodium/iodide symporter gene. Biochem 

Biophys Res Commun 240:488-491. 

Poliak AL. 1988a. [Effect of iodine vapors on the oral mucosa of workers in iodine manufacture.] Gig 

Tr Prof Zabol 7:26-28. (Russian) 

Poliak AL. 1988b. [Experimental data on the effect of iodine vapors on the tissues and organs of the oral 

cavity.] Gig Tr Prof Zabol 9:48-49. (Russian) 

*Pomroy C. 1979. Surveys of lab technicians for 125I thyroid burdens. Occup Health Safe 48(4):40-42. 

Porri F, Vervloet D. 1994. [Reactions to iodinated contrast media.] Allerg Immunol (Paris) 26(10):374­

376. (French) 

Porterfield SP, Hendrich CE. 1991. The thyroidectomized pregnant rat-an animal model to study fetal 

effects of maternal hypothyroidism. In: Bercu BB, Shulman DI, eds. Advances in perinatal 

thyroidology. New York, NY: Plenum Press, 107-132. 

Porterfield SP, Hendrich CE. 1993. The role of thyroid hormones in prenatal and neonatal neurological 

development-current perspectives. Endocrine Rev 14(1):94-106. 

Postellon DC, Aronow R. 1982. Iodine in mother's milk. JAMA 247(4):463. 

*Poston TM. 1986. Literature review of the concentration ratios of selected radioisotopes in freshwater 

and marine fish. Battelle Pacific Northwest Labs Report No. DE86-015820 (NTIS/DE86015820), 1-21, 

82-84, 243-272. 

Potter GD, Taurog A, Chaikoff IL. 1956. The I131-irradiated rat thyroid: It's altered response to various 

stimuli and the changes induced in its iodine metabolism. Endocrinology 59(1):12-26. 

Pottern LM, Kaplan MM, Larsen PR, et al. 1990. Thyroid nodularity after childhood irradiation for 

lymphoid hyperplasia: A comparison of questionnaire and clinical findings. J Clin Epidemiol 43(5):449­

460. 

Poverennyi AM, Shinkarkina AP, Vinogradova YE, et al. 1996. [Probable consequence of damage by 

radioactive iodine to thyroid gland in the period of the Chernobyl accident.] Radiats Biol Radioecol 

36(4):632-640. (Russian) 

*Povinec PP, Oregioni B, Jull AJT, et al. 2000. AMS measurements of 14C and 129I in seawater around 

radioactive waste dump sites. Nucl Instrum Meth Phys Res Sect B 172:672-678. 

Powell E. 1978. Iodine and acetone-containing plastic spray dressings. Br Med J 2(6150):1500. 
 

 

IODINE 447 

9. REFERENCES 

*Prager EM, Gardner RE. 1979. Iatrogenic hypothyroidism from topical iodine-containing medications. 

West J Med 130(6):553-555. 

Pregliasco L, Bocanera L, Chester H, et al. 1991. Iodide inhibits thyroglobulin synthesis. In: Gordon A, 

Gross.J, Hennemann G, eds. Progress in thyroid research. Rotterdam, the Netherlands: Balkema, 491­

494. 

Premawardhana LDKE, Parkes AB, Smyth PPA, et al. 2000. Increased prevalence of thyroglobulin 

antibodies in Sri Lankan schoolgirls-is iodine the cause? Eur J Endocrinol 143(2):185-188. 

Prenger KB, Poeschmann PH, Smits PHJ, et al. 1984. Massive mediastinal hemorrhage following 

treatment of hyperthyroidism with radioactive iodine. Thorac Cardiovasc Surg 32:122-123. 

Prentice RL, Kato H, Yoshimoto K, et al. 1982. Radiation exposure and thyroid cancer incidence among 

Hiroshima and Nagasaki residents. Natl Cancer Inst Monogr 62:207-212. 

Press OW, Shan D, Howell-Clark J, et al. 1996. Comparative metabolism and retention of iodine-125, 

yttrium-90, and indium-111 radioimmunoconjugates by cancer cells. Cancer Res 56:2123-2129. 

Preston RL. 1994. Serum inorganic iodine dynamics in cattle following a single oral dose of several 

iodine sources. FASEB J 8(4-5):A431. 

Preuschof L, Keller F, Bogner U, et al. 1991. Plasma exchange and hemoperfusion in iodine-induced 

thyrotoxicosis. Blood Purif 9:164-168. 

*Prichard HM, Gesell TF Davis E. 1981. Iodine-131 levels in sludge and treated municipal waste waters 

near a large medical complex. AJPH 71:47-52. 

Primack A. 1971. Potassium iodide interatction with cyclophosphamide in mice. Proc Soc Exp Biol 

Med 137(2):604-606. 

Prinz RA, Oslapas R, Hofmann C, et al. 1982. Long-term effect of radiation on thyroid function and 

tumor formation. J Surg Res 32:329-337. 

*Prisyazhiuk A, Pjatak OA, Buzanov VA, et al. 1991. Cancer in the Ukraine, post-Chernobyl. Lancet 

338(8878):1134-1135. 

Pyati SP, Ramamurthy RS, Krauss MT, et al. 1977. Absorption of iodine in the neonate following 

topical used of povidone iodine. J Pediatr 91(5):825-828. 

*Que Hee SS, Boyle JR. 1988. Simultaneous multielemental analysis of some environmental and 

biological samples by inductively coupled plasma atomic emission spectrometry. Anal Chem 60:1033­

1042. 

*Quimby EH, Werner SC, Schmidt C. 1950. Influence of age, sex, and season upon radioiodine uptake 

by the human thyroid. Proc Soc Exp Biol Med 75:537-543. 

Rädlinger G, Heumann KG. 1998. Iodine determination in food samples using inductively coupled 

plasma isotope dilution mass spectrometry. Anal Chem 70:2221-2224. 
IODINE 448 

9. REFERENCES 

*Rädlinger G, Heumann KG. 2000. Transformation of iodine in natural and wastewater systems by 

fixation on humic substances. Environ Sci Technol 34:3932-3936. 

Radvila A, Roost R, Burgi H, et al. 1976. Inhibition of thyroglobulin biosynthesis and degradation by 

excess iodide. Synergism with lithium. Acta Endocrinol 81:495-506. 

*Rae JE, Malik SA. 1996. The determination of iodine in geochemical samples: The use of 

pyrohydrolytic decomposition. Chemosphere 33(11):2121-2128. 

*Raghavendran KV, Satbhai PD, Abhyankar B, et al. 1978. Long-term retention studies of 131I and 137Cs 

and 60Co in Indian workers. Health Phys 34:185-188. 

*Rajatanavin R, Safran M, Stoller WA, et al. 1984. Five patients with iodine-induced hyperthyroidism. 

Am J Med 77:378-384. 

Rajendran VM, Geibel J, Binder HJ. 1995. Chloride-dependent Na-H exchange. J Biol Chem 

270(19):11051-11054. 

*Rallison ML. 1996. Thyroid neoplasia from fallout near the Nevada test site. In: Nagataki S, 

Yamashita S, eds. Nagasaki symposium radiation and human health: Proposal from Nagasaki. 

Amsterdam, the Netherlands: Elsevier, 147-154. 

*Rallison ML, Dobyns BM, Keating FR, et al. 1974. Thyroid disease in children: A survey of subjects 

potentially exposed to fallout radiation. Am J Med 56:457-463. 

Rallison ML, Dobyns BM, Keating R, et al. 1975. Thyroid nodularity in children. JAMA 233(10):1069­

1072. 

*Rallison ML, Lotz TM, Bishop M, et al. 1990. Cohort study of thyroid disease near the Nevada test 

site: A preliminary report. Health Phys 59(5):739-746. 

Ramírez MJ, Peurto S, Galofre P, et al. 2000. Multicolour FISH detection of radioactive iodine-induced 

17cen-p53 chromosomal breakage in buccal cells from therapeutically exposed patients. Carcinogenesis 

21(8):1581-1586. 

*Ramírez MJ, Surralles J, Galofre P, et al. 1997. Radioactive iodine induces clastogenic and agedependent aneugenic effects in lymphocytes of thyroid cancer patients as revealed by interphase FISH. 

Mutagenesis 12(6):449-455. 

Ramírez MJ, Surralles J, Galofre P, et al. 1999. FISH analysis of 1cen-1q12 breakage, chromosome 1 

numerical abnormalities and centromeric content of micronuclei in buccal cells from thyroid cancer and 

hyperthyroidism patients treated with radioactive iodine. Mutagenesis 14(1):121-127. 

*Ramsden D, Passant FH, Peabody CO, et al. 1967. Radioiodine uptakes in the thyroid: Studies of the 

blocking and subsequent recovery of the gland following the administration of stable iodine. Health Phys 

13:633-646. 

Ranganathan S, Reddy V. 1995. Human requirements of iodine & safe use of iodized salt. Indian J Med 

Res 102:227-232. 
 

 

IODINE 449 

9. REFERENCES 

Rani CSS, Field JB. 1988. Comparison of effects of thyrotropin, phorbol esters, norepinephrine, and 

carbachol on iodide organification in dog thyroid slices, follicles, and cultured cells. Endocrinol 

122:1915-1922. 

Rao DV, Narra VR, Howell RW, et al. 1989. In-vivo radiotoxicty of DNA-incorporated 125I compared 

with that of densely ionising alpha-particles. Lancet 2:650-653. 

Rao DV, Narra VR, Howell RW, et al. 1990. Biological consequence of nuclear versus cytoplasmic 

decays of 125I: Cysteamine as a readioprotector against auger cascades in vivo. Radiat Res 124:188-193. 

Rapoport B, Spaulding SW. 1996. Mechanism of action of thyrotropin and other thyroid growth factors. 

In: Braverman LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 

Philadelphia, PA: Lippincott-Raven, 207-219. 

Rapoport B, Adams RJ, Rose M. 1977. Cultured thyroid cell adenosine 3',5'-cyclic monophosphate 

response to thyrotropin: Loss and restoration of sensitivity to iodide inhibition. Endocrinology 100:755­

764. 

Rapoport B, Caplan R, DeGroot LJ. 1973. Low-dose sodium iodide I 131 therapy in Graves disease. 

JAMA 224(12):1610-1613. 

Rapoport B, West MN, Ingbar SH. 1976. On the mechanism of inhibition by iodine of the thyroid 

adenylate cyclase response to thyrotropic hormone. Endocrinol 99:11-22. 

Rasmussen AK, Nygaard B, Feldt-Rasmussen U. 2000. 131I and thyroid-associated ophthalmopathy. Eur 

J Endocrinol 143(2):155-160. 

*Rasmussen RA, Khalil MAK, Gunwardenena R et al. 1982. Journal of Geophysical Research 87:3086­

3090. 

Rasmussen SN, Hjorth L. 1974. Determination of thyroid volume by ultrasonic scanning. J Clin 

Ultrasound 2(2):143-147. 

*Rasooly L, Burek CL, Rose NR. 1996. Iodine-induced autoimmune thyroiditis in NOD-H-2 h4 mice. 

Clin Immunol Immunopathol 81(3):287-292. 

Raspe E, Dumont JE. 1994. Control of the dog thyrocyte plasma membrane iodide permeability by the 

Ca2+-phosphatidylinositol and adenosine 3',5'-monophosphate cascades. Endocrinol 135(3):986-995. 

*Raspe E, Dumont JE. 1995. Tonic modulation of dog thyrocyte H2O2 generation and I-

 uptake by 

thyrotropin through the cyclic adenosine 3',5'-monophosphate cascade. Endocrinol 136(3):965-973. 

Rebello AD, Herms FW, Wagener K. 1990. The cycling of iodine as iodate and iodide in a tropical 

estuarine system. Mar Chem 29:77-93. 

Reddi OS. 1971. Long term genetic effects of 131I in mice. Indian J Med Res 59:1420-1423. 

Reddy AR, Kaul A. 1978. Microscopic dose distributions due to iodine isotopes in thyroid. Radiat 

Environ Biophys 15:229-239. 
IODINE 450 

9. REFERENCES 

Reddy PP, Reddy SB, Ebenezer DN, et al. 1982. Response of male germ cells of mouse to acute and 

fractionated doses of 131I induced radiation. Can J Genet Cytol 24:817-820. 

Reed HL. 1996. Environmental influences on thyroid hormone regulation. In: Braverman LE, Utiger 

RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: 

Lippincott-Raven, 259-265. 

Reed RR. 1997. Thyroid-associated ophthalmopathy: Treatment. In: Falk SA, ed. Thyroid disease: 

Endocrinology, surgery, nuclear medicine, and radiotherapy. Philadelphia, PA: Lippincott-Raven 

Publishers, 359-377. 

Rees Smith B, McLachlan SM, Furmaniak J. 1988. Autoantibodies to the thyrotropin receptor. 

Endocrine Rev 9(1):106-121. 

Reeve TS, Hales IB, Smith KV, et al. 1973. Carcinoma of the thyroid in a patient treated with 

radioiodine for hyperthyroidism. Med J Aust 1:993-996. 

*Reifenhauser C, Heumann KG. 1990. Development of a definitive method for iodine speciation in 

aquatic systems. Fresenius J Anal Chem 336:559-563. 

Reiners C. 1991. Radioiodine treatment of Basedow's disease: Interference and influence factors, risk 

estimation. Exp Clin Endocrinol 97:275-285. 

Reiners C, Herrmann H, Schaffer R, et al. 1983. Incidence and prognosis of thyroid cancer with special 

regard to oncocytic carcinoma of the thyroid. Acta Endocrinol Suppl 252:18. 

Reinhard W, Kohl S, Hollmann D, et al. 1998. Efficacy and safety of iodine in the postpartum period in 

an area of mild iodine deficiency. Eur J Med Res 3:203-210. 

*Reinhardt W, Luster M, Rudorff KH, et al. 1998. Effect of small doses of iodine on thyroid function in 

patients with Hashimoto's thyroiditis residing in an area of mild iodine deficiency. Eur J Endocrinol 

139:23-38. 

Reinhardt W, Paul TL, Allen EM, et al. 1988. Effect of l-thyroxine administration on the incidence of 

iodine induced and spontaneous lymphocytic thryoiditis in the BB/WOR rat. Endocrinology 

122(3):1179-1181. 

Reish DJ, Geesey GG, Wilkes FG, et al. 1982. Marine and estuarine pollution. J Water Pollut Control 

Fed 54:786-812. 

Revis NW, McCauley P, Holdsworth G. 1986. Relationship of dietary iodide and drinking water 

disinfectants to thyroid function in experimental animals. Environ Health Perspect 69:243-248. 

Ribela MTCP, Marone MMS, Bartolini P. 1999. Use of radioiodine urinalysis for effective thyroid 

blocking in the first few hours post exposure. Health Phys 76(1):11-16. 

Riccabona G, Zechmann W, Unterkircher S, et al. 1983. Epidemiology of thyroid cancer in an iodine 

deficient area during iodized salt prophylaxis. Acta Endocrinol Suppl 252:13. 

Richards EM, Marcus RE. 1993. Acute promyelocytic leukaemia following radioiodine therapy. Clin 

Lab Haematol 15:55-58. 
 

 

 

IODINE 451 

9. REFERENCES 

Richards GE, Brewer ED, Conley SB, et al. 1981. Combined hypothyroidism and hypoparathryoidism in 

an infant after maternal 131I administration. J Pediatr 99(1):141-143. 

Riddle WR, Roselli RJ, Pou NA. 1990. Modeling flux of free and protein-bound radioisotopes into the 

pulmonary interstitium. J Appl Physiol 68(6):2434-2442. 

*Riedel C, Levy O, Carrasco N. 2001. Post-transcriptional regulation of the sodium/thyroid symporter 

by thyrotropin. J Biol Chem 276(24):21458-21463. 

Rieger G, Winkler R, Buchberger W, et al. 1995. Iodine distribution in a porcine eye model following 

iontophoresis. Ophthalmologica 209:84-87. 

*Riggs DS. 1952. Quantitative aspects of iodine metabolism. Pharmacol Rev 4:284-370. 

Riley RG, Zachara JM, Wobber FJ. 1992. Chemical contaminants on DOE lands and selection of 

contaminant mixtures for subsurface science research. Washington, DC: U.S. Department of Energy. 

DE 92 014 826. 

Rillema JA, Marting C. 1998. Cyclic AMP impairs the PRL stimulation of iodide uptake into mouse 

mammary tissues. Proc Soc Exp Biol Med 219:37-40. 

*Rillema JA, Rowady DL. 1997. Characteristics of the prolactin stimulation of iodide uptake in mouse 

mammary gland explants. Proc Soc Exp Biol Med 215:366-369. 

Rillema JA, Yu TX. 1996. Prolactin stimulation of iodide uptake into mouse mammary gland explants. 

Am J Physiol 271(34):E879-E882. 

Rillema JA, Collins S, Williams CH. 2000a Prolactin stimulation of iodide uptake and incorporation into 

protein is polyamine-dependent in mouse mammary gland explants. Proc Soc Exp Biol Med 224(1):41­

44. 

*Rillema JA, Yu TX, Jhiang SM. 2000b Effect of prolactin on sodium iodide symporter expression in 

mouse mammary gland explants. Am J Physiol Endocrinol Metab 279:E769-E772. 

Rink T, Schroth H-J, Holle L-H, et al. 1999. [Effects of iodine and thyroid hormones in inducing and 

treating Hashimoto's thyroiditis.] Nuklearmedizin 38:144-149. (German) 

Ritter MA. 1981. The radiotoxicity of iodine-125 in ataxia telangiectasia fibroblasts. Biochim Biophys 

Acta 652:151-159. 

Rivera M, Teruel JL, Castano JC, et al. 1993. Iodine-induced sialadenitis: Report of 4 cases and review 

of the literature. Nephron 63:466-467. 

Rivkees SA, Sklar C, Freemark M. 1998. The management of Graves' disease in children, with special 

emphasis on radioiodine treatment. J Clin Endocrinol Metab 83(11):3767-3776. 

Rivlin RS. 1996a. Vitamin metabolism in hypothyroidism. In: Braverman LE, Utiger RD, eds. Werner 

and Ingbar's The thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 863­

865. 
IODINE 452 

9. REFERENCES 

Rivlin RS. 1996b. Vitamin metabolism in thyrotoxicosis. In: Braverman LE, Utiger RD, eds. Werner 

and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 693-695. 

Robbins J. 1983. Indications for using potassium iodide to protect the thyroid from low level internal 

irradiation. Bull N Y Acad Med 59(10):1028-1038. 

*Robbins J. 1996. Thyroid hormone transport proteins and the physiology of hormone binding. In: 

Braverman LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 

Philadelphia, PA: Lippincott-Raven, 96-110. 

Robbins J, Schneider AB. 2000. Thyroid cancer following exposure to radioactive iodine. Reviews in 

Endocrine & Metabolic Disorders 1(3):197-203. 

*Robbins J, Dunn JT, Bouville A, et al. 2001. Iodine nutrition and the risk from radioactive iodine: A 

workshop report in the Chernobyl long-term follow-up study. Thyroid 11(5):487-491. 

*Robens E, Aumann DC. 1988. Iodine-129 in the environment of a nuclear fuel reprocessing plant: I. 

129I and 127I contents of soils, food crops and animal products. J Environ Radioact 7:159-175. 

Robens E, Hauschild J, Aumann DC. 1988a. Iodine-129 in the environment of a nuclear fuel 

reprocessing plant: II. Iodine-129 and iodine-127 contents of soils, forage plants and deer thyroids. J 

Environ Radioact 7:265-274. 

Robens E, Hauschild J, Aumann DC. 1988b. Iodine-129 in the environment of a nuclear fuel 

reprocessing plant: III. Soil-to-plant concentration factors for Iodine-129 and iodine-127 and their 

transfer factors to milk, eggs and pork. J Environ Radioact 7:37-52. 

Robens-Palavinskas E, Hauschild J, Aumann DC. 1989. Iodine-129 in the environment of a nuclear fuel 

reprocessing plant: VI. Comparison of measurements of 129I concentrations in soil and vegetation with 

predictions from a radiological assessment model. J Environ Radioact 10:67-78. 

*Robertson JS, Gorman CA. 1976. Gonadal radiation dose and its genetic significance in radioiodine 

therapy of hyperthyroidism. J Nucl Med 17:826-835. 

*Robertson JS, Nolan NG, Wahner HW, et al. 1975. Thyroid radioiodine uptakes and scans in euthyroid 

patients. Mayo Clin Proc 50:79-84. 

Robinson GA, Easnidge DC, Floto F, et al. 1976. Ovarian 125I transference in the laying Japanese quail: 

Apparent stimulation by FSH and lack of stimulation by TSH. Poult Sci 55:1665-1671. 

*Robinson PS, Barker P, Campbell A, et al. 1994. Iodine-131 in breast milk following therapy for 

thyroid carcinoma. J Nucl Med 35:1797-1801. 

*Robison LM, Sylvester PW, Birkenfeld P, et al. 1998. Comparison of the effects of iodine and iodide 

on thyroid function in humans. J Toxicol Environ Health 55:93-106. 

*Robkin MA, Shleien B. 1995. Estimated maximum thyroid doses from 129I releases from the Hanford 

site for the years 1944-1995. Health Phys 69(6):917-922. 

Robson AM. 1981. Vocal-cord paralysis after treatment of thyrotoxicosis with radioiodine. Br J Radiol 

54:632. 
 

 

IODINE 453 

9. REFERENCES 

Roddy MT. 1975a. The effect of KI on the DUB/ICR strain mouse. Diss Abstr Int B 36(3):1034. 

Roddy MT 1975b. The effect of KI on the DUB/ICR strain mouse. Ph.D. Dissertation, The Catholic 

University of America. 70 p. 

*Rodeheaver G, Bellamy W, Kody M, et al. 1982. Bactericidal activity and toxicity of iodine-containing 

solutions in wounds. Arch Surg 117:181-186. 

Rodesch F, Rocmans P, Dumont JE. 1967. Stimulation of thyroidal radioiodine uptake by actinomycin 

D and fluorouracil-an indirect effect. Biochem Pharmacol 16:907-908. 

Rodrigues M, Havlik E, Peskar B, et al. 1998. Prostaglandins as biochemical markers of radiation injury 

to the salivary glands after iodine-131 therapy? Eur J Nucl Med 25(3):265-269. 

Rogahn J, Ryan S, Wells J. 2000. Randomised trial of iodine intake and thyroid status in preterm infants. 

Arch Dis Child Fetal Neonatal Ed 83(2):F86-F90. 

Rogau YI, Amvros'eu AP, Darokhina RI, et al. 1994. [Retardation of development of rat fetus by 

incorporation of iodine-131 isotopes during organogensis.] Vestsi Akad Navuk BSSR Ser Biyal Navuk 

3:55-58. (Russian) 

Rognoni JB, Lemarchand-Beraud T, Berthier C, et al. 1982. Effect of long-term iodide refeeding on the 

synthesis and secretion of T3, T4 and TSH in severe iodine deficient rats. Acta Endocrinol 101:377-385. 

Rognoni JB, Lemarchand-Beraud T, Berthier C. 1984. Respective roles of circulating T4 and T3 in 

control of TSH secretion in severely iodide-deficient rats. Experientia 40:215-217. 

Roland DA, McCready ST, Stonerock RH, et al. 1977. Hypercalcemic effect of potassium iodide on 

serum calcium in domestic fowl. Poult Sci 56:1310-1314. 

Romney BM, Nickoloff EL, Esser PD, et al. 1986. Radionuclide administration to nursing mothers: 

Mathematically derived guidelines. Radiology 160:549-554. 

Ron E. 1997. Cancer risk following radioactive iodine-131 exposures in medicine. In: Proceedings of 

the annual meeting of the National Council on Radiation Protection Measures: Implications of new data 

on radiation cancer risk. Bethesda, MD: National Cancer Institute, 65-77. 

Ron E, Modan B. 1984. Thyroid and other neoplasms following childhood scalp irradiation. In: Boice 

KD, Fraument JF, eds. Radiation carcinogenesis: Epidemiology and biological significance. New York, 

NY: Raven Press, 139-151. 

*Ron E, Doody MM, Becker DV, et al. 1998. Cancer mortality following treatment for adult 

hyperthyroidism. JAMA 280(4):347-355. 

*Ron E, Lubin JH, Shore RE, et al. 1995. Thyroid cancer after exposure to external radiation: A pooled 

analysis of seven studies. Radiat Res 141:259-277. 

Ron E, Modan B, Preston D, et al. 1989. Thyroid neoplasia following low-dose radiation in childhood. 

Radiat Res 120:516-531. 
IODINE 454 

9. REFERENCES 

*Rook HL, Suddueth JE, Becker DA. 1975. Determination of Iodine-129 at natural levels using neutron 

activation and isotopic separation. Anal Chem 47:1557-1561. 

Roos DE, Smith JG. 1999. Randomized trials on radioactive iodine ablation of thyroid remnants for 

thyroid carcinoma-a critique. Int J Radiat Oncol Biol Phys 44(3):493-495. 

Rosado M, Borrego LC, Paniagua ME. 1983. Incidence of hypothyroidism after radioiodine treatment 

for Graves disease. Bol Asoc Med P R 75(4):167-169. 

Rose MR, Prescott MC, Herman KJ. 1990. Excretion of iodine-123-hippuran, technetium-99m-red 

blood cells, and technetium-99m-macroaggregated albumin into breast milk. J Nucl Med 31(6):978-984. 

*Rose NR, Rasooly L, Saboori AM, et al. 1999. Linking iodine with autoimmune thyroiditis. Environ 

Health Perspect Suppl 107:749-752. 

*Rose NR, Saboori AM, Rasooly L, et al. 1997. The role of iodine in autoimmune thyroiditis. Crit Rev 

Immunol 17:511-517. 

*Rosen IB, Palmer JA, Rowen J, et al. 1984. Induction of hyperparathyroidism by radioactive iodine. 

Am J Surg 148:441-445. 

Rosen IB, Strawbridge HG, Bain J. 1975. A case of hyperparathyroidism associated with radiation to the 

head and neck area. Cancer 36:1111-1114. 

Rosenberg D, Grand MJH, Silbert D. 1963. Neonatal hyperthyroidism. N Engl J Med 268(6):292-296. 

*Rosenberg FR, Einbinder J, Walzer RA, et al. 1972. Vegetating iododerma. Arch Dermatol 105:900­

905. 

Rosenberg G. 1958. Biologic half-life of I131 in the thyroid of healthy males. J Clin Endocrinol Metab 

18:516-521. 

Rosenthal D. 1981. Kinetic analysis of iodine and thyroxine metabolism in "hot" thyroid nodules. 

