## TOXICOLOGICAL PROFILE FOR STRONTIUM

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Agency for Toxic Substances and Disease Registry

April 2004ii STRONTIUM



### 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.iii STRONTIUM



### UPDATE STATEMENT

A Toxicological Profile for strontium, Draft for Public Comment was released in July 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 30333vi
Background Information The toxicological profiles are developed by ATSDR pursuant to Section 104(i) (3) and (5) of the Comprehensive Environmental Response, Compensat ion, 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).vii STRONTIUM



### QUICK REFERENCE FOR HE ALTH 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 wi ll 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 subs tance. 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, re productive), 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 St atement to identify general health effects observed following exposure.
Pediatrics: Four new sections have been added to each Toxicological Profile to address child health issues: Section 1.6 How Can (Chemical X) Affect Children? Section 1.7 How Can Families Reduce the Risk of Exposure to (Chemical X)? Section 3.7 Children’s Susceptibility Section 6.6 Exposures of Children
Other Sections of Interest: Section 3.9 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 or dered through the ATSDR Information Center: Case Studies in Environmental Medicine: Taking an Exposure History —The importance of taking an exposure history and how to conduct one are desc ribed, 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.viii STRONTIUM

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 th at involve hazardous materials. Volume III— Medical Management Guidelines for Acute Chemical Exposure s—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 assist ance 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 e nvironmental agents on human health and well-being. Contact: NIEH S, 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), RE AC/TS trains, consults, or assists in the response to all kinds of radiation accidents. Contact: Oak Ri dge 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@or au.gov • website (including emergency medical guidance): http://www.orau.gov/reacts/default.htm

Referrals The Association of Occupational and Environmental Clinics (AOEC) has developed a network of clinics in the United States to provide expertise in o ccupational 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/.ix STRONTIUM

The American College of Occupational and Environmental Medicine (ACOEM) is an association of physicians and other health care providers sp ecializing 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.xi STRONTIUM



### CONTRIBUTORS

CHEMICAL MANAGER(S)/AUTHOR(S):
Alfred F. Dorsey, D.V.M ATSDR, Division of Toxicology, Atlanta, GA Margaret E. Fransen, Ph.D. Syracuse Research Corporation, North Syracuse, NY Gary L. Diamond, Ph.D. Syracuse Research Corporation, North Syracuse, NY Richard J. Amata, Ph.D. Syracuse Research Corporation, North Syracuse, NY

THE PROFILE HAS UNDERGONE THE FO LLOWING ATSDR INTERNAL REVIEWS:

1. Health Effects Review. The Health Effect s Review Committee examines the health effects chapter of each profile for consistency and accur acy 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 recommendati ons for derivation of MRLs.
3. Data Needs Review. The Research Implementa tion Branch reviews data needs sections to assure consistency across profiles and adherence to instructions in the Guidance.xiii STRONTIUM



### PEER REVIEW

A peer review panel was assembled for strontium. The panel consisted of the following members:
1. Adele L. Boskey, Ph.D., Professor of Biochemistry, Starr Chair in Mineralized Tissues, Hospital for Special Surgery, Weill Medical College of Cornell University, New York, New York,
2. Marvin Goldman, Ph.D., Emeritus Professor of Radi ation Biology, Department of Surgical and Radiological Sciences, University of California, Davis, California,
3. Richard Leggett, Ph.D., Life Sciences Divisi on, Oak Ridge National Laboratory, Knoxville, Tennessee, and
4. Bruce Muggenburg, D.V.M., Ph.D., Senior Scientis t and Veterinary Physiologist, Toxicology Division, Lovelace Respiratory Research Institute, Albuquerque, New Mexico.
These experts collectively have knowledge of st rontium's physical and chemical properties, toxicokinetics, key health end points, mechanis ms 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 Comp rehensive 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 al so 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.xv STRONTIUM



### CONTENTS

DISCLAIMER

.............................................................................................................................................. ii UPDATE STATEMENT

............................................................................................................... .............. iii FOREWORD

....................................................................................................................... ......................... v QUICK REFERENCE FOR HEALTH CARE PROVIDERS

.................................................................... vii CONTRIBUTORS

....................................................................................................................................... xi PEER REVIEW

......................................................................................................................................... xiii CONTENTS

....................................................................................................................... ......................... xv LIST OF FIGURES

................................................................................................................ ................... xix LIST OF TABLES................................................................................................................. ....................xxi
1. PUBLIC HEALTH STATEMENT

.................................................................................................... ...... 1 1.1 WHAT IS STRONTIUM?

....................................................................................................... .... 1 1.2 WHAT HAPPENS TO STRONTIUM WHEN IT ENTERS THE ENVIRONMENT?

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

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

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

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

................................................................... 8 1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO STRONTIUM?

............... 9 1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO STRONTIUM?

.................................................................................................................. . 10 1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO PROTECT HUMAN HEALTH?

.............................................................................................. 11 1.10 WHERE CAN I GET MORE INFORMATION?

..................................................................... 12
2. RELEVANCE TO PUBLIC HEALTH

................................................................................................. 15 2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO STRONTIUM IN THE UNITED STATES

.................................................................................................................. .. 15 2.2 SUMMARY OF HEALTH EFFECTS

...................................................................................... 16 2.3 MINIMAL RISK LEVELS

...................................................................................................... . 23
3. HEALTH EFFECTS

............................................................................................................. ................. 27 3.1 INTRODUCTION

............................................................................................................. ........ 27 3.2 DISCUSSION OF HEALTH EFFECTS OF STABLE STRONTIUM BY ROUTE OF EXPOSURE

....................................................................................................................... ....... 31 3.2.1 Inhalation Exposure

.................................................................................................... ...... 33 3.2.1.1 Death

................................................................................................................ ........ 33 3.2.1.2 Systemic Effects

..................................................................................................... .. 33 3.2.1.3 Immunological and Lymphoreticular Effects

.......................................................... 34 3.2.1.4 Neurological Effects

................................................................................................. 34 3.2.1.5 Reproductive Effects

................................................................................................ 3 4 3.2.1.6 Developmental Effects

............................................................................................. 34 3.2.1.7 Cancer

............................................................................................................... ....... 35 3.2.2 Oral Exposure

.......................................................................................................... ......... 35 3.2.2.1 Death

................................................................................................................ ........ 36 3.2.2.2 Systemic Effects

..................................................................................................... .. 36 3.2.2.3 Immunological and Lymphoreticular Effects

.......................................................... 58 3.2.2.4 Neurological Effects

................................................................................................. 58 3.2.2.5 Reproductive Effects

................................................................................................ 5 8STRONTIUM xvi

3.2.2.6 Developmental Effects

............................................................................................. 58 3.2.2.7 Cancer

............................................................................................................... ....... 59 3.2.3 Dermal Exposure

........................................................................................................ ...... 59 3.2.3.1 Death

................................................................................................................ ........ 60 3.2.3.2 Systemic Effects

..................................................................................................... .. 60 3.2.3.3 Immunological and Lymphoreticular Effects

.......................................................... 60 3.2.3.4 Neurological Effects

................................................................................................. 60 3.2.3.5 Reproductive Effects

................................................................................................ 6 0 3.2.3.6 Developmental Effects

............................................................................................. 60 3.2.3.7 Cancer

............................................................................................................... ....... 60 3.2.4 Other Routes of Exposure

............................................................................................... .. 60 3.3 DISCUSSION OF HEALTH EFFECTS OF RADIOACTIVE STRONTIUM BY ROUTE OF EXPOSURE

....................................................................................................................... ....... 62 3.3.1 Inhalation Exposure

.................................................................................................... ...... 63 3.3.1.1 Death

................................................................................................................ ........ 64 3.3.1.2 Systemic Effects

..................................................................................................... .. 65 3.3.1.3 Immunological and Lymphoreticular Effects

.......................................................... 73 3.3.1.4 Neurological Effects

................................................................................................. 74 3.3.1.5 Reproductive Effects

.................................................................................................. ....... 74 3.3.1.6 Developmental Effects

................................................................................................. ..... 74 3.3.1.7 Cancer

............................................................................................................... ....... 74 3.3.2 Oral Exposure

.......................................................................................................... ......... 76 3.3.2.1 Death

................................................................................................................ ........ 77 3.3.2.2 Systemic Effects

..................................................................................................... .. 80 3.3.2.3 Immunological and Lymphoreticular Effects

.......................................................... 93 3.3.2.4 Neurological Effects

................................................................................................. 94 3.3.2.5 Reproductive Effects

................................................................................................ 9 4 3.3.2.6 Developmental Effects

............................................................................................. 95 3.3.2.7 Cancer

............................................................................................................... ....... 97 3.3.3 External Exposure

...................................................................................................... ..... 100 3.3.3.1 Death

................................................................................................................ ...... 101 3.3.3.2 Systemic Effects

..................................................................................................... 101 3.3.3.3 Immunological and Lymphoreticular Effects

........................................................ 108 3.3.3.4 Neurological Effects

............................................................................................... 10 8 3.3.3.5 Reproductive Effects

.............................................................................................. 108 3.3.3.6 Developmental Effects

........................................................................................... 108 3.3.3.7 Cancer

............................................................................................................... ..... 108 3.3.4 Other Routes of Exposure

............................................................................................... 110 3.4 GENOTOXICITY

............................................................................................................. ...... 113 3.5 TOXICOKINETICS

........................................................................................................... ..... 118 3.5.1 Absorption

............................................................................................................. ......... 118 3.5.1.1 Inhalation Exposure

............................................................................................... 118 3.5.1.2 Oral Exposure

........................................................................................................ . 120 3.5.1.3 Dermal Exposure

.................................................................................................... 12 3 3.5.2 Distribution

........................................................................................................... .......... 125 3.5.2.1 Inhalation Exposure

............................................................................................... 125 3.5.2.2 Oral Exposure

........................................................................................................ . 126 3.5.2.3 Dermal Exposure

.................................................................................................... 12 9 3.5.3 Metabolism

............................................................................................................. ........ 129 3.5.3.1 Inhalation Exposure

............................................................................................... 130 3.5.3.2 Oral Exposure

........................................................................................................ . 130STRONTIUM xvii

3.5.3.3 Dermal Exposure

.................................................................................................... 13 0 3.5.4 Elimination and Excretion

.............................................................................................. 130 3.5.4.1 Inhalation Exposure

............................................................................................... 130 3.5.4.2 Oral Exposure

........................................................................................................ . 131 3.5.4.3 Dermal Exposure

.................................................................................................... 13 2 3.5.5 Physiologically Based Pharmacokine tic (PBPK)/Pharmacodynamic (PD) Models

....... 132 3.6 MECHANISMS OF ACTION

................................................................................................ 147 3.6.1 Pharmacokinetic Mechanisms

........................................................................................ 147 3.6.2 Mechanisms of Toxicity

................................................................................................. 150 3.6.3 Animal-to-Human Extrapolations

................................................................................... 154 3.7 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS

........................ 155 3.8 CHILDREN’S SUSCEPTIBILITY

......................................................................................... 156 3.9 BIOMARKERS OF EXPOSURE AND EFFECT

.................................................................. 162 3.9.1 Biomarkers Used to Identify or Quantify Exposure to Strontium

.................................. 163 3.9.2 Biomarkers Used to Characterize Effects Caused by Strontium

.................................... 164 3.10 INTERACTIONS WITH OTHER CHEMICALS

.................................................................. 164 3.11 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE

............................................. 165 3.12 METHODS FOR REDUCING TOXIC EFFECTS

................................................................. 167 3.12.1 Reducing Peak Absorption Following Exposure

........................................................ 168 3.12.2 Reducing Body Burden

.............................................................................................. 170 3.12.3 Interfering with the Mechanism of Action for Toxic Effects

..................................... 173 3.13 ADEQUACY OF THE DATABASE

...................................................................................... 173 3.13.1 Existing Information on Health Effects of Strontium

................................................. 173 3.13.2 Identification of Data Needs

....................................................................................... 176 3.13.3 Ongoing Studies

....................................................................................................... .. 187
4. CHEMICAL, PHYSICAL, and RADIOLOGICAL INFORMATION

............................................... 189 4.1 CHEMICAL IDENTITY

........................................................................................................ . 189 4.2 PHYSICAL, CHEMICAL, AND RADIOLOGICAL PROPERTIES

..................................... 189
5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL

.......................................................... 199 5.1 PRODUCTION

............................................................................................................... ........ 199 5.2 IMPORT/EXPORT

............................................................................................................ ..... 200 5.3 USE

...................................................................................................................... .................... 200 5.4 DISPOSAL

................................................................................................................. ............. 201
6. POTENTIAL FOR HUMAN EXPOSURE

......................................................................................... 205 6.1 OVERVIEW

................................................................................................................. ........... 205 6.2 RELEASES TO THE ENVIRONMENT

................................................................................ 208 6.2.1 Air

.................................................................................................................... ............... 208 6.2.2 Water

.................................................................................................................. ............. 213 6.2.3 Soil

................................................................................................................... ............... 213 6.3 ENVIRONMENTAL FATE

.................................................................................................... 214 6.3.1 Transport and Partitioning

............................................................................................. . 214 6.3.2 Transformation and Degradation

.................................................................................... 217 6.3.2.1 Air

.................................................................................................................... ........... 219 6.3.2.2 Water

................................................................................................................ ...... 219 6.3.2.3 Sediment and Soil

.................................................................................................. 21 9 6.3.2.4 Other Media

.......................................................................................................... . 220 6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT

............................... 220 6.4.1 Air

.................................................................................................................... ............... 220STRONTIUM xviii

6.4.2 Water

.................................................................................................................. ............. 222 6.4.3 Sediment and Soil

...................................................................................................... ..... 228 6.4.4 Other Environmental Media

........................................................................................... 229 6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE

..................................... 236 6.6 EXPOSURES OF CHILDREN

............................................................................................... 239 6.7 POPULATIONS WITH PO TENTIALLY HIGH EXPOSURES

........................................... 241 6.8 ADEQUACY OF THE DATABASE

...................................................................................... 241 6.8.1 Identification of Data Needs

........................................................................................... 242 6.8.2 Ongoing Studies

........................................................................................................ ...... 246
7. ANALYTIC AL METHODS

......................................................................................................... ...... 249 7.1 BIOLOGICAL MATERIALS

................................................................................................. 249 7.1.1 Internal Strontium Measurements

................................................................................... 249 7.1.2 In Vivo and In Vitro Radiostrontium Measurements

...................................................... 251 7.2 ENVIRONMENTAL SAMPLES

............................................................................................ 251 7.2.1 Field Measurements of Radiostrontium

.......................................................................... 252 7.2.2 Laboratory Analysis of Environmental Samples

............................................................ 252 7.3 ADEQUACY OF THE DATABASE

...................................................................................... 254 7.3.1 Identification of Data Needs

........................................................................................... 255 7.3.2 Ongoing Studies

........................................................................................................ ...... 255
8. REGULATIONS AND ADVISORIES

............................................................................................... 25 7
9. REFERENCES

................................................................................................................. ................... 277
10. GLOSSARY

.................................................................................................................. .................... 367
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-1xix STRONTIUM



### LIST OF FIGURES

3-1. Levels of Significant Exposure to St rontium—Chemical Toxicity—Oral

................................... 45
3-2. Levels of Significant Exposure to Str ontium—Radiation Toxicity—Inhalation

.......................... 69
3-3. Levels of Significant Exposure to St rontium—Radiation Toxicity—Oral

................................... 86
3-4. Conceptual Representation of a Physiologica lly Based Pharmacokinetic (PBPK) Model for a Hypothetical Chemical Substance

............................................................................................... 1 34
3-5. Compartment Model to Represent Particle Depos ition and Time-Dependent Particle Transport in the Respirat ory Tract

.......................................................................................................... .......... 136
3-6. Reaction of Gases or Vapors at Various Levels of the Gas-Blood Interface

............................... 138
3-7. The Human Respiratory Tract Model: Absorption into Blood

.................................................... 140
3-8. ICRP (1993) Model of Strontium Biokinetics

............................................................................. 145
3-9. Existing Information on Health Effects of Stable Strontium

....................................................... 174 3-10. Existing Information on Health Effects of Radioactive Strontium

.............................................. 175
6-1. Frequency of NPL Sites wi th Strontium Contamination

............................................................. 206
6-2. Frequency of NPL Sites with Strontium-90 Contamination

........................................................ 207
6-3. U.S. Daily Dietary Intake of 90 Sr, 1961–1992

............................................................................. 235xxi STRONTIUM



### LIST OF TABLES

3-1. Levels of Significant Exposure to St rontium—Chemical Toxicity—O ral

..................................... 37
3-2. Levels of Significant Exposure to Str ontium—Radiation Toxi city—Inhala tion

........................... 66
3-3. Levels of Significant Exposure to St rontium—Radiation Toxicity—O ral

.................................... 81
3-4. Levels of Significant Exposure to Str ontium—Radiation Toxi city—Exter nal

............................ 102
3-5. Genotoxicity of Stable and Radioactive Strontium In Vivo

.......................................................... 114
3-6. Genotoxicity of Stable and Radioactive Strontium In Vitro

......................................................... 115
3-7. Summary of Estimates of Absorpti on of Ingested Str ontium in Humans

.................................... 121
3-8. Reference Respiratory Values for a General Caucasian Popula tion at Different Levels of Activ ity

........................................................................................................................................... 137
3-9. Reference Values of Parameters for the Compartment Model to Represent Time-dependent Particle Transport from th e Human Respir atory Tract

.................................................................. 141
4-1. Chemical Identity of Stro ntium and Stron tium Com pounds

......................................................... 190
4-2. Physical and Chemical Properties of Strontium and St rontium Co mpounds

............................... 193
4-3. Percent Natural Occurrence and Radioact ive Properties of Isot opes of Strontium

...................... 196
6-1. Radiostrontium Releases from Nuclear Power Pl ants fo r 1993

.................................................... 210
6-2. Selected Bioconcentration Factors for 90 Sr in Aquatic, Wetland, and Te rrestrial Ecosystems at the Savannah Ri ver S ite

....................................................................................................................... 218
6-3. Average or Ranges of Concentrati on of Strontium in Earth Mate rials

......................................... 221
6-4. 90 Sr in Drinking Water (Composite s) for January–D ecember 1995

............................................. 224
6-5. Quarterly and Annual Deposition of 90 Sr in Selected U.S. C ites for the Year 1990

.................... 227
6-6. Concentration of Strontium in Fruit Juices and Produce

.............................................................. 230
6-7. 90 Sr in the Human Diets Duri ng 1982

............................................................................................ 23 2
6-8. 90 Sr in Pasteurized M ilk in Ju ly 1997

............................................................................................ 233
6-9. Strontium Concentrations in Human Body Fluids and Tissues

.................................................... 238 6-10. Ongoing Studies on the Environm ental Effects of Stron tium

....................................................... 247xxii STRONTIUM

7-1. Analytical Methods for Determining Strontium in Biological Samples

...................................... 250
7-2. Analytical Methods for Determining Strontium in Environmental Samples

............................... 253
8-1. Regulations and Guidelines A pplicable to Stable Strontium

....................................................... 258
8-2. Regulations and Guidelines App licable to Radioactive Strontium

.............................................. 260
8-3. Effective Dose Coefficients (e(50)) and Annual Limits on Intake (ALI) for Occupational Exposures to Radioactive Strontium Isotopes

............................................................................. 2731 STRONTIUM



### 1. PUBLIC HEALTH STATEMENT
This public health statement tells you about strontium and the effects of exposure.
The Environmental Protection Agency (EPA) identif ies the most serious hazardous waste sites in the nation. These sites make up the National Priori ties List (NPL) and are the sites targeted for long-term federal cleanup activities. Strontiu m and strontium-90 have been found in at least 102 and 12 of the 1,636 current or former NPL sites, respectively. However, the total number of NPL sites evaluated for strontium and strontium- 90 are not known. As mo re sites are evaluated, the sites at which strontium and strontium-90 are found may increase. This information is important because exposure to strontium and stro ntium-90 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 wh en you come in contact with it. You may be exposed by breathing, eating, or drinki ng the substance, or by skin contact. External exposure to radiation may occur from natural or man-made s ources. Naturally occurri ng sources of radiation are cosmic radiation from space or radioactive mate rials 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 fr om hospital waste and nuclear reactors.
If you are exposed to strontium, many factors determine whet her 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.

1.1 WHAT IS STRONTIUM?
Strontium is a natural and commonly occurring el ement. Strontium can exist in two oxidation states: 0 and +2. Under normal environmental conditions, only the +2 oxidation state is stable2 STRONTIUM 1. PUBLIC HEALTH STATEMENT 

### enough to be important. Pure strontium is a hard, white-colored metal, but this form is not found in the environment. Rather, strontium is usua lly found in nature in the form of minerals. Strontium can form a variety of compounds. St rontium compounds do not have any particular smell. There are two types of strontium compounds, those that di ssolve in water and those that do not. Natural strontium is not ra dioactive and exists in four stab le types (or isotopes), each of which can be written as 84 

### Sr, 86 

### Sr, 87 

### Sr, and 88 

### Sr, and read as strontiu m eighty-four, strontium eighty-six, etc. All four isotope s behave the same chemically, so any combination of the four would have the same chemical effect on your body.
Rocks, soil, dust, coal, oil, surface and undergrou nd water, air, plants, and animals all contain varying amounts of strontium. Typical concentr ations in most materials are a few parts per million (ppm). Strontium ore is found in nature as the minerals celestite (SrSO 4 

### ) and strontianite (SrCO 3 

### ). After the strontium is extracted from str ontium ore, it is concentrated into strontium carbonate or other chemical forms by a series of chemical processes. Strontium compounds, such as strontium carbonate, are used in making ceramics and glass products, pyrotechnics, paint pigments, fluorescent lights, medicines, and other products. For more information, see Chapter 5.
Strontium can also exist as radioactive isotopes (see Chapter 4). 90 

### Sr, or strontium ninety, is the most hazardous of the radioactive isotope s of the chemical element strontium. 90 

### Sr is formed in nuclear reactors or during the explosion of nuclear weapons. Each radioactive element, including strontium, constantly gives off radiatio n, and this process changes it into an isotope of another element or a different isotope of the same element. This process is called radioactive decay. 90 

### Sr gives off beta particles (sometimes refe rred to as beta radia tion) and turns into yttrium ninety ( 90 

### Y); 90 

### Y is also radioactive and gives off radiation to form zirconium ninety ( 90 

### Zr), which is a stable isotope. The radioactive half-life is the time that it takes for half of a radioactive strontium isotope to give off its radiation and change into a different element. 90 

### Sr has a half-life of 29 years.3 STRONTIUM 1. PUBLIC HEALTH STATEMENT

90 

### Sr has limited use and is considered a wa ste product. The radioactive isotope 89 

### Sr is used as a cancer therapeutic to alleviate bone pain. 85 

### Sr has also been used in medical applications. For more information about the properties and use of radioactive strontium, see Chapters 4 and 5.
Quantities of radioactive strontium, as well as ot her radioactive elements, are measured in units of mass (grams) or radioactivity (curies or becquerels). Both the curie (Ci) and the becquerel (Bq) tell us how much a radioa ctive material decays every se cond. The becquerel is a new international unit known as the SI unit, and the curie is an older unit; both are used currently. A becquerel is the amount of radi oactive material in which 1 at om transforms every second. One curie is the amount of radioactive materi al in which 37 billion atoms transform every second; this is approximately th e radioactivity of 1 gram of radium. For more information on radiation, see Appendix D and the glossary, Chap ter 10, at the end of this profile or the ATSDR Toxicological Profile for Ionizing Radiation.

1.2 WHAT HAPPENS TO STRONTIUM WHEN IT ENTERS THE ENVIRONMENT?
Stable and radioactive strontium compounds in th e air are present as du st. Emissions from burning coal and oil increase stable strontium levels in air. The average amount of strontium that has been measured in air from different parts of the United States is 20 nanograms per cubic meter (a nanogram is a trillion times smaller than a gram). Most of the strontium in air is in the form of stable strontium. Very small dust partic les of stable and radioact ive strontium in the air fall out of the air onto surface wate r, plant surfaces, and soil either by themselves or when rain or snow falls. These particles of strontium eventually end up back in the soil or in the bottoms of lakes, rivers, and ponds, where they stay and mix with stable and radioact ive strontium that is already there.

In water, most forms of stable and radioactive st rontium are dissolved. Stable strontium that is dissolved in water comes from strontium in ro cks and soil that water runs over and through. Only a very small part of the strontium found in water is from the settling of strontium dust out of the air. Some strontium is suspended in wa ter. Typically, the amount of strontium that has been measured in drinking water in different pa rts of the United States by the EPA is less than4 STRONTIUM 1. PUBLIC HEALTH STATEMENT 

### 1 milligram for every liter of water (1 mg/L). 90 

### Sr in water comes primarily from the settling of
90 

### Sr dust out of the air. Some 90 

### Sr is suspended in water. In general, the amount of 90 

### Sr that has been measured in drinking water in different parts of the United States by EPA is less than one-tenth of a picocurie for every liter of water (0.1 pCi/L or 0.004 Bq/L).
Strontium is found naturally in soil in amounts th at vary over a wide range, but the typical concentration is 0.2 milligrams per kilogram (kg) of soil (or 0.2 mg/kg). The disposal of coal ash, incinerator ash, and industrial wastes may incr ease the concentration of strontium in soil. Generally, the amount of 90 

### Sr in soil is very small and is onl y a fraction of the total concentration of strontium in soil. Higher concentrations of 90 

### Sr in soil may be found near hazardous waste sites, radioactive waste sites, and Department of Energy faci lities located around the United States. A major portion of stable and radioactive strontium in so il dissolves in water, so it is likely to move deeper into the ground and en ter groundwater. Howeve r, strontium compounds may stay in the soil for years without moving downward into groundwater. In the environment, chemical reactions can change the water-solu ble stable and radioactive strontium compounds into insoluble forms. In some cases, water-inso luble strontium compounds can change to soluble forms. For more information about the transport properties of stable and radioactive strontium in the environment, see Chapter 6.

1.3 HOW MIGHT I BE EXPOSED TO STRONTIUM?
Strontium is found nearly everywhere in small am ounts, and you can be exposed to low levels of strontium by breathing air, eating food, drinking water, or accidenta lly eating soil or dust that contains strontium. Food and drinking water are the largest sources of ex posure to strontium. Because of the nature of strontium, some of it gets into fish, vegetables, and livestock. Grain, leafy vegetables, and dairy products contribute the greatest percen tage of dietary strontium to humans. The concentration of strontium in l eafy vegetables, such as cabbage, grown in the United States is less than 64 mg in a kg of the fr esh vegetables (i.e., 64 pp m). For most people, the intake of strontium will be moderate. More information about strontium exposure can be found in Chapter 6.5 STRONTIUM 1. PUBLIC HEALTH STATEMENT

90 

### Sr is found nearly everywhere in small amounts from past nuclear accidents and fallout from nuclear explosions. You can be exposed to low levels of 90 

### Sr by eating food, drinking water, or accidentally eating soil or dust that contains 90 

### Sr. Food and drinking water are the largest sources of exposure to 90 

### Sr. Because of the nature of 90 

### Sr, some of it gets in to fish, vegetables, and livestock. Grain, leafy vegetables, and dairy products contribute the greatest percentage of dietary 90 

### Sr to humans. The concentration of 90 

### Sr in fresh vegetables grown in the United States is less than 9 pCi (or 0.3 Bq) in 1 kg of drie d vegetables (in a hot oven). The intake of radioactive strontium for most people will be small. You can take in more 90 

### Sr if you eat food that was grown on a radioactive strontium-contaminated hazardous waste site. More information about radioactive strontium expos ure can be found in Chapter 6.

1.4 HOW CAN STRONTIUM ENTER AND LEAVE MY BODY?

Both stable strontium and radi oactive strontium enter and leav e the body in the same way.
If a person breathes in vapors or dust containing a chemical form of strontium that is soluble in water, then the chemical will dissolve in the moist surface inside the lungs and strontium will enter the bloodstream relatively quickly. If the chemical form of stront ium does not dissolve in water easily, then particles may remain in the lu ng for a time. When you eat food or drink water that contains strontium, only a small portion l eaves the intestines and enters the bloodstream. Studies in animals suggest that infants may abso rb more strontium from the intestines than adults. If a fluid mixture of a strontium salt is placed on the skin, the strontium will pass through the skin very slowly and then enter the bloodstream. If the skin has scratches or cuts, strontium will pass through the skin much more quickly.

Once strontium enters the bloodstream, it is di stributed throughout the body, where it can enter and leave cells quite easily. In the body, strontium behaves ve ry much like calcium. A large portion of the strontium will accumulate in bone. In adults, strontium mo stly attaches to the surfaces of bones. In children, whose bones ar e still growing, strontium may be used by the body to create the hard bone mineral itself. As a result the strontium will be stored in the bone for a long time (years). Because of the way bone grows, strontium will be locally dissolved from6 STRONTIUM 1. PUBLIC HEALTH STATEMENT 

### bone and recirculate through the bloodstream, wher e it may be reused by growing bone, or be eliminated. This process accounts for the slow removal of strontium from the body.
Strontium is eliminated from the body through urine, feces, and sweat. Elimination through urine may occur over long periods, when small amounts of strontium are released from bone and do not get recaptured by bone. When strontium is taken in by mouth, the portion that does not pass through the intestinal wall to enter the bl oodstream is eliminated through feces during the first day or so after exposure.
See Chapter 3 for further information.

1.5 HOW CAN STRONTIUM AFFECT MY HEALTH?
To protect the public from the harmful effects of toxic chemicals and to fi nd ways to treat people who have been harmed, scientists use many tests.
One way to see if a chemical will hurt people is to learn how the chemical is absorbed, used, and released by the body. In the case of a radioactive chem ical, it is also im portant to gather information concerning the radiation dose and do se 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. W ithout laboratory animals, scientis ts 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 co mpassion. Laws today protect the welfare of research animals, a nd scientists must comply with strict animal care guidelines.

There are no harmful effects of stable strontium in humans at the levels typically found in the environment. The only chemical form of stable strontium that is very harmful by inhalation is strontium chromate, but this is because of toxi c chromium and not stro ntium itself. Problems with bone growth may occur in children eating or drinking unusually high levels of strontium, especially if the diet is low in calcium and pr otein. Ordinary strontiu m salts are not harmful when inhaled or placed on the skin.7 STRONTIUM 1. PUBLIC HEALTH STATEMENT



### Animal studies showed that eating or drinking ve ry large amounts of stable strontium can be lethal, but the public is not likely to encounter such high levels of strontium. In these unusually high amounts, so much strontium was taken into bone instead of calci um that growing bones were weakened. Strontium had more severe effects on bone growth in young animals than in adults.

It is not known whether stable strontium affects reproduction in pe ople. The effect of stable strontium on reproduction in animals is not known. The Department of Health and Human Services has determined that strontium chromate is expected to be a carcinogen, but this is because of chromium. There is no information th at any other form of stable strontium causes cancer in humans or animals.

The harmful effects of radioactive strontium are caused by the high energy effects of radiation. Since radioactive strontium is taken up into bone, bone itself and the soft tissues nearby may be damaged by radiation released ove r time. Because bone marrow is the essential source of blood cells, blood cell counts may be reduced if the dose is too high. Th is has been seen in humans who received injections of radioactive strontium ( 89 

### Sr) to destroy cancer tissu e that had spread to the bone marrow. Lowered blood cell counts were also seen in animals that breathed or swallowed radioactive strontium. Numerous problems occur when the number of blood cells is too low. A loss of red blood cells, anemia, prevents the body from getting sufficient oxygen, resulting in tiredness. A loss of platelets may prevent the blood from clotting properly, and may result in abnormal bleeding, especially in the intestines. A loss in white blood cells harms the body’s ability to fight infectious disease.
Radiation damage may also occur from exposure to the skin. Medicall y, radioactive strontium probes have been used intentionally to destroy un wanted tissue on the surface of the eye or skin. The eye tissues sometimes become inflamed or abnormally thin after a long time. Thinning of the lower layer of the skin (dermis) has also been reported in animal studies as a delayed effect.8 STRONTIUM 1. PUBLIC HEALTH STATEMENT 

### It is not known whether exposure to radioac tive strontium would affect human reproduction. Harmful effects on animal reproduc tion occurred at doses that we re more than a million times higher than typical exposure leve ls for the general population.
Radioactive strontium may cause ca ncer as a result of damage to the genetic material (DNA) in cells. An increase in leukemia over time was re ported in individuals in one foreign population who swallowed relatively large amounts of 90 

### Sr (and other radioactive ma terials) in river water contaminated by a nuclear weapons plant. Cancer s of the bone, nose, and lung (in the case of a breathing exposure), and leukemia we re reported in animal studies . In addition, skin and bone cancer were reported in animals that received radiation at high doses to the skin. The International Agency for Research on Cancer (I ARC) has determined that radioactive strontium is carcinogenic to humans, because it is deposited inside the body and emits beta radiation. The EPA has determined that radioactiv e strontium is a human carcinogen.

To learn more about the health effects of exposure to stable or radioactive strontium, see Chapter 3.

1.6 HOW CAN STRONT IUM AFFECT CHILDREN?
This section discusses po tential health effects from exposur es during the period from conception to maturity at 18 years of age in humans.
Children are exposed to stable strontium in the same manner as adults: usually in small amounts in drinking water and food. Young children who have more hand-to-mouth activity or who eat soil may accidentally eat more strontium. Infa nts and children with active bone growth absorb more strontium from the gut than adults.
Excess stable strontium causes pr oblems with growing bone. For this reason, children are more susceptible to the effects of stable strontium than adults who have mature bone. Children who eat or drink unusually high levels of stable st rontium may have problems with bone growth, but only if the diet is low in calciumand protein. Children who drink milk, especially milk fortified9 STRONTIUM 1. PUBLIC HEALTH STATEMENT 

### with vitamin D, are not likely to have bone problem s from exposure to exce ss stable strontium. The amount of stable strontium that is usually ta ken in from food or wate r or by breathing is too low to cause bone problems in children. No developmental studies in humans or animals examined the effect on the fetus when the mother takes in excess strontium. However, no problems are expected with fetal bone growth because only small amounts of strontium are transferred from the mother across the placenta to the fetus. Evidence suggests that stable strontium can be transferred from the mother to nursing infants through breast milk, but the presence of calcium and protein in milk protects against bone problems during nursing.
Children take in, use, and get rid of radioactive st rontium in the same ways as stable strontium. Children are likely to be more vulnerable than ad ults to the effects of radioactive strontium because relatively more goes into bone when it is growing. Also, children are potentially more vulnerable than adults to radiation damage because they keep radioactive strontium in bone for a longer time.
Children would be expected to have the same types of effects from exposure to radioactive strontium as exposed adults. Children can be exposed to radioactive strontium at levels higher than background without showing increases in cancer rates. Evidence from one foreign population showed that children w ho drank water containing unusually high levels of radioactive strontium for 7 years showed an in crease in leukemia. High levels of radioactive strontium cause more bone damage and higher bone cancer rates when animals are exposed before birth or as juveniles rather than as adults. In humans and animals, radioactive strontium can be transferred into milk or across the placenta into the fetus.

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPO SURE TO STRONTIUM?
If your doctor finds that you have been exposed to significant amounts of strontium, ask whether your children might also be exposed. Your doctor might need to ask your state health department to investigate. Public health o fficials may publish guideli nes for reducing exposure to strontium when necessary.10 STRONTIUM 1. PUBLIC HEALTH STATEMENT 

### It is possible that higher-than-nor mal levels of stable strontium may occur naturally in soil in some places or that higher levels of radioactive strontium may be found in soil near hazardous waste sites. Some children eat a lot of dirt. You should preven t your children from eating dirt. Make sure they wash their hands frequently, an d before eating. If you live near a hazardous waste site, discourage your children from putting their hands in their mouths or from engaging in other hand-to-mouth activities.

Since strontium is so common in the environment, and is naturally present in food and water, we cannot avoid being exposed to it. For several re asons, having a balanced diet with sufficient vitamin D, calcium, and protein will be protectiv e by reducing the amount of ingested strontium that is absorbed.

1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO STRONTIUM?
All people have small amounts of stable strontium in their bodies, mostly in bone. It can be measured in the blood, hair, feces, or urine. The amount is usually measured by its mass (grams). Measurements in urine can show whet her you have been exposed recently to largerthan-normal amounts of strontium. Measurements in hair can reveal whether you were exposed to high amounts of strontium in the past. Most physicians do not test for strontium in their offices, but can collect samples and send them to a special laboratory. X-rays can show changes in bone that may occur from exposure to high am ounts of strontium, but these changes may have other causes (a diet low in vitamin D or a high exposure to some other trace metal).
If a person has been exposed to radioactive stro ntium, special tests can be used to measure radioactive strontium in blood, feces, or urine. These tests are most useful when done soon after exposure, since radioactive strontium quickly en ters into bone and takes many years to be completely removed from bone. Radioactive str ontium can be measured by its mass (in grams) or by its radiation emissions. These emissi ons, which differ for the various isotopes of strontium, are used to tell the amount of radio active strontium (in curies or bequerels) and the radiation dose that it gives to your body (in sieverts or rem). In a procedure that is similar to11 STRONTIUM 1. PUBLIC HEALTH STATEMENT 

### being x-rayed, specialized equipment can meas ure radioactive strontium that has been incorporated into bone.
For more information, please read Chapters 3 and 7.

1.9 WHAT RECOMMENDATIONS HAS TH E FEDERAL GOVERNMENT MADE TO PROTECT HUMAN HEALTH?
The federal government develops regulations a nd recommendations to pr otect public health. Regulations can be enforced by law. Federal agencies that develop regulations for toxic substances include the Environmental Protecti on Agency (EPA), the Occupational Safety and Health Administration (OSHA), the Food and Dr ug Administration (FDA), and the U.S. Nuclear Regulatory Commi ssion (USNRC).
Recommendations provide valuable guidelines to protect public hea lth but cannot be enforced by law. Federal organizations that develop reco mmendations 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; they are then 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 str ontium include the following:
EPA recommends that drinking water levels of stable strontium should not be more than 4 milligrams per liter of water (4 mg/L).12 STRONTIUM 1. PUBLIC HEALTH STATEMENT



### The Department of Energy (DOE) established de rived air concentrations (DAC) for workplace exposure to radiation at DOE facilities. The DAC range s from 0.000000002 microcuries per milliliter (μCi/mL) (2x10 -9 

### μCi/mL of air = 70 μBq/mL of air) for radioactive particles remaining in the lung for 100 days to 0.000000008 μCi/mL (8x10 -9 

### μCi/mL of air = 300 μBq/mL of air) for radioactive particles re maining in the lung for less than 10 days. The USNRC established an annual intake limit of 20 μCi (7 MBq) for on-the-job exposure to 90 

### Sr in air.

EPA set standards for the concentration of 90 

### Sr in community water supplies. The average annual concentration of 90 

### Sr in water supplies should not exc eed 8 pCi/L (0.3 Bq/L). EPA also established maximum contaminant levels (MCLs) in drinking water for radionuclide activities to protect against harmful effects of 90 

### Sr. For beta particles like strontium, the MCL is 4 mrem per year (4x10 -5 

### Sv per year). The USNRC set a wor kplace value of 31 μCi (1.1 MBq) for the amount of 90 

### Sr that can be taken in by mouth in a year without any harmful effects.
More information on regulations and gui delines is available in Chapter 8.

1.10 WHERE CAN I GE T MORE INFORMATION?
If you have any more questions or concerns, plea se contact your community or state health or environmental quality department, your regional Nuclear Regulatory Commission office, or contact ATSDR at the addre ss and phone number below.
ATSDR can also tell you the location of occupati onal and environmental health clinics. These clinics specialize in recognizing, evaluating, and treating illnesses resulting from exposure to hazardous substances.
Toxicological profiles are al so available on-line at www.atsdr.cdc.gov and on CD-ROM. You may request a copy of the ATSDR ToxProf iles 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:13 STRONTIUM 1. PUBLIC HEALTH STATEMENT



### 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 For-profit organizations may request a c opy 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/15 STRONTIUM



### 2. RELEVANCE TO PUBLIC HEALTH

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO STRONTIUM IN THE UNITED STATES

Stable Strontium. Elemental strontium (atomic number 38) occurs naturally in the earth's mantle as a mixture of four stable isotopes, 88 Sr, 86 Sr, 87 Sr, and 84 Sr, and is present everywhere in very dilute concentrations. It is very similar to calcium in its environmental and physiological behavior. Strontium is generally found in molecular compounds with ot her elements. Commercially important strontium minerals include celestite (SrSO 4 ) and strontianite (SrCO 3 ). Strontium is used in the manufacture of ceramics and glass products, primarily in the faceplate glass of televisions and other cathode-ray-tube devices, where it serves to block x-ray emissions.
The general population is exposed to stable strontium primarily by ingestion of food and water, and to a lesser degree, by inhalation. The st rontium content in air averages 20 ng/m 3 , with higher concentrations resulting from stack emissions from coal-burning plants. S trontium is present in nearly all fresh waters in amounts generally ranging between 0.5 and 1.5 mg/L , with higher levels occurring where there are celestite-rich limestone deposits. The average concentra tion of stable strontium in soil is approximately 240 mg Sr/kg, but agricultural soils may be treated with phosphate fertilizer or limestone, which contain ~610 mg Sr/kg. Because strontium is chemically simi lar to calcium, it is taken up from the soil by fruits and vegetables. The average concentration of strontium in fruit produce ranged from 0.0416 to 2.232 μg/L. The total estimated daily exposure to stable strontium is approximately 3.3 mg/day (0.046 mg/kg/day): 400 ng/day from inhalation, 2 mg /day from drinking water, and 1.3 mg/day from the diet (see Chapter 6). Assuming a reference body weight of 70 kg, the typical daily strontium exposure is 46 μg/kg body weight. The strontium content of the human body is approximately 4.6 ppm by weight, 99% of which is localized in bones and teeth. Blood concentrations of strontium are in the range of 20–31 μg/L.

Radioactive Strontium. The radioactive isotopes of strontium do not occur naturally but are produced as a by-product of nuclear fission of 235 U, 238 U, or 239 Pu. The most significant isotopes are 90 Sr (half-life of 29 years), 89 Sr (half-life of 51 days), and 85 Sr (half-life of 65 days), which decay by the emission of beta particl es. 90 Sr is currently found in spent fuel rods in nucl ear reactors and is considered a waste product. Other radioactive strontium isotopes have been employed for medical uses: 89 Sr (as MetastronTM) as a cancer therapeutic for the relief of bone pain and 85 Sr in the radiologic imaging of bone. 85 Sr also has16 STRONTIUM 2. RELEVANCE TO PUBLIC HEALTH minor commercial applications in thermoelectric power generation, as a beta partic le standard source, and in instruments that measure the thickness and density of materials

. Disposal and handling of radioactive strontium isotopes are regulated by the U.S. Nuclear Regulatory Commission.
The general population is exposed to very small amounts of radioactive strontium from the ingestion of contaminated water and food; inhalation exposure is negligible. The average concentration of 90 Sr in drinking water in 1994 was estimated as 0.1 pCi/L; af ter 1994, estimates were based on gross beta activity and not reported by individual elements since the amounts were so small. Fresh vegetables contribute more than one third of the yearly dietary intake of 90 Sr, followed by grains and dairy products. The current total daily exposure levels to radioactive str ontium are estimated to be approximately 5.2 pCi/day (0.16 Bq/day; 0.074 pCi/kg/day): 5 pCi/day fr om food and 0.2 pCi/day from drinking water.
See Chapter 6 for more detailed info rmation regarding concentrations of stable and radioactive strontium in environmental media.

2.2 SUMMARY OF HEALTH EFFECTS

Stable Strontium. There is no direct evidence that stable strontium is toxic to humans under normal environmental exposures. The primary toxicological effect of absorbed excess strontium in laboratory animals is abnormal skeletal development (rickets), whic h occurs only at relatively high oral doses. The inhalation toxicity of pure stable strontium has not been evaluated. At levels normally encountered in the environment, strontium appears to have low toxicity to adults or to juveniles with adequate nutrition. Juveniles, especially those with poor nutrition, are vulnerable because strontium, as an imperfect surrogate for calcium, interferes with bone mineraliza tion in the developing skeleton. The data for adverse health effects of stable strontium in humans are sparse, but indicate a possibility of skeletal effects under special circumstances: an epidemiologi cal study of strontium-related rickets in Turkish children and a few studies of hemodialysis patients who developed osteomalacia because of strontium in dialysis water. Numerous animal studies demonstrated adverse effects on skeletal development in juveniles following ingestion of excess stable stron tium (discussed below under Skeletal Effects). No developmental or reproductive studies have been c onducted involving exposure to stable strontium during gestation. No studies examined whether stable str ontium is carcinogenic to humans or animals. One strontium compound, strontium chromate, is a genotox ic human carcinogen by the inhalation route, but the hazard is caused by hexavalent chromium and not strontium.17 STRONTIUM 2. RELEVANCE TO PUBLIC HEALTH Other effects have been observed sporadically and are of unclear physiological significance. Paralysis of the hindlimbs was observed in orally-exposed rats, but it is uncertain whether the cause was neurophysiological or the result of local neuronal dama ge secondary to deformation of the femora. Minor unspecified changes in hepatic histology and glycogen content were observed in orally-exposed rats. The following section discusses effects in the primary target of stable strontium, the skeleton, in greater detail.

Skeletal Effects. Although strontium, as a molecular surrogate for calcium, can be distributed throughout the body, its main target for deposition is the skeleton. On e suggestive epidemiological study found that increased strontium ingestion contributed to an increase in the prevalence of signs of rickets (craniomalacia, rachitic rosary, bulging at the wrist, bony deformities of the leg, and delayed closure of the fontanelles) in children in a region of Turke y. A significantly increased incidence of rickets was associated with a diet restricted to water and cereals grown locally in soils with strontium concentrations in excess of 350 mg/kg. Other contributing factors included probable deficiencies in vitamin D, protein, and calcium after weaning; breast feeding for >2 years appeared to be a protective factor against the development of rickets in this population. The only reports of strontium-related skeletal problems in adults concerned osteomalacia in hemodialysis patients exposed to strontium in dialysis wate r. D ialysis patients may be unusually susceptible because of their im paired handling of strontium. Stable strontium compounds have been used for the treatme nt of osteoporosis (see Section 2.3).

Anim al studies strongly support the identification of bone as the most sensitive target of strontium toxicity. Relatively high doses of strontium ( ≥ 500 mg/kg/day) caused a reduction in bone mineralization (ash weight) and an alteration in the chemical co mposition of organic bone matrix. In addition, the hypertrophic zones of the epiphyseal growth plat es of long bones became abnormally deep and wide, as calcification failed to occur. Severe weakening of the bones resulted from rickets, in which the skeleton could not support the body adequately; deformity of the head of the femur may have contributed to paralysis of the hind limbs in some cases. Young animals were more sensitive to the effect of excess strontium than older animals, possibly because the ab sorption and retention of strontium were higher in the young. In addition, inadequate calcium and vita min D in the diet increased the severity of skeletal effects. The chemical form of strontium may influen ce toxicity by affecting gast rointestinal absorption. One intermediate oral animal study that tested st rontium phosphat e re ported a much higher no-effect level than studies that tested strontium chloride or carbonate. However, cation effects on strontium toxicity have not been studied systematically.18 STRONTIUM 2. RELEVANCE TO PUBLIC HEALTH
Evidence from the few human studies and numerous anim al toxicity studies suggest that healthy adults living near hazardous waste sites are unlikely to be expo sed to levels of stable strontium sufficiently high to cause adverse skeletal effects. Children living in areas where the soil and drinking water contain relatively high amounts of strontium may be vulnerable to skeletal effects if their nutritional status is poor (deficient in calcium, vitamin D, and/or protein) and if the diet is restricted to foods grown locally. All these conditions are not likely to be common in the United States, since the food supply generally comes from a wide geographic area.

Radioactive Strontium. Exposure to radioactive strontium can re sult in health consequences that vary depending on the dose, the route of exposure, and the chemical form. Both 90 Sr and 89 Sr emit beta particles, which, in tissue, may ionize cellular mo lecules within a range of 1 cm, resulting in tissue damage and disruption of cellular function if the capac ity of natural repair mechanisms is exceeded. Adverse health effects occur at high levels of exposure that significantly exceed background levels encountered by the general population. It should be noted that no discernable adverse health effects were detected in the general population from chronic low-level exposure to 90 Sr in fallout during the period of aboveground weapons testing.

90 Sr represents the most significant isotope of concern because of its relatively long half-life (29 years) and because of the bone-seeking properties of strontium. The most serious effects of oral exposure to absorbed radioactive strontium are necrotic lesions and cancers of bone and the adjacent tissues. High level acute exposures can destroy hematopoietic bone marrow, leading to acute radiation syndrome (see below), the primary cause of mortality in the short term . At lower doses, irradiation of bone marrow may lead to chronic suppression of immune function.
The consequences of inhalation exposures in animals vary depending on the solu bility of the form of radiostrontium. Insoluble particles tend to be retain ed in the lung, resulting in pneumonitis; necrosis of the pulmonary, vascular, and adjacent myocardial tissu es; pulmonary fibrosis; a nd, later, pulmonary and vascular cancers. Inhalation of soluble radiostr ontium does not have these local effects because the material is absorbed and distributed in the skeleton. The effects of inhalation of soluble strontium are, therefore, similar to those described for the oral rout e: acute radiation syndrome and other hematopoietic effects, osteosarcoma, and immunosuppression.
External exposure to solid strontium sources placed near the skin or eye can cause local lesions when doses are significantly higher than background. E ffects observed in clinical studies on the eye included19 STRONTIUM 2. RELEVANCE TO PUBLIC HEALTH keratitis or scarring of the cornea, telangiectasis or scarring of the conjunctiva, iritis, conjunctivitis, mild irritation, and scleral thinning. Dermal effects in clinical studies range from erythema and pigmentation changes, dry and moist desquamation (which involv es destruction of the basal epithelial cells), and telangiectasis and increased vascular permeability, to l ong-term responses such as epithelial and dermal hyperplasia, chronic fibrosis, and dermal atrophy.

There is inconclusive evid ence in humans and definiti ve evidence in laboratory animals that exposure to radioactive strontium at very high doses in utero can lead to adverse developmental effects. Slight increases in developmental effects were noted in a po pulation of the former Soviet Union whose drinking water (the Techa River) was contaminated with multiple radioactive elements released from a plutonium production plant between 1949 and 1956

. These effects included slight increases in child mortality from chromosomal defects and from congenital anomalies of the nervous system, circulatory system, and other unspecified anomalies in the progeny of exposed i ndividuals. However, the specific contribution of radiostrontium to these effects is not known. Devel opmental effects in laboratory animals were noted at extremely high doses, as if, on a kilogram body weight basis, individual pregnant females were receiving daily the entire amount of 90 Sr currently released from one nuclear power plant into the environment during a year (see Table 6-1). There is evidence that maternal oral exposure to radioactive strontium can lead to reduced fetal and postnatal survival in the offspring, but there is no evidence for birth defect s. At the very highest doses of radioactive strontium inject ed into pregnant females, the offpsring exhibit increases in birth defects (skeletal anomalies and pa rtial atelectasis of the lungs), and cancers of soft tissues near bone (meningeal and pituitary tumors), as well as hyperplasia of lymph nodes and spleen and deficient hematopoiesis. Exposure to radioactive str ontium in milk from dams injected at very high doses reduces the numbers of early-stage oocytes in the ovary of neonatal mice, but the effect is less severe than when offspring are exposed only in utero

.

There is no evidence in humans that rad ioactive strontium leads to re productive effects, but there is some evidence in laboratory animals. Although the Techa River populations received the highest known extended oral exposure to radioactive strontium (and other radionuclides) of any human group, there were no significant effects on reproductive parameters (birth rate, fertility, incidence of spontaneous abortion)

. An increase in fetal deaths was noted in some studies in rats, but no reproductive effects were noted in larger laboratory animals at equivalent oral doses

. This difference appears to be related to the fact that in small animals, the bone marrow cavity diameters are not wide enough to leave the central hematopoetic tissues untouched by beta-irradiation emitted by radio active strontium bound to bone. Exposure to high20 STRONTIUM 2. RELEVANCE TO PUBLIC HEALTH doses of radioactive strontium by injection led to significant reproductive effects (reduced fertility, reduced gonadal cellularity, suppressed spermatocyte maturation) in mice.

Other effects of radioactive strontium have been observed sporadically in animal studies and are of unclear physiological significance. Anorexia, reduced body weight, and liver effects that were possibly secondary to radiation pneumonitis (c hronic passive congestion of the liv er and mild centrilobular hepatic fibrosis) were observed in beagles following a single inhalation exposure of insoluble 90 Sr particles at an initial lung burden of 25 : Ci/kg.
The populations potentially most sensitive to radiostrontium exposure include th e young and individuals that have poor nutrition or deficiencies in vitamin D. Infants and children are more vulnerable than adults because they absorb strontium through the gastrointestinal tract at slight ly higher rates and because they have actively growing bones that incorporate more strontium than mature bones. Very high prenatal exposure levels may cause major deve lopmental anomalies in the skeleton and adjacent areas if critical tissues are destroyed. In addition, since children have a higher proportion of mitotic cells than adults, their rates of genotoxic damage are higher. This is because genetic lesions become fixed mutations when mitosis occurs before genetic damage is repaired. Genetic lesions in genes controlling the cell cycle can lead to the development of cancer and may be the b asis of excess cancer cases attributed to exposure to radioactive strontium. Individuals with poor nutriti on or deficiencies in vitamin D, such as those with osteomalacia, are theoretically more vulnerable to ra dioactive strontium because their lower absorption of calcium results in relatively higher rates of str ontium incorporation into bone during the remodeling process that continues throughout life. The level of incorporation of radiostrontium into bone can be somewhat reduced by ingestion of alginates soon afte r exposure. Removal from bone after incorporation is not feasible.
The major adverse effects of exposure to radioactiv e strontium, non-cancerous lesions of hematopoietic bone marrow tissue, cancer, and dystrophic lesions of th e skeleton, are discussed below in greater detail. It should be noted that the large animal studies are more relevant than rodent studies to humans because the severity of bone marrow effects is inversely proportional to the diameter of the bone marrow cavity.

Non-Cance rous Bone Marrow Effects (Including Acute Radiation Syndrome). Bone marrow effects are the most serious immediate conseq uences of exposure to high levels of radioactive strontium by either the inhalation or oral route

. When absorbed radioactive strontium incorporates into bone, irradiation of the bone marrow results in hypo plasia of the hemopoietic tissue and pancytopenia,21 STRONTIUM 2. RELEVANCE TO PUBLIC HEALTH with the severity depending on the dose. At the highest doses, acute radiation syndrome (anorexia, bloody diarrhea) would be expected because of the virtual destruction of the bone marrow. Acute radiation syndrome was not observed in the orally-exposed Techa River population, but was observed in dogs several weeks after receiving long-term retained body burdens of ≥ 47 : Ci 90 Sr/kg ( ≥ 1.74 MBq/kg) following a single exposure to soluble 90 SrCl 2 by inhalation. Hemorrhaging is caused by the drastic depression in platelet counts; a severe drop in ne utrophil counts precedes death. At lower exposure levels, pancytopenia is detectable, but is not immediatel y life-threatening. This was observed in dogs that received long-term retained burdens >10 : Ci 90 Sr/kg (>0.37 MBq/kg) following a single inhalation exposure of soluble 90 SrCl 2
At lower levels of exposure, not all types of hema topoietic cells within bone marrow are affected, possibly because of differences in intrinsic rates of replacement. In the orally-exposed Techa River populations, milder chronic effects of bone marrow irra diation were reported in a small percentage of exposed individuals: leukopenia, thrombocytopeni a, and granulocytopenia, as well as lymphopenia involving T lymphocytes and large granulocytic lymphocytes. Reduced lymphocyte counts, indicators of weakened immune function, in some individuals wh o received radiation to the bone marrow in excess of 30 rem (0.3 Sv) per year, were implicated as the cause of the higher incidences of infectious disease in those who developed radiation-induced cancers. Suppression of the immune system is also supported by studies in pigs exposed to 625 : Ci 90 Sr/day (23.13 MBq/day) in feed fo r 4–9 months or in dogs receiving single inhalation exposures of soluble (long-term retained burden >10 : Ci 90 Sr/kg [>370 kBq/kg]) or insoluble (initial lung burden ≥ 5 : Ci 90 Sr/kg [ ≥ 185 kBq/kg]) radioactive strontium. mice indicate that natural killer cells were prefer entially eliminated. Chronic myeloid metaplasia, possibly related to genotoxicity, was another effect of bone marrow irradiation in orally-exposed pigs that received cumulative doses in excess of 40 rad (0.4 Gy) a nd in a small percentage of dogs that received ≥ 0.4 : Ci 90 Sr/kg/day (44.4 kBq/kg/day) from mid-gestation to 1.5 years. Injection studies in

Cancer. Radioactive strontium, like other radionu clid es, is a genotoxic carcinogen. Mutations in genes controlling the cell cycle can lead to cancer if the damage is not repaired before the next cell division; rapidly dividing cells, such as the hematopoie tic cells in bone marrow, are especially vulnerable. Incorporation of radioactive strontium into bone places bone and the adjacent soft tissues at risk for cancer. Chronic consumption of radioactive stron tium (and other radionuclides), leading to estimated doses to bone marrow in excess of 10 rem (0.1 Sv), si gnificantly increased the incidence of leukemia in the Techa River population, but this effect was not observed in offspring exposed in utero who received lower doses. Leukemia has also been observed in an imals exposed orally or by inhalation to soluble22 STRONTIUM 2. RELEVANCE TO PUBLIC HEALTH
radioactive strontium. Other cancers observe d in animal studies include osteosarcomas, hemangiosarcomas, cancers of other soft tissues n ear bone, and, in feeding studies, nasal, oral, and periodontal carcinomas. In dogs that inhaled insoluble 90 Sr, the particles lodged in the respiratory tract, causing cancers of the immediately surrounding tissu es: hemangiosarcomas of the lung and heart and carcinomas of the respiratory tract. External exposure to 90 Sr (solid source) in mice induced skin cancers (squamous cell carcinoma, basal cell carcinoma, fibrosarcoma) and, in one study, osteosarcomas. Immature organisms are potentially more vulnerable th an adults to radioactiv e strontium partly because they have a higher proporti on of cells in mitotic phase and partly because they incorporate relatively more radiostrontium into bone. In a multigenerational sw ine study, doses that were not carcinogenic in the females exposed as adults induced osteosarcomas in th e F1 or F2 generations exposed from conception

. National Council on Radiation Prot ection and Measurements concluded that uncertainties remain regarding extrapolation from the high doses of 90 Sr known to cause cancer in animals to the lower doses that might increase the incidence of leukemia in humans. The Council suggested that more basic knowledge on the mechanism of cancer induction by i onizing radiation would be required to understand the risk of internal exposure to 90 Sr. EPA has determined that radi oactive strontium is a known human carcinogen (Group A). EPA estimated that the risk of developing cancer following exposure to 8 pCi/L in drinking water is 1 in 100,000. The International Agency for Resea rch on Cancer has determined that internally deposited radionuclides, such as radioac tive strontium, are carcinogenic to humans (Group 1).

Skeletal Effects. Dyst rophic lesions of the skeleton occur when the level of oral exposure of soluble radioactive strontium is high enough that the amount inco rporated into bone results in irradiation of the bone at levels exceeding natural repa ir mechanisms. The effect could occur by acute exposure to a very high dose, by intermediate-duration exposure at a mo derate dose, or by chronic-duration exposure at a lower dose. Such lesions, primarily affecting articul ar and periarticular tissues, were reported in the Techa River populations that received mean radiation doses to the surface of bone in excess of 200 rem (2 Sv) following chronic oral exposure to radiostrontium, but not at the lower doses.
Animal oral exposure studies support the findings in humans . Skeletal or dental effects in adults are less severe than in developing animals because in adults, incorporation of radioactive strontium is mainly restricted to the surfaces of bone or teeth. Inco rporation throughout the de veloping bone renders it vulnerable to weakening as a result of focal necrosis from long-term irradiation. Intermediate-exposure at 6 μCi/kg/day for 1–10 months reduced numbers of osteocytes and damaged blood vessels in the bone of adult rabbits. More severe effects damaging the b one structure (necrosis of vasculature, impaired transformation into cortical bone, and fracturing) were observed in dogs exposed in utero and chronically23 STRONTIUM 2. RELEVANCE TO PUBLIC HEALTH into adulthood at 0.4 μCi/kg/day. Damage to developing teeth (disordered tooth structure and increased cell death of differentiating odontoblasts and pulp cells ) has been reported in rabbits following injection of a very high dose (600 μCi 90 Sr/kg), but effects were less severe in mature teeth.

2.3 MINIMAL RISK LEVELS

Inhalation MRLs

Stable Strontium. Data on the toxicity of inhaled stable str ontium are not suitable for derivation of an inhalation MRL: one case report of a woman exposed to an undetermined concentration of strontium mixed with other chemicals in smoke from an ignited flare (Federman and Sachter 1997).

Radioactive Strontium. The main sources on the toxicity of inha led radioactive strontium are two acuteduration studies in dogs reporting severe hematological and immunological effects following a single nose-only exposure to 90 Sr as fused clay particles for several minutes (Jones et al. 1976) or strontium chloride (Gillett et al. 1987a). Inhalation of 90 Sr fused-clay particles leading to initial lung burdens of 5 μCi 90 Sr/kg (185 kBq/kg) resulted in chronic signi ficant depression of lymphocyte counts and suppression of immune function (Jones et al. 1976). Chronic thrombocytopenia and neutropenia, which persisted for 1,000 days in dogs at all tested expos ure levels (long-term retain ed burdens at or above 1 μCi 90 Sr/kg; 0.04 MBq/kg), was observed in dogs exposed to soluble 90 SrCl 2 (Gillett et al. 1987a). These data were not considered adequate for deriva tion of an acute-duration inhalation MRL because the observed hematological and immunological effect s were considered severe adverse effects.

Oral MRLs

Stable Strontium.

• An MRL of 2.0 mg/kg/day has been derived for intermediate-duration oral exposure (15–364 days) to stable strontium and its compounds. The most consistent effects of oral exposure to ex cess stable strontium are rickets (impaired cartilage calcification) and osteomalacia (impaired bone minera lization), especially in the young. One Turkish epidemiological study provided indirect evidence th at excess oral exposure to strontium (in the presence of other predisposing factors) may contribute to the development of rickets in children (Ögzür et al. 1996). Overall, animal studies on strontium have concen trated on the evaluation of skeletal effects, with24 STRONTIUM 2. RELEVANCE TO PUBLIC HEALTH occasional consideration to body weight and serum chem istry. In young rodents, typical effects of excess strontium included an abnormal widening of the cartila ginous epiphyseal plates of the long bones, a lack of bone calcification, and abnormal deposition of unmi neralized bone matrix or osteoid (Johnson et al. 1968; Kshirsagar 1976; Marie and Hott 1986; Morohashi et al. 1994; Neufeld and Boskey 1994; Storey 1962). The skeletal effects of strontium are known to be related to its chemical similarity to calcium and its suppression of vitamin D metabolism and intestinal calcium absorption (Armbrecht et al. 1998). Effects are more severe in young rats than in adults b ecause the rate of skeletal incorporation of strontium is higher in young animals (see Section 3.5.2.2).
A lowest-observed-adverse-effect level (LOAEL) of 550 mg strontium/kg/day is identified for bone mineralization abnormalities in weanling rats that were exposed to dietary strontium carbonate for 20 days (Storey 1961). The epiphyseal plates of l ong bones were irregular and abnormally thick. Furthermore, areas of uncalcified bone matrix were deposited in the distal ends of the metaphyseal trabeculae and proximal end of the diaphyses. Irre gularities in the organization of the cells of the hypertrophic zone, in the pattern of calcification, a nd in the deposition of osteoi d were more conspicuous with increasing dose. In tibias, the dry weight, ash weight, ash percentage, and calcium in ash were significantly reduced with increased strontium intake. No effects on bone mineralization occurred in weanling rats ingesting 140 mg strontium/kg/day, the NOAEL for intemediate-duration exposure. In adult rats examined in this study, the effects of st rontium ingestion were less severe in that higher doses were required to produce the same effect. The no-e ffect level in adults was 690 mg strontium/kg/day, which was higher than the LOAEL for weanlings. In a dults, changes in tibial histology, such as abnormal thickening of the epiphyseal cartilages and abnormally widened metaphyseal osteoid seams, were noted at or above 1,370 mg strontium/kg/day. At 2,750 mg strontium/kg/day, osteoid tissue was deposited near vascular canals and the areas of bone resorption were re duced. In adult rat tibias, the dry weight, ash weight, ash percentage, and calcium in ash were only significantly affected at the highest dose. This study demonstrates the difference in sensitivity to strontium between young and old animals, which is caused by the higher rate of strontium incorporation into the developing skeleton in young animals.
The critical dose levels identified in the Storey (1961) study are supported by other studies in rodents. Similar LOAELs (500–565 mg strontium/kg/day) fo r abnormal bone mineralization are identified in several studies on weanling rats exposed to str ontium carbonate (Morohashi et al. 1994; Neufeld and Boskey 1994) or an unspecified form of strontium (Johnson et al. 1968). Slight skeletal effects were noted in mice exposed to 350 mg strontium/kg/day as strontium chloride (Marie and Hott 1986). In addition, similar no-observed-adverse-effect levels (NOAELs) in the range of 110–168 mg25 STRONTIUM 2. RELEVANCE TO PUBLIC HEALTH strontium/kg/day for skeletal effects were identif ied from studies in weanling rats exposed to an unspecified form of strontium (Grynpas et al. 1996), strontium chloride hexahydrate (Kroes et al. 1977), or strontium carbonate (Morohashi et al. 1994). The study by Storey (1961) is preferred as the basis for the intermediate MRL because both young and adult an imals were tested, the administered doses included NOAELs and LOAELs for both age groups, and th e evaluation of skeletal effects included histopathological analysis. Some of the other studies have serious deficiencies that render them unsuitable for deriving an MRL. Two studies admini stered single doses of 166–168 mg/kg, but reported no adverse effects (Grynpas et al. 1996; Kroes et al. 1977); although the results support the NOAEL by Storey (1961), the lack of higher doses causing positive results raises uncertainty about the experiments. The study by Johnson et al. (1968) administered a single dose of 565 mg/kg that was a serious LOAEL for increased mortality. Three of the other studies ha d deficiencies that rendered them less suitable than Storey (1961). The study by Morohashi et al. (1994) did not analyze bone histopathology. Studies by Marie and Hott (1986) and Neufield and Boskey (1 994) administered single doses of 350 and 500 mg/kg, respectively, which were LOAELs for skeletal effe cts, but the studies provided no information on noeffect levels or effects at higher doses. Therefore, the NOAEL of 140 mg strontium/kg/day for skeletal effects in weanling rats (Storey 1961) would appear to be the most appropriate basis for calculating an intermediate MRL. The NOAEL of 140 mg strontium/ kg/day was divided by an uncertainty factor of 30 (10 for extrapolation from animal to human and 3 for human variability) and a modifying factor of 3 (for short study duration and limited end point examina tion). A partial uncertainty factor was used to account for human variability because the selected NOA EL was based on the response of juveniles, which is also the most sensitive human group. The resulting MRL is calculated to be 2.0 mg strontium/kg/day, which is approximately 40 times higher than the tota l estimated daily exposure to stable strontium of 0.047 mg/kg/day. The MRL represents an estimate of daily human exposure that is likely to be without an appreciable risk of adverse health effects. Since the MRL is based on effects in young rats, it is considered to be protective of children, who are simi lar with respect to immaturity of the skeleton and high intestinal rates of strontium absorption.

MRLs were not derived for acute- or chronic-duration oral exposures to stable strontium. The relevant acute data are limited to two lethality studies in mice (Ghosh et al. 1990; Llobet et al. 1991a) and two toxicity studies in rats (Kshirsagar 1976; Kroes et al. 1977). The rat studies were not considered suitable for MRL derivation. In the Kshirsagar (1976) study, the only administered dose, 3,000 mg strontium per kg/day as strontium phosphate, resulted in severe bod y weight effects (62% reduction in body weight gain) and was higher than the LD 50 values reported for mice (Ghosh et al. 1990; Llobet et al. 1991a). The Kroes et al. (1977) study did not identify an adverse effect level. Limited data on the chronic toxicity of26 STRONTIUM 2. RELEVANCE TO PUBLIC HEALTH
stable strontium are available for humans and no data are available for animals. The available data involve patients with osteoporosis or other disorder s of bone mineralization who were treated for several years with low doses of strontium in the form of st rontium salts: strontium lactate (Shorr and Carter 1952), strontium gluconate or strontium carbonate (Skoryna 1981a, 1984), and strontium ranelate (Meunier et al. 2002, 2004; Reginster 2002, 2003, Re ginster et al. 2002). None of the studies reported adverse effects on bone or significant increases in side -effects related to treatment, but reporting was poor in some of the studies (Shorr and Carter 1952; Skoryna 1981a, 1984). These data are not suitable for MRL derivation for several reasons. All subjects in these studies were co-administered calcium and some were given vitamin D, both of which are known to interfere with strontium toxicity. In addition, all of the subjects were adults, the majority being postmenopausal women with os teoporosis. Considering that the intermediate oral MRL is based upon bone effects in juve nile rats, there is reason to suspect that a chronic oral MRL based on these data would not be protective of the most sensitive population (juveniles).

Radioactive Strontium. No MRLs were derived for oral exposure to radioactive strontium, although the database includes chronic-duration human studies and acu te-, intermediate-, and chronic-duration animal studies in several species. Strontium dosimetry inform ation is available for the populations affected by contamination of the Techa River, but these exposur es included simultaneous external gamma radiation from 137 Cs, 106 Ru, and 95 Z and internal radiation from 137 Cs, in addition to 89 Sr and 90 Sr (Kossenko et al. 1994). The combined exposure studies are not suitable for the derivation of MRLs. An increase in the incidence of leukemia was reported for Techa River individuals receiving estimated bone marrow doses, attributed to radioactive strontium, in excess of 10 rem (0.1 Sv) (Kossenko 1996; Kossenko et al. 1997, 2000, 2002). Dystrophic lesions of the skeleton were observed in individuals with mean radiation doses to the surface of bone in excess of 200 rem (2 Sv) (Akleyev et al. 1995). Studies on rodents are not suitable models for establishing MRL levels for human exposure to radioactive strontium because of their relatively smaller bone diameter which places their bone marrow tissues at greater risk of radiation damage. Most of the large animal studies reported serious hematological effects at all dose levels. Immunosuppression was observed in pigs fed 625 : Ci 90 Sr/day (23.13 MBq/day) for 4–9 months (Howard 1970; Howard and Clarke 1970). Chroni c myeloid metaplasia was another effect of bone marrow irradiation in orally-exposed pigs that r eceived cumulative doses in excess of 40 rad (0.4 Gy) and a small percentage of dogs that received ≥ 0.4 : Ci 90 Sr/kg/day (44.4 kBq/kg/day) from mid-gestation to 1.5 years (Dungworth et al. 1969; Howard 1970; Howa rd and Clarke 1970). These serious effects are not suitable bases for determining MRL levels.27 STRONTIUM



### 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 overa ll perspective on the toxicology of strontium. It contains descriptions and evaluations of toxicolo gical studies and epidemiological investigations and provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health.
A glossary and list of acronyms, abbreviations, and sy mbols can be found at the end of this profile. Appendix D contains background information on ra diation physics, chemistry, and biology.
Naturally occurring strontium is a mixture of four stable (nonradioactive) isotopes, 84 Sr, 86 Sr, 87 Sr, and
88 Sr, the last being the most abundant. Section 3.2 contains a discussion of the chemical toxicity of stable strontium; radiation toxicity associated w ith exposure to radiostrontium (primarily 90 Sr and 89 Sr) is discussed in Section 3.3. The chemical properties of stable and radioactive strontium isotopes are identical and are described in Chapter 4.
Strontium is fairly reactive and therefore is rarely found in its pure form in the earth’s crust. Examples of common strontium compounds include strontium car bonate, strontium chloride, strontium hydroxide, strontium nitrate, strontium oxide, and strontium titanate. The most toxic strontium compound is strontium chromate, which is used in the production of pigments and can cause cancer by the inhalation route. Strontium chromate is not included in the Levels of Significant Exposure (LSE) tables for strontium since the carcinogenic effects of the compound are a function of the concentration of hexavalent chromium, and strontium only contribut es to solubility. The Toxicological Profile for Chromium (Agency for Toxic Substances and Disease Re gistry 2000) should be consulted for additional information on the health effects of strontium chromate.

There is no direct evidence that strontium is toxic to humans, but there is suggestive epidemiological evidence that the oral toxicity observed at high do ses in juvenile laboratory animals may pertain to humans under special circumstances. Stable strontium is of relatively low toxicity. It comprises about 4.6 ppm by weight of the human body, but does not have any recognized essential biological role. Human exposure to strontium is primarily by the oral route (via fruits, vegetables, and drinking water),28 STRONTIUM 3. HEALTH EFFECTS although inhalation exposures are also possible. No t oxic effects of stable strontium have been reported for the exposure levels normally encountered in the environment. Strontium is not readily absorbed through intact skin, but is absorbed through abrade d skin and through puncture wounds. The biological effects of strontium are related to its chemical sim ilarity to calcium, with both elements being found in Group 2 of the periodic table and forming divalent cations . However, since strontium is not the same size as calcium, it does not substitute precisely for calcium in biological processes. At different stages of the life cycle, organisms vary in their ability to di scriminate between strontium and calcium, which may cause age-related differences in gastroin testinal absorption, and therefore in health effects. Because of its similarity to calcium, strontium accumulates to a hi gh degree in bone, and, in high concentrations, may seriously interfere with the normal process of bone development. The young are particularly vulnerable because a lack of discrimination between calcium and strontium occurs during a dynamic period of bone formation and growth. For this r eason, body burdens of strontium will be higher in children than in adults, and the health effects associated with high exposu re levels would be more severe. As suggested in one human study and demonstrated in several anim al studies, strontium ‘rickets’ is one potential consequence of childhood exposure to excess stable strontium.

Beta emissions from 90 Sr have a limited ability to penetrate through tissue (see Appendix D Section D.2.3). For that reason, radiostrontium must be internalized or placed in close contact with skin before adverse health effects will occur. The ‘bone -seeking’ behavior of strontium is the basis for concern regarding oral or inhalation exposur es to the radioactive isotopes, particularly 90 Sr, with its long half-life of 29 years and highly energetic 0.546 MeV be ta particles, plus the 2.2 MeV beta particles of its short-lived 90 Y decay product isotope. Radioactive strontiu m isotopes incorporate into bone and irradiate the bone cells, the hemopoietic bone marrow, a nd potentially, the soft tissues surrounding bone, especially in the skull. Human populations accidenta lly exposed to high levels of radiation from radiostrontium (and other radionuclides and external ra diation) experienced chronic radiation sickness (postirradiation changes in hematological parameters ) and increased leukemia and cancer mortality in the decades following exposure. In animal studies, high-level exposures to 90 Sr led to death within weeks because of radiation damage to hemopoietic tissues. Longer-term lower level exposures that overcome genetic repair mechanisms may lead to myeloid le ukemia, osteosarcoma, and lymphoma (only observed in some rodent studies). It should be understood that because strontium is retain ed for a long time in the skeleton, acute- or intermediate-duration uptakes (i .e., absorption events occurring within a period of <2 weeks or <1 year, respectively) can result in d ecade-long (i.e., chronic) effects from internal exposure to the radiation emitted from the retained isotopes. Children would appear to have a higher lifetime risk for cancer effects per unit uptake, because of their relatively higher rate of skeletal incorporation of29 STRONTIUM 3. HEALTH EFFECTS strontium and potentially longer radiation exposure period. Immediately nonlethal exposures to high levels of radioactive strontium may cont ribute to suppression of the immune system.
Limited human data are available regarding health effects that can be excl usively associated with exposure to radioactive strontium sources such as 90 Sr and 89 Sr. These radionuclides are products of nuclear fission and may, therefore, be released from sites where nuclear fission occurs, from radioactive material removed from such sites, or from leak age of radioactive strontium sources. Both 90 Sr and 89 Sr emit beta radiation that travels short distances and can penetrate the skin and superficial body tissues. The radiation dose from these radionuclid es 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 strontium ra dionuclides emitting beta radiation out side the body is normally of little health concern unless the radioactive material c ontacts the skin. Skin contact can allow the beta radiation to pass through the epidermis to live dermal tissue where it becomes a major contributor to a radiostrontium-generated radiation dose to the skin. At very high doses, the beta radiation can cause such adverse effects as erythema, ulceration, or even tissue necrosis.

Once radioactive strontium is internalized, it is abso rbed, distributed, and excreted in the same manner as stable strontium; the chemical similarity of str ontium to calcium results in deposition of radioactive strontium in bone. The internal radiation dose from strontium is actually a measure of the amount of energy that the beta emissions deposit in tissue. Th e short-range beta radiation produces a localized dose, generally to bone and the soft tissues adjacent to bone; hemopoietic bone marrow is the most biologically significant target of radioactive strontium emissions. Molecular damage results from the direct ionization of atoms that are encountered by beta radiation and by interactions of resulti ng free radicals with nearby atoms. Tissue damage results when the molecular damage is extensive and exceeds the capacity of natural repair mechanisms.
In radiation biology, the term absorbed dose is the amount of energy depos ited by radiation over time per unit mass of tissue, expressed in units of rad or gray (Gy) (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 rem or sievert (Sv). The quality factor is considered to be unity for the beta radiation emitted from 90 Sr and 89 Sr, so for these radionuclides, the absorbed dose (in rad or gray) is numerically identical to the dose equivalent (in rem or sievert). The dose30 STRONTIUM 3. HEALTH EFFECTS equivalent from internalized strontium radionuclides is estimated using the quantity of material entering the body (via ingestion or inhalation), the biokinetic pa rameters for strontium (retention, distribution, and excretion), the energies and intensities of the beta radiation emitted, and the parameters describing the profile of absorbed radiation energy within the body. If, for example, a person ingests a given activity of radiostrontium (measured in curies [Ci] or becquerels [Bq]), the tissues of the body will absorb some of the energy of the emitted beta radiation in a pattern reflecting the kinetics of distribution and elimination of the ingested radiostrontium, the rate at which th e radioactive isotope decays to a stable form, and the age of the person at the time of ingestion (which aff ects both the biokinetics of the radiostrontium and the potential length of time over which the tissues can be e xposed to the radiation). Each tissue, therefore, can receive a different dose equivalent. The total dose equivalent for the body will reflect the integration of the dose equivalents for the various tissues usi ng a weighting scheme for the relative sensitivities of tissues and organs.
The EPA has published a set of internal dose convers ion 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 2000e). For example, the EPA has estimated th at the dose equivalents following ingestion of 1 Bq of 90 Sr are 2.77x10 -8 and 2.77x10 -7 Sv, respectively, for the adult and infant (assuming an integration time of 50 years for an adult following the initial exposure). For 89 Sr, these values are 2.57x10 -9 Sv and 3.59x10 -8 Sv, respectively. Age-specifi c dose coefficients for inhalation and ingestion of any of the radioactive isotopes of strontium by the general public can be found in ICRP publications 71 (ICRP 1995) and 72 (ICRP 1996), respectively. Dose coefficien ts for inhalation and ingestion of strontium radionuclides can be found in U.S. EPA Federal Gu idance Report No. 11 (EPA 1988). Dose coefficients for external exposure to radioisotopes of strontium in air, surface water, or soil contaminated to various depths can be found in U.S. EPA Federal Guidance Report No. 12 (EPA 1993b).

Unless otherwise stated, exposure levels in the text are presented per kg of body weight. In Appendix D, standard and SI units of radiation activity (curies, becquerels) and absorbed dose (rad, gray) are compared in Table D-5 and are discussed in Sections D.2.2 Ha lf-Life and Activity and D.3.1.2 Absorbed Dose and Absorbed Dose-Rate.31 STRONTIUM 3. HEALTH EFFECTS
3.2 DISCUSSION OF HEALTH EFFECTS OF STABLE STRONTIUM BY ROUTE OF EXPOSURE
Section 3.2 discusses the chemical toxicity of strontium. Radiation toxicity resulting from exposure to radiostrontium is discussed in Section 3.3.
To help public health professiona ls 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 (deat h, systemic, immunological, neurological, reproductive, developmental, genotoxic, and carcinog enic 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-obser ved-adverse-effect levels (NOAELs) or lowestobserved-adverse-effect levels (LOAELs) reflect the act ual 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 appro ach to warrant an attempt at distinguishing between "less serious" and "serious" effects. The distinction be tween "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 NO AELs should also help in determining whether or not the effects vary with dose and/or duration, and pl ace into perspective the po ssible significance of these effects to human health.
The significance of the exposure levels shown in the Levels of Significant Exposure (LSE) tables and figures may differ depending on the user's perspective. Public health officials and others concerned with appropriate actions to take at hazardous waste s ites may want information on levels of exposure associated with more subtle effects in humans or animals (LOAELs) or exposure levels below which no32 STRONTIUM 3. HEALTH EFFECTS adverse effects (NOAELs) have been observed. Es timates of levels posing minimal risk to humans (Minimal Risk Levels or MRLs) may be of inte rest to health professionals and citizens alike.
Levels of exposure associated with carcinogenic effect s (Cancer Effect Levels, CELs) of strontium are indicated in Tables 3-2, 3-3, and 3-4 and Figures 3-2 and 3-3. Because cancer effects could occur at lower exposure levels, Figures 3-2 and 3-3 also s how 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.
Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been made for strontium. An MRL is defined as an estim ate 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 suffici ent data exist to identify the target organ(s) of effect or the most sensitive health effect(s) for a sp ecific duration within a given route of exposure. MRLs are based on noncancerous health effects only a nd do not consider carcinogenic effects. MRLs can be derived for acute, intermediate, and chronic dur ation 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 techniqu es. Furthermore, ATSDR acknowledges additional uncertainties inherent in the application of the pro cedures 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 hypersensitiv ity 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.33 STRONTIUM 3. HEALTH EFFECTS
3.2.1 Inhalation Exposure
3.2.1.1 Death
The only studies located regarding death in humans following inhalation exposure to stable strontium are related to strontium chromate. Strontium chromate has been implicated as a cause of increased deaths from lung cancer in occupational studies (Davies 1979, 1984) (see Section 3.2.1. 7). The toxicity of strontium chromate is attributed to hexavalent chro mium ion, which enters l ung cells and is metabolized to a genotoxic agent. Strontium itself contributes to solubility of strontium chromate, but any associated health effect is expected to be masked by that of the chromate. No studies were located regarding death in animals following inhalation exposure to stable strontium.

3.2.1.2 Systemic Effects
No data are available regarding systemic effects following inhalation exposure to stable strontium for which the exposure levels are known. For that reason, no LSE table has been created for stable strontium. No studies were located that descr ibed gastrointestinal, hematologi cal, hepatic, renal, body weight, metabolic, endocrine, dermal, or ocular effects in humans or animals following inhalation exposure to stable strontium.
Respiratory Effects. The only report of adverse respiratory effects in humans resulting from the inhalation of stable strontium is a case report of an anaphylactic reaction to smoke from an ignited roadside flare (Federman and Sachter 1997). The fl are contained approximately 75% strontium nitrate (31% strontium), among other known irritating ingredient s, and the exact contribution of strontium to the effect is uncertain. The anaphylactic reaction to the smoke included coughing, wheezing, and severe respiratory difficulties. This case report is discussed in Section 3.2.1.3 Immunological and Lymphoreticular Effects. No other reports were located describing longer-term respiratory effects following inhalation of stable strontium compounds by humans or animals.

Cardiovascular Effects. A single study documented adverse cardiovascular effects in humans resulting from the inhalation of stable strontium in smoke from an ignited roadside flare (Federman and Sachter 1997). Extreme tachycardia resulted as part of an anaphylactic reaction to the smoke, which contained ~31% strontium as strontium nitrate, in addition to other known irritants. The role of strontium34 STRONTIUM 3. HEALTH EFFECTS
in this reaction is not established. No other re ports were located describing longer-term cardiovascular effects following inhalation of stable str ontium compounds by humans or animals.

3.2.1.3 Immunological and Lymphoreticular Effects

The single located study of immunological effects in humans following inhalation exposure to stable strontium is a case report of an anaphylactic reac tion to smoke from an emergency roadside flare (Federman and Sachter 1997). A 35-year-old female paramedic developed a sudden, severe reaction upon inhaling fumes from a flare that contained approximat ely 31% strontium as strontium nitrate. Initial symptoms included coughing, wheezing, and shortness of breath that was not responsive to albuterol, epinephrine, or steroids; recovery ultimately required sedation, intubation, and intensive care for several days. Although the paramedic had been unsymptomatic before the incident, her medical history included several significant contributory factors: rheumatic fever requiring penicillin prophylaxis until age 12, a severe anaphylactic reaction to a bee sting at age 23, and adult-onset asthma at age 32. The ingredients of the flare (Road Fusee®; Standard Fusee Corporation, Easton, Maryland) included ±75% strontium nitrate (~31% strontium), ±10% potassium perchlorate, ± 10% sulfur, and ±10% sawdust/oil binder. Upon combustion, each of these would yield products known to be irritating to the respiratory tract: strontium oxide, nitrous oxide, potassium oxide, chlorine gas, su lfur dioxide, and particulates. Thus, the exact contribution of strontium to the development of an aphylaxis in this case is uncertain. However, see Section 3.6.2 for a possible mechanism by which strontium could contribute to an immunological effect. No studies were located regarding immunological e ffects in animals following inhalation exposure to stable forms of strontium.
No studies were located regarding the following e ffects in humans or animals following inhalation exposure to stable strontium:

3.2.1.4 Neurological Effects
3.2.1.5 Reproductive Effects
3.2.1.6 Developmental Effects35 STRONTIUM 3. HEALTH EFFECTS
3.2.1.7 Cancer

There were no reports regarding cancer in humans or animals resulting from inhalation exposure to stable strontium compounds except for strontium chromate. In an epidemiological study, no excess risk for lung cancer was found among workers in two Japanese factor ies who were involved in the production of strontium chromate pigment (Kano et al. 1993). However, exposures to strontium chromate in the factories may have been low because of suitable indus trial hygiene procedures. Another epidemiological study examined workers in British chromate pigmen t manufacturing plants (Davies 1979, 1984). In one factory, both lead and zinc chromate were produ ced until 1976, and strontiu m chromate was produced from 1950 to 1968. For lung cancer deaths in worker s exposed to ‘high’ and ‘medium’ levels of chromates before 1961, when industrial hygiene improvements were introduced, the observed/expected ratio (O/E) was 6/1.61, with a standard mortality ra tio (SMR) of 373 (p<0.01). For workers exposed to ‘high’ and medium’ levels from 1961 to 1967, the values were O/E=5/089, SMR=562 (p<0.01). The contribution of strontium to toxicity in these studies was not addressed.
No standard inhalation study of strontium chromate in animals was located. However, Levy et al. (1986) used an intrabronchial pellet implantation technique to evaluate the carcinogenicity of 23 different commercially available chromates, including two batches of strontium chromate. Metal pellets were coated with a mixture of cholesterol and strontium ch romate and implanted into the left bronchus of male and female young rats (100 per group). Of 198 lu ngs treated with strontium chromate, 105 (53%) had a primary keratinizing squamous carcinoma of the bronchial epithelium. The authors indicated that carcinogenicity was associated with sparingly so luble hexavalent chromium compounds such as strontium, calcium, or zinc chromates.

3.2.2 Oral Exposure

There are no direct dose-response data for adverse eff ects of exposure to stable strontium in humans, but one epidemiological study suggests that the skeletal toxicity observed at high oral doses in juvenile animals may be relevant to humans (see Musculoskeletal Effects). At low exposure levels, ingestion of stable strontium poses no harm to organisms with ac cess to adequate calcium, phosphorus, and vitamin D. At higher exposure levels, especially under conditions of inadequate calcium, phosphorus, and vitamin D, stable strontium will interfere with normal bone deve lopment, causing ‘strontium rickets’ of variable severity.36 STRONTIUM 3. HEALTH EFFECTS
3.2.2.1 Death
No deaths in healthy humans have been reported after or al exposure to stable strontium. Stable strontium caused death in laboratory animals only at doses that are very high compared to normal human exposure. In acute exposure studies in mice, the oral LD 50 for strontium nitrate was reported to be 2,350 mg strontium/kg in males (Llobet et al. 1991a). For stron tium chloride administered by gavage, the acute oral LD 50 in albino mice was reported to be 2,900 mg strontium/kg for males and 2,700 mg strontium/kg for females (Ghosh et al. 1990).
In intermediate-duration animal studies, ingesti on of excess stable strontium resulted in increased mortality. The premature death rate was 40% am ong weanling male Sprague-D awley rats fed stable strontium (form not specified) at a dose level of 565 mg strontium/kg/day for 43 days (Johnson et al. 1968). Weanling male Wistar rats exposed to strontium phosphate in the diet at a dose level of 2,820 mg strontium/kg/day for 4–6 weeks had a mortality rate of 30%, but no mortality occurred at 580 or 1,270 mg strontium/kg/day (Kshirsagar 1976). From an analysis of a pair-fed group (food intake matched to the high-dose group), the author concluded that the incr eased mortality in the high-dose group was not related to reduced food intake, but rather to the ingestion of strontium. No studies were located regarding death in animals following chronic-duration oral administration of stable strontium.
All reliable LOAEL values for death from stable strontium in each species and duration category are recorded in Table 3-1 and plotted in Figure 3-1.

3.2.2.2 Systemic Effects

No studies were located regarding dermal or ocular effects in humans or animals following oral exposure to stable strontium. The highest reliable NOAEL and all LOAEL values for the systemic effects from oral exposure to stable strontium in each species and duration category are shown in Table 3-1 and plotted in Figure 3-1.
Respiratory Effects. No studies were located regarding respir atory effects in humans following oral exposure to stable strontium. No studies were loca ted regarding acute or chronic respiratory effects in animals following exposure to stable forms of strontium. In one intermediate-duration study, respiratory difficulties were noted in rats following lethal inges tion of 565 mg strontium/kg/day of stable strontiumTable 3-1Levels of Significant Exposure to Strontium - Chemical Toxicity-OralExposure/LOAELDuration/aKey toSpeciesFrequencyNOAELLess SeriousSeriousReference(Specific Route)figure(Strain)System(mg/kg/day)(mg/kg/day)(mg/kg/day)Chemical FormACUTE EXPOSUREDeath1MouseonceGhosh et al. 19902900M(LD50)(albino)(GW)Strontium chloridec2700F(LD50)2MouseNRLlobet et al. 1991a2350M(LD50)(NS)(NS)Strontium nitrateSystemic3Rat2 wksKroes et al. 1977ad libHemato110(Wistar)Strontium chloride 6H2O(F)Musc/skel110Hepatic110Renal110Bd Wt110Table 3-1 Levels of Significant Exposure to Strontium - Chemical Toxicity -Oral(continued)aKey to Speciesfigure (Strain)Exposure/Duration/Frequency(Specific Route)SystemNOAEL(mg/kg/day)LOAELReferenceChemical FormLess Serious(mg/kg/day)Serious(mg/kg/day)456Rat2 wksad lib(Wistar)(F)INTERMEDIATE EXPOSUREDeathRatPND 21-64ad lib(SpragueDawley)(F)Rat4-6 wksad lib(Wistar)(F)GastroMusc/skelHepaticBd Wt3000 M (small intestine: decr acid &alkaline phosphatase;reversible)3000 M (bone: incr alkalinephosphatase; reversible)3000 M (incr alk phosphatase, decr acidphosphatase; reversible)3000 M (bd wt gain decr 62%)565 M (40% mortality)2820 M (30% mortality)Kshirsagar 1976Strontium phosphateJohnson et al. 1968(NS)Kshirsagar 1976Strontium phosphateaKey tofigureSpecies(Strain)LOAELLess SeriousNOAELSystemTable 3-1 Levels of Significant Exposure to Strontium - Chemical Toxicity -(mg/kg/day) (mg/kg/day)Exposure/Duration/Frequency(Specific Route)OralSerious(mg/kg/day)(continued)ReferenceChemical Form7Systemic(SpragueDawley)Rat8 wksad lib(W)Musc/skel168 MGrynpas et al. 1996(NS)Bd Wt168 MMetab168 M8(SpragueDawley)RatPND 21-64ad lib(F)Resp565 M (unspecified difficulties)Johnson et al. 1968NSMusc/skel565 M (rickets)9(Wistar)Rat90 dad lib(F)Hemato166 FKroes et al. 1977Strontium chloride 6H2OMusc/skel166 FHepatic166 FRenal166 FBd Wt166 FMetab166 FaKey tofigureSpecies(Strain)LOAELLess SeriousNOAELSystemTable 3-1 Levels of Significant Exposure to Strontium - Chemical Toxicity - Oral(mg/kg/day) (mg/kg/day)Exposure/Duration/Frequency(Specific Route)Serious(mg/kg/day)(continued)ReferenceChemical Form10(Wistar)Rat4-6 wksad lib(F)Cardio2820 M (hemorrhage)Kshirsagar 1976Strontium phosphateGastro580 M1270 M (small intestine: reversible decralkaline phosphatase)Musc/skel580 M1270 M (bone: incr alkalinephosphatase, reversible)Hepatic1270 M2820 M (reversible decr alkalinephosphatase)Bd Wt580 M1270 M (reversible decr in wt gain)11(SpragueDawley)Rat9 wksad lib(W)Musc/skel524 M633 M (bone calcification rate decr by17%)Marie et al. 1985Strontium chlorideBd Wt633 MMetab633 MTable 3-1 Levels of Significant Exposure to Strontium - Chemical Toxicity - Oral(continued)Exposure/LOAELDuration/aFrequencyReferenceKey to SpeciesNOAEL Less SeriousSerious(Specific Route)figure (Strain)System(mg/kg/day) (mg/kg/day)(mg/kg/day)Chemical Form12Rat4 wkMatsumoto 1976Musc/skel1970 M (tibiae: length decr 33%,ad lib(Wistar)epiphyseal plates 5 x wider,Strontium carbonate(F)decr mineralization)Bd Wt1970 M (bd wt gain decr by 60%)13Rat27 dMorohashi et al. 1994Gastroad lib102 510 F (20% decr net intestinal Ca2+(Wistar)Strontium carbonateabsorption)(F)Musc/skel102 510 F (decr bone formation,resorption, Ca2+ content ofbone)Bd Wt510 FMetab102 F 510 F (hypocalcemia)14Rat3 wkNeufeld and Boskey 1994Musc/skelad lib500 M (abnormal bone mineralization)(Sprague-Strontium carbonateDawley)(F)Bd Wt500 MMetab500 MaKey tofigureSpecies(Strain)LOAELLess SeriousNOAELSystemTable 3-1 Levels of Significant Exposure to Strontium - Chemical Toxicity - Oral(mg/kg/day) (mg/kg/day)Exposure/Duration/Frequency(Specific Route)Serious(mg/kg/day)(continued)ReferenceChemical Form15(EnglandWright Y)RatPND 21-41ad lib(F)Musc/skel1850 M (epiphyseal cartilagehistopathology)Reinholt et al. 1984(NS)Bd WtMetab1850 M1850 M (28% decr bd wt gain)16(NS)Rat20 dad lib(F)Musc/skel140Fb550 F (tibial epiphyseal cartilageabnormally wide)Storey 1961Strontium carbonateBd WtMetab1460 F4975 F2220 F (24% decr bd wt gain)17(NS)Rat20 dad lib(F)Musc/skel690 F1370 F (tibial epiphyseal cartilageabnormally wide; incrmetaphyseal osteoid)Storey 1961Strontium carbonateBd Wt2750 FMetab2750 FaKey tofigureSpecies(Strain)LOAELLess SeriousNOAELSystemTable 3-1 Levels of Significant Exposure to Strontium - Chemical Toxicity - Oral(mg/kg/day) (mg/kg/day)Exposure/Duration/Frequency(Specific Route)Serious(mg/kg/day)(continued)ReferenceChemical Form18(NS)Ratup to 7 monthsad lib(F)Musc/skel2160(rickets)Storey 1962Strontium carbonateBd Wt2160(30% decr bd wt gain)19(NS)Rat>7 moad lib(F)Musc/skel1570(rickets: abnormal bonemineralization)Storey 1962Strontium carbonate20(SpragueDawley)Rat26 dad lib(F)Musc/skel1520 M (rickets)Svensson et al. 1987Strontium chlorideEndocr1520 MBd Wt1520 M (16% decr bd wt gain)Metab1520 M21(C57BL/6J)Mouse29 dad lib(W)Musc/skel350 M (11% decr number ofosteoclasts; decr boneresorption; 10% incr osteoidsurface)Marie and Hott 1986Strontium chlorideBd Wt350 MMetab350 MTable 3-1 Levels of Significant Exposure to Strontium - Chemical Toxicity-Oral(continued)aKey tofigureSpecies(Strain)Exposure/Duration/Frequency(Specific Route)SystemNOAEL(mg/kg/day)Less Serious(mg/kg/day)LOAELSerious(mg/kg/day)ReferenceChemical Form22NeurologicalPND 21-64(F)(Sprague-Dawley)Rat565 M (paralysis of hindlimbs)Johnson et al. 1968NSaThe number corresponds to entries in Figure 3-1.bUsed to derive an intermediate oral MRL of 2.0 mg/kg/day. The MRL was derived by dividing the NOAEL by an uncertainty factor of 30(10 for extrapolation from animals tohumans, and 3 for human variability), and by a modifying factor of 3(for limited endpoint examination and short duration).cDifferences in levels of health effects and cancer effects between males and females are not indicated in Figure 3-2. Where such differences exist, only the levels of effect for themost sensitive gender are presented.Ad lib - ad libitum; Bd Wt = body weight; Cardio = cardiovascular; d = day(s); decr = decreased; (F) = food; Gastro = gastrointestinal; (GW) = gavage in water; Hemato =hematological; hr = hour(s); incr = increased; LD50 = lethal does, 50% kill; LOAEL = lowest-observed-adverse-effect level; Metab = metabolic; Musc/skel = musculoskeletal; NOAEL= no-observed-adverse-effect level; NR = not reported; (NS) = not specified; PND = post natal day; wk = week(s); x = time(s); yr = year(s)Gastrointestinal Hematological Musculoskeletal Hepatic Renal Body W10000 Death eightFigure 3-1 Levels of Significant Exposure to Strontium - Chemical Toxicity - OralAcute (≤14 days)Systemicmg/kg/day4r4r4r4r1m2m10003r3r3r3r3r100c-Cat-Humansf-Ferret n-MinkCancer Effect Level-AnimalsCancer Effect Level-HumansLD50/LC50d-Dog k-Monkey j-Pigeon o-OtherLOAEL, More Serious-AnimalsLOAEL, More Serious-Humans Minimal Risk Levelr-Rat m-Mouse e-GerbilLOAEL, Less Serious-AnimalsLOAEL, Less Serious-Humansfor effectsp-Pig h-Rabbit s-HamsterNOAEL - AnimalsNOAEL - Humansother thanq-Cow a-Sheep g-Guinea PigCancerRespiratory Cardiovascular Gastrointestinal Hematological Musculoskeletal Hepatic Renal10000 Death EndocrineFigure 3-1 Levels of Significant Exposure to Strontium - Chemical Toxicity - Oral (Continued)Intermediate (15-364 days)Systemicmg/kg/day6r10r10r18r12r15r19r20r20r17r10r10r10r100017r11r10r10r5r 8r8r16r11r13r14r13r21m7r9r9r9r9r16r13r13r100101c-Cat-Humansf-Ferret n-MinkCancer Effect Level-AnimalsCancer Effect Level-HumansLD50/LC50d-Dog k-Monkey j-Pigeon o-OtherLOAEL, More Serious-AnimalsLOAEL, More Serious-Humans Minimal Risk Levelr-Rat m-Mouse e-GerbilLOAEL, Less Serious-AnimalsLOAEL, Less Serious-Humansfor effectsp-Pig h-Rabbit s-HamsterNOAEL - AnimalsNOAEL - Humansother thanq-Cow a-Sheep g-Guinea PigCancerMetabolic Neurological10000 Body WeightFigure 3-1 Levels of Significant Exposure to Strontium - Chemical Toxicity - Oral (Continued)Intermediate (15-364 days)Systemicmg/kg/day16r17r17r16r18r12r15r15r20r20r16r10r100011r11r10r22r13r13r14r14r21m21m7r7r9r9r13r100101c-Cat-Humansf-Ferret n-MinkCancer Effect Level-AnimalsCancer Effect Level-HumansLD50/LC50d-Dog k-Monkey j-Pigeon o-OtherLOAEL, More Serious-AnimalsLOAEL, More Serious-Humans Minimal Risk Levelr-Rat m-Mouse e-GerbilLOAEL, Less Serious-AnimalsLOAEL, Less Serious-Humansfor effectsp-Pig h-Rabbit s-HamsterNOAEL - AnimalsNOAEL - Humansother thanq-Cow a-Sheep g-Guinea PigCancer48 STRONTIUM 3. HEALTH EFFECTS

(form unspecified) for 4–6 weeks (Johnson et al. 1968). No description of the respiratory effects or incidence data were reported.

Cardiovascular Effects. No studies were located regarding cardiovascular effects in humans following acute- or intermediate-duration oral exposure to stable strontium.
One epidemiological study examined the relationshi p between trace metals, including strontium, in drinking water and the rates of various kinds of v ascular disease in 24 communities in the lowest quartile of the economic scale in Texas (Dawson et al. 1978). The concentration of strontium was measured in samples of drinking water and 2,187 urine samples fr om subjects (aged 5–97 years) in families that had resided within their respective communities for at least 10 years. There was a significant correlation between mean strontium levels in drinking water a nd in the urine. However, the only statistically significant product-moment correlationship for strontium (in urine and in drinking water) was for a decreased community mortality rate (in people over 45 years old) for hypertension with heart disease. There was no correlation found between strontium a nd mortality from arteriosclerotic and degenerative heart disease, other heart diseases, hypertension, ge neral arteriosclerosis, or vascular diseases of the central nervous system.
No studies were located regarding cardiovascular effect s after acute- or chronic-duration oral exposure in animals. In male weanling Wistar rats (5–6 per group) given strontium as strontium phosphate in the diet for 4–6 weeks, hemorrhage (unspecified) occurred at 2,820 mg strontium/kg/day, possibly related to the increased mortality at this dose level, but not at or ≤ 1,270 mg strontium/kg/day (Kshirsagar 1976).

Gastrointestinal Effects. No studies were located regarding g astrointestinal effects in humans following oral exposure to stable strontium.
No studies were located regarding gastrointestinal effects in animals following chronic-duration oral exposure to various forms of stable strontium. Acut e- and intermediate-duration oral studies in animals have examined gastrointestinal effects that woul d be likely to influence calcium and phosphorus metabolism. Decreases in acid and alkaline phosphatase activities were observed in the small intestine of 5–6 male weanling (21 days old) Wi star rats given 3,000 mg strontium/kg/day as strontium phosphate for 2 weeks (Kshirsagar 1976). These effects were reversed by giving the rats a normal low-strontium diet for 2 weeks. The biological significance of the d ecreased phosphatase activities is not known. Studies in49 STRONTIUM 3. HEALTH EFFECTS
chickens first demonstrated the rela tionship between strontium toxicity, calcium, and vitamin D. In male white Leghorn chickens raised on a diet deficient in vi tamin D for the first 2 weeks of life, ingestion of >2,300 mg strontium/kg/day as strontium carbonate in a low-calcium, low-vitamin D diet for 11–14 days, affected calcium transport in th e duodenum (Omdahl and DeLuca 1972). Strontium ingestion reduced the duodenal activation of vitamin D 3 (conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol), reduced the activity of calcium bindi ng protein, and reduced the absorption of calcium by the duodenum. Similar effects were observed in chickens given excess strontium in a diet with adequate vitamin D, but deficient in calcium (0 .01%) (Corradino and Wasserman 1970; Corradino et al. 1971a, 1971b). In addition, excess strontium ingesti on significantly reduced the absorption of glucose, histidine, and alanine by the duodenum to levels typical of rachitic (vitamin D-deprived) chickens (Corradino et al. 1971b). The effects of strontium on calcium transport by the duodenum were reversed by transferring chickens to a normal low-strontiu m diet containing adequate amounts of vitamin D 3 and calcium. The chicken data are not included in Table 3-2, because the physiological rates are likely to be very different from mammals, and also because health risk assessment methodology is currently limited to mammals. However, these phenomena were confirme d in a recent study in rats (Armbrecht et al. 1998). Six days on a diet low in calcium, but containing 0.8% strontium, was sufficient to suppress the serum levels of activated vitamin D, the concentrations of calbindin D protein (two calcium-binding protein induced by vitamin D; see Sections 3.6.1 and 3.6.2), and the rates of calcium transport in the duodenum of young, adult, and old rats.
In male weanling (3 weeks old) Wistar rats (5–6 per group) given strontium phosphate in the diet for 6 weeks, a decrease in alkaline phosphatase activity in the small intestine occurred at 1,270 mg strontium/kg/day, but not at 580 mg strontium/kg/day (Kshirsagar 1976). This decrease in enzyme activity was partly reversed by feeding the rats a nor mal low-strontium diet for 2 weeks. As mentioned above, the biological significance of these changes in phosphatase activity is not known. In slightly older female juvenile Wistar rats (36 days old, 6–8 pe r group) that ingested 510 mg strontium/kg/day as strontium carbonate for 27 days, the net intestinal absorption of calcium was reduced by 20%, but no effects occurred at 100 mg strontium/kg/day (Morohash i et al. 1994). In male white Leghorn chickens fed 255 mg strontium/kg/day (probably as carbonate) in a diet low in vitamin D 3 for the first 16 days after hatching, the conversion of 25-hydr oxycholecalciferol to 1,25-dihydroxyc holecalciferol and the transport of calcium were suppressed in the duodenum (Omhda hl and DeLuca 1971). This study is omitted from Table 3-1 because of probable differences in physiology.50 STRONTIUM 3. HEALTH EFFECTS Hematological Effects. No studies were located regarding hematological effects in humans following oral exposure to stable strontium.
No studies were located regarding hematological e ffects in animals following chronic-duration oral exposure to stable strontium. In adult Wistar ra ts given up to 110 mg strontium/kg/day as strontium chloride in the diet for 2 weeks, the total number of erythrocytes was slightly elevated in both sexes, and the leucocyte count was slightly elevated in males at the highest dose level at termination (Kroes et al. 1977). However, since the results were not reported qu antitatively, the significance of this information is uncertain. No hematological changes were obser ved among weanling Wistar rats fed up to 166 mg strontium/kg/day as strontium chloride in the diet for 90 days (Kroes et al. 1977). However, the relatively high level of calcium (0.85%) in the diet given to these animals may have reduced absorption and therefore the effect of strontium.

Musculoskeletal Effects. No studies were located regarding mu sculoskeletal effects in humans after acute-duration oral exposure to stable strontium. The only long-term human exposure study is an epidemiological study that was carried out in the Ula ş Health Region of Sivas, Turkey (Özgür et al. 1996). This region has a high prevalence of childhood rickets, 32% compared to 4.4% nationally among children aged up to 5 years, and the study sought to determine whether higher levels of strontium in the soil might be a contributing factor. Soils surrounding 55 villages were characterized as to strontium concentration (Group 1, >350 ppm; Group 2, <350 pp m). A total of 2,140 children (ages 6–60 months) from these localities (613 in Group 1 and 1,527 in Group 2) were examined for one or more signs of rickets: craniotabes (localized cran iomalacia or thinning of cranium), rachitic rosary (beadlike growths at the ends of ribs where they join cartilage), conspic uous bulging at the wrist, bony deformities of the legs (bowleg, knock-knee), and delayed closure of the fontanelles. A significantly higher proportion of Group 1 children had one or more rachitic signs than t hose in Group 2: 37.5 vs 19.5%. In addition, the severity of disease (number of rachitic signs per ch ild) was proportionally higher in Group 1 (p<0.001). For each cohort, the incidence of rickets was higher in Group 1 than in Group 2 and the differences were statistically significant for ages 6–12, 13–18, 25–36, and 37–48 months (odds ratios 1.66–2.55). When the duration of breast feeding was considered, the incidence of rickets within the two groups did not differ for children breast fed for 24 months or longer. Howeve r, for shorter periods of breast feeding, between 0 and 24 months, the incidence of rickets was significantly higher in Group 1 (odds ratios 1.79–3.14). The implication of this study is that breast feeding may be protective against strontium toxicity in nursing infants, probably by providing both calcium and protei n, both of which tend to reduce the incorporation of strontium into bone (see Sections 3. 10, 3.11, and 3.12.2). The authors attributed the higher incidence of51 STRONTIUM 3. HEALTH EFFECTS rickets in Group 1 children to their diet, which, af ter weaning, is mainly based on grains grown in strontium-rich soil.
No studies were located regarding musculoskeletal eff ects in animals after chronic-duration oral exposure to stable strontium. Acute- and intermediate-dur ation studies in animals documented significant adverse effects of strontium on bone that were especially severe in the young. In an acute-duration study, there was no effect on bone in groups of adult SPF Wistar ra ts that ingested up to 110 mg strontium/kg/day as strontium chloride in the diet for 2 weeks (Kroes et al. 1977). Strontium was detected in bone following ingestion of 11 or 110 mg/kg/day, but not at lowe r doses (0.1 or 1.0 mg/kg/day). Among male weanling (21 days old) Wistar rats that ingested 3,000 mg st rontium/kg/day as strontium phosphate in the diet for 2 weeks, alkaline phosphatase activity was significan tly increased in bone compared to controls (Kshirsagar 1976). The author speculated that th e observed increase in alkaline phosphatase activity may have been related to a stimulation of osteoblast s, which secrete osteoid and have a high alkaline phosphatase content. In acute studies on young chicke ns fed 2,300–2,400 mg/kg/da y of strontium, and an inadequate level of calcium, severe defects in bone organization and decreased mineralization were observed within 1 or 2 weeks (Corradino and W asserman 1970; Corradino et al. 1971a, 1971b; Omdahl and DeLuca 1972): abnormally wide hypertrophic ca rtilaginous zone and impaired endochondral ossification (the removal of hypertrophic cartilage a nd its replacement by bone). As noted above, the chicken data are omitted from Table 3-1.

Numerous abnormalities of bone structure and bone mineralization were observed in weanling male Sprague-Dawley rats (100–125 g) that ingested 500 mg strontium/kg/day as strontium carbonate in the diet for 3 weeks (Neufeld and Boskey 1994). In strontium-fed rats, the ash weight (mineral content) of metaphyseal bone was reduced and the complexed acidic phospholipid content (lipid nucleator of bone mineral) was significantly higher than in controls. Large areas of nonmineralized bone (osteoid) were observed in epiphyseal bone and secondary spongiosa. The epiphyseal plates were abnormally wide and the metaphyses were abnormally long and dense. Th e diaphyses contained localized areas of decreased bone density. The primary spongiosa of the proximal tibia was longer and the trabeculae was disorganized and apparently disconnected from the ove rlying calcified cartilage. The authors suggested that since the levels of complexed acidic phospholip ids were high and vitamin D deficiency is known to increase complexed acidic phospholipid levels, that th e effect of strontium was probably not mediated through its effect on vitamin D. They suggested the binding of strontium to the surface of initial hydroxyapatite crystallites reduced their further pro liferation, resulting in a smaller crystal size.52 STRONTIUM 3. HEALTH EFFECTS Similarly, significant abnormalities of bone organizati on occurred in five weanling (21 days old) male England Wright Y rats that ingested 1,850 mg strontium/kg/day (form unspecified) for 20 days in a diet sufficient in calcium, phosphorus, and vitamin D (Reinholt et al. 1984). In treated rats, the mean thickness of the epiphyseal growth plate was 70% larger than normal. In the epiphyseal regions of long bones, the volume of each zone was larger than its normal counterpart, and in addition, the relative sizes were altered; the proportional volumes of the res ting, proliferative, and calcifying zones were significantly smaller and that of the hypertrophic zone was significantly larger than normal. There was an increase in the volume of extracellular matrix in bone, suggested to be associated with a reduced rate of extracellular matrix vesicle degradation. Another st udy from this laboratory examined the biochemistry of epiphyseal cartilage in rats treated as above (Reinholt et al. 1985). In strontium-treated rats, alterations were observed in the proteoglycan composition (slightly higher galactosamine content), chondroitin sulfate chain lengths (larger), regional distributions of large and small chondroitin sulfate peptides, and regional distributions of both non-sulfated c hondroitin sulfate disaccharides and hyaluronic aciddisaccharides. The authors suggested that these stron tium-induced alterations in cartilage matrix might affect the process of mineralization.
No effects on bone histology were observed in you ng female rats (40–60 g) that were fed 140 mg strontium/kg/day as strontium carbonate for 20 days, but histological abnormalities were detected at doses between 550 and 4,975 mg/kg/day (Storey 1961). Alte rations in the appearance of the cartilage plate (irregular, thicker, with areas of uncalcified bone matr ix in the distal ends of the metaphyseal trabeculae and proximal end of the diaphysis) were observed at 550 mg strontium/kg/day. Irregularities in the organization of the cells of hypertrophic zone (distorting the usual parallel arrangement of intercellular matrix columns), in the pattern of calcification, and in deposition of osteoid were more conspicuous with increasing dose. At higher doses, bands of uncalcified cartilage matrix were isolated between areas of osteoid tissue. In tibias, the dry weight, ash weight , ash percentage, and calcium in ash were significantly reduced with increased strontium intake. In the same study, adult female rats given doses of 170– 2,750 mg strontium/kg/day exhibited milder effects in bone. Histological changes in the tibia (thicker epiphyseal cartilage, increased width of metaphyseal osteoid seams) were noted at 1,370 or 2,750 mg strontium/kg/day only. Other significant effects seen only at 2,750 mg strontium/kg/day included the deposition of osteoid tissue near vascular canals, a redu ction in the area of bone resorption, and reductions in the dry weight, ash weight, ash percentage, and calcium in ash of bone (Storey 1961).

A 24% reduction in bone forma tion rate, 28% reduction in b one resorption rate (based on 45 Ca uptake), and a significantly reduced calcium content in ashed fe murs, but no change in ash weight were observed53 STRONTIUM 3. HEALTH EFFECTS after female juvenile Wistar rats (36 days old) ingested 510 mg strontium/kg/day as strontium carbonate in the diet for 27 days (Morohashi et al. 1994). Th ese rats were also significantly hypocalcemic. No effects were observed at 50 or 100 mg strontium/kg/day other than an unexplained increase in calcium content of bone at 50 mg strontium/kg/day (Morohashi et al. 1994). Minor bone effects occurred in 21-day-old male C57BL/6J mice after ingesting 350 mg strontium/kg/day as strontium chloride in the drinking water for 29 days (Marie and Hott 1986). St rontium had no significant effect on tibial length or bone mineral content (percent ash, calcium, or phosphorus). In vertebrae, strontium had no effect on the osteoblastic surface (percent endosteal surface showi ng plump osteoblasts), bone matrix apposition rate, osteoid seam thickness (average width of all endos teal osteoid seams), or calcified bone volume. However, exposure to strontium resulted in a 10% in crease in osteoid surface (percent endosteal surface covered by an osteoid seam) and an 11% reduc tion in the number of active osteoclasts.
There was radiographic evidence of abnormally thicke ned epiphyseal cartilage plates in the long bones of weanling male Wistar rats exposed to strontium phosphate in the diet at a dose level of 2,820 mg strontium/kg/day for 4–6 weeks, but no effect at 580 mg strontium/kg/day and little effect at 1,270 mg strontium/kg/day (Kshirsagar 1976). Ingestion of 565 mg strontium/kg/day for 43 days resulted in several bone abnormalities in young Sprague-Dawle y rats (Johnson et al. 1968). The level of sodium in bone was significantly lowered, and the level of potassium was significantly increased, and the overall index of bone mineralization (percent bone ash ) was decreased. Unmineralized osteoid was visible in histological sections of vertebrae. Rats became rachitic and osteomalacic and exhibited paralysis of the hindlimbs.

Beneficial effects of a low dose of strontium were noted on bone mineralization, such as a 17% increase in mineral bone volume and a 70% increase in the numb er of bone forming sites, with no adverse effect on the hydroxyapatite mineral particle size in 28-da y-old male Sprague-Dawley rats ingesting 168 mg strontium/kg/day in an unspecified form for 8 week s (Grynpas et al. 1996) or in young SPF Wistar rats fed doses up to 166 mg strontium/kg/day as strontium chlo ride in the diet for 90 days (Kroes et al. 1977). Stimulation of calcified bone growth was noted am ong male weanling Sprague-Dawley rats ingesting between 316 and 524 mg strontium/kg/day as strontium chloride for 9 weeks, but reduced bone calcification was observed at 633 mg/kg/day (Marie et al. 1985). In male weanling Sprague-Dawley rats ingesting 1,520 mg strontium/kg/day for 26 days , epiphyseal growth plates had abnormally thick hypertrophic zones and impaired calcification and resorption at the metaphyseal side (Svensson et al. 1985, 1987). In addition, cartilage from strontium-tr eated rats contained 75% less calcium and had a 60% lower rate of synthesis of glycosaminoglycans and co llagen. When 4-week-old male Wistar rats (50– 60 kg body weight) were fed 1,970 mg strontium/kg/day as strontium carbonate in a diet low in calcium54 STRONTIUM 3. HEALTH EFFECTS (0.04%), bone mineralization was significantly affected (Matsumoto 1976). This study is presented in detail in Section 3.2.2.6 Developmental Effects, as an example of skeletal anomalies in young animals resulting from strontium ingestion.
In another intermediate-duration animal study, young (50–70 g) rats ingested 2,160 mg strontium/kg/day and adult rats ingested 1,570 mg strontium/kg/day as strontium carbonate for 7 months (Storey 1962). At 3 weeks, young rats developed a rachitic gait, and subsequently, so me rats (numbers not specified) developed spinal kyphosis, bent tibiae, and irregular discolored enamel on anterior teeth. Histological abnormalities in long bone differe ntiation included reduced calcification, excess growth of epiphyseal cartilage, abnormal deposition of oste oid (unmineralized bone) in the metaphysis, fragmentation of the epiphyseal plates, and isolated nodules of cartilage. Osteoid accumulation was observed in the skull. Adult rats were affected by strontium ingestion in the same way, but to a lesser degree than young animals. Abnormal depositions of os teoid in long bones and skull were not as extensive as in young rats. The epiphyseal plate did not become fragmented. Tooth enamel was abnormally white and pitted.
Hepatic Effects. No studies were located regarding hepatic effects in humans following oral exposure to stable strontium.
No studies were located regarding hepatic effects in an imals after chronic-duration oral exposure to stable strontium. In acute- and intermediate-duration studi es, in which the diet contained adequate amounts of calcium and vitamin D, few hepatic effects were repo rted. No histological changes were observed in the livers of adult Wistar rats given up to 110 mg strontium/kg/day as strontium chloride in the diet for 2 weeks (Kroes et al. 1977). Acid phosphatase activit y decreased by about 8% in the livers of 5–6 male weanling (21 days old) Wistar rats given 3,000 mg strontium/kg/day as strontium phosphate for 2 weeks (Kshirsagar 1976). However, this effect was reversib le by feeding the rats a normal, low-strontium diet for 2 weeks. In male weanling Wistar rats, inges tion of strontium phosphate in the diet for 4–6 weeks resulted in a >26% decrease in hepatic alkaline phospha tase activity at 2,820 mg strontium/kg/day, but no decrease at 1,270 mg strontium/kg/day (Kshirsagar 1976). The biological significance of these small, but statistically significant, changes in hepatic phospha tase activity is not known. Among weanling male and female Wistar rats fed strontium chloride in the diet for 90 days, the only hepatic effects were ‘slight histological changes’ (not described) and an ‘increase in peripheral glycogen’ in females at the highest dose (166 mg strontium/kg/day); no other hepa tic effects were observed in either sex ≤ 146 mg strontium/kg/day (Kroes et al. 1977).55 STRONTIUM 3. HEALTH EFFECTS
Renal Effects. No studies were located regarding renal effects in humans after oral exposure to stable strontium.
No studies were located regarding renal effects in an imals after chronic-duration oral exposure to stable strontium. In acute- and intermediate-duration studi es, in which the diet contained adequate amounts of calcium and vitamin D, no renal effects were reported. No organ weight or histological changes were observed in the kidneys of adult Wistar rats given up to 110 mg strontium/kg/day as strontium chloride in the diet for 2 weeks (Kroes et al. 1977). Simila rly, no such changes were observed among weanling Wistar rats fed up to 166 mg strontium/kg/day as strontium chloride in the diet for 90 days (Kroes et al. 1977). In male white Leghorn chickens raised on a diet deficient in vitamin D for the first 2 weeks of life, ingestion of 2,350 mg strontium/kg/day in a low-cal cium, low-vitamin D diet for 7 additional days, reduced the activation of vitamin D 3 in mitochondria of the kidney (Omdahl and DeLuca 1972). Because of physiological differences between birds and mammals, this study is omitted from Table 3-1.

Endocrine Effects. Few studies were located regarding endocrine effects in humans after oral exposure to stable strontium. Vezzoli et al. (199 8) reported that strontium absorption was inversely correlated with parath yroid hormone levels.
No studies were located regarding endocrine effect s in animals of acute- or chronic-duration oral exposure to stable forms of strontium. There were no histological changes in the parathyroid gland or alterations in parathyroid horm one levels observed in male w eanling Sprague-Dawley rats given 1,520 mg strontium/kg/day in the diet for 26 days (Svensson et al. 1987). The authors cautioned that their biochemical methods could not distinguish between active and inactive forms of the hormone. A few organ weight changes were observed among weanling Wi star rats fed up to 166 mg strontium/kg/day as strontium chloride in the diet for 90 days (Kroes et al. 1977). The relative thyroid weight was significantly heavier in males at 36 and 146 mg strontium/kg/day and the relative pituitary weight was significantly decreased in females at 10 and 166 mg strontium/kg/day, but in neither case was there a clear dose-response. Slight histological changes in the thyroid were reported.
Body Weight Effects. No studies were located regarding body weight effects in humans after oral exposure to stable strontium.
No studies were located regarding body weight effects in animals after chronic-duration oral exposure to stable strontium. In acute- and intermediate-dura tion animal studies, the effective dose levels for body56 STRONTIUM 3. HEALTH EFFECTS weight effects were relatively hi gh and young animals were more sens itive than adults. In an acuteduration study, there was no effect on body weight in groups of adult SPF Wistar rats that ingested up to 110 mg strontium/kg/day as strontium chloride in the diet for 2 weeks (Kroes et al. 1977). Body weight gain was reduced by 62% among male weanling (21-day-old) Wistar rats that ingested 2,820 mg strontium/kg/day as strontium phosphate in the diet for 2 weeks, but this effect was reversible by feeding rats a diet low in strontium for 2 weeks (Kshirsagar 1976). From an analysis of a pair-fed control group (food intake matched to this high-dose group), the aut hor concluded that the severe effects were a result of excess strontium, and not the reduced diet. I ngestion of 1,090 or 1,63 0 mg strontium/kg/day as strontium lactate reduced body weight gain in 5-week-old albino rats within several days (Teree et al. 1965). However, it seems likely that the reduced bod y weight gains resulted from an observed (but not measured) reduction in food intake, possibly because of reduced palatibility at the higher dose levels. Since the reduction appears not to be a systemic effect of strontium ingestion, this study is omitted from Table 3-1.
Most of the intermediate-duration oral exposure studies in weanling rodents have reported no effect on body weight for exposures <633 mg strontium/kg/day (ra ts: Grynpas et al. 1996; Kroes et al. 1977; Marie et al. 1985; Morohashi et al. 1994; Neufeld and Bosk ey 1994; Skoryna 1981a; and mice: Marie and Hott 1986). Intermediate-duration exposures to stable st rontium at levels above 1,000 mg/kg/day adversely affected body weight. A 15% reduction in body we ight gain was observed among weanling (21-day-old) male Wistar rats that ingested 1,270 mg strontium/kg/day as strontium phosphate for 4–6 weeks, but no reduction was observed at 580 mg strontium/kg/day (K shirsagar 1976). The body weight gain was 28% lower than controls in weanling (21-day-old) male England Wright Y rats that ingested 1,850 mg strontium/kg/day (form unspecified) for 20 days (Reinholt et al. 1985). The terminal body weight was 16% lower than normal in male weanling Sprague-Dawle y rats that ingested 1,520 mg strontium/kg/day (form not specified in this paper, but other publications from this lab used strontium chloride) for 26 days (Svensson et al. 1987).
A >30% loss in body weight occurred in young female rats (40–60 g) that were fed 4,975 mg strontium/kg/day as strontium carbonate for 20 days (Storey 1961); body weight gain was reduced by 24% at 2,220 mg, but was unaffected at 1,460 mg stron tium/kg/day. Food intake was not reported, so it is uncertain to what extent these results are attributable to unpalatability. Similarly treated adult female rats exhibited no significant body weight changes at 2,750 mg strontium/kg/day (Storey 1961). Body weight gain was about a third lower than controls in young (50–70 g) rats that ingested 2,160 mg57 STRONTIUM 3. HEALTH EFFECTS strontium/kg/day as strontium carbonate for 7 months (Storey 1962); no quantitative body weight data were reported for young or adult animals.

In acute- and intermediate-duration studies, str ontium effects on body weight were more severe in animals on diets low in calcium. Reduced body weight gain was reported in young white Leghorn chicks following ingestion of a high strontium/low calcium diet for 1 or 2 weeks (Corradino and Wasserman 1970; Corradino et al. 1971a, 1971b). The body weight gain of male weanling Wistar rats was reduced by 60% after ingestion of strontium carbonate (1,960 mg strontium/kg/day) in a diet low in calcium (0.04%) for 4 weeks (Matsumoto 1976).

Metabolic Effects. No studies were located regarding metabolic effects in humans after oral exposure to stable strontium.
No studies were located regarding metabolic effects in animals after chronic-duration oral exposure to stable strontium. In animal studies, few metabolic effects resulted from acute- or intermediate-duration oral exposure to stable strontium. In chicks given a normal Vitamin D 3 -containing diet for 2 weeks after hatching, ingestion of a diet containing excess stron tium reduced the plasma concentration of calcium, probably a consequence of reduced calcium absorpti on by the duodenum (Corradino et al. 1971a). Intermediate-duration exposures to 150–1,850 mg st rontium/kg/day as strontium carbonate or strontium chloride had no effects on the serum levels of cal cium, phosphorus, or magnesium in young or adult rodents given adequate dietary calcium, phosphorus, a nd vitamin D (rats: Grynpas et al. 1996; Kroes et al. 1977; Marie et al. 1985; Neufeld and Boskey 1994; Svensson et al. 1985, 1987; Reinholt et al. 1984; Skoryna 1981a; and mice: Marie and Hott 1986). No effects on serum calcium levels were observed in young female rats (40–60 g) that were fed 4,975 mg strontium/kg/day as strontium carbonate for 20 days or in adult female rats similarly fed 2,750 mg strontium/kg/day (Storey 1961). At 4,975 mg strontium/kg/day in the young rats, the calcium/stron tium ratio was 1, whereas the ratio at 2,750 mg strontium/kg/day in adult rats was 1.4. A 13% reduction in serum calcium was observed in female juvenile Wistar rats (36-day-old, 6–8 per group) that ingested 510 mg strontium/kg/day as strontium carbonate in the diet for 27 days, but no effect was observed at 100 mg strontium/kg/day (Morohashi et al. 1994).58 STRONTIUM 3. HEALTH EFFECTS
3.2.2.3 Immunological and Lymphoreticular Effects

No studies were located that reported immunological or lymphoreticular effects in humans or animals following oral exposure to stable strontium.

3.2.2.4 Neurological Effects

No studies were located that reported neurological effects in humans following oral exposure to stable strontium. No behavioral effects were observed in ra ts that ingested strontium chloride at levels up to 110 mg strontium/kg/day for 2 weeks or 166 mg strontium/kg/day for 90 days (Kroes et al. 1977). Johnson et al. (1968) reported paralysis of the hindlimbs in weanling male Sprague-Dawley rats that were fed 565 mg/kg/day of stable strontium (form not speci fied) for 43 days. It is not clear whether the observed paralysis was neurological or muscular, but it could have been rela ted to abnormal calcium signaling in muscle or nerve. It is unlikely that the paralysis was due to the deformation of the femora as severely rachitic and osteomalacic rodents are not generally paralyzed. The NOAEL and LOAEL are recorded in Table 3-1 and plotted in Figure 3-1.

3.2.2.5 Reproductive Effects

No studies were located regarding reproductive effect s in humans or animals following oral exposure to stable strontium.

3.2.2.6 Developmental Effects

No studies were located regarding developmental effects in humans following acute- or intermediateduration oral exposure to stable forms of strontium. The only chronic-duration study is the Turkish epidemiological analysis that found a relationship betw een the concentration of strontium in the local soil and the prevalence of rickets in children between the ag es of 6 months and 5 years (Ögzur et al. 1996). A relatively short period of breast feeding, which presumably affected calcium intake, and soil levels of strontium higher than 350 ppm, which probably determ ined the level of strontium in dietary grains consumed after weaning, were associated with an incr ease in the prevalence and sev erity of rickets. This study is discussed above in Section 3.2.2.2 Musculoskeletal Effects.59 STRONTIUM 3. HEALTH EFFECTS No studies were located that examined the effect of exposure to stable strontium in utero following oral maternal exposure in animals. However, the studi es discussed in Section 3.2.2. 2 Musculoskeletal Effects address the effects of strontium on bone organogenesi s, in particular, endochondral ossification, a developmental process that continues long after birth. For example, in a study in which 4-week-old male Wistar rats (50–60 g body weight) were fed 1,970 mg strontium/kg/day as strontium carbonate in a diet low in calcium (0.04%), bone mineralization was significantly affected (Matsumoto 1976). Tibial length was reduced by 33% and the tibial proximal and dist al epiphyseal plates were both about 5 times wider than normal. Microradiographic and histological analyses of tibial proximal heads revealed that no mineralization was detectable, that the organization of chondroblasts was irregular, and that osteoid rather than mineralized bone was deposited. Other studi es on weanlings were conduc ted for acute durations (rat: Kshirsagar 1976) and intermediate durations (rat: Grynpas et al. 1996; Kroes et al. 1977; Morohashi et al. 1994; Neufeld and Boskey 1994; Reinholt et al. 1984, 1985; Svensson et al. 1985, 1987; and mice: Marie and Hott 1986). Intermediate-duration studies on rats demonstrated that ingestion of strontium resulted in more severe skeletal effects in young animals than in adults (Storey 1961, 1962). These studies are described in Section 3.2.2.2 Musculoskeletal Effects and are listed in Table 3-1 and Figure 3-1 under that category.

3.2.2.7 Cancer

No studies were located that demonstrated cancer eff ects of stable strontium following oral exposure in humans or animals. In one case-control study, no association was found between the incidence of liver cancer in 1984 on Chongming Island in China and the levels of stable strontium detected in hair (Wang et al. 1990).

3.2.3 Dermal Exposure

No studies were located regarding the following hea lth effects in humans or animals after dermal exposure to stable strontium:60 STRONTIUM 3. HEALTH EFFECTS
3.2.3.1 Death
3.2.3.2 Systemic Effects
3.2.3.3 Immunological and Lymphoreticular Effects
3.2.3.4 Neurological Effects
3.2.3.5 Reproductive Effects
3.2.3.6 Developmental Effects
3.2.3.7 Cancer

3.2.4 Other Routes of Exposure
This section includes injection and in vitro studies that provide evidence for the biological basis of toxicity of stable strontium in humans and animals. Since these studies are not directly relevant to general population exposure conditions, no LSE tables have been created for this section.

Cardiovascular Effects. Cardiovascular effects of strontium have been investigated by intravenous infusion studies in dogs. Infusions of strontium (as chloride or gluconate) averaging 172 mg strontium/kg under conditions of lowered potassium induced accelerated ventricular escape beats, ventricular tachycardia, or atrial fibrillation (Foster et al. 1977). High levels of strontium also induced oscillatory potentials and prolonged depolarization (precursors to arrhythmia) in Purkinje fibers of isolated sheep hearts (Gonzalez and Vassalle 1990). Whereas intrave nous infusions at 4 mg strontium/kg had no effect on cardiac physiology, infusions at ~15 mg strontium/kg that brought the strontium/Ca ratio above 1 had a temporary negative chronotropic effect, redu ced cardiac output, increased pulmonary vascular resistance, and systemic vascular resistance, but had no effect on pulmonary or systemic arterial pressure or pulmonary wedge pressure (Barry et al. 1972; Skoryna et al. 1986). The concentrations of strontium used in these studies are very high relative to the mean concentration of strontium in human blood, 27 μg strontium/L (see Table 6-9).
Hematological Effects. Because of its molecular similarity to calcium, the association of stable strontium with several kinds of blood cells has been investigated in a number of in vitro experiments. Strontium ions were found to be transported across the cell membrane of human erythrocytes by means of an ATP-dependent calcium pump (de la Sierra et al. 1990; Olson 1979; Olson and Cazort 1969; Porzig 1973). In washed platelets from human and rabbit, strontium stimulated the secretion of61 STRONTIUM 3. HEALTH EFFECTS 5-hydroxytryptamine (Best et al. 1981; Bone et al. 19 80; Togna et al. 1989). Best et al. (1981) concluded that strontium activates the release of arachidona te from platelet membrane phospholipid, with the subsequent synthesis of thromboxane A 2 , a reaction that was antagonized by aspirin. These authors also suggested that strontium, because of its smaller hydrat ed ionic radius compared to calcium, is able to enter the platelet and mimic the rise in cytosolic cal cium concentration that normally serves to activate secretion of 5-hydroxytryptamine (Best et al. 1981). Strontium was also found to stimulate degranulation of human large granular lymphocytes, which resulte d in the inhibition of natural killer (NK) cells (Neighbour et al. 1982). The content of strontium (and calcium) was found to be significantly elevated above healthy control levels in granulocytes isolat ed from Swedish patients with active rheumatoid arthritis or seronegative spondarthritis (Hällgren et al . 1984). The strontium overload was thought to be linked to the degree of inflammation, and was positively related to serum levels of the acute-phase protein haptoglobin; corticosteroid therapy differentially redu ced the strontium content of granulocytes compared to calcium. The authors suggested that leukocyte endogenous mediator (LEM) regulated the accumulation of strontium in granulocytes.
Immunological and Lymphoreticular Effects. Several in vitro experiments have demonstrated that strontium, although less efficient than calcium, is able to stimulate histamine release from rat mast cells (Alm and Bloom 1981a, 1981b; Atkinson et al. 1979; Foreman 1977; Foreman and Mongar 1972a, 1972b; Foreman et al. 1977). This is probably releva nt to humans, since strontium has been shown to degranulate human lymphocytes (Neighbor et al. 1982) and stimulate the release of 5-hydroxytryptamine by human platelets (Best et al. 1981) (see Hematological Effects above). In rabbit blood treated with strontium chloride in vitro, the bacterocidal properti es of serum were reduced (Toshioka et al. 1974); this effect was attributed to the inhibition of complement.
Neurological Effects. In vitro studies have demonstrated subtle differences between strontium and calcium with respect to neurological function at the cellular level. In a calcium-free medium, strontium ion weakly supported the generation of excitatory postsynaptic potentials following stimulation of guinea pig superior cervical ganglia (i.e., the release of a cetylcholine was less efficien t than when calcium was present) (McLachlan 1977). Calcium is sequestered in mitochondria and smoot h endoplasmic reticulum of isolated presynaptic nerve terminals in preference to strontium (Rasgado-Flores et al. 1987). Strontium ion inhibits the uptake of calcium by synaptic vesicl es in vitro, thereby blocking the antiport-regulated release of H+ (Gonçalves et al. 1999). Strontium i on was slightly more efficient than calcium ion in supporting the release of neurotransmitter from syna ptosomes induced by leptinotoxin-h (Madeddu et al. 1985). Strontium ion was found to support the asynchrono us mode of transmitter release in isolated layer62 STRONTIUM 3. HEALTH EFFECTS V pyramidal cells of the prefrontal cortex (Aghajani an and Marek 1999). This is apparently mediated through calcium-binding protein synaptotagmin III, as strontium does not support the function of calcium-binding synaptotagmins I and II (Li et al. 1995).
Reproductive Effects. The results of one in vitro study suggest that stable strontium is not directly harmful to human spermatozoa. In developing an improved method to be used by fertility clinics for testing the functional capacity of human spermatozoa, it was found that inclusion of strontium chloride in the testing medium improved the rate of penetra tion compared to calcium chloride (Mortimer 1986; Mortimer et al. 1986).
Developmental Effects. Subcutaneous injection of up to 82 mg strontium/kg/day as strontium nitrate into female Wistar rats be tween days 9 and 19 of gestation ha d no teratogenic effect, no adverse effect on the ossification of the skeleton, and no e ffect on the number of resorptions (Lansdown et al. 1972).

3.3 DISCUSSION OF HEALTH EFFECTS OF RADIOACTIVE STRONTIUM BY ROUTE OF EXPOSURE
Section 3.3 discusses radiation toxicity associated with exposure to radionuclides of strontium 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 carcinog enic 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 NOAELs or LOAELs reflect the actual dose (levels of exposure) used in the studies. Refer to Secti on 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 effect s (Cancer Effect Levels, CELs) of radiostrontium are indicated in Tables 3-2, 3-3, and 3-4 and Figures 3-2 and 3-3. Because cancer effects could occur at lower exposure levels, Figures 3-2 and 3-3 also s how 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.63 STRONTIUM 3. HEALTH EFFECTS Refer to Appendix B for a User's Guide, which shoul d aid in the interpretation of the tables and figures for Levels of Significant Exposure.

3.3.1 Inhalation Exposure
The two major sources of data regarding health effects of inhaled radioactive strontium are long-term studies using beagles at the Lovelace Foundation, Albuquerque, New Mexico (now known as the Lovelace Respiratory Research Institute). One study examined the acute inhalation effects of a relatively soluble aerosol of 90 SrCl 2 , and the other examined the acute inhalation effects of relatively insoluble particles of 90 Sr fused to aluminum silicate (‘ 90 Sr fused-clay particles’).
In the soluble aerosol study, beagles were exposed by nose breathing for varying exposure durations (2–22 minutes) to graded concentrations (2.16–419 μCi 90 Sr/L; 0.08–15.5 MBq/L) of 90 SrCl 2 to produce graded levels of initial body burde ns. Individual variations in the degree to which aerosol was cleared from the respiratory tract and swallowed contributed to variability in the initial rapid rate of clearance during the first few days. Therefore, exposures were expressed in terms of the long-term retained burden (LTRB), which ranged from 1.08 to 119 μCi (0.04–4.4 MBq) 90 Sr/kg of body weight. Radiostrontium quickly passed through the lungs and was overwhelmingly retained in the skeleton, where initial skeletal dose rates were calculated to be 0.43–55 rad/day (0.0043–0.55 Gy/day). Clearance of radiostrontium from the skeleton was gradual. For that reason, the initial and long-term health effects were primarily related to hemopoietic bone marrow and oste ogenic tissues. Reports relating to the 90 SrCl 2 aerosol study include Benjamin et al. (1974b, 1975, 1976a, 1976c, 1979), Boecker et al. (1969, 1991), Fission Product Inhalation Project (1967a), Gillett et al. (1987a, 1987b), Hahn et al. (1991), McClellan et al. (1973, 1983a), and Muggenburg et al. (1977, 1978, 1979).
In the other study, beagles were exposed by nose-only inhalation to 90 Sr fused-clay particles for initial lung burdens ranging from 0.21 to 94 μCi 90 Sr/kg (0.008–3.5 MBq/kg) of body weight. Control animals were exposed to similar aluminosilicate clay particles fused to stable strontium. Early and late-occurring health effects of inhaled particulate radiostrontiu m were primarily associated with the lung. Some particles were cleared into the lung-associated lymph nodes, where radiation damage led to their entry into the circulatory system, leading to distribution to spleen, liver, and possibly other tissues. Trapping of radioactive particles by these tissues created possible sites for radiation damage and tumor development. The biological retention half-time for 90 Sr in fused-clay particles was approximately 490 (±320 days standard deviation). Reports relating to 90 Sr fused clay particles include Benjamin et al. (1974a, 1975),64 STRONTIUM 3. HEALTH EFFECTS Griffith et al. (1992), Hahn et al. (1983a), Hobbs et al. (1972), Jones et al. (1972, 1976), Scott (1980), and Snipes et al. (1974a, 1974b, 1976, 1977, 1978, 1979). A similar study with a smaller group of dogs was carried out by Benjamin et al. (1976c).

3.3.1.1 Death

No studies were located regarding death in hum ans following inhalation exposure to radioactive strontium. Information on the lethality of inhaled radioactive strontium is limited to acute exposure studies. Because of the bone-seeking behavior of strontium, an acute exposure to airborne 90 Sr results in chronic exposure to radiation from 90 Sr incorporated into bone. If insoluble radiostrontium compounds are inhaled, there could be long-term lung exposure (see discussion of the study by Willard and Snyder (1966) in Section 3.5.1.1).
In two different experiments briefly described in a report by the Lovelace Foundation (now known as the Lovelace Respiratory Research Institute), young male and female Holtzman rats were exposed once to
90 Sr by whole body inhalation for initial bod y burdens ranging from 170 to 1,660 μCi 90 Sr/kg (0.63– 61.4 MBq/kg) of body weight and average skelet al radiation doses ranging from 12,600 to 19,000 rad (126–190 Gy) (Fission Product Inhalation Project 1967b). Survival was inversely proportional to dose, with rats receiving the lowest dose living for more than 700 days, and those receiving the highest dose living less than 200 days. In the two experiments, 77% of the rats that died and 47% of the rats that were killed in a moribund state were found to have osteosar coma. Among rats dying with tumors, the average skeletal dose was 81 rad/day, compared to 62 rad/day fo r rats without tumors (0.81 vs 0.62 Gy/day). The small sample sizes in this study do not pe rmit its inclusion in the LSE Table 3-2.
In acute inhalation studies in beagle dogs , high-dose radiation effects of inhaled 90 SrCl 2 on bone marrow resulted in death within days or weeks of expos ure, whereas lower doses reduced long-term survival through carcinogenetic effects. For all exposed dogs, the mean survival time was 3,000 days, comparedto 4,500 days for the controls (Gillett et al. 1987b). Among dogs receiving high or medium doses (longterm retained body burdens between 47 and 120 μCi 90 Sr/kg (1.74 and 4.44 MBq/kg), 6/22 died within 32 days from severe hypoplasia of the bone marro w (Gillett et al. 1987a; Muggenburg et al. 1979). Individual neutrophil counts were the most reliable predictors of lethality. Death from primary bone tumors occurred from 2 to 10 years after exposure to inhaled 90 SrCl 2 (Gillett et al. 1987b). Fibrosarcomas and metastasizing hemangiosarcomas occurred somewhat earlier than osteosarcomas and were the major65 STRONTIUM 3. HEALTH EFFECTS
contributors to shortened mean survival times for the dogs exposed to inhaled 90 SrCl 2 (Gillett et al. 1987b). Deaths from myelomonocytic leukemia and fro m bone-associated soft tissues of the skull were also concluded to be associated with radiostrontiu m; the long-term retained burdens were 9.2–27 μCi
90 Sr/kg (0.34–1.0 MBq/kg) and 21–35 μCi 90 Sr/kg (0.081–1.3 MBq/kg), respectively. These are extreme doses.
In beagle dogs exposed by acute inhalation to 90 Sr fused-clay particles, the pattern of mortality was different since the radioactive particles were initially embedded in the lung. No deaths occurred until the 5 th month postexposure. Of 36 d ogs with initial lung burdens ≥ 25 μCi 90 Sr/kg (925 kBq/kg) of body weight, 35 died within the first 2 years, primarily of radiation pneumonitis and/or pulmonary fibrosis (Snipes et al. 1979). Subsequently, within the 2 nd to 7 th years after exposure, deaths from hemangiosarcoma and carcinoma of the lung were common. None of the control dogs died during the 9 years following exposure (Snipes et al. 1979), indicating that the observed mortality was not caused by inhalation of nonradioactive aluminum silicate pa rticles alone. Among dogs dying prematurely from neoplasms of the lung, the initial lung burdens we re between 3.7 and 94 μCi/kg (0.14–3.5 MBq/kg) and the doses to the lungs ranged from 43,000 to 67,000 rad (430–670 Gy) (Benjamin et al. 1975).
The percent mortality values for dogs from exposure to radioactive strontium by the inhalation route are presented in Table 3-2 and plotted in Figure 3-2.