Metabolism 30(4):384-392.
 

Ross DS. 1996a. Subclinical hypothyroidism. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's
 

the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 1010-1015. 

Ross DS. 1996b. Subclinical thyrotoxicosis. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's
 

the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 1016-1020. 

Ross DS. 1998. Syndromes of thyrotoxicosis with low radioactive iodine uptake. Endocrinol Metab 

Clin North Am 27(1):169-185. 

Ross DS, Daniels GH, De Stefano P, et al. 1983. Use of adjunctive potassium iodide after radioactive 

iodine (131I) treatment of Graves' hyperthyroidism. J Clin Endocrinol Metab 57(2):250-253. 

Rothschild HC. 1974. A criteria digest on radioactivity in the environment. Ottawa, Canada: National 

Research Council Canada. 

*Roti E, Uberti E. 2001. Iodine excess and hyperthyroidism. Thyroid 11(5): 493-500. 
 

 

IODINE 455 

9. REFERENCES 

*Roti E, Vagenakis AG. 2000. Effect of excess iodide: Clinical aspects. In: Braverman LE, Utiger RD, 

eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 8th ed. Philadelphia, PA: 

Lippincott-Williams and Wilkins, 316-329. 

Roti E, Gnudi A, Braverman LE. 1983. The placental transport, synthesis and metabolism of hormones 

and drugs which affect thyroid function. Endocrine Rev 4:131-149. 

Roti E, Minelli R, Gardini E, et al. 1990. Iodine-induced hypothyroidism in euthyroid subjects with a 

previous episode of subacute thyroiditis. J Clin Endocrinol Metab 70:1581-1585. 

Roti E, Minelli R, Gardini E, et al. 1992. Iodine-induced subclinical hypothyroidism in euthyroid 

subjects with a previous episode of amiodarone-induced thyrotoxicosis. J Clin Endocrinol Metab 

75(5):1273-1277. 

Roudebush CP, Hoye KE, DeGroot LJ. 1977. Compensated low-dose 131I therapy of Graves' disease. 

Ann Intern Med 87:441-443. 

*Royaux IE, Suzuki K, Mori A, et al. 2000. Pendrin, the protein encoded by the Pendred Syndrome gene 

(PDS), is an apical porter of iodide in the thyroid and is regulated by thyroglobulin in FRTL-5 cells. 

Endocrinology 141(2):839-845. 

Rozenson R, Gusev B, Hoshi M, et al. 1996. A brief summary of results of radiation studies on residents 

in the Semipalatinsk area, 1957-1993. In: Nagataki S, Yamashita S, eds. Nagasaki symposium radiation 

and human health: Proposal from Nagasaki. Amsterdam, The Netherlands: Elsevier, 127-145. 

Rubery ED. 1990. Practical aspects of prophylactic stable iodine usage. In: Rubery E, Smales E, eds. 

Iodine prophylaxis following nuclear accidents. Oxford, UK: Pergamon Press, 141-150. 

*Rubow S, Klopper J, Wasserman H, et al. 1994. The excretion of radiopharmaceuticals in human breast 

milk: Additional data and dosimetry. Eur J Nucl Med 21:144-153. 

Ruegsegger GJ, Schultz LH. 1980. Iodine in field milk samples [Abstract]. J Dairy Sci 63(Suppl 1):115. 

Ruiz De Ona C, Obregon MJ, Escobar Del Rey F, et al. 1988. Developmental changes in rat brain 5'­

deiodinase and thyroid hormones during the fetal period: The effects of fetal hypothyroidism and 

maternal thyroid hormones. Pediatr Res 24(5):588-594. 

Russell JL, Hahn PB. 1971. Public health aspects of iodine-129 from the nuclear power industry. Radiol 

Health Data Rep 12(4):189-194. 

*Russell KP, Rose H, Starr P. 1957. The effects of radioactive iodine on maternal and fetal thyroid 

function during pregnancy. Surg Gynecol Obstet 104:560-564. 

*Ruwhof C, Drexhage HA. 2001. Iodine and thyroid autoimmune disease in animal models. Thyroid 

11(5):427-436 

Rybakowa M, Tylek D, Soltysik-Wilk E, et al. 1991. [Epidemiologic study in children from the Krakow 

region following the Chernobyl accident.] Endokrynol Pol 42(2):253-261. (Polish) 
 

 

IODINE 456 

9. REFERENCES 

*Saboori AM, Rose NR, Bresler HS et al. 1998a. Iodination of human thyroglobulin (Tg) alters its 

immunoreactivity. I. Iodination alters multiple epitopes of human Tg. Clin Exp Immunol 113:297-302. 

*Saboori AM, Rose NR, Burek CL. 1998b. Iodination of human thyroglobulin alters its 

immunoractivity. II. Fine specificity of a monoclonal antibody that recognizes iodinated thyroglobulin. 

Clin Exp Immunol 113:303-308. 

*Saboori AM, Rose NR, Yuhasz SC, Amzal M, Burek CL.1999. Peptides of human thyrogolbulin 

reactive with sera of patients with autoimmune thyroid disease. J Immunol 163:6244-6250. 

*Sachs BA, Siegel E, Horwitt BN, et al. 1972. Bread iodine content and thyroid radioiodine uptake: A 

tale of two cities. Br Med J 1:79-81. 

Saddok C, Gafni M, Gross J. 1978. Effect of iodide on the adenyl cyclase system of the mouse thyroid in 

vivo. Acta Endocrinol 88:517-527. 

Safa A, Schumacher OP. 1976. Follow-up of children treated with 131I. N Engl J Med 294(1):54. 

Safa AM, Skillern PG. 1975. Treatment of hyperthyroidism with a large initial dose of sodium iodide I 

131. Arch Intern Med 135:673-675. 

Safa AM, Schumacher OP, Rodriguez-Antunez A. 1975. Long-term follow-up results in children and 

adolescents treated with radioactive iodine (131I) for hyperthyroidism. N Engl J Med 292:167-171. 

*Safran M, Braverman LE. 1982. Effect of chronic douching with polyvinylpyrrolidone-iodine on iodine 

absorption and thyroid function. Obstet Gynecol 60(1):35-40. 

*Safran M, Paul TL, Roti TL, et al. 1987. Environmental factors affecting autoimmune thyroid disease. 

Endocrinol Metab Clin N Am 16(2): 327-342. 

Saito K, Kaneko H, Sato K, et al. 1991. Hepatic UDP-glucuronyltransferase(s) activity toward thyroid 

hormones in rats: Induction and effects on serum thyroid hormone levels following treatment with 

various enzyme inducers. Toxicol Appl Pharmacol 111:99-106. 

Saito K, Yamamoto K, Takai T, et al. 1983. Inhibition of iodide accumulation by perchlorate and 

thiocyanate in a model of the thyroid iodide transport system. Acta Endocrinol 104(4):456-461. 

Saji M, Kohn LD. 1990. Effect of hydrocortisone on the ability of thyrotropin to increase 

deoxyribonucleic acid synthesis and iodide uptake in FRTL-5 rat thyroid cells: Opposite regulation of 

adenosine 3',5'-monophosphate signal action. Endocrinology 127(4):1867-1876. 

Saji M, Kohn LD. 1991. Insulin and insulin-like growth factor-I inhibit thyrotropin-increased iodide 

transport in serum-depleted FRTL-5 rat thyroid cells: Modulation of adenosine 3',5'-monophosphate 

signal action. Endocrinology 128:1136-1143. 

Saji M, Isozaki O, Tsushima T, et al. 1988. The inhibitory effect of iodide on growth of rat thyroid 

(FRTL-5) cells. Acta Endocrinol 119:145-151. 

*Salbu B, Steinnes E, Pappas AC. 1975. Multielement neutron activation analysis of fresh water using 

Ge(Li) gamma spectrometry. Anal Chem 47:1011-1016. 
IODINE 457 

9. REFERENCES 

*Saller B, Fink H, Mann K. 1998. Kinetics of acute and chronic iodine excess. Exp Clin Endocrinol 

Diabetes 106(Suppl 3):S34-S38. 

Samuel AM, Unnikrishnan TP, Baghel NS, et al. 1995. Effect of radioiodine therapy on pulmonary 

alveolar-capillary membrane integrity. J Nucl Med 36:783-787. 

Samuel S, Pildes RS, Lewison M, et al. 1971. Neonatal hyperthyroidism in an infant born of an 

euthyroid mother. Am J Dis Child 121:440-443. 

Santana C, Burek CL, Talor M, et al. 1997. Evaluation of thyroid glands from NOD-H-2h-4 mice with 

iodine-induced thryoiditis [Abstract]. Mol Biol Cell 8(Suppl):453A. 

Santisteban P, Obregon MJ, Rodriguez-Pena A, et al. 1982. Are iodine-deficient rats euthyroid? 

Endocrinology 110(5):1780-1789. 

Sapozink MD, Palos B, Goffinet DR, et al. 1983. Combined continuous ultra low dose rate irradiation 

and radiofrequency hyperthermia in the C3H mouse. Int J Radiat Oncol Biol Phys 9:1357-1365. 

Sarkar SD, Beierwaltes WH, Gill SP, et al. 1976. Subsequent fertility and birth histories of children and 

adolescents treated with 131I for thyroid cancer. J Nucl Med 17:460-464. 

Sasaki H, Matsumoto S, Shuyo H, et al. 1992. Gross ascites as a first manifestation of primary 

hypothyroidism due to post-treatment of radioiodine therapy for Graves' disease. Intern Med 31:256-259. 

Sastry KSR. 1992. Biological effects of the Auger emitter iodine-125: A review. Report No. 1 of 

AAPM Nuclear Medicine Task Group No. 6. Med Physics 19(6):1361-1370. 

Sato A, Ohtake M, Kotani M, et al. 1972. Effects of methimazole and propylthiouracil on blood 

disappearance and urinary excretion of iodide in the rat. Proc Soc Exp Biol Med 141(1):119-122. 

Sato K, Robbins J. 1981. Thyroid hormone metabolism in primary cultured rat hepatocytes. J Clin 

Invest 68:475-493. 

Sato T, Inoue M, Suzuki Y, et al. 1975. [Hypothyroidism caused by 131I contained in mothers' milk: Its 

association with polycystic ovary and kidney calculus.] Horumon To Rinsho 23(6):535-538. (Japanese) 

*Savoie JC, Massin JP, Thomopoulos P, et al. 1975. Iodine-induced thyrotoxicosis in apparently normal 

thyroid glands. J Clin Endocrinol Metab 41:685-691. 

Sawers JSA, Toft AD, Irvine WJ, et al. 1980. Transient hypothyroidism after iodine-131 treatment of 

thyrotoxicosis. J Clin Endocrinol Metab 50:226-229. 

Sawin CT, Castelli WP, Hershman JM, et al. 1985. The aging thyroid: Thyroid deficiency in the 

Framingham study. Arch Intern Med 145:1386-1388. 

*Saxena Km, Chapman EM, Pryles CV. 1962. Minimal dosage of iodide required to suppress uptake of 

iodine-131 by normal thyroid. Science 138:430-431. 

Scanlon MF, Toft AD. 1996. Regulation of thyrotropin secretion. In: Braverman LE, Utiger RD, eds. 

Warner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 

220-240. 
 

 

IODINE 458 

9. REFERENCES 

Schaffer R, Muller HA, Ebelt R. 1983. Distribution pattern of malignant thyroid tumors in an endemic 

goitre area. Acta Endocrinol Suppl 252:13-14. 

*Schaug J, Rambaek JP, Steinnes E, et al. 1990. Multivariate analysis of trace element data from moss 

samples used to monitor atmospheric deposition. Atmos Environ 24A(10):2625-2631. 

Scherbaum WA. 1996. Iodine-induced thyroiditis in the non-obese diabetic (NOD) mouse-more 

questions than answers. Exp Clin Endocrinol Diabetes 104(Suppl 3):20-23. 

Scheuttelkopf H. 1979. [Radioecological reduction of acute and long-term contamination of the 

environment by iodine-129]. (German). In: Kernforshungszent. Karlsruhe, [Ber.] KFK, KFK 2770, 

Samml. Vortr. Jahreskolloquim 1978 Proj Nukl Sicherheit, 206-225. 

Schilling YR, Abellan F, Escribano JRD, et al. 1998. Acute leukemias after treatment with radioiodine 

for thyroid cancer. Haematologica 83(8):767-768. 

Schlenker RA. 1985. Internal emitter limits for iodine, radium and radon daughters. Proc Annu Meet 

Natl Counc Radiat Prot Meas 6:131-181. 

Schlumberger MJ. 1988. Papillary and follicular thyroid carcinoma. N Engl J Med 338(5):297-306. 

Schlumberger M, Caillou B. 1996. Miscellaneous tumors of the thyroid. In: Braverman LE, Utiger RD, 

eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: LippincottRaven, 961-965. 

Schlumberger M, De Vathaire F. 1996. [131 Iodine: Medical use. Carcinogenetic and genetic effects.] 

Ann Endocrinol (Paris) 57:166-167. (French) 

Schlumberger M, De Vathaire F, Ceccarelli C, et al. 1996. Exposure to radioactive iodine-131 for 

scintigraphy or therapy does not preclude pregnancy in thyroid cancer patients. J Nucl Med 37(4):606­

612. 

Schlumberger M, Parmentier N, Chavaudra J, et al. 1988. [Management in cases of accidental 

contamination by iodine radioisotopes.] Presse Med 17(8):386-388. (French) 

Schlumberger M, Parmentier C, de Vathaire F, et al. 1997. Iodine-131 and external radiation in the 

treatment of local and metastatic thyroid cancer. In: Falk SA, ed. Thyroid disease: Endocrinology, 

surgery, nuclear medicine, and radiotherapy. Philadelphia, PA: Lippincott-Raven Publishers, 601-617. 

*Schmidt A, Schnabel C, Handle J, et al. 1998. On the analysis of iodine-129 and iodine-127 in 

environmental materials by accelerator mass spectrometry and ion chromatography. Sci Total Environ 

223:131-156. 

*Schmitt TL, Espinoza CR, Loos U. 2000. Cloning and characterization of repressory and stimulatory 

DNA sequences upstream the Na/I-symporter gene promoter. Horm Metab Res 32(1):1-5. 

*Schmitt TL, Espinoza CR, Loos U. 2001. Transcriptional regulation of the human sodium/iodide 

symporter gene by Pax8 and TTF-1. Exp Clin Endocrinol Diabetes 109(1):27-31. 
 

 

 

IODINE 459 

9. REFERENCES 

Schmucki O, Sulmoni A, Pupato F. 1973. [Late bladder complications after radioactive iodine therapy of 

thyroid tumors.] Urologe A 12(3):130-133. (German) 

Schmutzler C. 2001. Regulation of the sodium/iodide symporter by retinoids-a review. Exp Clin 

Endocrinol Diabetes 109(1):41-44. 

Schneeweiss FHA, Myers DK, Tisljar-Lentulis G, et al. 1985. Low oxygen enhancement ratios for 

strand breaks induced by decays of 125I in DNA of human T1 cells stored at 0 degrees C. Radiat Prot 

Dosim 13(1-4):237-239. 

Schneider AB, Ron E. 1996. Carcinoma of follicular epithelium. In: Braverman LE, Utiger RD, eds. 

Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 

902-909. 

Schneider AB, Gierlowski TC, Shore-Freedman E, et al. 1995. Dose-response relationships for 

radiation-induced hyperparathyroidism. J Clin Endocrinol Metab 80(1):254-257. 

Schneider AB, Recant W, Pinsky SM, et al. 1986. Radiation-induced thyroid carcinoma. Ann Intern 

Med 105:405-412. 

Schneider AB, Ron E, Lubin J, et al. 1993. Dose-response relationships for radiation-induced thyroid 

cancer and thyroid nodules: Evidence for the prolonged effects of radiation on the thyroid. J Clin 

Endocrinol Metab 77(2):362-369. 

Schneider AB, Shore-Freedman E, Ryo UY, et al. 1985. Radiation-induced tumors of the head and neck 

following childhood irradiation. Medicine 64(1):1-15. 

Schneppe MM. 1972. Determination of total iodine and iodate in sea water and in various evaporites. 

Anal Chim Acta 58:83-89. 

Schnyder UW, Taugner M, Rossbach J. 1969. [Histology of pathological iodine reactions of the skin.] 

Dermatologica 139(4):266-270. (German) 

Schober O, Gunter H-H, Schwazrock R, et al. 1987. [Hematologic long-term modifications after radioiodine therapy of the carcinoma of the thyroid gland: I. Peripheral blood count modifications.] 

Strahlenther Onkol 163:464-474. (German) 

Schreiber G, Southwell BR, Richardson SJ. 1995. Hormone delivery systems to the brain-transthyretin. 

Exp Clin Endocrinol 103:75-80. 

Schreiber V, Rohacova J. 1971. Increase in thyroid radioiodine uptake following the administration of 

cyproterone acetate. Experientia 27(7):848-849. 

Schroder-van der Elst JP, van der Heide D, Kastelijn J, et al. 2001. The expression of the sodium/iodide 

symporter is up-regulated in the thyroid of fetuses of iodine-deficient rats. Endocrinology 142(9):3736­

3741. 

*Schull WJ, Otake M, Yoshimaru H. 1988. Effect on intelligence test score of prenatal exposure to 

ionizing radiation in Hiroshima and Nagasaki: A comparison of the T65DR and DS86 dosimetry 

systems. Radiation Effects Research Foundation. RERF TR 3-88. Research project 24-62. 
IODINE 460 

9. REFERENCES 

*Schuppert F, Ehrenthal D, Frilling A, et al. 2000. Increased major histocompatibility complex (MHC) 

expression in nontoxic goiters is associated with iodide depletion, enhanced ability of the follicular 

thyroglobulin to increase MHC gene expression, and thyroid antibodies. J Clin Endocrinol Metab 

85(2):858-867. 

Schurizek BA, Kraglund K, Andreasen F, et al. 1989. Antroduodenal motility and gastric emptying. 

Gastroduodenal motility and pH following ingestion of paracetamol. Aliment Pharmacol Ther 3:93-101. 

Schwarz G, Hoffman FO. 1979. Imprecision of dose predictions for radionuclides released to the 

atmosphere: An application of the Monte-Carlo-Simulation-Technique for iodine transported via the 

pasture-cow-milk pathway. Presented at the 1979 Winter Meeting of the American Nuclear Society, 

November 11-16, 1979. San Francisco, California. CONF-791103–48. 

Schwarzfischer P, Harlass G, Kreul H-G, et al. 1981. [Iodine induced hyperthyroidism in old age. Part 

1: Multimorbidity, autonomous tissue and possibilities for iodine contamination.] Fortschr Med 

99(44):1834-1838. (German) 

Schwarzfischer P, Harlass G, Kreul H-G, et al. 1982. [Iodine-induced hyperthyroidism in the aged. 2. 

Pathomechanism, differential diagnosis and therapy problems.] Fortschr Med 100(5):153-158. 

(German). 

*Scott DA, Wang R, Kreman TM, et al. 2000. Functional differences of the PDS gene product are 

associated with phenotypic variation in patients with Pendred syndrome and non-syndromic hearing loss 

(DFNB4). Hum Mol Gen 9(11):1709-1715. 

Scott GR, Forfar JC, Toft AD. 1984. Graves' disease and atrial fibrillation: The case for even higher 

doses of therapeutic iodine-131. Br Med J 289:399-400. 

Scully JM, Uno JM, McIntyre M, et al. 1990. Radiation-induced prostatic sarcoma: A case report. J 

Urol 144:746-748. 

*Seabold JE, Ben-Haim S, Pettit WA, et al. 1993. Diuretic-enhanced I-131 clearance after ablation 

therapy for differentiated thyroid cancer. Radiology 187:839-842. 

Sedelnikova OA, Panyutin IG, Thierry AR, et al. 1998. Radiotoxicity of iodine-125-labeled 

oligodeoxyribonucleotides in mammalian cells. J Nucl Med 39(8):1412-1418. 

Segers O, Musch W, Schoors DF. 1993. Early complications of radioiodine treatment for 

hyperthyroidism. Acta Clin Belg 48(4):253-258. 

*Segers O, Spapen H, Steenssens L, et al. 1988. Treatment of severe iodine-induced hyperthyroidim 

with plasmapheresis. Acta Clin Belg 43:335-343. 

Segura ET, Roussel JD, Satterlee DG, et al. 1979. Interaction of exogenous corticotropin and 

environment on protein bound iodine and other plasma biochemical parameters. J Dairy Sci 62:278-283. 

*Sekura RD, Sato K, Cahnmann HJ, et al. 1981. Sulfate transfer to thyroid hormones and their analogs 

by hepatic aryl sulfotransferases. Endocrinology 108(2):454-456. 

Self GJ, Rigby PJ, Passarelli MC, et al. 1990. Characteristics and localisation of 125I ion binding in 

mammalian airways. Eur J Pharmacol 176:169-176. 
 

 

 

 

IODINE 461 

9. REFERENCES 

Senczuk W, Slusarek D. 1981. [Effect of detergents on iodophor toxicity. I. Effect of detergents on 

acute toxicity and iodophor cumulation coefficient.] Rocz Panstw Zakl Hig 32(3):197-200. (Czech.) 

Senczuk W, Slusarek D. 1982. [Effect of detergents on iodophor toxicity. III. Effect of detergents on 

iodine absorption into blood, retention in the organs and urinary excretion.] Rocz Panstw Zakl Hig 

33(3):207-213. (Czech.) 

Senczuk W, Slusarek D, Sadowski C. 1982. [Effect of detergents on iodophor toxicity. IV. Iodine 

content of the blood, urine and tissues of animals exposed to the long-term action of iodophor.] Rocz 

Panstw Zakl Hig 33(4):307-309. (Czech.) 

Senekowitsch R, Kriegel H. 1984. Diaplacental transfer and distribution of some radionuclides in fetal 

organs at different stages of gestation - experimental results. EUR 8067:183-197. 

Senior B, Chernoff HL. 1971. Iodide goiter in the newborn. Pediatrics 47(3):510-515. 

*Setchell BP, Waites GMH. 1975. The blood-testis barrier. In: Creep RO, Astwood EB, Geiger SR, 

eds. Handbook of physiology: Endocrinology V. Washington, DC: American Physiological Society. 

Shafer RB, Nuttall FQ. 1975. Acute changes in thyroid function in patients treated with radioactive 

iodine. Lancet 2(7936):635-637. 

Shah DH, Patel MC, Sulkhe PV. 1969. Effect of actinomycin D on the uptake of radioiodine by 

thyroidal and extrathyroidal tissues-I. Biochem Pharmacol 18:1487-1493. 

Shah KH, Oslapas R, Calandra DB, et al. 1983. Effects of radiation on parafollicular C cells of the 

thyroid gland. Surgery 94(6):989-994. 

Shanshiashvill TA, Gracheva LM. 1981. Genetic effects of decay of radionuclde products of division of 

nucleofuel in cells of the yeast saccharomyces cerevisiae. Role of transmutation: I. Lethal mutagenic 

effects and the nature of mutations induced by yttrium-91 decay. Sov Genet 17:1370-1376. Translation 

of Genetika, 17(12):2115-2124. 

Shao J, Chen Q, Guo C, et al. 1995. [Effect of lithium on iodine uptake in thyroid cells in culture.] 

Zhonghua Heyixue Zazhi 15(4):242-244. (Chinese) 

Shapiro B. 1993. Optimization of radioiodine therapy of thyrotoxicosis: What have we learned after 50 

years? J Nucl Med 34(10):1638-1644. 

Sheeler LR, Skillern PG, Schumacher OP, et al. 1984. Radioiodine-induced thyroid storm: A point of 

controversy. Am J Med 76(4):A98. 

Sheldon J. 1983. Effects of amiodarone in thyrotoxicosis. Br Med J 286:267-268. 

*Shelly WB. 1967. Generalized pustular psoriasis induced by potassium iodide. JAMA 201(13):133­

138. 

*Shen DHY, Kloos RT, Mazzaferri EL, Jhiang SM. 2001. Sodium iodide symporter in health and 

disease. Thyroid 11(5):415-425. 
 

 

 

IODINE 462 

9. REFERENCES 

Shennan DB. 2001. Iodine transport in lactating rat mammary tissues via a pathway independent from 

the Na+

/I- cotransporter: evidence for sulfate/iodide exchange. Biochem Biophys Res Commun 

280(5):1359-1363. 

Sheppard MI, Hawkins JL. 1995. Iodine and microbial interactions in an organic soil. J Environ 

Radioact 29(2):91-109. 

Sheppard MI, Thibault DH. 1988. Migration of technetium, iodine, neptunium, and uranium in the peat 

of two minerotrophic mires. J Environ Qual 17(4):644-653. 

Sheppard MI, Thibault DH. 1991. A four-year mobility study of selected trace elements and heavy 

metals. J Environ Qual 20:101-114. 

*Sheppard MI, Thibault DH, Mcmurry J, et al. 1995. Factors affecting the soil sorption of iodine. Water 

Air Soil Pollut 83:51-67. 

Sheppard SC. 1995. When does chemical toxicity of 129I become important? In: Environmental impact 

of radioactive releases: Proceedings of an international symposium on environmental impact of 

radioactive releases. Vienna, Austria: International Atomic Energy Agency, 837-883. 

Sheppard SC, Evenden WG. 1995. Toxicity of soil iodine to terrestrial biota, with implications for 129I. J 

Environ Radioact 27(2):99-116. 

*Sheppard SC, Evenden WG, Amiro BD. 1993. Investigation of the soil-to-plant pathway for I, Br, Cl 

and F. J Environ Radioact 21:9-32. 

*Sheppard SC, Evenden WG, Schwartz WJ. 1995. Ingested soil: Bioavailability of sorbed lead, 

cadmium, cesium, iodine, and mercury. J Environ Qual 24:498-505. 

Sherer TT, Thrall KD, Bull RJ. 1991. Comparison of toxicity induced by iodine and iodide in male and 

female rats. J Toxicol Environ Health 32:89-101. 

*Sheridan PJ, Zoller WH. 1989. Elemental composition of particulate material sampled from the Arctic 

haze aerosol. J Atmos Chem 9:363-381. 

Sherwin JR. 1978. Iodide induced suppression of thyrotropin-stimulated adenosine 3',5'-monophosphate 

production in cat thyroid slices. Horm Res 9:271-278. 

Sherwin JR, Seaford JW. 1986. Effect of valinomycin on thyroid iodide transport and TSH-stimulated 

cAMP formation. Am J Physiol 250(13):E164-E168. 

*Shetty KR, Duthie EH. 1990. Thyrotoxicosis induced by topical iodine application. Arch Intern Med 

150:2400-2401. 