3.3.1.2 Systemic Effects

No studies were located that described endocrine, dermal, or ocular effects in humans or animals following inhalation exposure to radioactive stron tium. The highest NOAEL values and all reliable LOAEL values in each species and duration category for systemic effects from radiation exposure to strontium by the inhalation route are presented in Table 3-2 and plotted in Figure 3-2.
Respiratory Effects. The only respiratory effects reported for the study in which beagle dogs were exposed to soluble aerosols of 90 SrCl 2 (Boecker et al. 1969; Gillett et al. 1987b) were late primary cancers of the respiratory tract or tumors metastasizing to th e lung. These effects are discussed in Section 3.2.1.7 Cancer.Table 3-2 Levels of Significant Exposure to Strontium - Radiation Toxicity - InhalationExposure/LOAELDuration/aFrequencyReferenceKey to SpeciesNOAEL Less SeriousSerious(Specific Route)figure (Strain)System(μCi/kg) (μCi/kg)(μCi/kg)Chemical FormACUTE EXPOSUREDeath1Dog2-22 minGillett et al. 1987a47 [LTRB] (6/24 died from boneonce(Beagle)marrow hypoplasia)Strontium-90 (chloride)Systemic2DogonceBenjamin et al. 1976cCardio25 [ILB] (damaged pulmonary(Beagle)vasculature; hypertrophic rightSr-90 (fused-clay particles)ventricle; congestive heartfailure)Hepatic25[ILB] (all with chronic passivecongestion; one with mildcentrilobular fibrosis)Bd Wt25[ILB] (emaciation)3Dog2-22 minGillett et al. 1987aGastro47[LTRB] (anorexia, bloodyonce(Beagle)diarrhea from acute radiationStrontium-90 (chloride)syndrome)Hemato1.5[LTRB] (60% decr plateletcount)Renal47[LTRB] (incr blood ureanitrogen, decr urine output fromacute radiation syndrome)Table 3-2 Levels of Significant Exposure to Strontium - Radiation Toxicity - Inhalation(continued)Exposure/LOAELDuration/aFrequencyReferenceKey to SpeciesNOAEL Less SeriousSerious(Specific Route)figure (Strain)System(μCi/kg) (μCi/kg)(μCi/kg)Chemical Form4Dog2-22 minMuggenburg et al. 1977Gastro1.9 [LTRB] (malabsorptiononce(Beagle)syndrome at age >11 yrs)Strontium-90 (chloride)Bd Wt1.9[LTRB] (decr bd wt)5DogonceSnipes et al. 1979Resp25 [ILB] (pulmonary pneumonitis,(Beagle)fibrosis)Sr-90 (fused-clay particles)Gastro4.1[ILB] (ulcerating lesion ofpharynx; anorexia)Immuno/ LymphoretonceBenjamin et al. 1976c6Dog25 [ILB] (50% decr lymphocytes(Beagle)for 28 weeks)Sr-90 (fused-clay particles)7Dog2-22 minGillett et al. 1987a10 [LTRB] (22% decr lymphocyteonce(Beagle)count lasting 3 years)Strontium-90 (chloride)8DogonceJones et al. 19765 [ILB] (lymphocyte counts decr(Beagle)40% for two years)Sr-90 (fused-clay particles)Table 3-2 Levels of Significant Exposure to Strontium - Radiation Toxicity - Inhalation(continued)Exposure/LOAELDuration/aFrequencyReferenceKey to SpeciesNOAEL Less SeriousSerious(Specific Route)figure (Strain)System(μCi/kg) (μCi/kg)(μCi/kg)Chemical FormCancer9RatonceLovelace Foundation 1967210 (CEL: osteosarcoma)(Holtzman)Strontium-90/yttrium-9010DogonceBenjamin et al. 19753.7 [ILB] (CEL: hemangiosarcoma(Beagle)of lung, heart)Sr-90 (fused-clay particles)11Dog2-22 minGillett et al. 1987b7 [LTRB] (CEL: osteosarcoma)once(Beagle)Strontium-90 (chloride)9 [LTRB] (CEL: leukemia)27[LTRB] (one premature deathafter 585 days from leukemia)2 [LTRB] (CEL: nasal carcinoma)aThe number corresponds to entries in Figure 3-2.Bd Wt = body weight; Cardio = cardiovascular; CEL = cancer effect level; decr = decreased; Gastro = gastrointestinal; (GW) = gavage in water; Hemato = hematological; hr = hour(s);[ILB] = initial lung burden; incr = increased; LOAEL = lowest-observed-adverse-effect level; [LTRB] = long-term retained burden; min = minute(s); NOAEL =no-observed-adverse-effect level; Resp = respiratoryDeath Respiratory Cardiovascular Gastrointestinal Hematological Hepatic Renal Body W Immuno/L Cancer *1000 eight ymphorFigure 3-2 Levels of Significant Exposure to Strontium - Radiation Toxicity - InhalationAcute (≤14 days)SystemicuCi/kg9r1001d3d3d11d5d2d2d2d6d107d11d11d8d5d10d11d3d4d4d1*Doses represent the lowest dose tested per study that produced a tumorigenicresponse and do not imply the existence of a threshold for the cancer endpoint.0.1c-Cat-Humansf-Ferret n-MinkCancer Effect Level-AnimalsCancer Effect Level-HumansLD50/LC50d-Dog k-Monkey j-Pigeon o-OtherLOAEL, More Serious-AnimalsLOAEL, More Serious-Humans Minimal Risk Levelr-Rat m-Mouse e-GerbilLOAEL, Less Serious-AnimalsLOAEL, Less Serious-Humansfor effectsp-Pig h-Rabbit s-HamsterNOAEL - AnimalsNOAEL - Humansother thanq-Cow a-Sheep g-Guinea PigCancer70 STRONTIUM 3. HEALTH EFFECTS Respiratory effects were more pronounced in beagle dogs that were exposed to 90 Sr fused-clay particles by inhalation (Benjamin et al. 1976c; Snipes et al. 1979). The primary cause of early death among dogs exposed to initial lung burdens ≥ 25 μCi 90 Sr/kg (925 kBq/kg) was ra diation pneumonitis and/or pulmonary fibrosis (Snipes et al. 1979). No such e ffects were reported in control dogs exposed to nonradioactive aluminosilicate-fused clay particles (S nipes et al. 1979). Clinical signs included an increased respiratory rate, dyspnea, cyanosis, and dry and moist rales (Benjamin et al. 1976c). Radiographically, the dogs showed increased focal or diffuse lung-field densities. The pneumonitis was characterized by acute and chronic inflammation with increased numbers of alveolar macrophages, hypertrophy and hyperplasia of alveolar lining ce lls, degeneration of the bronchiolar epithelium and alveolar ducts, focal emphysema, and edema. The fibrosis involved the alveolar septa, pleura, and perivascular regions, with substantial scarring. V ascular damage in the lungs was characterized by congestion, hemorrhage (possibly related to thromboc ytopenia), fibrin exudation, and occasional vessels with fibrinoid necrosis or intimal proliferation.

Cardiovascular Effects. Acute inhalation of radiostrontium was reported to lead to adverse cardiovascular effects in dogs. Among beagles that died within 5–15 months following inhalation exposure to 90 Sr fused-clay particles, most exhibited myocardial necrosis or dege neration, and fibrosis, primarily of the right atrium (Hobbs et al. 1972); these animals had initial lung burdens between 33 and 100 μCi/kg (1.2–3.7 MBq/kg) and cumulative beta radi ation doses to the lung of 34,000 to 82,000 rad (340–820 Gy). In a later report of the same study, acute and chronic vascula r lesions, characterized as inflammatory or degenerative, affected the elastic and muscular pulmonary arteries in dogs with initial lung burdens between 16 and 94 μCi/kg (0.6–3.5 MB q/kg) and doses to the lung between 40,000 and 96,000 rad (400–960 Gy) at the time of death (Snipes et al. 1977). Vascular damage in the lungs was characterized by congestion, hemorrh age, fibrin exudation, and occasiona l vessels with fibrinoid necrosis or intimal proliferation (Benjamin et al. 1976c). These e ffects were attributed to the direct effect of beta radiation (from radiostrontium particles embedded in the lung) on adjacent tissue. In addition, presumably as a consequence of radiation damage to the pulmonary vasculature, the right ventricle became dilated and hypertrophic with congestiv e heart failure. Hemangiosarcomas resulting from radiostrontium exposure in this study ar e discussed in Section 3.3.1.7 Cancer.

Gastrointestinal Effects. Gastrointestinal effects were observed in beagle dogs receiving single high doses (long-term retained body burdens betw een 47 and 83 μCi/kg; 1.74 and 3.07 MBq/kg) of soluble aerosols containing 90 SrCl 2 (Gillett et al. 1987a). Anorexia and, 2 days before death, bloody diarrhea, developed in six dogs that died between 18 and 32 days after the extreme radiation dose rate71 STRONTIUM 3. HEALTH EFFECTS induced acute radiation syndrome (Gillett et al. 1987a). It is likely that severe thrombopenia, one of the features of radiation-induced bone marrow hypoplasia, contributed to hemorrhage in the gastrointestinal tract as elsewhere in the body. In addition, some effects could have been due to inhaled 90 SrCl 2 droplets being transported from the mucoid, ciliated nasopharyng eal and tracheobronchial epithelia to the pharynx and then swallowed. The gastrointestinal epitheliu m then would have been exposed directly to beta emissions from radiostrontium for a day or two. Another report of the same study described three exposed dogs that died at age >11 years with a ma labsorption syndrome (Muggenburg et al. 1977). All of the dogs exhibited chronic diarrhea with anorexia, and at necropsy, contained chronic degenerative and inflammatory lesions of the small intestines. Th eir long-term retained bur dens were 1.9–9.6 μCi/kg (70.3–355.2 kBq/kg) and the absorbed doses to the sk eleton were calculated to be 530–5,600 rad (5.3– 56 Gy). Although the authors could not firmly establish whether the syndrome was a consequence of exposure or of age, the cumulative radiation dose to th e digestive tract was likely to have been very low and this argues against 90 Sr as the cause.
One beagle dog that was exposed to 90 Sr fused-clay particles and had an initial lung burden of 4.1 μCi/kg (151.7 kBq/kg) and a cumulative radiation dose to the lung of 20,000 rad (200 Gy) died 9 years after exposure with anorexia and an ulcerative lesion to the pharynx (Snipes et al. 1979). Whether the pharyngeal lesion was related to exposure is uncerta in, since the report was preliminary and no other response to radiation had been observed in this animal.
Hematological Effects. Profound hematological effects were observed in beagle dogs that were exposed once by inhalation either to soluble aerosols containing 90 SrCl 2 , or to 90 Sr fused to aluminosilicate particles that produced extremely la rge radiation dose rates and doses in the affected tissues sufficient to induce acute radiation syndrome.
Significant dose-related pancytopenia devel oped in dogs that were exposed to 90 SrCl 2 aerosols and had long-term retained burdens >10 μCi (370 kBq) 90 Sr/kg (Gillett et al. 1987a). Profound decreases in platelet numbers were evident by 7 days and we re maximal by 28 days. Drastic thrombocytopenia (platelets reduced >90%) probably contributed to wi despread hemorrhaging and premature death in dogs with long-term retained burdens ≥ 47 μCi/kg ( ≥ 1.7 MBq/kg). Significant immediate reductions in platelet counts (>60%) occurred in surviving dogs with long-term retained burdens of ≥ 1.5 μCi/kg ( ≥ 0.56 MBq/kg). However, even dogs with the lowestlong-term retained burdens (1–10 μCi/kg; 0.04– 0.36 MBq/kg), which otherwise showed little immediate effect, exhibited long-term (>3 years) depression in platelet counts compared to controls. The pattern of neutropenia followed a similar exposure-response,72 STRONTIUM 3. HEALTH EFFECTS and profound neutropenia was the most accurate pred ictor of death. In surviving dogs that were immediately affected by exposure, neutrophil count s recovered, but in these dogs, as well as those immediately unaffected, significant long-term (>3 years) suppression was observed compared to controls. Similarly, lymphocyte counts were drastically reduced (by 75%) in dogs dying within weeks of exposure with long-term retained burdens ≥ 47 μCi/kg ( ≥ 1.7 MBq/kg). Surviving dogs with long-term retained burdens >10 μCi (370 kBq) 90 Sr/kg exhibited a long-term (>3 years) suppression of lymphocyte counts (>30%). Dogs with long-term re tained burdens between 6 and 10 μCi/kg (0.26–0.36 MBq/kg) exhibited normal lymphocyte counts that were normal over 1,40 0 days except for periods of significant depression at 60–120 and 900–1,000 days. Dogs with long-term retained burdens betw een 1 and 3 μCi/kg (0.04– 0.12 MBq/kg) had lymphocyte counts that were not significantly different from controls. Reduced erythrocyte mass, as exemplified by decreases in hematocrit, red blood ce ll counts, and hemoglobin levels, occurred between 2 and 3 week s after exposure (slightly later than the depression in platelet andwhite cell counts). In the most severely affected dogs, red blood cell counts fell to 70–80% of preexposure values, with maximal depression at 32 days . Prolonged depression of erythrocyte counts was observed in surviving dogs with long-term retained burdens ≥ 27 μCi/kg ( ≥ 1 MBq/kg).
Significant suppression of peripheral lymphocyte counts was observed in beagle dogs that were exposed by inhalation to 90 Sr fused-clay particles (Jones et al. 1976). Lymphocytes declined gradually over time in all exposed groups (initial lung burdens ≥ 5 μCi/kg; ≥ 185 kBq/kg), and remained more than 50% lower than controls after 2 years.
Hepatic Effects. No studies were located that described hepatic effects in humans following inhalation exposure to radioactive strontium. A ll beagle dogs that died from radiation pneumonitis following a single inhalation exposure to high concentrations of 90 Sr fused-clay particles (25 μCi 90 Sr/kg of body weight; 925 kBq/kg) exhi bited chronic passive congestion of the liver, and one had mild centrilobular fibrosis (Benjamin et al. 1976c).

Renal Effects. No studies were located that described renal effects in humans following inhalation exposure to radioactive strontium isotopes. Some be agle dogs in the terminal stages of acute radiation syndrome following inhalation exposure to aerosols of 90 SrCl 2 (long-term retained burden 47–83 μCi 90 Sr/kg; 1.74–3.07 MBq/kg) had low urine output and elevated blood urea nitrogen (Gillett et al. 1987a).73 STRONTIUM 3. HEALTH EFFECTS Body Weight Effects No studies were located that described body weight effects in humans following inhalation of radiostrontium. Anorexia and reduced body weight were observed among beagle dogs with long-term retained burdens between 45 a nd 119 μCi/kg (1.7–4.4 MBq/kg) following inhalation of 90 SrCl 2 aerosols (Gillett et al. 1987a; Muggenburg et al . 1977) or initial lung burdens between 25 and 32 μCi/kg (0.93–1.2 MBq/kg) following inhalation of 90 Sr fused-clay particles (Benjamin et al. 1976c).

3.3.1.3 Immunological and Lymphoreticular Effects

No studies were located regarding immunological e ffects in humans following inhalation exposure to radioactive strontium isotopes. However, profound ef fects on the immune system were a consequence of acute inhalation exposure to radiostrontium in dog studies. Effects in dogs exposed to soluble aerosols of
90 SrCl 2 were sequelae of general irradiation of the bone marrow from 90 Sr incorporated into bone. Significant dose-related lymphopenia was observed in young adult beagle dogs (12–14 months old) after a single inhalation exposure to 90 SrCl 2 at long-term retained burdens >10 μCi 90 Sr/kg (370 kBq/kg; Gillett et al. 1987a). Furthermore, there was some evid ence of immunosuppression in dogs with average initial body burdens of 35 μCi 90 Sr/kg (1.3 MBq/kg) (Fission Product Inhalation Project 1967a); titers for infectious canine hepatitis and leptospira vaccines were depressed more than 30% following exposure to
90 SrCl 2 aerosols. Effects in dogs exposed to relatively insoluble 90 Sr fused-clay particles were primarily a consequence of irradiation of the blood as it circul ated through the lungs, although some damage to thoracic lymph nodes was observed. Among beagle dogs (17–20 months old) exposed by nose-only inhalation to 90 Sr fused clay particles (initial lung burdens 25–32 μCi 90 Sr/kg; 0.925–1.18 MBq/kg), the numbers of peripheral lymphocytes were de pressed by more than 50% during the 12 th through 28 th weeks after exposure, although recovery was observed by week 44 (Benjamin et al. 1976c). The cumulative radiation dose to the lungs ranged from 35,000 to 43,000 rad (350–430 Gy). During the period of lymphocyte suppression, the immune response to phytohemagglutinin antigen tested in vitro was depressed 10-fold in the dog that had the highest initial lung burden (32 μCi/kg; 1.18 MBq/kg) and was the first to die. In this animal, the tracheobronchi al and sternal lymph nodes, which received a significant radiation dose from 90 Sr, were depleted of lymphocytes, alt hough peripheral nodes, which received much lower doses, were nearly normal. In the main study that employed 1-year-old beagles, the highest initial lung burdens of 90 Sr fused-clay particles resulted in severe at rophy and fibrosis of the tracheobronchial lymph nodes (Snipes et al. 1977). In other dogs, whic h had initial lung burdens averaging between 5 and 19 μCi/kg (185 and 703 kBq/kg), fluctuations in the peripheral lymphocyte numbers were observed, but the values remained depressed by 40% for 2 years following inhalation exposur e (Jones et al. 1976).74 STRONTIUM 3. HEALTH EFFECTS Cumulative doses in these dogs ranged from 1,055 to 4, 005 rad (10.5–40 Gy). None of the dog studies reported whether there was a NOAEL identified for immunological effects. Significant chronic suppression of the immune system is considered a seri ous effect because of the impaired resistance to infectious disease.

3.3.1.4 Neurological Effects

No studies were located that described neurological effects in humans following inhalation exposure to radioactive strontium. A beagle dog that w as exposed to the highest concentration of 90 SrCl 2 aerosol (long-term retained burden of 119 μCi/kg or 4.4 MB q/kg) succumbed with epileptic seizures, but the authors deemed these to be unrelated to exposure (Gillett et al. 1987b). Serious neurological effects (convulsions, paralysis) were observed in several dogs that were in the terminal stages of cancer following inhalation of 90 Sr fused clay particles (Snipes et al. 1977, 1978). No other studies addressed neurological effects in animals following inhalatio n exposure to radioactive strontium isotopes.
The highest NOAEL values and all reliable LOAEL values in each species and duration category for neurological effects from exposure to radioactive st rontium by the inhalation route are presented in Table 3-2 and plotted in Figure 3-2.
No studies were located regarding the following e ffects in humans or animals following inhalation exposure to radioactive strontium:

3.3.1.5 Reproductive Effects
3.3.1.6 Developmental Effects

3.3.1.7 Cancer

No studies were located regarding cancer in hum ans following inhalation exposure to radioactive strontium isotopes, but several studies reported carcinoge netic effects in animals. The types of cancers produced varied with the form of strontium administer ed. In studies using soluble forms of radioactive strontium, (e.g., 90 SrCl 2 ), bone-associated cancers were the predominant types, because absorbed strontium primarily incorporates into bo ne. Studies using relatively insoluble 90 Sr fused-clay particles75 STRONTIUM 3. HEALTH EFFECTS reported lung-related cancers as the major initial types, since the particles were initially embedded in the lungs. As particles slowly dissolved (releasing 90 Sr) or were cleared from the lungs, tumors were induced in other tissues.
In two different experiments described in a report by the Lovelace Foundation (now known as the Lovelace Respiratory Research Institute), young male and female Holtzman rats were exposed once to an aerosol of 90 Sr in cesium chloride by whole body inhalati on for initial body burdens ranging from 170 to 1,660 μCi 90 Sr/kg (6.3–61.4 MBq/kg) of body weight (Fi ssion Product Inhalation Project 1967b). The average skeletal radiation doses over their remaini ng lifespans averaged from 12,600 to 25,900 rad (126– 259 Gy). In the two experiments, 77 or 47% of the rats that died or were euthanized in a moribund state were found to have bone tumors (osteosarcomas). Am ong rats dying with tumors, the average skeletal dose rate was 81 rad/day, compared to 62 rad/day for rats without tumors (0.81 vs 0.62 Gy/day).
Primary bone cancer was the most frequent cause of death in beagle dogs (30/66) given a single inhalation exposure to 90 SrCl 2 aerosol and then observed for their lifespans (Benjamin et al. 1974a, 1976a, 1979; Gillett et al. 1987b; McClellan et al. 1973; Mu ggenburg et al. 1977, 1978 , 1979). The cumulative absorbed doses of beta radiation to bone ranged from 12 to 1,200 rad (0.012–12 Gy) at 30 days and from 200 to 170,000 rad (2–1,700 Gy) at 1,000 days after exposure. In dogs with bone-related tumors, the long-term retained burdens ranged from 2 to 119 μCi 90 Sr/kg (0.081–4.4 MBq/kg ) of body weight. Bone-tumor-related deaths occurred 759–3,472 days after exposure (median survival time of 1,702 days, compared to 4,500 days for controls). Twenty-sev en tumors were classified as different subtypes of osteosarcoma, 14 as hemangiosarcomas, 3 as fibrosarcomas, and 1 as a myxosarcoma. Four additional animals developed carcinomas in soft tissues adjacent to the bones of the skull: invasive baso-squamous carcinoma, transitional carcinomas of the nasal cavity, and an adenocarcinoma in the maxilloturbinate region (Benjamin et al. 1979). In addition, two dogs died from myelomonocytic leukemia resulting from irradiation of bone marrow. Metastasis occurred fro m 21 tumors, in particular the hemangiosarcomas, with the lungs being the most freque nt site of metastasis (76%).
Among 127 beagle dogs exposed by inhalation to 90 Sr fused-clay particles, deaths from primary pulmonary tumors were common: 19 dogs with hemangi osarcomas (one each also with bronchioalveolar carcinoma, nasal squamous cell carcinoma, or pulmonary epidermoid carcinoma), and one with pulmonary squamous cell carcinoma (Snipes et al. 1979). All 34 dogs exposed to 90 Sr fused clay particles with cumulative exposures of >29,000 rad (290 Gy ) developed pulmonary hemangiosarcoma. The heart wall was the other primary location of hemangiosarco ma (11 dogs), the others being the mediastinum,76 STRONTIUM 3. HEALTH EFFECTS spleen, rib, lung-associated lymph nodes, and liver (Snipes et al. 1979). Hemangiosarcomas were metastatic in all but one affected dog. Among dogs dying prematurely from neoplasms of the lung, the initial lung burdens were 3.7–94 μCi/kg (0.14–3.5 MBq/kg) and the estimated cumulative doses to the lungs ranged from 43,000 to 67,000 rad (430–670 Gy) (Ben jamin et al. 1975). Considering all dogs with tumors, pulmonary carcinomas or sarcomas occurred in 3/12 dogs that received cumulative radiation doses of 17,000–25,000 rad ( 170–250 Gy), but no pulmonary tumors were reported for three dogs with cumulative exposure levels of 11,000–15,0 00 rad (110–150 Gy; Hahn et al. 1983a).
The highest NOAEL values and all reliable LOAEL values in each species and duration category for cancer effects from exposure to radioactive strontium by the inhalation route are presented in Table 3-2 and plotted in Figure 3-2.

3.3.2 Oral Exposure

Upon ingestion, radioactive strontium isotopes b ecome incorporated into bone, and irradiate the surrounding hard and soft tissues, resulting in hypopl asia of the bone marrow or various forms of cancer (osteosarcoma, leukemia). Adverse effects are associat ed with higher skeletal burdens of radioactive strontium. Younger organisms are more vulnerable to adverse effects of both stable and radioactive strontium. Maternal oral exposure to sufficient ra dioactive strontium can adversely affect the fetus.
The database for oral exposures to radioactive strontiu m is substantial. Human health effect data are derived primarily from long-term and ongoing studies of a population that was exposed to contaminated drinking water and food following the release of larg e quantities of radioactive materials into the Techa River from a Soviet nuclear weapons facility between 1949 and 1956. This population received a mixed exposure to external gamma radiati on and to internal radiation from 89 Sr, 90 Sr, and 137 Cs (Akleyev et al. 1995; Kossenko et al. 2000). Animal data include several large, long-term studies in dogs, miniature pigs, and rodents. In addition to the papers cite d below, interim reports and analyses for the beagle lifetime study (Laboratory for Energy-Related Health R esearch at the University of California at Davis) were published by Nilsson and Book (1987), Nilsson et al. (1985), Pool et al. (1972, 1973b), and Raabe et al. (1981a, 1981b, 1983, 1994).77 STRONTIUM 3. HEALTH EFFECTS
3.3.2.1 Death

In the Techa River population that was exposed to ra diostrontium and radiocesium in drinking water and food between 1949 and 1956, an increase in the num ber of deaths from leukemia and solid cancers was reported (Kossenko 1996). In the e xposed group, the standardized mortality rate was 140 (95% CI: 131– 150) per 100,000 compared to 105 (95% CI: 101–109) per 100,000 in the control group during the followup period (1950–1982). Absorbed doses to the red bone marrow in the study group were between 17.6 and 164 rad (0.176 and 1.64 Gy). No increase in cancer mortality was observed among offspring of exposed individuals. These data are omitted from Ta ble 3-3 because the exposures were to multiple sources of radiation.
Oral exposure to radioactive strontium caused dose-rela ted increases in mortality in animal studies. In general, younger animals were more se nsitive to the effects of radiation th an older animals. There was an increase in deaths in a small number (6 out of 7) of Rhesus monkeys given 100 μCi of 90 Sr per day (3.7 MBq/day) by gavage for 5 or 10 days (Casar ett et al. 1962). One monkey given 11 μCi/kg/day (0.42 MBq/kg/day) for 5 days died 4 years after tr eatment from leukemia with a total skeletal dose of 4,300 rad (43 Gy). One monkey given a dose of 28 μCi/kg/day (1.0 MBq/kg/day) for 10 days died within 4 months of treatment from pancytopenia with an es timated skeletal dose of 4,500 rad (45 Gy). Two others exposed to an average of 18 μCi/kg/day (0.6 7 MBq/kg/day) for 10 days died from bone associated cancers within 36 months of treatment, and with estimat ed skeletal doses of 4,700–9,500 rad (47–95 Gy). Because of the small sample size and the fact that th e animals were of different ages, this study serves as an indicator, but not as proof of dose-response effects of ingested radiostrontium.
In experiments in which weanling (30 days old) and adult Long-Evans rats were given 90 Sr in drinking water for 10 days, survival at 5 months was reduced by 80% in the weanlings consuming at least 297– 386 μCi 90 Sr/kg/day (11 MBq/kg/day; total 464 μCi or 17 MB q), but was unaffected in adults consuming 64–194 μCi 90 Sr/kg/day (7.2 MBq/kg/day; total 650 μCi or 24.1 MBq; Casarett et al. 1962). The reduced survival of the weanlings was consistent with thei r higher skeletal burden at 5 months: >20 times higher than in the adults. In another acute study, six yo ung female dairy cattle (three sets of twins from three different strains, ages 398 and 479 days and weighing 145–349 kg at the start of treatment) were given 44 μCi 90 Sr/kg/day (1.63 MBq/kg/day) ‘orally’ for 5 days (Cragle et al. 1969). The four youngest (398 days) and lightest heifers (145–212 kg), which were administered a total of 32–46 mCi (1.18– 1.70 GBq), died of radiation sickness between 93 a nd 132 days after treatment was started, whereas the older and heavier animals (342–349 kg), wh ich had received a total of 75–77 mCi of 90 Sr (2.78–78 STRONTIUM 3. HEALTH EFFECTS
2.85 GBq), were still alive 3 years after treatment. In addition to age-related differences, strain differences may have contributed to the results; the older cows were Ho lsteins, which have more massive skeletons than the Brown Swiss and Jersey strains. The authors suggested th at the larger animals survived because of the wider diameter of the marro w cavity, which possibly shielded the central marrow from beta radiation released from 90 Sr (and its 90 Y decay product) deposited at the periphery of the bone shaft.
In an intermediate-duration experiment, young (87-day-old) Long-Evans rats were treated with up to 104 μCi of 90 Sr per kg of body weight per day (3.8 MBq/kg/day) for 30 days over a period of 37 days (Casarett et al. 1962; Hopkins et al. 1966); the total amount administered was 790 μCi (29.2 MBq). In these rats, the estimated skeletal activity of 90 Sr at 5 months was 11 μCi (407 kBq) and survival was reduced by about 36%. In the young rats treated for 30 days, skeletal activity was higher and survival was reduced accordingly compared to the adult rats tr eated for 10 days (see previous paragraph), but the differences were out of proportion to the total amounts of 90 Sr administered to the two sets of rats. The total amount given to adults was 18% less than to the juveniles, but the skeletal doses in the adults were 82% less, suggesting age-related differences in incorporation.
In a lifetime study, adult CF-1 mice that were exposed to 90 Sr beginning at ages 110–250 days were less vulnerable to continuous exposure than mice that had been exposed since conception (Finkel et al. 1960). The adult lifespan was shortened by 17% in mice given 31 μCi 90 Sr/kg/day (1.15 MBq/kg/day), but was unaffected by administration of up to 16 μCi 90 Sr/kg/day (592 kBq/kg/day). In mice exposed from conception, the lifetime was shortened by 40% when given 36 μCi 90 Sr/kg/day (1.33 MBq/kg/day), and by 26% when given between 4 and 19 μCi 90 Sr/kg/day (148 and 703 kBq/kg/day), but was unaffected by 0.05–0.4 μCi 90 Sr/kg/day (1.85–14.8 kBq/kg/day). In al bino rats that were fed 0.5 or 2 μCi 90 Sr/kg/day (18.5 or 74 kBq/kg/day) for their postweaning lifetime, the lifespan was shortened, by about 18 or 30%, respectively, compared to controls (Zapol’skaya et al. 1974). The authors calculated that the lifespan was shortened by 0.09 day per rad. A plot of mortality against absorbed dose showed maximum mortality (40%) against a skeletal absorbed dose of 4,000 rad (40 Gy). In a study in which eight weanling Dutch rabbits were fed approximately 6 μCi/kg/day (218 kBq/kg/day) in pellets once a day for 31–280 days, some died within a few weeks with bone marrow that was slightly hypoplastic (Downie et al. 1959). The bone marrow was entirely atrophic in rabbits dying several months later with osteogenic sarcoma.
Two related long-term oral exposure studi es demonstrated dose-related effects of 90 SrCl 2 on survival in beagle dogs. In the main study, groups of pregnant beagles were fed 0.002–3.6 μCi 90 Sr/kg/day (0.074–79 STRONTIUM 3. HEALTH EFFECTS
133.2 kBq/kg/day) from gestational day 21 through lact ation to postnatal day 44, and the pups were fed the same doses from weaning at day 42 through day 540 (Raabe et al. 1983; White et al. 1993). Survival of the pups was reduced by 18, 64, and 85% at the th ree highest levels (0.4, 1.2, and 3.6 μCi/kg/day or 14.8, 44.4, and 133.2 kBq/kg/day, respectively). Survival was not significantly different from the controls for exposures of 0.002–0.13 μCi/kg/day (0.074–4.8 kBq/kg/day). Mean absorbed skeletal absorbed doses at or below 2,250 rad (22.5 Gy) had no effect on mortality, whereas increased mortality was observed at or above 5,040 rad (50.4 Gy). The secondary study had a similar protocol, except that the dogs were given doses of 0.13–1.2 μCi/day (4.81– 44.4 kBq/day) from gestational day 21 throughout their entire lifetime (Book et al. 1982). The mean lif etime absorbed skeletal doses were 2,840–11,190 rad (28.4–111.9 Gy). The median lifespans were reduced by 11–65%, which was similar to the results of the main study. This implies that irradiation after day 540 did not significantly change the survival rate and that survival was shortened because of exposure at a young age. The two main radiation-related causes of death in these studies were myeloproliferative synd rome and skeletal sarcomas (see Section 3.3.2.7 Cancer).
In a multigenerational study of female Pitman-Moore mi niature swine, there were dose-related effects on mortality following chronic ingestion of 90 Sr in the form of strontium chloride (Clarke et al. 1970; McClellan et al. 1963; Ragan et al. 1973). Sows ingesting 3,100 μCi 90 Sr/day (114.7 MBq/day) from age 9 months did not survive their first pregnancy, succu mbing from the destruction of hemopoietic tissue in the bone marrow. The sows devel oped anemia, leukopenia, thrombocytope nia, and terminal hemorrhagic syndrome (Clarke et al. 1972). Exposure to 25, 125, or 625 μCi 90 Sr/day (0.925, 4.625, or 23.13 MBq/day) significantly increased mortality af ter 11, 5, and 1 year(s), respectively, whereas exposure to 1 or 5 μCi 90 Sr/day (37 or 185 kBq/day) had no effect on survival. Effects on the F1 females exposed from the time of conception we re more severe, even though, af ter weaning, their administered dose level was only a fraction of the maternal level until the age of 6 months. None of the F1 females exposed to 625 μCi 90 Sr/day (23.13 MBq/day) survived to the ag e of 9 months, whereas that dose was not immediately fatal to the parental generation of so ws. Furthermore, the F1 females receiving 25 μCi
90 Sr/day (925 kBq/day) showed a significant increase in cumulative mortality after 7 years, rather than 11. However, the 1 and 5 μCi 90 Sr/day levels (37 and 185 kBq/day), as in the parental generation, had no effect on survival. In this study, the average attained body burden was 10, 50, 250, 1,250, and 4,700 μCi (0.37, 1.85, 9.25, 46.25, and 173.9 MBq) for the 1, 5, 25, 125, and 625 μCi 90 Sr/day (0.037, 0.185, 0.925, 4.625, and 23.13 MBq/day) levels, respectively.80 STRONTIUM 3. HEALTH EFFECTS All reliable LOAEL values for death from oral exposur e to radioactive strontium in each species and duration category are recorded in Table 3-3 and plotted in Figure 3-3.

3.3.2.2 Systemic Effects
No studies were located regarding endocrine, dermal, or metabolic effects in humans or animals after oral exposure to radioactive strontium. The highest reliable NOAEL and all LOAEL values for the systemic effects from oral exposure to radioactive strontium ar e shown in Table 3-3 and plotted in Figure 3-3.
Respiratory Effects. No studies were located regarding respir atory effects in humans following oral exposure to radioactive strontium isotopes. No st udies were located regarding respiratory effects in animals following acute- or intermediate-duration expo sure to radioactive strontium. In a chronicduration beagle study, animals exposed to 0.4 or 1.2 μCi/kg/day (14.8 or 44.4 kBq/kg/day) of 90 Sr in utero from gestational day 21, throughout lactation, and from weaning on day 42 to day 540 exhibited only secondary respiratory effects (Dungworth et al . 1969); lungs showed varying degrees of myeloid infiltration (see Section 3.3.2.7 Cancer). Since this effect is not the direct result of the action of radiostrontium on lung tissue, but rather a secondary eff ect of myeloid proliferation induced by irradiation of bone marrow, it is not categorized under Systemic: Respiratory Effects in Table 3-3.

Cardiovascular Effects. No studies were located regarding cardiovascular effects in humans after oral exposure to radioactive strontium isotopes. No studies were located regarding cardiovascular effects in animals after acute- or intermediate-duration or al exposure to radioactive strontium isotopes. Petechiae, ecchymoses, and gastrointestinal bleedi ng were found postmortem in some beagles in a chronic-duration study, in which animals were exposed to 0.002–1.2 μCi 90 Sr/kg/day (0.074– 44.4 kBq/kg/day) in utero from gestational day 21, throughout lactation, and from weaning on day 42 to day 540 (Dungworth et al. 1969). These findings, obser ved in high dose animals (0.4 and 1.2 μCi/kg/day; 14.8 and 44.4 kBq/kg/day), indicated the presence of a hemorrhagic disorder related to thrombocytopenia (see Hematological Effects below).
The highest reliable NOAEL and all LOAEL values for cardiovascular effects from oral exposure to radioactive strontium in each species and duration category are shown in Table 3-3 and plotted in Figure 3-3.Table 3-3 Levels of Significant Exposure to Strontium - Radiation Toxicity - OralExposure/LOAELDuration/aFrequencyReferenceKey to SpeciesNOAEL Less SeriousSerious(Specific Route)figure (Strain)System(uCi/kg/day) (uCi/kg/day)(uCi/kg/day)Chemical FormACUTE EXPOSUREDeath1Monkey5-10 dCasarett et al. 196228 M (1/1 dead within 4 months(Rhesus)(GW)from pancytopenia; estStrontium-90skeletal dose at death=4,500 rad)2Rat10 dCasarett et al. 1962297 M (lifespan decr 80%)(Long- Evans)ad libStrontium-90(W)3Cow5 dCragle et al. 196944 F (4/6 died within 5 months)1 x/dStrontium-90Systemic4Rat10 dCasarett et al. 1962Hemato297 M (hypoplasia of bone marrow)(Long- Evans)ad libStrontium-90(W)Musc/skel297 M (failure of osteogenesis)5Rat10 dCasarett et al. 1962ad libHemato64 M (slight hypoplasia of bone(Long- Evans)marrow)Strontium-90(W)6Cow5 dCragle et al. 1969Gastro44 F (intestinal hemorrhage)1 x/dStrontium-90Hemato44 F(severe leukopenia,thrombocytopenia)Reproductive7RatonceHoward and Clarke 19700.15 F (20% fetal mortality)(G)Strontium-90Table 3-3 Levels of Significant Exposure to Strontium - Radiation Toxicity -Oral(continued)aKey tofigureSpecies(Strain)Exposure/Duration/Frequency(Specific Route)SystemNOAEL(uCi/kg/day)LOAELReferenceChemical FormLess Serious(uCi/kg/day)Serious(uCi/kg/day)891011121314CancerMonkey5-10 d1 x/d(Rhesus)(GW)Rat10 d(Long- Evans)ad lib(W)Rat10 d(Long- Evans)ad lib(W)INTERMEDIATE EXPOSUREDeathRat30 d(Long- Evans)ad lib(W)Rabbit31-280 d1 x/d(Dutch)(F)SystemicRat30 d(Long- Evans)ad lib(W)Rabbit31-280 d1 x/d(Dutch)(F)HematoMusc/skelHematoMusc/skel11 (CEL: leukemia in 1/1)300 M (CEL: osteosarcoma)135 M (CEL: 2 x incr in incidence ofmalignancies)74 M (35% decr survival)6 (premature death from bonemarrow hypoplasia)74 M (moderate bone marrowhypoplasia)74 M (damaged epiphyseal cartilage)6 (bone marrow hypoplasia;anemia, reduced platelets)6(decr osteocytes, decr bloodvessels of bone)Casarett et al. 1962Strontium-90Casarett et al. 1962Strontium-90Casarett et al. 1962Strontium-90Casarett et al. 1962Strontium-90Downie et al. 1959Strontium-90Casarett et al. 1962Strontium-90Downie et al. 1959Strontium-90Table 3-3 Levels of Significant Exposure to Strontium - Radiation Toxicity- Oral(continued)aKey tofigureSpecies(Strain)Exposure/Duration/Frequency(Specific Route)SystemNOAEL(uCi/kg/day)Less Serious(uCi/kg/day)LOAEL(uCi/kg/day)SeriousReferenceChemical Form1516Reproductive(CF-1)(F)600 dad libMouseCancer(Long- Evans)(W)30 dad libRat31 F74 (CEL: 28% osteosarcoma,11% skin carcinoma, 6%leukemia compared tonone in control group)MFinkel et al. 1960Strontium-90Casarett et al. 1962Strontium-9017(Long- Evans)37 d1 x 30 dad libRat74 F (CEL: osteosarcoma)Hopkins et al. 196690Sr(W)1819(Dutch)(F)31-280 d1 x/dRabbitCHRONIC EXPOSUREDeath(albino)372-620 ddailyad libRat6 (CEL: osteosarcoma;multiple myeloma)0.5 (18% mortality)Downie et al. 1959Strontium-90Zapol’skaya et al. 1974Strontium-90(F)20(CF-1)Mouse(F)600 dad lib31 F (survival decr 17%)Finkel et al. 1960Strontium-9021(CF-1)Mouse(F)GD0-PND 414ad lib4 F (survival decr 36%)Finkel et al. 1960Strontium-90Table 3-3 Levels of Significant Exposure to Strontium - Radiation Toxicity -Oral(continued)aKey tofigureSpecies(Strain)Exposure/Duration/Frequency(Specific Route)SystemNOAEL(uCi/kg/day)LOAELReferenceChemical FormLess Serious(uCi/kg/day)Serious(uCi/kg/day)2223242526SystemicRat(albino)Mouse(CF-1)Dog(Beagle)Dog(Beagle)Dog(Beagle)372-620 ddailyad lib(F)GD0-PND 414ad lib(F)GD40-deathad lib(F)GD40-PND540ad lib(F)GD40-PND540ad lib(F)HematoBd WtMusc/skelCardioHematoHepaticBd WtMusc/skel36 F0.5 (~21% leukopenia lasting 2yrs)0.4 M (osteodystrophy)0.4 M (petechiae, ecchymoses,gastrointestinal bleeding)0.4 M (leukopenia, anemia,thrombocytopenia;poikilocytosis, anisocytosis,hypochromasia oferythrocytes)0.4 M (periacinar lipidosis;terminal necrosis)0.4 M (progressive weight lossin anemic dogs)0.4 M (osteolytic lesions,osteoporosis, corticalsclerosis and thickening,mottling)Zapol’skaya et al. 1974Strontium-90Finkel et al. 1960Strontium-90Book et al. 1982Strontium-90Dungworth et al. 1969Strontium-90Momeni et al. 1976Strontium-90Table 3-3 Levels of Significant Exposure to Strontium - Radiation Toxicity -Oral(continued)aKey tofigureSpecies(Strain)Exposure/Duration/Frequency(Specific Route)SystemNOAEL(uCi/kg/day)LOAELReferenceChemical FormLess Serious(uCi/kg/day)Serious(uCi/kg/day)27282930313233Immuno/ LymphoretDogGD40-PND540ad lib(Beagle)(F)DevelopmentalMouse600 dad lib(CF-1)(F)CancerRat372-620 ddaily(albino)ad lib(F)Mouse600 dad lib(CF-1)(F)MouseGD0-PND 414ad lib(CF-1)(F)DogGD40-deathad lib(Beagle)(F)DogGD40-PND540(Beagle)ad lib(F)0.4 M (splenic myeloid metaplasia)3 F (decr postnatal survivalfrom cancer)2 (CEL: lymphosarcoma,osteosarcoma)0.03 F (CEL: reticular tumors)36 F (CEL: 4x incr reticulocytetumors; osteosarcoma)0.4 M (premature death fromcancer)1.3 M (CEL: osteosarcoma)0.4 M (incr death from cancer)Dungworth et al. 1969Strontium-90Finkel et al. 1960Strontium-90Zapol’skaya et al. 1974Strontium-90Finkel et al. 1960Strontium-90Finkel et al. 1960Strontium-90Book et al. 1982Strontium-90White et al. 1993Strontium-90aThe number corresponds to entries in Figure 3-3.Ad lib - ad libitum; Bd Wt = body weight; Cardio = cardiovascular; CEL = cancer effect level; d = day(s); decr = decreased; (F) = food; (G) = gavage; Gastro = gastrointestinal; GD =gestational day; (GW) = gavage in water; Hemato = hematological; incr = increased; LOAEL = lowest-observed-adverse-effect level; min = minute(s); mo = month(s); Musc/skel =musculoskeletal; NOAEL = no-observed-adverse-effect level; PND = post natal day; (W) = water; wk = week(s); x = time(s); yr = year(s)Gastrointestinal Hematological Musculoskeletal Reproductive Cancer *1000 DeathFigure 3-3 Levels of Significant Exposure to Strontium - Radiation Toxicity - OralAcute (≤14 days)SystemicuCi/kg9r10r2r4r4r1005r3q6q 6q1k8k1017r*Doses represent the lowest dose tested per study that produced a tumorigenicresponse and do not imply the existence of a threshold for the cancer endpoint.0.1c-Cat-Humansf-Ferret n-MinkCancer Effect Level-AnimalsCancer Effect Level-HumansLD50/LC50d-Dog k-Monkey j-Pigeon o-OtherLOAEL, More Serious-AnimalsLOAEL, More Serious-Humans Minimal Risk Levelr-Rat m-Mouse e-GerbilLOAEL, Less Serious-AnimalsLOAEL, Less Serious-Humansfor effectsp-Pig h-Rabbit s-HamsterNOAEL - AnimalsNOAEL - Humansother thanq-Cow a-Sheep g-Guinea PigCancerHematological Musculoskeletal Reproductive Cancer *100 DeathFigure 3-3 Levels of Significant Exposure to Strontium - Radiation Toxicity - Oral (Continued)Intermediate (15-364 days)SystemicuCi/kg11r13r13r16r17r15m1012h14h14h18h*Doses represent the lowest dose tested per study that produced a tumorigenicresponse and do not imply the existence of a threshold for the cancer endpoint.1c-Cat-Humansf-Ferret n-MinkCancer Effect Level-AnimalsCancer Effect Level-HumansLD50/LC50d-Dog k-Monkey j-Pigeon o-OtherLOAEL, More Serious-AnimalsLOAEL, More Serious-Humans Minimal Risk Levelr-Rat m-Mouse e-GerbilLOAEL, Less Serious-AnimalsLOAEL, Less Serious-Humansfor effectsp-Pig h-Rabbit s-HamsterNOAEL - AnimalsNOAEL - Humansother thanq-Cow a-Sheep g-Guinea PigCancerCardiovascular Hematological Musculoskeletal Hepatic Body W Immuno/L Developmental Cancer *100 Death eight ymphorFigure 3-3 Levels of Significant Exposure to Strontium - Radiation Toxicity - Oral (Continued)Chronic (≥365 days)SystemicuCi/kg23m31m20m1021m28m29r33d119r22r25d 25d24d26d25d25d27d32d33d0.130m*Doses represent the lowest dose tested per study that produced a tumorigenicresponse and do not imply the existence of a threshold for the cancer endpoint.0.01c-Cat-Humansf-Ferret n-MinkCancer Effect Level-AnimalsCancer Effect Level-HumansLD50/LC50d-Dog k-Monkey j-Pigeon o-OtherLOAEL, More Serious-AnimalsLOAEL, More Serious-Humans Minimal Risk Levelr-Rat m-Mouse e-GerbilLOAEL, Less Serious-AnimalsLOAEL, Less Serious-Humansfor effectsp-Pig h-Rabbit s-HamsterNOAEL - AnimalsNOAEL - Humansother thanq-Cow a-Sheep g-Guinea PigCancer89 STRONTIUM 3. HEALTH EFFECTS
Gastrointestinal Effects. No studies were located regarding gastrointestinal effects in humans after oral exposure to radioactive strontium. Intestinal hemorrhage occurred in cows succumbing to radiation sickness 3 months after ingesting 44 μCi 90 Sr/kg/day (1.63 MBq/kg/day) for 5 days (Cragle et al. 1969). It is likely that other reports of terminal hemorrhag ic effects (see Hematological Effects below) following high doses of radiostrontium encompassed intestinal hemorrhage whether or not it was specifically mentioned.
Hematological Effects. In human and animal studies, adverse hematological affects were associated with beta radiation of bone marrow following incorporation of radiostrontium into bone.
The Techa River population exposed to chronic combined external gamma radiation and internal radiation due to 90 Sr and 137 Cs exhibited alterations in hematol ogical parameters, including leukopenia, thrombocytopenia, and granulocytopenia (Akleyev et al. 1995). These effects were observed in a portion of the exposed population that received radiation doses to the bone marrow at rates in excess of 30– 50 rem (0.3–0.5 Sv) per year. These data are omitte d from Table 3-3 because exposures were to multiple sources of radiation.
Among Rhesus monkeys given 1,000 μCi (37 MBq) of 90 Sr over 10 days, the one with the highest dose on a kg body weight basis (28 μCi/kg/day; 1.0 MBq/kg/day) died from pancytopenia within 4 months of treatment (Casarett et al. 1962). Among young (30 days old) Long-Evans rats that were given >300 μCi
90 Sr/kg/day (11 MBq/kg/day) in drinking water for 10 days (total 460 μCi; 17 MBq), the bone marrow was extremely hypoplastic. Hypoplastic effects we re slight among adult males given doses of 64 or 135 μCi/kg/day or adult females given 92 or 194 μCi/kg/day (total 330 or 650 μCi; total 12.2 or 24.1 MBq; Casarett et al. 1962). Skeletal radiation doses were about 15 times higher in the younger rats. In another acute study, six young female dairy cattle (three sets of twins, ages 398 and 479 days and weighing 145–349 kg at the start of treatment) were given 44 μCi 90 Sr/kg/day (1.63 MBq/kg/day) for 5 days (Cragle et al. 1969). All six heifers exhibited decreases in leukocyte and platelet counts by the first month. In surviving animals, the counts plateaued at about 60% of the normal value. In four animals, the youngest (398 days old) and lightest (145–212 kg) at the time of dosing, leukocyte and platelet counts dropped severely after 80 days, shortly be fore the onset of the terminal stages of radiation sickness.
In an intermediate-duration study in young Long-Ev ans rats, moderate hypoplasia of the bone marrow occurred among males (87 days old) given 74 μCi/ kg/day and females given 104 μCi/kg/day (2.7 and90 STRONTIUM 3. HEALTH EFFECTS
3.8 MBq/kg/day, respectively) of 90 Sr in drinking water for 30 days (total 790 μCi; 29.2 MBq) (Casarett et al. 1962). Hypoplasia of the bone marrow leading to anemia and thrombocytopenia developed in Dutch rabbits that were fed approximately 6 μCi 90 Sr/kg/day (218 kBq/kg/day) in pellets for 31–280 days (Downie et al. 1959).
Chronic-duration studies in several species reported suppression of hematopoiesis. In albino rats fed ≥ 0.5 μCi 90 Sr/kg/day (18.5 kBq/kg/day) for their post-weaning lifetime, hematopoiesis was significantly depressed (Zapol’skaya et al. 1974). Lymphocytes we re the first cells affected, then neutrophils, thrombocytes, and after 1 year, erythrocytes. Morphological abnormalities included binucleation. At 0.5 μCi 90 Sr/kg/day (18.5 kBq/kg/day), leukocyte numbers remained 20% depressed by the end of the second year. The authors calculated that the mini mal dose to induce leukopenia was 150–200 rad. The reduction in leucocytes plateaued at about 30–35% for absorbed doses between 400 and 2,000 rad. Hematological effects were reported in a chronic-dura tion beagle study, in which animals were exposed to 0.002–1.2 μCi/kg/day (0.074–44.4 kBq/kg/day) of 90 Sr in utero from gestational day 21, throughout lactation, and from weaning on day 42 to day 540 (Dungworth et al. 1969). Six years after exposure began, the following effects were observed at doses of 0.44 or 1.2 μCi/kg/day (14.8 or 44.4 kBq/kg/day): abnormal erythrocyte morphology (primarily poikilocyto sis, anisocytosis, and hypochromasia, with some instances of macrocytosis), dose-related, radiation-i nduced leukopenia, an abnormal number of immature granulocytes, one case of unusual giant neutophils, a reduction in the number of platelets, anemia, and splenomegaly. Similarly, female Pitman-Moore miniature swine exposed to 3,100 μCi 90 Sr/day (114.7 MBq/day) as strontium chloride died within 3–4 months from destruction of hematopoietic tissue in bone marrow, which resulted in anemia, leukopenia, thrombocytope nia, and terminal hemorrhagic syndrome (Clarke et al. 1972). In addition, two animals in this group developed myeloid metaplasia.

Musculoskeletal Effects. Skeletal effects following oral exposu re to radioactive strontium have been reported in humans and animals. Dystrophic lesi ons of the skeleton, primarily affecting articular and periarticular tissues, were observed in the Techa River populations that were chronically exposed to radiostrontium and other radionuclides in contaminated food and water (Akleyev et al. 1995). The incidence of skeletal lesions was significantly high er for mean radiation doses to the surface of bone in excess of 200 rem (2 Sv).
In an acute uptake, chronic radiation study, male an d female 30-day-old Long-Evans rats that were given 300 or 390 μCi 90 Sr/kg/day, respectively (11 or 14.4 MBq/kg/day) in drinking water for 5–10 days (total 460 μCi; 17 MBq) exhibited signs of abnormal osteog enesis more than 10 months after administration91 STRONTIUM 3. HEALTH EFFECTS (Casarett et al. 1962). As marrow failed to invade into metaphyseal cartilage, the cartilage resumed active proliferation. Resorption failed to occur in metaphyseal cartilage and metaphyseal spongiosa failed to transform to lamellar bone. Often, cartilage and fi brous marrow were incorporated into cortical bone, sometimes causing fracture and deformation.
In an intermediate uptake, chronic radiation study on young (87 days old) Long-Evans rats, ingestion of 74 (males) or 104 (females) μCi 90 Sr /kg/day (2.7 or 3.8 MBq/kg/day) in drinking water for 30 days (total 790 μCi; 28.9 MBq) adversely affected the vasculature of the bone, which interfered with the normal transformation of cartilage into bone (Casarett et al. 1962). At the end of the long bones, the cartilage discs were damaged, with detachment of primary spongiosa and failure of resorption. In another intermediate-duration study, numbers of osteocytes (bone cells surrounded by a mineralized matrix and connected by a mesh-work of processes) were reduced in Dutch rabbits that ingested approximately 6 μCi
90 Sr/kg/day (218 kBq/kg/day) in pellets for 48 days (Downie et al. 1959).
Bone damage was a notable effect of chronic-duratio n oral exposure to radioactive strontium in dogs (Momeni et al. 1976). Groups of pregnant beagles were fed 0.002–3.6 μCi 90 Sr/kg/day (0.074– 133.2 kBq/kg/day) from gestational day 21 through lact ation to PND 44, and the pups were fed the same doses from weaning at day 42 through day 540 (Raabe et al. 1983; White et al. 1993). Ten years from the start of the study, dose-related skeletal effects in cluded mild trabecular osteopenia, endosteal and periosteal cortical changes (sclerosis and thickening), and mottling or focal osteolytic lesions (Momeni et al. 1976). These occurred in all the dogs in the 3.6 μCi/kg/day group and also in the 1.2 and 0.4 μCi/kg/day groups (133.2, 44.4, and 14.8 kBq/kg/day, respectively). Radiation-induced osteodystrophy was noted in three out of four beagle dogs that received 1.2 μCi 90 Sr/kg/day (44.4 kBq/kg/day) for life beginning at midgestion (Book et al. 1982); the average dose rate (cumulative dose divided by lifespan) for these dogs was 4 rad/day (0.04 Gy/day). Radiation osteonecrosis was said to be a common finding among female Pitman-Moore miniature swine that died with hematopoietic disorders or bone marrow hypoplasia after ingesting 90 SrCl 2 at levels between 1 and 3,100 μCi/day (0.37– 114.7 MBq/day) until death (Clarke et al. 1972). The incidence of osteonecrosis at each dose level was not reported. Bone cancers that were reporte d in these chronic studies are discussed below in Section 3.3.2.7.
Hepatic Effects. No studies were located regarding hepatic effects in humans after oral exposure to radioactive strontium isotopes. No studies were locat ed regarding hepatic effects in animals after acuteor intermediate-duration oral exposure to radioactiv e strontium isotopes. In a chronic-duration beagle92 STRONTIUM 3. HEALTH EFFECTS study, animals exposed to 0.4 or 1.2 μCi 90 Sr/kg/day (14.8 or 44.4 kBq/kg/day) in utero from gestational day 21, throughout lactation, and from weaning on day 42 to day 540 exhibited only secondary hepatic effects (Dungworth et al. 1969). Livers were someti mes enlarged from myeloid infiltration and periacinar lipidosis, sometimes with terminal necrosis, in dogs with severe anemia. Since the observed myeloid infilitration was a secondary effect resulting from i rradiation of the bone marrow, it is not categorized under Systemic: Hepatic Effects in Table 3-3.

Renal Effects. No studies were located regarding renal effects in humans after oral exposure to radioactive strontium isotopes. Approximately 19% of adult Long-Evans rats ingesting 65 μCi 90 Sr/day (2.41 MBq/day; 135 or 194 μCi/kg/day, 5 or 7.2 MBq/kg/day for males and females, respectively) of in drinking water for 10 days developed chronic inte rstitial nephritis, a common disease in older rats, during their remaining lifespan (Casarett et al. 1962). It is very unlikely that the ingestion of radiostrontium was related to the occurrence of nephritis.

Ocular Effects. No studies were located regarding ocular effects in humans after oral exposure to radioactive strontium isotopes.
No studies were located regarding ocular effects in animals after acute- or intermediate-duration oral exposure to radioactive strontium isotopes. In one ch ronic-duration study, 2 out of 403 beagles that had been exposed to 90 Sr in utero from gestational day 21, during lactation, and from weaning on day 42 to day 540, developed a benign melanoma of the eye, but the dose-level was not reported (Raabe et al. 1994). Statistical analysis showed that these tumors (not found in controls, but also found in dogs irradiated through other exposure routes, or with other radionuclides) were significantly related to exposure to ionizing radiation. According to a 6-year report from the same chronic-duration beagle study, animals exposed to 0.4 or 1.2 μCi 90 Sr/kg/day (14.8 or 44.4 kBq/kg/day) in utero from gestational day 21, throughout lactation, and from weaning on day 42 to day 540 exhibited only indirect ocular effects (Dungworth et al. 1969). The eyes of dogs with a myeloproliferative disorder exhibited some slight degree of myeloid infiltration (see Section 3.3.2.7 Can cer). Since this was a secondary effect resulting from irradiation of bone marrow and not the direct response of the eye tissues to radiostrontium, it is not categorized under Ocular Effects in Table 3-3.
Body Weight Effects. No studies were located regarding body weight effects in humans after oral exposure to radioactive strontium isotopes. No studi es were located regarding body weight effects in animals after acute- or intermediate oral exposure to radioactive strontium. No effect on body weight was93 STRONTIUM 3. HEALTH EFFECTS observed among female CF-1 mice that had been exposed to 90 Sr in utero , during lactation, and up to day 414 at doses of up to 36 μCi of 90 Sr/kg/day (1.33 MBq/day) (Finkel et al. 1960). Progressive weight loss was observed among beagle dogs that developed anem ia after having been exposed to 0.4–1.2 μCi of
90 Sr/kg/day (148–444 kBq/kg/day) from mid-gestation to age 1.5 years (Dungworth et al. 1969).

3.3.2.3 Immunological and Lymphoreticular Effects

Immunological changes were reported in the Techa River population that was exposed to chronic combined external gamma radiation and internal radiation from 90 Sr and 137 Cs between 1949 and 1956 (Akleyev et al. 1995). Immunological disorders pe rsisted for 30 years and included decreased expression of antigens of differentiating T-lymphocytes, decreased T-lymphoblast transformation, and reduced counts of large granulocytic lymphocytes. Granulocytopenia developed in a portion of the exposed population that received radiation to the bone marrow at rates in excess of 30–50 rem (0.3–0.5 Sv) per year. Akleyev et al. (1995) suggested that radiation-induced immunodeficiency may have contributed to the higher incidence of leukemia in the exposed po pulation (see Section 3.3.2.7 Cancer). Clinical manifestations of immune insufficiency in expo sed cancer patients included 3-fold increases in the incidences of infectious diseases (chronic pneumonia, chronic bronchitis, pulm onary tuberc ulosis, and osteomyelitis) compared to a nontumor-bearing group. These data are omitted from Table 3-3 because of the mixed exposures.

No animal studies were located that described i mmunological effects following acute oral uptake of radiostrontium. Intermediate-to-chronic-duration exposures to radiostrontium resulted in impaired immune function in animals. In Pitman-M oore miniature pigs that were fed 625 μCi 90 Sr/day (23.13 MBq/day) as strontium chloride for 9 months, the antibody response to inoculated Brucella abortus (strain 19) antigen was determined by the plate a gglutination test to be less than half that of controls (Howard 1970). In another test, periphera l leukocyte cultures were prepared from these same animals at monthly intervals, in medium containing phytohemagglutinin (PHA). In pigs that were fed 625 μCi 90 Sr/day (23.13 MBq/day) for 4–5 months, periphe ral lymphocytes lost the ability to respond to PHA stimulation; this adverse effect was sustained for at least 6 months. The author attributed these immunological effects to exposure to 90 Sr. Myeloid metaplasia also afflicted female Pitman-Moore miniature swine that were fed 3,100 μCi 90 Sr/day (114.7 MBq/day) until the end of life at age 3–4 months (Howard and Clarke 1970). The cumulative doses at the time of death ranged from 40 to 10,000 rad (0.4– 100 Gy).94 STRONTIUM 3. HEALTH EFFECTS In a 6-year status report of a chronic uptake study in which beagle dogs were exposed to 90 Sr from midgestion to age 1.5 years, 1.3% of dogs receiving 0.4 μCi 90 Sr/kg/day (14.8 kBq/kg/day) and 3.7% of dogs receiving 1.2 μCi 90 Sr/kg/day (44.4 kBq/kg/day) developed myeloid metaplasia of the spleen (Dungworth et al. 1969).
The highest reliable NOAEL values and all LOA EL values for immunological and lymphoreticular effects from oral exposure to radioactive strontium in each species and duration category are recorded in Table 3-3 and plotted in Figure 3-3.

3.3.2.4 Neurological Effects

Nervous system disorders (weakness, apathy, fatigue) were reported in the Techa River population that was chronically exposed to combined external gamma radiation and internal radiation from 90 Sr and 137 Cs (Akleyev et al. 1995). Neurological effects were observed at chronic dose rates in excess of 40–50 rad (0.4–0.5 Gy) per year and persisted for 14–20 years in the exposed population. However, it is not clear to what extent strontium-derived radiation contributed to neurological effects, compared to external gamma radiation. These data are omitted from Ta ble 3-3 because of the mixed exposures.
No studies were located that reported neurological effects in animals following oral exposure to radioactive strontium isotopes.

3.3.2.5 Reproductive Effects

No significant reproductive effects were reported in the Techa River population that was exposed to combined external gamma radiation and internal radiation from 90 Sr and 137 Cs between 1949 and 1956 (Kossenko et al. 1994). Exposure had no effect on birt h rate, fertility, or the incidence of spontaneous abortions in the study group that had received aver age doses to the gonads of up to 74 rem (0.74 Sv), primarily from external gamma radiation (Akleyev et al. 1995). An increase in the incidence of ectopic pregnancies was not dose-associated. These data are omitted from Table 3-3 because exposures were to multiple sources and it is probable that radiostrontium had a minor effect on the gonadal radiation dose.
In one acute study, female rats were given a single dose of 400 μCi 90 Sr/kg by gavage 1–10 days before impregnation (Moskalev et al. 1969). At the time of conception, the maternal skeletal dose was 800 rad95 STRONTIUM 3. HEALTH EFFECTS (8 Gy) and soft tissue dose was 10 rad (0.1 Gy). Fe tuses received skeletal doses of 20 rad (0.2 Gy). Under these conditions, 22% of fetuses died. In an intermediate-duration study, groups of 230– 339 female CF-1 mice were fed 90 Sr in the diet at doses between 0.03 and 31 μCi/kg/day (1.11 and 1,147 kBq/day; Finkel et al. 1960). Dams and males bred while on the radiostrontium diet, and dams were maintained on diet throughout gestation and l actation. Radiostrontium feeding had no effect on fertility, the number of live offspring, or the num ber of female offspring surviving at PND 35.
In a multigenerational study, 9-month-old female Pitman-Moore miniature swine were fed a diet containing between 1 and 3,100 μCi 90 Sr/day (0.037 and 114.7 MBq/day) and then were bred with males that were only exposed to 90 Sr during the period of mating (Clarke et al. 1970, 1972; McClellan et al. 1963). Ingestion of radioactive strontium had no effect on fertility or fecundity. Pregnant sows receiving 3,100 μCi 90 Sr/day (114.7 MBq/day) did not survive to the end of the period of gestation because of bone marrow hypoplasia, but their fetuses were apparently normal (McClellan et al. 1963). For doses between 1 and 625 μCi 90 Sr/day (0.037 and 23.13 MBq/day), there was no significant effect on litter size, percentage of stillborn, or birth weight. Exposure had no effect on frequency and duration of the estrus cycle or in the number of repeat breedings. Howeve r, the F1 offspring of the sows ingesting 625 μCi
90 Sr/day (23.13 MBq/day) did not survive to adulthood . Survival of the F2 offspring was apparently similar to the F1 generation, but their reproductive cap acity was not reported, since later studies focused on cancer effects.
The highest reliable NOAEL values and all LOAEL va lues for reproductive effects from oral exposure to radioactive strontium in each species and duration cat egory are recorded in Table 3-3 and plotted in Figure 3-3.

3.3.2.6 Developmental Effects

Few developmental effects were re ported in the progeny of the Techa River population that was exposed to combined external gamma radiation and internal radiation from 90 Sr and 137 Cs between 1949 and 1956 (Kossenko et al. 1994). The cohort of women in the st udy received radiation doses to the gonads of up to 74 rem (0.74 Sv), primarily from external gamma radi ation (Akleyev et al. 1995); the proportion of the dose attributable to radiostrontium was not specified, but is likely to have been relatively small. No increase in the incidences of spontaneous abortion, mi scarriages, or stillbirths was observed. However, there were slight increases in child mortality from chromosomal defects and from congenital anomalies of96 STRONTIUM 3. HEALTH EFFECTS the nervous system, circulatory system, and other un specified anomalies in the progeny of the exposed group compared to controls. Considering deaths fro m these anomalies, from labor complications, or from unspecified perinatal causes, the mortality coefficien t of the offspring of parents with gonadal doses of 11 rem (0.11 Sv) was double that of the unexposed co ntrol group. Kossenko et al. (1994) calculated that the gonadal doses required to double the incidences of stillbirths, miscarriages, early neonatal mortality, or lethal developmental effects were rather high, ranging from 20 to 480 rem (0.2–4.8 Sv) for the different end points. These data are omitted from Table 3-3 because of the combined internal and external radiation exposures.
In one animal study, CF-1 mice were exposed to 90 Sr from the time of conception; breeding adults were fed a diet containing 0.03–31 μCi 90 Sr/kg/day (1.11–1,147 kBq/kg/day), and the dams were fed the same diet throughout gestation and lactation (Finkel et al. 1960). The offspring were fed the same diet throughout their lifetimes. Gesta tional exposure to radiostrontium did not affect litter size or early survival of offspring, and no teratogenic effects we re noted. However, survival of the offspring was shortened at doses of 3 μCi 90 Sr/kg/day (111 kBq/kg/day) or higher, which was related to the higher incidence of bone-related cancer (see Section 3.3.2. 7 Cancer). Autoradiographs demonstrated the uniform distribution of 90 Sr in the skeleton, which probabl y contributed to these effects.
In a large multigenerational study, 9-month-old fema le Pitman-Moore miniature swine were fed a diet containing between 1 and 3,100 μCi 90 Sr/day (0.037 and 114.7 MBq/day) and then were bred with males that were only exposed to 90 Sr during the period of mating (Clarke et al. 1970, 1972; McClellan et al. 1963). Ingestion of radioactive strontium had no effect on fertility or fecundity. Fetuses were apparently unaffected, even those of sows that died during pr egnancy from bone marrow hypoplasia after ingesting 3,100 μCi 90 Sr/day (114.7 MBq/day; McClellan et al . 1963). For doses between 1 and 625 μCi 90 Sr/day (0.037 and 23.13 MBq/day), there was no significant eff ect on litter size, percentage of stillborn, or birth weight. In offspring of sows ingesting 625 μCi 90 Sr/day (23.13 MBq/day), the weaning weight was reduced because radiation-induced hematopoietic effect s reduced the output of milk (Clarke et al. 1970). After weaning, the F1 offspring were fed 90 Sr in the diet at graded levels that, by 6 months, equaled the maternal level, 1–625 μCi 90 Sr/day (0.037–23.13 MBq/day). The 625 μCi 90 Sr/day (23.13 MBq/day) F1 females did not survive to be bred at 9 months. These results indicate an age-related vulnerability to 90 Sr, since the 625 μCi 90 Sr/day (23.13 MBq/day) dosage was not lethal to the parental generation (pigs exposed from age 9 months).97 STRONTIUM 3. HEALTH EFFECTS The highest reliable NOAEL values and all LOAEL va lues for developmental effects from oral exposure to radioactive strontium in each species and duration category are recorded in Table 3-3 and plotted in Figure 3-3.

3.3.2.7 Cancer

Epidemiological studies have found little or no association between oral exposure to radioactive strontium from fallout and cancer effects in humans. In an ep idemiological study using the Danish cancer registry, no association was found between the incidence of thyroid cancer in Denmark between 1943 and 1988 and the levels of skeletal incorporation of 90 Sr from fallout (Sala and Olsen 1993). In another epidemiological study, data collected between 1959 and 1970 in a 90 Sr monitoring program in Glasgow, Scotland, were used to identify three cohorts with respect to the hypothetical risk for leukemia and nonHodgkin’s lymphoma, acute myeloid leukemia, all childhood cancers combined, and bone tumors (Hole et al. 1993). The three cohorts were a high risk gr oup born in 1963–1966 (exposed to high levels of fallout, i.e., 90 Sr, at a young age), a medium risk group born in 1959–1962 (exposed to high levels at an older age), and a low risk group born after 1966. Cumulative incidences for all cancers, leukemia and non-Hodgkin’s lymphoma, and acute myeloid leukemi a all showed a secular (progressive, noncyclical) increasing trend for children born before 1982. Howe ver, the study found no evidence for increased risks of total cancers, leukemia and Non-Hodgkin’s lymphom a, or acute myeloid leukemia for cohorts born during the period of highest fallout (radiostrontium) exposure. The few cases of bone tumors showed a statistically nonsignificant increase for child ren born during the ‘high risk’ period.
In contrast, the Techa River population that was expo sed to contaminated water and food as a result of releases from a nuclear weapons facility exhibited a significant increase in the incidence of leukemia (Kossenko 1996; Kossenko et al. 1997 , 2000, 2002). An excess of le ukemia cases (0.85 excess cases per 10,000 person-year Gy (95% CI: 0.2; 1.5) was observed in groups of individuals with estimated bone marrow doses in excess of 10 rem (0.1 Sv), and the risk of mortality from leukemia increased with increasing dose (Kossenko, 1997, 2002). This find ing can be related to the body burdens of 90 Sr, which in the Techa River cohort, have been >100 times highe r than fallout-related exposures during the same period (Shagina et al. 2000). No increase in cancer rates has been observed in the progeny of the Techa River cohort (Kossenko 1996).98 STRONTIUM 3. HEALTH EFFECTS As shown in numerous animal studies, oral exposure to radioactive strontium may increase the incidence of cancers of bone and bone marrow. In a sm all study in which young monkeys were given 90 Sr by gavage, one given 11.2 μCi 90 Sr/kg/day (0.42 MBq/kg/day) for 5 days died of leukemia, with a final skeletal dose of 4,300 rad (43 Gy) 4 years after treatme nt (Casarett et al. 1962). Two others exposed to an average of 18 μCi 90 Sr/kg/day (0.67 MBq/kg/day) for 10 da ys died from bone-associated cancers (chondrosarcoma, osteosarcoma) within 36 months of treatment, with estimated skeletal doses of 4,700– 9,500 rad (47–95 Gy).
Acute-duration experiments using Lo ng-Evans rats demonstrated that weanlings, with their relatively higher rate of incorporation of strontium into the skeleton, were more vulnerable than adults to the carcinogenetic effects of 90 Sr (Casarett et al. 1962). Weanlings (30 days old) were given 46 μCi 90 Sr/day (1.7 MBq/day) and adults were given 33 or 65 μCi 90 Sr/day (1.2 or 2.4 MBq/day) in drinking water for 10 days; on a body weight basis, the amounts gi ven were >300 μCi/kg/day (11 MBq/kg/day) for weanlings, 64 or 135 μCi/kg/day for adult males, or 92 or 194 μCi/kg/day for adult females. After 5 months, 33 μCi (1.2 MBq) of radi oisotope were detected in the skeletons of weanlings that received 460 μCi (17 MBq), but only 1 or 2 μCi (37 or 74 kBq) were detected in the skeletons of adults that received 330 or 650 μCi (12.2 or 24.1 MBq), respect ively. The differences in incorporation of 90 Sr probably accounted for the age-related differences in th e incidence of osteosarcoma; 17.5% of weanlings developed osteosarcoma compared to none of the a dults. However, in the high dose adults, the overall incidence of malignancy (leukemia, squamous cell carcinoma of the skin, various other carcinomas) was more than doubled, compared to controls. At the lo wer dose, the overall rate of malignancies in adults was lower than in controls (6.25% compared to 16.2%) . In an intermediate-duration experiment, in which male 87-day-old Long-Evans rats were given 74 μCi 90 Sr/kg/day (2.7 MBq/kg/day) and females were given 104 μCi 90 Sr/kg/day (3.8 MBq/kg/day) in drinking water for 30 days (total 790 μCi; 29.2 MBq), the incidence of osteosarcomas was 27.5% compared to none in the controls. Overall, the incidence of malignancy in the treated group was more than double that of controls; other neoplasms included 11.25% skin carcinoma (facial) and 6.25% leukemia. The 87- day-old rats treated for 30 days had a 5-month skeletal burden of about 11μCi (407 kBq), which, on a kg body weight basis, was less than one quarter that of weanlings treated for 10 days. This discrepancy reflects differences in rates of absorption and osteogenesis, which are higher in the younger rats. Th e older rats had a higher incidence of osteosarcoma than the weanlings because they survived beyond the latency period for the cancer. In another intermediate-duration rat study, oral exposure to 90 Sr for 37 days (total dose of 790 μCi; 29.2 MBq) increased the incidence of osteolysis and osteoge nic sarcoma by 21% (Hopkins et al. 1966). The radiation dose to the skeleton after 150 days was 4,000 rad (40 Gy). Young rabbits (~52 days old) that99 STRONTIUM 3. HEALTH EFFECTS were fed an average of 6 μCi 90 Sr/kg/day (218 kBq/kg/day) 90 Sr in pellets for 224–280 days developed multiple osteogenic sarcomas in the skull and at the rapidly growing ends of the long bones within 6– 8 months (Downie et al. 1959).
Relatively large studies in rats, mice, dogs, and pi gs demonstrated increased tumor induction following chronic ingestion of 90 Sr. In the rat study, albino rats were fed between 0.05 and 2 μCi 90 Sr/kg/day for their post-weaning lifetime, resulting in exposures between 0.01 and 0.4 μCi/day (Zapol’skaya et al. 1974). In rats consuming 2 μCi 90 Sr/kg/day, the number of rats with malignant tumors was 18.7%, compared to 1.3% for controls. At 0.5 90 Sr/kg/day, the tumor incidence was 3–6 times lower (not specified numerically), but the outcome at 0.05 90 Sr/kg/day was not reported. The most common malignancies were lymphosarcoma (8%), osteosarcoma (6.7%), and “leukosis” (4%). The latency periods were 300–540 days for lymphosarcomas and 450–660 days for “leukosis” and osteosarcoma. The cumulative absorbed doses averaged 1,350 rad (13. 5 Gy) just before the onset of lymphosarcoma, 2,200 rad (22 Gy) just before the onset of ‘leukosis ’, and 2,400 rad (24 Gy) just before the onset of osteosarcoma.
In the mouse study, mice were exposed either as adults (beginning at age 110–250 days) or from conception to 0.05–36 μCi 90 Sr/kg/day (Finkel et al. 1960). There was a higher incidence of reticular tumors in blood-forming tissues, but no evidence of osteogenic sarcoma in all adult exposed groups. Possibly because of the experimental design-groups we re not exposed simultaneously and were subjected to environmental differences-tumor incidence in adults did not show a clear dose-response. However, the tumor incidence was significantly elevated in mice exposed to 90 Sr from conception. The highest dose level resulted in the early appearance of reticular tumo rs, especially lymphomas; 24% of mice at this level died with reticular-tissue tumors by 525 days, compar ed to 6% in controls. Other tumors unique to the high-dose level included six osteogenic sarcomas, four osteolytic tumors, and two epidermoid carcinomas of the oral cavity. Radiography demonstrated that radioactive strontium was ubiquitously distributed throughout the skeleton of mice exposed from conception.
In the dog study, groups of pregnant beag les were fed between 0.002 and 3.6 μCi 90 Sr/kg/day (0.074 and 133.2 kBq/kg/day) from day 21 of gestation to postnat al day 42 (White et al. 1993). The pups were weaned and then fed a diet containing the same 90 Sr/calcium ratio as the dam until day 540. Bone sarcoma deaths occurred in dogs ingesting between 0.13 and 3.6 μCi 90 Sr/kg/day (4.8–133.2 kBq/kg/day) resulting in bone doses at death of 5,000–10,700 rad (50–107 Gy), but no t at 0.002–0.043 μCi 90 Sr/kg/day (0.1–1.6 kBq/kg/day) with doses to death of 100– 2,300 rad (1–23 Gy). The higher the amount of 90 SrSTRONTIUM 100 3. HEALTH EFFECTS given, the earlier the age of onset of sarcomas and the more likely they were to be osteosarcomas. Of 66 sarcomas, 75% were osteosarcomas; other types were chondrosarcoma, hemangiosarcoma, fibrosarcoma, and undifferentiated sarcoma. Multiple tumors occurred only at the two highest doses. Other cancer deaths occurred at high doses: radiation-induced myeloid leukemia (43 deaths), oral or nasal carcinoma (29 deaths), and periodontal carcinoma (16 deaths). The leukemic animals (average age at death 1,156 days) were not at risk for osteosarcoma, which had an average age of onset of 2,864 days. The mean cumulative skeletal doses at the time of onset in the four highest exposure groups for dogs with tumors were between 3,100 and 11,600 rad (31–116 Gy). The authors indicated that of the exposures that did not give rise to tumors, the lowest exposure (8 mrad/day; 0.08 mGy/day) was 25 times higher than background and the highest (146 mrad/day; 1.46 mG y/day) was 500 times higher than background. Therefore, lifetime chronic exposure to low linear ener gy transfer (LET) beta particle radiation up to 500 times background showed no apparent carcinogenic potential in dogs.
Stage-specific differences in carcinogenetic effects we re reported in a large multigenerational study of female Pitman-Moore miniature swine th at were fed between 1 and 3,100 μCi 90 Sr/day (0.037–114.7 MBq/day) for life (Clarke et al. 1972; Howard 1970; Howard and Clarke 1970). In the parental generation, which was started on the regime n at age 9 months of age, myeloid metaplasia was observed at nearly all levels, and lymphoid or my eloid neoplasms were observed when between 1 and 125 μCi 90 Sr/day were ingested. The aver age doses to the skeleton for the parental females were between 40 and 10,000 rad. No bone cancer occurred in the parental generation, whereas osteosarcomas occurred in F1 or F2 offspring exposed from conception to 12 5 or 625 μCi/day with average skeletal doses higher than 9,000 rad (90 Gy). Osteosarcoma had a longe r latency period and occurred at higher exposure levels. Myeloid metaplasia and myeloid and lymphoid neoplasms deve loped sooner and more frequently in the F1 and F2 generations than in the parental generation.
The cancer effect levels (CELs) resulting from oral e xposure to radioactive strontium in each species and duration category are recorded in Table 3-3 and plotted in Figure 3-3.

3.3.3 External Exposure
Cardiovascular, dermal, ocular, and cancer effects have been reported following acute- or intermediateduration external exposure to beta radiation from a solid radioactive strontium s ource apposed to the skin or eye. In these studies, 90 Sr was considered to be in equilibrium with 90 Y; that is, following decay of 90 Sr, some radiation emissions could be expected from decay of its transformation product, 90 Y.STRONTIUM 101 3. HEALTH EFFECTS
3.3.3.1 Death

No studies were located regarding death in humans or animals after external exposure to radioactive strontium.

3.3.3.2 Systemic Effects

No studies were located regarding respiratory, gast rointestinal, hematological, musculoskeletal, hepatic, renal, or endocrine effects in humans or animals afte r external exposure to radioactive strontium isotopes.

Cardiovascular Effects. Exposure to excessive ionizing radiat ion is known to affect the integrity of the vasculature of the skin, increasi ng the permeability of the vasculature to plasma protein. A study by Song et al. (1968) examined the ability of several an ti-inflammatory agents to suppress this radiationinduced increase in vascular permeability. Albino male guinea pigs were exposed to 3,000 rep (Roentgen equivalent, physical) (3,230 rad; 1 rep . 0.93 rad) of particles (800 rad/min; 8.0 Gy/min) from a 90 Sr/ 90 Y source. Immediately after irradiation, 125 I-labeled guinea pig serum albumin was injected into the heart as a tracer. The peak increase in v ascular permeability, as measured by the ratio of accumulation of labeled plasma protein in the nonirradiated control and beta-irr adiated skin, was determined to occur at 18 hours. In the group receiving no anti-inflammatory drug, the irradiated epidermis and dermis exhibited approximately 3- and 1.6-fold increases in the peak accumulation of plasma protein, respectively.
The highest reliable NOAEL values and all LOAEL values for cardiovascular effects from external exposure to radioactive strontium in each species a nd duration category are recorded in Table 3-4.

Dermal Effects. Several studies in humans and animals have reported damage to the skin following external exposure to radioactive strontium. Beta radiation from 90 strontium has been used to treat hemangiomas in children and adults. One study d escribed some delayed effects of this radiation treatment within patients in one medical practice in Belgrad, Yugoslavia (now Serbia; Bekerus 1970). The beta source was a 50 mCi 90 Sr plate with a diameter of 9.9 mm. Adults were treated with an initial dose of 1,600 rad (16 Gy) and subsequent doses of 1,080–1,600 rad ( 10.8–16 Gy) in succeeding months,aKey tofigureSpecies(Strain)Exposure/Duration/Frequency(Specific Route)SystemNOAEL(rad)Less Serious(rad)LOAEL(rad)SeriousReferenceChemical FormACUTE EXPOSURESystemic1Humanonce<1 minOcular1700(scleral thinning in diabeticpatient)Wesberry and Wesberry 1993Strontium-90Table 3-4 Levels of Significant Exposure to Strontium - Radiation Toxicity - External Radiation2Mouse1-60 minHopewell et al. 1986onceDermal2200 M (50% incr moist desquamation)(SAS/4)Strontium-90/yttrium-903Mouse9 minHoshino and Tanooka 1975Dermal2700 F (acute injury, scarring)once(ICR)Strontium-90/yttrium-904MouseonceRandall and Coggle 1995Dermal5000 M (late chronic fibrosis)(CD-1)Strontium-90/yttrium-905MouseonceRandall and Coggle 1995Dermal5000 M (late chronic fibrosis)(CBA/caStrontium-90/yttrium-90agouti)Table 3-4 Levels of Significant Exposure to Strontium - Radiation Toxicity - External Radiation (continued)Exposure/LOAELDuration/aKey to SpeciesFrequencyNOAEL Less SeriousSeriousReference(Specific Route)figure (Strain)System(rad)(rad)(rad)Chemical Form6Gn Pig1.4 to 8.3 minEtoh et al. 1977onceDermal1000 M (reversible 25% loss of basal(albino)cells; erythema; hair loss)Strontium-90/yttrium-907Gn Pig4 minSong et al. 1968onceCardio3230 M (incr vascular permeability in(albino)dermis)Strontium-90/yttrium-908Pig1-60 minHamlet et al. 1986Dermal2000 F (late 35% dermal atrophy)once(Large White)Strontium-90/yttrium-909PigonceHopewell et al. 19853 to 12 minDermal2340 F (moist desquamation)Large WhiteStrontium-9010Pig1-60 minHopewell et al. 1986onceDermal3000 F (50% incr moist desquamation)(Large White)Strontium-90/yttrium-90Table 3-4 Levels of Significant Exposure to Strontium - Radiation Toxicity - External Radiation (continued)Exposure/LOAELDuration/aKey to SpeciesFrequencyNOAEL Less SeriousSeriousReference(Specific Route)figure (Strain)System(rad)(rad)(rad)Chemical Form11Pig1-60 minPeel et al. 1984.onceDermal3000 F (50% incr moist desquamation)(Large White)Strontium-90/yttrium-90Cancer12Mouse1 hrHoshino and Tanooka 197517800 F (CEL: 1/5 fibrosarcomaonce(ICR)of skin)Strontium-90/yttrium-90INTERMEDIATE EXPOSURESystemic13Human1 yrBekerus 1970~1 x/moDermal220 (delayed telangiectasis, slight~min/datrophy)Strontium-90Table 3-4 Levels of Significant Exposure to Strontium - Radiation Toxicity - External Radiation (continued)Exposure/LOAELDuration/aKey to SpeciesFrequencyNOAEL Less SeriousSeriousReference(Specific Route)figure (Strain)System(rad)(rad)(rad)Chemical Form14Human3 wkTong et al. 19691 x/wkOcular1075 (conjunctival telangiectasis,<1 min/dscarring; abnormal nuclei ofStrontium-90conjunctival epithelium)Cancer15Mouse43 wksHoshino and Tanooka 197517800 F (CEL: 1/5 reticulocyte1 x/wk(ICR)sarcoma)Strontium-90/yttrium-901 hr16Mouse177-300 dOotsuyama and Tanooka 1988150 F (CEL: fibrosarcoma;3 x/wk(ICR)squamous cellStrontium-90/yttrium-90~min/dcarcinoma; basalcell carcinoma)17Mouse177-300 dOotsuyama and Tanooka 1989150 F (CEL: osteosarcoma)3 x/wk(ICR)Strontium-90/yttrium-90~min/daThere is no corresponding LSE figure.1 In these studies, a solid radioactive source was placed adjacent to the eye or skin.~ = approximately; CEL = cancer effect level; d = day(s); Gn pig = guinea pig; hr = hour(s); incr = increased; LOAEL = lowest-observed-adverse-effect level; min = minute(s); NOAEL= no-observed-adverse-effect levelSTRONTIUM 106 3. HEALTH EFFECTS not exceeding a total of 7,530 rad (75.3 Gy). Childre n were treated with an initial dose of 200–300 rad (2–3 Gy) and additional treatments over 6–16 months , for a total exposure of 2,420–6,130 rad (24.2– 61.3 Gy) in some cases. Eight or 10 years after treatm ent, about a third of the patients developed delayed reactions to radiation: achromia, excess pigmentation, slight atrophy, and telangiectasis. The author did not specify the exposure levels that resulted in these effects.

Acute dermal reactions to 90 Sr have been described for depilated sk in in mice, guinea pigs, and pigs. In mice, skin exposed to a single 2,000–5,000 rad (20–50 Gy) dose of beta radiation from a 90 Sr- 90 Y source sustained an acute reaction (Hoshino and Tanooka 19 75; Randall and Coggle 1995). For example, all mice exposed once to 5,000 rad (50 Gy) from a 1 mm diameter source developed an acute skin reaction with the following characteristics (Randall and Coggle 1995). After an asymptomatic period of 3 or 4 days, the skin exhibited increasing erythema and pi gmentation changes, leading to dry desquamation by day 10. Within a few days, exposed skin entered a period of moist desquamation, during which a serum scab was formed that was prevalent between days 15 and 25. Re-growth of the epithelium commenced at the edges of the irradiated field and from surviving hair follicles. By 1 month postirradiation, the epidermis was overtly normal, although histologically h yperplastic. Chronic fibrosis was a delayed skin reaction that was not apparent until 3–6 months postirradiation.
Dose-related effects were noted in guinea pig sk in that was treated with a 25x25 mm square 90 Sr source (Etoh et al. 1977). At 1,000 rad, there was a tran sient 25% reduction in the number of basal epithelial cells by day 10, which approached normality by day 15. At 2,200 rad, the epithelial basal cell population dropped by about 60% at day 12, but was slightly above normal by day 20. At 3,000 and 5,000 rad, the basal epithelial cell population was reduced 75%, but hype rplasia was also detected at the margin of the field. Hyperplasia was maintained for the 50-day observation period following exposure to 2,200– 5,000 rad. At 3,000 rad, erythema was noted by da y 14, followed by dry desqua mation and complete hair loss by day 21. A similar pattern, with ulceration at 1 month, was seen at 5,000 rad.
Within certain ranges, field-size e ffects for acute, localized external exposures to radioactive strontium have been demonstrated in mice and pigs. Hopewe ll et al. (1986) exposed young SAS/4 male mice to different levels of radiation from 90 Sr sources varying in diameter between 1 and 22.5 mm. The ED 50 values for moist desquamation were 2,200–2,750 rad (22–27.5 Gy) for the 22.5-mm source and 7,500– 9,000 rad for the 5-mm source. Acute tissue breakdown was only achieved in mouse skin by very high doses (ED 50 ≥ 14,000 rad) when the smallest sources were employed ( ≤ 2 mm in diameter). In a parallel study in pigs, moist desquamation occurred at 2,25 0–7,500 rad (22.5–75 Gy) and acute tissue necrosisSTRONTIUM 107 3. HEALTH EFFECTS
occurred at doses of ≥ 14,000 rad (140 Gy) (Hopewell et al. 1985, 1986). Peel et al. (1984) compared the effect on pigskin of acute exposure to 90 Sr sources with diameters between 1 and 40 mm. The effects of acute beta radiation included epithelial cell death with in the first 16 weeks, and subsequently, dermal necrosis that was attributed to vascular damage. The rate of repair was dependent on the size of the exposed area, since repair was dependent upon the migr ation of healthy cells into the wound. Transient moist desquamation associated with bright red erythema was observed between 4 and 6 weeks. At ‘high’ doses, this intensified and the dermis became ul cerated, but healed with scarring. After doses ≥ 4,000 rad (22.5-mm source), 6,600 rad (11-mm source), or 12,500 rad (5-mm source), a dusky red or mauve erythema followed by dermal necrosis occurred between weeks 10 and 16. In pigs that were acutely exposed to the same range of 90 Sr sources at the age of 3 months, dose-dependent dermal atrophy was detected in the irradiated field 2 years later, reach ing a maximal 55% reduction in dermal thickness for all doses above 4,500 rad (45 Gy; Hamlet et al. 1986). Dermal atrophy was produced by doses below the threshold required to induce moist desquamation. The threshold dose for moist desquamation following irradiation by the 22.5 mm source (2,250 rad) prod uced a 38% thinning of the dermis. Irradiation from the 1-mm source produced 30% dermal thinning at th e threshold (7,250 rad). Irradiation from the 5-mm source (2,000 rad) reduced the thickness of the de rmis by 35%. For the 11–22.5-mm sources, above doses that caused maximal thinning (in the range of 12,000–6,250 rad, respectively), the relative dermal thickness increased slightly, but rema ined 30–40% thinner than normal.
The highest reliable NOAEL values and all LOAEL valu es for dermal effects from external exposure to radioactive strontium in each species and dura tion category are recorded in Table 3-4.

Ocular Effects. Beta radiation has been employed medically to treat pterygium, an alteration in the conjunctival connective tissue that resu lts in the penetration of the superficial corneal stroma by vascular connective tissue (Tong et al. 1969; Wesberry and Wesberry 1993). As an adjunct to surgical removal of the pterygium, a solid 90 Sr source is apposed to the site in or der to reduce neovascularization. Several clinical studies reported complications resulting from this procedure. Serious effects (radiation cataracts, keratinization and telangiectasis of the conjunctiva) resulted from the high dose levels used when the technique was first employed usi ng other beta-emitting radionuclides (Merriam 1955). Atrophy of the sclera occurred after a dose of 1,600 rad from 90 Sr. In a later study, 78 eyes in 62 patients were treated with 1,080 rad (10.8 Gy) of beta radiation from a 90 Sr source repeated at weekly intervals (total dose 3,200 rad; 32 Gy; Tong et al. 1969). Because pterygia recurred within 2–18 months, six patients were retreated as before, two were given a single dose of 2,1 00 rad (21 Gy), and one of these two received a third dose of 2,100 rad (21 Gy). One eye, which had received treatments of 5,380 rad (53.8 Gy) each to twoSTRONTIUM 108 3. HEALTH EFFECTS adjacent fields, developed keratitis of the cornea. Ot her complications noted were telangiectasis of the conjunctiva (27%), scarring of the conjunctiva (14%), and scarring of the cornea (3%); the authors did not specify the exposure levels at which these side effects occurred. A more recent study described results for 171 eyes that had been treated with single doses of 1,700–1,800 rad (17–18 Gy) (Wesberry and Wesberry 1993). During follow-up periods lasting between 1 a nd 19 years, the only complications noted were one case each of corneal scarring, iritis, conjunctivitis, mild irritation, and, in a diabetic patient, scleral thinning. A complication rate of 1.8% was reported for a study of 490 eyes (399 patients) that received doses between 31 and 42 Gy (3 ,100–4,200 rad) in four or five fractions over 29 days (Nishimura et al. 2000). Scleral thinning, not severe enough to requir e treatment, was reported for four eyes in three patients 0.5, 2, and 9 years after treatment. Infectious scleral ulcer occurred within weeks of treatment in one male. Ischemic necrosis of the sclera in one male and adhesion of the eyelid and eyeball in one female occurred several years after repeat treatme nts for recurring pterygia; adhesive scarring of the eyelid occurred in one female 7 years after treatment.
No studies were located regarding ocular effects in animals after external exposure to radioactive strontium isotopes.
The highest reliable NOAEL values and all LOAEL va lues for ocular effects in humans from external exposure to radioactive strontium in each dur ation category are recorded in Table 3-4.
No studies were located regarding the following effect s in humans or animals af ter external exposure to radioactive strontium isotopes:

3.3.3.3 Immunological and Lymphoreticular Effects 3.3.3.4 Neurological Effects
3.3.3.5 Reproductive Effects
3.3.3.6 Developmental Effects

3.3.3.7 Cancer

Development of skin cancers in mice following loca lized exposure to beta radiation from a solid 90 Sr- 90 Y source depended on the dose and on strain susceptibilities (Hoshino and Tanooka 1975). In experimentsSTRONTIUM 109 3. HEALTH EFFECTS using a 40 mCi (1.48x10 9 Bq) 90 Sr- 90 Y source that delivered doses of 290 rad/min (2.9 Gy/min) to the skin, ICR mice exposed to a single localized dose of 2,700 rad (27 Gy) developed an acute skin reaction within the first month (see Section 3.3.4.2 Dermal Effects), but did not develop skin cancer during a 23-month observation period (Hoshino and Tanooka 1975). When the exposure was repeated 7 times for a total dose of 17,800 rad (178 Gy), one fibrosarcoma of the skin appeared after 10 months among five mice. Even extending the duration of the repeated 17,800 rad treatment for 43 weeks did not increase the incidence of malignant skin tumor; a single reticulocyt e sarcoma developed in one out of five mice. Mice from a different strain, Japanese ddN, exposed to si ngle doses of up to 17,400 rad (174 Gy) did not develop skin tumors during a 1-year observation period (Hoshino and Tanooka 1975). In the acute dermal toxicity experiments described above, Randall and Coggle (1995) selected the exposure level of 5,000 rad (50 Gy) for their mouse studies since it is known to be a critical dose for carcinogenetic effects in humans exposed to ionizing radiation.
Ootsuyama and Tanooka (1988, 1989) exposed the back s of female ICR mice to beta radiation from a 40,000 μCi (1,500 MBq) source of 90 Sr– 90 Y, which delivered a surface dose rate of 228 rad/minute (2.28 Gy/minute) and a 20–80% lower dose rate to the t op of the vertebrae. Mice were irradiated 3 times weekly at skin entrance doses per exposure of 135–1,180 rad (1.35 –11.8 Gy), and irradiation was continued until a palpable tumor appeared (up to 86 weeks). Tumors arising included squamous cell carcinomas, basal cell carcinomas, fibrosarcomas, and osteosarcomas. No skin tumors arose in mice receiving 135 rad/day (1.35 Gy/day). The total number of irradiations (and total dose) needed to induce 50% incidence of skin tumors ranged from 252 sessions for a total of 37,800 rad (378 Gy) for the 150 rad/day level and 156 sessions for a total of 192,300 rad (1,923 Gy) for the 1,180 rad/day level. Osteosarcomas were induced at lower doses, most frequently with skin surface doses of 250–350 rad (2.5–3.5 Gy) per exposure. In time, 100% of mice developed tumors in grou ps receiving 250–1,180 rad per exposure. Ootsuyama and Tanooka (1988) suggested that the 135 rad/day dose might represent a threshold dose, since no tumors formed. However, in their experimental design, they arbitrarily terminated exposures at this dose level on day 300, wh ich conceivably could be shorter than the latency period for tumor development at that dose.
The CELs resulting from external exposure to radioactive strontium in each species and duration category are recorded in Table 3-4.STRONTIUM 110 3. HEALTH EFFECTS
3.3.4 Other Routes of Exposure

This section includes injection and in vitro studies that provide evidence for the biological basis of toxicity of stable and radioactive strontium in hum ans and animals. Since these studies are not directly relevant to general population expos ure conditions, no LSE tables have been created for this section.
Hematological Effects Hematological effects have been obser ved in several clinical studies in which 89 Sr, one of the shorter-lived radioactive isotopes of strontium, has been u sed in cancer therapy for the relief of pain by irradiating and destroying tumors that have metast asized to the bone marrow (Baziotis et al. 1998; Ben-Josef et al. 1995b; Blake et al. 1987c; Breen et al. 1992; Kan 1995; Lee et al. 1996; Piffanelli et al. 2001; Sciuto et al. 2001). Sign ificant reductions in platelet and white blood cell counts (averaging 70 and 30%, respectively) were seen 3 months after patients were injected with a single therapeutic dose (40 μCi 89 Sr/kg; 1.5 MBq/kg) (Lee et al. 1996). In two patients who received two doses of 60 μCi 89 Sr/kg (2.2 MBq/kg) 6 months apart, platelet counts were significantly reduced (>30%) for at least 1 year. Similar effects have been observed in animals. Hypoplasia of the bone marrow has been observed in mice injected with 90 Sr (Ito et al. 1976; Nilsson 1970) or 89 Sr, the latter of which has been used intentionally to create mice with aplastic bone marrow (Bennett et al. 1976; Haller and Wigzell 1977; Levy et al. 1981; Merluzzi et al. 1978; Oghiso et al. 1988; Sawyer et al. 1982). CBA/J mice injected with fixed doses of 89 Sr that differed in the specific ac tivity of the preparation, showed quantitative differences in the degree of bone marrow suppression (Shibata et al. 1985). Acute hematological symptoms (depression of hemopoiesis lead ing to anemia or hemorrhage) were observed in beagles beginning several weeks after injection of 64 or 98 μCi 90 Sr/kg (Dougherty et al. 1972). Transient neutropenia occurred at the 10.8 μCi 90 Sr/kg level, and prolonged (36-m onth) depression of all types of leukocytes was reported at 32.7–98 μCi 90 Sr/kg. No hematological effects were noted at levels between 0.57 and 3.46 μCi 90 Sr/kg.

Musculoskeletal Effects. Osteonecrosis was reported after 2 da ys for 2-day-old rats that were injected intraperitoneally with 2 mCi 90 Sr/kg of body weight (Hopkins and Casarett 1972). In weanling rabbits, injection of 600 μCi 90 Sr/kg resulted in increasing cell death of differentiating odontoblasts and pulp cells of immature teeth and disordered tooth st ructure (Rushton 1963). Mature teeth in the same animal, or teeth in adults injected at the age of 3 years or older, were not affected as severely.
Immunological and Lymphoreticular Effects. Evidence from injection studies in animals corroborates the sensitivity of the immune system to radioactive strontium. In mice that have beenSTRONTIUM 111 3. HEALTH EFFECTS injected with 89 Sr or 90 Sr to deplete bone marrow, NK cells are preferentially eliminated (Emmanuel et al. 1981; Gidlund et al. 1990; Haller and Wigzell 1977; Wiltr out et al. 1989). The loss of this cell population results in a reduced ability to defend against lymphoi d tumors (Haller and Wigzell 1977; Luevano et al. 1981) or a transplanted methylcholanthrene-induced sarcoma (Scuderi and Rosse 1981b). In CBA/SU mice injected with 90 Sr(NO 3 ) 2 , the responsiveness of spleen cells to activation by B-cell mitogen lipopolysaccharide was reduced, which was attributed to the cytotoxic effect of 90 Sr on bone marrow, a source of precursor cells for the spleen (Bie rke 1990). In mice injected with 400–800 μCi 90 Sr/kg to deplete bone marrow, the thymus went through two ph ases of weight loss and regeneration within 50 days (Järplid 1973).
Reproductive Effects. Numerous animal studies demonstrated adverse reproductive effects of injected radioactive strontium. For the first 4 week s after male CBA mice were injected intraperitoneally with 18 μCi of 90 Sr and mated with untreated females, feta l deaths were 5–10% higher than controls (Lüning et al. 1963a). The increase in fetal mortality was much less (only ~2 %) when the same males were mated 11–15 weeks postinjection (Lüning et al. 1963b). In a similar study using male C 3 H/He mice, a single injection of 1,160 μCi 90 SrCl 2 /kg resulted in fetal death rates 7–8% higher than normal for matings conducted 10–40 weeks after injection (Reddi 1971). Autoradiography demonstrated that 90 Sr selectively accumulated in testicular stem cells.
When female CBA mice were injected with 90 Sr(NO 3 ) 2 on the 19 th day of pregnancy, a dose of ≥ 43 μCi
90 Sr(NO 3 ) 2 /kg ( ≥ 1,600 kBq/kg) transiently suppressed spermatocyte maturation of the male offspring, but the spermatid numbers had recovered by day 56 (De Rooij and Rönnbäck 1989). After the recovery period, the reproductive capacity (number of litters, litter size) of male offspring at the highest dose level (86 μCi 90 Sr(NO 3 ) 2 /kg; 3,200 kBq/kg) was unaffected. No testicular effects were observed at doses of 11 or 21 μCi 90 Sr(NO 3 ) 2 /kg (400 or 800 kBq/kg). Compared to th e effect on male offspring, reproductive effects were more severe in female offspring of dams exposed to 90 Sr(NO 3 ) 2 on the 19 th day of pregnancy (Rönnbäck 1980). Dose-related decreases in the numb er of differentiating oocytes in the ovary were observed up to day 84 at all dose levels ranging from 5.5 to 43 μCi 90 Sr(NO 3 ) 2 /kg (200–1,600 kBq/kg). Injection on the 16–19 th day was found to have more severe effects than injection earlier in gestation (Nilsson and Henricson 1969; Rönnbäck 1979). A longe r-term study demonstrated that the radioactivestrontium-induced decrease in the number of oocyt es in the ovary persisted for at least 10 months (Rönnbäck 1981b). Furthermore, the reproductive capacity (number of fertile females, number of litters, number of young per litter) of females treated in utero was significantly reduced at the two highest maternal dose levels (43 and 86 μCi 90 Sr(NO 3 ) 2 /kg; 1,600 and 3,200 kBq/kg). Rönnbäck (1981a) alsoSTRONTIUM 112 3. HEALTH EFFECTS examined the effect of exposure via l actation using CBA mice receiving 21 μCi 90 Sr(NO 3 ) 2 /kg (800 kBq/kg). Ovarian cellularity, especially the ear liest stages of oogenesis, was reduced in females exposed in utero , whether or not they suckled milk contaminated with 90 Sr. However, early stage oocyte numbers were somewhat improved by sucking uncon taminated milk. When unexposed newborn females were exposed to contaminated milk, the numbers of early stage oocytes was significantly reduced, but not as severely as in females exposed in utero . These studies suggest that reproductive capacity, particularly in females, may be adversely affected by gestational exposure to high levels of radioactive strontium. These levels are high compared to reported releases of 90 Sr from nuclear power facilities (see Table 6-1).
Developmental Effects. Injection of relatively high doses of radioactive strontium into pregnant animals resulted in severe developmental effects. A single dose of ≥ 764 μCi 90 Sr/kg into female LongEvans rats had no effect on fetal mortality when ad ministered on gestational day 10, but significantly increased fetal mortality when administered on gestational day 2 (Hopkins et al. 1967). In addition, there were dose-related increases in the in cidence of fetuses with skeletal abnormalities (general stunting, lack of ossification, fusion of ribs, vertebral anomali es, missing tail). The incidence of micropthalmia was also significantly increased at the higher activity level (1,488 μCi 90 Sr/kg). The offspring of female Wistar rats injected with ≥ 100 μCi 90 Sr(NO 3 ) 2 at gestational day 18 showed no gross malformations, but there was a significant increase in the incidence of meningeal and pituitary tumors (Schmahl and Kollmer 1981; Schmahl et al. 1979). This was shown to be connected with a late gestational increase in the transfer of transplacental strontium to the basio ccipital and sphenoid bones of the skull. Tumor development was probably assisted by the position of th e pituitary gland within the sella turcica, which resulted in the gland being irradiated from the ventral a nd lateral surfaces. The total radiation dose rate at that position was calculated to be between 60 and 120 rad for the lifesp an of 30 months. After pregnant dogs were injected with 1 mCi of radiostrontium per kg (80–99% 89 Sr and 1–20% 90 Sr) 6 days prior to delivery, the puppies dying within 11 weeks exhib ited abnormalities of the skeleton (underdevelopment of the jaws, incomplete and abnormal ossification, abnormal epiphyseal cartilage), partial atelectasis of the lungs, hyperplasia of lymph nodes and spleen, or deficient hematopoiesis (Finkel and Biskis 1969; Finkel et al. 1972). Puppies injected subcutaneously 12 days after birth showed some skull abnormalities and developed osteosarcomas. Effects on the reproductive system following in utero exposure to radioactive strontium are discussed in the preceding paragraphs. Cancer effects in animals exposed to radioactive strontium in utero are discussed in the next paragraph.

Cancer. Numerous studies in several species reported the induction of malignant tumors in response to injection of radioactive strontium (mice: Ash and Lo utit 1977; Bierke and Nilss on 1990; Ito et al. 1976;STRONTIUM 113 3. HEALTH EFFECTS Loutit 1976; Nilsson 1971, 1972; Nil sson et al. 1980a; Reif and Triest 1982; Chinese hamsters: Benjamin et al. 1976b; Brooks et al. 1974; rabbits: Kshirsagar et al. 1965; Vaughan and Williamson 1969; mongrel dogs: Finkel and Biskis 1969; Finkel et al. 1971; beagle dogs: Lloyd et al. 1995; Taylor et al. 1966). In general, osteosarcomas and bone hemangiosarcomas de veloped at higher dose levels, and lymphomas and leukemias developed at lower levels. Carcinomas of soft tissues adjacent to bone also developed. The offspring of pregnant rats that were injected on g estational day 18 had a higher incidence of pituitary adenoma and meningeal sarcoma (Schmahl and Kollmer 1981; Schmahl et al. 1979). These findings were attributed to the higher incorporation of 90 Sr to the skull at that developmental period and to the anatomical position of the pituitary within the sella tu rcica, which subjected it to radiation from all but the dorsal surface. The female offspring of pregnant mi ce that were injected intravenously with 90Sr on gestational day 19 developed a higher incidence of tubular adenoma of the ovaries (Rönnbäck and Nilsson 1982).

3.4 GENOTOXICITY
There is little evidence for genotoxicity of stable st rontium. However, radioactive strontium isotopes release ionizing radiation that, within an effec tive radius, is known to damage DNA (see Appendix D Section D.4.1 Radiation Effects at the Cellular Level). Summaries of in vivo and in vitro genotoxicity data are presented in Tables 3-5 and 3-6, respectively.

In Vivo Exposure

Stable Strontium. No studies were located regarding genotoxi c effects in humans following exposure to stable strontium. The only in vivo genotoxicity study for stable strontium in animals involved acute oral exposure. Oral administration of 130 mg strontium/kg body weight as strontium chloride to Swiss albino female mice increased the incidence of chromosomal aberrations (gaps, breaks, nondisjunction, and polyploidy) in bone marrow cells 5-fold after 6 hours (Ghosh et al. 1990). Genotoxicity in male mice administered a similar dose (140 mg/kg) was only doubled, and therefore, was less severe than in females. At higher doses (440–1,400 mg/kg), the incidence of chromosomal aberrations was similar in both sexes after 6, 12, or 24 hours.

Radioactive Strontium. Human in vivo genotoxicity data are available from studies of the Techa River populations exposed to combined external ga mma radiation and internal radiation from 90 Sr and 137 Cs between 1949 and 1956 and from studies on patients exposed to 89 Sr as a radiopharmaceutical. The stableSTRONTIUM 114 3. HEALTH EFFECTS 

### Table 3-5. Genotoxicity of St able and Radioactive Strontium In Vivo Species (test system) End point Results Reference Stable Strontium Strontium chloride: Mouse (bone marrow) Chromosomal gaps, breaks, + Ghosh et al. 1990 polyploidy, centric fusion Radioactive Strontium 89 Strontium chloride: Human (lymphocytes) Transient increase in + Watanabe et al. 1998 micronuclei 90 Strontium: Human (lymphocytes) Chromosomal aberrations + Ilynskikh et al. 1999 (rings, dicentric, tricentric) Mouse (skin) Unscheduled DNA synthesis + Ootsuyama and Tanooka 1986 Mouse (thymus, lymph Aneuploidy + Ito et al. 1976 nodes, bone marrow) Chinese hamster (bone Chromosomal breaks, + Brooks and McClellan marrow) exchanges, rings 1969 Miniature swine Chromosomal breaks in + Clarke et al. 1972; (leukocytes) leukemic cells Howard 1970

+ = positive results; – = negative re sults; DNA = deoxyribonucleic acidSTRONTIUM 115 3. HEALTH EFFECTS 

### Table 3-6. Genotoxicity of St able and Radioactive Strontium In Vitro
Results With Without Species (test system) End point activation activation Reference Stable Strontium Strontium chloride: In vitro DNA synthesis reaction Lack of fidelity in DNA – – Loeb et al. 1977 synthesis Prokaryotic organisms:
Bacillus subtilis Rec - Growth inhibition – – Kanematsu et al. 1980 Eukaryotic cells: Chinese hamster ovary cells Reduced cloning – – Tan et al. 1984 efficiency Radioactive Strontium

90 Strontium: Human (blood) Chromosomal rings, + de Oliveira et al. dicentrics, acentrics 2001 DNA damage in + electrophoretic assay Human (lymphocytes) Micronucleus formation + Mills et al. 1996 Human (lymphocytes) Micronucleus formation + Hall and Wells 1988

– = negative result; + = positive result; (+) = weakly positive result; DNA = deoxyribonucleic acidSTRONTIUM 116 3. HEALTH EFFECTS chromosomal translocation frequency in peripheral lymphocytes was evaluated in 73 radiation-exposed individuals from the Techa River area and 39 une xposed individuals from noncontaminated areas (Bauchinger et al. 1998). The mean genomic frequency of translocations per cell in the exposed group (12.8±1.5x10 -3 ) was significantly elevated compared to unexposed controls (5.7±1.0x10 -3 ). Furthermore, the translocation frequency per cell was significantly higher in the subgroup that had been exposed to radiation as teenagers (22±4.3x10 -3 ) compared to the subgroup exposed as adults (9.7±2.3x10 -3 ).
Increased skeletal incorporation of radiostrontium in teenagers, leading to higher radiation doses to the bone marrow, probably contributed to the observed incr ease in translocation frequency for this subgroup. In a more recent study of the Techa River popul ations, there was a dose relationship between the frequency of chromosomal aberrations (dicentric, ring) in T-lymphocytes (assessed in 1994–1996) and whole body 90 Sr activity (detected by human radiation counter in 1993) for individuals residing in the Muslyumovo settlement (Ilyinskikh et al. 1999). The frequency of chromosomal aberrations was 3.8±0.8 for a non-exposed control group (whole-body 90 Sr activity <100 nCi), and 8.9±0.7, 12.9±1.2, and 18.7±1.9%, respectively, for exposed individuals with 90 Sr activity levels of 100–500, 500–1,000, and ≥ 1,000 nCi. In a few cancer patients who were injected with 3 mCi (111 MBq) of 89 SrCl 2 to treat severe pain from multiple bone metastases, the number of micronuclei present in the lymphocytes tripled in the week after exposure, but declined in succeeding week s (Watanabe et al. 1998). The authors found that the percentage of micronuclei, indicative of chro mosomal damage, was equivalent to the damage observed in a separate in vitro experiment in which cells received a dose of 53 rad (0.53 Gy) by X-irradiation.
In a long-term feeding study, chromosomal breaks were noted in leukocytes of miniature pigs that had developed leukemia as a result of exposures of 25 μCi 90 Sr/day (925 kBq/day) or more for >1 year (Clarke et al. 1972; Howard 1970). Unexpected (“un scheduled”) DNA synthesis w as detected in the skin of female ICR mice several hours after external exposure to 10,000–30,000 rad (100–300 Gy) from a
90 Sr- 90 Y disk applicator (surface dose rate 228 rad/mi n) (Ootsuyama and Ta nooka 1986). Tritiated thymidine incorporation related to DNA repair was elev ated to a greater degree in epithelial cells of the irradiated epidermis than in the dermis. This difference appeared to be intrin sic to the cell type, since thymidine incorporation in hair follicle epithelium situated at the same depth as fibroblastic dermal cells, occurred at a faster rate. The authors suggested that the somewhat slower rate of DNA repair in the dermis could contribute to the higher risk of cancer in the dermis, compared to the epidermis, following exposure to ionizing radiation.STRONTIUM 117 3. HEALTH EFFECTS A single intraperitoneal injection of 90 Sr– 90 Y into Chinese hamsters (200–5,000 μCi/kg) resulted in an increasing number of chromosomal breaks/cell over time (between 2 and 224 days), as the cumulative radiation dose to the skeleton increased (Brooks a nd McClellan 1969). The number of chromosomal breaks and chromatid/isochromatid de letions per bone marrow cell increased as a function of dose rate, or as the activity of radionuclide injected per body weight. The relative number of chromatid exchanges and rings and dicentrics decreased with time after expos ure, whereas the number of chromosomal exchanges increased. Abnormal chromosomal numbers were detected in the thymus, lymph nodes, and bone marrow of female ICR/JCL mice as late as 90 days after interperitoneal injection with 1 mCi/kg of 90 Sr (Ito et al. 1976).

In Vitro Exposure

Stable Strontium. In mutagenicity assays using the Rec - (recombination-repair-deficient) strain of Bacillus subtilis , strontium chloride had a negative effect in vitro (Kanematsu et al. 1980). Furthermore, in a survey of the effect of metal salts, strontium was found to have no adverse effect on the fidelity of DNA synthesis in vitro , which was thought to be consistent with its reported lack of mutagenicity and carcinogenicity (Loeb et al. 1977).
The only stable strontium compound known to be genot oxic is strontium chromate. Strontium chromate induced sister chromatid exchang es in Chinese hamster ovary cells in vitro (Venier et al. 1985). In the Ames test using the Salmonella typhimurium strain TA100, strontium chromate induced mutations in the presence, but not in the absence of S9 microsomes. The genotoxicity of strontium chromate is related to the ability of the hexavalent chromium ion to ente r cells and become metabolized, forming a reactive DNA-adduct. Strontium only contributes to the solubility of the salt (Elias et al. 1989, 1991).

Radioactive Strontium. Radioactive strontium has been shown to be genotoxic to human cells in vitro

. In lymphocytes from freshly-drawn human blood, do ses of 0.2–5.0 Gy (0.002–0.05 rad) increased the frequency of chromosomal aberrations (de Oliveira et al. 2001). Acentric aberrations (acentrics and double minutes) increased at ≥ 0.2 Gy (0.002 rad), dicentric aberrations increased at ≥ 0.5 Gy (0.005 rad), and there was a slight indication that the frequency of centric rings increased at ≥ 3.0 Gy (0.03). In the same study, results of an electrophoretic assay (comet assay) on single exposed lymphocytes revealed that DNA damage (evaluated by visual inspection and tail moment) occurred at doses as low as 0.2 Gy (0.002 rad). The varying frequencies for the differe nt types of chromosomal aberrations were associated with the number of DNA breaks required for their formation and whether one or more chromosomes wereSTRONTIUM 118 3. HEALTH EFFECTS involved: acentrics requiring a single break and dicentrics requiring at least two breaks on different chromosomes. Dose-related increases in micronucleus formation, predominantly derived from acentric chromosomes, were reported in human lymphocyt es irradiated at doses between 0.3 and 3.0 Gy (0.003 and 0.030 rad) (Hall and Wells 1988; Mill et al. 1996).

3.5 TOXICOKINETICS
3.5.1 Absorption
3.5.1.1 Inhalation Exposure
Evidence for absorption of inhaled strontium in hum ans is provided by several cases of accidental exposure of workers to airborne radiostrontium (N avarro and López 1998; Petkau and Pleskach 1972; Rundo and Williams 1961). Although these cases do not provide a complete quantitative description of the absorption of inhaled strontium in humans, they de monstrate clearly that inhaled aerosols of strontium compounds (e.g., SrCl 2 , SrTiO 3 ) can be absorbed, as indicated by the detection of radiostrontium in urine and feces.
In one case, a worker accidentally inspired an unknown quantity of 90 SrCl 2 (physical form unknown) and over the subsequent 800 days, 90 Sr was excreted in the urine with half-times of 3.3 (52%), 17 (7%), and 347 days (18%) (Petkau and Pleskach 1972). The urinary:fecal excretion ratio was 3:1. In a second case, a worker was exposed to 90 SrCO 3 (physical form unknown) with deposition within the nasal tract as well as the hands, face, and hair. The actual inhaled dose could not be determined; however, based on the excretion kinetics of 90 Sr over the subsequent 300 days, the rec onstructed internal dose was estimated to have been approximately 300–400 nCi (11.1–14.8 kBq) (Rundo and W illiams 1961). Excretion in urine occurred with half-times of 2.2 (>90% ), 15, and 175 days, and the urinary:fecal excretion ratio over the first 24 days was 0.71. In a third case, two workers accidentally inhaled 90 SrTiO 3 (physical form unknown), and 90 Sr was detected in urine over a period of 225 days (Navarro and López 1998).

Studies conducted in animals have shown that the rate of absorption depends on the chemical form of the inhaled strontium aerosol. Compounds of greater solub ility are, in general, more rapidly cleared from the lung. For example, strontium is rapidly cleared from the lung after inhalation of SrCl 2 . In dogs that received a 2–22-minute nose-only exposure to an aerosol of 85 SrCl 2 (activity median aerodynamic diameter [AMAD] 1.4–2.7 μm, geometric standard de viation [GSD] 2.0), <1% of the initial lung burden remained in the lung 12 hours after the exposure; 37% of the body burden was distributed to the skeletonSTRONTIUM 119 3. HEALTH EFFECTS within 12 hours after the exposure, and 84% was in the skeleton 4 days after the exposure (Fission Product Inhalation Project 1967a). In contrast to the relatively rapid absorption of inhaled SrCl 2 , after exposures to strontium in particles of fused clay, abso rption is much slower. In dogs that received a noseonly exposure to 90 Sr in fused montmorillonite clay particles (AMAD 2.2 μm, GSD 1.7), the average halftime of elimination of strontium from the lung was 490 days (Snipes et al. 1974a, 1974b). Thus, strontium compounds of lower solubility are more slowly absorbed from the lung. Support for this also comes from studies in which the rates of absorption of various compounds of strontium were compared in rats. Rats were exposed to aerosols of 85 Sr carbonate, phosphate, fluoride, oxid e, or titanate (particle sizes and doses not specified) (Willard and Snyder 1966). Greater than 99% of the initial lung burden of 85 Sr was cleared from the lung 5 days after inhalation of the carbonate, phosphate, fluoride, or oxide, whereas 60% of the 85 Sr remained in the lung after inhalation of the more insoluble strontium titanate.
In rats exposed to airborne fly ash (sieved to have a particle diamet er of distribution of 90% less than 20 μm) for 6 hours, strontium was eliminated from the lung with a half-time of 23 days (observations were made for 30 days) (Srivastava et al. 1984b). On e day after the exposure, the tissue:plasma strontium concentration ratios were 0.3–0.5 in the liver, kidney, sm all intestine, and heart. The report of this study does not indicate whether whole-body or nose-only exposur es were utilized in the study; therefore, it is not possible to know for certain how much of the absorption may have resulted from ingestion of fly ash deposited on the animals. Furthermore, given the relatively large particle size of the fly ash, it is likely that deposition in the respiratory tract was largely in the tracheobronchial and nasopharyngeal region, from which the strontium may have been cleared mechanically to the esophagus and swallowed. Nevertheless, studies in which 89 Sr-enriched fly ash was instilled into the trachea of rats indicate that strontium in this form was partly absorbed and app eared in plasma and other tissues within days of the exposure (Srivastava et al. 1984a).
Although intratracheal instillation does not precisely replicate inhalation exposure, these studies provide additional evidence that strontium compounds of greater solubility are absorbed more rapidly from the lung. Strontium was cleared relatively rapidly from the lungs of rats that received an intratracheal dose of SrCl 2 (half-times <1 day) and was eliminated from the body in the urine (4–6% of the initial body burden) and in the feces (10–18%) (Naményi et al. 1986). By contrast, in rats that received an intratracheal dose of 360–760 μg Sr as SrTiO 3 , strontium was eliminated from the lung with half-times of 0.4 days (85%) and 130 days (15%); the long retention phase reflec ts the slow absorption of the insoluble SrTiO 3 deposited in the lung, whereas the rapid phase reflects the mechanical clearance from the tracheobronchial region (Anderson et al. 1999b).STRONTIUM 120 3. HEALTH EFFECTS

Strontium has been shown to be absorbed from the nasopharyngeal region of the respiratory tract. In hamsters administered 85 SrCl 2 (in saline solution) directly into the nasal tract, 67% of the 85 Sr was absorbed in 4 hours and 63% was estimated to have been absorbed directly from the nasopharynx region of the respiratory tract (Cuddihy and Ozog 1973).

3.5.1.2 Oral Exposure
The fractional absorption of ingested strontium has b een estimated in healthy human subjects or hospital patients who received an oral dose of strontium chloride (SrCl 2 ) or ingested strontium in the diet (Table 3-7). Absorption was quantified in these studies from measurements of plasma strontium concentration-time profiles for ingested and intravenously injected strontium (bioavailability), or from measurements of the difference between the amount ingested and excreted in feces (balance). Collectively, the results of these studies indicate th at approximately 20% (range, 11–28%) of ingested strontium is absorbed from the gast rointestinal tract. Balance measur ements can be expected to yield underestimates of absorption as a result of excre tion of absorbed strontium in the feces (see Section 3.5.4); nevertheless, the two methods ha ve yielded similar estimates of absorption.
Vezzoli et al. (1998) compared the area under the plasm a strontium concentration-time curves in adult males and females and found no significant differenc e (males, 10.6±0.6 mmol/L-minute; females, 9.3±0.6 mmol/L-minute). The subjects included groups of healthy age-matched men and women (15 males, 12 females) and groups of normocalcuri c patients (29 males, 18 females) who had calciumoxalate urinary tract stones. Although the fraction ab sorbed could not be estimated in this study because the area under the curve for an intrav enous dose was not measured, the results suggest that there were no substantive differences in absorptio n between males and females. This conclusion may not be valid for physiologic states in which there is an increased de mand for calcium such as pregnancy and lactation. Calcium absorption is higher in these states, and studi es in animals suggest that strontium absorption may also be higher (Kostial et al. 1969b). In general, strontium absorption appears to be a good indicator of calcium absorption in adult humans as both elements appear to share common mechanisms of absorption (Bianchi et al. 1999; Blumsohn et al . 1994; Milsom et al. 1987; Reid et al. 1986; Sips et al. 1994) (see Section 3.6.1).

Studies conducted in infants and children indicate th at approximately 15–30% of dietary strontium is absorbed, similar to estimates in adults (Alexander et al. 1974; Harrison et al. 1965; Kahn et al. 1969a;STRONTIUM 121 3. HEALTH EFFECTS 

### Table 3-7. Summary of Estimates of Abso rption of Ingested Strontium in Humans
Dose and Absorption media a Subjects (N) b (% of dose) c Comment Reference Tracer
44 mg, SrCl 2 44 mg, SrCl 2 88 mg, SrCl 2

219 mg, SrCl 2

Tracer

1.45 mg/kg, SrCl 2

Tracer

44 mg, SrCl 2

219 mg, SrCl 2 Adults (9M)
Adults (8M)
Adults (8M)
Adults (8M)

Adults (6M, 11F)

Adults (3M)

Adults (6M, 4F)
Adults (12)

Adults (43M, 20F)

Adults (6M)

Tracer in milk Adults (5)

Tracer Adults (4F) 28±3

25±7

25±6

19±5

20

21 (18–24)

22±2

17 (8–34)

13

20

11

42 (25–59) Healthy adults. Absorption estimate based on whole body retention (R): R oral /R iv . Healthy, fasted subjects adults. Absorption estimate based on plasma AUC oral /AUC iv . d Healthy fasted subjects. Absorption estimate based on plasma AUC oral /AUC i . Healthy subjects. Dose administered with meal. Absorption estimate based on plasma AUC oral /AUC iv . Patients with osteoporosis or chronic renal failure. Dose administered with meal. Absorption estimate based on plasma AUC oral /AUC iv . Patients with osteoporosis. Dose administered with meal. Absorption estimate based on plasma AUC oral /AUC iv . Healthy fasted subjects. Absorption estimate based on fraction of dose in plasma at 3 hours. Healthy subjects without a pre-dosing fast. Absorption estimate based on whole body counting. Fasted patients with growth hormone deficiency, osteoporosis, hypothyroidism or hypercalcuric urinary tract stones. Absorption estimate based on fraction of dose in plasma at 4 hours. Healthy fasted subjects. Absorption estimated from cumulative urinary excretion. Healthy subjects. Dose administered in milk, daily for 21–32 days. Absorption estimated from whole body retention kinetics. Two health subjects, two patients with osteoporosis. Absorption estimated from intake minus 20-day fecal excretion, corrected for fecal excretion after an intravenous dose. Likhtarev et al. 1975 Sips et al. 1995
Sips et al. 1996
Sips et al. 1996

Blumsohn et al. 1994

Hart and Spencer 1967

Bianchi et al. 1999
LeRoy et al. 1966
Sips et al. 1994

Leeuwenkamp et al. 1990 Rundo and Lilligraven 1966
Uchiyama et al. 1973

0.8 mg/day Adults (11M) 18 (-17–42) Patients wi th various disorders, including Warren and diet osteoporosis. Absorption estimate based on Spencer 1976STRONTIUM 122 3. HEALTH EFFECTS 

### Table 3-7. Summary of Estimates of Abso rption of Ingested Strontium in Humans
Dose and Absorption media a Subjects (N) b (% of dose) c Comment Reference

Tracer Adults (11M)

1,500 mg/day Adults (5F, 1M)

Diet Adults (9)

5–100 mg, Children (5) SrCl 2 4–14 years

100 μg Infants 6–8 breast milk days (12)
600 μg Infants diet 20 days–1 year (21) 18 (-17–42)

22 (20–28)

12 (0–48)

22

15 (-47–59)

28 (12–43) 6-day balance; dietary intake minus fecal excretion e

. Patients wi th various disorders, including osteoporosis. Absorption estimate based on estimated from 6-day balance; dietary intake minus fecal excretion e

. Patients with various illnesses. Absorption estimated from dietary intake minus fecal excretion minus fecal excretion after and I.V. dose (endogenous fecal excretion). Patients with various illnesses. Absorption estimate based on estimated from 6-day balance; dietary intake minus fecal excretion. e
Patients with various illnesses. Dose administered for 24–28 days. Absorption estimated from dose minus 14-day fecal excretion. Healthy breast-feeding subjects. Absorption estimate based on estimated from 3-day balance intake minus fecal excretion. e Healthy subjects. Absorption estimate based on estimated from seven sequential 28-day balances; dietary intake minus fecal excretion. e Warren and Spencer 1976

Spencer et al. 1960

Spencer et al. 1972a

Sutton et al. 1971b

Harrison et al. 1965

Kahn et al. 1969a

a Doses are in mass of strontium. b Number of males (M) or females (F) is presented if reported. c Values are reported means ± standard deviation; values in parentheses are reported ranges. d AUC refers to the area under the plasma strontium concentration-time curve. e Calculated from reported individual subject data.STRONTIUM 123 3. HEALTH EFFECTS Sutton et al. 1971a). Although ag e-related changes in strontium ab sorption cannot be discerned from the studies in humans, age-related changes in absorption of strontium have been observed in rats, suggesting the possibility of increased absorption of strontium during the neonatal period in humans. Adult male rats that received a single oral dose of 1.4 mg Sr as SrCl 2 absorbed 19% (±5 standard deviation [SD]) of the dose (Sips et al. 1997); this value is similar to that reported for humans (Sips et al. 1995, 1996).
However, when absorption was estimated at various ages, absorption was found to decrease from 85% of the dose at 15 days of age to 8% of the dose at ages older than 89 days (Forbes and Reina 1972). The differences between the adult estimates in these two studies may reflect the different methodologies; in the Sips et al. (1997) study, absorption was es timated from the area under the plasma strontium concentration-time curve for orally and intravenously administered strontium, whereas in the Forbes and Reina (1972) study, the absorption estimate was based on the measureme nts of 8-hour body burdens of strontium minus strontium in the gastrointestinal tract.
The fractional absorption of strontium appears to incr ease in rats during lactation. Rats that received a tracer dose of 85 Sr as SrCl 2 in drinking water between 14 and 16 days after the start of lactation absorbed twice as much strontium as control rats that were not lactating and received the same oral dose of strontium; 11% of the dose was absorbed in lactating rats compared to 5% in controls (Kostial et al. 1969b). Absorption was estimated in this study as the fraction of the dose in the skeleton, urine, and pups 3 days after the start of exposure.
The exact site of absorption of str ontium in the gastrointestinal tract is not known; however, studies in hamsters suggest the possibility of absorption in both the stomach and small intestine. In hamsters that received a gavage tracer dose of 85 SrCl 2 , 37% was absorbed, whereas 20% was absorbed when the dose was administered to hamsters that had their pylo ric sphincter ligated (Cuddihy and Ozog 1973). Studies in preparations of in vitro and in situ isolated intestine of the rat pr ovide direct evidence for strontium absorption in the small intestine (see Section 3.6.1).

3.5.1.3 Dermal Exposure
There is little evidence for systemic toxicity followi ng dermal exposure to strontium compounds, which would suggest that they are not read ily absorbed across the skin of humans. Ilyin et al. (1975) estimated absorption rates for solutions of strontium chloride across intact or abraded skin of human subjects. Three groups of three male volunteers received topical applications of 85 Sr as strontium chloride inSTRONTIUM 124 3. HEALTH EFFECTS aqueous solution (pH 7.0) without a carrier. In the first group, intact forearm skin (average area 8 cm 2 ) was exposed for 6 hours. In the second and third gr oups, the skin of the fo rearm was abraded with a metal grater just before the solution was applied; exposures were 6.1 cm 2 for 30 minutes and 6.9 cm 2 for 6 hours, respectively. For comparison, a four th group received an intravenous injection of 85 SrCl 2 . After exposure and decontamination of the skin, radioactiv ity measurements were taken over 40 days of the 85 Sr present in the whole body, the patella, the right unexposed forearm, and, during the first 20 days, in daily urine samples. Absorption of strontium was estimated from whole body or partial body 85 Sr burdens, or urinary excretion of 85 Sr in comparison to the same end points after an intravenous dose of 85 SrCl 2 . The absorption of radiostrontium through intact skin ove r 6 hours was estimated to be 0.26% (range, 0.14– 0.37%) of the applied dose, indicating that undamaged sk in is a relatively effective barrier to penetration by strontium. Strontium absorption was greater thr ough scratched and abraded skin. An average of 38% (range, 25.5–45.8%) of the applied dose was absorbed af ter 30 minutes and an average of 57.4% (range of coefficients, 55.7–65.3%) was absorbed after 6 hours. No other studies were located regarding dermal absorption of strontium compounds in humans.

An in vitro study evaluated penetration of 90 Sr through abdominal skin removed from 5- or 9-day-old Wistar rats and arranged in vertical penetration cells (Bauerová et al. 2001). The radionuclide in a chloride carrier solution (0.01–1.0% strontium chlo ride w/v) was applied to the epidermal surface; radioactivity of the permeated 90 Sr in the receptor chamber solutio n was measured by liquid scintillation spectrometry. Penetration was inversely related to c oncentration of the carrier solution. Penetration of the radiostrontium through the hairless skin of 5-da y-old rats over 24 hours was 4 times lower than through the hairy skin of 9-day-old rats: at a carri er concentration of 0.1%, penetration was 0.5% for hairless skin of 5-day old rats compared to 2% for 9-da y old rats. The authors attributed this difference to the barrier provided by the intact stratum corneum in 5-day skin, indicating that hair follicles in skin of 9-day-old rats increase the permeability of skin to stro ntium. In experiments in which epidermal layerswere stripped (by the 20x repeated application of adhesive tape) or entirely removed from skin of 5-dayold rats, penetration was a pproximately 25% over 24 hours.STRONTIUM 125 3. HEALTH EFFECTS
3.5.2 Distribution
3.5.2.1 Inhalation Exposure

Information on the distribution of inhaled strontium in humans is not available; however, it is reasonable to assume that the distribution of strontium absorbed into the systemic circulation after deposition in the respiratory tract would be similar to that absorbed after ingestion (see Section 3.5.2.2).

Studies in animals have shown that strontium that is absorbed after an initial deposition in the respiratory tract ultimately distributes primarily to the skeleton. In dogs that received a 2–22-minute nose-only exposure to aerosols of 85 SrCl 2 (AMAD 1.4–2.7 μm, GSD 2.0), 37% of the body burden was distributed to the skeleton within 12 hours after the exposure a nd 84% was in the skeleton 4 days after the exposure (Fission Product Inhalation Project 1967a). Four to 6 days after a 30-minute inhalation exposure of rats to aerosols of 85 Sr carbonate, phosphate, fluoride, or oxide (p article sizes and doses not specified), >99% of the body burden of 85 Sr was in the skeleton (Willard and Snyde r 1966). Two days after rats received a 10-minute head-only exposure to tracer levels of 85 Sr or a mixture of 85 Sr and 90 Sr aerosols (AMAD 1.8–2.8), at which time radioactive strontium could no l onger be detected in the lung, the concentration in bone was 100–2,000 times that in soft tissues (Fission Product Inhalation Project 1967b). The rank order of soft tissue concentrations (highest to lowest) was muscle > skin > liver > kidney. In rats exposed to airborne fly ash (sieved to have a particle diameter of distribution of 90% less than 20 μm) for 6 hours, strontium was detected in various tissues; 1 day after the exposure, the tissue:plasma strontium concentration ratios were 0.3–0.5 in the liver, kidney, small intestine, and heart (Srivastava et al. 1984b).
Information on the distribution of strontium absorbed after deposition in the respiratory tract can be derived from studies in which strontium compounds were instilled directly into the trachea. Although intratracheal instillation does not precisely replicate i nhalation exposure, the distribution of the absorbed strontium is likely to be similar to that which would be absorbed after i nhalation. In rats that received an intratracheal dose of 89 Sr-enriched fly ash (sieved to have a par ticle diameter of distribution of 90% less than 20 μm), radioactivity was eliminated from the lung and appeared in plasma and other tissues within days of the exposure; tissue:plasma concentration ra tios were >1 (1.5–2) in the liver, kidney, stomach, and small intestine, and <1 (0.7–0.9) in the spleen , heart, and brain (Srivastava et al. 1984a). The relatively high concentrations of strontium in the gastrointestinal tract ma y reflect the mechanical clearance of strontium from the airways to the esophagus.STRONTIUM 126 3. HEALTH EFFECTS Although placental transfer of strontium has been demonstrated in humans and animals exposed to strontium by other routes of exposure (see Section 3.5.2.2), only one study has examined placental transfer after a dose to the respiratory tract. Pr egnant rats received an intratracheal dose of 89 Sr-enriched fly ash (sieved to have a particle diameter of distribution of 90% less than 20 μm) on days 14–18 of gestation. The concentrations of strontium in w hole fetus, liver, lung, heart, and kidney were not significantly different from controls that received an instillation of saline (Srivastava et al. 1990).

3.5.2.2 Oral Exposure
The distribution of absorbed strontium in the human body is similar to that of calcium, with approximately 99% of the total body burden in the sk eleton (ICRP 1993). The skeletal burden of stable strontium has been estimated from analyses of bone samples from human autopsies (Herring and Keefer 1971a; O’Connor et al. 1980; Papworth and Vennart 1984; Tanaka et al. 1981). Skeletal burden was estimated in Japanese adult males to be approximately 440 mg compared to 850 g of calcium (Tanaka et al. 1981).
Papworth and Vennart (1984) analyzed published data on 90 Sr and calcium concentrations in human bone tissues and diets of people in the United Kingdom during the period from 1955 to 1970 and concluded that approximately 4.75% of the dietary intake of 90 Sr was taken up by the adult skeleton. Approximately 7.5% of the cortical bone 90 Sr burden was eliminated from bone each year (equivalent to elimination halftimes of approximately 9.2 years). The rate of elimination from trabecular bone was approximately 4 times this value. The same analysis yielded estimat es of skeletal uptakes of strontium that varied with age, being highest, approximately 10%, in infants and during adolescence, ages in which bone growth rates are high relative to other ages.
Strontium distributes relatively uniformly within th e bone volume where it exchanges with calcium in hydroxyapatite (see Section 3.6.1), although small diffe rences in the calcium and strontium distributions within bone have been reported. The Sr:Ca concentration ratio in bone increases with age from approximately 0.3 mg strontium/g Ca at birth to a value of 0.5 in adults (Papworth and Vannart 1984; Tanaka et al. 1981). The Sr:Ca ratio in bone also h as been shown to vary with the bone type; ratios in cortical bone were approximately 10–20% higher than in trabecular bone (Tanaka et al. 1981).

Information on the distribution of strontium in soft tissu e is extremely limited. In rats that were exposed to 3.4 mg strontium/L (as SrCl 2 ) in drinking water for 3 months, the serum concentration of strontium wasSTRONTIUM 127 3. HEALTH EFFECTS
8.7 mg/L and tissue:serum strontium concentration ra tios (based on the latter mean serum concentration) were as follows: liver, 0.7; heart, 1.2; muscle, 1.1; adrenal, 1.3; brain, 1.2; and bone, 1,300 (Skoryna 1981b). Strontium:calcium ratios in these tissues were approximately 0.05–0.1. Tissue:plasma strontium concentration ratios in rats 1–5 hours after they received an intraperitoneal injection of strontium revealed ratios <1 in the fat, spleen, liver, ovary, testis, skeletal muscle, and heart; and values of 1.2–1.7 in the lung, small intestine, salivary gland, kidney, and skin (Brues et al. 1969). Tissue:plasma concentration ratios of seminal vesicles in mice increased to valu es exceeding 2 several days after an intraperitoneal dose of strontium (Brues et al. 1967).

Information on the subcellular location of strontium in so ft tissues is also extremely limited. In rats that were exposed to 1.9 mg strontium/L (as SrCl 2 ) in drinking water for 3 months, the strontium concentrations (per mg protein) in the mitochondrial, lysosomal, and microsomal fractions of liver were approximately 5 times that of cytosol (Skoryna 1981b) . A major fraction of the strontium in tissues, possibly as much as 50–80% appears to be bound to protein (Kshirsagar 1977).
The partitioning of strontium in blood has not been extensively explored. The concentrations of strontium in the erythrocyte and plasma fractions of human blood obtained from blood banks were 7.2 μg/L in the erythrocyte fraction and 44 μg/L in the plasma fraction, suggesting that most of the strontium in blood resides in the plasma (Olehy et al. 1966). The strontium concentration in serum from 100 human subjects (health status not reported) was 53 μg/L, similar to the value reported for blood bank serum (Skoryna 1981b). Strontium binds to proteins in human serum; however, the specific proteins to which strontium binds have not been characterized . Alda and Escanero (1985) found that 45% of the strontium incubated with human serum at a concentrati on of 10 mg/L was ultrafilterable. Harrison et al. (1955) reported a value of 60% for the ultrafilterable fraction of plasma at a plasma concentration of 3.5 mg/L in two subjects who received an intravenous dose of 20 or 100 mg strontium chlorides. Note that this concentration is 300–1,000 times that reported for serum concentrations in subjects that were not receiving strontium supplements (Olehy et al. 1966; S koryna 1981b); at lower concentrations, a larger fraction of the serum strontium may be bound, as bi nding appears to be saturable (Alda and Escanero 1985; Berg et al. 1973). Values of 40–60% bound to pr otein have been reported for guinea pig and rabbit plasma or serum, respectively (Lloyd 1968; Twardock et al. 1971).

Strontium in the maternal skeleton can be transferred to the fetus during pregnancy. Studies of residents of the Techa River who were exposed to strontium as result of releases from a plutonium production plant provide evidence for fetal transfer of strontium (Tolstykh et al. 1998, 2001). The fetal:maternal transferSTRONTIUM 128 3. HEALTH EFFECTS
coefficient—the ratio of 90 Sr concentrations in the fetal and mate rnal skeletons (expressed in becquerels per gram of calcium)—was determined for six subject s who were exposed prior to pregnancy and their seven stillborn infants (Tolstykh et al. 1998). The tran sfer coefficients varied from 0.012 to 0.24, with the higher values associated with maternal exposures that occurred during adulthood and lower values associated with maternal exposures during childhood or adolescence. The difference was not related to the maternal strontium burden at pregnancy and may re flect a lower availability of strontium deposited in cortical bone during periods of active bone growth.
Studies in animals provide additional evidence for transf er of strontium through the placenta to the fetus. The fetus begins to accumulate strontium as the fetal sk eleton develops. In mice, ossification of the fetal skeleton begins on approximately the 14 th day of gestation, at which point, the fetal strontium burden begins to increase (Olsen and Jonsen 1979). In pregna nt mice that received an injection of strontium at different stages of pregnancy, fetal strontium burden was 4.5% of the maternal dose administered on the 18 th day of pregnancy compared to 0.7% of the maternal dose administered on the 14 th day of pregnancy (Rönnbäck 1986). Thus, fetal transfer was highest when the maternal dose o ccurred at the time of greatest skeletal growth. A similar observation has been made in rats; uptake of strontium by the fetus is highest (1–2% of an injected maternal dose) if the maternal dose is given on or after the 16 th day of gestation when ossification of the fetal skeleton begins (Hartsook and Hershberger 1973; Wykoff 1971). The distribution of strontium in the fetus at the end of gestation is similar to that of the mother with most of the strontium burden in the skeleton. In mice, the skeletal (long bones):soft tissue concentration ratio was approximately 40 in both the fetuses and dams (Jacobsen et al. 1978).
Strontium enters mammary milk in humans and can be transferred to newborns during breast feeding (Harrison et al. 1965). The concentration of strontiu m in breast milk of 12 healthy women was estimated to be 74 μg/L (range, 39–93) and the Sr:Ca concentrat ion ratio was 0.24 μg strontium/mg Ca (Harrison et al. 1965). In a study of the transport of trace elem ents, the concentration of strontium in colostrum samples collected from 29 healthy women during th e first 3 days after delivery was found to be comparable to that in serum from venous blood samp les taken 20 minutes before delivery (Rossipal et al. 2000). In contrast, the concentration of calcium in colostrum was significantly increased over the level in maternal serum, which was indicative of active trans port. The authors concluded that the transfer of strontium was based primarily on a concentration gradient mode of action. Numerous studies in animals provide additional evidence for transfer of strontiu m from breast milk to newborns during lactation (Hopkins 1967; Jacobsen et al. 1978; Kostial et al. 1969b; Rönnbäck et al. 1968). In lactating rats that received an oral exposure to tracer concentrations 85 Sr in drinking water during the 14 th through 16 th daysSTRONTIUM 129 3. HEALTH EFFECTS of lactation, approximately 5% of the ingested dose was recovered in the nursing pups 24 hours after the end of the 2-day exposure (Kostial et al. 1969b). In a study in which lactating mice received an intraperitoneal injection of radioactive strontium, strontium levels of the nursing pups was approximately 20% of that of the dams (Rönnbäck et al. 1968). These results are consistent with the oral exposure study (Kostial et al. 1969b), if one assumes that approximately 25% of the oral dose was absorbed by the dam. The tissue distribution of strontium in lactating mice a nd their offspring was found to be similar after an intraperitoneal dose to the dams during lactation; concentrations in bone were approximately 1,000 times higher than liver and kidney (Jacobsen et al. 1978). The strontium concentration in calvaria of the lactating pups, after 5 days of lactation, was appr oximately 3 times that of the dams, whereas the concentration in long bones of pups and dams were si milar (Jacobsen et al. 1978). The difference in the bone concentrations in the dams and pups may reflect the relatively higher rate of bone formation in the pups and associated incorporation of strontium into the new bone.

3.5.2.3 Dermal Exposure
In volunteers who were exposed to dermally applied 85 SrCl 2 in the left forearm, 85 Sr was detected by external counting of the patella and right forear m 3 and 6 hours after the exposure was initiated, suggesting that the absorbed strontium had been take n up by bone (Ilyin et al. 1975). Although no other studies were located regarding the distribution of de rmally absorbed strontium, it is likely that the distribution would be similar to that absorbed from the or al route, with the most of the body burden in the skeleton (see Section 3.5.2.2).

3.5.3 Metabolism
The metabolism of strontium consists of binding interac tions with proteins and, based on its similarity to calcium, probably complex formation with various inor ganic anions such as carbonate and phosphate, and carboxylic acids such as citrate and lactate (Alda a nd Escanero 1985; Inoue et al. 1988; Kshirsagar 1977; Lloyd 1968; Twardock et al. 1971). These types of in teractions would be expected for all routes of exposure. These types of interactions would be expected for all routes of exposure including the following:STRONTIUM 130 3. HEALTH EFFECTS
3.5.3.1 Inhalation Exposure
3.5.3.2 Oral Exposure
3.5.3.3 Dermal Exposure

3.5.4 Elimination and Excretion

3.5.4.1 Inhalation Exposure
Whole body elimination times have been measured in dogs and rats that received inhalation exposures to SrCl 2 . In dogs that were exposed to aerosols of 85 SrCl 2 (AMAD 1.4–2.7 μm, GSD 2.0), elimination halftimes were 0.6 (59%), 9 (12%), and 300 days (29% ) (Fission Product Inhalation Project 1967a). The rapid early phase of elimination reflects the mech anical clearance of strontium deposited in the tracheobronchial region of the respiratory tract and transf er to the gastrointestinal tract and feces, whereas the slower elimination component reflects the elim ination from the skeleton. A similar pattern of elimination has been observed in rats. In ra ts that were exposed to tracer levels of 85 Sr or a mixture of
85 Sr and 90 Sr aerosols (AMAD 1.8–2.8), the long-term whol e-body elimination half-time, measured 5– 230 days after exposure, was 330 days (F ission Product Inhalation Project 1967b).

Strontium that is absorbed after an initial deposition in the respiratory tract is excreted in feces and urine. Evidence for this comes from accidental exposures to radioactive strontium. In one case, a worker accidentally inspired an unknown quantity of 90 SrCl 2 (physical form unknown) and, over the subsequent 800 days, the urinary:fecal excretion ratio was 3:1 (Petkau and Pleskach 1972). The urinary:fecal excretion ratio of 3 is consistent with observations of long-term urinar y:fecal excretion ratios observed in people who ingested radioactive strontium or short- term ratios in people who received an intravenous dose of radioactive strontium (see Section 3.5.4. 2). In a second case, a worker was exposed to 90 SrCO 3 with deposition within the nasal tract as well as the ha nds, face, and hair and the urinary:fecal excretion ratio over the first 24 days was 0.71 (Rundo and Williams 1961). The lower ratio in this case probably reflects the fecal contribution of strontium that was mechanically cleared from the respiratory tract over the shorter observation period (24 days compared to 8 00 days). Similar observations have been made in animals. In dogs that received a 2–22-minute nose-only exposure to aerosols of 85 SrCl 2 (AMAD 1.4–2.7 μm, GSD 2.0), an initially large fecal comp onent of excretion was followed by urinary:fecal excretion ratios of 1.0–1.4 (Fission Product Inhala tion Project 1967a). An increase over time in theSTRONTIUM 131 3. HEALTH EFFECTS urinary:fecal excretion ratios from values <1 to 2–4 has also been observed after intratracheal instillation of SrCl 2 in rats (Fission Product Inhalation Project 1967b; Namenyi et al. 1986).