Shevchenko VA, Ramaya LK, Pomerantseva MD, et al. 1989. Genetic effects of 131I in reproductive 

cells of male mice. Mutat Res 226:87-91. 

Shibuya M. 1991. Studies on the iodine-binding factors of human parotid saliva. Shika Gakuho 

91(12):1587-1603. 
 

 

 

IODINE 463 

9. REFERENCES 

*Shilo S, Hirsch HJ. 1986. Iodine-induced hyperthyroidism in a patient with a normal thyroid gland. 

Postgrad Med J 62:661-662. 

Shimizu T, Shishiba Y. 1975. Effect of triidothyronine or iodide on the thyroidal secretion in vitro: 

Inhibition of TSH- and dibutyryl-cyclic-AMP induced endocytosis. Endocrinol Jpn 22(1):55-60. 

Shimon I, Kneller A, Olchovsky D. 1995. Chronic myeloid leukaemia following 131I treatment for 

thyroid carcinoma: A report of two cases and review of the literature. Clin Endocrinol 43:651-654. 

Shimura H, Endo T, Tsujimoto G, et al. 1990. Characterization of alpha1-adrenergic receptor subtypes 

linked to iodide efflux in rat FRTL cells. J Endocrinol 124:433-441. 

*Shimura H, Haraguchi K, Miyazaki A, et al. 1997. Iodide uptake and experimental 131I therapy in ­ transplanted undifferentiated thyroid cancer cells expressing the Na +/I symporter gene. Endocrinology 

138(10):4493-4496. 

Shinohara K. 1994. [A preliminary study on the effects of start age of uptake on dose assessment for 

chronic ingestion of radionuclides.] Hoken Butsuri 29(2):201-205. (Japanese) 

*Shinonaga T, Gerzabek MH, Strebl F, et al. 2001. Transfer of iodine from soil to cereal grains in 

agricultural areas of Austria. Sci Total Environ 267(1-3):33-40. 

*Shipler DB, Napier BA, Farris WT, et al. 1996. Hanford environmental dose reconstruction project - an 

overview. Health Phys 71:532-544. 

Shishiba Y, Solomon DH. 1967. Effect of amphotericin B on thyroidal iodide concentration. 

Endocrinology 81:467-474. 

Shleien B, Halperin JA, Bilstad JM, et al. 1983. Recommendations on the use of potassium iodide as a 

thyroid-blocking agent in radiation accidents: An FDA update. Bull N Y Acad Med 59(10):1009-1019. 

Sho FK, Kondo Y. 1988. Inhibition by islet-activating protein, pertussis toxin, of P2-purinergic receptormediated iodide efflux and phosphoinositide turnover in FRTL-5 cells. Endocrinology 123(2):1035­

1043. 

Sho K, Okajima F, Akiyama H, et al. 1989. Requirement of insulin growth factor I plus hydrocortisone 

for the regeneration of thyrotropin (TSH)-dependent mechanism of I- efflux and CA2+ mobilization in 

FRTL-5 cells during TSH depletion. Endocrinology 124:598-604. 

Shopsin B, Shenkman L, Blum M, et al. 1973. Iodine and lithium-induced hypothyroidism: 

Documentation of synergism. Am J Med 55:695-699. 

Shore RE. 1989. Risk of thyroid cancer after diagnostic doses of radioiodine. J Natl Cancer Inst 

81(9):713-715. 

*Shore RE. 1992. Issues and epidemiological evidence regarding radiation-induced thyroid cancer. 

Radiat Res 131:98-111. 

Shore RE, Albert RE, Pasternack BS. 1976. Follow-up study of patients treated by x-ray epilation for 

tinea capitis. Arch Environ Health 31:14-24. 
 

 

 

IODINE 464 

9. REFERENCES 

Shore RE, Hildreth N, Dvoretsky P, et al. 1993a. Benign thyroid adenomas among persons x-irradiated 

in infancy for enlarged thymus glands. Radiat Res 134:217-223. 

Shore RE, Hildreth N, Dvoretsky P, et al. 1993b. Thyroid cancer among persons given x-ray treatment 

in infancy for an enlarged thymus gland. Am J Epidemiol 137(10):1068-1080. 

Sichuk G, Money WL, Der BK, et al. 1968. Cancer of the thyroid, goitrogenesis and thyroid function in 

Syrian (golden) hamsters. Cancer 21(5):952-963. 

Siegemund B, Weyers W. 1987. [Teratological studies of low-molecular weight polyvinylpyrrolidoneiodine complex in rabbits.] Arzneim Forsch 37(3):340-341. (German) 

Sikov MR. 1969. Effect of age on the iodine-131 metabolism and the radiation sensitivity of the rat 

thyroid. Radiat Res 38:449-459. 

Sikov MR, Meznarich HK, Traub RJ. 1991. Comparison of placental transfer and localization of 

caesium strontium and iodine in experimental animals and women. Int J Radiat Biol 60(3):553-555. 

Silberstein T, Hallak M, Gonen R, et al. 2001. Toxic trace elements (TE) can be found in the maternal 

and fetal compartments. Am J Obstet Gynecol 184(1):S177. 

Silva CAM, Merkt H, Bergamo PNL, et al. 1987. Consequence of excess iodine supply in a 

thoroughbred stud in southern Brazil. J Reprod Fertil Suppl 35:529-533. 

*Silva JE. 2000a. Catecholamines and the sympathoadreanl system in thyrotoxicosis. In: Braverman 

LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 8th ed. 

Philadelphia, PA: Lippincott-Raven, 642-651. 

*Silva JE. 2000b. Catecholamines and the sympathoadrenal system in hypothyroidism. In: Braverman 

LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 8th ed. 

Philadelphia, PA: Lippincott-Raven, 820-823. 

Sim RTS. 1993. Thrombocytopenia associated with exposure to iodine. Hawaii Med J 52(10):262. 

Simon SL. 1996. A summary of health, environmental and sociological consequences from atomic 

testing in the Marshall Islands. In: Nagataki S, Yamashita S, eds. Nagasaki symposium radiation and 

human health: Proposal from Nagasaki. Amsterdam, The Netherlands: Elsevier, 155-165. 

Simon SL, Graham JC. 1996. Dose assessment activities in the Republic of the Marshall Islands. Health 

Phys 71(4):438-456. 

*Simon SL, Graham JC. 1997. Findings of the first comprehensive radiological monitoring program of 

the Republic of the Marshall Islands. Health Phys 73(1):66-85. 

*Simon SL, Lloyd RD, Till JE, et al. 1990. Development of a method to estimate thyroid dose from 

fallout radioiodine in a cohort study. Health Phys 59(5):669-691. 

*Simon SL, Luckyanov N, Bouville A, et al. 2002. Transfer of 131I into human breast milk and transfer 

coefficients for radiological dose assessments. Health Phys 82(6):796-806. 
IODINE 465 

9. REFERENCES 

Simonnet F, Orts JC, Simonnet G. 1989. Destruction of genotoxic wastes mixed with radioactive 

products. Health Phys 57(6):885-890. 

Simonovic I, Kargarcin B, Kostial K. 1986. The effect of composite oral treatment for internal 

contamination with several radionuclides on 131I thyroid uptake in humans. J Appl Toxicol 6(2):109-111. 

Simonovic I, Kostial K, Kargacin B. 1984. 131I uptake in human thyroid after antidote treatment for 

mixed fission products contamination. Int J Radiat Biol 46(4):459-462. 

Simpson CL, Hempelmann LH, Fuller LM. 1955. Neoplasia in children treated with x-rays in infancy 

for thyroid enlargement. Radiology 64:840-845. 

Sinclair WK, Abbatt JD, Farran HEA, et al. 1956. A quantitative autoradiographic study of radioiodine 

distribution and dosage in human thyroid glands. Br J Radiol 29:36-41. 

Sindainovic J, Liewendahl K. 1976. Studies on proteolytic activity and function of the thyroid gland in 

rats administered excess iodide. Acta Endocrinol 82:728-736. 

Singh B, Dhawan D, Chand B, et al. 1994. Biokinetics of iodine-131 in rat thyroid following lead and 

lithium supplementation. Biol Trace Elem Res 40:287-293. 

Singh B, Dhawan D, Mangal PC, et al. 1992. The influence of lead toxicity on the biological half-life of 

iodine-131 Rose Bengal in rat liver. Med Sci Res 20(17):623-624. 

Singh VN, Chaikoff IL. 1966. Effects of 1-methyl-2-mercaptoimidazole and perchlorate on the insulinmediated enhancement of 131I incorporation into iodoamino acids by fetal thyroid glands in organ culture. 

Endocrinology 78:339-342. 

Singhal RK, Narayanan U, Bhat IS. 1998. Investigations on interception and translocation of airborne 

85Sr, 131I, 137Cs in beans, spinach and radish plants. Water Air Soil Pollut 101:163-176. 

Sinniah R, Lye WC. 2001. Acute renal failure from hemoglobinuric and interstitial nephritis secondary 

to iodine and mefenamic acid. Clin Nephrol 55(3):254-258. 

Sit KH, Kanagasuntheram R. 1972. A structural analysis of congenital limb deformities in experimental 

hyperthyroid tadpoles. J Embryol Exp Morphol 28(1):223-234. 

Skare S, Frey HMM. 1980. Iodine induced thyrotoxicosis in apparently normal thyroid glands. Acta 

Endocrinol 94:332-336. 

Sleight SD, Mangkoewidjojo S, Akoso BT, et al. 1978. Polybrominated biphenyl toxicosis in rats fed an 

iodine-deficient, iodine-adequate, or iodine-excess diet. Environ Health Perspect 23:341-346. 

*Small MD, Bezman A, Longarni AE, et al. 1961. Absorption of potassium iodide from gastro-intestinal 

tract. Proc Soc Exp Biol Med 106:450-452. 

Smallridge RC. 1996. Metabolic, physiologic, and clinical indexes of thyroid function. In: Braverman 

LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: 

Lippincott-Raven, 397-405. 
 

 

IODINE 466 

9. REFERENCES 

Smallridge RC, Gist ID, Ambroz C. 1991. 8-Diethylamino-octyl-3,4,5-trimethyoxybenzoate, a calcium 

store blocker, increases calcium influx, inhibits alpha-1 adrenergic receptor calcium mobilization, and 

alters iodide transport in FRTL-5 rat thyroid cells. Endocrinology 129(1):542-549. 

Smallridge RC, Gist ID, Kiang JG. 1992. Na+

-H+ antiport and monesin effects on cytosolic pH and 

iodide transport in FRTL-5 rat thyroid cells. Am J Physiol 262(25):E834-E839. 

Smallridge RC, Wartofsky L, Burman KD. 1982. The effect of experimental hyperthyroidism and 

hypothyroidism on 5'-monodeiodination of 3,3',5'-triiodothyronine and 3',5'-diiodothyronine by rat liver 

and kidney. Endocrinology 111:2066-2069. 

*Smanik PA, Liu Q, Furminger TL, et al. 1996. Cloning of the human sodium iodide symporter. 

Biochem Biophys Res Commun 226:339-345. 

*Smanik PA, Ryu K-Y, Theil KS, et al. 1997. Expression, exon-intron organization, and chromosome 

mapping of the human sodium iodide symporter. Endocrinology 138(8):3555-3558. 

Smerdely P, Boyages SC, Wu D, et al. 1989. Topical iodine-containing antiseptics and neonatal 

hypothyroidism in very-low-birthweight infants. Lancet 2(8664):661-664. 

Smidt KP, Johnson E. 1975. Undetected iatrogenic hypothyroidism: A late complication of radio-iodine 

therapy. N Z Med J 81:325-328. 

Smit E, Whiting DA, Feld S. 1994. Iodine-induced hyperthyroidism caused by acne treatment. J Am 

Acad Dermatol 31(1):115-117. 

Smit JWA, Schroder-van der Elst JP, Karperien M, et al. 2000. Reestablishment of in vitro and in vivo 

iodide uptake by transfection of the human sodium iodide symporter (hNIS) in a hNIS defective human 

thyroid carcinoma cell line. Thyroid 10(11):939-943. 

Smith CS, Howard NJ. 1973. Propanolol in treatment of neonatal thyrotoxicosis. J Pediatr 83(6):1046­

1048. 

Smith GE. 1917. Fetal athyrosis. A study of the iodine requirement of the pregnant sow. J Biol Chem 

29:215-225. 

Smith JM, Broadway JA, Strong AB. 1978. United States population dose estimates for iodine-131 in 

the thyroid after the Chinese atmospheric nuclear weapons tests. Science 200:44-46. 

*Smith MB, Xue H, Takahashi H, et al. 1994. Iodine 131 thyroid ablation in female children and 

adolescents: Long-term risk of infertility and birth defects. Ann Surg Oncol 1(2):128-131. 

Smith RN, Wilson GM. 1967. Clinical trial of different doses of 131I in treatment of thyrotoxicosis. Br 

Med J 1:129-132. 

Smith TJ. 1996a. Connective tissue in hypothyroidism. In: Braverman LE, Utiger RD, eds. Werner and 

Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 796-798. 

Smith TJ. 1996b. Connective tissue in thyrotoxicosis. In: Braverman LE, Utiger RD, eds. Werner and 

Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 598-606. 
 

 

IODINE 467 

9. REFERENCES 

Smyth PPA. 1999. Variation in iodine handling during normal pregnancy. Thyroid 9(7):637-642. 

*Snyder PJ. 2000a. The pituitary in hypothyroidism. In: Braverman LE, Utiger RD, eds. Werner and 

Ingbar's the thyroid: A fundamental and clinical text. 8th ed. Philadelphia, PA: Lippincott-Raven, 836­

840. 

*Snyder PJ. 2000b. The pituitary in thyrotoxicosis. In: Braverman LE, Utiger RD, eds. Werner and 

Ingbar's the thyroid: A fundamental and clinical text. 8th ed. Philadelphia, PA: Lippincott-Raven, 634­

636. 

Snyder RD. 1988. Role of active oxygen species in metal-induced DNA strand breakage in human 

diploid fibroblasts. Mutat Res 193:237-246. 

Snyder S. 1978. Vocal cord paralysis after radioiodine therapy. J Nucl Med 19(8):975-976. 

Sobrinho LG, Limbert ES, Santos MA. 1977. Thyroxine toxicosis in patients with iodine induced 

thyrotoxicosis. J Clin Endocrinol Metab 45:25-29. 

Socolow EL, Hashizume A, Neriishi S, et al. 1963. Thyroid carcinoma in man after exposure to ionizing 

radiation. N Engl J Med 268(8):406-410,444. 

*Sodd VJ, Velten RJ, Saenger EL. 1975. Concentrations of the medically useful radionuclides, 

technetium-99m and iodine-131 at a large metropolitan waste water treatment plant. Health Phys 28:355­

359. 

*Solans R, Bosch J-A, Galofre P, et al. 2001. Salivary and lacrimal gland dysfunction (Sicca Syndrome) 

after radioiodine therapy. J Nucl Med 42(5):738-743. 

*Soldat JK. 1976. Radiation doses from iodine-129 in the environment. Health Phys 30:61-70. 

Soliman M, Kaplan E, Abdel-Latif A, et al. 1995. Does thyroidectomy, radioactive iodine therapy, or 

antithyroid drug treatment alter reactivity of patients' T cells to epitopes of thyrotropin receptor in 

autoimmune thyroid diseases? J Clin Endocrinol Metab 80:2312-2321. 

Sololowska R, Fuks T, Olejnik E. 1976. [Determination of the level of iodine content in milk caused by 

the penetration of same from iodophoric preparations used during milking.] Rocz Panstw Zakl Hig 

27(1):33-40. (Czech.). 

Solomon BL, Evaul JE, Burman KD, et al. 1987. Remission rats with antithyroid drug therapy: 

Continuing influence of iodine intake? Ann Intern Med 107:510-512. 

Solov'ev AS, Gurova NV, Shchebnikova NE. 1996. [The effect of incorporation of various doses of 131I 

on the immunological reactions.] Byull Eksp Biol Med 121(6):664-666. (Russian) 

Sonmez S, Ikbal M, Yildirim M, et al. 1997. Sister chromatid exchange analysis in patients exposed to 

low dose of iodine-131 for thyroid scintigraphy. Mutat Res 393:259-262. 

Sorcini MC, Diodata A, Fazzini C, et al. 1988. Influence of environmental iodine deficiency on neonatal 

thyroid screening results. J Endocrinol Invest 11:309-312. 
 

 

 

IODINE 468 

9. REFERENCES 

*Soria C, Allegue F, Espana A, et al. 1990. Vegetating iododerma with underlying systemic diseases: 

Report of three cases. J Am Acad Dermatol 22:418-422. 

Spate VL, Morris JS, Nichols TA, et al. 1998. Longitudinal study of iodine in toenails following IV 

administration of an iodine-containing contrast agent. J Radioanal Nucl Chem 236(1-2):71-76. 

*Spaulding SW, Burrow WR Himmelhoch HM et al. 1972. The inhibitory effect of lithium on thyroid 

hormone release in both euthyroid and thyrotoxic patients. J Clin Endocrinol Metab 35:905-911. 

Speck WT, Carr HS, Rosenkranz HS. 1976. DNA damage produced by povidone-iodine in cultured 

human diploid cells. J Toxicol Environ Health 1:977-980. 

Spector R, Lorenzo AV. 1974. The effects of salicylate and probenecid on the cerebrospinal fluid 

transport of penicillin, aminosalicylic acid and iodide. J Pharmacol Exp Ther 188(1):55-65. 

Speert H, Quimby EH, Werner SC. 1951. Radioiodine uptake by the fetal mouse thyroid and resultant 

effects in later life. Surg Gynecol Obstet 91:230-242. 

Speight JW, Baba WI, Wilson GM. 1968. The effect of propylthiouracil and 131I on rat thyroid 

chromosomes. J Endocrinol 42:267-275. 

Spencer CA. 1996. Thyroglobulin. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's the 

thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 406-415. 

Spencer RP, Chapman CN, Rao H. 1983. Thyroid carcinoma after radioiodide therapy for 

hyperthyroidism: Analysis based on age, latency, and administered dose of I-131. Clin Nucl Med 

8(5):216-219. 

*Spencer RP, Spitznagle LA, Karimeddini MK, et al. 1986. Breast milk content of 131I in a hypothyroid 

patient. Nucl Med Biol 13(5):585. 

Spezzano P, Giacomelli R. 1990. Radionuclide concentrations in air and their deposition at Saluggia 

(northwest Italy) following the Chernobyl nuclear accident. J Environ Radioact 12:79-91. 

Spiegel W, Reiners C, Borner W. 1985. Sialadenitis following iodine-131 therapy for thyroid carcinoma. 

J Nucl Med 26(7):816-817. 

*Spitzweg C, Dutton CM, Castro MR, et al. 2001. Expression of the sodium iodide symporter in human 

kidney. Kidney Int 59(3):1013-1023. 

*Spitzweg C, Joba W, Eisenmenger W. 1998. Analysis of human sodium iodide symporter gene 

expression in extrathyroid tissues and cloning of its complementary deoxyribonucleic acids from salivary 

gland, mammary gland, and gastric mucosa. Journal of Endocrinology & Metabolism 83(5):1746-1751. 

*Spitzweg C, Joba W, Schriever K, et al. 1999. Analysis of human sodium iodide symporter 

immunoreactivity in human exocrine glands. Journal of Endocrinology & Metabolism 84(11):4178-4184. 

Spryshkova NA, Egorova LT, Palinkashi DG. 1976. [Study of different states of iodine metabolism in 

rats by means of whole-body radiometry.] Probl Endokrinol (Mosk) 22(2):70-75. (Russian) 
 

 

 

IODINE 469 

9. REFERENCES 

Sridama V, McCormick M, Kaplan EL, et al. 1984. Long-term follow-up study of compensated lowdose 131I therapy for Graves' disease. N Engl J Med 311(7):426-432. 

Stabin MG, Watson EE, Marcus CS, et al. 1991. Radiation dosimetry for the adult female and fetus from
 

iodine-131 administration in hyperthyroidism. J Nucl Med 32(5):808-813. 

Stadel BV. 1976. Dietary iodine and risk of breast, endometrial, and ovarian cancer. Lancet 

1(7965):890-891. 

Staffurth JS. 1987. Hypothyroidism following radioiodine treatment of thyrotoxicosis. J R Coll Phys
 

London 21(1):55-57. 

Staffurth JS, Holl-Allen RTJ. 1988. Follicular carcinoma of the thyroid following radioactive iodine 

treatment for Graves' disease. Postgrad Med J 64:878-880. 

Stanbury JB. 1990. The physiological basis for blockade of radioiodine retention by iodine. In: Rubery
 

E, Smales E, eds. Iodine prophylaxis following nuclear accidents. Oxford, UK: Pergamon Press, 57-64. 

Stanbury JB. 1992. Iodine and human development. Med Anthropol 13:413-423. 

*Stanbury JB, Wyngaarden JB. 1952. Effect of perchlorate on the human thyroid gland. Metabolism
 

1:533-539. 

*Stanbury JB, Ermans AE, Bourdoux P, et al. 1998. Iodine-induced hyperthyroidism: Occurrence and 

epidemiology. Thyroid 8(1):83-100. 

Stara JF, Hoar RM, Ball HH. 1966. Localization of radioiodine during early organogenesis by means of 

autoradiography [Abstract]. Health Phys 12:1206. 

Starr P. 1974. Thyroid cancer after iodine-131 therapy [Letter]. JAMA 227(8):940. 

*Stassi G, DiLiberto, Todaro, et al. 2000. Control of target cell survival in thyroid autoimmunity by T 

helper cytokines via regulation of apoptotic proteins. Nat Immunol 6:483-488. 

*Stather JB, Greenhalgh JR. 1983. The metabolism of iodine in children and adults. National Radiation 

Protection Board, Chilton, Didcot, Oxfordshire, England. Report No. NRPB-R140. 

Steen M. 1993. Review of the use of povidone-iodine (PVP-I) in the treatment of burns. Postgrad Med J 

69(Suppl 3):S84-S92. 

Steidle B. 1989. Iodine-induced hyperthyroidism after contrast media: Animal experimental and clinical 

studies. Fortschr Geb Rontgenstrahlen Nuklearmed Erganzungsbd 128:6-14. 

Steidle B, Grehn S, Seif FJ. 1980. [Hyperthyroidism induced by iodine-containing contrast medium.]
 

Minerva Med 71(22):1560-1565. (Italian) 

Steinnes E. 1995. A critical evaluation of the use of naturally growing moss to monitor the deposition of 

atmospheric metals. Sci Total Environ 160/161:243-249. 

Steinnes E, Rambek JP, Hanssen JE. 1992. Large scale multi-element survey of atmospheric deposition 

using naturally growing moss as biomonitor. Chemosphere 25(5):735-752. 
 

 

 

IODINE 470 

9. REFERENCES 

Stenback F, Rowland J. 1978. Carcinogenic activation of benzo(a)pyrene by iodine and ferric chloride in 

the respiratory tract of Syrian golden hamsters. Experientia 34(8):1065-1066. 

Stepanov SA, Tupikinia EB. 1997. [Histofunctional state of the thyroid gland in pregnancy and in 

progeny under experimental regime of iodine intake.] Arkh Patol 59(5):39-44. (Russian) 

*Stephenson M, Motycka M. 1994. Review and assessment of methods for the measurement and 

speciation of iodine in fresh water. Atomic Energy of Canada Ltd., Whiteshell Laboratories, Pinawa, 

Manitoba (NTIS PB95-160487). 

*Sternthal E, Lipworth L, Stanley B, et al. 1980. Suppression of thyroid radioiodine uptake by various 

doses of stable iodide. N Engl J Med 303(19):1083-1088. 

*Stetar EA, Boston HL, Larsen IL, et al. 1993. The removal of radioactive cobalt, cesium, and iodine in 

a conventional municipal wastewater treatment plant. Water Environ Res 65(6):630-639. 

Stevens RH, Cheng HF. 1987. Lymphocyte proliferative responses to mitogens in rats having an 

ancestry of a perinatal iodine-131 insult. Environ Res 44:94-102. 

Stevens RH, Cole DA, Liu PT, et al. 1983. Postpartum cell-mediated immunity induced in the rat 

following perinatal exposure to iodine-131. Anticancer Res 3:347-352. 

Stevens RH, Lindholm PA, Cole DA, et al. 1986. Genealogical memory to perinatal iodine-131 

exposure in rats: I. Alteration in natural immunity. Anticancer Res 6:925-930. 

*Stewart JC. 1975. Epidemiology and pathogenesis of iodine-induced thyrotoxicosis in Northern 

Tasmania. N Z Med J 81:25-26. 

*Stewart JC, Vidor GI. 1976. Thyrotoxicosis induced by iodine contamination of food-a common 

unrecognised condition? Br Med J 1:372-375. 

Stewart RB, May FE, Cullen SI. 1979. Dermatologic adverse drug reactions in hospitalized patients. 

Am J Hosp Pharm 36:609-612. 

*St. Germain DL. 1997. Molecular basis of thyroid disease. In: Falk SA, ed. Thyroid disease: 

Endocrinology, surgery, nuclear medicine, and radiotherapy. Philadelphia, PA: Lippincott-Raven 

Publishers, 183-208. 

*Stieglitz KJL. 1995. Identification and quantification of volatile organic components in emissions of 

waste incinerator plants. Chemosphere 30:1249-1260. 

*Stockigt JR. 2000. Serum thyrotropin and thyroid hormone measurements and assessment of thyroid 

hormone transport. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental 

and clinical text. 8th ed. Philadelphia, PA: Lippincott-Raven, 376-392. 

Stockton LK, Thomas WC. 1978. Absence of neonatal goiter during maternal use of iodinated water. 

Am J Clin Nutr 31:717. 

Stoffer SS, Hamburger JI. 1976. Inadvertent 131I therapy for hyperthyroidism in the first trimester of 

pregnancy. J Nucl Med 17(2):146-149. 
IODINE 471 

9. REFERENCES 

Stoffer SS, Hamburger JI. 1978. Avoiding inadvertent fetal radiation resulting from 131I therapy for 

hyperthyroidism. In: Spencer RP, ed. Therapy in nuclear medicine. New York, NY: Grune & Stratton, 

129-138. 

Stolberg HO, McClennan BL. 1991. Ionic versus nonionic contrast use. Curr Probl Diagn Radiol 

20(2):47-88. 

Stolc V. 1972. Regulation of iodine metabolism in human leukocytes by adenosine 3',5'-monophosphate. 

Biochim Biophys Acta 264:285-288. 

Stolc V. 1975. Effect of pituitary factor on iodine uptake and cyclic adenosine 3',5'-monophosphate 

formation in human polymorphonuclear leukocytes. Biochem Med 12:226-233. 

Stoll R, Maraud R. 1963. [Induction of thyroid tumors in rats treated with propylthiouracil and
 

radioactive iodine.] Bull Assoc Fr Etude Cancer 50(3):389-398. (French) 

Stoll R, Maraud R, Laplanche P, et al. 1966. [On gamma adenomas of the thyroid in rats subjected to 

cancerogenic and non-cancerogenic treatments.] C R Seances Soc Biol Fil 160(12):2288-2291. (French) 

Stone OJ. 1971. What are the non-endocrine biologic effects of iodides? Med Times 99(12):143­

149,155,200.
 

*Stone OJ. 1985. Proliferative iododerma: A possible mechanism. Int J Dermatol 24(9):565-566. 

Stowe CM. 1981. Iodine, iodides, and iodism. J Am Vet Med Assoc 179(4):334-336. 

Stowe HD, Rangel F, Anstead C, et al. 1980. Influence of supplemental dietary vitamin A on the 

reproductive performance of iodine-toxic rats. J Nutr 110:1947-1957. 

Strain GM, Flory W. 1981. Toxicology of ethylenediamine dihydriodide [Letter]. J Am Vet Med Assoc 

179:751,72. 

*Straub CP, Murthy GK, Campbell JE. 1966. Iodine-131 in foods. Residue Rev 13:33-68. 

Strum JM. 1979. Effect of iodide-deficiency on rat mammary gland. Virchows Arch B 30:209-220. 

Stubbe P, Schulte F-J, Heidemann P. 1986. Iodine deficiency and brain development. Bibl Nutr Dieta 

38:206-208. 

Stubner D, Gartner R, Greil W, et al. 1987. Hypertrophy and hyperplasia during goitre growth and 

involution in rats - separate bioeffects of TSH and iodine. Acta Endocrinol 116:537-548. 

Studer H, Kohler H, Burgi H, et al. 1970. Goiters with high radioiodine uptake and other characteristics 

of iodine deficiency in rats chronically treated with aminoglutethimide. Endocrinology 87:905-914. 

Studer H, Kohler H, Burgi H, et al. 1972. Possible importance of thyroidal iodine compartments in the 

adaptation of thyroid hormone secretion to antithyroid drugs. Endocrinology 91:1154-1159. 

Stuges WT, Shaw GE. 1993. Halogens in aerosols in central Alaska. Atmos Environ 27A(17/18):2969­

2977. 
IODINE 472 

9. REFERENCES 

Sturgis CD. 1999. Radioactive iodine-associated cytomorphologic alterations in thyroid follicular 

epithelium: Is recognition possible in fine-needle aspiration specimens? Diagn Cytopathol 21(3):207­

210. 

Suarez RC, Lopez Bejerano GM, Arado JO, et al. 1998. [System for whole-body measurement and 

estimation of doses by different irradiation routes in a group of infants from areas affected by the 

Chernobyl accident.] Rev Cubana Fis 15(2):130-133. (Spanish) 

Subramanyam S, Murthy DK, Reddi OS. 1975. Cytological investigations on the effects of I131 in male 

mice. Indian J Med Res 63(12):1680-1687. 

Sugawara M, Yamaguchi DT, Lee HY, et al. 1990. Hydrogen peroxide inhibits iodide influx and 

enhances iodide efflux in cultured FRTL-5 rat thyroid cells. Acta Endocrinol 122:610-616. 

Sunder S, Vikis AC. 1987. Raman spectra of iodine oxyacids produced by the gas-phase reaction of 

iodine with ozone in the presence of water vapour. Can J Spectrosc 32(2):45-48. 

Sundick RS. 1990. Iodine in autoimmune thyroiditis. Immunol Ser 52:213-228. 

*Sundick RS, Herdegen DM, Brown TR, et al. 1987. The incorporation of dietary iodine and 

thyroglobulin increases its immunogenicity. Endocrinology 120:2078-2084. 

Sunitha Y, Udaykumar P, Raghunath M. 1997. Changes in blood-brain barrier nutrient transport in the 

offspring of iodine-deficient rats and their preventability. Neurochem Res 22(7):785-790. 

Surks MI. 1967. Determination of iodide clearance and exit rate constants in incubated thyroid lobes. 

Endocrinology 80:1020-1027. 

Svadlenkova M, Konecny J, Obdrzalek M, et al. 1990. Distribution and transport kinetics of 

radionuclides 99Mo and 131I in a simulated aquatic ecosystem. Bull Environ Contam Toxicol 44:535-541. 

Swedlund HA. 1971. Iodide myxedema with facial swelling simulating angioneurotic edema. Allergy 

47(6):341-345. 

*Szabolcs I, Podoba J, Feldkamp J, et al. 1997. Comparative screening for thyroid disorders in old age 

in areas of iodine deficiency, long-term iodine prophylaxis and abundant iodine intake. Clin Endocrinol 

47:87-92. 

Szabolcs I, Schultheiss H, Astier H, et al. 1991. Effects of triiodothyronine, triiodothyroacetic acid, 

iopanoic acid and iodide on the thyrotropin-releasing hormone-induced thyrotropin release from 

superfused rat pituitary fragments. Acta Endocrinol 125:427-434. 

Sztanyik LB, Turai I. 1988. Modification of radioiodine incorporation into the fetuses and newborn rats 

by thyroid blocking agents. Acta Physiol Hung 72(3-4):343-354. 

Tabintharan S, Sundram FX, Chew LS. 1997. Radioiodine (I-131) therapy and the incidence of 

hypothyroidism. Ann Acad Med Singapore 26:128-131. 

Tadrose TG, Maisey MN, Fui SCNT, et al. 1981. The iodine concentration in benign and malignant 

thyroid nodules measured by x-ray fluorescence. Br J Radiol 54:626-629. 
 

 

IODINE 473 

9. REFERENCES 

Taher MA, Loken MK, Bantle JP. 1991. Radioiodine therapy in thyrotoxicosis. J Indian Med Assoc 

89(4):86-88. 

Tai M, Zhi-heng Y, Ti-zhang L, et al. 1982. High-iodide endemic goiter. Chin Med J 95(9):692-696. 

*Tajiri J, Higashi K, Morita M, et al. 1986. Studies of hypothyroidism in patients with high iodine 

intake. J Clin Endocrinol Metab 63:412-417. 

*Takahashi T, Fujimori K, Simon SL, et al. 1999. Thyroid nodules, thyroid function and dietary iodine 

in the Marshall Islands. Int J Epidemiol 28:742-749. 

*Takahahi T, Schoemaker MJ, Trott KR, et al. 2003. The relationship of thyroid cancer with radiation 

exposure from nuclear weapon testing in the Marshall islands. J Epidemiol 13(2):99-107. 

*Takahashi T, Trott KR, Fujimori K, et al. 1997. An investigation into the prevalence of thyroid disease 

on Kwajalein Atoll, Marshall Islands. Health Phys 73(1):199-213. 

*Takasu N, Handa Y, Shimizu Y, et al. 1984. Electrophysiological and morphological cell polarity and 

iodine metabolism in cultured porcine and human (normal and Graves') thyroid cells. J Endocrinol 

101:189-196. 

Takasu N, Ohno S, Takasu M, et al. 1988. Polarized thyroid cells in monolayers cultured on collagen 

gel: Their cytoskeleton organization, iodine uptake, and resting membrane potentials. Endocrinology 

122:1021-1026. 

Takasu N, Sato A, Yamada T, et al. 1982. Refractoriness of TSH- and PGE2-stimulated iodine 

metabolism in cultured porcine thyroid cells, evidence for refractoriness at the level of cAMP action. 

Acta Endocrinol 99:530-539. 

Takegawa K, Mitsumori K, Onodera H, et al. 1998. Induction of squamous cell carcinomas in the 

salivary glands of rats by potassium iodide. Jpn J Cancer Res 89:105-109. 

Takegawa K, Mitsumori K, Onodera H, et al. 2000. Studies on the carcinogenicity of potassium iodide 

in F344 rats. Food Chem Toxicol 38(9):773-781. 

Takeuchi K, Suzuki H, Sawada M, et al. 1970. Effect of excessive iodide administration on the 

proteolytic activity of the thyroid gland. Endocrinology 86:1239-1244. 

Takeuchi S, Hosokawa S, Kachi T, et al. 1966. [A case of thyroid crisis followed to 131I therapy-with 

special reference to the hepatic lesions.] Naika 18(1):163-166. (Japanese) 

Takiyama Y, Tanaka H, Takiyama Y, et al. 1994. The effects of hydrocortisone and RU486 

(mifepristone) on iodide uptake in porcine thyroid cells in primary culture. Endocrinology 135(5):1972­

1979. 

Tallstedt L, Lundell G. 1997. Radioiodine treatment, ablation, and ophthalmopathy: A balanced 

perspective. Thyroid 7(2):241-245. 

Tallstedt L, Lundell G, Torring O, et al. 1992. Occurrence of ophthalmopathy after treatment for Graves' 

hyperthyroidism. N Engl J Med 326:1733-1738. 
 

 

IODINE 474 

9. REFERENCES 

Tam M. 1988. Australian Dermato-Pathology Society case presentation: Acute painful nodules on the 

head and neck. Australas J Dermatol 29:179-180. 

Tamdor J. 1971. Consideration of stable iodine in the environment in the evaluation of maximum 

permissible concentrations for iodine-129. Radiol Health Data Rep 12(12):611-614. 

Tamura T, Mitsumori K, Onodera H, et al. 1999. Inhibition of thyroid iodine uptake and organification 

in rats treated with kojic acid. Toxicol Sci 47:170-175. 

Tan TT, Morat P, Ng ML, et al. 1989. Effects of Lugol's solution on the thyroid function in normals and 

patients with untreated thyrotoxicosis. Clin Endocrinol 30:645-649. 

Tanaami S, Katamine S, Hoshino N, et al. 1985. Histopathological study on rats fed iodine-enriched 

eggs long-term (7 and 9 months). J Nutr Sci Vitaminol 31:29-42. 

Tanigawa K, Yamishita S, Nagataki S. 1995. Pancytopenia after repeated radioiodine treatment on 

metastatic thyroid cancer to bone. Chin Med J 108:796-797. 

Taniguchi S-I, Shong M, Giuliani C, et al. 1998. Iodide suppression of major histocompatibility class I 

gene expression in thyroid cells involves enhancer A and the transcription factor NF-kb. Mol Endocrinol 

12:19-33. 

Tarasenko LV, Varga SV, Demchenko VN, et al. 1994. [Effect of 131I incorporation on male rat 

reproductive system and dose-dependent effects.] Probl Endokrinol (Mosk) 40(3):45-47. (Russian) 

Targovnik HM, Gluzman BE, Coleoni AH, et al. 1980. Effects of phenylbutazone on thyroid iodine 

metabolism in vitro. Acta Endocrinol 94:64-70. 

Tarutani O, Kondo T, Horiguchi-Sho K. 1975. The effect of iodide administration on hog thyroid gland 

and the composition of thyroglobulin and 27-S iodoprotein. Endocrinol Jpn 22(5):389-397. 

Taurog A. 1970. Thyroid peroxidase-catalyzed iodination of thyroglobulin; inhibition by excess iodide. 

Arch Biochem Biophys 139:212-220. 

*Taurog A. 1996. Hormone synthesis. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's the 

thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 47-84. 

*Taurog A. 2000. Hormone synthesis: Thyroid iodine metabolism. In: Braverman LE, Utiger RD, eds. 

Werner and Ingbar's the thyroid: A fundamental and clinical text. 8th ed. Philadelphia, PA: LippincottWilliams and Wilkins, 61-84. 

*Taurog A, Dorris M, Doerge DR. 1994. Evidence for a radical mechanism in peroxidase-catalyzed 

coupling: I. Steady state experiments with various peroxidases. Arch Biochem Biophys 315:82. 

*Taylor JP, Metcalfe RA, Watson PF, et al. 2002. Mutations of the PDS gene, encoding pendrin, are 

associated with protein mislocalization and loss of iodide efflux: Implications for thyroid dysfunction in 

Pendred Syndrome. J Clin Endocrinol Metab 87(4):1778-1784. 

Taylor DM. 1981. The radiotoxicology of iodine. J Radioanal Chem 65(1-2):195-208. 
IODINE 475 

9. REFERENCES 

*Tazebay UH, Wapnir IL, Levy O, et al. 2000. The mammary gland iodide transporter is expressed 

during lactation and in breast cancer. Nat Med 6(8):859-860. 

Terahara A, Nakano T, Ishikawa A, et al. 1996. Dose-volume histogram analysis of high dose rate 

intracavitary brachytherapy for uterine cervix cancer. Int J Radiat Oncol Biol Phys 35(3):549-554. 

Teraoka K, Minakuchi K, Kuzime T, et al. 1991. Lithium and carbamazepine effects on iodide 

metabolising enzymes from the porcine thyroid. Lithium 2:37-42. 

Tezelman S, Grossman RF, Siperstein AE, et al. 1994. Radioiodine-associated thyroid cancers. World J 

Surg 18:522-528. 

Theodoropoulos LE, Braverman LE, Vagenakis AG. 1979. Iodide-induced hypothyroidism: A potential 

hazard during perinatal life. Science 205:502-503. 

*Thieblemont P, Marble G, Perrault G, et al. 1965. Evaluation de la retention respiratoire et de 

l'elimination du radioiode apres contamination aerienne du singe. Int J Radiat Biol 9(3):219-231. 

Thiessen KM, Thorne MC, Maul PR, et al. 1999. Modelling radionuclide distribution and transport in 

the environment. Environ Pollut 100:151-177. 

Thomas GA, Williams ED. 1999. Thyroid stimulating hormone (TSH)-associated follicular hypertrophy 

and hyperplasia as a mechanism of thyroid carcinogenesis in mice and rats. In: Capen CC, Dybing E, 

Rice JM, et al., eds. Species differences in thyroid, kidney and urinary bladder carcinogenesis. Lyon, 

France: International Agency for Research on Cancer, 45-59. 

Thomas PJ. 1997. Predicting Chernobyl childhood thyroid cancers from incoming data. Nucl Energy 

(Br Nucl Energy Soc) 36(3):209-221. 

*Thomas RL, Scott JK, Chiffelle TL. 1970. Metabolism and toxicity of inhaled and injected 131I in the 

rat. Am Ind Hyg Assoc J 31:213-220. 

Thomas WC, Malagodi MH, Oates TW, et al. 1979. Effects of an iodinated water supply. Trans Am 

Clin Climatol Assoc 90:153-162. 

*Thompson DE, Mabuchi K, Ron E, et al. 1994. Cancer incidence in atomic bomb survivors. Part II: 

Solid tumors, 1958-1987. Radiat Res 137:S17-S67. 

Thomson CD, Packer MA, Butler JA, et al. 2001. Urinary selenium and iodine during pregnancy and 

lactation. J Trace Elem Med Biol 14(4):210-217. 

Thomson CD, Woodruffe S, Colls AJ, et al. 2001. Original communication. Urinary iodine and thyroid 

status of New Zealand residents. Eur J Clin Nutr 55(5):387-392. 

Thomson JA, Riley ID. 1966. Neonatal thyrotoxicosis associated with maternal hypothyroidism. Lancet 

1(7438):635-636. 

Thomson WH, Harding LK. 1995. Radiation protection issues associated with nuclear medicine outpatients. Nucl Med Commun 16:879-892. 
 

 

IODINE 476 

9. REFERENCES 

Thorpe SM. 1976. Increased uptake of iodide by hormone-responsive compared to hormoneindependent mammary tumors in GR mice. Int J Cancer 18:345-350. 

Thorsteinsson B, Kirkegaard C. 1977. Iodine-induced hyperthyroidism and bronchial asthma. Lancet 

2(8032):294. 

*Thrall KD, Bull RJ. 1990. Differences in the distribution of iodine and iodide in the Sprague-Dawley 

rat. Fundam Appl Toxicol 15:75-81. 

Thrall KD, Sauer RL, Bull RJ. 1992. Evidence of thyroxine formation following iodine administration in 

Sprague-Dawley rats. J Toxicol Environ Health 37:535-548. 

Thurston V, Williams ED. 1982. The effect of radiation on thyroid C cells. Acta Endocrinol 99:72-78. 

Tighe WJ. 1952. Temporary hypoparathyroidism following radioactive iodine treatment for 

thyrotoxicosis. J Clin Endocrinol Metab 12:1220-1222. 

Tiku ML, Farias AE, Johnson SC. 1976. Iodide myxoedema simulating filariasis. Indian J Med Sci 

30(9):291-292. 

Tisell L-E, Carlsson S, Fjalling M, et al. 1985. Hyperparathyroidism subsequent to neck irradiation. 

Cancer 56:1529-1533. 

*Todd CH, Allain T, Gomo ZAR, et al. 1995. Increase in thyrotoxicosis associated with iodine 

supplements in Zimbabwe. Lancet 346:1563-1564. 

Toft AD, Irvine WJ, Hunter WM, et al. 1974a. Anomalous plasma TSH levels in patients developing 

hypothyroidism in the early months after 131I therapy for thyrotoxicosis. J Clin Endocrinol Metab 39:607­

609. 

Toft AD, Seth J, Hunter WM, et al. 1974b. Plasma-thyrotropin and serum-thyroxine in patients 

becoming hypothyroid in the early months after iodine-131. Lancet 1(7860):704-705. 

Tokuda Y, Kasagi K, Iida Y, et al. 1988. Inhibition of thyrotropin-stimulated iodide uptake in FRTL-5 

thyroid cells by crude immunoglobulin fractions from patients with goitrous and atrophic autoimmune 

thyroiditis. J Clin Endocrinol Metab 67(2):251-258. 

Tomlinson C, Nowles KW, McDougall IR. 1991. Papillary cancer in a patient treated with radioiodine 

for Graves' hyperthyroidism: Case report and a review of the risk. Clin Nucl Med 16(10):729-731. 

Tomonaga M, Nonaka H, Matsuo T. 1996. Atomic bomb irradiation and human leukemias. In: 

Nagataki S, Yamashita S, eds. Nagasaki symposium radiation and human health: Proposal from 

Nagasaki. Amsterdam, The Netherlands: Elsevier, 197-215. 

Tonacchera M, Agretti P, Ceccarini G, et al. 2001. Autoantibodies from patients with autoimmune 

thyroid disease do not interfere with the activity of the human iodide symporter gene stably transfected in 

CHO cells. Eur J Endocrinol 144(6):611-618. 

*Tong Q, Ryu K-Y, Jhiang SM. 1997. Promoter characterization of the rat Na +/I-

 symporter gene. 

Biochem Biophys Res Commun 239:34-41. 
 

 

 

IODINE 477 

9. REFERENCES 

Tony JC, Verghese R, Mathew G. 1994. Radio iodine induced thyroid storm. J Assoc Physicians India 

42(11):924-925. 

*Topliss DJ, Kolliniatis E, Barlow JW, et al. 1989. Uptake of 3,5,3'-triiodothyronine by cultured rat 

hepatoma cells is inhibitable by nonbile acid cholephils, diphenylhydantoin, and nonsteriodal 

antiinflammatory drugs. Endocrinology 124:980-986. 

Toran L. 1994. Radionuclide contamination in groundwater: Is there a problem? In: Environmental 

science pollution control series. New York, NY: M. Dekker, 437-453. 

*Tosti A, Vincenzi C, Bardazzi F, et al. 1990. Allergic contact dermatitis due to povidone-iodine. 

Contact Dermatitis 23:197-198. 

Townsend JD. 1961. Hypoparathyroidism following radioactive iodine therapy for intractable angina 

pectoris. Ann Intern Med 55:662-663. 

*Tracy BL, Walker WB, McGregor RG. 1989. Transfer of milk to 131I and 137Cs released during the 

Chernobyl reactor accident. Health Phys 56(2):239-243. 

Tran N, Laplante M, LeBel E, et al. 1970. The effect of sodium iodide on the oxidation in vivo of [1-14C] 

L-tyrosine to 14CO2 in normal rats: A vibrating-reed electrometer-ionization chamber method. Arch Int 

Physiol Biochim 78:909-917. 

Trapasso F, Martelli ML, Battaglia C, et al. 1996. The v-erbA oncogene selectively inhibits iodide 

uptake in rat thyroid cells. Oncogene 12(9):1879-1888. 

Traynor K. 2002. FDA offers guidance on prophylaxis for exposure to radioiodines. Am J Health Syst 

Pharm 59(4):324-326. 

*Tresch DD, Sweet DL, Keelan MHJ, et al. 1974. Acute iodide intoxication with cardiac irritability. 

Arch Intern Med 134:760-762. 

Triggs SM, Williams ED. 1977. Irradiation of the thyroid as a cause of parathyroid adenoma. Lancet 

1:593-594. 

*Tronko ND, Bogdanova TI, Epstein EV, et al. 1996. Thyroid cancer in children and adolescents in 

Ukraine (analysis of the situation in 1994). In: Nagataki S, Yamashita S, eds. Nagasaki symposium 

radiation and human health: Proposal from Nagasaki. Amsterdam, The Netherlands: Elsevier, 3-13. 

*Trowbridge FL, Matovinovic J, McLaren GD, et a l. 1975. Iodine and goiter in children. Pediatrics 

56:82-90. 

*Truesdale VW, Smith PJ. 1975. The automatic determination of iodide or iodate in solution by catalytic 

spectrophotometry, with particular reference to river water. Analyst 100:111-123. 

Tseng F-Y, Rani CSS, Field JB. 1989. Effect of iodide on glucose oxidation and 32P incorporation into 

phospholipids stimulated by different agents in dog thyroid slices. Endocrinology 124(3):1450-1455. 

Tsuchiya T, Ito K, Murata M. 1996. [An evaluation of the incidence of hyperparathyroidism after 131I 

treatment for Basedow disease (Part I).] Kaku Igaku 33(7):729-735. (Japanese) 
 

 

IODINE 478 

9. REFERENCES 

Tsuchiya Y, Saji M, Isozaki O, et al. 1990. Effect of litium on deoxyribonucleic acid synthesis and 

iodide uptake in porcine thyroid cells in culture. Endocrinology 126(1):460-465. 

*Tsukada H, Ishida J, Narita O. 1991. Particle-size distributions of atmospheric 129I and 127I aerosols. 

Atmos Environ 25A(5/6):905-908. 

*Tsunoda A, Shibusawa M, Kamiyama G, et al. 2000. Iodine absorption after intraperative bowel 

irrigation with povidone-iodine. Dis Colon Rectum 43(8):1127-1132. 

*Tsunogai S. 1971. Determination of iodine in sea water by an improved Sugawara method. Anal Chim 

Acta 55:444-447. 

Tsushima T, Arai M, Isozaki O, et al. 1994. Interaction of endothelin-1 with porcine thyroid cells in 

culture: A possible autocrine factor regulating iodine metabolism. J Endocrinol 142:463-470. 

Tsushima T, Arai M, Saji M, et al. 1988. Effects of transforming growth factor-bets on deoxyribonucleic 

acid synthesis and iodine metabolism in porcine thyroid cells in culture. Endocrinology 123:1187-1194. 

*Tubiana M. 1982. Metabolism and radiotoxicity of radionuclides: Iodine. In: Radionuclide: 

Metabolism and toxicity. Proceedings of the symposium. Paris, France: Masson, 49-81. 

Tucker MA, Jones PHM, Boice JD, et al. 1991. Therapeutic radiation at a young age is linked to 

secondary thyroid cancer. Cancer Res 51:2885-2888. 

Tunbridge WMG, Evered DC, Hall R, et al. 1977. The spectrum of thyroid disease in a community: The 

Whickham survey. Clin Endocrinol 7:481-493. 

Tunbridge WMG, Harsoulis P, Goolden AWG. 1974. Thyroid function in patients treated with 

radioactive iodine for thyrotoxicosis. Br Med J 3:89-92. 

Turner FB, Martin WE. 1964. Food-chain relationships of iodine-131 in Nevada following the Sedan 

test of July 1962. Laboratory of Nuclear Medicine and Radiation Biology, University of California, Los 

Angeles, California. PNE-236f, Project 62.83. 

Tvedten HW, Till GO. 1985. Effect of povidone, povidone-iodine, and iodide on locomotion (in vitro) 

of neutrophils from people, rats, dogs, and rabbits. Am J Vet Res 46(8):1797-1800. 

Tyler DD. 1968. Influence of mitochondrial inhibitors on the respiration and energy-dependent uptake of 

iodide by thyroid slices. Biochem J 107:121-123. 

Tzen K-Y, Oster ZH, Wagner HJ, et al. 1980. Role of iron-binding proteins and enhanced capillary 

permeability on the accumulation of gallium-67. J Nucl Med 21(1):31-35. 

Uchida S, Muramatsu Y, Sumiya M, et al. 1991. Biological half-life of gaseous elemental iodine 

deposited onto rice grains. Health Phys 60(5):675-679. 

Uchimura H, Amir SM, Ingbar SH. 1979. Failure of organic iodine enrichment to influence the binding 

of bovine thyrotropin to rat thyroid tissue. Endocrinology 104:1207-1210. 

Ulmer DD. 1977. Trace elements. N Engl J Med 6:318-321. 
IODINE 479 

9. REFERENCES 

Umans RS, Leski SA, Ts'o POP. 1969. Chemical linkage of carcinogenic 3,4-benzpyrene to DNA in 

aqueous solution induced by peroxide and iodine. Nature 221:763-764. 

Umeki K, Kotani T, Kawano J, et al. 2002. Two novel missense mutations in the thyroid peroxidase 

gene. R665W and G771R, result in a localization defect and cause congenital hypothyroidism. Eur J 

Endocrinol 146(4):491-498. 

Underwood EJ. 1971. Iodine. In: Trace elements in human and animal nutrition. New York, NY: 

Academic Press, 281-322. 

Unger J. 1989. Thionamides and iodide in iodine-induced thryotoxicosis [Letter]. Acta Clin Belg 

44(1):61. 

Unger J, Boeynaems JM, Van Herle A, et al. 1979. In vitro nonbutanol-extractable iodine release in dog 

thyroid. Endocrinology 105(1):225-231. 

Unger J, Surmont DWA, Sarot J, et al. 1989. 24 H-kinetics of iodide uptake in amiodarone induced 

hypothyroidism. Thyroidology 2:101-102. 

*UNSCEAR. 1993. Sources, effect and risks of ionizing radiation. Report to the general assembly, New 

York: United Nations. 

*UNSCEAR. 2000. Sources, effect and risks of ionizing radiation. Report to the general assembly, New 

York: United Nations. ANNEX J. Exposures and Effects of the Chernobyl Accident, 451-566. 