3.5.4.2 Oral Exposure
The long-term (decades) elimination of strontium ha s been studied in people who were exposed to strontium in the Techa River area of Russia after fission products from a plutonium production process were released in the area. Whole-body elimination half-times were estimated in a study population of 361 males and 356 females to be 28 years in males and 16 years in females (Tolstykh et al. 1997). Most of the difference in the elimination rate estimated for males and female s resulted from a pronounced increase in the elimination rate in females after ag e 50 years. The increase most likely reflects the increase in bone resorption that tends to occur in females after menopause. Müller et al. (1966) estimated a similar value, 25 years, for the long-term elimination half-time of strontium in 56 radium dial painters. In two dial painters, long-term elimination half-tim es were estimated to be 9 years (Wenger and Soucas 1975). Estimates of the long-term elimination half-tim es of strontium reflect primarily the storage and release of strontium in bone. Over shorter time periods after exposure, faster elimination rates are observed that reflect soft-tissue elimination as well as elimination from a more rapidly exchangeable pool of strontium in bone. When whole-body elimination of a tracer dose of 85 Sr was measured for periods of 42–108 days in nine subjects, the mean elimination half-time was 91 days (±32, SD) (Likhtarev et al. 1975). In three healthy subjects that received a single oral dose of SrCl 2 , the estimated average wholebody elimination half-times, estimated over 13 days, were 2 (30%) and 59 days (70%) (Uchiyama et al. 1973). Similar short-term rates of elimination have been observed within days to a few weeks after an intravenous injection of SrCl 2 (MacDonald et al. 1965; Newton et al. 1990).

Strontium that has been absorbed fro m the gastrointestinal tract is excreted primarily in urine and feces. In two dial painters, rates of urinary and fecal ex cretion of radium approximately 10 years after the exposure were approximately 0.03 and 0.01% of the body burden per 24 hours, respectively (Wenger and Soucas 1975). The urine:fecal excretion ratio of 3 th at was observed in the radium dial workers is consistent with ratios of 2–6 observed several days to weeks after subjects received an intravenous injection of SrCl 2 (Bishop et al. 1960; Blake et al. 1989a, 1989b; Likhtarev et al. 1975; Newton et al. 1990; Samachson 1966; Snyder et al. 1964; Uchiyama et al. 1973). Thus, urine appears to be the major route of excretion of absorbed strontium. The ob servation of fecal excretion of radioactive strontium weeks to decades after an oral exposure or over s horter time periods after an intravenous exposure suggests the existence of a mechanism for transfer of ab sorbed strontium into gast rointestinal tract, eitherSTRONTIUM 132 3. HEALTH EFFECTS from the bile or directly from the plasma. Evidence fo r direct secretion of strontium from the plasma into the intestine is provided by studies in animals (see Section 3.5.1). The available information does not address the extent to which biliary excretion may al so contribute to fecal excretion of strontium.
As discussed in Section 3.5.2.2, absorbed strontium is eliminated in breast milk during lactation. The concentration of strontium in breast milk of 12 h ealthy women was estimated to be 74 μg/L (range, 39– 93) and the Sr:Ca concentration ratio was 0.24 μg strontium/mg Ca (Harrison et al. 1965).

Strontium has been detected in human saliva and semina l fluid. In healthy subjects who received a single intravenous injection of SrCl 2 , the saliva:plasma concentration ratio was 0.9 and the semen:plasma ratio was 0.6 (Harrison et al. 1967a).

3.5.4.3 Dermal Exposure
In volunteers who were exposed to dermally applied 85 SrCl 2 in the left forearm, 85 Sr was excreted in urine (fecal excretion was not measured in this study) (Ilyin et al. 1975). Although no other studies were located regarding the excretion of dermally absorbed strontium, it is likely that the excretion would be similar to that absorbed from the or al route, with urinary excretion being approximately 2–3 times greater than fecal excretion (see Section 3.5.4.2).

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 ar e also called biologically based tissue dosimetry models. PBPK models are increasingly used in risk a ssessments, 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 speci es (Clewell and Andersen 1985). Physiologically based pharmacodynamic (PBPD) models use mathematical descriptions of the dose-response function to quantitatively describe the relationship between target tissue dose and toxic end points.

PBPK/PD models refine our unde rstanding of complex quantitativ e dose behaviors by helping to delineate and characterize the relationships between: (1) the external/exposure concentration and targetSTRONTIUM 133 3. HEALTH EFFECTS 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 ar e 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 subpopul ations within a species. The biological basis of PBPK models results in more meaningful extrapolati ons than those generated with the more conventional use of uncertainty factors.

The PBPK model for a chemical substance is deve loped 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 deve loped for a number of toxicologically important chemical substances, bot h volatile and nonvolatile (Krishnan and Andersen 1994; Leung 1993). PBPK models for a particular subs tance require estimates of the chemical substancespecific physicochemical parameters, and species-specif ic 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. Computer s 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 impor tance, and model validation is essential to the use of PBPK models in risk assessment.
PBPK models improve the pharmacoki netic extrapolations used in ri sk assessments that identify the maximal (i.e., the safe) levels for human exposure to chemical substances (Andersen and Krishnan 1994). Similar models have been devel oped for radionuclides. These PBPK models provide a scientifically sound means to predict the target tissue dose of chem icals in humans who are exposed to environmental levels (for example, levels that might occur at hazar dous waste sites) based on the results of studies where doses were higher or were administered in differe nt species. Figure 3-4 shows a conceptualized representation of a PBPK model. Figures 3-5 through 3-8 show models for ra dionuclides in general or specifically for strontium.

### Lungs

Liver

Fat

S low ly perfused

tissues Richly perfused

tissues

K idney

Skin V E N O U S

B L O O D A R T E R I A L

B L O O D V max 

### K m 

### Ingestion Inhaled chem ical E xhaled chem ical

GI Tract

Feces

Urine

C hem icals in air contacting skin Source: adapted from Krishnan et al. 1994 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 liv er, and excreted in the urine or by exhalation. STRONTIUM 134 3. HEALTH EFFECTS 

### Figure 3-4. Conceptual Represen tation of a Physiologically Based Pharmacokinetic (PBPK) Model for a

Hypothetical Chemical SubstanceSTRONTIUM 135 3. HEALTH EFFECTS Human Respiratory Tract Model for Radiological Protection (ICRP 1994a).

Deposition. The ICRP (1994a) has developed a deposition m odel for behavior of aerosols and vapors in the respiratory tract. It was developed to estimate th e fractions of radioactivity in breathing air that are deposited in each anatomical region of the respiratory tract. ICRP (1994a) provides inhalation dose coefficients that can be used to estimate the co mmitted equivalent and effective doses to organs and tissues throughout the body based on a unit intake of ra dioactive 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, which can be adjusted for various segments of the population (e.g., sex, age, level of physical exertion). This model also allows one to evaluate the bounds of uncertainty in deposition estimates. Uncertainties arise from natural biological variability among individuals and the need to interpret some experimental evidence that remains inconclusive. It is applicable to particulate aerosols containing strontium, 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 3-5). The model was developed with the following 5 compartments: (1) the anterior nasal passages (ET 1 ); (2) all other extrathoracic airways (ET 2 ) (posterior nasal passages, the nasoand oropharynx, and the larynx); (3) the bronchi (BB) ; (4) the bronchioles (bb); and (5) the alveolar interstitium (AI). Particles deposited in each of the regions may be removed from each region and redistributed either upward into the respiratory tree or to the lymphatic system and blood by different particle removal mechanisms.
For extrathoracic deposition of particles, the model us es experimental data, wher e deposition is related to particle size and airflow parameters, and scales depos ition for women and children from adult male data. Similarly, to the extrathoracic region, experimental data served as the basis for lung (bronchi, bronchioles, and alveoli) aerosol transport and deposition. A theo retical model of gas trans port and particle deposition was used to interpret data and to predict deposition for compartments and subpopulations other than adult males. Table 3-8 provides reference respiratory values for the general Ca ucasian population under several levels of activity.
Deposition of inhaled gases and va pors is modeled as a partitioning process which depends on the physiological parameters noted above as well as th e solubility and reactivity of compound in theSequestered in Tiss ue S urface Tr ansp or t Sequestered in Tiss S rface r sp rt
AnteriorAnterior ET 1 14 ET 1 14 1 Nasal 

### Extrathoracic Environment 16 Environment 16

Naso-oro­Naso-oropharynx Larynx 0.001 ET SEQ 12 LN ET 13

Bronchi

bb 2 BB 2

bb SEQ LN TH 0.03 2 0.01

0.01 8 BB SEQ 9

5 6

10 Al 3 0.0001 BB 1

bb 1 7

4

Al 1 Al 2 0.001 0.02

1 2 3 GI Tract ET 2 11 15 100

Bronchioles

Alveolar Interstitium 0.03 10

0.00002 0.001 ET SEQ 12 LN ET 13

Bronchi

bb 2 BB 2

bb SEQ LN TH 0.03 2 0.01

0.01 8 BB SEQ 9

5 6

10 Al 3 0.0001 BB 1

bb 1 7

4

Al 1 Al 2 0.001 0.02

1 2 3 GI Tract ET 2 11 15 100

Bronchioles

Alveolar Interstitium 0.03 10

0.00002



### Thor acichor

*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 3-9. Source: ICRP 1994a STRONTIUM 136 3. HEALTH EFFECTS 

### Figure 3-5. Compartment Model to Represent Particle Deposition and Time-Dependent Particle Trans port in the Respiratory Tract*STRONTIUM 137 3. HEALTH EFFECTS


### Table 3-8. Reference R espiratory Values for a G eneral Caucasian Population at Different Levels of Activity Activity: Resting (sleeping) Sitting aw ake Light exercise Heavy exercise Maximal workload: 8% 12% 32% 64% Breathing V T B f R V T B f R V T B f R V T B f R parameters: (L) (m 3 h -1 ) (min -1 ) (L) (m 3 h -1 ) (min -1 ) (L) (m 3 h -1 ) (min -1 ) (L) (m 3 h -1 ) (min -1 ) Age Sex 3 months 0.04 0.09 38 N/A N/A N/A 0.07 0.19 48 N/A N/A N/A 1 year 0.07 0.15 34 0.1 0.22 36 0.13 0.35 46 N/A N/A N/A 5 years 0.17 0.24 23 0.21 0.32 25 0.24 0.57 39 N/A N/A N/A 10 years Male: 0.841 2.22 44 Both: 0.667 1.84 46 Female: 0.3 0.31 17 0.33 0.38 19 0.58 1.12 32 15 years Male: 0.500 0.42 14 0.533 0.48 15 1.0 1.38 23 1.352 2.92 36 Female: 0.417 0.35 14 0.417 0.40 16 0.903 1.30 24 1.127 2.57 38 Adult Male: 0.625 0.45 12 0.750 0.54 12 1.25 1.5 20 1.923 3.0 26 Female: 0.444 0.32 12 0.464 0.39 14 0.992 1.25 21 1.364 2.7 33

a See Annex B (ICRP 1994a) for data from whic h these reference values were derived. B = ventilation rate; f R = respiration frequency; h = hour; min = minute; N/A = not applicable; V T = tidal volumeSTRONTIUM 138 3. HEALTH EFFECTS respiratory tract (Figure 3-6). The ICRP (1994a) 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 H 2 , He). These compounds do not significantly interact with the respiratory tract tissues and essentially all of the compound that is inhaled is exha led. 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 ga ses 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.

• 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 Tract. This portion of the model identifies the principal clearance pathways within the respiratory tract. Th e model was developed to predict the retention of various radioactive materials. Figure 3-7 presents the compartmental model and is linked to the deposition model (Figure 3-5) and to reference valu es presented in Table 3-9. Table 3-9 provides clearance rates and deposition fractions for each compar tment for insoluble particles. The table provides rates of insoluble particle transport for each of th e compartments, expressed as a fraction per day and also half-time. ICRP (1994a) 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 r oute. 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., BB 1 , BB 2 , BB seq ), the ICRP model overcomes problems associated with time-dependent functions. Each comp artment clears to other compartments by constant rates for each pathway.Airway Uptake Gas or Vapor Lumen
Airway

Fluid

Tissue

Blood Blood S b Reaction Product

Reaction Product Bound

Product Material Gas/Vapor

Gas/Vapor

Reaction Gas/Vapor

From ICRP 1994a Convection Diffusion STRONTIUM 139 3. HEALTH EFFECTS 

### Figure 3-6. Reaction of Gases or Vapors at Vari ous Levels of the Gas-Blood Interface

### Figure 3-7. The Human Respiratory Tract Model: Absorption into Blood

Particulate Material

Bound Material Dissociated Material Particulate Material

Bound Material Dissociated Material Dissolution

Uptake

Blood

Source: ICRP 1994a STRONTIUM 140 3. HEALTH EFFECTSSTRONTIUM 141 3. HEALTH EFFECTS


### Table 3-9. Reference Values of Para meters for the Compartment Model to Represent Time-dependent Pa rticle Transport from the Human Respiratory Tract Part A Clearance rates for insoluble particles Pathway From To Rate (d -1 ) Half-time a

m 1,4 AI 1 bb 1 0.02 35 days

m 2,4 AI 2 bb 1 0.001 700 days

m 3,4 AI 3 bb 1 0.0001 7,000 days

m 3,10 AI 3 LN TH 0.00002 No data

m 4,7 bb 1 BB 1 2 8 hours

m 5,7 bb 2 BB 1 0.03 23 days

m 6,10 bb seq LN TH 0.01 70 days

m 7,11 BB 1 ET 2 10 100 minutes

m 8,11 BB 2 ET 2 0.03 23 days

m 9,10 BB seq LN TH 0.01 70 days

m 11,15 ET 2 GI tract 100 10 minutes

m 12,13 ET seq LN ET 0.001 700 days

m 14,16 ET 1 Environment 1 17 hoursSTRONTIUM 142 3. HEALTH EFFECTS



### Table 3-9. Reference Values of Para meters for the Compartment Model to Represent Time-dependent Pa rticle Transport from the Human Respiratory Tract Part B Partition of deposit in each region between compartments b Fraction of deposit in region Region or deposition site Compartment assigned to compartment c ET 2 ET 2 0.9995 ET seq 0.0005 BB BB 1 0.993- f s BB 2 f s BB seq 0.007 bb bb 1 0.993- f s bb 2 f s bb seq 0.007 AI AI 1 0.3 AI 2 0.6 AI 3 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 Al 3 to LN TH , since this rate was chosen to direct the required amount of material to the lymph nodes. The clearance half-time of compartment Al 3 is determined by the sum of the clearance rates from it. b See paragraph 181, Chapter 5 (ICRP 1994a) for default values used for relating f s to d ae . c It is assumed that the slow-cleared fraction f s is size-dependent. For modeling purposes f s is taken to be: 

### f

s 

### = 0 5

. for d a e 

### ≤

. ρ χμ 25 / m and

0 63 d /

− .) .( ρ χ 25 ae 

### f

s 

### = 0 5

. e for d ae 

### >
. ρ χμ 25 / m AI = alveolar-interstitial region; BB = br onchial region; bb = bronchiolar region; BB seq = compartment representing prolonged retention in airway walls of small fracti on of particles deposited in the bronchial region; bb seq = compartment representing prolonged re tention in airway walls of small fraction of particles deposited in the bronchiolar region; d = day(s); ET = extrathoracic region; ET seq = compartment representin g prolonged retention in airway tissue of small fraction of particles deposited in the nasal passages; GI = gastrointestinal; LN ET = lymphatics and lymph nodes that drain the extrathoracic region; LN TH = lymphatics and lymph nodes that drain the thoracic region Source: ICRP 1994aSTRONTIUM 143 3. HEALTH EFFECTS Particle transport from all regions is toward both the lymph nodes and the pharynx, and a majority of deposited particles end up being swallowed. In the front part of the nasal passages (ET 1 ), nose blowing, sneezing, and wiping remove most of the deposited particl es. Particles remain here for about a day. For particles with AMADs a few micrometers or greater, the ET 1 compartment is probably the largest deposition site. A majority of particles deposited at th e back of the nasal passages and in the larynx (ET 2 ) are removed quickly by the fluids that cover the airway s. 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 mo st particles deposited here toward the pharynx, a fraction of these particles are cleared more slowly. Evidence for this is found in human studies. For humans, retention of particles deposited in the lungs (BB and bb) is apparently biphasic. The “slow” action of the cilia may remove as many as half of the bronchi- and bronchiole-deposited particles. In human bronchi and bronchiole regions, mucus moves more slowly the closer it is to the alveoli. For the faster compartment, it has been estimated that it ta kes 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 approxima tely equal fractions deposited between BB 2 and bb 2, and both with clearance half-times estimated at 20 days. Particle size is a primary determinant of the fraction deposited in this slow thoracic compartment. A sm all fraction of particles deposited in the BB and bb regions is retained in the airway wall for even longer periods (BB seq and bb seq ).
If particles reach and become deposited in the alveo li, they tend to stay imbedded in the fluid on the alveolar surface or move into the lymph nodes. Th e one mechanism by which particles are physically resuspended and removed from the AI region is coug hing. 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 regi on has been measured in human subjects. 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, excep t in the anterior nasal passages (ET 1 ), where no absorption occurs. Absorption is essentially a 2-stage process, as shown in Figure 3-7. First, there is a dissociationSTRONTIUM 144 3. HEALTH EFFECTS (dissolution) of particles; then, the dissolved molecul es 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 (f ast), M (medium), S (slow), and V (instantaneous):

C 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 ET 2 . Thus, for nose breathing, there is rapid absorption of approximately 25% of the deposit in ET and 50% for mouth breathing.

C 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 ET 2 . Thus, there is rapid absorption of approximately 2.5% of the deposit in ET for nose breathing, and 5% for mouth breathing.

C 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.

C For Type V, complete absorption (100%) is considered to occur instantaneously. ICRP (1995) considers the experimental data on stront ium carbonate, and chloride, and sulfate to support classification of these compounds as Type F. Data on strontium particulates released from irradiated fuel support their classification as either Type F or M. Data on strontium in fused aluminosilicate particles support a classification as Type S. ICRP (1995) recommends assigning all strontium aerosols to Type M in the absence of specific information s upporting an alternative classification.
ICRP (1993) Strontium Biokinetics Model Description of the model. ICRP (1993) developed a compartmental model of the kinetics of alkaline earth elements, including strontium, in humans that is applicable to infants, children, adolescents, and adults. The model is based on a nearly identical model developed by Leggett (1992). The fraction of ingested strontium that is absorbed (uptake to blo od) is assumed to vary with age and have values of 0.6 in infants up to 12 months of age, 0.4 from 12 months of age through 15 years, and 0.3 from age 15 years through adulthood. Absorbed strontium that enters the blood plasma is assumed to distribute to the skeleton, liver, and other tissues (Figure 3-8). Excretion pathways included in the model are plasma to urine, plasma to feces, and liver to feces. Tran sfer rate coefficients between compartments are agespecific and, depending on the specific coefficient, values can change at ages 3 months, 1 year, 5 years, 10 years, 15 years, and adult (>15 years). The model assumes that 99% of the strontium that enters the

### Figure 3-8. ICRP (1993) M odel of Stront ium Biokinetics

Feces Intermed Turnover

Cortical Surface

Trabecular

Surface 

### R B C

Other Kidney Tissue Urinary

Path KIDNEY Liver 1

Liver 2

GI Tract Contents Rapid Turnover Slow Turnover MASSIVE

SOFT TISSUES

Urinary Bladder Contents Cortical Volume
Nonexch Exch

Trabecular Volume
Nonexch Exch 

### P L A S M A

P L A S M A SKELETON

Urine STRONTIUM 145 3. HEALTH EFFECTSSTRONTIUM 146 3. HEALTH EFFECTS body and is not excreted is ultimately transferred to the skeleton and 1% is in soft tissues. Skeletal deposition is assumed to distribute initially to the bone surface of either cortical or trabecular bone, from which it can exchange relatively rapidly with calcium in plasma or more slowly with calcium in the bone volume. Two pools are assumed to exist within the bone volume, an exchangeable pool that communicates with surface bone, and a nonexchangeable pool from which strontium can be returned to plasma as a result of bone resorption. Approximately 55% of the transfer from plasma to bone in adults is to the trabecular bone surface and 45% to the cortical bone surface.

Validation of the model. The extent to which the ICRP model h as been validated is not described in ICRP (1993).

Risk assessment. The model has been used to establish radiation dose equivalents (Sv/Bq) of ingested 89 Sr and 90 Sr for ages 3 months to 70 years (ICRP 1993). The model has also been applied by the ICRP to calculate limits on inhalation for 89 Sr and 90 Sr (ICRP 1995) and limits on inhalation or ingestion for 80 Sr, 81 Sr, 82 Sr, 83 Sr, 85 Sr, 85m Sr, 87m Sr, 91 Sr, and 92 Sr (ICRP 1994b). It was used in the U.S. Federal Guidance Report No. 13 (EPA 2000e) to calculate i nhalation risk coefficients and ingestion risk coefficients (separately for food and water) for the following radionuclides: 80 Sr, 81 Sr, 82 Sr, 83 Sr, 85 Sr,
85m Sr, 87m Sr, 89 Sr, 90 Sr, 91 Sr, and 92 Sr.
Target tissues. The model is designed to calculate 89 Sr and 90 Sr intake limits, based on radiation dose to all major organs, including the bone surfaces, bone marrow, and liver, to which the highest doses would be expected.
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 intended for applica tion to strontium reaching blood by absorption from lungs, gastrointestinal tract, or wound, or by injection.STRONTIUM 147 3. HEALTH EFFECTS
3.6 MECHANISMS OF ACTION
3.6.1 Pharmacokinetic Mechanisms
Absorption. Airborne particulate aerosols of strontium can be deposited in the respiratory tract when the aerosols are inhaled. Amounts and patterns of de position of particulates in the respiratory tract are affected by the size of the inhaled particles, age-re lated factors that determine breathing patterns (e.g., nose breathing vs mouth breathing), airway geometry, and airstream velocity within the respiratory tract (Gehr 1994; James et al. 1994; Roy et al. 1994). In general, large particles (>2.5 μm) deposit in the nasopharyngeal tract where high airstream velocities and airway geometry facilitate inertial impaction (Chan and Lippman 1980; James et al. 1994). In the tracheobronchial and alveolar regions, where airstream velocities are lower, processes such as sedimentation and interception become important for deposition of smaller particles (<2. 4 μm). Breathing patterns, airflow velocity, and airway geometry change with age, giving rise to age-related diffe rences in particle deposition (James 1978; James et al. 1994; Phalen et al. 1985). Deposition in the various re gions of the respiratory tract in children may be higher or lower than in adults depending on particle size; for submicron particles, fractional deposition in 2-year-old children has been estimated to be 1.5 tim es greater than in adults (Xu and Yu 1986). Absorption of insoluble strontium is influenced by particle size and solubility as well as the pattern of regional deposition within the respiratory tract. La rger particles (>2.5 μm) that are deposited in the ciliated airways (nasopharyngeal and tracheobronchial regions) can be transferred by mucociliary transport into the esophagus and swallowed. Particles deposited in the alveolar region can be absorbed after extracellular dissolution or ingestion by phagoc ytic cells. Strontium-bearing pulmonary alveolar macrophages (PAMs) can migrate either to the airway s where mucocilliary transport to the esophagus can occur or to tracheobronchial lymph n odes. The relative contributions of these two pathways to strontium absorption have not been quantified.
The exact site of absorption of str ontium in the gastrointestinal tract is not known; however, studies in hamsters suggest the possibility of absorption in both the stomach and small intestine. In hamsters that received a gavage tracer dose of 85 SrCl 2 , 37% was absorbed, whereas 20% was absorbed when the dose was administered to hamsters that had their pylo ric sphincter ligated (Cuddihy and Ozog 1973). In isolated, everted segments of small intestine of the ra t, transfer from the mucosa l (lumen) to the serosal (blood) side of the duodenum, jejunum, and ileum was observed. The serosal:mucosal strontium concentrations were approximately 0.2–0.4, whereas the ratio for calci um in preparations of duodenum was 1.98 (Stantic and Gruden 1974). Ratios >1 woul d be indicative of an active transport process; therefore, this study did not detect an active component of strontium transfer across the small intestine.STRONTIUM 148 3. HEALTH EFFECTS Measurements of the rate of uptake of strontium into slices of rat small intestine when incubated with increasing concentrations of strontium suggested the existence of a saturable uptake mechanism in the intestinal epithelium (Papworth and Patrick 1970). The fractional absorption of a gavage dose of strontium appears to be a relatively constant ratio to that of calcium. In rats, the strontium:calcium absorption ratio was 0.75 over a fairly wide range of absorbed fractions of calcium (Marcus and Wasserman 1965). This suggests that strontium and calcium may be absorbed by similar mechanisms. Strontium has been shown to be a substrate for a Ca 2+ -ATPase on the basolateral membrane of the renal proximal tubule in the rat, which is thought to play an important role in the tubule reabsorption of calcium (Sugihira et al. 1992).
Active vitamin D (calcitriol or 1,25(OH) 2 D 3 ) has an indirect, delayed effect on the gastrointestinal absorption of strontium or calcium by inducing the synthesis of calcium-binding proteins in both humans and animals (Bianchi et al. 1999). A calcitriol-inducible Ca 2+ -ATPase has been shown to be important in the absorption of calcium in the rat intestine, a nd may provide a common mechanism for absorption of calcium and strontium (Bronner et al. 1986). Ot her possible common mechanisms may involve binding of calcium and strontium to an intracellular cal cium-binding protein, calbindin-D, which is a 1,25(OH) 2 D 3 -inducible calcium binding protein that is thought to play an important role in calcium absorption (Gross and Kumar 1990). In a group of 18 66-year-old women who received calcitriol at a daily dose of 0.5 μ g of calcitriol for two years, the intestinal absorption of strontium was 13.7% compared to 10.4% for the untreated controls (Sairanen et al. 2000); the basal absorption percentages before treatment were 8.7 and 9.2%, respectively. Age-rela ted decreases in the gastrointestinal absorption of strontium in men (ages 20–79) were found to be positiv ely correlated with serum levels of insulin-like growth factor I (IGF-I) (Fatayerji et al. 2000). Th ese authors proposed that IGF-I increases strontium absorption by maintaining the structural integrity of the intestine and the sensitivity of the intestine to 1,25(OH) 2 D and increasing the synthesis of calcium-binding protein in that tissue. IGF-I also acts by stimulating the synthesis of 1,25(OH) 2 D in the kidney (Audi et al. 1999; Fatayerji et al. 2000).

Distribution. The close similarity in the distribution of strontium and calcium derives from the ability of strontium to interact with ligands that normally bind calcium (Skoryna 1981b). These include hydroxyapatite, the main component of mineralized bone (Harrison et al. 1959; Schoenberg 1963) and a variety of calcium binding and transport proteins th at are important in the physiological disposition of calcium in cells, including Ca 2+ -ATPases (Berman and King 1990; Mermier and Hasselbach 1976; Pfleger and Wolf 1975; Sugihira et al. 1992; Yu and Inesi 1995), Na + -Ca + -antiport (McCormack andSTRONTIUM 149 3. HEALTH EFFECTS Osbaldeston 1990; Niggli 1989; Richard et al. 1989), and Ca 2+ channels (Fukushi et al. 1995a, 1995b; Gregoire et al. 1993).

Metabolism. As noted in Section 3.5.3, the metabolism of strontium consists of binding interactions with proteins and probably comple x formation with various inorganic anions such as carbonate and phosphate, and carboxylic acids such as citrate and lactate.

Excretion. The renal clearance of strontium has been measured in human subjects who received an intravenous injection of a dose of SrCl 2 and is approximately 4–10 L/day and 2–3 times greater than renal calcium clearance (Blake et al. 1986, 1989a, 1989b; Harrison et al. 1955, 1966a; Newton et al. 1990; Samachson 1966). Based on these estimates, the renal cl earance of strontium is s ubstantially less than the product of the glomerular filtration rate in humans (approximately 180–200 L/day) and the estimated rate of filtration of strontium, assuming that approximately 50% of the strontium in plasma is ultrafilterable (Harrison et al. 1955). Thus, strontium appears to undergo net tubular reabsorption in the human kidney. The mechanism by which strontium is reabsorbed in the renal tubule has not been determined, although it is likely that it may share common transport m echanisms with calcium, possibly including the Na +

­ Ca 2+ -antiport, Ca 2+ -ATPase and membrane Ca 2+ channels, all of which are thought to play a role in the reabsorption of calcium (Friedman and Gesek 1995). Direct evidence for this comes from in vitro studies of basolateral membranes isolated form the rat rena l cortex (primarily proximal tubule). In this preparation, strontium has been shown to be a substrate for a Ca 2+ -ATPase, which transports calcium from the proximal tubular cells into the plasma (Sugihira et al. 1992).

The observation of fecal excretion of radioactive str ontium for weeks to decades after an oral exposure or over shorter time periods after an intravenous exposure suggests the exis tence of a mechanism for transfer of absorbed strontium into gastroin testinal tract, either from the bile or directly from the plasma. Evidence for direct secretion of strontium from the plasma into the intestine is provided by studies conducted with the in situ lumen-perfused rat intestine. When th e lumen of either the small or large intestine was perfused (below th e entrance of the bile duct) in situ , and radioactive strontium was injected intravenously, radioactive strontium was detected in the lumen, indicating that strontium was secreted from blood into the intestine (Palmer and Thompson 1961) . The amount of strontium secreted into the small intestine was approximately 4–8 times that in the large intestine; however, the strontium:calcium secretion ratio was approximately 1 in the small intestine and 1.3 in the large in testine. The mechanism by which strontium is secreted into the intestine has not been determin ed. Transfer of strontium from the serosal (blood) side of the intestinal epithelium to the mucosal (lumen) side of the epithelium has beenSTRONTIUM 150 3. HEALTH EFFECTS
demonstrated in in vitro preparations of isolated rat colon mucosa. Serosal-to-mucosal transfer was observed to be completely dependent on the transepithelial electrochemical potential for strontium, completely insensitive to calcium concentration of the serosal bathing medium, and unaffected by prior treatment of the rats with 1,2,-dihydroxyvitamin D 3, which stimulated calcium transport in the same preparation (Karbach and Rummel 1987). Based on these observations, transfer of strontium into the lumen of the colon in this preparation app eared to be explainable as a passive process.

3.6.2 Mechanisms of Toxicity
The fact that strontium is chemically similar to cal cium allows it to exchange for calcium in bone and other cellular compartments that are enriched in cal cium. Many enzymes that are calcium-dependent will function when strontium is substituted, but changes in kinetic parameters may occur. As discussed in Section 3.6.1, strontium can interact with secondary cell messenger systems and transporter systems that normally use calcium. Furthermore, as described in Section 3.2.4 (Neurological Effects), synaptic transmission may be variably affected by strontium. Consequently, at high concentrations, differences in the chemical characteristics between strontium a nd calcium may be the basis for neurotoxic and neuromuscular perturbations associated with strontium intoxication.
Effect of Metabolism on Toxicity. Variations in the rate of absorption of soluble strontium compounds will affect the severity of their effects following or al exposure. One report identified polymorphisms in three alleles for the vitamin D receptor that imparted a 40% difference in efficiency in intestinal strontium absorption in humans (Gennari et al. 1997). The si gnificance of this finding is unresolved, since other studies have found no link between vitamin D receptor genotypes and enteral absorption rates for calcium or strontium (Vezzoli et al. 2002; Wolf et al. 2000). Furthermore, no association was found between vitamin D receptor polymorphisms and bone mineral density when ot her parameters are taken into consideration (Poggi et al. 1999). Ho wever, daily administration of 0.5 μ g of activated vitamin D to 66-year-old women over 2 years increased both the ra te of strontium absorption and the bone mineral density at the femoral neck and the lumbar spine (Sairanen et al. 2000). The rate of strontium incorporation into bone may be influenced by other factors thought to affect bone mineralization, such as parathyroid hormone receptor, estrogen receptor 1, a nd others (Audi et al. 1999; Duncan et al. 1999). However, the effects of these factors on strontium utilization have not been established definitively. Genetic variants of the parathyroid hormone receptor 1 result in either increased or decreased bone mineralization (Duncan et al. 1999). There is a potential physiological link between the estrogen receptor and vitamin D in osteoblasts, although the relationshi p to bone mineralization has not been establishedSTRONTIUM 151 3. HEALTH EFFECTS (Audi et al. 1999); vitamin D regulates the expression of P450 aromatase, an enzyme expressed in osteoblasts that modulates the availability of estrogen to its receptor. The cytokine interleukin-6 is associated with osteoclast differentiation, and therefore, could potentially be invo lved with the removal of strontium from bone (Audi et al. 1999; Duncan et al. 1999). Persons with chronic kidney failure may be more susceptible to effects of excess strontium b ecause of a reduced ability to excrete strontium (Apostolidis et al. 1998; see Section 3.12); in this st udy, plasma levels of strontium were 60% higher in afflicted patients compared to controls. A study in ra ts demonstrated that protein deficiency, especially in combination with ethanol consumption, may increase strontium incorporation into bone while reducing fecal and urinary excretion of strontium (Gonzales-Reimers et al. 1999; see Section 3.12).
Differences in bone physiology suggest that adult rats may have a higher susceptibility to stable or radioactive strontium effects than adult humans. Unlike most mammals (including humans), the epiphyseal growth plate of the long bones of rats never entirely transforms into bone after sexual maturity, so that bone growth continues throughout life (although reduced after the age of 12 months) (Leininger and Riley 1990). Thus, incorporation of st rontium into the skeleton is likely to be relatively higher in adult rats compared to other mammals.

Stable Strontium. The toxicity of excess stable strontium is related to its interference in biological processes that normally involve calcium, mo st notably, skeletal development.
Calcium Absorption. In animals, excess strontium indirec tly suppresses the activation of vitamin D 3 in the kidney, which severely reduces the expression of calbindin D mRNA and the translation of calbindin D protein in the duodenum (Armbrecht et al. 1979, 1998; Omdahl and DeLuca 1972). As a result, duodenal absorption of calcium is reduced. The reported inverse correlation between the amount of strontium that is absorbed and the levels of pa rathyroid hormone (Vezzoli et al. 1998) suggest that changes in parathyroid hormone leve ls mediate this effect. While there are no data on strontium-binding to the calcium receptor of the parathyroid gland, it is likely that strontium binds in place of calcium, mimicking calcium and thereby suppressing parathyroi d hormone levels. A re duction in parathyroid hormone levels will decrease the level of 1- hydroxylase available to activate vitamin D 3 . Bone Toxicity. In addition to its effect on calcium absorption, excess absorbed strontium adversely affects bone development in several ways, leading to the development of rickets in young laboratory animals and possibly in children under special ci rcumstances (Özgür et al. 1996). Strontium binds directly to hydroxyapatite crystals, which may interfere with the normal crystalline structure of boneSTRONTIUM 152 3. HEALTH EFFECTS (Storey 1961). In addition, excess strontium may prevent the normal maturation of chondrocytes in the epiphyseal plates of long bones (Matsumoto 1976). Excess strontium apparently interferes with the mineralization of complexed acidic phospholipids that is thought to help initiate the formation of hydroxyapatite crystals in developing bone (Neufeldand Boskey 1994). As a result, affected bone contains an excess of complexed acidic phospholipid and a significantly lower ash weight. Insufficient mineralization reduces the strength of bones, so that the inability to resist compression from increasing body weight results in bone distortion (bowing).
Anaphylactic Response After Inhalation Exposure. There was one case of anaphylaxis reported in a paramedic who inhaled strontium-containing smoke in an enclosed space (Federman and Sachter 1997; see Section 3.2.1.2). Although other irritants in the sm oke may have contributed to the incident, there is supporting evidence that large concentrations of stable strontium can stimulate the release of histamine from mast cells (Alm and Bloom 1981a, 1981b; At kinson et al. 1979; Foreman 1977; Foreman and Mongar 1972a, 1972b; Foreman et al. 1977). Stable strontium stimulates degranulation in several cell types (see Section 3.2.5 Hematological Effects) and it has been suggested that it acts by mimicking the receptor-linked rise in calcium that is the usual trigger fo r such events (Best et al. 1981). It is conceivable that the conditions of the paramedic’s exposure were such to result in locally high concentrations of strontium in the respiratory tract, thereby eliciting histamine release and contraction of smooth muscle.

Radioactive Strontium. The adverse health effects of radioactive strontium are related to its sequestration in bone, the high energy of its beta emissions, and, in the case of 90 Sr, its long half-life and the radiation from the decay product, 90 Y, produced in the body after intake of 90 Sr. An extensive discussion of ionizing radiation and its health effects is found in the Appendix D of this document and in the Toxicological Profile for Ionizing Radiation (Agenc y for Toxic Substances and Disease Registry 1999). There is some evidence that body size or skeletal density may affect the outcome of exposures to radioactive strontium. It was suggested that two cows that survived large oral doses of 90 Sr owed their survival to their breed characteristics (Cragle et al. 1969). The massive skeletons of Holsteins have wide bone marrow cavities so that tissue in the center of the bone marrow is not within range of the 1 cm beta emissions from radiostrontium (and radioyttrium) bou nd to bone. Conversely, mice and rats are more vulnerable than large animals to radioactive stron tium because all bone marrow tissues are within striking range. This renders rats and mice less useful than larger mammals as models for human exposure to radioactive strontium. In addition, adult rats are less satisfactory models than adults of other species because of the persistence of the epiphyseal cartilaginous plate, which will result in the incorporation of larger amounts of radioactive strontium into bone.STRONTIUM 153 3. HEALTH EFFECTS

Bone Toxicity. Beta emissions from radiostrontium bound to bone resulted in various bone lesions (trabecular osteoporosis, sclerosis, osteolytic lesions ), particularly in animals that were exposed chronically (Book et al. 1982; Clarke et al. 1972; Mo meni et al. 1976). In young rats and rabbits exposed orally to 90 Sr, necrotic effects on the vasculature of developing bone secondarily disrupted the process of osteogenesis (Casarett et al. 1962; Downie et al. 1959). Disruption in the metaphyseal microvasculature disorganized the transformation of cartilage into bo ne, so that chondrocytes inappropriately resumed active proliferation.
Pancytopenia. The severe reduction in hematopoetic tissue r esults from irradiation of the bone marrow by radiostrontium incorporated into bone. At high ex posure levels, thrombocytopenia may lead to platelet loss severe enough to cause hemorrhaging and the resulti ng anemia will be exacerbated by destruction of erythropoietic tissue. Impaired immune function results from the genetic damage to lymphocytes.
Carcinogenicity. Radioactive strontium is a genotoxic carcinogen. Following exposure in vivo , cytogenetic analysis has revealed aneuploidy, chro mosomal breaks, gaps, rings, and exchanges (see Table 3-5), which are manifestations of unrepairable changes in DNA. It is generally understood that radiation-induced damage to genes that regulate cell growth is a major factor in the development of cancer in affected cells, and the observation of chro mosomal breaks in leukemic cells of miniature swine following chronic oral exposure to 90 SrCl 2 is consistent with this idea (Clarke et al. 1972; Howard 1970). However, the specific genes involved in radiostrontiu m-induced malignancies have not been identified. Because of strontium’s chemical properties, which determine its distribution in the body, exposure to sufficient radiostrontium results in an increased risk of malignancy for particular tissues. In dogs, acute inhalation of insoluble 90 Sr particles that lodged in the lungs resulted in chronic radiation exposure to the lungs, leading to pulmonary hemangiomas and carcinomas of pulmonary epithelia (Snipes et al. 1979). Other tissues were subsequently affected as the ra dioactive particles were cleared from the lungs. Following acute inhalation of soluble 90 SrCl 2 aerosols, some dogs developed carcinomas of nasal airway tissues, probably resulting from irradiation of these tissues from the 90 Sr bound to the underlying bone (Gillett et al. 1987b). Following oral or inhalation exposures, absorbed 90 Sr was distributed to bone, from which it irradiated the surrounding tissues and induced various kinds of osteosarcomas, as well as malignancies of hematopoietic tissues in bone marrow (see Section 3.3.2.7).
Induction of Delayed Fibrosis Following External Exposure. A single high-dose external exposure to beta radiation can elicit acute epidermal reactions, late connective tissue damage, and carcinogenesis inSTRONTIUM 154 3. HEALTH EFFECTS murine skin, as was demonstrated in experiments that used 90 Sr as a convenient beta source (Randall and Coggle 1996; see Section 3.3.3.7). A biochemical change that is associated with both acute and late effects is the enhanced expression of mRNA and pr otein for transforming growth factor beta 1 (TGF-beta l, Randall and Coggle 1995, 1996). Follow ing an acute exposure to beta radiation from a 90 Sr source that is sufficient to generate moist desquamation, CBA/ca mouse skin exhibited two separate peaks of TGF-beta l expression (Randall and Coggle 1996). The first, occurring within the first few weeks after exposure, coincided with a period of epithelial hyperp lasia that occurred during and after the phase of reepithelialization. TGF-beta l expression declined to a low at 3 months postexposure, but then rose to another peak at about 9 months. Expression was especia lly high in the fibrotic dermis, which was also the site of skin tumors that appeared at about 9 mont hs. TGF-beta l expression in tumors was elevated by 1.8 to 87 times the level in unirradiated control skin from the same animal. The implication of this study is that sustained high expression of transforming grow th factor-betal may drive the progressive fibrosis and, possibly, contribute to malignancy following radiation damage. Another study from this laboratory indicates that there may be genetic differences in th e control of TGF-beta l expression, and therefore, susceptibility to long-term effects of radia tion damage (Randall and Coggle 1995).

3.6.3 Animal-to-Human Extrapolations

The toxic effects of stable and radioactive strontium ha ve been similar in all species studied. However, as mentioned in Section 3.6.2, adult rats are not an optimal model for bone effects in adult humans because of the lack of a Haversian (bone remodeling) system in the rat and because of the persistence of the epiphyseal cartilaginous plate into adulthood (Lei ninger and Riley 1990). Because the epiphyseal cartilage persists, the long bones of rats continue to lengthen during adulthood, and therefore, the rates of incorporation of strontium will be proportionally higher . This will make adult rats more susceptible to adverse effects of both stable and radioactive strontiu m. This caveat does not apply to young rats, which are comparable to the young of other species. In general, rodents are not optimal models for radiostrontium effects because their small size ensur es that most of their tissues will be within the effective range of beta emissions from radiostrontium bound to bone. Larger laboratory animals, such as dogs or non-human primates, avoid the problems of both radiation scatter to adjacent tissues and closure of the epiphysis as they become adults.STRONTIUM 155 3. HEALTH EFFECTS
3.7 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS
Recently, attention has focused on th e 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 re mains 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 natu rally occurring estrogen, or other such endocrine effect[s]...”. To meet this manda te, EPA convened a panel called the Endocrine Disruptors Screening and 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 scientis ts agree that chemicals w ith 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-ac tive chemicals do not pose a significant health risk, particularly in view of the fact that hormone mimi cs exist in the natural environment. Examples of natural hormone mimics are the isoflavinoid phytoestr ogens (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 el imination of natural hormones in the body responsible for maintaining homeostasis, re production, development, and/or behavior (EPA 1997c). Stated differently, such compounds may cause toxicities that ar e mediated through the neuroendocrine axis. As a result, these chemicals may play a role in alte ring, for example, metabolic, sexual, immune, and neurobehavioral function. Such chemicals are also thought to be involved in inducing breast, testicular, and prostate cancers, as well as endometriosis (Berger 1994; Giwercman et al. 1993; Hoel et al. 1992).
No studies were located regarding endocrine disruptiv e effects in humans resulting from inhalation, oral, or dermal exposure to stable or radioactive strontiu m. Stable strontium, as an analog to calcium, is unlikely to cause endocrine disruption at normal levels of exposure. Endocrine glands, such as the pituitary, that are in close association with bone could potentially be damaged by irradiation from radioactive strontium incorporated into bone. For example, increases in tumors of the pituitary andSTRONTIUM 156 3. HEALTH EFFECTS
ovaries were observed in rats followi ng gestational exposure to injected 90 Sr (Rönnbäck and Nilssen 1982; Schmahl and Kollmer 1981; Schmahl et al. 1979; Section 3.4.5.7). However, endocrine function was not tested in these studies. Ingested radioac tive strontium had no effect on reproductive function in animals, suggesting that it did not affect reproductive hormones to an obvious degree (Clarke et al. 1972; Finkel et al. 1960). However, no study has specifically investigated the endocrine system.

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 bi ological systems will have fully developed. Potential effects on offspring resulting from exposures of parental germ cells are considered, as well as any indirect effects on the fetus and neonate resulting from mate rnal exposure during gestation and lactation. Relevant animal and in vitro models are also discussed.
Children are not small adults. They differ from a dults in their exposures and may differ in their susceptibility to hazardous chemicals. Children’s uni que physiology and behavior can influence the extent of their exposure. Exposures of children ar e discussed in Section 6.6 Exposures of Children.
Children sometimes differ from adults in their susceptib ility 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 ofte n depends on developmental stage. There are critical periods of structural and functional devel opment during both prenatal and postnatal life and a particular structure or function will be most sensitiv e to disruption during its critical period(s). Damage may not be evident until a later stage of developmen t. There are often differences in pharmacokinetics and metabolism between child ren and adults. For example, absorption may be different in neonates because of the immaturity of their g astrointestinal tract and their larg er skin surface area in proportion to body weight (Morselli et al. 1980; NRC 1993); the gastroin testinal 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 ex tracellular water and their brains and livers are proportionately larger (Altman and Dittmer 1974; Fomon 1966; Fom on 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 growthSTRONTIUM 157 3. HEALTH EFFECTS and development, levels of particular enzymes ma y be higher or lower than those of adults, and sometimes unique enzymes may exist at particular de velopmental 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 whethe r the relevant enzymes are involved in activation of the parent compound to its toxic form or in detoxifica tion. There may also be differences in excretion, particularly in newborns who all ha ve a low glomerular filtration rate and have not developed efficient tubular secretion and resorption capacities (Altman a nd Dittmer 1974; NRC 1993; West et al. 1948). Children and adults may differ in their capacity to repa ir damage from chemical insults. Children also have a longer remaining lifetime in which to express da mage from chemicals; this potential is particularly relevant to cancer.
Certain characteristics of the developing human may increase exposure or susceptibility, whereas others may decrease susceptibility to the same chemical. For example, although infants breathe more air per kilogram of body weight than adults breathe, this di fference might be somewhat counterbalanced by their alveoli being less developed, which results in a di sproportionately smaller surface area for alveolar absorption (NRC 1993).
The ubiquitous nature of stable strontium in soils and water supplies, and the chemical similarity of strontium to calcium, ensure that strontium will unavoidably be incorporated into the human body to some degree. Because of the requirement for high cal cium intake during the period of bone development, the absorption and retention of strontium is higher in children than in adults; an ICRP (1993) model postulates that the fractional gastro intestinal absorption of strontium by infants (up to 12 months) is double that of adults (see Sections 3.5.1.2 and 3.5.5). Consequently, children are more at risk than adults from exposures to excess stable strontium or radioactive strontium.

Stable Strontium. A Turkish epidemiological study indicated that children with probable deficient vitamin D status (from insufficient exposure to sunlight ) and diets low in calcium and animal protein were more likely to develop rickets as a result of exposure to excess dietary strontium (Özgür et al. 1996). The rachitic signs of craniotabes, rachitic rosary, bulging at the wrist, genu valgus, genu varus, and delayed closure of the fontanelles represented biomarkers of e ffect in children exposed to excess strontium. This study is consistent with numerous animal studies th at demonstrated abnormal skeletal development (i.e., rickets) in young animals exposed to sufficiently high levels of dietary strontium (Kshirsagar 1976; Matsumoto 1976; Morohashi et al. 1994; Reinholt et al. 1985; Storey 1961, 1962; Svensson et al. 1985,STRONTIUM 158 3. HEALTH EFFECTS 1987). Young rats may be sensitive to levels of ingested strontium that have no effect on adults (Storey 1961).
Children or young animals are likely to be more sensitiv e than adults to excess st rontium, in part, because the rates of intestinal strontium absorption may be higher, although this has not been consistently demonstrated in humans (see Section 3.5.1.2 and Ta ble 3-7). The ICRP (1993) biokinetic model for strontium assumes that the fraction of ingested stron tium that is absorbed decreases from 0.6 in infancy to 0.3 in adulthood (see Section 3.5. 5); some models assume the absorbed dose may be 8 times higher in infants compared to adults (NCRP 1991). These estimates are consistent with rat studies in which rates of strontium absorption were much higher (4–8 times) in weanlings compared to adults (Forbes and Reina 1972; Harrison et al. 1966b). This age-dependent diff erence in absorption may be partly explained by the duodenal level of vitamin-D-dependent calbindin D pr otein (a calcium-binding protein involved in absorption), which is much lower in old rats than in young rats (Armbrecht et al. 1979). Armbrecht et al. (1998) have demonstrated that the translation of calbindin D-9k mRNA into protein declines in the rat duodenum with age and this would be expected to redu ce the rates of intestinal absorption of calcium and strontium in older animals.
Children are particularly vulnerable to excess strontiu m because the immature skeleton has a high rate of bone remodeling, and strontium adversely affects bone development in several ways, as demonstrated in animal studies. In chickens and rats, excess strontium suppresses the activation of vitamin D 3 in the kidney, which severely reduces the expression of calbindin D mRNA and the translation of calbindin D protein in the duodenum (Armbrecht et al. 1979, 1998; Omdahl and DeLuca 1972). As a result, duodenal absorption of calcium is reduced. Strontium also bi nds directly to hydroxya patite crystals, which may interfere with the normal crystalline structure of bone in rats (Storey 1961). In addition, excess strontium may prevent the normal maturation of chondrocytes in the epiphyseal plates of long bones of rats (Matsumoto 1976). Excess strontium apparently interferes with the mineralization of complexed acidic phospholipids that is thought to help initiate the formation of hydroxyapatite crystals in developing bone (Neufeld and Boskey 1994). As a result, aff ected bone contains an excess of complexed acidic phospholipid and a significantly lower ash weight. This finding is consistent with the reduced rate of matrix vesicle degradation observed by Reinholt et al . (1984) in rachitic cartilage in strontium-treated rats.
The placenta does not accumulate strontium nor does it prevent transfer of strontium to the fetus following maternal exposure (see Section 3.5.2.2). However, no studies were located that addressedSTRONTIUM 159 3. HEALTH EFFECTS developmental effects following maternal exposure to stable strontium in humans or animals. Stable strontium is also transferred to nursing infants th rough breast milk of exposed mothers at a ratio of approximately 0.24 μg strontium/mg Ca (Harris on et al. 1965). These levels are unlikely to be sufficiently high to perturb bone development in the fe tus. Strontium stored in maternal bone because of prior exposure can be mobilized during pregnancy or lactation, resulting in fetal or infant exposure (Tolstykh et al. 1998).
Alginates, carbohydrates rich in guluronic acid, have been found to reduce peak exposure to strontium (see Section 3.12.1). Sutton et al. (1971a) showed that gastrointestinal absorption of stable 84 Sr was reduced 4-fold in children who were simultaneously given 10% sodium alginate-97% guluronic acid. Exposure to sunlight to enhance vitamin D status and diets with adequate calcium, phosphorus and protein may be considered to some degree protec tive against the effects of stable strontium (see Section 3.12).

Radioactive Strontium. During the period of above-ground nuclear weapons testing, the possible effects in children resulting from exposure to 90 Sr in radioactive fallout was a matter of concern. However, no studies have been able to identify unequivocally an y increase in infant mortality, childhood cancers, or genetic damage in humans that could be attr ibuted to oral or inhalation exposure to 90 Sr in fallout (NCRP 1991; Shaw and Smith 1970). In the Techa River popula tions that received higher oral doses of radiation, including radiostrontium, individuals who were e xposed as teenagers exhibited a significantly higher frequency of stable chromosomal translocations comp ared to individuals who were exposed as adults (Bauchinger et al. 1998). Adverse pregnancy out comes (mortality from developmental anomalies, chromosomal anomalies, labor complications, and othe r unspecified perinatal conditions) were elevated in the progeny of exposed individuals from the Te cha River cohort, 60% of whom were exposed to radiation as teenagers (Kossenko et al. 1994). However, Kossenko et al. (1994) calculated that relatively high radiation doses (20–480 rem or 0.2–4.8 Sv) to th e parental gonad would be required to double the incidences of stillbirths, miscarriages, early neonatal mo rtality, or lethal developmental effects. (Note that the gonadal radiation doses may have primarily b een caused by exposure to external gamma radiation [Akleyev et al. 1995]). No increase in cancer in cidence was observed among the progeny of the exposed Techa River population (Kossenko 1996). Dermal effects (slight dermal atrophy, telangectiasis, and pigmentation changes) were reported as delayed reactions to superficial 90 Sr treatments for facial hemangiomas in adults and children (Bekerus 1970). However, this study did not compare the relative sensitivity of children and adults.STRONTIUM 160 3. HEALTH EFFECTS It would not be expected that the immediate conse quences of radioactive strontium exposure would differ in children and adults at the cellular level; that is, the initial damage to proteins and nucleic acids caused by ionizing radiation would be the same. Thus, child ren and adults might be expected to have similar effects following exposure to solid radiostrontium sources apposed to the skin or to insoluble particles of radiostrontium lodged in the lungs. However, as discussed in Appendix Section D.4.1, ionizing radiation is more damaging to actively mitotic cells than to differentiated postmitotic ce lls, largely because genetic lesions become permanent when cell division occurs before repair can occur. Since children have proportionally more mitotic cells than adults, the biol ogical effect of radiation exposure in children would be expected to be proportionally more severe. Other developmental aspects contribute to the higher potential vulnerability of children to radiation effects. One is the higher rate of gastrointestinal absorption in children, as discussed for Stable Strontium, above . In addition, animal studies indicate that the young are more vulnerable than adults to inhalation or oral exposures to radioactive strontium in soluble form, because of higher rates of retention in the developi ng skeleton (see Stable Strontium section above). Thus, a given absorbed dose of soluble radiostron tium will have a longer biological half-life in young animals compared to adults, leading to higher cumu lative radiation doses to bone and surrounding soft tissues and more severe adverse effects (see Section 3. 3). Examples of this age-related difference in severity are discussed under Section 3.2.2.2 Musculoskelet al Effects (especially Storey 1961, the basis for the intermediate oral MRL) and Section 3.3.2. 2 Hematological Effects (Cragle et al. 1969), and Section 3.3.2.6 Reproductive Effects (Clarke et al. 1970). Young animals exhibit the same types of effects as adults (e.g., malignancies), in addition to ot her effects specific to their developmental stage. For example, radioactive strontium disturbed osteogenesis of long bones in young rats by damaging the epiphyseal cartilaginous discs, and the vasculature th at supports resorption (Casarett et al. 1962). In weanling rats, irradiation of the marrow prevented its invasion of metaphyseal cartilage, thereby causing cartilage to resume active proliferation, rather than undergo transformation into bone. Because of disruption of these processes, cartilage and fibrous marrow were sometimes incorporated into cortical bone, resulting in weakness or fracture. For all species studied, a long-term effect of 90 Sr incorporation in young animals or in utero was a higher incidence of bone-asso ciated cancers compared to animals exposed as adults (Clarke et al. 1972; Finkel et al. 1960; White et al. 1993). Size differences may contribute to the possible higher vulnerability of children to bone marrow effects from retained radiostrontium. Since bone marrow cavities in children have smaller diameters, a larger proportion of the hemopoietic bone marrow is within the approximate centimeter range of beta radiation emitted from radiostrontium bound to the endochondral surface.STRONTIUM 161 3. HEALTH EFFECTS There are two theoretical ways in which the fetus might be exposed to radiation from the decay of radioactive strontium: from transfer of strontium across the placenta or from proximity to radiation emitted from the maternal body. Placental transfer of radioactive strontium to the fetus has been demonstrated in humans (Sikov et al. 1991, Stather et al. 1992) and animals (rodent: Onyskowova and Josifko 1985, Taylor and Bligh 1992; pig: Palmer et al. 1969). Studies of residents of the Techa River who were exposed to strontium as a result of an accident at a plutonium production plant provide evidence that fetal exposures can result from previous maternal exposures. The fetal:maternal strontium concentration ratio in four subjects who were exposed prior to pregnancy varied from 0.012 to 0.24, with the higher values associated with maternal exposur es that occurred during adulthood and lower values associated with maternal exposures during childhood or adolescence (Tolstykh et al. 1998). A dosimetry study in minipigs determined that exposure of the fetal thymus (ages 55–110 days of gestation) to radiostrontium ( 90 Sr– 90 Y) is related to the amount that is incorpor ated by the fetus after placental transfer; no appreciable radiation reached the thymus from radiostrontium in the maternal uterine wall (Palmer et al. 1969). Palmer et al. (1969) indicated that resu lts might vary for other organs, for younger fetuses (which may be relatively closer to the maternal uterine wall or pelvic bone), or for single fetuses compared to multiple fetuses (as in the pig). As discussed in Section 4.2, strontium isotopes and their transformation product isotopes differ with respect to their emission energies; this factor is another variable that will determine whether the fetus is subject to radiation from the maternal body.
Animal studies demonstrate that the developmental consequences of injecting pregnant females with radioactive strontium are qualitatively different depending on the gestational day of administration (Finkel and Biskis 1969; Finkel et al. 1972; Hopkins et al. 1967). This is partly related to temporal differences in the onset of osteogenic activity and calci fication in different parts of the skeleton. For example, the increase in calcification of the basiocci pital and sphenoid bones of the skull occurring by gestational day 18 of the rat probably contributed to the development of pituitary gland tumors after an injection of 90 Sr was administered that day (Schmahl and Kollmer 1981; Schmahl et al. 1979). A single injection administered to pregnant mice late in gesta tion transiently affected fertility of male offspring by suppressing spermatocyte maturation, but severely depressed oocyte maturation of the female offspring (De Rooij and Rönnbäck 1989; Nilsson and Henr icson 1969; Rönnbäck 1979, 1980, 1981a, 1981b).

Radioactive strontium, like stable strontium, can be transferred to infants through breast milk of exposed mothers (Harrison et al. 1965). Rönnbäck (1981a) dem onstrated that the numbers of oocytes (all stages) in the ovary was reduced in neonatal mice that were exposed to radioactive st rontium in the milk of surrogate females that had been given high doses by injection.STRONTIUM 162 3. HEALTH EFFECTS Various methods for reducing the body burden and to xic effect of radioactive strontium have been investigated (see Section 3.12). Only the administration of alginates high in guluronic acid, described in the previous section, has been validated in children (S utton et al. 1971a). A single oral dose of aluminum phosphate antacid gel taken soon af ter exposure is a recommended treatment for reducing absorption of ingested strontium (Ellenhorn et al. 1997; Haddad et al. 1998). This would be a suitable treatment for children as long as the dosage recommendations were followed, since excess ingestion of aluminum phosphate can cause rickets (Chines and Pacifici 1990; Pivnick et al. 1995). A diet high in calcium would tend to reduce the incorporation of radioac tive strontium into bone (Steinbach 1968).

3.9 BIOMARKERS OF EXPOSURE AND EFFECT

Biomarkers are broadly defined as indicators signaling ev ents 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 interpre tation 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. Ho wever, 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 me asured 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 subs tance (e.g., biologic half-life) and environmental conditions (e.g., duration and route of exposure), the s ubstance 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 a nd fluids (e.g., essential mineral nutrients such as copper, zinc, and selenium). Biomarkers of expos ure to strontium are discussed in Section 3.9.1.
Biomarkers of effect are defined as any measurable bi ochemical, 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 definiti on encompasses biochemical or cellular signals ofSTRONTIUM 163 3. HEALTH EFFECTS tissue dysfunction (e.g., increased liver enzyme activity or pathologic changes in female genital epithelial cells), as well as physiologic signs of dysfunction su ch as increased blood pressure or decreased lung capacity. Note that these markers are not often substance specific. They also may not be directly adverse, but can indicate potential health impairment (e.g., DNA adducts). Biomarkers of effects caused by strontium are discussed in Section 3.9.2.
A biomarker of susceptibility is an indicator of an inhe rent or acquired limitation of an organism's ability to respond to the challenge of exposure to a specific xenobi otic 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 res ponse. 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 Strontium

The biomarkers to quantify exposure to stable or radi oactive strontium are similar in children and adults.
Stable strontium is ubiquitous in the diet and can be measured in urine, blood and feces by a number of methods outlined in Section 7.1. After exposure, a pproximately 99% of the absorbed strontium that is retained is found in bone and connective tissues (Sch roeder et al. 1972). Normal background levels of strontium were measured by emission spectrography in cadaver tissue from 168 American subjects (Tipton 1981; Tipton and Cook 1963). Average stron tium levels in human tissues expressed as ppm ash were as follows: rib bone 110 ppm, vertebra 100 pp m, aorta 33 ppm, ileum 25 ppm, duodenum 11 ppm, lung 8.2 ppm, kidney 5.2, heart 2.6 ppm, and liver 1.6 ppm. In a small group of adult males, the mean strontium concentration in plasma was 29 μg/L (Sutton et al. 1971b).

Soluble radioactive strontium can be detected in ur ine, blood, or feces by li quid scintillation counting. Whole body counters (or chest counters for inhalation exposures) can measure internal radioactive strontium deposited in bone following high level ex posures (see Section 7.1.1). Children tend to incorporate strontium more homogenously th roughout bone than is the case for adults.STRONTIUM 164 3. HEALTH EFFECTS
3.9.2 Biomarkers Used to Characterize Effects Caused by Strontium

Deformities of bone in response to excess strontium can be detected by radiography. Exposure to excess stable strontium may cause specific abnormalities in bone calcification that can lead to obvious bone deformities, particularly in the young. Such ‘rach itic’ signs in children include craniotabes, rachitic rosary, conspicuous bulging at the wrist, genu valgus , genu varus, and delayed closure of the fontanelles (Özgür et al. 1996). However, excess exposure to other metals, such as aluminum (Bhattacharyya et al. 1995; Carmichael et al. 1984; Chines and Pacifici 1990; Pivnick et al. 1995; Woodson 1998) or deficiencies in calcium, vitamin D, and/or phosphate can generate the same effects. Thus, this is not a specific biomarker for strontium, but can be confirmatory. Although bone biopsies can measure strontium chemically, these tests are not warranted because of the relatively high risk/benefit ratio.
Exposure to radioactive strontium may result in lowe red blood cell counts, which can be detected using standard clinical laboratory methods. However, exposure to other sources of ionizing radiation has similar effects. Sufficien tly high exposures to radioactive stron tium can result in genetic damage to tissues adjacent to bone. Recently, Sutherland et al. (2000a, 2000b) develope d a molecular biological strategy to identify clustered lesions in DNA resulting from in vitro cellular exposure to gamma radiation. It is possible that this technique might be adapted to evaluate genetic damage in blood cells following exposure to radioactive strontium, although, again, it would not be specific for radiostrontium, but rather for ionizing radiation. It is uncertain whether the technique would be applicable for the chronic exposures characteristic of absorbed radiostrontium compared to the acute high-dose exposures for which it was designed.

3.10 INTERACTIONS WITH OTHER CHEMICALS

Several agents reduce the absorption or retenti on of strontium, reducing its toxic effects (see Section 3.12).

Calcium. Strontium has chemical properties similar to calci um, but is less efficient than calcium in most biological processes. Calcium and strontium appear to compete for the same transporter elements in the intestine (Bianchi et al. 1999; Blumsohn et al. 1994; Milsom et al. 1987; Reid et al. 1986; Sips et al. 1994), but calcium is preferentially absorbed. Co -administration strontium and calcium reduces theSTRONTIUM 165 3. HEALTH EFFECTS uptake of strontium and also reduces skeletal retention of strontium (Palmer et al. 1958; Roushdy et al. 1980, 1981; Steinbach 1968).

Anions. Oral administration of phosphate, as aluminum phosphate antacid gel, reduces the gastrointestinal absorption of strontium by increasing its excretion in feces (Carr and Nolan 1968; Keslev et al. 1972; Spencer et al. 1969a, 1969b). Oral administration of sulfates at the same time as strontium reduces its retention in the skeleton (Volf 1964). These agents are discussed in Section 3.12.1.

3.11 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE

A susceptible population will exhibit a different or enha nced response to strontium than will most persons exposed to the same level of strontium in the envi ronment. Reasons may include genetic makeup, age, health and nutritional status, and exposure to othe r toxic substances (e.g., cigarette smoke). These parameters result in reduced detoxification or excretion of strontium, or compromised function of organs affected by strontium. Populations who are at greater risk due to their unusually high exposure to strontium are discussed in Section 6.7, P opulations With Potentially High Exposures.
In general, children, who are in the stage of activ e bone synthesis and growth, are more vulnerable to adverse effects of strontium. A more detailed di scussion of children’s susceptibility can be found in Section 3.8. The following discussion is limited to other individual variations or health conditions that may modify the usual effects of strontium.
Protein Deficiency and Ethanol Consumption. Protein-deficient diets may increase the adverse effects of exposure to excess stable strontium or to radio active strontium, by reducing clearance and increasing incorporation into bone. A metabolic experiment in a dult male Wistar rats showed that consumption of a protein-deficient diet increased the intestinal absorp tion of dietary strontium and its incorporation into bone, while reducing fecal and urinary excretion of strontium (Gonzales-Reimers et al. 1999). When rats were given ethanol in addition to the protein-deficient diet, incorporation of strontium into bone was significantly enhanced, although ethanol given with a protein-normal diet tended to reduce strontium incorporation through its diuretic effects.

Renal Disorders. Patients with chronic kidney failure may be more susceptible to excess strontium than the general population, because of a reduced ability to excrete strontium and retain calcium (Apostolidis et al. 1998). In such patients, plasma levels of strontium were found to be 60% higher compared toSTRONTIUM 166 3. HEALTH EFFECTS controls. In a variety of studies, uremic patients on dialysis were found to have significantly higher levels of strontium in serum, muscle, and brain tissue comp ared to normal undialized controls (Alfrey et al. 1975; Couttenye et al. 1999; D’Haese and De Broe 1996; D’Haese et al. 1999, 2000; Krachler et al. 2000; Schrooten et al. 1999). Although the high level of st rontium in serum in uremic patients was correlated with the high level of strontium in the local tap wate r, it is also possible that uremic patients may have reduced rates of strontium excretion.
Paget’s Disease (osteitis deformans). Patients with Paget’s disease (osteitis deformans) had a higher than normal retention rate following administration of 85 Sr (Tothill et al. 1983). Part-body retention measurements demonstrated that diseased bone had relatively higher uptakes of strontium compared to undiseased bone. Pagetic bone contains a higher proportion of small mineral crystals with greater surface area, which accounts for its increased ability to accu mulate strontium. Reflecting the high degree of osteoclast activity in Paget’s disease, di seased bone had an increased turnover of 85 Sr, compared to undiseased bone in the same patient. Since bone metabolism is locally accelerated in persons with this disease, they are likely to develop higher body burdens of radioactive strontium than healthy adults.
Rheumatoid Arthritis or Seronegative Spondarthritis. Patients with active rheumatoid arthritis or seronegative spondarthritis were found to have significan tly higher levels of strontium and calcium in their granulocytes (Hällgren et al. 1984). The str ontium overload was thought to be linked to the degree of inflammation and was positively related to serum levels of the acute-phase protein haptoglobin; corticosteroid therapy differentially reduced the stron tium content of granulocytes compared to calcium. It is not known whether granulocytes in persons with active disease would take up relatively more radiostrontium from plasma, and therefore incur mo re damage, than would be the case for otherwise healthy individuals under an identical exposure scenario.

Diabetes. Persons with diabetes may be more vulnera ble to adverse effects from dermally-applied radioactive strontium. Thinning of the sclera deve loped in a diabetic patient who had been treated for pterygium with a single dose (1,700–1,800 rad; 17–18 Gy) of 90 Sr (Wesberry and Wesberry 1993; see Section 3.3.3.2). This reaction was not observed in 17 0 other eyes treated at that dose level; however, the authors did not state whether other diabetics were in the group that was unaffected. Conversely, in rats made diabetic by injection of streptozotocin , the absorption of strontium in the duodenum was significantly reduced, which would appear to be protective (Miller and Schedl 1976).STRONTIUM 167 3. HEALTH EFFECTS Genetic Polymorphisms. Polymorphisms in genes that may affect rates of strontium (calcium) absorption and bone mineralization are currently under investiga tion. In a study of postmenopausal women with osteoporosis, polymorphisms of vitamin D receptor genes apparently caused a 40% variation in the rate of strontium absorption (Gennari et al. 1997); however , another study found no asso ciation between vitamin D receptor polymorphisms and bone mineral density in osteoporotic women (Poggi et al. 1999). Similarly, 3’-end region polymorphisms of the vitamin D receptor were found to have no effect on enteral strontium absorption or bone mineral density in pa tients with calcium kidney stone disease (Vezzoli et al. 2002). Insulin-like growth factor (IGF-I) is correlated with age-related changes in strontium absorption in men (Fatayerji et al. 2000), but polymorphisms have not been evaluated. Other candidate genes that may affect bone mineralization include the parathyroid hor mone receptor 1, the estradiol receptor, collagen type I alpha 1, transforming growth factor-beta 1, interleukin-6, calcitonin receptor, alpha2-HSglycoprotein, osteocalcin, calcium-sensing receptor, interleukin-1 receptor antagonist, beta-3-adrenergic receptor, apolipoprotein E, glucocorticoid receptor, and epidermal growth factor (Audi et al. 1999; Duncan et al. 1999). The relative contribution of these factors on bone mineralization has yet to be clarified and whether any polymorphisms increase suscep tibility to adverse effects of strontium remains to be determined.

3.12 METHODS FOR REDUCING TOXIC EFFECTS

This section will describe clinical practice and resear ch concerning methods for reducing toxic effects of exposure to strontium. 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 strontium. When specific exposures have occurred, poison control cente rs and medical toxicologists should be consulted for medical advice. The following texts provide sp ecific information about treatment following exposures to strontium:
Ellenhorn MJ, Schonwald S, Ordog G, et al., eds. 1997. Medical toxicology: Diagnosis and treatment of human poisoning. 2 nd ed. Baltimore, MD: Williams & Wilkins, 1682–1723. Haddad LM, Shannon MW, Winchester JF, eds. 1998. Clinical management of poisoning and drug overdose. 3 rd ed. Philadelphia, PA: W.B. Saunders, 413–425. Viccellio P, ed. 1998. Emergency toxicology. 2 nd ed. Philadelphia, PA: Lippincott-Raven, 991–996.STRONTIUM 168 3. HEALTH EFFECTS
3.12.1 Reducing Peak Absorption Following Exposure

Human exposure to strontium and its compounds occurs primarily by inhalation and ingestion, since absorption is poor following dermal contact. Current suggestions for reducing absorption of radiostrontium include ingestion of antacids cont aining aluminum phosphate (Ellenhorn et al. 1997; Haddad et al. 1998). Treatment is most effective wh en it is initiated within 2 hours of exposure.
The threat of nuclear fallout from atomic weapons testing was the impetus for a large number of studies that investigated methods to prevent absorption of radiostrontium, while not adversely affecting the absorption of calcium. Reasonably effective strategi es have included alginates, aluminum phosphate, and sulfates. Less effective or less practical strategies have included cold, diet, dietary fiber, flavones, and stable strontium.
Alginates. Alginates are carbohydrates derived from seaweed that have been found to reduce the absorption of strontium in humans and animals, without significantly affecting the absorption of calcium. When 10% sodium alginate-97% guluronic acid was given orally along with the stable marker 84 SrCl 2 to children (ages 2.5–10 years), plasma 84 Sr was reduced by 75% and urinary excretion of the tracer was reduced 72% (Sutton et al. 1971a). The authors concluded that absorption was reduced 4-fold. In adults, sodium alginate extracts administered as a liquid or in bread, reduced stron tium absorption by 50% in humans and 3-fold in rats (Gong et al. 1991). Alginates with a high guluronic acid/mannuronic acid ratio were found to be more effective in humans and rats (Carr and Nolan 1968; Gong et al. 1991). Sodium alginate administered orally to rats effectively reduced the whole body retention of 85 strontium that had been administered intratracheally (Naményi et al. 1986 ). Calcium alginate added to the diet of female goats reduced the transfer of 85 strontium to milk, which was attri buted to a reduction in strontium absorption (Beresford et al. 1999). In rats given 89 Sr and 45 Ca by gavage, alginate treatment, particularly in combination with stable calcium, diffe rentially increased the fecal excretion of 89 Sr and reduced the skeletal retention of 89 Sr (Light et al. 1970a).
Aluminum Phosphate Antacid Gel. Aluminum phosphate antacid gels, administered just prior to or shortly after oral strontium exposure, have been s hown to reduce absorption of strontium by increasing its excretion in feces in humans (Spencer et al. 1969a , 1969b), rats (Carr and No lan 1968), and mice (Keslev et al. 1972). A practical advantage of this treatment is that the gels are readily available as over-thecounter pharmaceuticals. In elderly men who had been maintained on a low calcium diet for several weeks, oral administration of an antacid gel just prior to oral 85 Sr/ 45 Ca exposure reduced plasmaSTRONTIUM 169 3. HEALTH EFFECTS radiostrontium levels by 88%, but reduced radiocalcium levels by only 38% (Spencer et al. 1969a). In the same study group, antacid treatment reduced strontium absorption by 57% when given 0.5 hours after exposure, but by only 43%, 1 hour after exposure (S pencer et al. 1969b). In similar studies on rats fed antacid for several days prior to exposure, the absorption of strontiu m was reduced by 83%, whereas there was no effect on the absorption of calcium (Carr a nd Nolan 1968). In mice, an aluminum phosphate gel reduced the absorption of strontium by about 13-fold and of calcium by about 3-fold (Keslev et al. 1972).
Sulfates. In rats orally exposed to radiostrontium and monitored on day 2, oral administration of barium sulfate in combination with sodium sulfate or magnesium sulfate reduced radiostrontium retention in the femur by nearly 80% (Volf 1964). Treatment was eff ective if given within 10 minutes of exposure, but not if delayed more than 80 minutes. Strontium sulfate was less effective, reducing radiostrontium retention by only 30%. Volf (1964) did not determ ine whether the effectiveness of the barium sulfate combination therapy was a result of increased diuresis or decreased bioavailability by means of adsorption to radiostrontium in the intestine.
The following treatments have been shown to be less effective or less practical.
Diet or Dietary Fiber. A pulverized solid diet administered to rat sucklings over 8 hours resulted in 10– 20% less whole body retention of 85 Sr (reduced absorption) than cow milk (Kostial et al. 1981b, 1984). Supplementing cow milk with trace elements did not improve its effectiveness, ruling out the possibility that trace elements in the food competitively inhibite d intracellular transport of ingested strontium. Rather, the authors suggested that the solid diet c ontained ligands for strontium that reduced the amount of strontium available for transport. Another study de monstrated that the inclusion of cellulose fiber into the diet of suckling rats decreased the retention of simultaneously administered 85 Sr/ 45 Ca by 20% (Mom č ilovi č and Gruden 1981). However, cellulose fiber w as less satisfactory than alginates, both in effectiveness and in the lack of discrimination between strontium and calcium.