Untoro J, Schultink W, Gross R, et al. 1998. Efficacy of different types of iodized oil [Letter]. Lancet 

351:752-753. 

Upton AC. 1981. Health impact of the Three Mile Island accident. Ann N Y Acad Sci 365:63-75. 

Ursu HI, Dumitriu L, Grigorie D, et al. 1993. Effects of radioioine therapy in hyperthyroidism (thyroid 

function, thyroid volume, Graves' ophtalmopathy, thyrotoxic heart disease). Rom J Endocrinol 31(3­

4):155-163. 

Usala SJ. 1997. Thyroid hormone resistance syndromes. In: Falk SA, eds. Thyroid disease: 

Endocrinology, surgery, nuclear medicine, and radiotherapy. Philadelphia, PA: Lippincott-Raven 

Publishers, 223-230. 

*USC. 2001. Listed precursor for controlled substance. U.S. Code. 21 USC 802. 

http://www4.law.cornell.edu/uscode/21/802.text.html. May 16, 2001. 

*U.S. DHHS. 1985. SEER cancer incidence and mortality in the United States, 1973-1981. Publ No. 

85-1837, Bethesda, MD. 

Usenko VS, Lepekhin EA, Kornilovska IN, et al. 1998. Immunohistochemical study of fibronectin and 

thyroglobulin in the thyroid gland of female rats after exposure to radioactive iodine. Anat Rec 252:600­

607. 

Usenko V, Lepekhin E, Lyzogubov V, et al. 1999. The influence of low doses 131I-induced maternal 

hypothyroidism on the development of rat embryos. Exp Toxicol Pathol 51:223-227. 
IODINE 480 

9. REFERENCES 

*USGS. 1984. Element concentrations in soils and other surficial materials of the conterminous United 

States. Washington, DC: United States Government Printing Office. U.S. Geological Survey Professioal 

Paper 1270. 

*USGS. 1998. Iodine. USGS Minerals Information. 

http://minerals.usgs.gov/minerals/pubs/commodity/iodine/index.html. 

*USGS. 1999. Iodine. United States Geological Survey. 

http://minerals.usgs.gov/minerals/pubs/commodity/iodine/770499.pdf. 

*USGS. 2001. Iodine. U.S. Geological Survey, Mineral Commodities Summaries. January 2001. 

*USGS. 2002. Iodine. United States Geological Survey. 

http://minerals.usgs.gov/minerals/pubs/commodity/iodine/770302.pdf. 

*USNRC. 1979. A dynamic model of the global iodine cycle for the estimation of dose to the world 

population from releases of iodine-129 to the environment. U.S. Nuclear Regulatory Commission, 

Division of Safeguards, Fuel Cycle, and Environmental Research. NUREG/CR-0717. 

*USNRC. 1981. On the long-term behavior of 129I in the terrestrial environment. U.S. Nuclear 

Regulatory Commission, Division of Safeguards, Fuel Cycle, and Environmental Research. IAEA-SDM257. 

*USNRC. 1984. Lower limit of detection: definition and elaboration of a proposed position for 

radiological effluent and environment measurements. Washington, D.C.: Nuclear Regulatory 

Commission. U.S. Report NUREG/ CR-4604. 

USNRC. 1987. Interpretative analysis of data for solute transport in the unsaturated zone. Washington, 

DC: U.S. Nuclear Regulatory Commission, Office of Nuclear Material Safety and Safeguards, Division 

of Waste Management. NUREG/CR-4737. 

*USNRC. 1997. Minimum detectable concentrations with typical radiation survey instruments for 

various contaminants and field conditions. Nuclear Regulatory Commission. Rockville MD: NRC; U.S. 

Report NUREG-1507. 

*USNRC. 2001a. Index of radioisotopes: Iodine. U.S. Nuclear Regulatory Commission. 

http://www.nrc.gov. 

*USNRC. 2001b. Byproduct material list. U.S. Nuclear Regulatory Commission. http://www.nrc.gov. 

*USNRC. 2001c. Packaging and transportation of radioactive material. Determination of A1 and A2. 

U.S. Nuclear Regulatory Commission. Code of Federal Regulations. 10 CFR 71, Appendix A. 

http://ecfrback.access.gpo.gov/otcgi/cfr/otfilter.cgi. May 16, 2001. 

*USNRC. 2001d. Waste classification. U.S. Nuclear Regulatory Commission. Code of Federal 

Regulations. 10 CFR 61.55. http://ecfrback.access.gpo.gov/otcgi/cfr. May 16, 2001. 

*USNRC. 2002. NRC Regulations. Appendix B. U.S. Nuclear Regulatory Commission. 10 CFR. 

http://www.nrc.gov/reading-rm/doc-collections/cfr/part020/part020-appb.html. 
IODINE 481 

9. REFERENCES 

*USNRC. 2003. NRC Regulations (10 CFR). Requirements binding on all persons and organizations 

who receive a license from NRC to use nuclear materials or operate nuclear facilities. Washington, D.C.: 

Nuclear Regulatory Commission. http://www.nrc.gov/reading-rm/doc-collections/cfr. 

Uy HL, Reasner CA, Samuels MH. 1995. Pattern of recovery of the hypothalmic-pituitary-thyroid axis 

following radioactive iodine therapy in patients with Graves' disease. Am J Med 99:173-179. 

*Uyttersprot N, Pelgrims N, Carrasco N, et al. 1997. Moderate doses of iodide in vivo inhibit cell 

proliferation and the expression of thyroperoxidase and Na +/I-

 symporter mRNAs in dog thyroid. Mol 

Cell Endocrinol 131:195-203. 

Vadstrup S. 1989. Renal iodide clearance in rabbits. Acta Endocrinol 21:246-250. 

*Vadstrup S. 1993. Comparative aspects of iodine conservation in mammals. Comp Biochem Physiol 

106A(1):15-17. 

Vagenakis A, Abreau C, Braverman L. 1971a. Effect of tracer doses of 131I on serum protein bound 

iodine and serum thyroxine concentration. J Nucl Med 12:637-638. 

Vagenakis AG, Braverman LE, Foster AE, et al. 1971b. Stimulatory effect of 5-fluorouracil in 

thyroid/serum iodide concentration ratios in the rat. Endocrinology 88:1250-1252. 

Vagenakis AG, Downs P, Braverman LE, et al. 1973. Control of thyroid hormone secretion in normal 

subjects receiving iodides. J Clin Invest 52:528-532. 

*Vagenakis AG, Wang C-A, Burger A, et al. 1972. Iodide-induced thyrotoxicosis in Boston. N Engl J 

Med 287(11):523-527. 

Valenta LJ. 1974. Effect of iodide and thyrotrophin on in vitro 14C-amino acid incorporation into rat 

thyroid proteins. Acta Endocrinol 76:273-285. 

van Best JA. 1981. Dose calculations for 123I, 124I, 125I and 131I in the thyroid gland of the mouse, rat and 

man and comparison with thyroid function for mice and rats. Phys Med Biol 26(6):1035-1053. 

Van Best JA. 1982. Comparison of thyroid function in mice after various injected activities of 123I, 125I 

and 131I. Int J Radiat Biol 42(5):545-557. 

*Vandecasteele CM, Van Hees M, Hardeman F, et al. 2000. The true absorption of 131I , and its transfer 

to milk in cows given different stable iodine diets. J Environ Radioact 47(3):301-317. 

Vandenbroucke MF, Herveg JP, Beckers C, et al. 1967. Iodide uptake studies on isolated thyroid cells. 

Arch Int Physiol Biochim 75(1):185-186. 

van den Hove MF, Beckers C, Devlieger H, et al. 1999. Hormone synthesis and storage in the thyroid of 

human preterm and term newborns: Effect of thyroxine treatment. Biochimie 81:563-570. 

van der Heyden JTM, Docter R, van Toor H, et al. 1986. Effects of caloric deprivation on thyroid 

hormone tissue uptake and generation of low-T3 syndrome. Am J Physiol 251(14):E156-E163. 

*Vanderpas JB, Contempre B, Duale NL et al. 1990. Iodine and selenium deficiency associated with 

cretinism in Northern Zaire. Am. J Clin. Nutr. 52:1087-1093. 
 

 

 

IODINE 482 

9. REFERENCES 

*Vanderpump MPJ, Tunbridge WMG. 2000. The epidemiology of thyroid diseases. In: Braverman LE, 

Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 8th ed. Philadelphia, 

PA: Lippincott-Raven, 474-482. 

Vanderpump MPJ, Ahlquist JAO, Franklyn JA, et al. 1996. Consensus statement for good practice and 

audit measures in the management of hypothyroidism and hyperthyroidism. Br Med J 313:539-544. 

Van Der Willigen AH, Habets JMW, Van Joost T, et al. 1988. Contact allergy to Japanese sargassum. 

Contact Dermatitis 18(4):250-252. 

*Van Dilla MA, Fulwyler MJ. 1963. Thyroid metabolism in children and adults using very small 

(nanocurie) doses of iodine125 and iodine131 . Health Phys 9:1325-1331. 

*Van Dilla MA, Fulwyler MJ. 1964. Radioiodine metabolisms in children and adults after the ingestion 

of very small doses. Science 144:178-179. 

Van Herle AJ, Van Herle KA. 1997. Thyroglobulin in benign and malignant thyroid disease. In: Falk 

SA, ed. Thyroid disease: Endocrinology, surgery, nuclear medicine, and radiotherapy. Philadelphia, PA: 

Lippincott-Raven Publishers, 587-599. 

Van Middlesworth I. 1971. Persistence of 125I in thyroid. N Engl J Med 286(3):161. 

*Van Middlesworth L. 1954. Radioactive iodide uptake of normal newborn infants. Am J Dis Child 

88:439-442. 

*Van Middlesworth L. 1993. 129I and 137Cs fission products in thyroids of animals, 1984-1991. Health 

Phys 64(1):52-58. 

Van Nostrand D, Neutze J, Atkins F. 1986. Side effects of "rational dose" iodine-131 therapy for 

metastatic well-differentiated thyroid carcinoma. J Nucl Med 27:1519-1527. 

Van Sande J, Dumont JE. 1973. Effects of thyrotropin, prostaglandin E1 and iodide on cyclic 3',5'-AMP 

concentration in dog thyroid slices. Biochim Biophys Acta 313:320-328. 

Van Sande J, Cochaux P, Mockel J, et al. 1983. Stimulation by forskolin of the thyroid adenylate 

cyclase, cyclic AMP accumulation and iodine metabolism. Mol Cell Endocrinol 29:109-119. 

Van Sande J, Deneubourg F, Beauwens R, et al. 1990. Inhibition of iodide transport in thyroid cells by 

dysidenin, a marine toxin, and some of its analogs. Mol Pharmacol 37:583-589. 

Van Sande J, Erneux C, Dumont JE. 1977. Negative control of TSH action by iodide and acetylcholine: 

Mechanism of action in intact thyroid cells. J Cyclic Nucleotide Res 3:335-345. 

Van Sande J, Grenier G, Willems C, et al. 1975. Inhibition by iodide of the activation of the thyroid 

cyclic 3',5'-AMP system. Endocrinology 96:781-786. 

Van Wyngaarden M, McDougall IR. 1996. What is the role of 1100 MBq (<30 mCi) radioiodine 131I in 

the treatment of patients with differentiated thyroid cancer. Nucl Med Commun 17:199-207. 
IODINE 483 

9. REFERENCES 

*Vargo GJ. 2000. The Chernobyl accident: A comprehensive risk assessment. Columbus, OH: Battelle 

Press. 

Varma SK, Murray R, Stanbury JB. 1978. Effect of maternal hypothyroidism and triiodothyronine on 

the fetus and newborn in rats. Endocrinology 102(1):24-30. 

Varma VM, Beierwaltes WH, Nofal MM, et al. 1970. Treatment of thyroid cancer: Death rates after 

surgery and after surgery followed by sodium iodide I 131. JAMA 214(8):1437-1442. 

Varrone S, Consiglio E, Covelli I. 1970. The nature of inhibition of mitochondrial malate dehydrogenase 

by thyroxine, iodine cyanide and molecular iodine. Eur J Biochem 13:305-312. 

Vasilenko IY. 1980. Iodine isotopes in radiation hygiene. J Hyg Epidemiol Microbiol Immunol 

24(2):142-149. 

*Vasilenko IY. 1986. A radiation-hygienic appraisal of biosphere contamination with 129I. J Hyg 

Epidemiol Microbiol Immunol 30:243-248. 

Vassilopoulou-Sellin R, Sellin JH. 1996a. The gastrointestinal tract and liver in hypothyroidism. In: 

Braverman LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 

Philadelphia, PA: Lippincott-Raven, 816-820. 

Vassilopoulou-Sellin R, Sellin JH. 1996b. The gastrointestinal tract and liver in thyrotoxicosis. In: 

Braverman LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 

Philadelphia, PA: Lippincott-Raven, 632-636. 

Vatulina GG. 1977. [Metabolic changes in rat muscle tissue under separate and combined exposure to 

Iodine 131 and Strontium 89.] Radiobiologiia 17(5):728-732. (Russian) 

Vejjajiva S, Poshyachinda M, Yenbutra D. 1979. 131I treated hypothyroidism and thyroid antibody 

levels. J Med Assoc Thai 62(2):51-53. 

Veldhuis JD. 1978. 131I-induced hypothyroidism before recurrence of hyperthyroidism. Lancet 

1(8071):993-994. 

Velkeniers B, Cytryn R, Vanhaelst I, et al. 1988. Treatment of hyperthyroidism with radioiodine: 

Adjunctive therapy with antithyroid drugs reconsidered. Lancet 1:1127-1129. 

Venderpas JB, Rivera-Vanderpas MT, Bourdoux P, et al. 1986. Reversibility of severe hypothyroidism 

with supplmentary iodine in patients with endemic cretinism. N Engl J Med 315(13):791-795. 

Venkataraman GM, Yatin M, Ain KB. 1998. Cloning of the human sodium-iodide symporter promoter 

and characterization in a differentiated human thyroid cell line, KAT-50. Thyroid 8(1):63-69. 

Venturi S, Donati FM, Venturi A, et al. 2000. Environmental iodine deficiency: A challenge to the 

evolution of terrestrial life? Thyroid 10(8):727-729. 

*Verger P, Aurengo A, Geoffroy B, et al. 2001. Iodine kinetics and effectiveness of stable iodine 

prophylaxis after intake of radioactive iodine: A review. Thyroid 11(4):353-360. 
 

 

 

IODINE 484 

9. REFERENCES 

*Verma S, Hutchins P, Guo J et al. 2000. Role of MHC class I expression and CD8+ T cells in the 

evolution of iodine-induced thyroiditis in NOHh2h4 and NOS mice. Eur J Immunol 30:1191-1202. 

*Verma KK, Jain A, Verma A. 1992. Determination of iodide by high-performance liquid 

chromatography after precolumn derivatization. Anal Chem 64:1484-1489. 

*Versloot PM, Schroder-van der Elst JP, van der Heide D, et al. 1997. Effects of marginal iodine 

deficiency during pregnancy: Iodide uptake by the maternal and fetal thyroid. Am J Physiol 273:E1121­

E1126. 

Versloot PM, Schroder-van der Elst JP, van der Heide D, et al. 1998. Effects of marginal iodine 

deficiency on thyroid hormone production, distribution and transport in nonpregnant and near-term 

pregnant rats. Eur J Endocrinol 138:713-718. 

Vestergaard H, Laurberg P. 1989. Radioiodine and aggravation of Graves' ophthalmopathy. Lancet 

2(8653):47. 

Vetter RJ. 1997. Regulations for radioiodine therapy in the United States: Current status and the process 

of change. Thyroid 7(2):209-211. 

*Vicens-Calvet E, Potau N, Carreras E, et al. 1998. Diagnosis and treatment in utero of goiter with 

hypothyroidism caused by iodide overload. J Pediatr 133:147-148. 

Vickery ALJ, Williams ED. 1971. Comparative biological effects of 125I and 131I on the rat thyroid. Acta 

Endocrinol 66:201-212. 

*Vieira I, Sonnier M, Cresteil T. 1996. Developmental expression of CYP2E1 in the human liver: 

Hypermethylation control of gene expression during the neonatal period. Eur J Biochem 238:476-483. 

Vieira JGH, Brandao CMA, Kasamatsu TS, et al. 1991. Parathyroid hormone secretory reserve in 

patients submitted to 131-iodine therapy for hyperthyroidism. Braz J Med Biol Res 24:1103-1105. 

Vilijn F, Carrasco N. 1989. Expression of the thyroid sodium/iodide symporter in Xenopus laevis 

oocytes. J Biol Chem 264(20):11901-11903. 

Villa SM, Alexander NM. 1987. Carbamazepine (Tegretol) inhibits in vivo iodide uptake and hormone 

synthesis in rat thyroid glands. Endocr Res 13(4):385-397. 

*Virion A, Deme D, Pommier J, et al. 1980. Opposite effects of thiocyanate on tyrosine iodination and 

thyroid hormone synthesis. Eur J Biochem 112:1-7. 

*Visser TJ. 1990. Importance of deiodination and conjugation in the hepatic metabolism of thyroid 

hormone. In: Greer MA, ed. The thyroid gland. New York, NY: Raven Press, Ltd, 255-283. 

*Visser TJ. 1994. Role of sulfation in thyroid hormone metabolism. Chem Biol Interact 92:293-303. 

*Visser TJ, Kaptein E, van Raaij JAGM, et al. 1993. Multiple UDP-glucuronyltransferases for the 

glucuronidation of thyroid hormone with preference for 3,3',5'-triiodothyronine (reverse T3). FEBS Lett 

315(1):65-68. 
 

 

IODINE 485 

9. REFERENCES 

Vobecky M, Babicky A, Lener J, et al. 1997. [Environmental bromine and iodine interaction.] Hygiena 

42(2):86-91. (Czech) 

*Vogt R, Sander R, Von Glasgow R, et al. 1999. Iodine chemistry and its role in halogen activation and 

ozone loss in the marine boundary layers: A model study. J Atmos Chem 32:375-395. 

Voigt G. 1993. Chemical methods to reduce the radioactive contamination of animals and their products 

in agricultural ecosystems. Sci Total Environ 137:205-225. 

*Voigt G, Henrichs K, Prohl G, et al. 1988. Measurements of transfer coefficients fro 137Cs, 60Co, 54Mn, 

22Na, 131I and 95mTc from feed into milk and beef. Radiat Environ Biophys 27:143-152. 

*Voigt G, Muller H, Prohl G, et al. 1989. Experimental determination of transfer coefficients of 137Cs 

and 131I from fodder into milk of cows and sheep after the Chernobyl accident. Health Phys 57(6):967­

973. 

Voigt G, Schotola C, Probstmeier G, et al. 1994. Influence of stable iodine on the transfer of 131I into 

cows' milk. Radiat Environ Biophys 33:243-250. 

Volkov AA, Iulbarisov AV, Zaitsev VM, et al. 1982. [Use of sodium iodide labeled with short-lived 

123I for the study of the iodine absorption and topography of the thyroid.] Med Radiol 27(2):34-36. 

(Russian). 

Voltti H, Piha RS. 1978. Iodine in the treatment of alloxan diabetes in rats. Isr J Med Sci 14(10):1081­

1083. 

Voltti H, Piha RS, Alavaikko M, et al. 1973. Antitumour activity of iodine in acidic medium with 

calcium. Nature 246:98-100. 

Von Hofe SE, Dorfman SG, Carretta RF, et al. 1978. The increasing incidence of hypothyroidism within 

one year after radioiodine therapy for toxic diffuse goiter. J Nucl Med 19:180-184. 

*Von Zallinger C, Tempel K. 1998. Transplacental transfer of radionuclides. A review. Zentralbl 

Veterinarmed A 45:581-590. 

Vorhees CV, Butcher RE, Brunner RL. 1984. Developmental toxicity and psychotoxicity of potassium 

iodide in rats: A case for the inclusion of behaviour in toxicological assessment. Food Chem Toxicol 

22(12):963-970. 

Vorherr H, Vorherr UF, Mehta P, et al. 1980. Vaginal absorption of povidone-iodine. JAMA 

244(23):2628-2629. 

Vormittag W, Ring F, Kunze-Muhl E, et al. 1982. Structural chromosomal aberrations before and after 

administration of 20 uCi iodine-131. Mutat Res 105:333-336. 

*Vought RL, Brown FA, Wolff J. 1972. Erythrosine: An adventitous source of iodide. Journal of 

Clinical Endocrinology and Metabolism 34:747-752. 

­ *Vroye L, Beauwens R, Van Sande J, et al. 1998. The Na +-I cotransporter of the thyroid: 

Characterization of new inhibitors. Pflugers Arch(Eur J Physiol) 435:259-266. 
IODINE 486 

9. REFERENCES 

Vulsma T, Menzel D, Abbad FCB, et al. 1990. Iodine-induced hypothyroidism in infants treated with 

continuous cyclic peritoneal dialysis [Letter]. Lancet 336:812. 

Vulsma T, Rammeloo JA, Gons MH, et al. 1991. The role of serum thyroglobulin concentration and 

thyroid ultrasound imaging in the detection of iodide transport defects in infants. Acta Endocrinol 

124:405-410. 

Vykhovanets EV, Chernyshov VP, Slukvin II, et al. 1997. 131I dose-dependent thyroid autoimmune 

disorders in children living around Chernobyl. Clin Immunol Immunopathol 84(3):251-259. 

Wachholz BW. 1990. Overview of the National Cancer Institute's activities related to exposure of the 

public to fallout from the Nevada test site. Health Phys 59(5):511-514. 

Wadeleux PA, Etienne-Decerf J, Winand RJ, et al. 1978. Effects of thyrotropin on iodine metabolism of 

dog thyroid cells in tissue culture. Endocrinology 102(3):889-902. 

Wagar G. 1971. Increase in thyroid uptake of radioiodine induced by actinomycin D. Acta Endocrinol 

67:605-615. 

*Wagner HN, Nelp WB, Dowling JH. 1961. Use of neutron activation analysis for studying stable 

iodide uptake by the thyroid. J Clin Invest 40:1984-1992. 

Wahl VR, Oekonomopoulos R, Steiner B, et al. 1973. Einflub von dijofphenolsulfonsaure (DJPS) auf 

den jodstoffwechsel der ratte und auf die bindung von thyroxin an humanserumpraalbumin. Arzneim 

Forsch 23(8):1009-1014. 

Wahlberg P. 1976a. Thyrotoxicosis induced by iodine in food [Letter]. Br Med J 2(6043):1070. 

Wahlberg P. 1976b. Thyrotoxicosis induced by iodine in food [Letter]. Br Med J 1(6016):1016. 

Wakeford R. 1999. Accidents and their consequences. J Radiol Prot 19(4):291-292. 

Waldhausen JHT. 1997. Controversies related to the medical and surgical management of 

hyperthyroidism in children. Semin Pediatr Surg 6(3):121-127. 

Waldstein SS. 1997. Replacement and suppressive treatment with thyroid hormone. In: Falk SA, ed. 

Thyroid disease: Endocrinology, surgery, nuclear medicine, and radiotherapy. Philadelphia, PA: 

Lipponcott-Raven Publishers, 475-494. 

Walgraeve D, Verhoef G, Stul M, et al. 1991. Chronic myelogenous leukemia after treatment with 131I 

for thyroid carcinoma: Report of a case and review of the literature. Cancer Genet Cytogenet 55:217­

224. 

Walicka MA, Adelstein SJ, Kassis AI. 1998. Indirect mechanisms contribute to biological effects 

produced by decay of DNA-incorporated iodine-125 in mammalian cells in vitro: Clonogenic survival. 

Radiat Res 149:142-146. 

Walinder G. 1971. Determination of the 131I dose to the mouse thyroid. Acta Radiol Ther Phys Biol 

10:558-578. 
IODINE 487 

9. REFERENCES 

Walinder G. 1972. Quantitative effects of 131I on different tissue components in foetal and goitrogen 

challenged mouse thyroids. Acta Radiol 11:1-23. 

Walinder G, Feinstein RE, Gimeno EJ. 1986. Effect of high 131I doses on the bone uptake and retention 

of 90Sr and 90Y. Acta Radiol Oncol 25:255-260. 

Walls RP. 1976. The characteristics and physiologic implications of the interaction of iodide with 

human erythrocytes. Diss Abstr Int B 36(11):5542-B.
 

*Walser M, Rahill WJ. 1965. Renal tubular reabsorption of iodide as compared with chloride. J Clin 

Invest 44(8):1371-1381. 

Walsh JP, Dayan CM, Potts MJ. 1999. Radioiodine and thyroid eye disease. Br Med J 319:68-69. 

Walthard VB. 1963. [Structural change of the struma maligna with respect to iodine prophylaxis of 

goiter.] Schweiz Med Wochenschr 93(23):809-814. (German) 

Wang JF, Becks GP, Hanada E, et al. 1991. Hormonal regulation of insulin-like growth factor (IGF)­

binding proteins secreted by isolated sheep thyroid epithelial cells: Relationship with iodine 

organification. J Endocrinol 130:129-140. 

Wang J-X, Boice JD, Li B-X, et al. 1988. Cancer among medical diagnostic x-ray workers in China. 

Journal of the National Cancer Institute 80:344-350. 

Wang Z, Boice JD, Wei L, et al. 1990. Thyroid nodularity and chromosome aberrations among women 

in areas of high background radiation in China. J Natl Cancer Inst 82:478-485. 

*Waran KD, Munsick RA. 1995. Anaphylaxis from povidone-iodine. Lancet 345:1506. 

Warner TFCS. 1979. Iodine-131 and malignancy [Letter]. Lancet 1(8106):38. 

Warters RL. 1977. 125-Iodine: A probe in radiobiology [Abstract]. Diss Abstr Int B 38(4):1598B. 

Warters RL, Hofer KG. 1977. Radionuclide toxicity in cultured mammalian cells: Elucidation of the 

primary site for radiation-induced division delay. Radiat Res 69:348-358. 

Warters RL, Hofer KG, Harris CR, et al. 1977. Radionuclide toxicity in cultured mammalian cells: 

Elucidation of the primary site of radiation damage. Curr Top Radiat Res Q 12:389-407. 

Wartofsky L. 1995. Summation, commentary, and overview: Concerns over aggravation of Graves'
 

ophthalmopathy by radioactive iodine treatment and the use of retrobulbar radiation therapy. J Clin 

Endocrinol Metab 80(2):347-349. 

Wartofsky L. 1996a. Myxedema coma. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's the 

thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 871-877. 

Wartofsky L. 1996b. Thyrotoxic storm. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's the 

thyroid: A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven, 701-707. 

Wartofsky L. 1997. Radioiodine therapy for Graves' disease: Case selection and restrictions 

recommended to patients in North America. Thyroid 7(2):213-216. 
IODINE 488 

9. REFERENCES 

Wasserman HJ, Klopper JF. 1993. Analysis of radiation doses received by the public from 131I treatment 

of thyrotoxic outpatients. Nucl Med Commun 14:756-760. 

Wasserman J, Blomgren H, Petrini B, et al. 1988. Changes of the blood lymphocyte subpopulations and 

their functions following 131I treatment for nodular goitre and 32P treatment for polycythemia vera. Int J 

Radiat Biol 53(1):159-167. 

Wassermann M, Wassermann D, Kedar E, et al. 1972. Effects of dieldrin and gamma BHC on serum 

proteins and PBI. Bull Environ Contam Toxicol 8(3):177-185. 

Watanabe N, Yokoyama K, Kinuya S, et al. 1998. Radiotoxicity after iodine-131 therapy for thyroid 

cancer using the micronucleus assay. J Nucl Med 39(3):436-440. 

Waterfall WK. 1980. Iodide. Br Med J 281:988-989. 

Waters W, Kutsim H, Wellner U. 1984. The influence of elevated iodide supply on the autonomously 

functioning thyroid gland. Nuklearmedizin 23:93-99. 

Watson AB, Brownlie BEW, Frampton CM, et al. 1988. Outcome following standardized 185 MBq dose 

131I therapy for Graves' disease. Clin Endocrinol 28:487-496. 

*Wayne EJ, Koutras DA, Alexander WD. 1964. Clinical aspects of iodine metabolism. Philadelphia, 

PA: F.A. Davis Company. 

Weber G, Vigone MC, Rapa A, et al. 1998. Neonatal transient hypothyroidism: Aetiological study. 

Arch Dis Child 79:F70-F72. 

*Weetman AP. 2000. Chronic autoimmune thyroiditis. In: Braverman LE, Utiger RD, eds. Werner and 

Ingbar's the thyroid: A fundamental and clinical text. 8th ed. Philadelphia, PA: Lippincott-Raven, 721­

732. 

*Wehmann G. 1963. Comparison of ingestion to inhalation dose to man from I131 . Health Physics 

9:1221. 

*Weinberg HG, Yamada H. 1997. Sub part-per-billion analysis of bromate, iodate, and chlorite in 

drinking water using a new post ion chromatography column reaction and UV detection. In: Water 

quality technology conference proceedings, November 9-12, 1997, Denver, Co., 4B1/1-4B1/13. 

Weinreich R. 1984. Iodine-124 in nuclear medicine: A critical evaluation. Radiakt Isot Klin Forsch 

16(2):555-563. 

*Weiss SJ, Philp NJ, Ambesi-Impiombato FS, et al. 1984a. Thyrotropin-stimulated iodide transport 

mediated by adenosine 3',5'-monophosphate and dependent on protein synthesis. Endocrinology 

114(4):1099-1107. 

*Weiss SJ, Philip NJ, Grollman EF. 1984b. Effect of thyrotropin on iodide efflux in FRTL-5 cells 

mediated by Ca2+. Endocrinology 114:1108-1113. 

Weiss WJ, Philp NJ, Grollman EF. 1984c. Iodide transport in a continuous line of cultured cells from rat 

thyroid. Endocrinology 114:1090-1098. 
IODINE 489 

9. REFERENCES 

*Wellner U, Eschner W, Hillger HW, et al. 1998. [The exposure of relatives to patients of a nuclear 

medicine ward after radio iodine therapy by inhalation of 131I in their home.] Nuklearmedizin 37:113­

119. [Erratum published in "Nuklearmedizin 37(4):49 (1998)" attached] (German) 

Werner SC, Hamilton HB, Leifer E, et al. 1950. An appraisal of the radioiodine tracer technic as a 

clinical procedure in the diagnosis of thyroid disorders: Uptake measurement directly over the gland and 

a note on the use of thyrotropin (T.S.H.). J Clin Endocrinol 10:1054-1076. 

*West JR, Smith HW, Chasis H. 1948. Glomerular filtration rate, effective renal blood flow, and 

maximal tubular excretory capacity in infancy. J Pediatr 32:10-18. 

Whaley JM, Little JB. 1990. Efficient mutation induction by 125I and 131I decays in DNA of human cells. 

Radiat Res 123:68-74. 

*Whitehead DC. 1979. Iodine in the U.K. environment with particular reference to agriculture. J Appl 

Ecol 16:269-279. 

*Whitehead DC. 1984. The distribution and transformations of iodine in the environment. Environ Int 

10:321-339. 

*Whitnack GC. 1975. Single-sweep polarographic techniques useful in micropollution studies of ground 

and surface waters. Anal Chem 47:618-621. 

Whybrow PC. 1972. Synergistic action between iodine and lithium [Letter]. JAMA 221(5):506. 

Whybrow PC. 1996a. Behavioral and psychiatric aspects of hypothyroidism. In: Braverman LE, Utiger 

RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: 

Lippincott-Raven, 866-870. 

Whybrow PC. 1996b. Behavioral and psychiatric aspects of thyrotoxicosis. In: Braverman LE, Utiger 

RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. Philadelphia, PA: 

Lippincott-Raven, 696-700. 

*Wichers M, Benz E, Palmedo H, et al. 2000. Testicular function after radioiodine therapy for thyroid 

carcinoma. Eur J Nucl Med 27(5):503-507. 

*Widdowson EM, Dickerson JWT. 1964. Chemical composition of the body. In: Comar CL, Bronner 

F, eds. Mineral metabolism: An advanced treatise. Volume II: The elements Part A. New York, NY: 

Academic Press. 

Wiener JD, Thijs LG, Meijer S. 1975. Thyroid carcinoma after 131I treatment for hyperthyroidism. Acta 

Med Scand 198:329-330. 

Wiersinga WM. 1998. Preventing Graves' ophthalmopathy. N Engl J Med 338(2):121-122. 

Wiesenfeld D, Webster G, Cameron F, et al. 1983. Salivary gland dysfunction following radioactive 

iodine therapy. Oral Surg Oral Med Oral Pathol 55(2):138-141. 

Wilkin JK, Strobel D. 1985. Iododerma occurring during thyroid protection treatment. Cutis 36(4):335­

337. 
 

 

IODINE 490 

9. REFERENCES 

*Willard DH, Bair WJ. 1961. Behaviour of I131 following its inhalation as a vapour and as a particle. 

Acta Radiol 55:486-496. 

Williams ED. 1990. TSH and thyroid cancer. Horm Metab Res suppl 23:72-75. 

Williams ED, Doniach I, Bjarnason O, et al. 1977. Thyroid cancer in an iodide rich area. Cancer 

39:215-222. 

*Williams JA. 1969. Electrical polarization of thyroid follicles in the perfused rabbit thyroid gland. Am 

J Physiol 217(4):1094-1100. 

Williams JA, Malayan SA. 1975. Effects of TSH on iodide transport by mouse thyroid lobes in vitro. 

Endocrinology 97:162-168. 

Williams JA, Berens SC, Wolff J. 1971. Thyroid secretion in vitro: Inhibition of TSH and dibutyryl 

cyclic-AMP stimulated and 131I release by Li+1. Endocrinology 88:1385-1388. 

Williams RL, Lipari F, Potter RA. 1990. Formaldehyde, methanol and hydrocarbon emissions from 

methanol-fueled cars. J Air Waste Manage Assoc 40:747-756. 

Wilmott S, Nair S, Ponting AC. 1991. An uncertainty analysis of the ingestion dose following a discrete 

deposition from atmosphere. EUR EUR 13013/2:891-907. 

Wilson LM, Barrington SF, Morrison ID, et al. 1998. Therapeutic implications of thymic uptake of 

radioiodine in thyroid carcinoma. Eur J Nucl Med 25:622-628. 

Wilson MG. 1962. The effect of maternal medications upon the fetus and the newborn infant. Am J 

Obstet Gynecol 83(6):818-825. 

Wilson O, Stone JM, Monty DE. 1983. Long-term study of thyroid function in healthy beagle dogs, 

using 125I. Am J Vet Res 44(7):1392-1398. 

Wingert DJ, Friesen SR, Iliopoulos JI, et al. 1986. Post-thyroidectomy hypocalcemia. Am J Surg 

152:606-610. 

Winslow CP, Meyers AD. 1998. Hypocalcemia as a complication of radioiodine therapy. Am J 

Otolaryngol 19(6):401-403. 

Winternitz SR, Winternitz WW. 1976. Fatal hypothyroidism following treatment of Graves' disease: A 

preventable complication. J Ky Med Assoc 74(9):459-460. 

Winters JC, Fuselier HAJ. 1992. Invasive bladder cancer following 125iodine implants. J Urol 148:1898­

1900. 

Wiseman JC, Hales IB, Joasoo A. 1982. Two cases of lymphoma of the parotid gland following ablative 

radioiodine therapy for thyroid carcinoma. Clin Endocrinol 17:85-89. 

Wiszniewska B, Marchlewicz M, Piasecka M, et al. 1998. Phospholipid content and lamellar structures 

in the epididymal epithelial cells of rats treated chronically with lead acetate [Pb(II)]. Folia Biol 46:215­

224. 
 

 

IODINE 491 

9. REFERENCES 

Wolf M, Leventon G. 1990. Acute iodide-induced enlargement of the salivary glands. J Oral Maxillofac 

Surg 48:71-72. 

*Wolff J. 1964. Transport of iodide and other anions in the thyroid gland. Physiol Rev 44:45-90. 

Wolff J. 1980. Physiological aspects of iodide excess in relation to radiation protection. J Mol Med 

4:151-165. 

*Wolff J. 1983. Congenital goiter with defective iodide transport. Endocrine Rev 4(3):240-254. 

Wolff J. 1989. Excess iodide inhibits the thyroid by multiple mechanisms. Adv Exp Med Biol 261:211­

244. 

Wolff J. 1996. Iodide prophylaxis for reactor accidents. In: Nagataki S, Yamashita S, eds. Nagasaki 

symposium radiation and human health. Amsterdam, The Netherlands: Elsevier Science, 227-237. 

*Wolff J, Chaikoff IL. 1948. Plasma inorganic iodide as a homeostatic regulator of thyroid function. J. 

Biol Chem 74:555-564. 

*Wolff J, Chaikoff IL, Goldberg RC, et al. 1949. The temporary nature of the inhibitory action of excess 

iodide on organic iodine synthesis in the normal thyroid. Endocrinol 45:504-513. 

Wollman SH. 1995. Thyroid radioiodide transport: Models, rate-limiting steps, and relation to 

formation of iodoprotein. Eur J Cell Biol 66:217-225. 

Wollman SH, Reed FE. 1959. Transport of radioiodide between thyroid gland and blood in mice and 

rats. Am J Physiol 196(1):113-120. 

Wondisford FE, Magner JA, Weintraub BD. 1996. Thyrotropin: Chemistry and biosynthesis of 

thyrotropin. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and 

clinical text. Philadelphia, PA: Lippincott-Raven, 190-207. 

*Wong FL, Ron E, Gierlowski T, et al. 1996. Benign thyroid tumors: General risk factors and their 

effects on rediation risk estimation. Am J Epidemiol 144:728-733. 

*Wong GTF, Cheng X-H. 1998. Dissolved organic iodine in marine waters: Determination, occurrence 

and analytical implications. Mar Chem 59:271-281. 

Wongphatarakul V, Friedlander SK, Pinto JP. 1998. A comparative study of PM2.5 ambient aerosol 

chemical databases. Environ Sci Technol 32:3926-3934. 

*Wood DH, Elefson EE, Horstman VG, et al. 1963. Thyroid uptake of radioiodine following various 

routes of administration. Health Phys 9:1217-1220. 

*Woodbury DM, Woodbury JW. 1963. Correlation of micro-electrode potential recordings with 

histology of rat and guinea-pig thyroid glands. J Physiol 169:553-567. 

Woolf PD. 1997. Thyroiditis. In: Falk SA, ed. Thyroid disease: Endocrinology, surgery, nuclear 

medicine, and radiotherapy. Philadelphia, PA: Lippincott-Raven Publishers, 393-410. 
 

 

IODINE 492 

9. REFERENCES 

Worley RJ, Crosby WM. 1974. Hyperthyroidism during pregnancy. Am J Obstet Gynecol 119(2):150­

155. 

Worthington-Roberts B. 1997. The role of maternal nutrition in the prevention of birth defects. J Am 

Diet Assoc 97(Suppl 2):S184-S185. 

Wright EM. 1974. Active transport of iodide and other anions across the choroid plexus. J Physiol 

240:535-566. 

Wu JY, Shu SG, Yang CF, et al. 2002. Mutation analysis of thyroid peroxidase gene in Chinese patients 

with total iodide organification defect: Identification of five model mutations. J Endocrinol 172(3):627­

635. 

Wuttke K, Streffer C, Muller WU, et al. 1996. Micronuclei in lymphocytes of children from the vicinity 

of Chernobyl before and after 131I therapy for thyroid cancer. Int J Radiat Biol 69(2):259-268. 

Wyburn JR. 1972. Human breast milk excretion of radionuclides following administration of 

radiopharmaceuticals. J Nucl Med 14(2):115-117. 

Xiangbao L, Yangzhong X. 1992. Relationship between 131I ground surface contamination activity and 

gamma spectra above ground. Health Phys 62(4):328-331. 

*Xie Y-L, Hopke PK, Paatero P, et al. 1999. Identification of source nature and seasonal variations of 

Arctic aerosol by the multilinear engine. Atmos Environ 33:2549-2562. 

Yadav HS, Chaudhuri BN, Mukherjee SK. 1970. Effect of ethyl alcohol on thyroidal iodide trapping and 

renal clearance of 131I label in rats. Indian J Med Res 58:1421-1427. 

Yalow RS. 1983. Risks in mass distribution of potassium iodide. Bull N Y Acad Med 59(10):1020­

1027. 

Yalow R. 1990. Editorial: The contributions of 131I to the understanding of radiation carcinogenesis. 

Endocrinology 126(4):1787-1789. 

Yamamoto K, Onaya T, Yamada T, et al. 1972. Inhibitory effect of excess iodide on thyroid hormone 

release as measured by intracellular colloid droplets. Endocrinology 90:986-991. 

Yamane T, Yan Y, Yang L, et al. 1992. Tissue developmental anomalies of Corti's organ of the inner ear 

in experimental cretin rats [Abstract]. Teratology 46(6):44B. 

Yamashita H, Noguchi S, Murakami N, et al. 1994. Effect of thyroid-stimulating hormone on cultured 

thyrocytes obtained from patients with Graves' disease and inhibitive effect by sodium iodide: A 

functional study. Pathol Int 44:827-831. 

Yamashita K, Aiyoshi Y, Oka K, et al. 1975. Effects of calcium ionophore (A-23187) on glucose 

oxidation and iodide transport in dog thyroid slices. Endocrinol Jpn 22(5):415-418. 

Yamashita S, Ito M, Namba H, et al. 1996. Screening for childhood thyroid diseases around Chernobyl. 

In: Nagataki S, Yamashita S, eds. Nagasaki symposium radiation and human health: Proposal from 

Nagasaki. Amsterdam, The Netherlands: Elsevier, 103-116. 
IODINE 493 

9. REFERENCES 

Yan T, Wang D, Zhang H, et al. 1994. Effect of iodine deficiency on the development of cerebral cells 

in rats. Teratology 50(6):49B. 

Yan Y, Liu J, Yamane T, et al. 1993. Developmental anomalies of cerebellar cortex in experimental 

cretin rats [Abstract]. Teratology 48(5):531. 

Yang CM, Olsen KR, Schwade JG, et al. 1993. Dose rate effect of 125I irradiation on normal rabbit eyes 

and experimental choroidal melanoma. Exp Eye Res 57:577-585. 

Yasui LS. 1992. Cytotoxicity of 125I decay in the DNA double strand break repair deficient mutant cell 

line, xrs-5. Int J Radiat Biol 62(5):613-618. 

Yasui LS, Hofer KG. 1986. Role of mitochondrial DNA in cell death induced by 125I decay. Int J Radiat 

Biol 49(4):601-610. 

Yeh SDJ, La Quaglia MP. 1997. 131I therapy for pediatric thyroid cancer. Semin Pediatr Surg 6(3):128­

133. 

Yi T. 1995. A case of blindness caused by acute iodine poisoning. Chin Med J 108(7):555-556. 

Yiou F, Raisbeck GM, Christensen GC, et al. 2002. 129I/127I, 129I/137Cs and 129I/99Tc in the Norwegian 

coastal current from 1980 to 1998. J Environ Radioact 60:61-71. 

Yokoyama N, Tominaga T, Eishima K, et al. 1991. Effect of iodide on human thyroid peroxidase in 

thyroid cells. In: Gordon A, Gross J, Hennemann G, eds. Progress in thyroid research. Rotterdam, the 

Netherlands: Balkema, 483-485. 

Yoosufani Z, Slavin JD, Hellman RM, et al. 1987. Preleukemia following large dose radioiodide therapy 

for metastatic thyroid carcinoma. J Nucl Med 28:1348-1350. 

*Yoshida A, Sasaki N, Mori A, et al. 1997. Different electrophysiological character of I-

, ClO4, and 

SCN-

 in the transport by NA +/I- symporter. Biochem Biophys Res Commun 231:731-734. 

*Yoshida A, Taniguchi S, Hisatome I, et al. 2002. Pendrin is an iodide-specific apical porter responsible 

for iodide efflux from thyroid cells. J Clin Endocrinol Metab 87(7):3356-3361. 

Yoshida K, Aizawa Y, Kaise N, et al. 1998. Role of thyroid-stimulating blocking antibody in patients 

who developed hypothryoidsim with one year after 131I treatment for Graves' disease. Clin Endocrinol 

48:17-22. 

Yoshimura S, Shishiba Y, Shimizu T. 1973. Evidence for stimulation of thyroidal secretion by 

iodoaminoacids or iodide. Endocrinol Jpn 20(2):217-219. 

Yoshinari M, Tokuyama T, Okamura K, et al. 1988. Iodide-induced thyrotoxicosis in a thyroidectomized 

patient with metastatic thyroid carcinoma. Cancer 61:1674-1678. 

*Young WF. 1990. Human liver tyrosylsulfotransferase. Gastroenterology 99:1072-1078. 

*Yuita K. 1994a. Overview and dynamics of iodine and bromine in the environment: 1. Dynamics and 

iodine and bromine in soil-plant system. JARQ 28:90-99. 
 

 

IODINE 494 

9. REFERENCES 

Yuita K. 1994b. Overview and dynamics of iodine and bromine in the environment: 2. Iodine and 

bromine toxicity and environmental hazards. JARQ 28:100-111. 

Yukimura Y, Ikejiri K, Kojima A, et al. 1976. Effects of excess iodide and other anions on thyroid 

hormone secretion in normal or hypophysectomized rats treated with graded doses of thyroid hormone. 

Endocrinology 99:541-548. 

Zagrodzki P, Nicol F, McCoy MA, et al. 1998. Iodine deficiency in cattle: Compensatory changes in 

thyroidal selenoenzymes. Res Vet Sci 64(3):209-211. 

Zagrodzki P, Szmigiel H, Ratajczak R, et al. 2000. The role of selenium in iodine metabolism in children 

with goiter. Environ Health Perspect 108(1):67-71. 

Zanzonico PB. 1997. Radiation dose to patients and relatives incident to 131I therapy. Thyroid 7(2):199­

204. 

*Zanzonico PB, Becker DV. 2000. Effects of time of administration and dietary iodine levels on 

potassium iodide (KI) blockade of thyroid irradiation by 131I from radioactive fallout. Health Phys 

78(6):660-667. 

Zanzonico PB, Becker DV, Bigler RE, et al. 1987. Fetal radiation dosimetry for maternally administered 

I131-iodide: Effect of maternal thyroid function. J Nucl Med 28(4):581. 

Zec N, Donovan JW. 1993. Reply to letter. N Engl J Med 328(5):356. 

Zeighami EA, Morris MD. 1986. Thyroid cancer risk in the population around the Nevada test site. 

Health Phys 50(1):19-32. 

Zelicoff AP, Pezzullo JC. 2002. Thyroid cancer 15 years after Chernobyl. Lancet 359(9321):1946-1947. 

*Zemlyn S, Wilson WW, Hellweg PA. 1981. A caution on iodine water purification. West J Med 

135:166-167. 

Zhang M-L, Sugawa H, Mori T. 1995. Inhibition of thyrocyte iodide uptake by H +K+

ATPase inhibitor, 

timoprazole. Endocr J (Tokyo) 42(4):489-496. 

*Zhao J, Wang P, Shang L, et al. 2000. Endemic goiter associated with high iodine intake. Am J Public 

Health 90(10):1633-1635. 

Zhao W, Zhu H, Yu Z, et al. 1998. Long-term effects of various iodine and fluorine doses on the thyroid 

and fluorosis in mice. Endocr Regul 32:63-70. 

Zhorno LI, Il'in BN, Mikhaidarova PP. 1982. [Morphofunctional changes in the thyroid after separate 

and combined exposure to iodine radioisotope.] Radiobiologiia 22(4):553-556. (Russian) 

Zhu X, Lu T, Song X, et al. 1984. Endemic goiter due to iodine rich salt and its pickled vegetables. 

Chin Med J 97(7):545-548. 

*Ziegler EE, Edwards BB, Jensen RL, et al. 1978. Absorption and retention of lead by infants. Pediatr 

Res 12:29-34. 
IODINE 495 

9. REFERENCES 

Zimmermann M, Adou P, Torresani T, et al. 2000. Persistence of goiter despite oral iodine 

supplementation in goitrous children with iron deficiency anemia in Cote d'Ivoire. Am J Clin Nutr 

71(1):88-93. 

Zsebok Z, Baumgartner E. 1978. [Chromosomal changes following irradiation with small doses (author's 

translation).] Fortschr Geb Rontgenstrahlen Nuklearmed Erganzungsbd 129(6):781-784. (German) 

Zuckier LS, Dadachova E, Dohan O, et al. 2001. The endogenous mammary gland Na+

/I- symporter may 

mediate effective radioiodide therapy in breast cancer. J Nucl Med 42(6):987-988. 

Zuckier LS, Li Y, Chang CJ. 1998. Evaluation in a mouse model of a thyroid-blocking protocol for 131I 

antibody therapy (short communication). Cancer Biother Radiopharm 13(6):457-460. 

Zuker CS, Cowman AF, Rubin GM. 1985. Isolation and structure of a rhodopsin gene from D. 

melanogaster. Cell 40:851-858. 

Zvonova IA. 1989. Dietary intake of stable I and some aspects of radioiodine dosimetry. Health Phys 

57(3):471-475. 

Zvonova IA. 1996. The principles of radioiodine dosimetry following a nuclear accident. In: 

Radiodosimetry and preventative measures in the event of a nuclear accident. Austria: International 

Atomic Energy Agency, 15-33. IAEA-TECDOC-893. 

IODINE 497 

10. GLOSSARY 

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 of a radioactive element 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. 
 

 

IODINE 498 

10. GLOSSARY 

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 180E 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. 
 

 

IODINE 499 

10. GLOSSARY 

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. 

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. 

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. 
 

 

IODINE 500 

10. GLOSSARY 

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. 

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. 

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. 
IODINE 501 

10. GLOSSARY 

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). 

 Femtocurie (fCi)—One-billionth of a microcurie (3.7x10-5 disintegrations per second).

 Megacurie (MCi)—One million curies (3.7x1016 disintegrations per sec). 

 Microcurie (μCi)—One-millionth of a curie (3.7x104

 disintegrations per sec). 

 Millicurie (mCi)—One-thousandth of a curie (3.7x107 disintegrations per sec). 

 Nanocurie (nCi)—One-billionth of a curie (3.7x101 disintegrations per sec). 

 Picocurie (pCi)—One-millionth of a microcurie (3.7x10-2 disintegrations per second). 

Daughter Products—See Progeny and Decay Product 
IODINE 502 

10. GLOSSARY 

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). 

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. 
IODINE 503 

10. GLOSSARY 

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 

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). 
IODINE 504 

10. GLOSSARY 

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. 

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. 
IODINE 505 

10. GLOSSARY 

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 

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. 
IODINE 506 

10. GLOSSARY 

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. 

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. 
 

 

IODINE 507 

10. GLOSSARY 

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. 

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.” 

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." 

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. 

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. 
 

 

IODINE 508 

10. GLOSSARY 

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. 

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. 
IODINE 509 

10. GLOSSARY 

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. 

Morbidity—State of being diseased; morbidity rate is the incidence or prevalence of disease in a specific 

population. 

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. 
IODINE 510 

10. GLOSSARY 

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. 

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 

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. 

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. 
IODINE 511 

10. GLOSSARY 

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. 

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). 

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. 

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. 

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." 
 

 

IODINE 512 

10. GLOSSARY 

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) or particles. 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.). However, radiation also occurs 

as corpuscular emission, such as alpha and beta radiation, neutrons, or rays of mixed or unknown type, 

such 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. 

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). 
IODINE 513 

10. GLOSSARY 

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. 

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. 

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). 
IODINE 514 

10. GLOSSARY 

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 (esu) of electrical charge in 1 cubic centimeter or 

2.58x10-4 coulombs per kilogram 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. 

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 radioactive element in a material 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). 
IODINE 515 

10. GLOSSARY 

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. 

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. 
IODINE 516 

10. GLOSSARY 

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. 

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. 
 

 

IODINE 517 

10. GLOSSARY 

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. 

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. 

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. 

IODINE 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. 
IODINE A-2 

APPENDIX A 

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 

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, 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, Agency for Toxic Substances and Disease 

Registry, 1600 Clifton Road NE, Mailstop F-32, Atlanta, Georgia 30333. 
 

 

 

 

 

 

 

IODINE A-3 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Iodine (sodium iodide, potassium iodide) 

CAS Number: 7553-56-2 (7681-82-5, 7681-11-0) 

Date: March 2004 

Profile Status: Draft 3 Post Public 

Route: [ ] Inhalation [X] Oral 

Duration: [X] Acute [ ] Intermediate [ ] Chronic 

Graph Key: 6 

Species: Human 

Minimal Risk Level: 0.01 [X] mg/kg/day [ ] ppm 

The administered doses of iodide (as sodium iodide) were 250, 500, or 1,500 μg I/day for 14 days (Paul et 

al. 1988); or 500, 1,500, or 4,500 μg I/day (Gardner et al. 1988). The pre-existing dietary iodide intakes 

were estimated from the reported 24-hour urinary iodide excretion rate, which was 200 μg/day (Paul et al. 