Flavones. In rats given doses of flavone (Iprifl avone, 7-isopropyl-isoflavone, or Morin, 2',2,4',5,7-pentahydroxy-flavone) for 3 weeks prior to acute oral exposure to radiostrontium, the whole body retention of radiostrontium was reduced by 50 and 30%, respectively, after 1 month (Gachályi et al. 1988). Similar experiments on pregna nt rats demonstrated that both flavones reduced fetal uptake of radiostrontium administered to dams on gestational days 17/18 and 19/20. No studies were located that demonstrated the usefulness of flavones for emergency situations, rather than as pretreatments.STRONTIUM 170 3. HEALTH EFFECTS
Stable Strontium. In weanling rats previously given varying amounts of strontium lactate in the diet, 4 or 6% strontium lowered the retention of injected radios trontium to a greater extent than the retention of injected radiocalcium (Teree et al. 1965). The disadvant age of this treatment is the adverse effect on bone development caused by excess stable strontium.

3.12.2 Reducing Body Burden

Absorption of strontium can vary with the chemical form of the compound and its solubility. Those strontium compounds that are readily absorbed foll owing inhalation or oral exposure are rapidly distributed throughout the body (see Section 3.5). Becau se of its similarity to calcium, strontium entering the circulation preferentially accumulates in bone . Methods for reducing the body burden of radiostrontium that have been tested in animals include calcium, chelators (with variable results), hemodialysis, and magnesium sulfate. Exposure to cold temperatures, use of the few pharmacological agents that have been tested, and use of stab le strontium are less satisfactory treatments.

Calcium. In human patients with osteoporosis who were injected with tracer doses of 85 SrCl 2 , intravenous infusions of calcium gluconate significantl y increased urinary excretion of strontium, but had no effect on fecal excretion (Spencer et al. 1967d). This effect was attributed to the decreased renal tubular reabsorption of calcium under these conditions . Calcium gluconate was more effective than magnesium chloride tested in the same study. A 10-day series of injections with a combination of calcium and calciferol reduced the retention of 90 Sr in rabbits by 70%, if the treatments started as soon as 24 hours after exposure (George et al. 1979). If tr eatments were delayed 96 hours, the removal of strontium was reduced by 50%. Slightly less effectiv e treatments included calcium alone, sodium citrate, or a combination of calcium and magnesium, which reduced strontium retention by 40, 30, and 20%, respectively. A 3-week diet high in calcium and lo w in phosphorus, initiated 24 hours after injection of
90 Sr into rats, significantly reduced the incorporation of the isotope into bone (Steinbach 1968). In rats, pretreatment with diets rich or adequate in calcium tend to result in lower accumulations of radiostrontium in bone following exposure than diets poor in calcium (Palmer et al. 1958; Roushdy et al. 1980, 1981). However, administration of a high-calcium diet to rats following a month-long parenteral exposure to radiostrontium, only slightly reduced the st rontium content of the femur after 65 days (Ray et al. 1956).

Chelators. Chelators are not effective once strontium has become incorporated into hydroxyapatite. A variety of chelators have been tested in rodents, with variable results. In general, chelators did notSTRONTIUM 171 3. HEALTH EFFECTS successfully increase the excretion of radiostrontium, if administered 6 or 24 hours after exposure (e.g., Llobet et al. 1991a, 1991b, 1992a). In tests on ra ts, the cryptator hexaoxa-diamine macrobicycle was effective when given simultaneously with radios trontium (Müller 1970). The aza crown ether 2NaCa Kryptofix 22 was effective in tests on mice and rats when administered intraven ously or intratracheally within 1 hour of exposure to radiostrontium (Var ga et al. 1994). Other aza crown ethers and other chelators have been tested on mice following parenteral exposure to strontium, but their effectiveness has been so variable and no consistent conclusions can be drawn (Colomina et al. 1991; Llobet et al. 1992b; Ortega et al. 1989). For example, Na 2 Ca EGTA (Na 2 Ca ethylenglycol-bis-( β -amino-ethyl-ether)-N,N’­ tetraacetic acid) increased fecal excretion of subc utaneously administered strontium (nitrate), but decreased urinary excretion to the same degree, and thus, there was no net change (Colomina et al. 1991).

Chelators that were not at all effective in r odent studies include monosodium glutamate, Tiron (4,5-dihydroxy-1,3-benzene-disulfonic acid), DMSA (2 ,3-dimercaptosuccinic acid), succinic acid, malic acid, CaNa 2 CTDA (cyclohexanediaminetetraacetic acid), and THPC, a cyclic derivative of EDTA (Kostial et al. 1979; Llobet et al. 1992b; Ortega et al. 1989).
The chelating agent, zirconium citrate, administered intraperitoneally in several injections soon after parenteral exposure to 90 Sr, significantly reduced the number of mice with bone tumors, reduced the multiplicity of tumors, and delayed the onset of tumors (Zander-Principati and Kuzma 1964). Measurements of external brehmsstrahlung emissions 10–12 months later demonstrated that mice treated with zirconium citrate had a reduced body burden of radiostrontium, which is the likely cause of the reduced tumor rate. One source of uncertainty regardi ng this study, despite the claims of low toxicity for zirconium citrate, is the unexplained reduction in lif espan in all the groups treated with the chelator.

Cold. In mice exposed to low temperature (9 E C), the rate of urinary excretion of a radiostrontium tracer was increased (Wedin 1972; Wedin et al. 1972). This was attributed to a specific effect of cold on the rate of diuresis. However, since the rate of calcium excretion was not measured in this study, but is also known to be increased by cold, the usefulness of this finding is not clear. Urinary excretion rates of radioactive strontium in mice in traperitoneally injected with 85 Sr were increased about 10% by transfer to 4 E C (Nilsson and Rönnbäck 1988).

Hemodialysis. Hemodialysis is only effective if administer ed soon after exposure to strontium. In 100-day-old calves injected with 85 Sr, a 12-hour hemodialysis session administered 4, 14, or 24 hoursSTRONTIUM 172 3. HEALTH EFFECTS later resulted in removal of only 14, 4, and 2.5% of the administered dose, respectively (Downey et al. 1964).
Magnesium. In human patients with osteoporosis w ho were injected with tracer doses of 85 SrCl 2 , intravenous infusions of magnesium chloride significantly increased urinary excretion of strontium, but had no effect on fecal excretion (Spencer et al. 1967a). Magnesium chloride was not as effective as calcium gluconate tested in the same study. Magnesium sulfate injected 10 minutes after 85 SrCl 2 significantly reduced the body burd en of strontium in rats, irrespective of the dietary calcium or vitamin D status (Roushdy et al. 1980, 1981).
Pharmacological Agents. Tests of the effectiveness of hormones or drugs in reducing the body burden of strontium have been disappointing. In rats, prog esterone had no significant effect on radiostrontium retention, whereas estrogen actually increased the amount of 90 Sr in the femur (Steinbach 1968). In rabbits, the steroid prednislone, thyroxine, and the di uretic furosemide removed only about 30, 15, and 10%, respectively, of the administered dose of 90 Sr (George et al. 1979).
Phosphorus-reduced Diet. A diet low in phosphorus (0.017%, Ca/P ratio of 21.5) was most effective in mobilizing radiostrontium from the rat skeleton (Ray et al. 1956). Nearly 85% of the strontium incorporated into the femur was removed by the 50 th day; only 0.24% of the inj ected dose remained in the femur. However, this diet caused serious adverse effects: minimal increase in body weight, delayed growth and narrowing of epiphyseal discs in the tibia, reduced ash weight of the femur, and poor health necessitating termination of the experiment. Consum ption for 64 days of a diet ‘subminimal’ in phosphorus (0.21%, Ca/P ratio of 2.19) removed nearly 64% of the radiostrontium incorporated into the femur. Rats exhibited normal body weight gain and ash weight of the femur, but there were histopathological changes in the epiphyseal discs and trabeculae of the tibia. Although the low and ‘subminimal’ phosphorus diets were re latively effective in reducing the body burden of radiostrontium, the potential for adverse health effects from inad equate phosphorus intake reduces the value of this strategy.
Strontium-free Diet. In young rats maintained on a diet high in strontium for 28 days, returning to a normal diet low in strontium noticeably reversed the adverse effect on bone mineralization (Johnson et al. 1968). The reduced percentage of ash in bone began to show improvement after 2 weeks and was nearly normal after 5 weeks. In addition, the abnormal deposition of osteoid in vertebrae was repaired.STRONTIUM 173 3. HEALTH EFFECTS
3.12.3 Interfering with the Mechanism of Action for Toxic Effects

Hyperbaric oxygen therapy was successfully used to treat a case of scleral necrosis resulting from 90 Sr therapy following pterygiectomy (Green and Bra nnen 1995). Repeated hyperoxygenation enhanced neovascularization and regrowth of the scleral tissue that had become avascular and abnormally thin as a result of exposure to beta radiation.
In tests on irradiated skin of guinea pigs, anti-infl ammatory compounds reduced the permeability of the dermal vasculature to plasma proteins by up to 30% (Song et al. 1968). However, since drug treatment was administered both before and after irradiation, th is study is not definitive proof of the efficacy of these compounds.

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 strontiu m is available. Where adequate information is not available, ATSDR, in conjunction w ith the National Toxicology Program (NTP), is required to assure the initiation of a program of research designed to determin e the health effects (and techniques for developing methods to determine such health effects) of strontium.
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 substan ce-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 id entified data needs will be evaluated and prioritized, and a substance- specific research agenda will be proposed.

3.13.1 Existing Information on Health Effects of Strontium

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals are summarized in Figure 3-9 for stable strontium and in Figure 3-10 for radioactive strontium. The purpose of these figures is to illustrate the existing information concerning the health effects of strontium. Each dot in the figure indicates that one or more studies pr ovide information associated with that particularSTRONTIUM 174 3. HEALTH EFFECTS 

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ExternalSTRONTIUM 176 3. HEALTH EFFECTS 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

In the following discussion, the toxicity (carcinogenicity ) of inhaled strontium chromate is omitted, since its adverse effects are attributed to hexavalent chro mium (see Section 3.2.1.7). Unless otherwise stated, the proposed investigations refer to studies of health effects in animals.
Acute-Duration Exposure.

Stable Strontium. Information from injection and kinetic studies in humans and oral, inhalation, and injection studies in animals indicates that bone is the pr imary target tissue of absorbed stable strontium. The acute database is inadequate for deriving MRLs. A data need for an acute inhalation study is discussed under Data Needs for Immunotoxicity. Animal studies have shown that stable strontium is not toxic at low doses (Kroes et al. 1977). On the other hand, high oral doses of stable strontium can severely depress the serum levels of 1,25-dihydroxyvitamin D in rats within a week, which has an adverse effect on calcium absorption (Armbrecht et al. 1979, 1998). Of the two available acute oral toxicity studies, one employed ineffective doses, and the other used a single high dose (Kroes et al. 1977; Kshirsagar 1976).

Thus, there is a need for an acute-duration oral st udy that would enable an analysis of dose-response relationships with regard to strontium ingestion and skeletal effects. Consideration should be given to comparing the relative effects of different forms of strontium (e.g., strontium chloride, strontium carbonate, strontium phosphate), and different modes of delivery (in food, in water), since these factors probably affect the bioavailability of ingested strontiu m. In addition, such a study could provide a basis for investigating possible biomarkers of effect (by m onitoring changes in the serum levels of vitamin D, 1,25-dihydroxyvitamin D, calcium, phosphorus, phosphatases, and other biomarkers) that could be used to characterize the early systemic response to strontium.STRONTIUM 177 3. HEALTH EFFECTS
Radioactive Strontium. Acute-duration inhalation or oral administ ration of radioactive strontium caused adverse effects. No dermal st udies were conducted. Rather, external studies used solid strontium apposed to the skin, which did not provide an opp ortunity for dermal absorption (Hoshino and Tanooka 1975; Randall and Coggle 1995; Song et al. 1968). In dogs, inhalation of relatively insoluble particles of radiostrontium resulted in prominent damage to pul monary tissues (Benjamin et al. 1975, 1976c; Snipes et al. 1979). Inhalation or ingestion of soluble radi ostrontium resulted in radiostrontium incorporation into bone and subsequent chronic radiation exposure of the surrounding tissues (inhalation: Gillett et al. 1987a, 1987b; oral: Casarett et al. 1962; Cragle et al. 1969). No inhalation or oral MRLs could be derived because the effects of exposure, even at the lowest levels, were serious. There is a need for an inhalation study using soluble strontium aerosols that would test a lower range of exposure levels than had previously been employed, primarily to assess the effects on the lymphocyte population; existing studies found chronic depression of lymphocyte numbers even at the lowest concentrations. Existing acute-duration oral studies are inadequate because either the study size was small and/or a single dose was used. There is a need for an acute oral multi-dose study, in particular, one comparing effects in young and adult animals, primarily for the purpose of relating genotoxicity to dosage. Dermal studies using strontium applied to the skin should be conducted to evaluate systemic effects that might occur following the kind of exposure that might occur in the vicinity of a hazardous waste site.
Intermediate-Duration Exposure.

Stable Strontium. An intermediate oral MRL was derived on th e basis of a study that showed young rats were more susceptible to adverse skeletal effects (ri ckets) than adults (Storey 1961). A considerable number of studies support this finding (see Section 3.2. 2.2 Musculoskeletal Effect s). No intermediate inhalation study was located. The necessity for an in termediate inhalation study should be evaluated once the data from the proposed acute inhalation study are assessed. No intermediate dermal study was located, but given the low cytotoxicity of stable strontium, such a study does not seem necessary.

Radioactive Strontium. No intermediate-duration inhalation, oral , or dermal studies were located. There is a need for intermediate-duration inhalation and oral studies, using low levels of exposure, to help define the risk associated with longer-term exposures, such as may occur from radiostrontium releases at nuclear fuel reprocessing facilities or nuclear power plants into air, into drinking water, or settling onto croplands. The primary focus of these studies should be hematological and immunological effects. Some information is available in intermediate external st udies, but in these, radiostrontium was not applied to the skin in a form that could be absorbed. Dermal studies need to be conducted to assess the systemic risks that children might incur by playing in the open after radiostrontium has settled on the ground.STRONTIUM 178 3. HEALTH EFFECTS

Chronic-Duration Exposure and Cancer.

Stable Strontium. There were no adequate chronic-duration stud ies of stable strontium effects in humans or animals. In a review paper, Skoryna (1981a) brie fly mentioned that oral administration of low doses of strontium had no adverse effect in rats over a 3-year period or over several generations, but provided no experimental details. A chronic-duration oral study would be useful for evaluating the long-term health effects of strontium ingestion. Some considera tion should be given to comparing the effects of compounds having different chemical properties (e.g ., strontium chloride, strontium carbonate, and strontium phosphate).
Although there are no chronic studies of stable strontium exposure, the rest of the database provides no evidence to suspect that stable strontium might be carcinogenic. It does not appear that a long-term carcinogenesis study would prove useful.

Radioactive Strontium. There is no chronic inhalation study for radioactive strontium. Such a studyshould be considered after an intermediate inhalation study is conducted, as a means of evaluating longterm exposure to low levels of radioactivity on th e immune system. The Techa River cohort represents the major source of information regarding the health effects of chronic exposure to radiostrontium: suppression of hematopoiesis and immune function (Akleyev et al. 1995). Chronic oral administration of radioactive strontium has been shown to suppress hematopoiesis and lymphocyte function in animals (Dungworth et al. 1969; Howard 1970). Since these eff ects were observed at the lowest exposure levels, chronic oral studies using even lower exposure levels are needed to evaluate potential adverse effects on the immune system. A single clinical study repor ted late-developing changes in the skin following chronic application of solid strontium (external exposure) to treat hemangioma (Bekerus 1970). It is not clear that the database needs a chronic dermal study of radiostrontium applied to the skin in a form that might be absorbed, since significant dermal absorption of strontium only occurs through abraded skin (see Section 3.5.1.3).

An increase in the incidence of le ukemia has been reported in the T echa River cohort, which received doses of 10 rem (0.1 Sv) or more from radioactive strontium (Kossenko 1996; Kossenko et al. 2000). Chronic oral administration of radioactive stron tium was shown to increase the incidence of boneassociated cancer in animals (Book et al. 1982; Clarke et al. 1972; Finkel et al. 1960; White et al. 1993; Zapol’skaya et al. 1974). No chronic inhalation or dermal studies were located. Since the dynamics of strontium uptake into bone are known, estimations of the risk of cancer in humans following inhalationSTRONTIUM 179 3. HEALTH EFFECTS exposure can be derived using dose-response data fro m the Techa River cohort and the beagle inhalation studies. There is no realistic scenario for chronic dermal exposure at damaging levels.
Genotoxicity.

Stable Strontium. In vitro studies listed in Table 3-6 demonstrate a lack of adverse effects from treatment with stable strontium. A single gavage study in mice is the only evidence for genotoxicity of stable strontium (at doses of 140–1,400 mg/kg), but it seems likely that the bolus delive ry may have influenced the outcome (Ghosh et al. 1990). None of the intermediate-duration studies (no chronic study is available) presented any evidence of effects that could be attributed to genotoxicity. Additional genotoxicity studies on stable strontium appear to be unnecessary.

Radioactive Strontium. The genotoxicity of radioactive strontium is well-documented. In the Techa River cohort, an elevated frequency of stable chromo somal translocations was observed (Bauchinger et al. 1998). Other evidence includes in vitro cytogenetic studies (see Table 3–6), and, by implication, the increased cancer rates that were observed in most inv estigations (see Data Needs for Cancer). However, the mechanism of radiostrontium genotoxicity (i.e., the specific DNA alterations that occur following exposure) has yet to be characterized. Recently, Sutherland et al. (2000a, 200 0b) developed molecular biological assays for characterizing clustered DNA le sions caused by exposure to gamma radiation. If such a technique were to be developed for radios trontium-exposed cells, it might provide a means of recording molecular damage.
Reproductive Toxicity.

Stable Strontium. There is no evidence regarding the effect of stable strontium on reproduction, but levels of exposure possible by inhalatio n or dermal routes are not likely to be harmful. Stable strontium was found to have beneficial effects when it was u sed in solutions designed for testing the functional capacity of human spermatozoa in vitro (Mortimer 1986; Mortimer et al. 1986). The possible consequences of excess strontium ingestion on reprod uction need to be explor ed. Such experiments should compare the relative toxicity of stable strontium compounds that have different properties and may have different rates of absorption (e.g., strontium chloride, strontium carbonate and strontium phosphate).

Radioactive Strontium. In the Techa River cohort, average radiat ion doses to the gonads of up to 74 rem (0.74 Sv) had no effect on birth rate, fertility, or th e incidence of spontaneous abortions (Kossenko et al. 1994). However, the contribution of radiostrontium to the gonadal radiation dose is likely to have beenSTRONTIUM 180 3. HEALTH EFFECTS negligible compared to that of external gamma radiation. Multigenerational oral studies in animals demonstrated a dose-dependent effect of radioactive strontium on reproduction. In pigs, only the highest doses affected fetal survival, and in those treated as a dults, there was no effect on litter size, percentage of stillborn, or birth weight (Clarke et al. 1970, 1972; McClellan et al. 1963). Injection studies have reported a higher incidence of adverse reproductive effects, perh aps because of the higher dose levels. Injection of male mice prior to mating increase the rate of fetal death, and there is some evidence that radioactive strontium selectively accumulates in the testis (Reddi 1971). Injection of pregnant female mice reduced the reproductive capacity of female offspring, reducing the numbers of oocytes of all stages in the ovary (Rönnbäck 1981a, 1981b). Thus, the fetal reproductive system appears to be vulnerable to radioactive strontium. Further studies to evaluate the dose-res ponse of gonadal effects, including cytogenetic aspects, would appear to be warranted.
Developmental Toxicity.

Stable Strontium. The main developmental effect of stable strontium is impaired bone development (rickets) following oral exposure at high doses (J ohnson et al. 1968; Kshirsagar 1976; Marie and Hott 1986; Neufeld and Boskey 1994; Ögzur et al. 1996; Reinholt et al. 1984; Storey et al. 1961, 1962). Inhalation and dermal exposures are unlikely to be hi gh enough to have an adverse effect. The oral developmental toxicity studies have concentrated on the initiation of rickets in young children or young animals during the postnatal or juvenile periods, but none have addressed the effect of maternal exposures on the fetus during gestation or on the neonate during lactation. The relative effectiveness of strontium compounds that have different properties (e.g., str ontium chloride, strontium carbonate, and strontium phosphate) needs to be evaluated with regard to maternal absorption, pl acental transfer, fetal toxicity, and postnatal toxicity during lactation. In addition, behavioral testing should be conducted on the young animals to determine whether there are any neurological consequences of fetal exposure to excess stable strontium.

Radioactive Strontium. In the Techa River cohort, individuals who were exposed to high levels of radiostrontium as teenagers had a higher frequency of st able transformations than those who were adults at the time (Bauchinger et al. 1998); the differences were attributed to increased skeletal incorporation of radiostrontium in the young. The progeny of the expo sed cohort showed an elevated incidence of adverse pregnancy outcomes (mortality from developmenta l anomalies, chromosomal anomalies, labor complications, and other unspecified perinatal cond itions), but no increase in the incidence of cancer (Kossenko et al. 1994). Multigenerational oral studies in animals showed no teratogenic effect of radioactive strontium administered from the time of c onception, but showed reduced survival of the F1STRONTIUM 181 3. HEALTH EFFECTS generation because of an increased incidence of bone- associated cancer (Clarke et al. 1970; Finkel et al. 1960; McClellan et al. 1963). Injection of high doses of radioactive strontium during gestation had teratogenic effects on the fetus, primarily skeletal abnormalities (Hopkins et al. 1967; Finkel and Biskis 1969). Injections had qualitatively different eff ects depending on the day of gestation, because of regional differences in rates of bone mineralization during gestation. More information is needed regarding the effect of the timing of maternal expos ure relative to developmental stages. In addition, developmental studies that evaluate neurological effects in the offspring are needed.
Immunotoxicity.

Stable Strontium. There is no evidence that oral or dermal exposures to stable strontium affect the immune system. However, one case report described an anaphylactic reaction to inhalation of smoke that contained ~30% strontium among other irritants (Federman and Sachter 1997). Strontium’s possible involvement is supported by reports that excess st rontium elicits degranulation of mast cells in vitro , causing histamine release (Alm and Bloom 1981a, 1981b; Atkinson et al. 1979; Foreman 1977; Foreman and Mongar 1972a, 1972b; Foreman et al. 1977). For this reason, a short-term inhalation study would help to determine whether strontium by itself can e licit anaphylaxis and, if so, identify the effective concentration levels.

Radioactive Strontium. There is evidence that immunosuppression, resulting from irradiation of bone marrow, may occur in humans and animals follo wing absorption of radioactive strontium. Immunological effects were noted in the Techa Rive r cohort, which received relatively high radiation doses to bone marrow following ingestion of food and water contaminated with radiostrontium (Akleyev et al. 1995). In animal studies, the lowest applied inhalation or oral doses were reported to result in lymphopenia lasting as long as 2 years (Benjamin et al. 1976c; Howard 1970; Jones et al. 1976). There appears to be a need for studies that examine the effect of a lower range of exposures on immune function. Another reason for such studies comes fro m the reports demonstrating that NK cells may be preferentially eliminated following injection of 89 Sr or 90 Sr (Emmanuel et al. 1981; Gidlund et al. 1990; Haller and Wigzell 1977; Wiltrout et al. 1989), with the result that the organism’s ability to defend against lymphoid tumors is impaired (Haller and Wigzell 1977; Luevano et al. 1981). The implication is that reduced cellular defenses may compound the effect of genotoxicity, increasing the risk of cancer. However, it is not known whether NK cells are equally vulnerable at lower exposure levels.STRONTIUM 182 3. HEALTH EFFECTS Neurotoxicity.

Stable Strontium. The only evidence for neurotoxicity of stable strontium is a report of hindlimb paralysis following intermediate-duration ingestio n of excess strontium (Johnson et al. 1968). Given the absence of any other evidence for neurotoxicity, it is possible that, in this case, the paralysis may have resulted from compression of the hypertrophic epiphyseal cartilage, which was insufficiently mineralized to support the weight of the body. Additional neurot oxicity studies in adult animals for stable strontium do not appear to be necessary.

Radioactive Strontium. Neurological effects were reported in the Techa River population that was exposed to radiostrontium from water and food c ontaminated from releases at a plutonium processing plant between 1949 and 1956 (Akleyev et al. 1995). However, external gamma radiation, also released at this time, undoubtedly contributed to these effects. A single instance of epilepsy in a dog exposed by inhalation to a high concentration re presents the only evidence for neurotoxicity of radioactive strontium in animals (Gillett et al. 1987b). The authors conclu ded that epilepsy was not related to treatment. However, no studies have specifically measured behavioral or neurological deficits in exposed animals. The database needs studies that measure neurol ogical effects in offspring following exposure in utero and/or during lactation.
Epidemiological and Human Dosimetry Studies.

Stable Strontium. Strontium is ubiquitous in the environment, so everyone is exposed to it to some degree. Children who exhibit pica behavior or persons living in areas with high levels of strontium in the drinking water may have higher exposures than the ge neral population. A Turkish epidemiological study demonstrated a higher incidence of rickets among ch ildren living in rural communities whose diet was based on grain crops grown in local soil containing hi gh levels of strontium (Özgür et al. 1996). This study did not attempt to measure strontium levels in th e affected children. In addition, this study may not be directly applicable to conditions in the United States, given the different diet and the availability of foods from a wider geographic range. One epidemiologi cal study found that relatively high levels of strontium in the drinking water had no adverse effect on cardiovascular health, and, in fact appeared to have a beneficial effect on the rate of mortality from hypertension with heart disease (Dawson et al. 1978). Information regarding the higher levels in drinking water could be used to design animal experiments for evaluating chronic exposure effects, wh ich are currently lacking in the database. In one case-control study that tried to account for the higher incidence of liver cancer in 1984 on ChongmingSTRONTIUM 183 3. HEALTH EFFECTS Island in China, no association was found with the levels of stable strontium detected in hair (Wang et al. 1990).

Radioactive Strontium. Dosimetry data are available for approximately 16,000 members of the Techa River population that was exposed to radiostrontium because of releases from a plutonium processing plant between 1949 and 1956 (Kossenko et al. 1997). Since exposure levels in this population were 30– 100 times higher than the maximum exposure from global fallout, this cohort represents the largest group of subjects available for examining health effects of chronic radiation exposure. Subpopulations living in certain regions within the Techa River area receiv ed different levels of exposure, so that dose relationships are being established for health effects. In addition, investigators ha ve been able to examine the effect of developmental age at the time of expos ure on health outcomes. Although individuals were exposed to multiple sources of radiation during the first years (including 137 Cs bound in soft tissues), in recent decades, their radiation exposure was primarily from 90 Sr incorporated into bone. The health effects have been similar to those observed for anim als exposed chronically to radiostrontium, and have included suppression of hematopoeisis and leukemia (Akleyev et al. 1995; Kossenko 1996; Kossenko et al. 1997, 2000).
A Danish epidemiological study found no associati on between the incidence of thyroid cancer in Denmark between 1943 and 1988 and the leve ls of skeletal incorporation of 90 Sr from fallout (Sala and Olsen 1993). However, the reason for this study is uncer tain since strontium is not taken up preferentially in the thyroid, unlike iodine, which is incorporated into thyroid hormones (T 3 and T 4 )

. A Scottish epidemiological study found no evidence for in creased risks of total cancers, leukemia and nonHodgkin’s lymphoma, or acute myeloid leukemia for cohorts of children born during the period of highest fallout (radiostrontium) exposure (Hole et al. 1993). The few cases of bone tumors showed a nonsignificant increase for children born during the ‘hi gh risk’ period. The reduction in fallout from above-ground nuclear weapons testing has reduced the exposure of the general population to radioactive strontium. Currently, populations working at or living in the vicinity of nuclear power plants or reprocessing facilities might have higher than background exposures. Workers at the facilities may have less exposure because protective equipment and safety pr ocedures are in use. Environmental levels of radiostrontium that are measured near these facilities could be used to guide exposure levels in the toxicity experiments proposed above.STRONTIUM 184 3. HEALTH EFFECTS Biomarkers of Exposure and Effect. Exposure.

Stable Strontium. Levels of stable strontium can be measured in blood or urine to determine exposures of any duration. Within a few days, most of the re tained strontium is found in bone, but because of bone remodeling, strontium will be released over time and be detectable in blood and urine. Inductively coupled plasma mass spectroscopy (ICP-MS) was able to detect strontium in amniotic fluid and maternal plasma at levels of 0.03 and 0.06 ppb, respectively, in untreated humans (Silberstein et al. 2001). The sensitivity of this method is adequate to detect unusual accumulations of strontium. No additional biomarkers of exposure to stable strontium appear to be needed.

Radioactive Strontium. Exposures to radioactive strontium can be determined readily by measuring levels of radioactivity in blood or urine by liquid scintillation counting techniques. In addition, whole body counters can determine the level of radiostrontium retained in the skeleton. There appears to be no need for additional biomarkers of exposure to radioactive strontium.

Effect.

Stable Strontium. The typical signs of rickets (craniotabes, rachitic rosary, bulging at the wrist, genu valgus, genu varus, and delayed cl osure of the fontanelles) represent biomarkers of exposure to excess stable strontium in children (Özgür et al. 1996). Excess strontium ingestion has been shown to depress serum levels of 1,25-dihydroxyvitamin D in rats (A rmbrecht et al. 1998). Since vitamin D insufficiency by itself can also cause rickets, measurement of bot h vitamin D levels and strontium levels in serum would be required to determine the role of stron tium in a particular case. As mentioned above (Data Needs for Acute-Duration Studies), the proposed toxicity studies could be used to develop biomarkers for early effects following exposure to excess strontium. An array of biomarkers could possibly be developed to monitor the course of pathology before the signs of rickets fully appear.

Radioactive Strontium. A reduction in blood cell counts is a biomarker of effect for radioactive strontium. However, many other conditions can have the same result. Cytogenetic analysis of blood cells can reveal whether exposure to radioactive stron tium has been sufficient to cause genotoxicity (see Table 3-5). A new method for evaluating DNA damage in cells exposed to gamma radiation has been developed using molecular biological techniques (Sutherland et al. 2000a, 2000b). It may be possible toSTRONTIUM 185 3. HEALTH EFFECTS develop such an assay for evaluating exposure to radi oactive strontium, which would also specifically identify the kind of DNA lesions produced.
Absorption, Distribution, Metabolism, and Excretion. More information is needed comparing the relative rates of absorption for different chemical forms of strontium that may vary in solubility. Solubility differences would affect the duration of re sidence of particles in the lung, which might have significant effects in the case of radiostrontium expos ure. A comparison of gastrointestinal absorption rates for different chemical forms and for different vehicles of administration (food or water) has not been conducted. Results of such studies would help predic t outcomes following different kinds of exposure. Nothing is known regarding dermal absorption of strontium taken up in soil, which is a type of exposure that children would be likely to encounter. Howeve r, studies of dermal absorption from soil would be of low priority given that significant dermal absorpti on of soluble strontium only occurred through abraded skin (See Section 3.5.1.3) and the amounts available from dry soil would be biologically insignificant under any realistic exposure scenario. Absorbed stro ntium is understood to distribute primarily to the bone and to be retained longer in the young than in ad ults. The combination of the ICRP PBPK model for strontium and animal-based studies on Observed Ratios of strontium and calcium (Comar and Wasserman 1964) is sufficient to estimate strontium turnover du ring pregnancy and lactation and in the elderly.
Comparative Toxicokinetics. The target organ for stable and radi oactive strontium is the same in humans and animals, namely, bone. Young rats can ser ve as a model for children’s exposures, but adult rats are less suitable, since the ep iphyseal plate remains cartilaginous into adulthood (Leininger and Riley 1990). For this reason, adult rats could be expect ed to incorporate proportionally higher levels of strontium than adult humans. Furthermore, remodeling of bone in rats is not analogous to that in humans. The rat would probably not be a good model for evalua ting placental transfer of strontium to the fetus because of differences in placental tissue organization.
Methods for Reducing Toxic Effects. Both stable and radioactive str ontium are readily absorbed by the intestine, apparently through calcium transporter elements (Bianchi et al. 1999; Blumsohn et al. 1994; Milsom et al. 1987; Reid et al. 1986; Sips et al . 1994). Numerous methods have been tested for alleviating the effects of exposure to strontium (see S ection 3.12). Oral administration of alginates with a high guluronic acid content or a single dose of aluminum phosphate antacid gel are currently recommended for reducing peak absorption of strontiu m shortly after exposure. The toxicities of excess stable and radioactive strontium are related to thei r rapid sequestration into bone. Most strategies for treatment involve high calcium in co mbination with other agents to enhance the replacement of strontiumSTRONTIUM 186 3. HEALTH EFFECTS in bone by calcium. There does not appear to be a need for new studies at this time. However, as mentioned in Section 3.6.2, polymorphisms in gene tic factors that may affect rates of strontium absorption and bone mineralization are currently under investigation and potentially could regulate the effectiveness of treatment. If relevant polymorphi sms are identified, then the existing methods for reducing toxic effects should be tested using stable strontium tracers to determine whether genetic factors affect the outcome of treatment.
Children’s Susceptibility.

Stable Strontium. The effect of excess stable strontium ingestion on bone development is well documented: strontium-induced rickets has been repor ted in children and young animals. The particular vulnerability of children, because of the immaturity of the skeleton, is well understood. The intestinal rate of strontium absorption and the retention of stro ntium in the developing bone is known to be higher in infants and children than in adults. It is known that the fetus can be exposed to strontium following previous maternal exposure, but adequate informa tion regarding changes in the rates of strontium mobilization from the maternal skeleton or changes in rates of intestinal absorption of strontium during the course of pregnancy is lacking. There is a need for studies to develop this information to fill in gaps in existing PBPK models for strontium; this effort would have the additional be nefit of being applicable to other bone-seeking radioisotopes. Another issue to be considered is the relative bioavailability of strontium in the different chemical compounds (e.g ., strontium chloride, strontium carbonate, strontium phosphate). Since children may be exposed to strontium by pica behavior, there is a need for animal studies that would investigate variations in absorption (bioavailability) when stro ntium is ingested in the form of soil.
Biomarkers of exposure and effect are established fo r children. Since the primary biomarker of effect, rickets, is a late-stage phenomenon, it would be useful to precisely establish a constellation of biomarkers that would identify a precursor condition. Such marker s might include relative serum levels of vitamin D, calcium, phosphorus, and alkaline phosphatases, as well as strontium itself. The alginate method for reducing peak absorption of strontium has been validated in children (Sutton et al. 1971a).

Radioactive Strontium. Numerous oral exposures have demonstrated the enhanced risk of reproductive effects and cancer in animals exposed to radiostrontium in utero or during lactation. At the higher levels used in injection studies, teratogenic effects were observed on bone development. The possibility of neurological deficits from gestational exposure to radioactive strontium, re sulting from radiostrontium incorporation into the cranium and subsequent irradi ation of adjacent brain tissue, should be explored.STRONTIUM 187 3. HEALTH EFFECTS
The toxicokinetic and bioa vailability issues mentioned in the previ ous section on stable strontium apply to radioactive strontium. Low-level exposure studies should be conducted to evaluate possible impairment of immune function, which results from irradiation of bone marrow by radiostrontium incorporated into bone and which has been observed in animal studies at higher levels.
Radioactive strontium is its own biomarker of exposure in children and adults. The primary biomarkers of effect, also applicable to children and adults, ar e a reduction in lymphocyte and other blood cell counts, which closely match the intensity of exposure. The alginate method for reducing peak absorption, described above, has been validated for children (Sutton et al. 1971a). It is not clear whether another recommended treatment, a single dose of aluminum phosphate antacid gel, would be safe for children, since it can have toxic effects in children at high doses. Either method would only be effective if administered very soon after exposure (within an hour).
Data needs relating to both prenatal and childhood exposures and developmental effects expressed either prenatally or during childhood, are discussed in deta il in the Developmental T oxicity subsection above.
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

Stable Strontium. Two currently funded research programs that specifically mention stable strontium are probably using it as a surrogate for calcium in physiological experiments. In a study sponsored by the National Institute of Mental Health, Dr. J.A. Dzubay (1997) of the Oregon Health Sciences University is conducting in vitro experiments on the activity of NMDA (N-methyl D-aspartate) channels in the hippocampus; these are membrane channels controlled by NMDA receptors that regulate the influx of calcium into neurons. In work funded by the Nationa l Institute of Neurological Disorders and Stroke, Dr. David Lovinger (1999) of Vanderbilt University Me dical Center is studying glutamatergic and dopaminergic synaptic transmission in the neostriatu m. In a third study, sponsored by the National Institute of General Medical Scie nces, Dr. J. Bell (1998) of Fayetteville State University in North Carolina is examining the effect of metal salts on th e fidelity of DNA synthesis. It appears that this research may provide additional genotoxicity information regarding stable strontium.STRONTIUM 188 3. HEALTH EFFECTS
Radioactive Strontium. The single largest population available for studying the long-term health effects of radiostrontium is the Techa River cohort that w as exposed from contaminated drinking water and food following releases from a plutonium processing plant between 1949 and 1956 (Akleyev et al. 1995; Bauchinger et al. 1998; Kossenko 1996 ; Kossenko et al. 1994, 1997, 2000; Shagina et al. 2000; Tolstykh et al. 1998). In addition to the studies reviewed in this toxicological profile, further analysis of this population is expected to continue under the auspi ces of the Urals Research Center for Radiation Medicine.
Additional information regarding the toxicity of ra dioactive strontium is likely to emerge from studies related to the therapeutic use of strontium isotopes. In programs funded by the National Heart Lung and Blood Institute, Dr. Sou-Tung Chiu-Tsao (1999) of th e Beth-Israel Medical Center, New York, and Dr. Ravinder Nath (1999) of Yale Universi ty Medical Center, are investigating 90 Sr along with other isotopes for intravascular brachytherapy delivered at the time of angioplasty. Dr. Carl J. Pepine (1998) of the Department of Veterans Affairs Me dical Center, Gainesville, Florida, is conducting a clinical trial to evaluate a commercial product for intravascular brachytherapy. Dr. Timothy Kuzel (1999) of the Department of Veterans Affairs Medical Center, Ch icago, Illinois, is conducting a Phase I/II trial of 89 Sr in conjunction with mitoxantrone a nd hydrocortisone in the treatment of bone metastases in patients with hormone-refractory prostate cancer. In work funded by the National Center of Research Resources, Dr. Franco Muggia (1999) of the New York University Medical Center is conducting an open label Phase II study to evaluate the effect and toxicity of Doxil, a liposomal encapsulated doxirubicin, and 89 Sr in combination for treating hormone-refractory metastatic prostate cancer. In a study sponsored by the National Institute on Deafness and Other Communication Disorders, Dr. Gina M. Nelson (1999) of the University of Alabama at Birmingham is conducting la boratory tests in rodents in order to develop a radiation treatment for cancer of the mouth that w ill be less likely to destroy the sense of taste than current procedures. Radiostrontium will be held in a device to expose the tongue to beta radiation.STRONTIUM 189



### 4. CHEMICAL, PHYSICAL, and RADIOLOGICAL INFORMATION

4.1 CHEMICAL IDENTITY
Strontium is an alkaline earth element in Group IIA of the periodic table. Because of its high reactivity, elemental (or metallic) strontium is not found in na ture; it exists only as molecular compounds with other elements. The chemical information for elemental strontium and some of its compounds is listed in Table 4-1. Radioactive isotopes of strontium (e.g., 89 Sr and 90 Sr, see Section 4.2) are the primary cause of concern with regard to human health (see Chapter 3).

4.2 PHYSICAL, CHEMICAL, AND RADIOLOGICAL PROPERTIES
The physical properties of strontium metal and selected strontium compounds are listed in Table 4-2. The percent occurrence of strontium isotopes and the radi ologic properties of strontium isotopes are listed in Table 4-3.
Strontium can exist in two oxidation states: 0 and +2. Under normal environmental conditions, only the +2 oxidation state is stable enough to be of practi cal importance since it readily reacts with both water and oxygen (Cotton and Wilkenson 1980; Hibbins 1997). There are 26 isotopes of strontium, 4 of which occur naturally. The four stable isotopes, 84 Sr, 86 Sr, 87 Sr, and 88 Sr, are sometimes referred to as stable strontium. The most important radioactive isotopes, 89 Sr and 90 Sr, are formed during nuclear reactor operations and during nuclear explosions by the nuclear fission of 235 U, 238 U, or 239 Pu. For example, 235 U is split into smaller atomic mass fragments such as 90 Sr by a nuclear chain reaction initiated by high energy neutrons of approximately 1 million electron volts (or 1 MeV). These smaller atomic mass fragments are referred to as fission by-products. This process is illustrated below:

235 U + 1 n 6 90 Sr + 89 Sr + other fission by-products

90 Sr is the more dangerous of the two isotopes due to its long half-life (29 years). 90 Sr decays by emission of a beta-particle with a maximum energy of 0.546 MeV and the creation of an 90 Y isotope, or progeny product. Unlike other radioactive isotopes that decay by beta-emission, 90 Sr does not directly release high energy photons or gamma-ray radiation ( γ ). However, the progeny product of 90 Sr, 90 Y, is both a betaparticle (2.28 MeV maximum energy) emitter and to a minor degree for 0.02% of all disintegrations, aSTRONTIUM 190 4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION 

### Table 4-1. Chemical Identity of Strontium and Strontium Compounds
Strontium Strontium Strontium Strontium Property Strontium (0) acetate carbonate chloride chromate Chemical formula Sr C 4 H 6 O 4 Sr CO 3 Sr Cl 2 Sr CrH 2 O 4 Sr Chemical structure Sr Sr(O 2 CCH3) 2 SrCO 3 SrCl 2 SrCrO 4 O O O - O Sr +2 Sr +2 O Cr O Sr O - O Cl - Cl -

- O O O - Sr +2 Sr +2 Synonyms None Strontium Carbonic acid, Strontium Chromic acid, diacetate strontium salt dichloride strontium salt (1:1); strontianite Trade names No data No data No data No data No data Identification numbers CAS registry 7440-24-6 543-94-2 1633-05-2 10476-85-4 7789-06-2 NIOSH RTECS WK7849000 AJ4725000 No data WK8400000 GB3240000 EPA hazardous No data No data No data No data D007 waste

OHM/TADS No data No data No data No data No data DOT/UN/NA/IMO UN 1383/IMO No data No data No data 9149/NA 9149 shipping 4.2 HSDB 2545 No data 5845 No data 2545 NCI No data 75799 112224 No data No data STCC No data No data No data No data 49 633 77STRONTIUM 191 4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION


### Table 4-1. Chemical Identity of Strontiu m and Strontium Compounds
Strontium Strontium Strontium Strontium Strontium Property fluoride hydroxide nitrate phosphate oxide Chemical formula F 2 Sr H 2 O 2 Sr N 2 O 6 Sr O 8 P 2 Sr3 OSr Chemical structure SrF 2 Sr(OH) 2 Sr(NO 3 ) 2 Sr 3 (PO 4 ) 2 SrO O O N + P O

- O O - O O Sr +2 Sr +2 Sr +2 Sr +2 Sr +2 Sr + S r O F - F - OH - OH -

- O O O N +

- O O P O O Synonyms Strontium Strontium Nitrate de No data Strontia, difluoride hydrate strontium strontium (French); monoxide Nitric acid, strontium salt; strontium dinitrate; strontium(II) nitrate (1:2) Trade names No data No data No data No data No data Identification numbers CAS registry 7783-48-4 18480-07-4 10042-76-9 7446-28-8 1314-11-0

NIOSH WK8925000 WK9100000 WK9800000 No data No data RTECS EPA hazardous No data No data No data No data No data waste OHM/TADS No data No data No data No data No data DOT/UN/NA/IMO No data No data UN 1507 No data No data shipping Oxidizer IMO 5.1 HSDB No data No data No data No data No data NCI No data No data No data No data No data STCC No data No data 49 187 54 No data No data ­

­ ­

­

­

­STRONTIUM 192 4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION 

### Table 4-1. Chemical Identity of Strontium and Strontium Compounds
Strontium Strontium Strontium Strontium Property peroxide sulfate sulfide titanate Chemical formula O 2 Sr O 4 SSr SSr O 3 SrTi Chemical structure SrO 2 SrSO 4 SrS SrTiO 3 O O Sr +2 O S O - Ti S r S

- O O -

- O O O - Sr +2 Sr +2 Synonyms Strontium Celestine, Strontium No data dioxide celestite monosulfide Trade names No data No data No data No data Identification numbers CAS registry 1314-18-7 7759-02-6 1314-96-1 12060-59-2 NIOSH RTECS WL0100000 No data WL0400000 No data EPA hazardous No data No data P107/D003 No data waste OHM/TADS No data No data No data No data DOT/UN/NA/IMO UN 1509 No data No data No data shipping Oxidizer IMO 5.1 HSDB 788 No data 12 No data NCI No data No data No data No data STCC 49 187 55 No data No data No data 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 = Nationa l Cancer Institute; NIOS H = National Institute for Occupational Safety and Health; OHM/TADS = Oil and Ha zardous Materials/Technical Assistance Data System; RTECS = Registry of Toxic Effects of Chemical Substances; STCC = Standard Transportation Commercial Code Source: ChemFinder 2002; HSDB 2002; Lide 2000STRONTIUM 193 4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION 

### Table 4-2. Phys ical and Chemical Properti es of Strontium and Strontium Compounds a

Property Strontium (0) Strontium acetate b,c Strontium carbonate b,c Strontium chloride c Strontium chromate Molecular weight, 87.62 205.71 147.63 158.53 203.62 g/mole Color Pale yellow White White White Yellow Physical state Melting point Solid 777 °C Solid Decomposes Solid 1,497 °C d Solid 875 °C Solid No data Boiling point 1,382 °C Not applicable Decomposes at 1,250 °C No data Density, g/cm 3 2.64 2.099 1,100 °C 3.5 3.05 3.90 Odor No data No data Odorless No data No data Odor threshold: Water No data No data No data No data No data Air No data No data No data No data No data Solubility: Water Decomposes 369 g/L (cold) 0.11 g/L at 538 g/L 30 g/L at 18 °C at 20 °C 100 °C Organic Alcohol Alcohol, No data Alcohol, Acetic acid solvents(s) slightly acetone
Partition coefficients: Log K ow No data No data No data No data No data Log K oc No data No data No data No data No data Vapor pressure 5 mmHg No data No data No data No data at 847 °C Henry’s Law No data No data No data No data No data constant Autoignition No data No data No data No data No data temperature Flashpoint No data No data No data No data No data Flammability limits No data No data No data No data No data Explosive limits No data No data No data No data No dataSTRONTIUM 194 4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION 

### Table 4-2. Phys ical and Chemical Properti es of Strontium and Strontium Compounds a

Property Strontium fluoride e,c Strontium hydroxide c Strontium nitrate c Strontium phosphate f Strontium oxide c Molecular weight, g/mole Color Physical state Melting point Boiling point Density, g/cm 3 Odor Odor threshold: 125.62 White Solid Decomposes >100 °C 2,489 °C 4.24 No data 121.64 Colorless Solid 375 °C No data 3.63 No data 211.63 Colorless Solid 570 °C 645 °C 2.98 Odorless 452.80 White Solid No data No data No data No data 103.62 Yellow Solid 2,430 °C 3,000 °C 4.56 No data
Water Air No data No data No data No data No data No data No data No data No data No data Solubility: Water Organic solvents(s) 0.12 g/L at 18 °C Alcohol, acetone 470 g/L at 100 °C Alcohol 790 g/L at 18 °C Slightly in alcohol and acetone Insoluble No data 229 g/L at 100 °C Slightly in alcohol

Partition coefficients: Log K ow Log K oc No data No data No data No data No data No data No data No data No data No data Vapor pressure Henry’s Law constant 1 mmHg at 921 °C No data No data No data No data No data No data No data No data No data
Autoignition temperature 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 No data No data No data No data No data No data No data No data No dataSTRONTIUM 195 4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION 

### Table 4-2. Phys ical and Chemical Properti es of Strontium and Strontium Compounds a
Strontium Strontium Strontium Strontium Property peroxide sulfate sulfide titanate Molecular weight, 119.63 183.68 119.70 183.52 g/mole Color White Colorless Gray White Physical state Solid Solid Solid Solid Melting point Decomposes at 1,605 °C >2,000 °C No data 215 °C Boiling point No applicable No data No data No data Density, g/cm 3 4.56 3.96 3.70 4.810 Odor Odorless No data Hydrogen No data sulfide in moist air Odor threshold: Water Not applicable No data No data No data Air Not applicable No data No data No data Solubility: Water Decomposes 0.14g/L at Decomposes Insoluble 30 °C Organic Alcohol Slightly in No data No data solvents(s) alcohol
Partition coefficients: Log K ow No data No data No data No data Log K oc No data No data No data No data Vapor pressure No data No data No data No data Henry’s Law No data No data No data No data constant Autoignition No data No data No data No data temperature Flashpoint No data No data No data No data Flammability limits No data No data No data No data Explosive limits No data No data No data No data

a Source: HSDB 2002, unless otherwise stated b Merck 1989 c Lide 1995 d At 69 atmospheres pressure e Sigma-Aldrich 2000 f Lide 2000STRONTIUM 196 4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION


### Table 4-3. Percent Natural Oc currence and Radioact ive Properties of Isotopes of Strontium

Natural CAS registry abundance Beta energies, Isotope number (by weight %) MeV Half-life Activity, Ci/gram 84 Sr 15758-49-3 0.56 No data Stable No data

85 Sr 13967-73-2 No data 1.065 a 65 days 35,400

86 Sr 13982-14-4 9.86 No data Stable No data

87 Sr 13982-64-4 7.00 No data Stable No data

88 Sr 14119-10-9 82.58 No data Stable No data

89 Sr 14158-27-1 No data 1.495 51 days 27,800

90 Sr 10098-97-2 No data 0.546 29 years 143

91 Sr 14331-91-0 No data 2.707 10 hours 3.4x10 6

92 Sr 14928-29-1 No data 1.911 3 hours 1.1x10 7

a Decay mechanism by electron capture with gamma emission Source: Lide 19956 STRONTIUM 197 4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION beta-particle and gamma-ray (2.19 ke V) emitter. The decay product of 90 Y is 90 Zr, a stable isotope. The reaction is:

90 Sr (t 1⁄2 =29 yrs) 6 90 Y (t 1⁄2 =64 hrs) + β - (0.546MeV) 6 90 Zr (stable) + β - (2.28 MeV) (99.98 %)
90 Zr (stable) + β - (0.523 MeV) + γ (1.75 MeV)

89 Sr, like 90 Sr, is a fission product of 235 U, 238 U, or 239 Pu. It decays to 89 Y by emission of a beta-particle of 1.495 MeV 89 Y. 89 Sr has half-life of 51 days (Lide 1995).STRONTIUM 199



### 5. PRODUCTION, IMPORT/E XPORT, USE, AND DISPOSAL

5.1 PRODUCTION
Strontium is a naturally occurring element that makes up approximately 0.02–0.03% of the earth’s crust. In nature, strontium is present in igneous rocks in amounts averaging 375 ppm. The principal strontium minerals of commercial interest are celestite (SrSO 4 ) and strontianite (SrCO 3 ). Strontium is also a minor component of other mineral deposits and may occur in or near sedimentary rocks associated with beds or lenses of gypsum, anhydrite, and rock salt; in veins associated with limestone and dolomite; or dispersed in shales, marls, and sandstones. In the United States, there are deposits of celestite in Texas, Washington, Arizona, Ohio, and California. The U.S. Geological Survey (USGS) estimated U.S. resources of celestite and strontian ite at 2,500,000 tons, containing 1, 130,000 tons of strontium (Adams 1975). However, domestic deposits of these minerals ar e not economically exploitable, and strontium has not been mined in the United States since 1959.

Celestite is converted to SrCO 3 , the common commercial form of strontium. The black ash method (alternatively known as the calcining method) and the soda method (also known as direct conversion) are the two most common recovery techniques for stron tium. The black ash method produces chemical grade strontium carbonates, which are 98% strontium carbonate and 2% byproducts and impurities. The soda ash method produces technical grade strontium carbonates, containing at least 97% strontium carbonate. The black ash method is the preferred means of strontium carbonate production because it yields a highergrade product (USGS 1998).
During World War II, the U.S. government began stockp iling celestite for defense applications. In 1963, Congress determined that the stockpile was unnecessary , and by 1973, all of the stockpiled high-grade celestite was sold. The remaining low-grade celestite material, approximately 12,000 metric tons, has been listed by the Defense National Stockpile Center of the Defense Logistics Agency as valueless. In 1998, Congress authorized the remaining stockpile for disposal. The only U.S. strontium carbonate producer using celestite is the Chemical Products Corporation of Cartersv ille, Georgia. A number of U.S. companies manufacture strontium compounds from stron tium carbonate. Mallinkrodt Inc. of St. Louis, Missouri, produces strontium chloride, and Rockwood Pigments Corporation of Beltsville, Maryland, produces strontium chromate. Production of other strontium compounds is on a limited scale (USGS 1998, 1999).STRONTIUM 200 5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL

Radioactive strontium, or 89 Sr and 90 Sr, does not occur in nature. It is the direct result of anthropogenic activity. As discussed in Chapter 4, 89 Sr and 90 Sr are produced by nuclear fission. Nearly all of the 90 Sr generated in the United States is present in spent nuclear reactor fuel rods. These fuel rods are currently located at the commercial reactor facilities or at De partment of Energy (DOE) facilities across the United States. After 1 year of decay of nuclear fuel rods, 90 Sr represents 3.7% by mass of the total fission product inventory. A limited amount of 89 Sr and 90 Sr is produced for industrial, scientific, and medicinal applications through the process of fission produc t recovery. During the period of 1974–1984, 90 Sr was recovered and converted into solid forms. Typically, 90 Sr is combined with fluorine to produce strontium fluoride ( 90 SrF 2 ) or with chlorine (Cl 2 ) to produce strontium chloride ( 90 SrCl 2 ). These solids were placed in double walled capsules to be used for commercial and medical applications. 90 Sr is available from Pacific Northwest National Laboratory located at the DOE facility in Hanford, Washington. The Hanford inventory of 90 Sr embodies one of the largest sources of this nuclide in the world (DOE 1996b, 1996c).

5.2 IMPORT/EXPORT
In 2001, 100% of celestite used in the United Stat es was imported from Mexico. Of the 38,500 metric tons of strontium minerals and compounds importe d in 2001, approximately 94% were imported from Mexico, 6% from Germany, and 2% from other countries. From the period of 1954–1974, demand for strontium imports (both mineral and compound) has steadily increased from approximately 3,200 to 16,000 metric tons. From 1994 to 2001, the im portation of strontium minerals and compounds for consumption has remained relatively steady at approx imately 31,000–38,500 metric tons. The apparent consumption of all strontium imports in the United St ates is 97%. The total export volume of strontium compounds during 1993–2001 was more than 20 times lowe r than the quantities of strontium minerals and compounds imported during the same period. Ex ports of strontium compounds has varied from 1,120 metric tons in 1994 to 1,040 metric tons in 2001 (USGS 1998, 1999, 2002).

5.3 USE
In 2001, more than 85% of all strontium consumed in the United States was used in the manufacture of ceramics and glass products, primarily in television f aceplate glass and secondarily in ceramic ferrite magnets (strontium ferrite) and othe r ceramic and glass applications. All color televisions and other devices containing cathode-ray tubes (CRT) sold in the United States are required by law to containSTRONTIUM 201 5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL strontium in the faceplate glass of the picture tube to block x-ray emissions. Major manufacturers of television picture tube glass incorporate about 8% by weight of strontium oxide (SrO) into the glass faceplate material. Strontium is added to the glass melt in the form of strontium carbonate. Upon heating and solidification, it is transformed to SrO. Ot her uses for strontium compounds include pyrotechnics (strontium nitrate), paint pigments (strontium chro mate), fluorescent lights (strontium phosphate), getters in zinc production (strontium carbonate), alloy (s trontium metal), and medicines (strontium chloride, strontium peroxide). Strontium metal has limited co mmercial use. One minor use of strontium is as an alloy material for the production of aluminum cas tings. Most commercial uses of strontium compounds and products use strontium carbonate as the f eed material (Hibbins 1997; USGS 1999, 2002).
The radioactive isotope 89 Sr (also known by the pharmaceutical brand name MetastronTM) is used as a cancer therapeutic to alleviate bone pain. 85 Sr has been used in medical applications, such as radiologic imagining of bones, in minor commercial applications , such in radioisotope thermoelectric generators (RTG), as a beta-particle standard source, and in instruments that measure thickness and density of materials (Murray 1994). 90 Sr has been used in RTGs at remote locations (e.g., lighthouses) throughout the former Soviet Union (Alimov 2003). Many of these 90 Sr RTGs in the former Soviet Union are completely unguarded against potential thieves or intruders, lacking such minimal security measures as fences or even signs warning of radioactive dange rs. The biggest danger coming from these unprotected RTGs is their availability to terrorists w ho can use the radioactive materials (e.g., 90 Sr) contained in them to make so-called “dirty bombs”, which are bombs that are triggered by standard explosives, but disperse radioactivity.

5.4 DISPOSAL
Most nonradioactive strontium minerals, strontium co mpounds, and strontium-containing materials do not require special disposal and 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 s hould be investigated and subsequently followed with regard to disposal and ha ndling of the specific chemical form of the strontium compound or material.
Radioactive strontium does require special disposal and handling requirements and is regulated by the Nuclear Regulatory Commission (USNRC). Radioactive waste-containing radioactive strontium can beSTRONTIUM 202 5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL grouped into three categories: low-level waste (LLW ); high-level waste (HLW) and spent nuclear fuel; and mixed waste. As defined by the Nuclear Wast e Policy Act, high-level radioactive waste is “the highly radioactive material resulting from the reproce ssing of spent nuclear fuel, including liquid waste produced directly in reprocessing and any solid materi al derived from such liquid waste that contains fission products in sufficient concentration.” Howeve r, most classifications of HLW also include spent nuclear fuel. Most HLW was generated from the produc tion of plutonium. A sma ll 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-pro ducts as well as other long-lived isotopes, hazardous chemicals, and toxic heavy metals. 90 Sr contamination is only a small fraction of the activity of HLW. Liquid HLW is typically stored in large undergro und tanks of either stainless steel or carbon steel, depending on whether they are acid or alkaline solu tions. There are about 1 00 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, solid s, and sludges. Some of the liquid wastes have been solidified into glass, ceramic slag, sa lt cakes, and sludges (DOE 1996a; Murray 1994).
Spent nuclear fuels, such as fuel elements and irradi ated 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 concentrati on of fission products and must be stored in special water-cooled pools that shield and cool the material. Most of the 90 Sr 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 Laboratory, 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 commerci al nuclear reactor sites around the United States. The establishment of an HLW and spent fuel repository for both DOE and commercial waste is currently under evaluation at Yucca Flats, Nevada. It is not pr ojected to be in operation until after the year 2010 (DOE 1996b; Eisenbud 1987; Murray 1994).

Mixed waste contains both radioactive and chemical ly hazardous materials such as toxic, corrosive, flammable, or explosive materials. The radioactiv e component may be either HLW or LLW. All liquid HLW is mixed waste, usually in the presence of or ganic solvents or heavy metals in addition to radioactive components. Disposal of mixed wastes is regulated by EPA under the Resource Conservation and Recovery Act (RCRA) and by the USNRC under the Atomic Energy Act. EPA and USNRC have developed special procedures on how to handle and dis pose of this special category. DOE operates an incinerator in Oak Ridge, Tennessee that burns mi xed hazardous radioactive wastes (DOE 1996a).STRONTIUM 203 5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL
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 practi cally 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 typ es that may be contaminated with 90 Sr include both wet and dry wastes. Examples of the physical form of LLW ar e spent ion exchange resins, filter sludges, filter cartridges, evaporator bottoms, compactable trash, non-compactable trash, irradiated components, ashes produced from the incineration of combustible material, contaminated detergents or solvents, organic liquids, and discarded contaminated equipment or tool s. 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. Radiostrontium contamination accounts for only a small fraction of the activity of LLW. LLW is typically packaged in drums or boxes and buried in shallow pits or trenches. Approximately 3 million cubic meters of LLW generated in the United States ha ve been disposed of this way. LLW from DOE sources is currently disposed of at several DOE fac ilities across the United States . Only two sites accept non-DOE LLW, Barnwell, South Carolina and Richland, Washington. 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 in the 1985 amendments, states or interstate compacts are required to build facilities to contain LLW generate d from sources within their boundaries. However, other than Barnwell, South Carolina and Richland, W ashington 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; Murray 1994).STRONTIUM 205



### 6. POTENTIAL FO R HUMAN EXPOSURE

6.1 OVERVIEW

Strontium and 90 Sr have been identified in at least 102 and 12, respectively, of the 1,636 hazardous waste sites that have been proposed for inclusion on th e EPA National Priorities List (NPL) (HazDat 2003). However, the number of sites evaluated for strontiu m and strontium-90 are not known. The frequency of these sites can be seen in Figures 6-1 and 6-2, respectively. Of these sites, all are located within the United States and none are located in the Commonwealth of Puerto Rico.
Strontium is widely distributed in the earth’s crust an d oceans. Strontium is released into the atmosphere primarily as a result of natural sources, such as entrai nment of dust particles and resuspension of soil. Radioactive strontium is released into the environm ent as a direct result of anthropogenic activities. Stable strontium can neither be created nor destroyed. However, strontium compounds may transform into other chemical compounds. Radioactive stron tium is formed by nuclear reactions. Radioactive decay is the only mechanism for decreasing the conc entration of radiostrontium. The half-life of 90 Sr is 29 years. Eventually, all of the radioactive str ontium will be converted to stable zirconium (see Section 4.2).
Strontium present in the atmosphere is in the form of wet or dry aerosols. The principal chemical species in the air is strontium oxide (SrO). Strontium oxide will react rapidly in the presence of moisture to form Sr +2 and SrOH + ions. Strontium is dispersed by atmospheric cycling and is subsequently deposited by wet deposition on the earth’s surface. In surface water and groundwater, strontium exists primarily as a hydrated ion. Strontium can form ionic complexes wi th other inorganic or orga nic substances. Strontium is relatively mobile in water. However, the formatio n of insoluble complexes or sorption of strontium to soils can reduce its mobility in water. Strontium sorbs to soils by ion exchange , and tends to be more mobile in soils with a high concentration of excha ngeable ions or in soils with low cation exchange capacities. Strontium is taken up and retained by aquatic and terrestrial plants and is concentrated in the boney tissues of animals that eat contaminated vegeta tion. The average concentration of strontium in urban air is 20 ng/m 3 (Dzubay and Stevens 1975). The concentration of 90 Sr in the atmosphere has steadily decreased since its maximum concentration in 1963. The mean concentration of strontium in U.S. surface water is <1 mg/L. Dissolved strontium has been detected in groundwater and surface water used for drinking water supplies with average concen trations of 0.81 and 1.1 mg/L, respectively (EPASTRONTIUM 206 6. POTENTIAL FOR HUMAN EXPOSURE 

### Figure 6-1. Frequency of NPL Sit es with Strontium Contamination

Frequency of

NPL Sites

Derived from HazDat 2003 2 3 5 6 8 10207 STRONTIUM 6. POTENTIAL FOR HUMAN EXPOSURE 

### Figure 6-2. Frequency of NPL Sites with Strontium-90 Contamination

Frequency of

NPL Sites

1 2 3
Derived from HazDat 2003STRONTIUM 208 6. POTENTIAL FOR HUMAN EXPOSURE 2002b). The median concentration of 90 Sr in drinking water for 1995 was 0.1 pCi/L (3.7 mBq/L). Human exposure to strontium and radiostrontium can result from consumption of food, drinking water, or incidental ingestion of soil or dust contaminated with strontium. Food and drinking water are the largest sources of exposure to strontium and radiostrontium. Grain, leafy vegetables, and dairy products contribute the greatest percentage of dietary strontium and radiostrontium to humans.

6.2 RELEASES TO THE ENVIRONMENT
The TRI data should be used with caution because only certain types of facilities are required to report. This is not an exhaustive list.

6.2.1 Air
Strontium naturally occurs in the earth’s crust and is released into the atmosphere as a result of natural processes such as entrainment of dust particles, resusp ension of soil by wind, and sea spray. Entrainment of soil and dust particles with significant concentra tions of strontium would be most significant in areas with higher soil strontium concentrations. Coastal regions have higher concentrati ons of strontium due to sea spray (Capo et al. 1998). Human activities, including milling and processing of strontium compounds, burning of coal, land application of phos phate fertilizers, and using pyrotechnic devices, release strontium into the atmosphere (Lee a nd von Lehmden 1973; Ondov et al. 1989; Perry 1999; Que Hee et al. 1982; Raven and Loeppert 1997). The e ffect of these activities is illustrated by the deposition rates of strontium measured in peat cores of northern Indiana. Deposition has increased by a factor of 7 from 8.1 mg strontium/m 2 /year in presettlement times (1339–1656) to 57.0 mg strontium/m 2 /year between 1970 and 1973 (Cole et al. 1990).
Strontium discharged into the atmosphere from the ope ration of coal fired power plants depends on the strontium concentration in coal, the amount of coal burned, and the efficiency of fly ash recovery. Approximately 90% of coal mass is consumed during the combustion process, leaving 10% as a residual nonvolatile material (fly ash) containing 100–4,000 ppm (or mg/kg) of strontium (Furr et al. 1977). Atmospheric concentrations of strontium emitted from coal fired power plants ha ve been found to range from 17 to 2,718 μ g/m 3 in the western United States and are approximately 9,786 μ g/m 3 in the eastern United States (Ondov et al. 1989; Que Hee et al. 1982). Phosphate fertilizers are known to contain between 20 and 4,000 μg strontium/g solid by weig ht (Lee and von Lehmden 197 3; Raven and LoeppertSTRONTIUM 209 6. POTENTIAL FOR HUMAN EXPOSURE 1997). Strontium can be released into the atmosphe re in windblown soil to which phosphate fertilizers have been applied. Pyrotechnic displays relea se low levels of strontium on the order of 9 ng/m 3 in the immediate environment of the display (Perry 1999).

Strontium has been identified in air at 9 sites co llected from the 102 NPL hazardous waste sites where it was detected in some environmental media (HazDat 2003).
Radioactive strontium (e.g., 90 Sr) was released into the atmosphere from aboveground testing of nuclear weapons during the period of 1945–1980. Nuclear w eapon testing injects radioactive material into the stratosphere, which results in wide dispersal of radionuclides. However, atmospheric deposition of 90 Sr has steadily decreased from a high in 1963 of approximately 1.10x10 8 GBq (3.0 MCi) to <3,000 Ci in 1990, which suggests that global concentrations of 90 Sr in the atmosphere have declined (DOE 1996c). Other sources of regional contamination from radi ostrontium include large-scale nuclear power plant accidents such as the Chernobyl disaster in the Ukrain e (April 1986), which resulted in releases of about 2.2 MCi (8.1x10 7 GBq) of 89 Sr and 0.22 MCi (8.1x10 6 GBq) of 90 Sr into the atmosphere (Eisenbud 1987). However, although some 90 Sr reached the upper atmosphere and w as subsequently transported around the world, most of the radiostrontium was deposited as re gional fallout in eastern Eu rope (Eisenbud 1987). Routine releases of radiostrontium in 1993 from the ope ration of nuclear power plants around the United States are summarized in Table 6-1 (USNRC 1993a). In 1993, releases of radiostrontium (i.e., 89 Sr, 90 Sr, and 91 Sr) for boiling water reactors (BWR) and pressurized water reactors (PWR) (the two common designs of nuclear reactors in the United States) were 72.1 and 3.3 mCi (2.67 and 0.12 GBq), respectively. The total annual releases of radiostr ontium from nuclear power plants in the United States (75.4 mCi or 2.79 GBq) are insignificant compared to releases of 90 Sr from the testing of nuclear weapons. In the former Soviet Union between the years 1949 and 1956, large-scale environmental contamination occurred in the region surrounding the Mayak plutonium production complex in the Ural region of Russia (Eisenbud and Gesell 1997). Releases of radioactive liquid wastes into the Techa River, both planned and accidental, of about 10 17 Bq (2.7 MCi) resulted. 90 Sr contributed about 12% (or 0.23 MCi) to the total activity released (Tokareva et al. 2000). Other minor releases of 90 Sr have involved accidents with rockets or satellites that have disint egrated in the atmosphere. The Soviet satellite Cosmos 954 powered by a plutonium fueled nuclear reactor released 3.1x10 3 GBq (83 Ci) of 90 Sr to the regional atmosphere in northern Ca nada in 1978 (Eisenbud 1987). The Department of Energy (DOE) and its predecessor agencies have been i nvolved in operations that have released radiostrontium into the atmosphere. Over the 43-year operating period at the DOE Savannah River Site in South Carolina, about 1.1x10 2 GBq (3 Ci) of 90 Sr were released into the atmosphere, primarily from the chemical separation andSTRONTIUM 210 6. POTENTIAL FOR HUMAN EXPOSURE


### Table 6-1. Radi ostrontium Releases from N uclear Power Plants for 1993
Annual total site environmental releases for 1993 Water Air Installation Location a 89 Sr, 90 Sr, 91 Sr, 92 Sr, mCi 89 Sr, mCi 90 Sr, 91 Sr, mCi mCi mCi mCi mCi Boiling Water Reactors Browns Ferry b Decatur, AL 41.1 2.05 No data 0.40 0.19 No data No data Brunswick b Wilmington, No data No data No data 0.0062 0.099 0.0027 No data NC Clinton Clinton, IL No data No data No data No data 0.06 No data No data Cooper Omaha, NE 4.69 15.8 No data 0.082 No data No data No data Dresden b Joliet, IL 0.056 0.085 No data No data 0.67 0.004 No data

Duane Arnold Cedar Rapids, No data No data No data No data 0.018 0.0009 No data IA Edwin I. Hatch Baxley, GA 6. 29 0.43 5.20 0.65 12.0 0.24 No data Fermi Laguna 0.19 No data No data No data 0.14 0.0003 4.0 Beach, MI Grand Gulf Vicksburg, MS 0.32 0.29 No data No data 0.003 0.002 No data Hope Creek Wilmington, No data No data No data No data No data No data No data DE Humbolt Bay b Eureka, CA No data 36.5 No data No data No data 0.002 No data James A. Syracuse, NY 0.44 No dat a No data No data 0.045 7.3x10 -7 No data

Fitzpatrick LaCrosse b LaCross, WI No data 0.28 No data No data No data 0.0003 No data

LaSalle Ottawa, IL No data No data No data No data No data No data No data Limerick Phildelphia, 20.0 0.44 No data No data 16.4 0.31 No data PA Millstone New London, 3.30 0.15 No data 0.55 0.22 0.0006 No data CT Monticello St.Cloud, MN No data No data No data No data 0.59 0.003 No data Nine Mile Point Oswego, NY <0.0001 No data No data No data 5.90 0.004 No data Oyster Creek Toms River, No data No data No data No data 1.17 0.014 No data NJ Peach Bottom Lancaster. PA 0.19 0.056 No data No data 4.9 0.021 3.76 Perry Painesville, 0.22 0.008 No data No data 1.8 0.009 4.87 OH Pilgram Boston, MA 1.63 0.086 No data No data 5.8 0.024 No data Quad-Cites Moline, IL 0.050 0.018 No data 0.12 0.61 0.0014 No data River Bend Baton Rouge, 5.3 0.31 No data No data 0.30 0.0095 No data LA Shoreham Brookhaven, 0.025 No data No data No data No data No data No data NY Susquehanna Berwick, PA 0.0088 No data No data 0.0011 0.0003 No data No data Vermont Yankee Brattleboro, No data No data No data No data 2.83 0.054 No data VT WNP-2 Richland, WA 0.55 0.057 No data No data 3.5 0.012 1.61STRONTIUM 211 6. POTENTIAL FOR HUMAN EXPOSURE


### Table 6-1. Radi ostrontium Releases from N uclear Power Plants for 1993
Annual total site environmental releases for 1993 Water Air Installation Location a 89 Sr, 90 Sr, 91 Sr, 92 Sr, mCi 89 Sr, mCi 90 Sr, 91 Sr, mCi mCi mCi mCi mCi Total 84.4 56.6 5.20 1.81 57.2 0.72 14.2 Pressurized Water Reactors Arkansas One Russellville, 2.81 1.17 No data 0.59 0.000955 No data No data AR Beaver Valley Shippingport, No data No data No data 0.08 No data No data No data PA Big Rock Point Charlevoix, MI 0.02 0.17 No data No data 0.21 0.006 2.73 Braidwood Joliet, IL 3.68 158.4 No data 0.017 No data No data No data Byron Byron, IL 152.4 0.56 No data No data No data No data No data

Callaway Fulton, MO 17.6 1.12 No data No data 0.004 No data No data Calvert Cliffs Washington, 0.83 0.37 No data No data No data No data No data DC Catawaba Rock Hill, SC No data No data No data 0.41 No data No data No data Comache Peak Glen Rose, TX No data No data No data 0.029 No data No data No data Crystal River Tampa, FL 3.03 10.2 No data 3.57 0.001 0.001 No data Davis-Besse Toledo, OH No data No data No data No data No data No data No data Diablo Canyon San Luis 0.16 0.057 No data 0.003 No data No data No data Obispo, CA Donald C. Cook St. Joseph, MI No data 0.029 No data No data 0.080 0.0005 No data Fort Calhoun Omaha, NE 0.61 0.77 No data No data No data 0.0007 No data

H.B. Robinson Hartsville, SC No data No data No data No data No data No data No data Haddam Neck Middletown, 0.076 1.52 No data No data 0.0002 0.0002 No data CT Harris b Raleigh, NC No data No data No data No data No data No data No data Indian Point b Peekskill, NY 0.077 0.007 No data No data No data No data No data Joseph M. Dothan, AL No data 0.028 No data 0.10 No data No data No data

Farley Kewaunee Green Bay, WI 0.92 0.051 No data No data No data No data No data Maine Yankee Wicassett, ME 0.15 No data No data No data No data No data No data McGuire Charlotte, NC 0.20 No dat a No data No data No data No data No data North Anna c NW No data No data No data No data No data No data No data Richmond, VA Oconee Greenville, SC No data No dat a No data No data No data No data No data Palisades South Haven, 0.003 0.012 No data No data 0.011 0.0042 No data MI Palo Verde Phoenix, AZ No data No data No data No data 0.19 0.0009 No data Point Beach Manitowoc, WI 0.012 0.11 0.0052 No data No data 0.0001 No data Prairie Island Minneapolis, No data No data No data 0.029 0.0006 0.0003 No data MN R.E. Ginna Rochester, NY 0.30 0.090 No data No data No data No data No dataSTRONTIUM 212 6. POTENTIAL FOR HUMAN EXPOSURE


### Table 6-1. Radi ostrontium Releases from N uclear Power Plants for 1993
Annual total site environmental releases for 1993 Water Air Installation Location a 89 Sr, 90 Sr, 91 Sr, 92 Sr, mCi 89 Sr, mCi 90 Sr, 91 Sr, mCi mCi mCi mCi mCi Rancho Seco b Sacramento, No data 0.0013 No data No data No data No data No data CA San Onofre b San Clemente, 4.26 0.36 No data 0.48 No data No data No data CA Seabrook Portsmouth, No data No data No data No data No data No data No data NH Sequoyah Daisy, TN 0.35 0.29 0. 023 0.54 No data No data No data South Texas Bay City, TX No data No data No data No data No data No data No data St. Lucie Ft. Pierce, FL 1.21 1.83 No data No data No data 0.0012 No data Summer Columbia, SC 0.0007 0.021 No data No data No data No data No data Surry Newport No data No data No data No data No data No data No data News, VA Three Mile Harrisburg, PA 0.034 0.83 No data No data No data 0.0003 No data

Island b Trojan b Portland, OR 0.24 0.029 No dat a No data No data No data No data Turkey Point b Florida City, 12.7 3.55 No data No data No data No data No data FL Vogtle Augusta, GA 1.64 0.19 No data No data 0.0025 0.0003 No data Waterford New Orleans, No data No data No data 0.23 No data No data No data LA Wolf Creek Burlington, KS No data 0.092 0.0087 No data No data No data No data Yankee Rowe b Greenfield, MA No data No data No data No data No data No data No data

Zion Waukegan, IL No data No data No data 5.93 No data No data No data Total 207.1 182.8 0.04 11.5 0.50 0.02 2.73

a Post office state abbreviations used b Facilities that are permanently or indefinitely shut down c Air 85 Sr 8.17x10 6
Source: NRC 1993bSTRONTIUM 213 6. POTENTIAL FOR HUMAN EXPOSURE reprocessing of nuclear fuel (Carlton et al. 199 8, 1999). Between 1944 and 1972, about 64 Ci (2.4x10 3 GBq) of 90 Sr and 700 Ci (2.6x10 4 GBq) of 89 Sr was released into the atmosphere at the DOE Hanford site in Washington state from the routine opera tion of chemical plants used to separate plutonium from spent reactor fuel (CDC 1994).