1988) or 300 μg I/day (Gardner et al. 1988). The total intake of iodide was estimated as the sum of the 

administered iodide and the estimated dietary intake: 450, 700, or 1,700 μg/day (Paul et al. 1988); or 300, 

800, 1,800, or 4,800 μg/day (Gardner et al. 1988). The estimated dosages on a per kg body weight 

(70 kg) were: 0.0064, 0.010, or 0.024 mg/kg/day (Paul et al. 1988); or 0.011, 0.026, or 0.069 mg/kg/day 

(Gardner et al. 1988). 

In protecting public health ATSDR recommends using the conservative lower end of this calculated 

NOAEL range, 0.01 mg/kg/day, to derive an acute-duration MRL of 0.01 mg/kg/day. 

Reference: Gardner DF, Centor RM, Utiger RD. 1988. Effects of low dose oral iodide supplementation 

on thyroid function in normal men. Clin Endocrinol 28:283-288; Paul T, Meyers B, Witorsch RJ, et al. 

1988. The effect of small increases in dietary iodine on thyroid function in euthyroid subjects. 

Metabolism 37(2):121-124. 

Experimental design: Healthy euthyroid adults (9 males, 9 females) who had no history of thyroid 

disease or detectable antithyroid antibodies received daily oral doses of 250, 500, or 1,500 μg I/day as 

sodium iodide for 14 days (Paul et al. 1988). Based on 24-hour urinary excretion of iodide prior to the 

iodide supplement, the background iodine intake was estimated to be approximately 200 μg/day; thus, the 

total iodide intake was approximately 450, 700, or 1,700 μg I/day (approximately 0.0064, 0.01, or 

0.024 mg/kg/day, assuming a 70-kg body weight). 

Ten healthy, euthyroid, adult males received daily oral doses of 500, 1,500, or 4,500 μg I/day (as sodium 

iodide) for 14 days (Gardner et al. 1988). Based on 24-hour urinary excretion of iodide prior to the iodide 

supplement of 250–320 μg/day, the total estimated intakes were 800, 1,800, or 4,800 μg/day or 

approximately 0.011, 0.026, or 0.069 mg/kg/day. 

Effects noted in study and corresponding doses: In the Paul et al. (1988) study, subjects who received 

1,700 μg/day (0.024 mg/kg/day) had significantly depressed (5–10%) serum concentrations of TT4, FT4, 

and TT3 compared to pretreatment levels, and serum TSH concentrations were significantly elevated 

(47%) compared to pretreatment values. Hormone levels were within the normal range during treatment. 

In this same study, nine females received daily doses of 250 or 500 μg I/day for 14 days (total intake was 

approximately 450 or 700 μg/day [0.0064 or 0.010 mg/kg/day]) and there were no significant changes in 

serum hormone concentrations. 
 

 

 

 

 

 

IODINE A-4 

APPENDIX A 

In the Gardner et al. (1988) study, there were no effects on serum thyroid hormone or TSH concentrations 

at the 800 μg/day intake (0.011 mg/kg/day); however, intakes of 1,800 or 4,800 μg I/day (0.026 or 

0.064 mg/kg/day) produced small (10%), but significant, transient decreases in serum TT4 and FT4 

concentrations and an increase (48%) in serum TSH concentration, relative to the pretreatment values. 

Dose and end point used for MRL derivation: 0.01 mg/kg/day; reversible subclinical hypothyroidism. 

[X] NOAEL [ ] LOAEL 

Uncertainty Factors used in MRL derivation: 

[ ] 10 for use of a LOAEL 

[ ] 10 for extrapolation from animals to humans 

[ ] 10 for human variability
 

Although the acute NOAEL is derived from acute studies of healthy adults, supporting studies indicate 

that the NOAEL would be applicable to children and elderly adults (Boyages et al. 1989; Chow et al. 

1991). On this basis, an uncertainty factor is not needed to adjust the NOAEL to account for human 

variability in sensitivity. In the Chow et al. (1991) study, 30 healthy elderly adult females, without 

evidence of thyroid peroxidase antibodies (TPA), received daily doses of 500 μg I/day (as potassium 

iodide) for 14 or 28 days. Serum concentrations of FT4 were significantly decreased and serum TSH 

concentrations were significantly elevated in the women who received the iodide supplements, relative to 

a placebo control group. On average, the magnitude of the changes did not produce clinically significant 

depression in thyroid hormone levels; however, five subjects had serum TSH concentrations that 

exceeded 5 mU/L. The subjects had a lower dietary iodine intake than those in the Gardner et al. (1988) 

study; approximately 72–100 μg/day, based on urinary iodide measurements. Therefore, the total iodide 

intake was approximately 600 μg/day (0.0086 mg/kg/day). 

In the Boyages et al. (1989) study, thyroid status was compared in groups of children, ages 7–15 years, 

who resided in two areas of China where drinking water iodide concentrations were either 462 μg/L 

(n=120) or 54 μg/L (n=51) (Boyages et al. 1989; Li et al. 1987). Although the subjects were all euthyroid 

with normal values for serum thyroid hormones and TSH concentrations, TSH concentrations were 

significantly higher in the high iodine group. The high iodide group had a 65% prevalence of goiter and a 

15% prevalence of Grade 2 goiter compared to 15% for goiter and 0% for Grade 2 goiter in the low iodine 

group. Urinary iodine was 1,236 μg I/g creatinine in the high iodine group and 428 μg I/g creatinine in 

the low iodine group. Assuming a body weight of 40 kg and lean body mass of 85% of body weight, the 

above urinary iodine/creatinine ratios are approximately equivalent to iodine excretion rates, or steadystate ingestion rates of 1,150 μg/day (0.029 mg/kg/day) and 400 μg/day (0.01 mg/kg/day) in the high and 

low iodide groups, respectively. 

The MRL is higher than the National Research Council Recommended Dietary Allowance of 150 μg/day 

(0.0021 mg/kg/day for a 70-kg adult), with additional allowances of 25 μg/day (0.0025 mg/kg/day) and 

50 μg/day (0.0029 mg/kg/day) during pregnancy and lactation, respectively (NRC 1989). 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? No; however, 

urinary iodide levels were converted to estimates of iodine intakes. Steady-state baseline dietary intakes 

of iodide were assumed to be equivalent to the reported 24-hour urinary iodine excretion rates. This 

assumption is consistent with information available on the toxicokinetics of iodide that indicates nearly 

complete absorption of ingested iodide and that urinary excretion accounts for >97% of the absorbed dose 

(see Sections 3.4.1.2 and 3.4.4.2). The assumption is also supported by studies in which 24-hour urinary 

iodide was measured before and after supplementation (Kahaly et al. 1998; Konno et al. 1993b). For 
 

 

IODINE A-5 

APPENDIX A 

example, 31 patients received oral supplements of 382 μg I/day for 6 months. Prior to the 

supplementation, the mean 24-hour urinary iodide excretion rate was 36 μg/day (range, 13–69 ), whereas, 

after 6 months of iodide supplementation, the mean 24-hour urinary iodide excretion rate was 415 μg/day 

(Kahaly et al. 1998). The difference between these two values, 379 μg/day, is nearly identical to the 

supplemental dose of 382 μg/day. 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: NA 

Was a conversion used from intermittent to continuous exposure? No. 

Other additional studies or pertinent information that lend support to this MRL: Two other acute studies 

reported NOAELs and LOAELs of 0.3 and 1.0 mg/kg/day, respectively (Robison et al. 1998, 1999), 

which are substantially higher than those from the Paul et al. (1988) and Gardner et al. (1988) studies. 

These suggest that doses much higher than the MRL can be tolerated in some people without producing 

thyroid gland suppression. 

Agency Contact (Chemical Manager): John Risher, Ph.D. 
 

 

 

 

 

 

 

 

 

 

 

 

IODINE A-6 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Iodine (sodium iodide, potassium iodide) 

CAS Number: 7553-56-2 (7681-82-5, 7681-11-0) 

Date: March 2004 

Profile Status: Draft 3 Post Public 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [ ] Intermediate [X] Chronic 

Graph Key: 29 

Species: Human 

Minimal Risk Level: 0.01 [X] mg/kg/day [ ] ppm 

Iodine intakes estimated from urinary iodine levels (see below) were 400 and 1,150 μg/day. These 

correspond to 0.010 or 0.029 mg/kg/day for a 40-kg child of age 11 years. 

Reference: Boyages SC, Bloot AM, Maberly GF, et al. 1989. Thyroid autoimmunity in endemic goiter 

caused by excessive iodine intake. Clin Endocrinol 31:452-465; Li W, Qu C, Jia G, et al. 1987. 

Endemic goitre in Central China caused by excessive iodine intake. Lancet, August 1:257-258. 

Experimental design: Thyroid status was compared in groups of children, ages 7–15 years, who resided 

in two areas of China where drinking water iodide concentrations were either 462 μg/L (n=120) or 

54 μg/L (N=51) (Boyages et al. 1989; Li et al. 1987). Urinary iodine was 1,236 μg I/g creatinine in the 

high iodine group and 428 μg I/g creatinine in the low iodine group. Assuming a body weight of 40 kg 

and lean body mass of 85% of body weight, the above urinary iodine/creatinine ratios are approximately 

equivalent to iodine excretion rates, or steady state ingestion rates of 1,150 (29 μg/kg/day) and 

400 μg/day (10 μg/kg/day) in the high and low iodide groups, respectively. 

Effects noted in study and corresponding doses: Although the subjects were all euthyroid with normal 

values for serum thyroid hormones and TSH concentrations, TSH concentrations were significantly 

higher (33%) in the high iodine group. The high iodide group had a 65% prevalence of goiter and a 15% 

prevalence of Grade 2 goiter compared to 15% for goiter and 0% for Grade 2 goiter in the low iodine 

group. 

Dose and end point used for MRL derivation: 0.01 mg/kg/day; subclinical hypothyroidism with thyroid 

gland enlargement. 

[X] NOAEL [ ] LOAEL 

Uncertainty Factors used in MRL derivation: 

[ ] 10 for use of a LOAEL 

[ ] 10 for extrapolation from animals to humans 

[ ] 10 for human variability 

An uncertainty factor is not needed to adjust the NOAEL to account for human variability in sensitivity 

because the NOAEL is based on a sensitive end point in children, a sensitive subpopulation. Supporting 

studies indicate that the NOAEL would be applicable to elderly adults who may represent another 

sensitive subpopulation (Chow et al. 1991; Szabolcs et al. 1997). In the Chow et al. (1991) study, 

30 healthy elderly adult females, without evidence of thyroid peroxidase antibodies (TPA), received daily 

doses of 500 μg I/day (as potassium iodide) for 14 or 28 days. Serum concentrations of FT4 were 
 

 

IODINE A-7 

APPENDIX A 

significantly decreased and serum TSH concentrations were significantly elevated in the women who 

received the iodide supplements, relative to a placebo control group. On average, the magnitude of the 

changes did not produce clinically significant depression in thyroid hormone levels; however, five 

subjects had serum TSH concentrations that exceeded 5 mU/L. The pre-existing dietary iodine intake was 

approximately 72–100 μg/day, based on urinary iodide measurements. Therefore, the total iodide intake 

was approximately 600 μg/day (0.0086 mg/kg/day). 

Szabolcs et al. (1997) studied a group of elderly nursing home residents in the Carpathian Basin and 

revealed a prevalence of hypothyroidism that increased with increasing iodine intake. Subjects were from 

one of three regions where, based on reported urinary iodine levels of 72, 100, or 513 μg I/g creatinine, 

the iodine intakes were approximately 117, 163, or 834 μg/day (0.0017, 0.0023, or 0.012 mg/kg/day for 

low, n=119; moderate, n=135; or high intake, n=92, respectively). The prevalence of elevated serum 

TSH concentrations together with serum FT4 concentrations below the normal range, was 0.95, 1.5, and 

7.6% in the low, moderate, and high iodine groups, respectively. If a prevalence of abnormal thyroid 

hormone levels of less than 5% is considered a NOAEL, this study supports a NOAEL in elderly adults 

that is slightly below 0.012 mg/kg/day. Linear interpolation of the dose-prevalence data reported above 

yields an estimate of a 5% prevalence at an iodine intake of approximately 0.008 mg/kg/day. 

The MRL is higher than the National Research Council Recommended Dietary Allowance of 150 μg/day 

(0.0021 mg/kg/day for a 70-kg adult), with additional allowances of 25 μg/day (0.0025 mg/kg/day) and 

50 μg/day (0.0029 mg/kg/day) during pregnancy and lactation, respectively (NRC 1989). 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? No; however, 

urinary iodide levels were converted to estimates of iodine intakes. Urinary iodide:creatinine ratios were 

converted to estimated iodide intake as follows assuming a constant relationship between urinary 

creatinine excretion rate and lean body mass. The rate of creatinine excretion (e.g., UCr, mg 

creatinine/day) was calculated from the relationship between lean body mass (LBM) and Ucr: 

LBM = 0 0272 ⋅U&

Cr . + 858 .

where the constants 0.0272 and 8.58 are the weighted arithmetic mean of estimates of these variables 

from eight studies reported in Forbes and Bruining (1976). Lean body mass was calculated as follows 

(ICRP 1981): 

LBM = BW ⋅ 085 . , females 

LBM = BW ⋅ 088 . ,males 

where BW is the reported body weight for children of age 11 years (40 kg) (EPA 1997). Iodide intake 

was calculated as: 

& Intake I I Cr = U / ⋅UCr 

where UI/Cr is the urinary iodide:creatinine ratio (μg I/g creatinine). This approach yields relationships 

between 24-hour urinary iodide excretion rates and the urinary iodide:creatinine ratios that are in 

reasonable agreement with observation (Konno et al. 1993b). The approach is consistent with 
 

 

 

IODINE A-8 

APPENDIX A 

information available on the toxicokinetics of iodide that indicates nearly complete absorption of ingested 

iodide and that urinary excretion accounts for >97% of the absorbed dose (see Sections 3.4.1.2 and 

3.4.4.2). 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: NA 

Was a conversion used from intermittent to continuous exposure? No. 

Other additional studies or pertinent information that lend support to this MRL: One other study of 

elderly adults supports the MRL as being protective of this population. Thyroid status was compared in 

423 residents (ages 66–70 years) of Jutland, Denmark who had iodine intakes of 40–60 μg/day 

(0.7 μg/kg/day) and 100 residents of Iceland who had intakes of 300–350 μg/day (5 μg/kg/day) (Laurberg 

et al. 1998). Subjects from the high iodine intake region had a significantly higher prevalence (18%) of 

serum TSH levels above the high end of the normal range (>4 mU/L) compared to subjects from the low 

iodine region (3.8%). The prevalence of serum TSH concentrations above 10 mU/L was 4.0% in the high 

iodine region and 0.9% in the low iodine region. Females in both regions had a significantly higher 

prevalence of elevated TSH concentrations than males. Serum concentrations of T4 were not depressed, 

even in subjects with TSH concentrations that exceeded 10 mU/L. Thus, although the subjects appeared 

to be euthyroid, the higher iodine intakes were associated with a subclinical suppression of the thyroid 

gland as indicated by a high prevalence of elevated serum TSH concentrations. 

Agency Contact (Chemical Manager): John Risher, Ph.D. 
IODINE 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. 
 

 

 

IODINE 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 3.10, "Interactions with Other Substances,” and Section 3.11, "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. 
IODINE	 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 exists, 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 Table 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 3.5, "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 

regimen 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"). 
IODINE	 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 38r 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. 
IODINE	 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. 
1 3 4 SAMPLE → TABLE 3-1. Levels of Significant Exposure to [Chemical x] – Inhalation LOAEL (effect) Exposure Less serious Serious (ppm) frequency/ NOAEL (ppm) Key to figurea Species duration System (ppm) Re

2 → INTERMEDIATE EXPOSURE 5 6 7 8 9 10 → Systemic ↓ ↓ ↓ ↓ ↓ 

→ 18 Rat 13 wk 5 d/wk 6 hr/d Resp 3b 10 (hyperplasia) N

CHRONIC EXPOSURE Cancer 11 

↓

38 Rat 18 mo 

5 d/wk 7 hr/d 

20 (CEL, multiple 

organs) 

W

39 Rat 89-104 

5 d/wk 6 hr/d 

wk 10 (CEL, lung tumors, 

nasal tumors) 

NT

40 Mouse 79-103 

5 d/wk 

wk 10 (CEL, lung tumors, 

hemangiosarcomas) 

NT

6 hr/d 

12 → a The number corresponds to entries in Figure 3-1. 

b Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5x10-3 ppm; dose adjusted for iexposure and divided by an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for h


IODINE C-1 

APPENDIX C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS 

Some terms are generic and may not be used in this profile. 

ACGIH American Conference of Governmental Industrial Hygienists 

ACOEM American College of Occupational and Environmental Medicine 

ADI acceptable daily intake 

ADME absorption, distribution, metabolism, and excretion 

AED atomic emission detection 

AFID alkali flame ionization detector 

AFOSH Air Force Office of Safety and Health 

ALI annual limit on intake 

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 

DAC derived air concentration 

DHEW Department of Health, Education, and Welfare 

DHHS Department of Health and Human Services 

DNA deoxyribonucleic acid 

DOD Department of Defense 
 

 

IODINE C-2 

APPENDIX C 

DOE Department of Energy 

DOL Department of Labor 

DOT Department of Transportation 

DOT/UN/ Department of Transportation/United Nations/ 

NA/IMCO North America/International Maritime Dangerous Goods Code 

DWEL drinking water exposure level 

ECD electron capture detection 

ECG/EKG electrocardiogram 

EEG electroencephalogram 

EEGL Emergency Exposure Guidance Level 

EPA Environmental Protection Agency 

F Fahrenheit 

F1 first-filial generation 

FAO Food and Agricultural Organization of the United Nations 

FDA Food and Drug Administration 

FEMA Federal Emergency Management Agency 

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act 

FPD flame photometric detection 

fpm feet per minute 

FR Federal Register 

FSH follicle stimulating hormone 

g gram 

GC gas chromatography 

gd gestational day 

GLC gas liquid chromatography 

GPC gel permeation chromatography 

HPLC high-performance liquid chromatography 

HRGC high resolution gas chromatography 

HSDB Hazardous Substance Data Bank 

IARC International Agency for Research on Cancer 

IDLH immediately dangerous to life and health 

ILO International Labor Organization 

IRIS Integrated Risk Information System 

Kd adsorption ratio 

kg kilogram 

kkg metric ton 

Koc organic carbon partition coefficient 

Kow octanol-water partition coefficient 

L liter 

LC liquid chromatography 

LC50 lethal concentration, 50% kill 

LCLo lethal concentration, low 

LD50 lethal dose, 50% kill 

LDLo lethal dose, low 

LDH lactic dehydrogenase 

LH luteinizing hormone 

LOAEL lowest-observed-adverse-effect level 

LSE Levels of Significant Exposure 

LT50 lethal time, 50% kill 

m meter 

MA trans,trans-muconic acid 
 

 

IODINE C-3 

APPENDIX C 

MAL maximum allowable level 

mCi millicurie 

MCL maximum contaminant level 

MCLG maximum contaminant level goal 

MF modifying factor 

MFO mixed function oxidase 

mg milligram 

mL milliliter 

mm millimeter 

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 
IODINE C-4 

APPENDIX C 

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 

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 

USNRC United States Nuclear Regulatory Commission 

VOC volatile organic compound 

WBC white blood cell 
IODINE C-5 

WHO 

> ≥

= 

< ≤

% αβγδ

μm

μg q1

* 

– 

+ 

(+) 

(–) 

APPENDIX C 

World Health Organization 

greater than 

greater than or equal to 

equal to 

less than 

less than or equal to 

percent 

alpha 

beta 

 gamma 

delta 

 micrometer 

microgram 

cancer slope factor 

negative 

positive 

weakly positive result 

weakly negative result 

IODINE 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 materials (NORMs) exist in nature and no additional energy is 

necessary to place them in an unstable state. Natural radioactivity is the property of some naturally 

occurring, usually heavy elements, that are heavier than lead. Radionuclides, such as radium and 

uranium, primarily emit alpha particles. Some lighter elements such as carbon-14 and tritium (hydrogen3) primarily emit beta particles as they transform to a more stable atom. Natural radioactive atoms 

heavier than lead cannot attain a stable nucleus heavier than lead. Everyone is exposed to background 

radiation from naturally-occurring radionuclides throughout life. This background radiation is the major 

source of radiation exposure to man and arises from several sources. The natural background exposures 

are frequently used as a standard of comparison for exposures to various artificial sources of ionizing 

radiation. 

Artificial radioactive atoms are produced either as a by-product of fission of uranium or plutonium atoms 

in a nuclear reactor or by bombarding stable atoms with particles, such as neutrons or protons, directed at 

the stable atoms with high velocity. These artificially produced radioactive elements usually decay by 

emission of particles, such as positive or negative beta particles and one or more high energy photons 

(gamma rays). Unstable (radioactive) atoms of any element can be produced. 
IODINE D-2 

APPENDIX D 

Both naturally occurring and artificial radioisotopes find application in medicine, industrial products, and 

consumer products. Some specific radioisotopes, called fall-out, are still found in the environment as a 

result of nuclear weapons use or testing. 

D.2 RADIOACTIVE DECAY 

D.2.1 Principles of Radioactive Decay 

The stability of an atom is the result of the balance of the forces of the various components of the nucleus. 

An atom that is unstable (radionuclide) will release energy (decay) in various ways and transform to 

stable atoms or to other radioactive species called daughters, often with the release of ionizing radiation. 

If there are either too many or too few neutrons for a given number of protons, the resulting nucleus may 

undergo transformation. For some elements, a chain of daughter decay products may be produced until 

stable atoms are formed. Radionuclides can be characterized by the type and energy of the radiation 

emitted, the rate of decay, and the mode of decay. The mode of decay indicates how a parent compound 

undergoes transformation. Radiations considered here are primarily of nuclear origin, i.e., they arise from 

nuclear excitation, usually caused by the capture of charged or uncharged nucleons by a nucleus, or by the 

radioactive decay or transformation of an unstable nuclide. The type of radiation may be categorized as 

charged or uncharged particles, protons, and fission products) or electromagnetic radiation (gamma rays 

and x rays). Table D-1 summarizes the basic characteristics of the more common types of radiation 

encountered. 

D.2.2 Half-Life and Activity 

For any given radionuclide, the rate of decay is a first-order process that is constant, regardless of the 

radioactive atoms present and is characteristic for each radionuclide. The process of decay is a series of 

random events; temperature, pressure, or chemical combinations do not effect the rate of decay. While it 

may not be possible to predict exactly which atom is going to undergo transformation at any given time, it 

is possible to predict, on average, the fraction of the radioactive atoms that will transform during any 

interval of time. 

The activity is a measure of the quantity of radioactive material. For these radioactive materials it is 

customary to describe the activity as the number of disintegrations (transformations) per unit time. The 

unit of activity is the curie (Ci), which was originally related to the activity of one gram of radium, but is 

now defined as that quantity of radioactive material in which there are: 

1 curie (Ci) = 3.7x1010 disintegrations (transformations)/second (dps) or 2.22x1012 disintegrations 

(transformations)/minute (dpm). 

The SI unit of activity is the becquerel (Bq); 1 Bq = that quantity of radioactive material in which there is 

1 transformation/second. Since activity is proportional to the number of atoms of the radioactive 

material, the quantity of any radioactive material is usually expressed in curies, regardless of its purity or 

concentration. The transformation of radioactive nuclei is a random process, and the number of 

transformations is directly proportional to the number of radioactive atoms present. For any pure 

radioactive substance, the rate of decay is usually described by its radiological half-life, TR, i.e., the time 

it takes for a specified source material to decay to half its initial activity. The specific activity is the 

activity of a radionuclide per mass of that radionuclide. If properly qualified, it can refer to activity per 

unit mass of related materials, such as the element itself or a chemical compound labeled with the 

radionuclide. The higher the specific activity of a radioisotope, the faster it is decaying. 
 

 

 

 

 

 

 

 

 

IODINE 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 mass energy range a

 Charge 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. – 0 5 keV–100 keV b b Photon from 

photon) transition of an 

electron between 

atomic orbits 

Gamma (p) – 0 10 keV–3 MeV b b Photon from 

nuclear (e.m. photon) 

transformation 

a

 The rest mass (in amu) has an energy equivalent in MeV that is obtained using the equation E=mc2, where 1 amu = 932 MeV. b

 Path lengths are not applicable to x- and gamma rays since their intensities decrease exponentially; path lengths in solid tissue 

are variable, depending on particle energy, electron density of material, and other factors. 

 amu = atomic mass unit; e.m. = electromagnetic; MeV = Megaelectron Volts 

The specific activity is a measure of activity, and is defined as the activity of a radionuclide per mass of 

that radionuclide. This activity is usually expressed in curies per gram and may be calculated by 

curies/gram = 1.3x108

 / (Trad) (atomic weight) or 

[3.577 x 105 x mass(g)] / [Trad x atomic weight] 

where Trad is the radiological half-life in days. 

In the case of radioactive materials contained in living organisms, an additional consideration is made for 

the reduction in observed activity due to regular processes of elimination of the respective chemical or 

biochemical substance from the organism. This introduces a rate constant called the biological half-life 

(Tbiol) which is the time required for biological processes to eliminate one-half of the activity. This time 

is virtually the same for both stable and radioactive isotopes of any given element. 
 

 

 

IODINE D-4 

APPENDIX D 

Under such conditions the time required for a radioactive element to be halved as a result of the combined 

action of radioactive decay and biological elimination is the effective clearance half-time: 

Teff = (Tbiol x Trad) / (Tbiol + Trad). 

Table D-2 presents representative effective half-lives of particular interest. 

Table D-2. Half-Lives of Some Radionuclides in Adult Body Organs 

Half-lifea 

Radionuclide Critical organ Physical Biological Effective 

Uranium 238 

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 474 d 

Cobalt 60 Whole body 5.3 y 99.5 d 95 d 

Iron 55 Spleen 2.7 y 600 d 388 d 

Iron 59 Spleen 45.1 d 600 d 42 d 

Manganese 54 Liver 303 d 25 d 23 d 

Cesium 137 Whole body 30 y 70 d 70 d 

a

d = days, y = years

b

Mixed in body water as tritiated water 

D.2.3 Interaction of Radiation with Matter 

Both ionizing and nonionizing radiation will interact with materials; that is, radiation will lose kinetic 

energy to any solid, liquid or gas through which it passes by a variety of mechanisms. The transfer of 

energy to a medium by either electromagnetic or particulate radiation may be sufficient to cause 

formation of ions. This process is called ionization. Compared to other types of radiation that may be 

absorbed, such as ultraviolet radiation, ionizing radiation deposits a relatively large amount of energy into 

a small volume. 