90 Sr has been identified in air at 3 sites collected from the 12 NPL hazardous waste sites where it was detected in some environmental media (HazDat 2003).

6.2.2 Water
Releases of strontium to surface water and groundwater results from the natural weathering of rocks and soils and from the discharge of waste water direc tly into streams and aquifers. Intentional and unintentional releases of radioactive strontium directly into streams have occurred at DOE sites across the country. Over the period of 1954–1989, about 104 Ci (3.8x10 3 GBq) of 90 Sr and 216 Ci (8.0x10 3 GBq) of
89 Sr were released to streams in the vicinity of th e Savannah River Site (Carlton et al. 1998; Cummins et al. 1991). During the period from 1952 to 1991, >129 Ci of 90 Sr in waste water was discharged into pits, wells, and infiltration ponds at the Idaho Chemical Processing Plant in Idaho, some of which may have found its way into surface or groundwater (Bartholom ay et al. 1995). Minor releases of radioactive strontium to water occur annually from nuclear pow er plants. Table 6-1 summarizes the releases of radioactive strontium from nuclear power plants in to surface waters in 1993 (USNRC 1993a). Releases of radiostrontium (i.e., 89 Sr, 90 Sr, 91 Sr, and 92 Sr) into surface waters in 1993 from BWR and PWR were 146.2 mCi (5.41 GBq) and 401.4 mCi (14.9 GBq), respectively.
Strontium has been identified in surface water and gr oundwater at 25 and 55 sites, respectively, collected from the 102 NPL hazardous waste sites where it was detected in some environmental media. 90 Sr has been identified in surface water and groundwater at 3 and 7 sites, respectively, collected from the 12 NPL hazardous waste sites where it was detected in some environmental media (HazDat 2003).

6.2.3 Soil
Strontium is ubiquitous in the environment and is present in nearly all rocks and soils. It is released to land in solid waste and from the use of phosphate fertilizers. 90 Sr is found in nearly all soils in the United States. 90 Sr that is deposited at a specific site varies wi dely, depending primarily on rainfall. IntentionalSTRONTIUM 214 6. POTENTIAL FOR HUMAN EXPOSURE
and unintentional releases of radioactive strontium have occurred at DOE sites across the country. Between 1954 and 1989 at the Sa vannah River Site, 105 Ci (3.9x10 3 GBq) of 89 Sr and 299 Ci (1.1x10 4 GBq) of 90 Sr were released into onsite seepage basi ns (DOE 1991). About 100 million gallons of liquid HLW are stored in underground tanks in Hanford, Washington, Savannah River, South Carolina, Idaho National Engineering Laboratory, Idaho, and W est Valley, New York; these tanks contain a variety of radioactive liquids, solids, and sludges with unknown characteristics. Sixty-seven tanks at the Hanford site have suspected leaks of HLW into the surroundi ng soil. The largest three confirmed leaks at the Hanford site have released 115,000, 70,000, and 55,0 00 gallons of HLW, respectively, which may contain
90 Sr as well as other radionuclides (DOE 1996a).

Strontium has been identified in soil and sediment at 32 and 16 sites, respectively, collected from the 102 NPL hazardous waste sites where it was de tected in some environmental media. 90 Sr has been identified in soil and sediment at 3 and 1 sites, r espectively, collected from the 12 NPL hazardous waste sites where it was detected in some environmental media (HazDat 2003).

6.3 ENVIRONMENTAL FATE
6.3.1 Transport and Partitioning
Strontium, present in crustal materials, is released by the weathering force of wind and water. Strontium leaves the oceans, the largest reservoir of dissolv ed strontium, by deposition in marine carbonate sediment. Some strontium is transported from oceans to the atmosphere in sea spray, returning to the terrestrial environment in the form of precipitation (Capo et al. 1998).
Strontium released into the atmosphere from natura l and anthropogenetic activ ities is transported and redeposited on the earth by dry or wet deposition. Dry deposition results from gravitational settling, impact, and sorption on surfaces (NCRP 1984). Expe rimental data on dry deposition of strontium, present in the ambient atmosphere, is limited. Rain, sleet, snow, or other forms of moisture can wash airborne particles containing strontium from the at mosphere by the process of wet deposition. Wet deposition depends on conditions such as particle solubility, air concentra tion, rain drop size distribution, and rain fall rate (NCRP 1984). Hirose et al. ( 1993) examined the mechanism of aerial deposition of 90 Sr derived from the Chernobyl accident, and found that 96% of atmospheric 90 Sr returned to earth as wet deposition.STRONTIUM 215 6. POTENTIAL FOR HUMAN EXPOSURE Like calcium, strontium has moderate mobility in so ils and sediments, and sorbs moderately to metal oxides and clays (Hayes and Traina 1998). The Sr 2+ ion is strongly hydrated and is firmly coordinated with six or more water molecules in aqueous solution. When Sr 2+ ions sorb on negatively charged mineral surface sites, the hydration sphere is retained (O’Day et al. 2000). Strontium sorbs as hydrated ions on the surface of clay minerals (kaolinite), w eathered minerals (amorphous silica), and iron oxides (Sahai et al. 2000). Sorbed carbonate on iron oxides enhances the sorption of Sr 2+ and permits the nucleation of Sr 2+ as strontium carbonate (Sahai et al. 2000). On calcite (calcium carbonate), Sr 2+ sorption occurs by electrostatic attraction as hydrat ed ions. However, at higher concentrations, precipitation of strontianite (strontium carbonate) o ccurs, and strontium is likely to be less mobile (Parkman et al. 1998).

A wide variation of K d values have been publishe d in the literature for Sr 2+ sorption (NCRP 1984) that reflect differences in soil and sediment conditions as we ll as the analytical techniques used (Bunde et al. 1997). The in situ K d values of stable strontium and 90 Sr determined in soil cores taken from the fallout area of the 1945 blast in Nagasaki, Japan were 496 and 300 L/kg, respectively (Mahara 1993). Migration rates for 90 Sr in soils from this area were estimated to be 4.2 mm/year when the percolation rate of soil water was 2,500 mm/year. Most 90 Sr remained close to the soil surface in these soils. In 1996, at most sites in the contaminated zone n ear Chernobyl, the main content of 90 Sr (more than 95% of activity) was located in the upper 30-cm layer. Only at a few site s (<1% of all sites) had a significant part of the 90 Sr (>20%) migrate deeper than 30 cm (Kashparov et al. 2001). A high migration ability of 90 Sr is observed only in low-humus sands. In soils from Be larus near the Chernobyl accident site, K d values were 43, 59, and 150 L/kg for soddy-podzolic, soddy-loamy sandy, and peaty-gley soils, respectively (Sokolik et al. 2001). Organic matter in soils has a substantial effe ct on the transport of strontium through soils into groundwater. K d values decreased down the soil profile in Podzol forest soil with an organic rich top soil and lower clay layers, from 140 to 44 L/kg (Bunzl and Schimmack 1989). Sr 2+ chemically complexes with organic matter by partially neutralizing exchan geable sites on organic matter resulting in the precipitation of organic matter-Sr 2+ complexes (Helal et al. 1998a). High concentrations of ion exchangeable Ca 2+ in soil enhances the complexation of Sr 2+ with organic matter and increases the removal of Sr 2+ from solution, which results in reduced Sr 2+ mobility (Helal et al. 1998a). However, nitrate fertilizers inhibit the formation of Sr 2+ -organic matter complexes and increase Sr 2+ mobility (Helal et al. 1998b). K d values of 15–40 L/kg were measured for 90 Sr 2+ in aquifer sediments near Liquid Waste Disposal Facilities at the Hanford site in Washingt on, where rapid ion exchange dominates (DOE 1996d). K d was measured for 90 Sr 2+ in aquifer sediments beneath waste water ponds that contained high salt concentrations at the Idaho National Environmenta l and Engineering Laboratory (INEEL) (Bunde et al.STRONTIUM 216 6. POTENTIAL FOR HUMAN EXPOSURE 1998); and values ranged from 56 to 62 L/kg at initial c oncentrations of sodium and potassium of 300 and 150 mg/L, respectively. For initial aqueous concentr ations of sodium between 1,000 and 5,000 mg/L, K d values were 4.7 and 19 L/kg, respectively. At the Chalk River Nuclear Laboratory in Ontario, Canada, a
90 Sr waste plume in groundwater initially advanced rapidly as 90 Sr was out competed by high concentrations of Ca 2+ and Mg 2+ for sorption sites in sediments, and as concentrations of Ca 2+ and Mg 2+ declined, the migration of the 90 Sr plume slowed (Toran 1994). High salt concentrations (marine, brines, or high salinity water) can increase the mobility of 90 Sr 2+ by decreasing strontium sorption to sediments (Bunde et al. 1997, 1998) and increase the transport of str ontium with the environmental cycling of water.
Strontium is not necessary for growth or reproduction for most plants, but is typically absorbed to satisfy the plant’s metabolic requirements for calcium (NCRP 1984). Soil to plant concentration ratios for strontium (the ratio of the concentration of strontiu m in wet vegetation to the concentration of strontium in dry soil) are 0.017–1.0 (NCRP 1984), and indicate that strontium can be easily absorbed into plants from soil. The uptake of strontium by plants is greatest in sandy soils having low clay and organic matter content (Baes et al. 1986). The concentration of nutr itive mineral elements in soil such as calcium lower the intake of strontium to the aboveground phytom ass. The average reduction of the soil-to-plant concentration ratios for 90 Sr caused by amendment with Ca or K is around 50–60% (Lembrechts 1993).
Strontium may be deposited on plant surfaces from the atmo sphere, remain on the plant, be washed off, or be absorbed directly into the plan t through leaves. Contamination by direct deposition on foliage surfaces is predominantly a short-term mechanism with a weathering half-life of approximately 14 days (Lassey 1979). Carini et al. (1999) examined the mechanism of translocation in three species of fruit-bearing plants exposed to aerial deposition of 85 Sr and found that translocation of 85 Sr is localized to the area of contamination on the plant. However, uptake of strontium through the leaves is minor compared to root uptake. Once absorbed in the plant, strontium translocates to other parts of the plant, such as the leaves or fruit. Translocation of strontium in plants is affect ed by the particular species and stage of organism growth, and the most metabolically active parts (g rowing) will accumulate higher concentrations of strontium (Kodaira et al. 1973).
Strontium, taken up by plants and translocated to the aboveground plant compartments, has been observed for deep-rooted plants such as chasima (Chrysothamnus nauseosus) , mulberry vegetation (Morus alba) , quaking aspen (Populus tremuloides) , and red maple (Acer rubrum) growing on top of low level waste burial sites or contaminated soils (Cooper and Rahm an 1994; DOE 1995; Fresquez et al. 1996a). The top growth of the plant material releases strontium to th e soil surface through leaf fall. Downward migrationSTRONTIUM 217 6. POTENTIAL FOR HUMAN EXPOSURE
of 90 Sr is slowed by recycling of the contaminat ed litter by vegetation (Coo per and Rahman 1994). Subsurface 90 Sr can be transported from soil to top soil by burrowing animals, and is spread to the surrounding environment via animal tissues and fecal deposits. At the Subsurface Disposal Area at the INEL, deer mice had the highest contamination of all animals from ingestion of 90 Sr-contaminated low level nuclear waste. In addition, the biotic intr usion of soils covering the waste site brings water infiltration into buried LLW (Arthur and Janke 1986).
The uptake or bioaccumulation of strontium by pl ants and organisms is the mechanism by which strontium in air, water, and soil enters into the fo od chain of humans. Bioconcentration factors (BCFs) have been measured by several investigators in both aquatic and terrestrial organisms for 90 Sr (NCRP 1984). BCF values for 90 Sr in aquatic, terrestrial, and wetland ecosystems at the Savannah River Site were reported by Friday (1996) and are summarized in Table 6-2. The study illustrates that the organisms with the highest uptake are aquatic organisms such as fish (large-mouthed bass), macroinvertebrates (insects), macrophytes (white-water lilies and bladderw ort), and zooplankton. Because of the similarity of strontium to calcium, boney fish had a very high BCF, with a value >50,000 measured in the boney tissue (Friday 1996). In the muscle tissue of boney fish, BCF values for 90 Sr ranged from high (benthic invertebrate and fish feeders; 610) to very high (p iscivores; 3,400). Because strontium and calcium are chemically similar, the concentration of calcium in water can influence the bioaccumulation of strontium in biota. Organisms such as fish bioaccumulate strontium with an inverse correlation to levels of calcium in water. However, this correlation is not universal and does not apply to other organisms such as algae and plants (NCRP 1984).

6.3.2 Transformation and Degradation
Because strontium is an element, its atoms do not de grade by environmental processes such as hydrolysis or biodegradation. However, radioactive str ontium will be subject to radioactive decay and transformation to other elements. Eventually, all of the radioactive strontium will be transformed into stable zirconium by the process of radioactive decay (see Section 4.2):

90 Sr (t 1⁄2 = 29 years) – 90 Y (t 1⁄2 = 64 hours) + β - – 90 Zr (stable) + β Both radioactive and nonradioactive strontium co mpounds are subject to both biotic and abiotic transformation mechanisms.STRONTIUM 218 6. POTENTIAL FOR HUMAN EXPOSURE


### Table 6-2. Sel ected Bioconcentration Factors for 90 

### Sr in Aquatic, Wetland, and Terrestrial Ecosystems at the Savannah Ri ver Site
Bioconcentration factors for 90 Sr Organism Minimum Maximum Mean Algae 600 Clam, shell 1,300 Fish muscle Insect and bottom invertebrate feeders Piscivores Benthic invertebrate and fish feeders <48 3,400

610
Fish bone Insect and bottom invertebrate feeders Piscivores Benthic invertebrate and fish feeders Detritus and plankton feeders 2,400 63,000 57,000 51,000 Macroinvertebrates, larvae 520 54,000 27,300 Macrohytes (rooted vascular) 2,100 8,500 5,500 Macrophytes (floating vascular) 9,400 Zooplankton 3,900 Corn Grain Leaves 0.15 13.1 Pine tree, leaves 0.88 1.69 1.29 Soybeans 2.51 Tree (maple, sweetgum, and poplar) Wood Bark Leaf 0.81 11

3.8 Source: Friday 1996STRONTIUM 219 6. POTENTIAL FOR HUMAN EXPOSURE

6.3.2.1 Air
The presence of strontium and radioactive strontium compounds in the atmosphere results from both natural and anthropogenetic activities (see Section 6.2. 1). Strontium is emitted into the atmosphere as strontium oxide (SrO) during thermal processes. Sr O is unstable and reacts with moisture or carbon dioxide in the air to form strontium hydroxide (Sr[OH] 2 ) or strontium carbonate (SrCO 3 ), respectively. Sr[OH] 2 in contact with water in clouds or during washout by rain will ionize to form Sr 2+ and SrOH + ions. There is no evidence in the literature for interacti on of SrO with other compounds in the atmosphere.

6.3.2.2 Water
Strontium exists almost exclusively in the environment as a +2 cation, and will form different species, some of which are more soluble than others. Because the different species have different solubilities, they will have different mobilities in the environment and di fferent exposure potentials. Strontium exists as a hydrated cation, an ionic solution complex, or an ionic salt. In the environment, typical solution species for strontium are Sr 2+ and SrOH + , and some strontium compounds (SrCO 3 and SrSO 4 ) are practically insoluble in neutral water (Cotton and Wilkenson 1980; see Table 4-2).

6.3.2.3 Sediment and Soil
The principal abiotic processes that transform strontiu m in soils and sediments are mediated by sorption and desorption reactions between the soil solution a nd matrix (precipitation, complexation, and ion exchange), and controlled by pH, ionic strength, solution speciation, mineral composition, organic matter, biological organisms, and temperature (see Section 6.3.1). For many soil systems, in the short term, strontium sorption is dominated by simple ion exchange , and strontium ions are readily exchangeable. At longer timescales, however, strontium ions may relocated into sterically hindered sites that are not readily exchangeable (Bunker et al. 2000).
In the vicinity of the Chernobyl accident site, 90 Sr has leached from “hot” fuel particles (which have dissolved) and now may interact with natural soil components (Sokolik et al. 2001). In situations where soil is incorporated into a nuclear fireball (e.g., Semipalatinsk Nuclear Test Site, Kazakhstan), the resulting fused silicates that form are usua lly comparatively insoluble. Typically, 90 Sr in these particlesSTRONTIUM 220 6. POTENTIAL FOR HUMAN EXPOSURE are tightly bound with the majority of 90 Sr undergoing radioactive decay before being released by weathering (Gastberger et al. 2000).

6.3.2.4 Other Media
No data were located in the literature on the transport or degradation of stable or radioactive strontium in other media.

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT
Strontium is widely distributed throughout the earth and has continuously cycled between the atmosphere, biosphere, hydrosphere, and lithosphere for many millions of years. Table 6-3 illustrates the average or range of concentrations of strontium in earth mate rials (Capo et al. 1998). Anthropogenic activities have increased local concentrations of strontium as a c onsequence of the development of an industrialized human society. Before the 1940s, radioactive st rontium was not present in the environment at any measurable levels.
In the United States, commercial nuclear power plan t operators are required to monitor and report any detectable quantities of radioactive materials rele ased to the environment (USNRC 1996). Table 6-1 summarizes releases of radiostrontium isotopes with ha lf-lives >8 hours to the atmosphere and water for 1993 from PWR and BWR nuclear power plants. Nearly all of the radioactive material reported as released in effluents are from planned releases fro m normal plant operation or anticipated operational occurrences. The latter includes unpl anned releases of radioactive mate rials from miscellaneous actions such as equipment failure, operator error, or procedur e error, and are not of such consequence as to be considered an accident (USNRC 1993a).

6.4.1 Air
According to two surveys, the strontium content in urban air ranges from 4 to 100 ng/m 3 and averages 20 ng/m 3 (Dzubay and Stevens 1975). The arithmetic mean concentration of strontium in urban air was measured as 29.1 ng/m 3 in the Los Angeles basin during 1985 (Witz et al. 1986). Urban air in Illinois between 1985 and 1988 averaged 0.9–4.8 ng/m 3 (Sweet et al. 1993). Areas where higher strontiumSTRONTIUM 221 6. POTENTIAL FOR HUMAN EXPOSURE 

### Table 6-3. Average or Ranges of Concentration of Strontium in Earth Materials
Material Concentration of strontium Geologic (ppm) Average crust Exposed upper crust Soil: Soil minerals Soil (labile) Individual rock types: Basalt Carbonate High-Ca granite Low-Ca granite Sandstone Shale 370 337 240 0.2–20 465 610 440 100 20 300 Biologic (ppm) Wood Roots (spruce) Conifer needles 8–2,500 19 2–20 Hydrologic ( μ g/L) Seawater Rivers Rain Snow 7,620 6–800 0.7–383 0.01–0.76
Source: Capo et al. 1998STRONTIUM 222 6. POTENTIAL FOR HUMAN EXPOSURE concentrations are prevalent are near coal burning plants where strontium can be released with stack emissions (as discussed in Section 6.2.1).
Before the 1940s, radiostrontium was not present in the air at any significant concentrations. Concentrations of 90 Sr in the atmosphere peaked at about 10 MCi (0.37 GBq) in 1963 coincident with the period of extensive atmospheric nuclear weapons test ing. Since the signing of the Nuclear Test Ban Treaty of 1963, the concentration of 90 Sr has steadily dropped through the latter 35 years by deposition and radioactive decay (DOE 1996c; Eisenbud 1987). Recent levels of 90 Sr in air were not located.

6.4.2 Water
Surveys of strontium in surface waters and municipa l water supplies across the United States show that strontium is present in nearly all fresh waters in amounts <1 mg/L (USGS 1963). The National Drinking Water Contaminant Occurrence Database (NDOD), wh ich contains data from public water supplies (PWS), where testing is performed at many points in the system, including the intake and at various points in the treatment and distribution systems, as well as at the point where the drinking water can be labeled "finished", lists the numbe r of detections and concentrations of strontium. The average concentrations of strontium in PWS waters fro m the United States derived from surface water and groundwater were 1.10 (range, 0.2–3.68 mg/L) and 0.81 mg/L (range, 0.010–3.5 mg/L), respectively (EPA 2002b). The average concentrations of strontiu m in streams of the United States are between 0.5 and 1.5 mg/L. Strontium concentrations >1 mg/L ar e found in streams of the southwest, where the total dissolved solids content is the highest of any area of the continental United States. Streams of most of the Atlantic slope basins, southern United States, upper Great Lakes region, and Pacific northwest contain concentrations of strontium that are generally <0.5 mg/L strontium (USGS 1963). Some exceptions are areas where there are celestite-rich limestone deposits , such as regions of northwestern Ohio and eastern Florida (USGS 1963). The average concentration of strontium in sea water is approximately 8 mg/L (Demayo 1986). In groundwater, the average concentration of strontium is <0.5 mg/L. High concentrations of strontium, >1 mg/L, have been in observed in the southwestern United States. Unusually high concentrations of strontium, >20 mg/L, have been observed for some wells in central Wisconsin (USGS 1963). The NDOD lists the number of detections and concentrations of strontium in groundwater and surface water at several locations around the United States from ambient water samples (EPA 2002b). Dissolved strontium was detected in groundwater at 4,353 of 4,383 sites (99.3% of sites), with an average concentration of 1.6 mg/L (range, 0.0009–200 mg/L). The average dissolved strontium concentration in lake/reservoirs and springs were 1.09 mg/L (97.6% of sites; range, 0.002–170 mg/L) andSTRONTIUM 223 6. POTENTIAL FOR HUMAN EXPOSURE
0.64 mg/L (100% of sites; range, 0.028–3.2 mg/L), respectively. In other surface waters, dissolved strontium was detected at 1,572 of 1,595 sites (98. 6% of sites), with an average concentration of 362 μ g/L (range, 0.0005–30 mg/L). The concentration of dissolved strontium in publicly owned treatment works (POTW) influents was between 0.025 and 0.45 mg/L (EPA 1981). The average concentrations of strontium in rain and snow were 0.7–383 and 0.01–0.76 μ g/L, respectively (Capo et al. 1998).

90 Sr concentration in surface waters of the north P acific Ocean has decreased steadily since the early 1960s to present day levels of approximately 23–81 pCi/m 3 (1–3 Bq 90 Sr/m 3 ) sea water. This value is estimated by dividing the concentration levels for 137 Cs by the global fallout activity ratio measured for
137 Cs/ 90 Sr of 1.5 (Hamilton et al. 1996). The EPA ERAM S program monitors ambient concentrations of
90 Sr in drinking water at 78 sites. ERAMS data serve to assess tre nds and anomalies in concentrations, and to compare with standards set forth in th e EPA National Interim Primary Drinking Water Regulations. Table 6-4 summarizes drinking water composite samples for the period of January– December in 1995 taken at the 78 sites in major population centers or near selected nuclear facilities (EPA 2000a). The median concentration of 90 Sr in drinking water for this period was 0.1 pCi/L (4 mBq). Sites with above average levels of 90 Sr, Detroit and Niagara Falls, recorded levels of 0.4 and 0.5 pCi/L (~15 mBq/L), respectively. In a 1974 study, a concentration of 0.09 pCi/L 90 Sr (3 mBq/L) in drinking water was measured in Los Angeles, California (Kra ybill 1983). In a survey that examined 169 wells used for public drinking water in California (Storm 1994), 16 wells measured re cordable concentrations of 90 Sr, with an average concentration of 105 pCi/L (4 Bq/L). The NDOD lists the number of detections of 90 Sr in ambient groundwater at several locations around the United States. Dissolved 90 Sr was detected in groundwater at 18 out of 104 sites (17%), with an average concentration of 1.46 nCi/L (53.9 Bq) (EPA 2002b). The concentrations of 90 Sr in groundwater at the 91 waste sites located at 18 DOE facilities were between 0.05 and 231,000 pCi/L (2 mBq and 9 kBq) (DOE 1992). River water taken from the Ebro River basin (Northeast Spain) during 1994 had a mean 90 Sr level of 6.6 mBq (0.18 pCi) and ranged from 5.9 to 7.6 mBq/L (0.16 to 0.21 pCi/L) (Pujol and Sanchez-Cabeza 2000). 90 Sr in the Ebro River waters could be attributed solely to global fallout. The DOE Environmental Measurements Laboratory program measures the 90 Sr content of wet deposition in selected sites across the world to determine global trends in 90 Sr deposition. The data for the year 1990 are presented in Table 6-5 for cities in the United States. The average total annual wet deposition of 90 Sr in the United States was 5 pCi/m 2 (0.2 Bq/m 2 ) during this period. The precipitation samples with the highest total 90 Sr concentrations were obtained from New York City and Nome, Alaska with annual totals of 10 and 8 pCi/m 2 (0.4 and 0.3 Bq/m 2 ), respectively. In all cases, the 90 Sr concentrations in rain were low, whic h suggests that the atmospheric content of 90 Sr in 1990 was small and decreasing (DOE 1996c).STRONTIUM 224 6. POTENTIAL FOR HUMAN EXPOSURE


### Table 6-4. 90 

### Sr in Drinking Water (Composi tes) for January–December 1995

90 Sr State a City Total solids (mg/L) pCi/L ±2 F AK Fairbanks 162.0 0.0 0.2 AL Dothan 160.0 0.1 0.1 AL Montgomery 55.2 0.1 0.2 AL Muscle Shoals 82.0 0.2 0.2 AL Scottsboro 87.0 0.2 0.2 AR Little Rock 28.8 0.0 0.2 CA Berkeley 8.0 0.1 0.2 CA Los Angeles 318.0 0.0 0.1 CO Denver 140.0 0.0 0.2 CO Platteville 138.0 0.0 0.2 CT Hartford 36.6 0.3 0.2 DE Dover 191.0 ND — FL Miami 150.0 0.2 0.2 FL Tampa 252.0 0.3 0.2 GA Baxley 165.0 0.0 0.2 GA Savannah 147.0 ND — HI Honolulu 208.0 0.1 0.1 IA Cedar Rapids 121.0 0.1 0.2 ID Boise 95.5 ND — ID Idaho Falls 219.0 ND — IL Morris 474.0 ND — IL West Chicago 337.0 0.1 0.1 KS Topeka 364.0 0.2 0.2 LA New Orleans 226.0 0.2 0.2 MA Lawrence 93.8 0.2 0.2 MD Baltimore 89.8 0.1 0.2 MD Conowingo 155.0 0.1 0.2 ME Augusta 85.2 0.3 0.2STRONTIUM 225 6. POTENTIAL FOR HUMAN EXPOSURE


### Table 6-4. 90 

### Sr in Drinking Water (Composi tes) for January–December 1995

90 Sr State a City Total solids (mg/L) pCi/L ±2 F MI Detroit 79.8 0.4 0.2 MI Grand Rapids 125.0 0.3 0.2 MN Minneapolis 93.8 0.3 0.2 MN Red Wing 238.0 0.0 0.2 MO Jefferson City 283.0 0.0 0.2 MS Jackson 86.8 0.2 0.2 MS Port Gibson 313.0 0.0 0.1 MT Helena 61.8 0.1 0.2 NC Charlotte 46.8 0.1 0.2 NC Wilmington 110.0 0.2 0.2 ND Bismarck 329.0 0.0 0.2 NE Lincoln 305.0 0.1 0.2 NH Concord 81.2 0.1 0.2 NJ Trenton 92.7 0.1 0.2 NJ Waretown 52.0 0.0 0.2 NM Santa Fe 279.0 ND — NV Las Vegas 248.0 0.1 0.2 NY Albany 68.8 0.3 0.2 NY New York City 44.5 0.0 0.2 NY Niagara Falls 99.2 0.5 0.2 NY Syracuse 94.8 0.3 0.2 OH Cincinnati 198.0 0.2 0.2 OH Columbus 362.0 0.0 0.3 OH East Liverpool 215.0 0.3 0.2 OH Painesville 126.0 0.2 0.3 OH Toledo 148.0 0.3 0.3 OK Oklahoma City 62.6 0.3 0.2 OR Portland 19.2 0.1 0.2STRONTIUM 226 6. POTENTIAL FOR HUMAN EXPOSURE


### Table 6-4. 90 

### Sr in Drinking Water (Composites) for January–December 1995

90 Sr State a City Total solids (mg/L) pCi/L ±2 F PA Columbia 121.0 0.1 0.2 PA Harrisburg 51.2 0.1 0.2 PA Philadelphia 165.0 0.0 0.2 PA Philadelphia

- 207.0 0.1 0.2 Queen PA Philadelphia-Baxter 101.0 0.2 0.2 PA Pittsburgh 178.0 0.2 0.2 PC Corozal 71.6 0.1 0.2 RI Providence 52.8 0.3 0.2 SC Barnwell 73.6 0.0 0.2 SC Columbia 28.2 0.0 0.2 SC Jenkinsville 165.0 ND — SC Seneca 35.2 0.1 0.2 TN Chattanooga 82.2 0.2 0.2 TN Knoxville 93.8 0.0 0.2 TX Austin 180.0 0.0 0.2 VA Doswell 193.0 0.0 0.2 VA Lynchburg 45.2 0.1 0.2 VA Virginia Beach 91.2 0.3 0.2 WA Richland 77.2 0.1 0.2 WA Seattle 29.8 0.0 0.2 WI Genoa City 194.0 ND — WI Madison 234.0 ND —

a Post office state abbreviations used ND = not detected; 2 F = counting error term reported at the 2 F

 (95%) confidence level Source: EPA 1995STRONTIUM 227 6. POTENTIAL FOR HUMAN EXPOSURE 

### Table 6-5. Quarterly and Annual Deposition of 90 

### Sr in Selected U. S. Cites for the Year 1990
Quarter Annual total

Location First Second 90 SrDeposition a Precipitation b 90 SrDeposition a Precipitation b Third 90 SrDeposition a Precipitation b Fourth 90 SrDeposition a Precipitation b 90 SrDeposition a Precipitation b Anchorage, Alaska 0.0 8.5 0.0 6.5 — 15.9 — 29.7 0.0 60.5 Argonne, Illinois 0.1 18.6 0.1 33.4 0.1 26.9 0.0 29.5 0.2 108.4 Birmingham, Alabama 0.1 50.6 0.0 22.2 0.0 14.7 0.0 31.7 0.1 119.3 Chester, New Jersey Cold Bay, Alaska 0.0
0.0 23.2
20.3 0.1
0.0 44.7
14.7 0.1
0.1 39.2
29.5 0.1
0.0 39.3
31.1 0.2
0.1 146.4
95.5 Fairbanks, Alaska 0.0 3.4 0.0 5.6 0.1 25.9 0.1 12.1 0.2 47.1 Houston, Texas 0.0 31.4 0.0 26.0 0.0 22.0 0.0 21.8 0.0 101.2 Lihue, Hawaii 0.0 36.7 0.0 14. 5 0.0 12.2 0.1 36.6 0.1 100.0 Mauna Loa, Hawaii 0.0 54.5 0.0 0.3 0.1 7.5 0.0 44.9 0.1 107.2 Miami, Florida 0.0 9.4 0.0 54.8 0.0 48.0 0.1 19.1 0.2 131.1 New York, New York — 28.7 0.1 42.5 0.1 46. 0 0.1 37.5 0.4 154.7 Nome, Alaska 0.1 5.4 0.0 10. 8 0.2 27.0 0.1 13.2 0.3 56.3 Vermillion, South Dakota 0.0 5.5 0.0 28.7 0.0 20.6 0.0 6.0 0.1 60.7
West Los Angeles, California 0.1 16.7 0.1 5.3 0.1 0.1 0.0 4.1 0.2 26.2

Wooster, Ohio 0.0 16.5 0.1 28.0 0.0 43.5 0.0 36.9 0.1 124.8 Average 0.03 22.0 0.03 22.5 0. 06 25.3 0.04 26.2 0.2 96.0

a In Bq/m 3 b In cm Source: DOE 1996dSTRONTIUM 228 6. POTENTIAL FOR HUMAN EXPOSURE

6.4.3 Sediment and Soil
Table 6-3 summarizes the average or range of concentra tions of strontium in soils and bedrock minerals. The average concentrations of strontium in the ear th’s crust and the exposed upper crust are 370 and 337 mg/kg, respectively. Soils, on average, have a pproximately 240 mg/kg Sr (Capo et al. 1998; EPA 1995a). Some materials, such as soil amendments, ar e routinely applied to agricultural lands. Typical concentrations of strontium in soil amendments are: POTW sewage sludges, 250±192 ppm (mg/kg dry weight); phosphate fertilizers, 610 mg/kg; limestone, 610 mg/kg; and manure, 80 mg/kg dry weight (EPA 1995a; Mumma et al. 1984).
The background level of 90 Sr in soils of the United States from global fallout will depend upon the historical transport and deposition inventory at that particular location. The mean regional background concentration of 90 Sr in soils in proximity to the Los Alamos National Laboratory from 1974 to 1994 was 320±250 pCi/kg dry weight soil (Fresquez et al. 1996b). This value has decreased with time due to radioactive decay of 90 Sr. The range of concentrations for 90 Sr in soils and sediments at 91 waste sites located at the 18 DOE facilities around the United States was 0.02–540,000 pCi/kg (DOE 1992). The total content of 90 Sr on surface soil in the 30 km contaminated zone around Chernobyl accident site in the Ukraine (not including the reactor site and waste storage) was about 8.1x10 14 Bq (2.2x10 7 Ci) in 1997, which corresponds to about 0.4–0.5% of the Chern obyl reactor inventory at the time of the accident (Kashparov et al. 2001). Ten years after the accident, about 95% of the 90 Sr activity is associated with the upper 10–20 cm layer of soil for most of the soils in this area. Mean 90 Sr activity in soil at a Chernobylcontaminated field site in the Ukraine was 36 Bq dry weight (0.97 nCi dry weight) (Malek et al. 2002). Levels of 90 Sr in soils from Belarus situated at a distan ce of ~40 km from the Chernobyl accident site ranged from 50 to 640 kBq/m 2 (1.4–17 μ Ci/m 2 ), while levels at a distance of 200–250 km ranged from 10–80 kBq/m 2 (270–2,200 nCi/m 2 ) (Sokolik et al. 2001).
The mean activity of 90 Sr in lacustrine and marine sediments from Antarctica in 1989–1996 ranged from 0.17 to 0.76 Bq/kg dry weight (4.59–20.5 pCi/kg dry weight) and from <0.10 to 0.21 Bq/kg dry weight (<2.7–5.78 pCi/kg dry weight), respectively (Jia et al. 1999). The 90 Sr activities in marine sediments ranged from 117 to 1,277 mBq/kg (3.16 and 34.5 pCi/kg) and from 304 to 1,799 mBq/kg (8.21–48.6 pCi/kg) at two sites off atomic power stations in South Korea (Yang et al. 2002). 90 Sr 2+ ions in sediments are characterized by reversible ion exchange processes that lead to low 90 Sr activity in sediments (Jia et al. 1999).STRONTIUM 229 6. POTENTIAL FOR HUMAN EXPOSURE
6.4.4 Other Environmental Media
The range of concentrations of strontium in fruits and vegetables is summarized in Table 6-6 (Barnes 1997). The highest concentrations are observed in leafy vegetables, such as cabbage (64.2 mg Sr/kg dry weight) (USGS 1980).
The range of concentrations of 90 Sr in food stuffs is summarized in Ta ble 6-7. The highest concentrations were observed in fresh vegetables (8.8 pCi/kg dr y weight=0.33 Bq/kg dry weight) and dry beans (15.9 pCi/kg dry weight=0.59 Bq/kg dry weight) (Eisenbud 1987). The U.S. Food and Drug Administration Radionuclides in Foods program monitors radionuclides (e.g., 90 Sr) in the food supply as part of the Total Diet Study (TDS). For the years 1994 and 1995, about 60 foods with historically high
90 Sr levels were analyzed (Capar and Cunningham 2000). 90 Sr was detected in about 65% of these foods. The greatest concentration was in mixed nuts at 2 Bq/kg (50 pCi). Approximately 200 reactor-survey food test portions, including raw vegetables, food crops (primarily fruits), fish, and milk, were collectedin the vicinities of 33 nuclear reactors (Cunningham et al. 1994). Ninety-four percent of the reactorsurvey food test portions had 90 Sr activities between 0 and 0.74 Bq/kg (0 and 20 pCi), and 6% had activity concentration between 0.74 and 7.4 Bq/kg (20 an d 200 pCi/kg). The EPA ERAMS program monitors ambient concentrations of 90 Sr in pasteurized milk at 42 sites in major population centers, and is used to assess trends and anomalies in concentrations. Tabl e 6-8 summaries pasteurized milk samples for the period of July 1997 (EPA 2002b). The average concentration of 90 Sr in pasteurized milk during this period for the 42 sites was 0.9 pCi/L (33 mBq/L). Sites with above average levels of 90 Sr in pasteurized milk were observed at (listed in order of decreasing activity of 90 Sr): Minot, North Dakota; Grand Rapids, Michigan; Spokane, Washington; Cleveland, Ohio; Cincinnati, Ohio; Memphis, Tennessee; St. Paul, Minnesota; Chicago, Illinois; Detroit, Michigan; San Francisco, California; Baltimore, Maryland; and Wilmington, Delaware. Dietary intake of 90 Sr peaked in 1965 at 1.1 Bq/day (30 pCi/day), during a period of atmospheric testing of nuclear weapons, and has c ontinued to decline to <0.05 Bq/day (<1.2 pCi/day) after 1987 (Cunningham et al. 1989). Dietary intake of 90 Sr in the United States from 1961 to 1991 is illustrated in Figure 6-3.
Sato et al. (1977) determined the concentration of strontium in tobacco leaves as 141 μg/g. The average concentration of strontium in the ash of 12 bra nds of cigarettes was measured as 373 μg/g (Iskander 1986). No significant difference was observed in the c oncentration of strontium in the cigarette filter before and after smoking (Sato et al. 1977). The ranges of concentrations of strontium in waste materials are: municipal solid waste (MSW) 11–35 μg/g; incineration fly ash 110–220 μg/g (Lisk 1988); coal flySTRONTIUM 230 6. POTENTIAL FOR HUMAN EXPOSURE


### Table 6-6. Concentrati on of Strontium in Fruit Juices and Produce Fruit juice and produce Average liquid concentration Average solid concentration (μg/L) a (ppm) b Apple 13.58 Apple juice 0.1271 Banana 0.1297 Bean: Dry 6.63 Snap 21.7 Blackberry 0.2619 Boysenberry 0.9523 Cabbage 64.17 Corn: Sweet 0.416 Cucumber 24 Currant: Red 1.251 Grape: American 25.6 Concord 0.3661 European 38.4 Red 0.1086 White 0.6318 Kiwi 1.744 Lemon products: Lemon 0.0986 Bottled 0.5334 Lemonade 0.1653 Lettuce 22.26 Lime 0.3464 Mango 0.5121 Orange 25.56 Orange juice Brazilian 0.0417 California 0.5368 Florida 0.0933 Navel 0.5209 Pineapple 0.1612 Papaya 1.690 Peach 3.082 Pear 0.5912 Pineapple 0.0604STRONTIUM 231 6. POTENTIAL FOR HUMAN EXPOSURE


### Table 6-6. Concentrati on of Strontium in Fruit Juices and Produce Fruit juice and produce Average liquid concentration Average solid concentration (μg/L) a (ppm) b Potato 2.562 Raspberry 2.232 Strawberry 0.3001 Tangerine 0.0828 Tomato 9.96 Tomato sauce 0.8894

a Barnes 1997 b USGS 1980; values are parts per million, dry weight

### Table 6-7. 90 

### Sr in the Human Diets During 1982

New York City San Francisco

Diet category Intake kg/year g Ca/year Percent Percent Percent yearly pCi pCi yearly pCi pCi yearly intake Ca 90 Sr/kg 90 Sr/year intake 90 Sr 90 Sr/kg 90 Sr/year intake 90 Sr Dairy products Fresh vegetables Canned vegetables Root vegetables Potatoes Dry beans Total (vegetables)

Fresh fruit Canned fruit Fruit juice Total (fruits) Bakery products Flour Whole grain products Macaroni Rice Total (grains)

Meat Poultry Eggs

Fresh fish Shell fish Total (meat, eggs, and fish) Yearly intake Ca (total) 90 Sr (total) Ratio of 90 Sr/Ca Daily intake 200

48
22 10 38

3

59 11 28

44 34
11

3 3

79 20 15

8 1

- 216.0

18.7

4.4 3.8 3.8 2.1

9.4 0.6 2.5

53.7

6.5
10.3

0.6 1.1

12.6

6.0 8.7

7.6 1.6

-

370 g 58

9

3

20

10 3.2

8.8
5.4 3.4 2.3 15.9

2.6 1.1 1.7

3.0 4.5
6.2 2.4 0.6

0.4 0.3 0.6

0.2 0.2

- 641

422
119

34 88 48

152

12 48

131 153

69

7 2

35

6 10

1 <1

-

1978 pCi 5.3 pCi 90 Sr/g Ca 54 pCi/day 32

36

11

18

3 1.0

2.4
2.9 3.8 2.1 7.9

1.3 0.8 1.4

1.9 3.5
2.9 2.3 0.8

0.4 0.3 0.6

0.1 0.7

- 200

116

64 38 79 54

77

9 40

84 119

32

7 2

31

5 8

1 1

-

967 pCi 2.6 pCi 90 Sr/g Ca 2.6 pCi/day 21

36

13

25

5

1 pCi=37 mBq (conversion factor) Source: DOE 1984 STRONTIUM 232 6. POTENTIAL FOR HUMAN EXPOSURESTRONTIUM 6. POTENTIAL FOR HUMAN EXPOSURE 233

State a AL CA CA CA CO CT DE FL GA HI IA IL IN KY MA MD MI MN MN MO MS NC ND NJ NM NV NY NY OH 

### Table 6-8. 90 

### Sr in Pasteurized Milk in July 1997 City 90 Sr (pCi/L) Montgomery 0.98 Los Angeles 0.66 Sacramento 0.26 San Francisco 1.24 Denver 0.41 Hartford 1.31 Wilmington 1.00 Tampa 0.59 Atlanta 0.56 Honolulu 0.38 Des Moines 0.40 Chicago 1.38 Indianapolis 0.96 Louisville 0.20 Boston 0.77 Baltimore 1.06 Detroit 1.34 Grand Rapids 1.78 St. Paul 1.44 Kansas City 1.14 Jackson — Charlotte 1.25 Minot 2.12 Trenton 0.75 Albuquerque 0.53 Las Vegas 0.20 Buffalo 0.75 Syracuse 0.94 Cincinnati 1.60STRONTIUM 6. POTENTIAL FOR HUMAN EXPOSURE 234

State a OH OR PA PA PC PR SC TN TX TX VA VT WA WA 

### Table 6-8. 90 

### Sr in Pasteurized Milk in July 1997 City 90 Sr (pCi/L) Cleveland 1.60 Portland 0.79 Philadelphia 0.84 Pittsburgh 0.23 Cristobal 0.27 San Juan 0.51 Charleston 0.73 Memphis 1.54 Austin 0.29 Ft. Worth 0.50 Norfolk 0.89 Burlington 1.10 Seattle 0.49 Spokane 1.71

a Post office state abbreviations used Source: EPA 2000bSTRONTIUM 235 6. POTENTIAL FOR HUMAN EXPOSURE 

### Figure 6-3. U.S. Da ily Dietary Intake of 90 

### Sr, 1961–199290Sr (Bq/day)

0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6

1960 1965 1970 1975 1980 1985 1990 1995 Year

Source: Cunningham et al. 1994STRONTIUM 236 6. POTENTIAL FOR HUMAN EXPOSURE ash 30–7,600 μg/g; coal bottom ash 170–6,400 μg/g; flue-gas desulfurization by-products 70–3,000 μg/g; oil ash 50–920 μg/g; (Eary et al. 1990); and compost 260–420 μg/g (Evans and Tan 1998).

Levels of 90 Sr were measured in tissue samples of anim als killed by motorists near the low-level radioactive disposal site at Los Alamos National Laboratory and from background locations. The mean concentration of 90 Sr in tissues from deer and elk killed near th e low-level radioactive disposal site were 460 and 230 mBq/kg (12 and 7.0 pCi), respectively, wh ile concentrations at background locations were 130 and 6.3 mBq/kg (3.5 and 1.7 pCi), respectively (Ferenbaugh et al. 2002). Between 1994 and 1996, levels of skeletal 90 Sr in small mammals in the Exclusion Zone at Chernobyl, Ukraine averaged 297 Bq/g (8.0 nCi/g) (Chesser et al. 2000).

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE
The primary routes of human exposure to strontium are from inhalation of aerosols and ingestion of food and drinking water containing strontium. The inta ke of strontium, therefore, depends upon the concentration of strontium in air, drinking water, and in the food items that comprise a person’s diet, which may be highly variable. The average concentr ation of strontium in urban air is about 20 ng strontium/m 3 (see Section 6.4.1). Assuming that an adult breathes approximately 20 m 3 of air per day, the inhalation exposure would be 400 ng strontium/day. This value may be somewhat higher for persons living near sources of strontium emission. Worker s employed at industrial facilities that produce, process, and use strontium and strontium compounds will have higher exposures. Similarly, strontium is taken into the body by ingestion of drinking water. Using the concentration of strontium in U.S. drinking water to be 1 mg/L (see Section 6.4.2), and the cons umption rate as 2 L/day, the strontium intake from drinking water would be 2 mg/day. In a 1994 total diet study in the United Kingdom, the total dietary exposure to stable strontium was estimated at 1.3 mg /day (Ysart et al. 1999). As part of an Australian Market Basket Survey in 1994, the estimated daily intakes of strontium for female adults ranged from 0.89 to 1.2 mg/day (Gulson et al. 2001). Combining air, water, and diet exposures estimates, the total daily exposure to strontium is ~3.3 mg/day.
External exposure to 90 Sr is not a concern because of minor emission of penetrating radiation from 90 Sr. No estimate of the concentration of 90 Sr in air is available (see Section 6. 4.1). However, it is assumed that ambient concentrations of 90 Sr in the atmosphere are small relativ e to exposures from water and diet. If the concentration of 90 Sr in average U.S. drinking water is estimated as 0.1 pCi/L (4 mBq/L) or one radiochemical event per 5–10 minutes (see Section 6.4.2) , and the consumption rate of drinking water bySTRONTIUM 237 6. POTENTIAL FOR HUMAN EXPOSURE a normal adult is assumed to be 2 L/day, then the exposure from drinking water would be 0.2 pCi (7 mBq) per day. Since the inception of the TDS Radionuclides in Foods program in 1961, intake levels of 90 Sr in food have steadily declined from a peak le vel in 1965 of 1.1 Bq/day (30 pCi/day), to below 0.2 Bq/day (5 pCi/day) (Cunningham et al. 1989). A DOE Environmental Measurements Laboratory study estimated the average dietary intake of 90 Sr from 19 diet categories for individuals living in the urban areas of New York City and San Francisco. Ta ble 6-6 summarizes the data from this study (DOE 1984). For both locations, vegetables accounted for more than a third of the yearly dietary intake of 90 Sr at 36%. In the vegetable group, fresh vegetables were the largest contributors of 90 Sr dietary intakes. The next largest contributor of 90 Sr was grains and dairy products. Us ing a conservative estimate of total dietary exposure for 90 Sr of 5 pCi/day (0.19 Bq/day) and drinking water exposure of 0.2 pCi/day (7 mBq/day), the total estimated daily exposure to str ontium is approximately 5.2 pCi/day (0.19 Bq/day). Current population exposure levels to 90 Sr will be lower than this value as a result of decreasing concentrations of 90 Sr in the environment. However, this value may be somewhat higher for persons living near sources of 90 Sr, such as DOE facilities, and for workers employed at government facilities that produce, process, and use 90 Sr and 90 Sr waste compounds.

Table 6-9 summarizes measurements of concentrations of strontium in human tissues and body fluids resulting from consumption of food and water and from natural ba ckground sources (Tsalev 1984); these are nonoccupationally exposed populations. The highest concentrations of strontium are in the bones and teeth (Iyengar et al. 1978; Tsalev 1984).

The distributions of 90 Sr in the body are significantly different for males and females. As expected, the highest concentrations of 90 Sr are measured in the boney tissue. Males and females averaged 10.4 and 65 pCi/kg (0.38 and 2.4 Bq/kg) wet weight, respectiv ely. Males had a much higher concentration of 90 Sr in the muscular tissue compared to females. The heart and psoas muscles had respective concentrations of 90 Sr for men averaging 13.9 and 18.7 pCi/kg (0.51 and 0.69 Bq) wet weight versus respective concentrations of 7.4 and 1.9 pCi/kg (0.27 Bq/kg an d 70 mBq/kg) wet weight for females (Baratta and Ferri 1966). Approximately 1,000 human teeth, co llected in southern Ukraine in 1990–1991, had 90 Sr activities ranging from 1.0 to 16.3 mBq/g ash (0.027–0.44 pCi/q ash) (Kulev et al. 1994).
Strontium can be released into the atmosphere as a result of glass manufacturing. In one study, the median ambient air concentration of strontium that both art glass makers and formers were chronically exposed was 0.1 μ g strontium/m 3 (Apostoli et al. 1998). A National Occupational Exposure Survey conducted by NIOSH during 1981–1983 estimated the number of workers potentially exposed toSTRONTIUM 238 6. POTENTIAL FOR HUMAN EXPOSURE


### Table 6-9. Strontiu m Concentrations in Human Body Fluids and Tissues Sample Units a Mean Range Blood μg/L 27 No data Bone μg/g 138 63–281 Brain μg/g 0.08 No data Dental plaque μg/g 48 <0.5–1,880 Erythrocytes μg/L 7.2 No data Feces μg/day 1.5 No data Hair μg/g 4.2 0.75–10.8 Kidney μg/g 0.1 No data Liver μg/g 0.15 No data Lung μg/g 0.38 No data Milk μg/L 20 17–295 Muscle μg/g 0.05 No data Nails (finger) μg/g(dry weight) No data 0.43–0.86 Plasma or serum μg/L 40 10–70 Saliva μg/L 11 8–63 Sweat mg/7 hour 0.96 No data Tooth (dentin) μg/g 115 14–286 Tooth (enamel) μg/g 128 14–286 Urine μg/L No data <0.01–0.03

a Values are per wet weight unless otherwise noted. Source: Tsalev 1984STRONTIUM 239 6. POTENTIAL FOR HUMAN EXPOSURE strontium compounds in the workplace: strontium chloride (8,289), strontium fluoride (5,607), strontium hydroxide (385), and strontium nitrate (1,895) (NOES 1983).
Workers engaged in nuclear fuel cycle operations, such as the handling of radioactive strontium wastes, decontamination and decommissioning workers, cont aminated soils, and waters may be potentially exposed to radioactive strontium. A case of accidental inhalation and dermal exposure to strontium titanate contaminated with 90 Sr used for lightning rods was recorded, which resulted in an exposure of approximately 10 5 Bq (2.7 mCi) to the work ers (Navarro and Lopez 1998).

6.6 EXPOSURES OF CHILDREN
This section focuses on exposures from conception to matu rity at 18 years in humans. Differences from adults in susceptibility to hazardous substan ces are discussed in 3.7 Children’s Susceptibility.
Children are not small adults. A child’s exposure ma y 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. Child ren crawl on the floor, put things in their mouths, sometimes eat inappropriate things (such as dirt or paint chips), and spend more time outdoors. Children also are closer to the ground, and they do not use the judgment of adults to avoid hazards (USNRC 1993a).
As part of an Australian Market Basket Survey in 1994, the estimated daily intakes of strontium for 6-month-old infants fed exclusively breast milk or infant formula were 47 and 254 μ g/day, respectively (Gulson et al. 2001). The mean concentration of strontium in amniotic fluid and placenta ranged from 0.03 to 0.05 mg/L and from 1.6 to 3.2 μ g/L, respectively, for mothers from Portugal (Carvalho et al. 2001). Harrison (1965) notes that strontium in human breast milk is transferred to newborns during breast feeding.
Specific information on the exposure of children to radios trontium is limited. As for adults in the general population, small exposures to children occur from no rmal ingestion of food and drinking water and inhaling air. These exposures may be higher in areas near nuclear fuel processing sites and hazardousSTRONTIUM 240 6. POTENTIAL FOR HUMAN EXPOSURE waste sites containing radiostrontium. Future accide ntal exposures could potentially occur from nuclear weapons detonation and con sequent contamination of air, water, and food.
Children typically ingest a higher percentage of diary products compared to adults. Levels of 90 Sr in body tissues tend to increase with age (Glowiak and Pacyna 1978). In a study in the Soviet Union between 1959 and 1971, children were reporte d to have elevated levels of 90 Sr in bone tissue between the ages of 1 and 4 years (Marei et al. 1976). The elevated levels of 90 Sr for children of this age were determined to be a direct result of diet, primarily from 90 Sr contaminated cow’s milk. In a 1978 study in Poland, females between 0 and 20 years of age had the highest level of 90 Sr accumulation in the gonad tissues for all age levels (Glowiak and Pacyna 1978). No explanation as to a cause for this accumulation was provided. For 1979–1994 births, the average concentration of 90 Sr in deciduous teeth from children of Western Suffolk County (New York), Eastern Su ffolk County (New York), Dade County (Miami, Florida), and Ocean County (New Jersey) were 1.56, 1.02, 2.80, and 1.54 pCi/g calcium, respectively (Gould et al. 2000). No additional information is ava ilable on whether children differ from adults in their weight-adjusted intake of stron tium. There is no information on 90 Sr levels in amniotic fluid, meconium, cord blood, neonatal blood, or breast milk.
At hazardous waste sites, radiostrontium that is found in excess of natural background levels is most likely to be in soil and presents a special hazard fo r young children. Hand-to-mouth activity resulting in inadvertent soil consumption or in tentional consumption of soil (pica behavior) will result in oral exposure to radiostrontium. Young children often play close to the ground and frequently play in dirt, which increases their dermal exposure to radiostrontiu m in dust and soil. The degree of hazard in each case depends on the form of strontium present at the waste site.
Compared to adults, the potential for radiostrontiu m exposure is greater for children who consume foods (e.g., milk, grains) produced in areas with elevated c oncentrations of radiostrontium in the soil and for children with elevated concentrations of radiostrontiu m in their drinking water. Children are more likely to be exposed to 90 Sr in cow’s milk produced in contaminated areas. Table 6-8 summaries pasteurized milk samples in the United States for July 19 97 (EPA 2002b). The average concentration of 90 Sr in pasteurized milk during this period was 0.9 pCi/L (33 mBq/L).
Other home exposures are unlikely since no household products or products used in crafts, hobbies, or cottage industries contain significant amounts of ra diostrontium. Radiostrontium exposure to children from parents’ work clothes, skin, hair, tools, or ot her objects from the workplace is possible if the parentSTRONTIUM 241 6. POTENTIAL FOR HUMAN EXPOSURE is exposed to radiostrontium at work. Howeve r, no specific cases of home contamination with radiostrontium were located in the literature.

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES
Cigarettes and tobacco leaves are known to contain strontium, and individuals who smoke may be exposed to higher levels of strontium. Strontiu m has been found in the tobacco leaves and ash of cigarettes at average levels of 141 and 373 mg/kg, respectively (Iskander 1986).
The potential for 90 Sr exposure is greater for individuals who consume foods grown in areas with elevated concentrations of 90 Sr in soil, and for individuals with elevated concentrations of 90 Sr in drinking water. Industries where higher exposures to 90 Sr are known to occur include nuclear weapons test sites, nuclear weapons production, and nuclear reactors facilities. Populations with potentia lly high exposure include DOE employees involved in heavy construction, deco ntamination activities, chemical processing, and fabrication.
Populations with a relatively short food chains (e.g ., Arctic peoples) and a hi gher per capita consumption of country foods that have elevated levels of contamination from radionuclides, will have a higher exposure to 90 Sr (Barrie et al. 1992). Caribou or reindeer f eeding on arctic vegetation are more likely to accumulate higher body burdens of 90 Sr in edible tissues than othe r herbivorous animals with less restrictive diets (Witkamp 1966). Concentrations of 90 Sr in caribou meat per gram of calcium were high (150 pCi/g Ca) compared with those of Alaskan-grown cabbage (6 pCi/g Ca) and potatoes (8 pCi/g Ca), marine fish (5 pCi/g Ca), and whale meat (1 pC i/g Ca). Arctic peoples, who depend on caribou and reindeer for sustenance, may ha ve an elevated body burden of 90 Sr compared to other people who consume a more varied diet (Witkamp 1966). However, the 1966 peak levels reported in this study are expected to have fallen to minuscule leve ls since the Test Ban Treaty of 1962.

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 strontiu m is available. Where adequate information is not available, ATSDR, in conjunction w ith the National Toxicology Program (NTP), is required to assure theSTRONTIUM 242 6. POTENTIAL FOR HUMAN EXPOSURE initiation of a program of research designed to determin e the health effects (and techniques for developing methods to determine such health effects) of strontium.
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 substan ce-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 id entified data needs will be evaluated and prioritized, and a substance-sp ecific research agenda will be proposed.

6.8.1 Identification of Data Needs
Physical and Chemical Properties. Relevant data on the physical and chemical properties of strontium and strontium compounds are available in th e literature and are sufficient to permit estimation of its environmental fate (ChemFinder 2002; Cotto n and Wilkenson 1980; Hibbins 1997; HSDB 2002; Lide 1995, 2000; Merck 1989; Sigma-Aldrich 2000) . The physical and chemical properties of radiostrontium and radiostronium compounds are expected to be equivalent to those for stable strontium. Data on the radioactive properties of isotopes of strontium are available (Lide 1995).
Production, Import/Export, Use, Release, and Disposal. Data regarding the past and present production and import/export volumes for strontium are available (Adams 1975; USGS 1998, 1999, 2002). The uses of strontium and strontium com pounds are well known with more than 85% of all strontium consumed in the United States used in th e manufacture of ceramics and glass products (Hibbins 1997; USGS 1999, 2002). Strontium is found in food products such as fruits and vegetables (Barnes 1997; USGS 1980). Since strontium is not covered under Superfund Amendments and Reauthorization Act (SARA), Title III, manufacturers and users are not required to report releases to the EPA’s Toxics Release Inventory (TRI). Most nonradioactive str ontium minerals, strontium compounds, and strontiumcontaining materials do not require special disposal and handling requirements.
Data regarding the past and present production and import/export volumes for radiostrontium are limited (DOE 1996b, 1996c). The uses of radiostrontium and radiostrontium compounds are restricted primarily to medicinal, analytical, and power generation applications (Alimov 2003; Murray 1994). Radioactive strontium (e.g., 90 Sr) was released into the atmosphere fro m aboveground testing of nuclear weapons during the period of 1945–1980. Nuclear weapon testing injects radioactive material into the stratosphere, which results in wide dispersal of radionuclides. However, atmospheric deposition of 90 SrSTRONTIUM 243 6. POTENTIAL FOR HUMAN EXPOSURE has steadily decreased from a high in 1963 of approximately 1.10x10 8 GBq (3.0 MCi) to <3,000 Ci in 1990, which suggests that global concentrations of 90 Sr in the atmosphere have declined (DOE 1996c). The disposal of radiostrontium and radiostrontium c ontaminated wastes is governed by the U.S. Nuclear Regulatory Commission (USNRC) regulations, and releases of radiostrontium and radiostrontium contaminated wastes are governed by USNRC and EPA regulations.

Environmental Fate. Information about the partitioning and mobility of strontium and strontium compounds in the environment is available (Bunde et al. 1997; Bunzl and Schimmack 1989; Hayes and Traina 1998; Helal et al. 1998a, 1998b; O’Day et al. 2000; Parkman et al. 1998; Sahai et al. 2000). Strontium released into the atmosphere from natura l and anthropogenetic activ ities is transported and redeposited on the earth by dry or wet deposition (N CRP 1984). Because strontium is an element, its atoms do not degrade by environmental processes such as hydrolysis or biodegradation.
Information about the partitioning and mobility of 90 Sr in environment is available (Bunde et al. 1997, 1998; DOE 1996d; Kashparov et al. 2001; Mahara 1993; Sokolik et al. 2001; Toran 1994). Radiostrontium released into the atmosphere fro m anthropogenetic activities is transported and redeposited on the earth by dry or wet deposition (NCRP 1984). Radiostrontium does not degrade by environmental processes such as hydrolysis or biodegrad ation. However, radioactive strontium will be subject to radioactive decay and transformation to ot her elements. Eventually, all of the radioactive strontium will be transformed into stable zirconi um by the process of radioactive decay. Additional information on the environmental fate of 90 Sr in different forms of mixed waste may be beneficial. Studies investigating mixed waste matrixes may be useful information for accessing the current and potential risk of the storage of liquid HLW in buried underground tanks. Mixed waste forms that pose the highest potential risk include mixtures such as me tals-radiostrontium, meta ls-radiostrontium-organic acids, metals-radiostrontium-complexing agents , and metals-radiostrontium-ketones (DOE 1992).
Bioavailability from Environmental Media. The absorption and distribution of strontium and radiostrontium as a result of inhalation, dermal, or or al exposures have been discussed in Sections 3.5.1 and 3.5.2. Limited information on the bioavailability of strontium and radiostrontium from environmental media (e.g., plants and animals) is available. Additional studies on the bioavailability of strontium and radiostrontium from envi ronmental media would be useful.

Food Chain Bioaccumulation. The uptake or bioaccumulation of strontium and radiostrontium by plants and organisms is the mechanism by which strontium and radiostrontium in air, water, and soil enterSTRONTIUM 244 6. POTENTIAL FOR HUMAN EXPOSURE into the food chain of humans. Information on tissue levels of strontium and radiostrontium indicating storage in the organism as a result of exposure to contaminated media would be useful. Information on whether strontium and radiostrontium are biomagnified (increased levels in predators resulting from the consumption of contaminated prey or ganisms) would also be helpful.
Exposure Levels in Environmental Media. Strontium has been detected in air (Dzubay and Stevens 1975; Sweet et al. 1993; Witz et al. 1986), water (Capo et al. 1998; EPA 1981, 2002b; USGS 1963), soil (Capo et al. 1998; EPA 1995a), plants (Sato et al. 1977), and foodstuff (Barnes 1997; USGS 1980). Reliable monitoring data for the levels of st rontium in contaminated media at hazardous waste sites are needed so that the information obtained on leve ls of strontium in the environment can be used in combination with the known body burden of strontiu m to assess the potential risk of adverse health effects in populations living in the vicinity of hazardo us waste sites. In a 1994 total diet study in the United Kingdom, the total dietary exposure to stable strontium was estimated at 1.3 mg/day (Ysart et al. 1999). As part of an Australian Market Basket Survey in 1994, the estimated daily intakes of strontium for female adults ranged from 0.89 to 1.2 mg/day (Gulson et al. 2001). Combining air, water, and diet exposures estimates, the total daily expo sure to strontium is ~3.3 mg/day.
Radiostrontium has been detected in air (DOE 1996c; Eisenbud 1987), water (DOE 1992, 1996c; EPA 2000a, 2002b; Hamilton et al. 1996; Kraybill 1983; Pu jol and Sanchez-Cabeza 2000), soil (DOE 1992; Fresquez et al. 1996b; Kashparov et al. 2001; Malek et al. 2002; Sokolik et al. 2001), and foodstuffs (Capar and Cunningham 2000; Cunningham et al. 1989, 1994; Eisenbud 1987; EPA 2002b). Information on levels of radiostrontium is needed. Exposure levels of 90 Sr in environmental media have decreased as a result of radioactive decay from a high in th e 1960s. However, updated information on the concentration levels in air, water, soil, and food (e.g., milk products) may be useful. Specific monitoring of radiostrontium in airborne particulates may also be beneficial. Reliable monitoring data for the levels of radiostrontium in contaminated media at hazardous w aste sites may be useful so that the information obtained on levels of radiostrontium in the environmen t can be used in combination with the known body burden of radiostrontium to assess the potential risk of adverse health effects in populations living in the vicinity of hazardous waste sites. Using a conservative estimate of total dietary exposure for 90 Sr of 5 pCi/day (0.19 Bq/day) (Cunningham et al. 1989) and drinking water exposure of 0.2 pCi/day (7 mBq/day) (EPA 2000a), the total estimated daily exposure to strontium is approximately 5.2 pCi/day (0.19 Bq/day).STRONTIUM 245 6. POTENTIAL FOR HUMAN EXPOSURE Exposure Levels in Humans. Strontium has been detected in human tissues, as illustrated in Table 6-9 (Tsalev 1984). The highest concentrations of strontium are in the bones and teeth (Iyengar et al. 1978; Tsalev 1984). However, these data are not current (within 3 years). Additional human tissue monitoring data for strontium is needed for popul ations surrounding hazardous waste sites. This information is necessary for asses sing the need to conduct health studies on these populations.

90 Sr has been detected in human tissues with the highest concentrations measured in boney tissues (Baratta and Ferri 1966; Kulev et al. 1994). However, these data are not current (within 3 years). Exposure levels of humans to 90 Sr have decreased as a result of ra dioactive decay from a high in the 1960s. Additional human tissue monitoring data for ra diostrontium is needed for populations surrounding hazardous waste sites. This information is necess ary for assessing the need to conduct health studies on these populations.
Exposures of Children. Children are exposed to strontium in the same manner as adults, primarily by food and water intake. No information was ava ilable on unique exposure pathways for children (e.g., pica children, dermal). However, children typically ingest a higher percentage of diary products compared to adults. Data exist on the levels of strontium in human breast milk (Gulson et al. 2001). Additional body burden studies on ch ildren are needed for strontium. Additional studies are needed to determine whether children are different in their weight -adjusted intake of strontium. Better and more recent information on exposure levels of strontium to children may be beneficial.
Children are exposed to radiostrontium in the same ma nner as adults, primarily by food and water intake. No information was available on unique exposure pathways for children (e.g., pica children, dermal). However, children typically ingest a higher percenta ge of diary products compared to adults. Exposure levels of children to 90 Sr have decreased as a result of radioactiv e decay from a high in the 1960s. Data exist on the levels of 90 Sr in deciduous teeth (Gould et al. 2000) . Additional body burden studies on children are needed for radiostrontium. Additional studies are needed to determine whether children are different in their weight-adjusted intake of radi ostrontium. Better and more recent information on exposure levels of radiostrontium to children may be beneficial.
Child health data needs relating to susceptibility are discussed in Section 3.13.2 Identification of Data Needs: Children’s Susceptibility.STRONTIUM 246 6. POTENTIAL FOR HUMAN EXPOSURE Exposure Registries. No exposure registries for strontium or radiostrontium were located. These substances are not currently compounds for which a s ubregistry has been established in the National Exposure Registry. These substances will be considered in the future when chemical selection is made for subregistries to be established. The informati on that is amassed in the National Exposure Registry facilitates the epidemiological resear ch needed to assess adverse health outcomes that may be related to exposure to this substance.

6.8.2 Ongoing Studies
The Federal Research in Progress (FEDRIP 2002) da tabase provides additional information obtainable from a few ongoing studies that may fill in some of the data needs identified in Section 6.8.1. These studies are summarized in Table 6-10.STRONTIUM 247 6. POTENTIAL FOR HUMAN EXPOSURE 

### Table 6-10. Ongoing Studies on the Environmental Effects of Strontium a

Investigator Affiliation Study Sponsor Ron, Elaine NIH Studies of populations exposed to occupational NIH sources of radiation Helt, JE ANL Waste volume reduction using surface DOE-OEM characterization and decontamination by laser ablation Todd, Terry A INEEL Laboratory radi oactive waste solvent extraction DOE-OEM and ion exchange Smith, Robert W INEEL Calcite precipitation and trace metal partitioning DOE-OEM in groundwater and the vadose zone: Remediation of 90 Sr and other divalent metals and radionuclides in arid western environments Louie, Gary D PNNL Chemical separations for nuclear waste disposal DOE-OEM Louie, Gary D PNNL Chemical specia tion of strontium, americium, and DOE-OEM curium in waste ANL = Argonne National Laboratory; DOE-OEM = Department of Energy-Offi ce of Environmental Management; INEEL = Idaho National Engineering and Environmental Labo ratory; NIH = National Institute of Health; PNNL = Pacific Northwest National Laboratory

a Source: FEDRIP 2002STRONTIUM 249



### 7. ANALYTICAL METHODS
The purpose of this chapter is to describe the analytical methods that are available for detecting, measuring, and/or monitoring strontium, its metabolit es, and other biomarkers of exposure and effect to strontium. 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 th e 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 fo r 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.
Its companion manual, the Draft Multi-Agency Radiological Laboratory Analytical Protocols (MARLAP) manual, robustly describes relevant analytical e quipment and methods, and became available for public comment in July 2001 (MARLAP 2001).

7.1 BIOLOGICAL MATERIALS
Strontium can enter the human body through inhalation, ingestion, or penetration through the skin. Measurement of the quantities of radiostrontium in the body can be performed by two primary methods, in vivo measurements and in vitro measurements. These types of measurements are called bioassays. In vivo techniques measure the quantities of internally deposited radiostrontium directly using a whole body counter, while in vitro techniques permit estimation of interna lly deposited strontium by analysis of body fluids, excreta, or (in rare instances) tissues obtained through biopsy or postmortem tissue sectioning. Some of these analytical methods are summarized in Table 7-1.