The method by which incident radiation interacts with the medium to cause ionization may be direct or 

indirect. Electromagnetic radiations (x rays and gamma photons) are indirectly ionizing; that is, they give 

up their energy in various interactions with cellular molecules, and the energy is then utilized to produce a 

fast-moving charged particle such as an electron. It is the electron that then may react with a target 

molecule. This particle is called a “primary ionizing particle. Charged particles, in contrast, strike the 

tissue or medium and directly react with target molecules, such as oxygen or water. These particulate 

radiations are directly ionizing radiations. Examples of directly ionizing particles include alpha and beta 

particles. Indirectly ionizing radiations are always more penetrating than directly ionizing particulate 

radiations. 

Mass, charge, and velocity of a particle, as well as the electron density of the material with which it 

interacts, all affect the rate at which ionization occurs. The higher the charge of the particle and the lower 

the velocity, the greater the propensity to cause ionization. Heavy, highly charged particles, such as alpha 
 

 

IODINE D-5 

APPENDIX D 

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. The alpha particles 

emitted by a given radionuclide have the same energy and intensity combination. Most of the alpha 

particles that are likely to be found have energies in the range of about 4 to 8 MeV, depending on the 

isotope from which they came. 

The alpha particle has an electrical charge of +2. Because of this double positive charge and their size, 

alpha particles have great ionizing power and, thus, lose their kinetic energy quickly. This results in very 

little penetrating power. In fact, an alpha particle cannot penetrate a sheet of paper. The range of an 

alpha particle (the distance the charged particle travels from the point of origin to its resting point) is 

about 4 cm in air, which decreases considerably to a few micrometers in tissue. These properties cause 

alpha emitters to be hazardous only if there is internal contamination (i.e., if the radionuclide is inside the 

body). 

D.2.4.2 Beta Emission. A beta particle (&) is a high-velocity electron ejected from a disintegrating 

nucleus. The particle may be either a negatively charged electron, termed a negatron (&-) or a positively 

charged electron, termed a positron (&+). Although the precise definition of "beta emission" refers to 

both &- and &+, common usage of the term generally applies only to the negative particle, as distinguished 

from the positron emission, which refers to the &+ particle. 

D.2.4.2.1 Beta Negative Emission. Beta particle (&-) emission is another process by which a 

radionuclide, with a neutron excess achieves stability. Beta particle emission decreases the number of 

neutrons by one and increases the number of protons by one, while the atomic mass number remains 

unchanged.1

 This transformation results in the formation of a different element. The energy spectrum of 

beta particle emission ranges from a certain maximum down to zero with the mean energy of the 

spectrum being about one-third of the maximum. The range of betas is much less in tissue than in air. 

Beta negative emitting radionuclides can cause injury to the skin and superficial body tissues, but mostly 

present an internal contamination hazard. 

D.2.4.2.2 Positron Emission. In cases in which there are too many protons in the nucleus, positron 

emission may occur. In this case a proton may be thought of as being converted into a neutron, and a 

positron (&+) is emitted.1 This increases the number of neutrons by one, decreases the number of protons 

by one, and again leaves the atomic mass number unchanged. The gamma radiation resulting from the 

annihilation (see glossary) of the positron makes all positron emitting isotopes more of an external 

radiation hazard than pure & emitters of equal energy. 

D.2.4.2.3 Gamma Emission. Radioactive decay by alpha, beta, or positron emission, or electron 

capture often leaves some of the energy resulting from these changes in the nucleus. As a result, the 

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 

1

 Neutrinos also accompany negative beta particles and positron emissions 
 

 

IODINE D-6 

APPENDIX D 

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 radiation to a unit mass of the tissue or organ. The unit of absorbed dose is the rad; 1 rad = 

100 erg/gram = 0.01 J/kg in any medium. An exposure of 1 R results in a dose to soft tissue of 

approximately 0.01 J/kg. The SI unit is the gray which is equivalent to 100 rad or 1 J/kg. Internal and 

external exposures from radiation sources are not usually instantaneous but are distributed over extended 

periods of time. The resulting rate of change of the absorbed dose to a small volume of mass is referred 

to as the absorbed dose rate in units of rad/unit time. 

D.3.1.3 Working Levels and Working Level Months. Working level (WL) is a measure of the 

atmospheric concentration of radon and its short-lived progeny. One WL is defined as any combination 

of short-lived radon daughters (through polonium-214), per liter of air, that will result in the emission of 

1.3x105

 MeV of alpha energy. An activity concentration of 100 pCi radon-222/L of air, in equilibrium 

with its daughters, corresponds approximately to a potential alpha-energy concentration of 1 WL. The 

WL unit can also be used for thoron daughters. In this case, 1.3x105

 MeV of alpha energy (1 WL) is 

released by the thoron daughters in equilibrium with 7.5 pCi thoron/L. The potential alpha energy 

exposure of miners is commonly expressed in the unit Working Level Month (WLM). One WLM 
IODINE D-7 

APPENDIX D 

corresponds to exposure to a concentration of 1 WL for the reference period of 170 hours, or more 

generally 

WLM = concentration (WL) x exposure time (months) (one “month” = 170 working hours). 

D.3.2 Dosimetry Models 

Dosimetry models are used to estimate the dose from internally deposited to radioactive substances. The 

models for internal dosimetry consider the amount of radionuclides entering the body, the factors 

affecting their movement or transport through the body, distribution and retention of radionuclides in the 

body, and the energy deposited in organs and tissues from the radiation that is emitted during spontaneous 

decay processes. The dose pattern for radioactive materials in the body may be strongly influenced by the 

route of entry of the material. For industrial workers, inhalation of radioactive particles with pulmonary 

deposition and puncture wounds with subcutaneous deposition have been the most frequent. The general 

population has been exposed via ingestion and inhalation of low levels of naturally occurring 

radionuclides as well as radionuclides from nuclear weapons testing. 

The models for external dosimetry consider only the photon doses (and neutron doses, where applicable) 

to organs of individuals who are immersed in air or are exposed to a contaminated object. 

D.3.2.1 Ingestion. Ingestion of radioactive materials is most likely to occur from contaminated 

foodstuffs or water or eventual ingestion of inhaled compounds initially deposited in the lung. Ingestion 

of radioactive material may result in toxic effects as a result of either absorption of the radionuclide or 

irradiation of the gastrointestinal tract during passage through the tract, or a combination of both. The 

fraction of a radioactive material absorbed from the gastrointestinal tract is variable, depending on the 

specific element, the physical and chemical form of the material ingested, and the diet, as well as some 

other metabolic and physiological factors. The absorption of some elements is influenced by age, usually 

with higher absorption in the very young. 

D.3.2.2 Inhalation. The inhalation route of exposure has long been recognized as being a major 

portal of entry for both nonradioactive and radioactive materials. The deposition of particles within the 

lung is largely dependent upon the size of the particles being inhaled. After the particle is deposited, the 

retention will depend upon the physical and chemical properties of the dust and the physiological status of 

the lung. The retention of the particle in the lung depends on the location of deposition, in addition to the 

physical and chemical properties of the particles. The converse of pulmonary retention is pulmonary 

clearance. There are three distinct mechanisms of clearance which operate simultaneously. Ciliary 

clearance acts only in the upper respiratory tract. The second and third mechanisms act mainly in the 

deep respiratory tract. These are phagocytosis and absorption. Phagocytosis is the engulfing of foreign 

bodies by alveolar macrophages and their subsequent removal either up the ciliary "escalator" or by 

entrance into the lymphatic system. Some inhaled soluble particles are absorbed into the blood and 

translocated to other organs and tissues. 

D.3.3 Internal Emitters 

An internal emitter is a radionuclide that is inside the body. The absorbed dose from internally deposited 

radionuclide depends on the energy absorbed per unit mass by the irradiated tissue. For a radionuclide 

distributed uniformly throughout an infinitely large medium, the concentration of absorbed energy must 

be equal to the concentration of energy emitted by the radionuclide. An infinitely large medium may be 

approximated by a tissue mass whose dimensions exceed the range of the particle. All alpha and most 

beta radiation will be absorbed in the organ (or tissue) of reference. Gamma-emitting radionuclide 

emissions are penetrating radiation, and a substantial fraction of gamma energy may be absorbed in 
 

 

IODINE D-8 

APPENDIX D 

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 essential cellular macromolecules. Morphological changes at 

the cellular level, the severity of which are dose-dependent, may also be observed. 

The sensitivity of various cell types varies. According to the Bergonie-Tribondeau law, the sensitivity of 

cell lines is directly proportional to their mitotic rate and inversely proportional to the degree of 

differentiation (Mettler and Moseley 1985). Rubin and Casarett (1968) devised a classification system 

that categorized cells according to type, function, and mitotic activity. The categories range from the 

most sensitive type, "vegetative intermitotic cells", found in the stem cells of the bone marrow and the 

gastrointestinal tract, to the least sensitive cell type, "fixed postmitotic cells," found in striated muscles or 

long-lived neural tissues. 

Cellular changes may result in cell death, which if extensive, may produce irreversible damage to an 

organ or tissue or may result in the death of the individual. If the cell recovers, altered metabolism and 

function may still occur, which may be repaired or may result in the manifestation of clinical symptoms. 

These changes may also be expressed at a later time as tumors or cellular mutations, which may result in 

abnormal tissue. 

D.4.2 Radiation Effects at the Organ Level 

In most organs and tissues the injury and the underlying mechanism for that injury are complex and may 

involve a combination of events. The extent and severity of this tissue injury are dependent upon the 

radiosensitivity of the various cell types in that organ system. Rubin and Casarett (1968) describe and 

schematically display the events following radiation in several organ system types. These include: a 

rapid renewal system, such as the gastrointestinal mucosa; a slow renewal system, such as the pulmonary 

epithelium; and a nonrenewal system, such as neural or muscle tissue. In the rapid renewal system, organ 

injury results from the direct destruction of highly radiosensitive cells, such as the stem cells in the bone 

marrow. Injury may also result from constriction of the microcirculation and from edema and 

inflammation of the basement membrane, designated as the histohematic barrier, which may progress to 
IODINE D-9 

APPENDIX D 

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 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 about 2 years, while other radiation induced cancers, such as osteosarcoma, have latent periods 

greater than 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 the major target molecule during exposure to ionizing radiation. Other macromolecules, such as 

lipids and proteins, are also at risk of damage when exposed to ionizing radiation. The genotoxicity of 

ionizing radiation is an area of intense study, as damage to the DNA is ultimately responsible for many of 

the adverse toxicological effects ascribed to ionizing radiation, including cancer. Damage to genetic 

material is basic to developmental or teratogenic effects, as well. However, for effects other than cancer, 

there is little evidence of human effects at low levels of exposure. 

D.5 UNITS IN RADIATION PROTECTION AND REGULATION 

D.5.1 Dose Equivalent (or Equivalent Dose) 

Dose equivalent (as measured in rem or sievert) is a special radiation protection quantity that is used for 

administrative and radiation safety purposes to express the absorbed dose in a manner which considers the 

difference in biological effectiveness of various kinds of ionizing radiation. ICRP (1990) changed this 

term to equivalent dose, but it has not yet been adopted by the USNRC or DOE. 

The USNRC defines the dose equivalent, H, as the product of the absorbed dose, D, and the quality 

factor, Q, at the point of interest in biological tissue. This relationship is expressed as H = D x Q. The 

dose equivalent concept is applicable only to doses that are not great enough to produce biomedical 

effects. 

The quality factor or radiation weighting factor is a dimensionless quantity that depends in part on the 

stopping power for charged particles, and it accounts for the differences in biological effectiveness found 

among the types of radiation. Originally relative biological effectiveness (RBE) was used rather than Q 

to define the quantity, rem, which was of use in risk assessment. The generally accepted values for 

quality factors and radiation weighting factors for various radiation types are provided in Table D-3. The 

dose equivalent rate is the time rate of change of the dose equivalent to organs and tissues and is 

expressed as rem/unit time or sievert/unit time. 
IODINE D-10 

APPENDIX D 

Table D-3. Quality Factors (Q) and Absorbed Dose Equivalencies 

Radiation Weighting Factor (wr)* 

Type of radiation Quality factor (Q) 

X, gamma, or beta radiation 1 1 

Alpha particles, multiple- 20 0.05 

charged particles, fission 

fragments and heavy particles of 

unknown charge 

Neutrons (other than thermal >> 10 20 

100 keV to 2 MeV), protons, 

alpha particles, charged 

particles of unknown energy 

Neutrons of unknown energy 10 

High-energy protons 10 0.1 

Thermal neutrons 5 

*Absorbed dose in rad equal to 1 rem or the absorbed dose in gray equal to 1 sievert. 

Source: USNRC. 2004. Standards for the protection against radiation, table 1004(b).1. 10 CFR 20.1004. U.S. Nuclear
 

Regulatory Commission, Washington, D.C. NCRP 1993 

D.5.2 Relative Biological Effectiveness 

RBE is used to denote the experimentally determined ratio of the absorbed dose from one radiation type 

to the absorbed dose of a reference radiation required to produce an identical biologic effect under the 

same conditions. Gamma rays from cobalt-60 and 200–250 kVp x-rays have been used as reference 

standards. The term RBE has been widely used in experimental radiobiology, and the term quality factor 

(or radiation weighting factor) used in calculations of dose equivalents for radiation safety purposes 

(ICRP 1977; NCRP 1971; UNSCEAR 1982). Any RBE value applies only to a specific biological end 

point, in a specific exposure, under specific conditions to a specific species. There are no generally 

applicable values of RBE since RBEs are specific to a given exposure scenario. 

D.5.3 Effective Dose Equivalent (or Effective Dose) 

The absorbed dose is usually defined as the mean energy imparted per unit mass to 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. ICRP (1990) changed this term to effective dose, but it 

has not yet been adopted by the USNRC or DOE. 

The effective dose equivalent, HE, is 

HE = (the sum of) Wt Ht 
 

 

IODINE D-11 

APPENDIX D 

where Ht is the dose equivalent (or equivalent dose) in the tissue t, Wt is the tissue weighting factor in that 

tissue, which represents the estimated proportion of the stochastic risk resulting from tissue, t, to the 

stochastic risk when the whole body is uniformly irradiated for occupational exposures under certain 

conditions (ICRP 1977). Tissue weighting factors for selected tissues are listed in Table D-4. 

D.5.4 SI Units 

The ICRU (1980), ICRP (1984), and NCRP (1985) now recommend that the rad, roentgen, curie, and rem 

be replaced by the SI units: gray (Gy), Coulomb per kilogram (C/kg), Becquerel (Bq), and sievert (Sv), 

respectively. The relationship between the customary units and the international system of units (SI) for 

radiological quantities is shown in Table D-5. 

Table D-4. Tissue Weighting Factors for Calculating Effective Dose 

Equivalent and Effective Dose for Selected Tissues
 

Tissue weighting factor 

Tissue NCRP115/ ICRP60 USNRC/ICRP26 

Bladder 0.05 – 

Bone marrow 0.12 0.12 

Bone surface 0.01 0.03 

Breast 0.05 0.15 

Colon 0.12 – 

Esophagus 0.05 – 

Gonads 0.20 0.25 

Liver 0.05 – 

Lung 0.12 0.12 

Skin 0.01 – 

Stomach 0.12 – 

Thyroid 0.05 0.03 

Remainder 0.05 0.30 

Total 1.00 1.00 

ICRP60 = International Commission on Radiological Protection, 1990 Recommendations of the ICRP 

NCRP115 = National Council on Radiation Protection and Measurements. 1993. Risk Estimates for Radiation Protection, 

Report 115. Bethesda, Maryland 

USNRC = Nuclear Regulatory Commission, Title 10, Code of Federal Regulations, Part 20 
 

 

IODINE D-12 

APPENDIX D 

Table D-5. Comparison of Common and SI Units for Radiation Quantities 

Customary 

Quantity units Definition SI units Definition 

Activity (A) curie (Ci) 3.7x1010 becquerel (Bq) s-1 

transformations s1 

Absorbed dose (D) rad 10-2 Jkg-1 gray (Gy) Jkg-1 

-1 -1 Absorbed dose rate rad per second 10-2 Jkg-1s gray per second Jkg-1 s

(Ď) (rad s-1) (Gy s-1) 

Dose equivalent (H) rem 10-2 Jkg-1 sievert (Sv) Jkg-1 

-1 -1 Dose equivalent rate rem per second 10-2 Jkg-1s sievert per second Jkg-1 s

( ) (rem s-1) (Sv s-1) 

Effective dose rem 10-2 Jkg-1 Sievert (Sv) Jkg-1 

Equivalent dose (H) rem 10-2 Jkg-1 Sievert (Sv) Jkg-1 

Linear energy kiloelectron 1.602x10-10 Jm-1 kiloelectron volts 1.602x10-10 Jm-1 

transfer (LET) volts per per micrometer 

micrometer (keV μm-1) 

(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 

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. 
IODINE D-13 

APPENDIX D 

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. 

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. 
IODINE D-14 

APPENDIX D 

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. 

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. 
IODINE E-1 

APPENDIX E. INDEX 

absorbed dose.............................................. 38, 43, 83, 92, 98, 125, 126, 127, 143, 161, 215, 218, 220, 301 

active transport..........................................................................................................................................206 

adipose tissue ..............................................................................................................................................67 

adrenal gland................................................................................................................................. 13, 45, 213 

adrenal glands ............................................................................................................................... 13, 45, 213 

adsorbed .................................................................................................................................... 275, 325, 332 

adsorption..................................................................................................................................................265 

anemia........................................................................................................................... 29, 44, 110, 117, 229 

bioaccumulation................................................................................................................................ 277, 308 

bioavailability ...........................................................................................................................................299 

biokinetic ..................................................................................................................................................164 

biokinetics............................................................. 38, 91, 141, 178, 185, 188, 190, 193, 194, 198, 216, 218 

biomarker .................................................................................................................................... 14, 219, 220 

biomarkers .............................................................................. 17, 45, 56, 212, 219, 220, 221, 238, 309, 313 

breast milk............................................................. 4, 22, 87, 92, 93, 145, 160, 161, 185, 188, 218, 299, 302
 

cancer ....................2, 4, 5, 21, 25, 29, 30, 31, 42, 77, 78, 79, 80, 86, 87, 88, 91, 93, 98, 100, 101, 103, 108, 

..............................110, 111, 117, 119, 121, 122, 123, 125, 126, 127, 128, 131, 132, 133, 134, 135, 138, 

.............................................................. 214, 215, 223, 228, 236, 250, 303, 305, 306, 347, 348, 349, 353 

carcinogenic .................................................................................................................................... 39, 40, 87 

carcinogenicity..........................................................................................................................................339 

carcinoma.............................................................................................. 31, 99, 102, 111, 136, 137, 305, 345 

carcinomas .................................................................................................... 95, 99, 128, 130, 134, 205, 306 

cardiovascular ........................................................................................... 13, 45, 81, 88, 211, 213, 227, 231
 

Chernobyl............................... 22, 24, 25, 26, 28, 29, 30, 31, 87, 88, 90, 91, 92, 93, 95, 101, 105, 109, 116, 

...................................................... 117, 118, 131, 132, 133, 134, 135, 137, 138, 216, 228, 236, 269, 300 

clearance ............139, 161, 164, 168, 171, 173, 175, 178, 183, 188, 207, 210, 223, 225, 226, 227, 306, 319 

death........................................................................................................ 39, 45, 86, 108, 110, 116, 120, 121 

dermal effects..............................................................................................................................................88 

DNA.......................................................................................................................................... 137, 219, 310 

dose coefficients............................................................................................ 38, 39, 103, 104, 106, 164, 354 

dose equivalent.............................................................................................. 38, 39, 188, 191, 304, 305, 353 

elimination half-time................................................................................................. 160, 190, 194, 197, 203 

elimination half-times ...............................................................................................................................190 

enantiomer ................................................................................................................................................206 

endocrine............................................................... 13, 14, 45, 80, 88, 96, 105, 111, 126, 132, 133, 212, 213
 

endocrine effects .........................................................................................................................................88 

Endocrine Effects...................................................... 14, 27, 28, 29, 45, 75, 76, 81, 84, 85, 86, 96, 213, 231
 

erythema......................................................................................................................................................37 

external radiation ............................................................................ 25, 30, 92, 117, 125, 138, 215, 303, 353 

fetal tissue ......................................................................................................................................... 303, 309 

fetus............................17, 19, 27, 67, 75, 76, 86, 90, 108, 148, 183, 185, 186, 188, 213, 217, 238, 303, 343 

follicle stimulating hormone ....................................................................................................... 29, 110, 111 

FSH ............................................................................................................................................. 29, 110, 111 

Gastrointestinal Effects......................................................................................................................... 27, 96 

general population............................................................................................... 25, 219, 261, 294, 307, 309
 

genotoxic............................................................................................................................................... 39, 87 

genotoxicity...............................................................................................................................................236 
 

 

IODINE E-2 

APPENDIX E 

groundwater ...................................................................... 260, 263, 269, 270, 272, 275, 282, 286, 309, 351 

growth retardation....................................................................................................... 25, 28, 76, 86, 98, 216 

half-life.................................................................... 14, 16, 94, 173, 219, 255, 259, 267, 269, 277, 318, 320 

hydrolysis..................................................................................................................................................161 

immunological ............................................................................................................ 39, 70, 74, 86, 90, 105 

immunological effects................................................................................................................... 70, 90, 105 

Kow ............................................................................................................................................ 244, 245, 246 

leukemia............................................................................................................................................ 120, 306 

lymphatic .......................................................................................................................................... 120, 167 

lymphoreticular................................................................................................................................... 71, 105 

menstrual......................................................................................................................................... 29, 76, 85 

metabolic effects .......................................................................................................................................147 

micronuclei ...............................................................................................................................................137 

milk .......................3, 5, 11, 12, 25, 87, 93, 94, 102, 103, 107, 109, 129, 130, 133, 136, 141, 161, 178, 183, 

...................................... 214, 218, 236, 260, 261, 276, 292, 297, 298, 300, 302, 308, 309, 320, 321, 323 

neonatal............................................................................................................... 19, 65, 67, 73, 84, 110, 237 

neoplasm ........................................................................................................................................... 131, 135 

neurobehavioral.........................................................................................................................................213 

neurodevelopmental.............................................................................................................................. 19, 67 

nuclear........................................ 1, 3, 12, 22, 24, 25, 30, 31, 68, 87, 88, 90, 91, 92, 94, 105, 109, 117, 118, 

............................................. 119, 127, 129, 131, 137, 215, 233, 236, 241, 249, 250, 251, 252, 255, 259, 

...................................... 260, 261, 268, 269, 270, 281, 282, 285, 286, 289, 292, 300, 302, 304, 305, 317 

odds ratio....................................................................................................................... 77, 97, 109, 116, 133 

partition coefficients .................................................................................................................................280 

pharmacodynamic .....................................................................................................................................162 

pharmacokinetic........................................................................................................................ 162, 163, 166 

pharmacokinetics ...................................................................................................................... 140, 164, 214 

photolysis ..................................................................................................................................................280 

placenta ............................................................... 14, 146, 147, 178, 183, 184, 186, 188, 205, 209, 224, 303 

rate constant ...................................................................................................................................... 193, 200 

retention ........................................................................ 38, 67, 171, 173, 175, 259, 272, 275, 308, 318, 353 

solubility ................................................................................................................... 164, 167, 272, 276, 280 

spermatozoa ........................................................................................................................................ 29, 110 

T3..........................15, 17, 32, 45, 46, 56, 59, 66, 82, 83, 101, 112, 146, 147, 149, 151, 155, 159, 161, 192, 

.............................................................................. 204, 206, 207, 209, 210, 217, 221, 222, 225, 226, 228 

T4............................................. 14, 17, 32, 45, 56, 57, 59, 60, 62, 64, 67, 70, 71, 81, 82, 83, 101, 142, 146, 

...............................147, 149, 151, 155, 159, 160, 161, 206, 207, 209, 210, 221, 222, 225, 226, 227, 231 

thyroid...................................... 2, 3, 4, 5, 6, 7, 11, 12, 13, 14, 16, 17, 18, 19, 20, 21, 22, 25, 26, 27, 28, 29, 

....................................... 30, 31, 32, 33, 34, 35, 42, 45, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 67, 68, 69, 

................................................... 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88,
 

....................................................... 90, 91, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 

..................................... 107, 108, 109, 110, 111, 117, 118, 119, 121, 122, 123, 125, 126, 127, 128, 129, 

..................................................... 130, 131, 132, 133, 134, 135, 137, 138, 140, 141, 142, 143, 144, 145, 

............................................. 146, 147, 148, 150, 151, 152, 155, 159, 161, 178, 181, 183, 184, 185, 188, 

..................................................... 190, 193, 194, 197, 198, 200, 201, 202, 203, 204, 205, 206, 207, 209, 

............................................................. 210, 211, 212, 213, 214, 215, 216, 217, 218, 220, 221, 222, 223, 

..................................................... 224, 225, 226, 227, 228, 229, 230, 231, 233, 236, 237, 238, 239, 240, 

..................................................... 250, 259, 261, 277, 286, 292, 294, 295, 298, 300, 301, 302, 303, 304, 

.............................................................................. 305, 306, 310, 313, 314, 317, 318, 320, 321, 345, 353 

thyroid stimulating hormone................................................................................................. 14, 45, 221, 222 

thyroxine ............................................................................................... 14, 45, 142, 147, 149, 209, 221, 222 
IODINE E-3 

APPENDIX E 

toxicokinetic................................................................................................................................ 37, 217, 238 

toxicokinetics .............................................................................................................. 43, 212, 216, 218, 238 

triiodothyronine............................................................................................................................. 14, 45, 221 

TSH.................................... 14, 17, 19, 25, 26, 32, 33, 34, 35, 45, 56, 57, 58, 59, 60, 61, 62, 63, 64, 66, 67, 

................................................... 70, 72, 73, 81, 82, 83, 98, 101, 102, 105, 147, 148, 155, 183, 203, 204, 

...................................................................... 205, 207, 210, 211, 212, 216, 221, 222, 225, 226, 227, 228 

tumors ......................................................................................... 12, 79, 80, 95, 97, 125, 126, 127, 138, 215
 

vapor pressure ................................................................................................................................... 278, 280 

volatility ....................................................................................................................................................272 

volatilization ..................................................................................... 259, 260, 265, 267, 275, 280, 282, 308