7.1.1 Internal Strontium Measurements

In vivo (or direct) measurements of radioactive strontium in the body are made with radiation detector systems and associated electronics called whole body c ounters that measure radiation as it leaves the body from internally deposited radioactive strontium. Th is system measures the emission of gamma rays or x-rays from internally deposited radionuclides. Th ese counters are insensitive to beta particles emittedSTRONTIUM 250 7. ANALYTICAL METHODS 

### Table 7-1. Analytical Me thods for Determining Stront ium in Biological Samples Sample Analytical Detection Percent matrix Sample preparation method limit recovery Reference Blood Acidification with nitric GFAAS 0.13 mg/L 94.5–102.5 Burguera et al. acid; dilution; addition of 1999 La matrix modifier Blood Acid digestion; iron TRXF 0.04 μg/mL No data Prange et al. 1989 extraction; clean-up by ion exchange; thin film deposition Blood Acid digestion; dilution ICP-AES 0.3 μg/L 113 NIOSH 1994; Piette et al. 1994 Blood serum Dry ashing; neutron TNA 0.02 μg/mL 75–90 Teree and Cohn activation; chemical 1966 separation Blood serum Acidification and dilution ICP-MS No data 99 Muñiz et al. 1999 Bone Acidification with nitric GFAAS 0.13 mg/L 96.5–102.9 Burguera et al. acid; dilution; addition of 1999 La matrix modifier. Bone Acid digestion ICP-MS 6 μg/g dry No data Outridge et al. 1996 weight Bone ash Acid dissolution; clean-up β -GPC No data No data Mutschke and by coprecipitation and Pribilla 1967 scavenging Hair Ashed PIXE 1 μg/g No data Clayton and Wooller 1985 Tissues Acid digestion; dilution ICP-AES No data 113 NIOSH 1994 Tissues Complexometric digestion GFAAS 2.2 ng/g 99±4.2 D’Haese et al. 1996 in TMAH/EDTA matrix with heat Urine Acidification with nitric GFAAS 0.13 mg/L 98.8–101.5 Burguera et al. acid; dilution; addition of 1999 La matrix modifier Urine Coprecipitation with LSC 7 dpm/L 95±5 Dietz et al. 1991 calcium phosphate; (0.82 Bq/L sample wet ashed with or nitric acid; extraction and 22 pCi/L) separation on Crown ether loaded chromatographic column Urine Wet ashed; precipitation LSC 0.6 pCi 100 Kramer and Davies with oxalate; acid (22 mBq) 1982 dissolution; chemical extraction β -GPC (total radioactive strontium) = beta gas proportional counter; Bq = Be cquerel; dpm = disintegrations per minute; EDTA = ethylenediamine tetraacetic acid; GFAAS (t otal strontium) = graphite furnace atomic absorption spectroscopy; ICP-AES (total strontium) = inductively c oupled plasma atomic emission spectroscopy; ICP-MS (isotopic strontium composition) = inductively coupled plasma-mass spectrometry; La = Lanthanum; LSC (isotopic quanitification of 89 Sr and 90 Sr) = liquid scintillation counting; pCi = pico curies (10 -12 curies); PIXE (total strontium) = proton induced x-ray emission; TMAH = tetramethylammonium hydroxide; TNA (total strontium) = thermal neutron activation and radiometric measurement; TRXF (tot al strontium) = total-reflection x-ray fluorescenceSTRONTIUM 251 7. ANALYTICAL METHODS from radiostrontium; thus, the utility for radiostron tium is limited to high exposure measurements. In vivo assays are the most direct method of quantifying in ternally deposited radioactive materials. The determinations of 90 Sr levels are achieved by measuring, with a phoswich detector, the bremsstrahlung of the 90 Y beta rays (photons with energies ranging fr om 30 to 160 keV). The most commonly used detectors for measurement of 90 Y bremsstrahlung (i.e., electromagnetic radiation) by in vivo counting are sodium iodide or phoswich (NaI and CsI sandwich) (Tokareva et al. 2000). For whole-body counting, a scanning-bed geometry in a special shielding room is typically used. Although whole body counters may be used in many configurations, a chest counter is usually used for inhaled radioactive materials. In vivo analysis is widely used throughout the nuclear i ndustry, both commercial and government, for quantifying levels of insoluble radioactive mate rials in the body (Kozheurov 1994).

In vivo counting systems are calibrated using tissue-e quivalent phantoms. These phantoms have shapes similar to the human torso and are made of polystyre ne or other tissue equivalent material. Standard radioactive strontium sources of known activity are inserted at locations where strontium would be expected to accumulate in a human body. Relati onships are determined between the radioactive strontium activity measured by the detection system and the known activity in the phantom (Kozheurov 1994).

7.1.2 In Vivo and In Vitro Radiostrontium Measurements

In vitro radioactive strontium analyses are routinely performed in support of a personnel monitoring program or in cases where the size of an operation does not justify the cost of whole body counter facilities. These analyses are usually done on urine samples, but other types of body materials (e.g., feces or blood) may also be used. Urinalysis is effective for analysis of transportable or soluble strontium. Strontium may also be measured in fecal material us ing the same methods identified above for urinalyses, except that this matrix requires extensive preparation.

7.2 ENVIRONMENTAL SAMPLES
Two types of methods are commonly used for me asurement of strontium and radiostrontium in environmental samples. The first is field surveys using portable survey instruments, and the second is analysis of samples procured in the field that ar e returned to the laboratory for quantification.STRONTIUM 252 7. ANALYTICAL METHODS
7.2.1 Field Measurements of Radiostrontium

Radiostrontium measurements in the fi eld are typically qualitative in nature in that the instruments simply respond to beta emissions, regardless of their origin. However, the levels can be measured quantitatively if key parameters are known, such as the relative abundances of all beta-emitting isotopes present, the thickness of the layer being assessed, and the detection efficiency of the instrument for the type of surfacebeing assessed. Measurements in the past have typically been made using portable, hand-held GeigerMueller or beta scintillation detectors equipped with a count rate meter, which det ect beta radiation while discriminating against other forms of ionizing radiatio n in the same area. Survey instruments can provide a quick estimate or a measure of the level of activity that might be present. However, more accurate measurements of radioactive strontium may require that samples be taken for laboratory analyses.

7.2.2 Laboratory Analysis of Environmental Samples
Analytical methods for measuring strontium in environm ental samples are summarized in Table 7-2. The available methods can be divided into two groups: chemical methods to determine the total mass of strontium in a sample and radiological methods to determine amounts of radioactive isotopes. Environmental media that have been tested for strontiu m include air filters, swipes, biota, water, soil, and others. A full range of laboratory analysis methods has been used to quantify the total strontium or its radioactive isotopes.
The chemical methods for detecting total strontium include spectrophotometry, fluorometry, kinetic phosphorescence, atomic absorption sp ectroscopy (e.g., flame and graphite furnaces), energy dispersive x-ray analysis (i.e., EDAX), x-ray fluorescence spectrometry, and inductively coupled plasma spectroscopy-atomic emission and mass spectrometry applications (i.e., ICP-AES and ICP-MS).
The quantity of radioactive strontium is typica lly determined by gas-flow proportional, liquid scintillation, and Cherenkov counting techniques (Scarp itta et al. 1999). The standard EPA analytical procedure to determine radiostrontium in water is Me thod 905.0, and several methods are permutations of this procedure. A stable strontium carrier is added to the water sample so that 89 Sr and 90 Sr are precipitated as insoluble carbonates. The sample th en undergoes a preliminary counting that represents the total strontium activity ( 89, 90 Sr) plus a small fraction of 90 Y that has grown in by radioactive decay.STRONTIUM 253 7. ANALYTICAL METHODS 

### Table 7-2. Analytical Methods for Determining Strontium in Environmental Samples Sample Percent Sample matrix Sample preparation Analytical method detection limit recovery References Air Particulate collection on cellulose filter; acid digestion Water Acid digestion

Water Filtration; acid digestion; add matrix modifier Water Wet acid digestion Drinking, raw, Wet acid digestion; and waste addition of Sr carrier water and precipitation as SrCO 3 ; extraction of Yttrium; precipitation of Yttrium oxalate. Water Complex EDTA; ion chromatography; precipitate Sr effluent fraction as SrCO 3 Water (high Sr Ion chromatography; concentration) dilution Saline water Dilution Soils and Digest organic sediments matter; pyrosulfate fusion; dissolve condensed phosphates Soils and Fuse with NaOHsediments Na 2 CO 3 ; dissolve in acid; ion exchange Vegetation and Dry ash; food complexation with EDTA; ion exchange chromatography; precipitate Sr effluent fraction as SrCO 3 Milk Complexation of Y in growth; extraction; precipitation as oxalate FAAS (Method D4185)
Spectrophotometric measurement (total strontium) (Method 911.03) FAAS (Method D3920; 7780) ICP-AES (Method 200.15) β -GPC (Method 973.66; 7500-Sr)

β -GPC (Method 008)

β -GPC FAAS (Method D3352) β -GPC

β -GPC (Method 008-S)
β -GPC (Method 008-V)

β -GPC (Method 974.37) 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 ATSM 1999

No data AOAC 1990

No data ASTM 1999; OSW 1992 No data EMMI 2000a 93–99 AOAC 1990; APHA 1992

No data EMMI 2000b

No data EMMI 2000c, 2000d 100–106 ASTM 1999 No data EMMI 2000c, 2000d

No data EMMI 2000b

No data EMMI 2000b

No data AOAC 1990

89 Sr and 90 Sr measured separately by measuring 90 Y in-growth ß-GPC (total radioactive strontium) = beta gas proportional counter; EDTA = ethylenediamine tetraacetic acid; FAAS (total strontium) = flame atomic abs orption spectroscopy; ICP-AES (total st rontium) = inductively coupled plasma atomic emission spectroscopySTRONTIUM 254

The 90 Y is allowed to reach equilibrium (e.g., approximat ely a 2-week period) and then is separated with stable yttrium-carrier as yttrium hydroxide (i.e., Y(OH) 3 ). The Y(OH) 3 precipitates are converted to the oxalate and the solid oxalate is beta counted in a low background gas-flow proportional counter. The 90 Sr concentration is determined from the 90 Y activity and the 89 Sr concentration by difference. Variations of the above method involve different techniques of selectively separating strontium from environmental samples. Using the various separation methods al ready described, Cherenkov counting, in conjunction with liquid scintillation, has also been use to detect 90 Sr by measuring the concentration of its progeny,
90 Y, in solution (Scarpitta et al. 1999).
Horwitz et al. (1991) developed an extraction chromatography technique in which strontium can be selectively separated from other interfering radionuclid es such as alkaline and alkaline earth element ions. The technique uses an extraction column (e.g., S r-resin) with a crown ether (4,4’(5’)-bis(tertbutylcyclohexano)-18-crown-6) sorbed on an inert polymeric porous support. A sample with 90 Sr digested in concentrated nitric acid is diluted and loaded on the Sr-resin column in ~3 M nitric acid. Interfering elements are removed from the column with ~1 M nitric acid and strontium ions are subsequently eluted with a dilute acid solution. 90 Sr ions are then beta counted using a low background gas flow proportional counter or Cherenkov counting of 90 Y as previously discussed (Grahek et al. 1999; Torres et al. 2000, 2002). One disadvantage with this t echnique is some ions interfere with the strontium separation. For example, potassium diminishes the capacity of the Sr-resin column to retain strontium; lead also shows a very strong retention on the Sr-resin and irreversibly blocks Sr adsorption sites (Miró et al. 2002). Recently, improvements have been made to the extraction process using a wetting film technique, which has been shown to reduce ionic interferences (Miró et al. 2002).

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 strontiu m is available. Where adequate information is not available, ATSDR, in conjunction w ith the National Toxicology Program (NTP), is required to assure the initiation of a program of research designed to determin e the health effects (and techniques for developing methods to determine such health effects) of strontium.
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 substan ce-specific informational needs that if met wouldSTRONTIUM 255 8. REGULATIONS AND ADVISORIES
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 id entified data needs will be evaluated and prioritized, and a substance-sp ecific research agenda will be proposed.

7.3.1 Identification of Data Needs
Methods for Determining Biomarkers of Exposure and Effect. Analytical methods with satisfactory sensitivity and precision are available to determine the levels of strontium in human tissues and body fluids. Strontium and radiostrontium are found in essentially all food, water, and air, so everyone is exposed to some levels. Recently, Sutherland et al. (2000a, 2000b ) developed a molecular biological strategy to identify clustered lesions in DNA resulting from in vitro cellular exposure to gamma radiation. It is possible that this technique might be adapted to evaluate genetic damage in blood cells following exposure to radioactive strontium. This method, however, will not be specific for 90 Sr effects.
Methods for Determining Parent Compounds and Degradation Products in Environmental Media. Analytical methods with the required sensitivit y and accuracy are available for quantification of strontium, both total and isotopic, in environmenta l matrices (Table 7-2). Knowledge of the levels of strontium in various environmental media, along with the appropriate modeling (see Chapters 3 and 5), can be used to evaluate potential human e xposures through inhalation and ingestion pathways.

7.3.2 Ongoing Studies
No ongoing studies investigating new methods for detec tion and speciation of strontium or radiostrontium were identified in the Federal Research in Progress database (FEDRIP 2002).STRONTIUM 257



### 8. REGULATIONS AND ADVISORIES
The international, national, and stat e regulations and guidelines regarding stable strontium in air, water, and other media are summarized in Table 8-1. The regulations and guidelines regarding radioactive strontium are summarized in Tables 8-2 and 8-3.

Stable Strontium. An MRL of 2.0 mg strontium/kg/day fo r intermediate-duration oral exposure to strontium was calculated by dividing a NOAEL of 140 mg strontium/kg/day for skeletal toxicity in young rats (Storey 1961) by an uncertainty factor of 30 and a modifying factor of 3 (see Appendix A).
The EPA derived a chronic reference dose (RfD) of 0. 6 mg/kg/day for strontium (IRIS 2002). The RfD is based on a NOAEL of 190 mg strontium/kg/day for skeletal toxicity in young rats (Storey 1961).
The EPA has not classified stable strontium for human carcinogenicity (IRIS 2002). A number of agencies have classified strontium chromate as a hum an carcinogen by the inhalation route, on the basis of occupational and animal studies. The carcinogenic ity of strontium chromate is attributed to the hexavalent chromium ion and not to strontium. The American Conference of Governmental Industrial Hygienists (ACGIH) has given strontium chromate the classification A2, suspected human carcinogen, and has established an 8-hour time-we ighted-average (TWA) of 0.0005 mg/m 3 for occupational exposure (ACGIH 2002). The International Agency for Research on Cancer (IARC) has assigned strontium chromate, along with other chromates, to Group 1, as a human carcinogen (IARC 1990, 2002a). No other stable strontium compound is listed by IARC.

Radioactive Strontium. No MRLs were derived for inhalation or oral exposures to radioactive strontium. The EPA has not derived reference concentrations (R fCs) or RfDs for radioactive strontium (IRIS 2002), nor does the Integrated Risk Information Syst em (IRIS) database provide cancer assessments for radioisotopes of strontium. This function is the r esponsibility of the EPA Offi ce of Radiation and Indoor Air (ORIA). All radionuclides, including radioisotopes of strontium, are classified as known human (Group A) carcinogens. This classification is based on results of epidemiological studies of Japanese atomic bomb survivors, underground uranium miners, radium dial painters, and patients subjected to a variety of radiation treatments, as well as results of laboratory animal research and mammalian tissue culture studies. ORIA has published cancer slope fact ors (mortality and morbidity cancer risk estimates) for all known radionuclides, by various exposure r outes (inhalation, drinking water ingestion, food ingestion, soil ingestion, immersion in a cloud, and external exposure from contam inated soil) for five ageSTRONTIUM 258 8. REGULATIONS AND ADVISORIES 

### Table 8-1. Regul ations and Guidelines Applicable to Stable Strontium Agency Description Information Reference INTERNATIONAL Guidelines: IARC Carcinogenicity classification IARC 1990, Strontium chromate Group 1 a 2001a NATIONAL Regulations and Guidelines: a. Air ACGIH TLV (8-hour TWA) ACGIH 2002 Strontium chromate 10x5 -4 mg/m 3 EPA HAP HSDB 2001 Strontium chromate NIOSH REL No data OSHA PEL No data b. Water EPA Drinking water guidel ine 4 mg/L HSDB 2001 Health Advisories EPA 2000d 10-kg child 1 Day 25 mg/L 10 Day 25 mg/L Lifetime 4 mg/L DWEL 20 mg/L USNRC Maximum ambient environmental level 10 mg/L HSDB 2001 in potable water c. Food No data d. Other ACGIH Carcinogenicity classification ACGIH 2002 Strontium chromate A2 b EPA Carcinogenicity cl assification Group D c EPA 2000d RfD 6x10 -1 mg/kg/day IRIS 2001 Reportable quantity EPA 2001a Strontium chromate 1,000 pounds 40CFR302.4 Toxic pollutants and hazardous EPA 2001b substances required to be identified 40CFR122, Appendix D STATE a. Air No data b. Water Florida Drinking water guideline 4.2 mg/L HSDB 2001 Maine Drinking water guideline 2.4 mg/L HSDB 2001 c. Food No data d. Other Arizona Soil remediation levels BNA 2001 Residential 4.6x10 4 mg/kg Non residential 1x10 6 mg/kgSTRONTIUM 259 8. REGULATIONS AND ADVISORIES 

### Table 8-1. Regulations and Guidelin es Applicable to Stable Strontium Agency Description Information Reference STATE ( cont. ) Florida Toxic substances in the workplace; Strontium chromate BNA 2001 Florida substance list

a Group 1: carcinogenic to humans (refers to hexavalent chromium) b A2: suspected human carcinogen (refers to hexavalent chromium) c Group D: not classifiable as to human carcinogenicity ACGIH = American Conference of Governmental Industr ial Hygienists; BNA = Bureau of National Affairs; CFR = Code of Federal Regulations; DWEL = drinking water equivalent level; EPA = Environmental Protection Agency; HAP = hazardous air pollutant; HSDB = Hazardous Substances Data Bank; IARC = International Agency for Research on Cancer; IRIS = Integrated Risk Information Syst em; NIOSH = National Instit ute for Occupational Safety and Health; OSHA = Occupational Safety and Health Administration; PEL = permissible exposure limit; REL = recommended exposure limit; RfD = reference dose; TLV = threshold limit values; TWA = time-weighted averages; USNRC = National Research CouncilSTRONTIUM 260 8. REGULATIONS AND ADVISORIES 

### Table 8-2. Regulat ions and Guidelines Applicable to Radioactive Strontium Agency Description Information Reference INTERNATIONAL Guidelines: a. Occupational ICRP

b. General Population IARC
ICRP

NATIONAL Regulations: a. Air EPA

OSHA

USNRC Recommended dose limits a; effective dose

Annual equivalent dose

Lens of the eye Skin c Hands and feet Carcinogenicity classification
Recommended dose limits a Effective dose

Annual equivalent dose in

Lens of the eye Skin c Hands and feet

Concentration levels for environmental compliance for 90 Sr Methods for estimating radionuclide emissions Test method for measuring radionuclide emissions from stationary sources Safety and health regulations for construction for ionizing radiation Toxic and hazardous substances for ionizing radiation Effluent concentrations in air

90 Sr

Class D f Class Y g Occupational values via inhalation

90 Sr

Class D f Class Y g 20 mSv per year, averaged over defined period of 5 years b ICRP 1994b

150 mSv 500 mSv 500 mSv Group 1 d IARC 2001b, 2001c 1 mSv per year e ICRP 1994b

15 mSv 50 mSv No data

1.9x10 -14 Ci/m 3

Method 114

10CFR20 regulations apply EPA 2001d 40CFR61, Appendix E EPA 2001m 40CFR61, Appendix D EPA 2001e 40CFR61, Appendix B OSHA 2001 29CFR1926.53
OSHA 2000 29CFR1910.1096

3x10 -11 μCi/mL 6x10 -12 μCi/mL
ALI (μCi) 2x10 1 4x10 0 DAC(μCi/mL) 8x10 -9 2x10 -9 USNRC 2001g 10CFR20, Appendix B USNRC 2001g 10CFR20, Appendix BSTRONTIUM 261 8. REGULATIONS AND ADVISORIES 

### Table 8-2. Regulat ions and Guidelines Applicable to Radioactive Strontium Agency Description Information Reference NATIONAL (cont.) b. Water EPA

USNRC

c. Food FDA

d. Other: Occupational DOE Analytical methods for radioactivity of 90 Sr
Detection limits for man-made beta particle and photon emitters for 90 Sr
Maximum contaminant levels in community water systems; average annual concentrations assumed to produce a total body or organ dose of 4 millirem/year

90 Sr Critical organ Monitoring frequency for radioactivity in community water systems; annual monitoring Effluent concentrations in water

90 Sr

Class D f Releases to sewers; monthly average concentration

90 Sr

Class D f

Sources of radiation used for inspection of food; sealed units producing radiation Individual monitoring
Limits for members of the public entering a controlled area (total effective dose equivalent in a year) Limits for the embryo/fetus from conception to birth Occupational dose limits for general employees; total effective dose equivalent Radio chemical EPA 2001g 40CFR141.25 (a) 2 pCi/L EPA 2001g 40CFR141.25 (c)(2), Table B EPA 2001f 40CFR141.16

8 pCi/L Bone marrow Analysis of four EPA 2001h quarterly samples 40CFR141.26 (b)(4) USNRC 2001g 10CFR20, 5x10 -7 μCi/mL Appendix B USNRC 2001g 10CFR20, 5x10 -6 μCi/mL Appendix B

≤ 2.2 million electron FDA 2000 volts 21CFR179.21

DOE 2001a 10CFR835.402 0.01 rem (0.001 Sv) DOE 2001b 10CFR835.208

0.5 rem (0.005 Sv) DOE 2001c 10CFR835.206 5 rems (0.05 Sv) DOE 2001d 10CFR835.202STRONTIUM 262 8. REGULATIONS AND ADVISORIES 

### Table 8-2. Regulat ions and Guidelines Applicable to Radioactive Strontium Agency Description Information Reference NATIONAL (cont.) DOE Occupational dose limits for general employees; sum of the deep dose equivalent for external exposures and the committed dose equivalent to any organ or tissue other than the lens of the eye Occupational dose limits for general employees

Lens of the eye dose equivalent Shallow dose equivalent to the skin or to any extremity Planned special exposures Occupational dose limits for minors (total effective dose equivalent in a year) Radiation standards; inhaled air DAC for lung retention

90 Sr

Class D h Class W i Class Y j DOT Activity values for radionuclides

90 Sr

A 1 A 2 Carriage by public highway; requirements for Class 7 (radioactive material); total transport index number General requirements for shipments and packages; Class 7 (radioactive) materials Scope and definitions General design requirementsTable of activity limitsexcepted quantities and articles General requirements for shipments and packages; Class 7 (radioactive) materials 50 rems (0.5 Sv) DOE 2001d 10CFR835.202

DOE 2001d 10CFR835.202 15 rems (0.15 Sv)
50 rems (0.5 Sv)

0.1 rem (0.001 Sv) DOE 2001e 10CFR835.207
DOE 2000b 10CFR835, Appendix A 8x10 -9 μCi/mL No data 2x10 -9 μCi/mL DOT 2001b 49CFR173.435 5.41 Ci 2.70 Ci 50 DOT 2001c 49CFR177.842

DOT 2001d 49CFR173 Subpart I 49CFR173.401 thru 403 49CFR173.410 49CFR173.425

DOT 2001d 49CFR173 Subpart ISTRONTIUM 263 8. REGULATIONS AND ADVISORIES 

### Table 8-2. Regulat ions and Guidelines Applicable to Radioactive Strontium Agency Description Information Reference NATIONAL (cont.) DOT Requirements for determiningA1 and A2 values for radionuclides and for the listing of radionuclides on shipping papers and labels Radiation level limitations; any normally occupied space except carriers operating under the provisions of a state or federally regulated radiation protection program and wearing radiation dosimetry devices Radiation level limitations; any point 2 meters (6.6 feet) from the outer lateral surfaces, excluding top and underside Radiation level limitations; external surface radiation level not to be exceeded under conditions normally incident to transportation packages exceeding the radiation limit Transport by exclusive use shipment Conditional maximum radiation level Outer surface of vehicles including top and underside Superfund; reportable quantity for 90 Sr

e. Other: General Population EPA Annual posse ssion quantities for environmental compliance of 90 Sr Gaseous form Liquid/powder forms Solid form 0.02 mSv/hour (2 mrem/hour)

0.1 mSv/hour (10 mrem/hour)

2 mSv/hour (200 mrem/hour) and the transport index (TI) is less than 10

10 mSv/hour (1,000 mrem/hour) 2 mSv/hour (200 mrem/hour) 0.1 pounds

5.2x10 -4 Ci/year 5.2x10 -1 Ci/year 5.2x10 2 Ci/year DOT 2001d 49CFR173.433

DOT 2001e 49CFR173.441

DOT 2001e 49CFR173.441

DOT 2001e 49CFR173.441

DOT 2001a 49CFR172.101, Appendix A, Table 2

EPA 2001d 40CFR61, Appendix ESTRONTIUM 264 8. REGULATIONS AND ADVISORIES 

### Table 8-2. Regulat ions and Guidelines Applicable to Radioactive Strontium Agency Description Information Reference NATIONAL (cont.) EPA Environmental standards for EPA 2001i management and storage of 40CFR191, spent nuclear fuel, high-level Subpart A and transuranic radioactive wastes; applicability and definitions Whole body 25 mrem

Thyroid 75 mrem Other critical organs 25 mrem Environmental standards for EPA 2001i disposal of spent nuclear fuel, 40CFR191, high-level and transuranic Subpart B radioactive wastes; applicability, definitions, containment and individual protection requirements Environmental standards for 1,000/1,000 MTHM EPA 2001i groundwater protection of 40CFR191, spent nuclear fuel, high-level Subpart C and transuranic radioactive wastes; applicability and definitions; release limits for containment requirements of 90 Sr Hazardous waste injection D004–D011 wastes EPA 2001j restrictions; waste specific 40CFR148.18 prohibitions; newly listed and identified wastes Land disposal restrictions; EPA 2001l effective dates of injected 40CFR268, prohibited hazardous wastes Appendix VIII Radioactive waste; release 1,000 Ci EPA 2001c limits for containment requirements k for 90 Sr 40CFR191, Appendix A Reportable quantity of 90 Sr 1x10 -1 Ci EPA 2001e 40CFR302.4, Appendix B Standards for the control of EPA 2001k residual radioactive materials 40CFR192, from inactive uranium Subpart A processing sites; definitions; control of residual radioactive materials and their listed constituentsSTRONTIUM 265 8. REGULATIONS AND ADVISORIES 

### Table 8-2. Regulat ions and Guidelines Applicable to Radioactive Strontium Agency Description Information Reference NATIONAL (cont.) EPA Standards for cleanup of land and buildings contaminated with residual radioactive materials from inactive uranium processing sites Guidance for implementation

Standards for management of uranium byproduct materials pursuant to Section 84 of the Atomic Energy Act of 1954, as amended Standards for management of thorium byproduct materials pursuant to Section 84 of the Atomic Energy Act of 1954, as amended Underground injection control regulations for Class V injection wells USNRC Activity values for radionuclides ( 90 Sr)

A 1 A 2 Specific gravity Byproduct material listing ( 90 Sr) Column 1 Column 2 Byproduct material listing

Dose to an embryo/fetus (dose equivalent during the entire pregnancy) Licensing ice detection devices ( 90 Sr) Occupational dose limits for adults (total effective dose equivalent) in a year Sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue other than the lens of the eye EPA 2001k 40CFR192, Subpart B

EPA 2001k 40CFR192, Subpart C EPA 2001k 40CFR192, Subpart D

EPA 2001k 40CFR192, Subpart E

EPA 2001n 63FR40586
USNRC 2001i 10CFR71, 5.41 Ci Table A-1 2.70 Ci 1.4x10 2 Ci USNRC 2001b 10CFR33.100, 1x10 -2 Ci Schedule A 1x19 -4 Ci 0.1 μCi USNRC 2001a 10CFR30.71, Schedule B 0.5 rem (5 mSv) USNRC 2001m 10CFR20.1208

≤ 50 μCi USNRC 2001c 10CFR31.10 5 rems (0.05 Sv) USNRC 2001n 10CFR20.1201 50 rems (0.5 Sv) USNRC 2001n 10CFR20.1201STRONTIUM 266 8. REGULATIONS AND ADVISORIES 

### Table 8-2. Regulat ions and Guidelines Applicable to Radioactive Strontium Agency Description Information Reference NATIONAL (cont.) USNRC Annual limits to the lens of the eye, to the skin, and to the extremities

Lens dose equivalent Shallow-dose equivalent to the skin or to any extremity Occupational dose limits for minors

Occupational values for oral ingestion (ALI) of 90 Sr Class D f
Medical use— 90 Sr as a use of unsealed byproduct material for uptake, dilution, and excretion studies Medical use— 90 Sr as a sealed source in an applicator for treatment of superficial eye conditions Physical protection for spent nuclear fuel and high-level radioactive waste Radioactive waste; classification of 90 Sr Column 1 l Column 2 Column 3 Standards for protection against radiation—dose limits for individual members of the public; total effective dose equivalent to individual Standards for protection against radiation; dose limits for individual members of the public; dose from external source Quality assurance— 90 Sr Quantity of licensed material requiring labeling containing 90 Sr USNRC 2001n 10CFR20.1201 15 rems (0.15 Sv) 50 rems (0.50 Sv)
10% of the annual dose USNRC 2001o limits specified for adult 10CFR20.1207 workers in 10 CFR 20.1201 USNRC 2001g 10CFR20, 3x10 1 μCi (bone surf) Appendix B 4x10 1 USNRC 2001k 10CFR35.100

USNRC 2001j 10CFR35.4000

USNRC 2001p 63FR26955
USNRC 2001l 10CFR61.55 0.04 Ci/m 3 150 Ci/m 3 7,000 Ci/m 3 0.1 rem/year USNRC 2001q 10CFR20.1301

0.002 rem/hour USNRC 2001q 10CFR20.1301

USNRC 2001h 10CFR32.62 1.2x10 -1 μCi USNRC 2001d 10CFR30, Appendix BSTRONTIUM 267 8. REGULATIONS AND ADVISORIES 

### Table 8-2. Regulat ions and Guidelines Applicable to Radioactive Strontium Agency Description Information Reference NATIONAL (cont.) USNRC Quantity of radioactive material requiring need for an emergency plan for responding to a release ( 90 Sr) Release fraction

Quantity Standards for protection against radiation; quantity of licensed material requiring labeling ( 90 Sr) NATIONAL Guidelines: a. Air ACGIH TLV-TWA ( 90 Sr)

Effective dose Any single year Averaged over 5 years Annual equivalent dose to

Lens of the eye Skin

Hands and feet Embryo-fetus exposures once the pregnancy is known

Monthly equivalent dose Dose to the surface of women’s abdomen (lower trunk) Intake of radionuclide NIOSH REL (TWA) b. Water EPA MCLG for beta particles MCL for beta particles Health advisory for beta particle activity in drinking water Cancer group c. Food FDA Derived intervention level n (DIL; Bq/kg food) for in accidentally-contaminated human food

89 Sr 90 Sr USNRC 2001f 10CFR30.72, Schedule C 0.01% 90 Ci 1x10 -1 μCi USNRC 2001e 10CFR20, Appendix C

Rdiation exposures must be kept as low as reasonable achievable
50 mSv 20 mSv
150 mSv 500 mSv 500 mSv ACGIH 2002

ACGIH 2002

ACGIH 2002

ACGIH 2002 0.5 mSv 2 mSv for the remainder of the pregnancy 1/20 ALI No data
No final MCLG, but zero proposed in 1991 4 mrem 4 mrem/year at 10 -4 cancer risk EPA 2000d
EPA 2000d EPA 2000d

Group A m EPA 2000d

FDA 1998

400 o 160 pSTRONTIUM 268 8. REGULATIONS AND ADVISORIES 

### Table 8-2. Regulat ions and Guidelines Applicable to Radioactive Strontium Agency Description Information Reference NATIONAL (cont.) d. Other EPA Effective dose equivalent Adult Lens of the eye All other organs Juvenile workers (<18 years old) Pregnant workers Carcinogenicity slope factors q Ingestion—lifetime excess total cancer risk/pCi Water

82 Sr 85 Sr 85m Sr 89 Sr 90 Sr 90+disentegration Sr 91 Sr 92 Sr Carcinogenicity slope factors q Ingestion—lifetime excess total cancer risk/pCi Food

82 Sr 85 Sr 85m Sr 89 Sr 90 Sr 90+disentegration Sr 91 Sr 92 Sr Carcinogenicity slope factors q Ingestion—lifetime excess total cancer risk/pCi Soil

82 Sr 85 Sr 85m Sr 89 Sr 90 Sr 90+disentegration Sr 91 Sr 92 Sr 5 rem/year 15 rem/year 50 rem/year 0.5 rem/year 0.5 rem/gestation period

3.13x10 -11 2.26x10 -12 1.67x10 -14 1.28x10 -11 5.59x10 -11 7.40x10 -11 3.22x10 -12 2.25x10 -12

4.48x10 -11 3.11x10 -12 2.31x10 -14 1.84x10 -11 6.88x10 -11 9.53x10 -11 4.66x10 -12 3.26x10 -12

8.47x10 -11 5.03x10 -12 3.74x10 -14 3.47x10 -11 9.18x10 -11 1.44x10 -10 8.81x10 -12 6.18x10 -12 EPA 1987 Federal Register Part II

EPA 2002

EPA 2002

EPA 2002STRONTIUM 269 8. REGULATIONS AND ADVISORIES 

### Table 8-2. Regulat ions and Guidelines Applicable to Radioactive Strontium Agency Description Information Reference NATIONAL (cont.) EPA Carcinogenicity slope factors r Inhalation—lifetime excess EPA 2002 total cancer risk/pCi 82 Sr 3.69x10 -11 85 Sr 2.56x10 -12 85m Sr 8.32x10 -15 89 Sr 2.34x10 -11 90 Sr 1.05x10 -10 90+disentegration Sr 1.13x10 -10 91 Sr 1.70x10 -12 92 Sr 1.03x10 -12 Carcinogenicity slope factors s External exposure—risk/year per pCi/g in soil 82 Sr 5.00x10 -11 EPA 2002

85 Sr 2.20x10 -6 85m Sr 8.21x10 -7 89 Sr 7.19x10 -9 90 Sr 4.82x10 -10 90+disentegration Sr 1.96x10 -8 91 Sr 3.30x10 -6 92 Sr 6.69x10 -6 NCRP Occupational exposures t Effective dose limits NCRP 1993

Annual 50 mSv Cumulative 10 mSv x age Occupational exposures t Equivalent dose annual limits for tissues and organs Lens of eye Skin, hands, and feet 150 mSv 500 mSv NCRP 1993

Public exposures (annual) Effective dose limit, 1 mSv NCRP 1993 continuous or frequent exposure s Public exposures (annual) Effective dose limit, infrequent exposure t 5 mSv NCRP 1993

Public exposures (annual) Equivalent dose limits for tissues and organs t Lens of eye Skin, hands, and feet 15 mSv 50 mSv NCRP 1993STRONTIUM 270 8. REGULATIONS AND ADVISORIES 

### Table 8-2. Regulat ions and Guidelines Applicable to Radioactive Strontium Agency Description Information Reference STATE a. Air Arkansas

Illinois Concentrations in air above natural background ( 90 Sr) Occupational

Non occupational
Concentrations in air above natural background S 1x10 -9 μCi/mL I 5x10 -9 μCi/mL S 3x10 -11 μCi/mL I 2x10 -10 μCi/mL S 3x10 -11 μCi/mL I 2x10 -10 μCi/mL BNA 2001

BNA 2001 New Jersey Maximum permissible average concentrations of radioactive materials in air ( 85m Sr) Occupational Non occupational S 4x10 -5 μCi/mL I 3x10 -5 μCi/mL S 1x10 -6 μCi/mL I 1x10 -6 μCi/mL BNA 2001

b. Water Alabama Alaska Drinking water guidelines MCL for drinking water ( 90 Sr ) 8 pCi/L 8 pCi/L HSDB 2001 ADEC 2000 Arkansas Concentrations in water above natural background ( 90 Sr) Occupational Non occupational S 1x10 -5 μCi/mL I 1x10 -3 μCi/mL S 3x10 -7 μCi/mL I 4x10 -5 μCi/mL BNA 2001

California Drinking water guidelines Primary MCL ( 90 Sr ) 8 pCi/L 8 pCi/L HSDB 2001 CA Department of Health Services 2000 Colorado Standards applicable to surface waters 8 pCi/L BNA 2001
Groundwater quality standards 8 pCi/L BNA 2001
Connecticut Drinking water guidelines 8 pCi/L HSDB 2001 Florida Drinking water guidelines MCL for groundwater ( 90 Sr) 4,200 μg/L 8 pCi/L HSDB 2001 FL DEP 2000 Idaho Primary constituent standards for groundwater ( 90 Sr) 8 pCi/L ID Department of Health & Welfare 1999 Illinois Drinking water guidelines Water quality standard ( 90 Sr) 8 pCi/L 1 and 2 pCi/L HSDB 2001 IL Environmental Protection Agency 1999STRONTIUM 271 8. REGULATIONS AND ADVISORIES 

### Table 8-2. Regulat ions and Guidelines Applicable to Radioactive Strontium Agency Description Information Reference STATE ( cont. ) New Jersey Maximum permissible average concentrations of radioactive materials in water ( 85m Sr) Occupational Non occupational
Indiana Maximum contaminant levels in community water systems;average annual concentrations assumed to produce a total body or organ dose of 4 millirem/year

90 Sr Critical organ Maine Drinking water guidelines Michigan Maximum contaminant levels in community water systems; average annual concentrations assumed to produce a total body or organ dose of 4 millirem/year

90 Sr Critical organ New Hampshire Drinking water guidelines Wisconsin Drinking water guidelines c. Food d. Other Arkansas Determination of A 1 and A 2 quantities ( 90 Sr)

A 1 A 2 Specific gravity Standard for protection against radiation Colorado Determination of A 1 and A 2 ( 90 Sr)

A 1 A 2 Delaware Average annual concentration assumed to produce a total body or organ dose of 4 rem/year ( 90 Sr)

Critical organ (bone marrow) Nevada Quantities of radioactive material for signs, labels, and signals BNA 2001

S 0.2 μCi/mL I 0.2 μCi/mL S 0.007 μCi/mL I 0.007 μCi/mL IN General Assembly 2000

8 pCi/L Bone marrow 2,400 μg/L HSDB 2001 MDEQ 2000

8 pCi/L Bone marrow 8 pCi/L HSDB 2001 8 pCi/L HSDB 2001 No data

BNA 2001 10 Ci 0.4 Ci 1.5x10 2 Ci/g 0.1 μCi BNA 2001
BNA 2001 5.41 Ci 2.70 Ci BNA 2001

8 pCi/L 0.1 μCi BNA 2001STRONTIUM 272 8. REGULATIONS AND ADVISORIES 

### Table 8-2. Regulat ions and Guidelines Applicable to Radioactive Strontium Agency Description Information Reference

a The limits apply to the sum of the relevant doses from external exposure in the spec ified 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 occupa tional exposure of pregnant women. c The limitation on the effective dos e provides sufficient protection for the skin aga inst stochastic effects. An additional limit is needed for localized exposures in order to prevent deterministic effects. d Group 1: human carcinogen e In special circumstances, a higher value of effective dos e could be allowed in a single year, provided that the average over 5 years does not exceed 1 mSv per year. f Class D: all soluble compounds except SrTiO g Class Y: all insoluble compounds and SrTiO h Class D: refers to materials with retention times in the pulmonary region of <10 days i Class W: refers to materials with retention times in the pulmonary region of 10–100 days j Class Y: refers to materials with retention times in the pulmonary region of >100 days k Release limit per 1,000 metric tons of heavy metal (MTHM) or other unit of waste l Column 1: The sum of the fractions rule for mixtures of radionuclides. For determining classification for waste that contains a mixture of radionuclides, it is necessary to determine the sum of fractions by dividing each nuclide’s concentration by the appropriate limit and adding the result ing values. The appropriate limits must all be taken from the same column of the same table. The sum of the fractions for the column must be less than 1.0 if the waste class is to be determined by the column. Example: A waste contains 90 Sr in a concentration of 50 Ci/m 3 and 137 Cs of 22 Ci/m 3 . Since the concentrations both exceed the values in Column 1, Table 2, they must be compared to Column 2 values. For 90 Sr fraction 50/150=0.33; for 137 Cs fraction, 22/44=0.5; the sum of the fractions=0.83. Since the sum is less than 1.0, the waste is Class B. m Group A: human carcinogen n Derived intervention levels (DIL) are concentrations of radioactivity in food whose consumption would deliver a committed effective dose equivalent equal to the most limit ing of the protection action guides (PAGs) developed by FDA (1998). o The FDA-recommended Derived Intervention Level (DIL) for radionuclides of 89 Sr, is defined as the DIL for the most sensitive age group (3 months) that wa s calculated from the most limiting Protective Action Goal (PAG; 50 mSv committed dose equivalent to the bone). p The FDA-recommended Derived Intervention Level (DIL) for radionuclides of 90 Sr, is defined as the DIL for the most sensitive age group (15 years) that wa s calculated from the most limiting Pr otective Action Goal (PAG; 50 mSv committed dose equivalent to the bone). q Radioactive slope factors calculated by EPA’s Office of Radiation and Indoor Ai r (ORIA). Slope factors are central estimates in a linear model of the age- averaged, lifetime attributab le radiation cancer inci dence (fatal and nonfatal cancer) risk per unit of activity ingested, expressed as risk per picocurie (pCi). r Inhalation slope factors are central estimates in a linear model of the age-average, lif etime attributable radiation cancer incidence (fatal and nonfatal cancer) risk per unit of activity inhaled, expressed as risk per picocurie (pCi). s External slope factors are central estima tes of the lifetime attribut able radiation cancer incidence risk for each year of exposure to external radiation from photon-emitting radionuc lides distributed uniformly in a thick layer of soil, expressed as risk/year per pCu per gram of soil. t Sum of external and internal exposures but excluding doses from natural sources. ACGIH = American Conference of Governmental Industrial Hygienists; ADEC = Alaska Department of Environmental Conservation; ALI = annual limits on intake; BNA = Bureau of National Affairs; CFR = Code of Federal Regulations; DAC = derived air concentration; DEP = Department of En vironmental Protection; DOE = Department of Energy; DOT = Department of Transportation; EPA = Envir onmental Protection Agency; FDA = Food and Drug Administration; HSDB = Hazardous Substances Data Bank; I = insoluble; IARC = International Agency for Research on Cancer; ICRP = International Commission on Radiological Protection; MCL = maximum contaminant level; MCLG = maximum contaminant level goal; MDEQ = Michigan Department of Environmental Quality; mSv = millisievert; MTHM = metric tons of heavy meta l; NCRP = National Council on Radiation Protection; NIOSH = National Institute for Occupational Safety a nd Health; USNRC = Nuclear Regulatory Commission; OSHA = Occupational Safety and Health Administration ; PAG = protective action guide; REL = recommended exposure limit; S = soluble; TWA = time-weighted averageSTRONTIUM 273 8. REGULATIONS AND ADVISORIES


### Table 8-3. Effect ive Dose Coefficients a 

### (e(50)) and Annual Limits on Intake b 

### (ALI) for Occupational Exposures to Radioactive Strontium Isotopes
Radionuclide Inhalation, 1μm AMAD c Inhalation, 5μm AMAD Ingestion Absorp- e inh (50) ALI ALI e inh (50) ALI ALI e ing (50) ALI ALI Half-life tion type f1 d (Bq) (mCi) (Bq) (mCi) (Bq) (mCi) 80 Sr 1.67 hr fast 0.3 7.6x10 -11 2.6x10 8 7.11 1.3x10 -10 1.5x10 8 4.158 3.4x10 -10 5.9x10 7 1.590 slow 0.01 1.4x10 -10 1.4x10 8 3.86 2.1x10 -10 9.5x10 7 2.574 3.5x10 -10 5.7x10 7 1.544 81 Sr 0.425 hr fast 0.3 2.2x10 -11 9.1x10 8 24.57 3.9x10 -11 5.1x10 8 13.860 7.7x10 -11 2.6x10 8 7.020 slow 0.01 3.8x10 -11 5.3x10 8 14.22 6.1x10 -11 3.3x10 8 8.861 7.8x10 -11 2.6x10 8 6.93 82 Sr 25.0 d fast 0.3 2.2x10 -9 9.1x10 6 0.245 3.3x10 -9 6.1x10 6 0.164 6.1x10 -9 3.3x10 6 0.089 slow 0.01 1.0x10 -8 2.0x10 6 0.054 7.7x10 -9 2.6x10 6 0.070 6.0x10 -9 3.3x10 6 0.090 83 Sr 1.35 d fast 0.3 1.7x10 -10 1.2x10 8 3.179 3.0x10 -10 6.7x10 7 1.801 4.9x10 -10 4.1x10 7 1.103 slow 0.01 3.4x10 -10 5.9x10 7 1.589 4.9x10 -10 4.1x10 7 1.103 5.8x10 -10 3.5x10 7 0.932 85 Sr 64.8 d fast 0.3 3.9x10 -10 5.1x10 7 1.386 5.6x10 -10 3.6x10 7 0.965 5.6x10 -10 3.6x10 7 0.965 slow 0.01 7.7x10 -10 2.6x10 7 0.702 6.4x10 -10 3.1x10 7 0.845 3.3x10 -10 6.1x10 7 1.638 85m Sr 1.16 hr fast 0.3 3.1x10 -12 6.5x10 9 174.00 5.6x10 -12 3.6x10 9 96.53 6.1x10 -12 3.3x10 9 88.61 slow 0.01 4.5x10 -12 4.4x10 9 120.00 7.4x10 -12 2.7x10 9 73.05 6.1x10 -12 3.3x10 9 88.61 87m Sr 2.8 hr fast 0.3 1.2x10 -11 1.7x10 9 45.05 2.2x10 -11 9.1x10 8 24.57 3.0x10 -11 6.7x10 8 18.02 slow 0.01 2.2x10 -11 9.1x10 8 24.57 3.5x10 -11 5.7x10 8 15.44 3.3x10 -11 6.1x10 8 16.38 89 Sr 50.5 d fast 0.3 1.0x10 -9 2.0x10 7 0.540 1.4x10 -9 1.4x10 7 0.386 2.6x10 -9 7.7x10 6 0.208 slow 0.01 7.5x10 -9 2.7x10 6 0.072 5.6x10 -9 3.6x10 6 0.097 2.3x10 -9 8.7x10 6 0.235 90 Sr 29.1 yr fast 0.3 2.4x10 -8 8.3x10 5 0.023 3.0x10 -8 6.7x10 5 0.018 2.8x10 -8 7.1x10 5 0.019 slow 0.01 1.5x10 -7 1.3x10 5 0.004 7.7x10 -8 2.6x10 5 0.007 2.7x10 -9 7.4x10 6 0.200 91 Sr 9.5 hr fast 0.3 1.7x10 -10 1.2x10 8 3.180 2.9x10 -10 6.9x10 7 1.864 6.5x10 -10 3.1x10 7 0.832 slow 0.01 4.1x10 -10 4.9x10 7 1.318 5.7x10 -10 3.5x10 7 0.948 7.6x10 -10 2.6x10 7 0.711 92 Sr 2.7 hr fast 0.3 1.1x10 -10 1.8x10 8 4.914 1.8x10 -10 1.1x10 8 3.003 4.3x10 -10 4.7x10 7 1.257 slow 0.01 2.3x10 -10 8.7x10 7 2.350 3.4x10 -10 5.9x10 7 1.590 4.9x10 -10 4.1x10 7 1.103

a ICRP (1994) b For internal exposures, ICRP (1994) recommends an effect ive dose limit of 100 mSv over 5 years (averaging 20 mSv per year). The Annual Limits on Intake (ALI in Bequerels) were calculated by dividing the annual effective dose limit (0.02 Sv) by the dose coefficient (e(50)) in Sieverts/Bequerel. c ICRP (1994) calculated inhalation dose coefficients for particles with AMAD of 1 or 5 μm. d Fractional absorption factor used by ICRP (1994: Annexes E and F) to calculate effective dose coefficients. A value of 0.3 was used for unspecified strontium com pounds and 0.01 was used fo r strontium titanate. ALI = Annual Limits on Intake; AMAD = Activity Median Average Diameters; Bq = Bequerels; Ci = Curies; d = day; hr = hour; yr = yearSTRONTIUM 274 8. REGULATIONS AND ADVISORIES groups and 14 radiogenic cancer cites (EPA 2000e). These factors are used to calculate the lifetime excess total cancer risk per unit intake or exposure to radiation (under the different exposure scenarios). Slope factors for radioactive strontium isotopes are lis ted in Table 8-2. IARC has determined that all internally deposited beta emitters , including radioactive strontium, are carcinogenic to humans and has assigned them to Group 1 (IARC 2001, 2002b).
Because of the potential for ionizing radiation to cause deterministic (acute radiation syndrome) and nondeterministic (cancer) health effects in exposed in dividuals, safe dose guidelines and regulations have been established for radionuclides in air and water by a number of international and national agencies (Tables 8-2 and 8-3). Regulations and guidelines that protect against deterministic effects are based on identified acute thresholds doses for those effects, with a reduction to protect sensitive populations and provide safety margins to account for uncertainties. Those that protect against nondeterministic effects use the observed frequencies with which those effect s occur at high doses, account for uncertainties that may exist, and assume a linear dose-effect relationshi p to calculate the doses at which the effects would be presumed to occur at some acceptable frequency, such as the range of 10 -4 –10 - 6, which EPA often considers. This proportionality assumes a linear no threshold (LNT) dose effect curve. During the last decade, there have been reductions in LNT-based public radiation dose limits and site cleanup levels that have increased the scope and cost of medical, occ upational, and environmen tal radiation protection efforts. Some recent studies found a reduction in hea lth effects when the dose was delivered at lower dose rates, indicating a potential application to future protection guidelines and regulations.
The International Commission on Radiological Prot ection (ICRP) provides guidance on the fundamental principles regarding the biological effects of expos ure to ionizing radiation and recommends exposure limits based on these analyses. In the United States, the National Council on Radiation Protection and Measurements (NCRP) was chartered in 1964 by the U. S. Congress to: (1) disseminate information of public interest and recommend ra diation levels to protect the public, (2) support cooperation among organizations concerned with radia tion protection, (3) develop basic c oncepts about radiation protection, and (4) cooperate with the ICRP and the In ternational Commission on Radiation Units and Measurements. Even though the NCRP is a nongove rnmental organization, it provides recommendations that guide the establishment of federal radiation po licies, agency requirements, and statutory laws. Through the governmental agencies that rely on NCRP recommendations, the work of this organization has a significant impact on the many activities in the United States involving the use of radiation and radioactive materials.STRONTIUM 275 8. REGULATIONS AND ADVISORIES The EPA sets radiation safety policy and basic safety st andards. The execution of this policy is assigned to the various regulatory agencies, including the EPA itself, for application to the specific activities that they regulate. The U.S. Nuclear Regulatory Commission (USNRC), an independent government agency, regulates commercial nuclear power reactors; research/t est/training reactors; fuel cycle facilities; and the transport, storage, and disposal of nuclear mate rials and waste (USNRC 1997). The EPA is responsible for protecting the public and the environment and for cleanup of radioactively contaminated sites (EPA 1997a).
The Food and Drug Administration (FDA) develops standa rds for radioactive material concentrations in food (FDA 1998) and in medical devices used in radiation therapy (FDA 1997). The FDA recently updated its guidance document that presents recomm ended action levels for accidental radioactive contamination of foods, both domestic and importe d (FDA 1998). These derived intervention levels (DILs) are estimated levels in food that could lead to individuals receiving a radiation equivalent dose equal to the FDA protection action guide (PAG) that is set as the more limiting of either 0.5 rem (5 mSv) for committed effective dose or 5 rem (50 mSv) comm itted dose equivalent to any individual tissue or organ. Derived intervention levels, which are based on food intake rates, are calculated for different age groups and the DIL for the most vulnerable group is then adopted to provide a conservative margin of safety for the entire population. For 90 Sr, with a half-life of 29 years, the DIL is based on the dose to the bone surface in 15-year-old individuals, who have the highest rate of bone growth. For 89 Sr, with a halflife of 50.5 days, 3-month-old infants represent the most sensitive group because of the higher doses to the lower intestine from milk consumption. Table 8-2 presents the DILs adopted for the two strontium isotopes.
Transport of radioactive materials is regulated by the Department of Transportation (DOT) in conjunction with the USNRC. Coordinating government emer gency response to accidents involving radioactive materials is the responsibility of the Federal Emergency Management Administration (FEMA).
National regulations governing the occupational e xposure to ionizing radiation include USNRC regulations (10 CFR 20), the Occupational Safety and Health Administration (OSHA) standards for ionizing radiation (29 CFR 1910.1096), and the Depart ment of Energy (DOE) standards for occupational radiation protection (10 CFR 835). National regulations concerning general population exposure to radiation have been developed as proposed by the EPA and as finalized by the USNRC based on the dose limit recommendations of the ICRP (ICRP 1996) and the NCRP (NCRP 1993). The EPA and USNRCSTRONTIUM 276 8. REGULATIONS AND ADVISORIES also use the BEIR reports of the National Academy of Sciences and the UNSCEAR reports on biological effects to help develop the U.S. standards in line with the NCRP and the ICRP consensus standards.
Currently, there are 29 "NRC Agreement States." An agre ement state is any state that has entered into an agreement with the USNRC under Section 274 of the Atomic Energy Act of 1954, as amended. The USNRC relinquishes to these states the majority of its regulatory authority over source, by-product, and special nuclear material in quantities not sufficient to form a critical mass. However, the regulation of nuclear reactors is under USNRC jurisdiction. In the remaining states, USNRC still handles all of the inspection, enforcement, and licensing responsibilities.
The basic philosophy of radiation safety is to mi nimize unnecessary radiation exposure. The specific objectives of radiation safety guidance as stated by NCRP are (1) to prevent the occurrence of severe radiation-induced deterministic (nons tochastic) disease, and (2) to limit the risk of the nondeterministic (stochastic) effects (fatal cancer and genetic effect s) to a reasonable level compared with nonradiation risks and in relation to societal needs, benefits gained, and economic factors. In addition to regulations that set upper limits on radiation dose, the concept of ALARA (As Low As Reasonably Achievable) was introduced to ensure that workplace endeavors resulting in exposures to radiation provide sufficient benefits that offset any potential detriment they cau se (ACGIH 2002). The goal is not to eliminate all radiation exposure, which would not be possible, but in stead to strive for an appropriate balance between protection of public health and reasonable costs (econo mic, social, etc.) while maintaining desirable dose limits. The ACGIH has adopted the occupational exposure guidance of the ICRP (ACGIH 2002)._______________________ STRONTIUM 277



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### 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. Fo r dermal exposure, this is the amount of material applied to the skin, and is normally divide d 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 abso rbed 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 coefficien t), 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=I o e -μx , I o is the initial intensity, I the intensity of the beam after passage through a thickness of the mate rial 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 ad ministered 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 transformati ons occurring in a material per unit time (see Curie, Becquerel). The term for activ ity per unit mass is specific activity. Activity Median Aerodynamic Diameter (AMAD)— The diameter of a unit-density sphere with the same terminal settling velocity in air as that of the aerosol particle whose activity is the median for the entire size distribution of the aerosol. Acute Exposure, Chemical— Exposure to a chemical for a duration of 14 days or less, as specified in the Toxicological Profiles.STRONTIUM 368 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 (K oc )— 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 (K d )— See Distribution Coefficient Alpha Particle— A positively charged particle ejected spontane ously 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 ionizati on) left in a medium by an alpha particle that has traveled through the medium. Annihilation (Positron-Electron)— An interaction between a positive and a negative electron in which they both disappear; their rest mass, being converted into electromagnetic radiation (called annihilation radiation) with two 0.51 MeV gamma photons emitted at an angle of 180 E 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 woul d 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 ma ss 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 ne utral 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.STRONTIUM 369 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 expr essed 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 extranuc lear 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 radi ation from naturally occurring radionuclides in the soil, cosmic radiation originating from outer space, and naturally occurring radi onuclides 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 (disin tegration) 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 particl es 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 concentra tion 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, marker s 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.STRONTIUM 370 10. GLOSSARY Branching— The occurrence of two or more modes by wh ich a radionuclide can undergo radioactive decay. For example, 214 Bi can undergo alpha or beta minus decay, 64 Cu 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 speci fied 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, includi ng 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 nu cleus 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 epithelia l 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 va riety of potential causative agents (such as toxic chemicals). In a case-controlled study, a group of pe ople 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 s hould 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 chem ical 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 speci fic 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.STRONTIUM 371 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 radia tion. 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 su bstance in such a way that it is prevented from being dispersed from its container or into the envi ronment, or is released only at a specified rate.
Contamination— Deposition of a stable or radioactive substa nce in any place where it is not desired. Cosmic Rays— High-energy particulate and electromagnetic radi ations 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 detect ed event. The term “count rate” refers to the total number registered in a given period of time. The te rm 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 ga s 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 3.7x10 10 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 (3.7x10 16 disintegrations per second). Microcurie (μCi)— One-millionth of a curie (3.7x10 4 disintegrations per second). Millicurie (mCi)— One-thousandth of a curie (3.7x10 7 disintegrations per second). Nanocurie (nCi)— One-billionth of a curie (3.7x10 1 disintegrations per second). Picocurie (pCi)— One-millionth of a microcurie (3.7x10 -2 disintegrations per second). Daughter Products— See Progeny and Decay ProductSTRONTIUM 372 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. So metimes, 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 radioactiv e 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 (a lso 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 unde r 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 whic h varies with the dose and for which a threshold is believed to exist (als o 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. A dverse 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 (K d )— Describes the distribution of a chemical between the solid and aqueous phase at thermodynamic equilibrium, is given as follows: 

### [C] s 

### K d 

### = [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 a queous phase in units of (mg)/(L solution). As the magnitude of K d decreases, the potential mobility of the chem ical to groundwater systems increases and vice versa.STRONTIUM 373 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 ab sorbed 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 i ndividual or a population group usually by means of predictive modeling techniques, sometim es 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 lo cation of interest. ICRP has changed its definition to be the product of the absorbed dose and the radiatio n 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 ra diation 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 (H T,50 )— The dose equivalent to organs or tissues of reference (T) that will be received from an intake of radioactiv e material by an individual during the 50 years following the intake. Committed Effective Dose Equivalent (H E,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 normaliz e 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 (w T ) for each tissue exposed. (E = ∑ D T,R w R w T) ). Effective Dose Equivalent (H E )— This dose type is limited to in ternal exposures and is the sum of the products of the dose equivalent to the organ or tissue (H T ) and the weighting factors (w T ) applicable to each of the body organs or tissues that are irradiated. (H E = ∑ w T H T ).STRONTIUM 374 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 (w R ) for that radiation ( ∑ D T,R w R ).
External Dose— That portion of the dose equivalent r eceived from radiation sources outside the body.
Internal Dose— That portion of the dose equivalent receive d 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 la rge group of animals or organisms. Also called the LD 50 , or LD 50/30 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 un it 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 milli on 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 variati ons, altered growth, and in utero death.STRONTIUM 375 10. GLOSSARY Energy— Capacity for doing work. Gravitationally, "poten tial energy" is the energy inherent in a mass because of its spatial relation to other masses. Chem ically or radiologically, “potential energy” is the energy released when a chemical reaction or radiolog ical 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 syst em 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 enri chment, 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 cons tituents of natural uranium ( 234 U, 235 U, 238 U) in the molecular form UF 6 . 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 federa l, 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 de fined human population during a specified period. Equilibrium, Radioactive— In a radioactive series, the state whic h 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 reac hed, 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 226 Ra and its transformation series to stable 206 Pb. The half-life of 226 Ra is about 1,600 years; of 222 Rn, 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.STRONTIUM 376 10. GLOSSARY Transient Equilibrium— If the half-life of the parent is short enough so the quantity present decreases appreciably during the pe riod under consideration, but is still longer than that of successive members of the series, a stage of equ ilibrium 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 th e 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 mo lecule can result from absorption of photons or from inelastic collisions with other particles. The excited st ate 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 th e 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, accomp anied 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 effect s 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, cl astogenic 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 T r

or T rad . Half-time, Biological— Time required for an organ, tissue, or the whole body to eliminate one-half of any absorbed substance by regular processe s 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 t biol or T b .STRONTIUM 377 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 T e or T eff . 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 char ge, usually referring to the electron and positive atomic or molecular residue resulting after the interaction of ioni zing 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 incl udes 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 g as, 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.STRONTIUM 378 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 th erefore 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 fro m gamma rays or neutrons to a unit mass of absorbing medium in the initial collision between the ra diation 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. LD 50/30 — 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) (LC Lo )— The lowest concentration of a chemical in air that has been reported to have caused death in humans or animals.
Lethal Concentration (50) (LC 50 )— 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) (LD Lo )— The lowest dose of a chemical introduced by a route other than inhalation that is expected to have caused death in humans or an imals within a specified time, usually 30 days.
Lethal Dose (50) (LD 50 )— The dose of a chemical which has been calculated to cause death in 50% of a defined experimental animal population.STRONTIUM 379 10. GLOSSARY

Lethal Time (50) (LT 50 )— 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 charge d 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 even ts 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 betw een 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 biological ly significant increases in frequency or severity of adverse effects between the exposed p opulation 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 pulm onary 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 adve rsely affect survival, development, or function. Mass Numbers (A)— The number of nucleons (protons and ne utrons) 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 th e genetic material in a cell. Mutations can lead to birth defects, miscarriages, or cancer. Necropsy— The gross examination of the organs and tissu es 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.STRONTIUM 380 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 (typi cally 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 constituti on of its nucleus. The nuclear constitution is specified by the number of protons (Z), number of ne utrons (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 un stable intermediates in nuclear reactions are not so considered. Octanol-Water Partition Coefficient (K ow )— 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 radi ation in which the incident photon is absorbed in the vicinity of the nucleus of the abso rbing 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 atmospheri c 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. Ther e 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, identif iable anatomic regions of the body whereas the physiologically-based model compartments represent real anatomic regions of the body.STRONTIUM 381 10. GLOSSARY
Pharmacokinetics— The dynamic behavior of a material in the body, used to predict the fate (disposition) of an exogen ous substance in an organism. Utilizi ng 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 rela tionship between target tissue dose and toxic end points. These models advance the importance of phys iologically 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, a nd 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 elect ron 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) w hose value is the product of its frequency ( ν ) in hertz and Planck's constant (h). The equation is: E = h ν
. 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 chai n continues until a stable nuclide is formed.
Proton— Elementary nuclear particle with a positive electri c 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 en ergy deposited by a particle along its track; radiations that produce different densities of ionization per unit intensity are said to have different "qualities."STRONTIUM 382 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). The term radiation or radiant energy, wh en unqualified, usually refers to electromagnetic radiation. Such radiation commonly is classified a ccording to frequency, as microwaves, infrared, visible (light), ultraviolet, and x and gamma rays (see Photon .) and, by extension, corpuscular emission, such as alpha and beta radiation, neutrons, or rays of mixed or unknown type, as cosmic radiation. Radiation, Annihilation— Photons produced when an electron and a positron unite and cease to exist. The annihilation of a positron-electron pair results in the production of two photons, each of 0.51 MeV energy. Radiation, Background— See Background Radiation. 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 whic h 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 ha ve 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 en ergy to produce its own ionization, such as bremsstrahlung or electrons knocked from atomic or bitals with enough energy to then produce ionization (see Delta Rays).STRONTIUM 383 10. GLOSSARY Radiation Weighting Factor (also called Quality Factor)— In radiation protection, a factor (1 for xrays, gamma rays, beta particles; 20 for alpha partic les) 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 exhi bited 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. Radiosensitiv ity 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 eff ects during a lifetime. The RfD is operationally derived from the NOAEL (from animal and human studies) by a cons istent 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 ch emical. 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 60 Co 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 qualit y factor (1 rem is equal to 0.01 sievert).STRONTIUM 384 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 di rected to the reproductive organs and/or the related endocrine system. The manifestation of such toxici ty may be noted as alterations in sexual behavior, fertility, pregnancy outcomes, or modifications in othe r functions that are dependent on the integrity of this system. Roentgen (R)— A unit of exposure (in air) to ionizing radiati on. It is the amount of x or gamma rays required to produce ions carrying 1 electrostatic unit of electrical charge in 1 cubic centimeter of dry air under standard conditions. Named after William Roentg en, a German scientist who discovered x rays in 1895. Retrospective Study— A type of cohort study based on a grou p 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 cau sal 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 absorpti on 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 a nd 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 surviv e 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, multip lied by the quality factor (1 sievert equals 100 rem). The sievert is also the SI unit for effective dose equi valent, which is the sum of the products of the dose equivalent to each organ or tissue and its corresponding tissue weighting factor. Specific-Activity— Radioactivity per unit mass of a radionuclide, expressed, for example, as Ci/gram or Bq/kilogram. Specific Energy— The actual energy per unit mass deposited per unit volume in a small target, such as the cell or cell nucleus, as the result of one or more energy-depositing events. This is a stochastic quantity as opposed to the average value over a la rge number of instance (i.e., the absorbed dose).STRONTIUM 385 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 a nd 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 eventual ly 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) ex tending 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 targ et) 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) ma y 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 us ed 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.STRONTIUM 386 10. GLOSSARY Tissue Weighting Factor (W t )— 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 (TD 50 )— 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 pa rticulate 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 218 Po and 214 Po, 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 at tached 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 sen sitivity 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.STRONTIUM 387 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 10 3 becquerel is 1 kBq).
Factor Prefix Symbol Factor Prefix Symbol 10 -18 atto A 10 3 kilo k 10 -15 femto F 10 6 mega M 10 -12 pico p 10 9 giga G 10 -9 nano N 10 12 tera T 10 -6 micro Μ 10 15 peta P 10 -3 milli M 10 18 exa E 10 -2 centi C

Units, Radiological— Units Equivalents Becquerel* (Bq) 1 disintegration per second = 2.7x10 -11 Ci Curie (Ci) 3.7x10 10 disintegrations per second = 3.7x10 10 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 daughter s in 1 liter of air that will result in the ultimate emission of 1.3x10 5 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 Leve l (WL) and the exposure time in nominal months (1 nominal month = 170 hours). Inhalation of air wi th a concentration of 1 WL of radon daughters for 170 working hours results in an exposure of 1 WLM. X rays— Penetrating electromagnetic radiati ons whose wave lengths are very much shorter than those of visible light. They are usually produced by bombar ding a metallic target with fast electrons in a high vacuum. X rays (called characteristic x rays) are al so produced when an orbital electron falls from a high energy level to a low energy level. Zero-Threshold Linear Hypothesis (o r 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.STRONTIUM A-1



### APPENDIX A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS
The Comprehensive Environmental Response, Compen sation, and Liability Act (CERCLA) [42 U.S.C. 9601 et seq.], as amended by the Superfund Amendmen ts 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 da ta needs associated with the substances.
The toxicological profiles include an examination, su mmary, and interpretation of available toxicological information and epidemiologic evaluations of a hazardous substance. During the development of toxicological profiles, Minimal Risk Levels (MRLs) ar e derived when reliable and sufficient data exist to identify the target organ(s) of effect or the most sen sitive 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 a dverse 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 contamin ants 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 a dverse health effects in the people most sensitive to such chemical-induced effects. MRLs are derived fo r 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 gene rally based on the most sensitive chemical-induced end point considered to be of relevance to humans. Seri ous 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 ad verse health effects will occur.
MRLs are intended only to serve as a screening tool to help public health professionals decide where to look more closely. They may also be viewed as a mechanism to identify those hazardous waste sites thatSTRONTIUM A-2 APPENDIX A are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of the lack of precise toxicological information on th e 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 addre ss this uncertainty consistent with the public health principle of prevention. Although human data are pr eferred, MRLs often must be based on animal studies because relevant human studies are lacking. In th e absence of evidence to the contrary, ATSDR assumes that humans are more sensitive to the effects of hazard ous 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 comment s 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 prev iously published levels. For additional information regarding MRLs, please contact the Division of To xicology, Agency for Toxic Substances and Disease Registry, 1600 Clifton Road NE, Mailstop F-32, Atlanta, Georgia 30333.STRONTIUM A-3 APPENDIX A 

### MINIMAL RISK LEVEL (MRL) WORKSHEET

Chemical name(s): Strontium CAS number(s): 7440-24-6 Date: March 2004 Profile status: Third draft, post-public Route: [ ] Inhalation [X] Oral Duration: [ ] Acute [X] Intermediate [ ] Chronic Key to figure: 16 Species: Rat
MRL: 2.0 [X] mg/kg/day [ ] ppm [ ] mg/m 3
Reference : Storey E. 1961. Strontium ‘rickets’: Bo ne calcium and strontium changes. Austral Ann Med 10:213-222. Experimental design : Groups of five young (40–60 g) and three adult (200–250 g) female rats were fed a diet containing 1.6% calcium, 0.9% phosphorus, and 0, 0.19, 0.38, 0.75, 1.0 (young only), 1.5, or 3% strontium as strontium carbonate for 20 days. Initial and final body weights were recorded. Terminal levels of calcium and strontium were measured in serum and in five selected ashed bones for each dose level. Both tibia from each animal were processed histologically, and the proximal epiphyseal cartilages were measured. Effects noted in study and corresponding doses : The strontium intakes were calculated to be 0, 140, 550, 1,080, 1,460, 2,220, or 4,975 mg strontium/kg/day in young rats, and 0, 170, 350, 690, 1,370, or 2,750 mg strontium/kg/day in adult rats. The serum calcium le vels were not significantly changed in either young or adult animals, but at the high doses, the serum ca lcium/strontium ratio was about 1 in young rats and 1.4 in adults. In young rats, increased strontium ingestion resulted in abnormal thickening of the epiphyseal cartilage plate, approximately doubled at the highest dose. No histological effect was noted at the lowest dose (140 mg strontium/kg/day), but alte rations in the appearance of the cartilage plate (irregular, thicker, with areas of uncalcified bone matr ix in the distal ends of the metaphyseal trabeculae and proximal end of the diaphysis) were observed at 550 mg strontium/kg/day. Irregularities in the organization of the cells of hypertrophic zone, in the pattern of calcification, and in the deposition of osteoid were more conspicuous with increasing dose. In tibias, the dry weight, ash weight, ash percentage, and calcium in ash were significantly re duced with increased strontium intake. Adult rats were less affected by strontium ingestion than young animals. In adult rats, the no-effect level was 690 mg strontium/kg/day. In adults, changes in tib ia histology (thicker epiphyseal cartilage, increased width of metaphyseal osteoid seams) were noted at or above 1,370 mg strontium/kg/day. At 2,750 mg strontium/kg/day, osteoid tissue was deposited near vascular canals and the areas of bone resorption were reduced. In adult rat tibias, the dry weight, ash we ight, ash percentage, and calcium in ash were only significantly affected at the highest dose. This study demonstrates the difference in sensitivity to strontium between young and old animals. The LOA EL for the young rats (550 mg/strontium/kg/day) is a NOAEL for the adults (<690 mg strontium/kg/day). Dose and end point used for MRL derivation : This study identifies a NOAEL of 140 mg/kg/day for skeletal toxicity in young rats. [X] NOAEL [] LOAEL:STRONTIUM A-4 APPENDIX A Uncertainty factors used in MRL derivation : [ ] 1 [ ] 3 [] 10 (for use of a LOAEL) [ ] 1 [] 3 [X] 10 (for extrapolation from animals to humans) [ ] 1 [X ] 3 [] 10 (for human variability) Modifying factor used in MRL derivation : 3 MRL = NOAEL / (UF)(MF) = 140 mg/kg/day / (30)(3) = 2 mg/kg/day Was a conversion factor used from ppm in food or water to a mg/body weight dose? Food intake was based upon an allome tric equation using the average body weight in kg (EPA 1988): F = 0.056 x bw 0.6611

. If an inhalation study in animals, list conversion f actors used in determining human equivalent dose : NA Was a conversion used from intermittent to continuous exposure? If so, explain : NA Other additional studies or pertinent info rmation that lend support to this MRL : If an MRL were to be derived from the adult rat NOAEL of 690 mg/kg/day, then an uncertainty factor of 100 would be applied (10 for interspecies extrapolation and 10 for human variability), giving a value of 690/100=6.9 mg/kg/day. Because th e young rats represent a sensitive popu lation, just as juveniles would be the most sensitive human group, the selection of the NOAEL implicitly factors in human variability to some degree. Therefore, a smaller uncertainty factor is chosen for intraspecies extrapolation (3 for human variability). However, since the study duration was only 20 days, there is uncertainty whether the NOAEL would be valid for intermediate exposures extendi ng up to 1 year. In addition, the focus of the study was skeletal effects, and no other organ syst em was examined. To adju st for these potential sources of uncertainty, a modifying factor of 3 is applied to the NOAEL. The MRL is derived using the young rat NOAEL of 140 mg/kg/day and a total uncertainty factor of 30 (10 for interspecies extrapolation and 3 for human variability), and a modifying factor of 3 (for short study duration and limited end point evaluation), giving a value of 140/(30x )=1.6 mg/kg/da y; rounding off to whole numbers, the intermediate oral MRL is 2.0 mg/kg/day. Abnormal bone mineralization (rickets) resulting from ingestion of excess strontium has been observed in many rodent studies. Several studies identified a similar NOAEL (110–168 mg strontium/kg/day) in weanling rats (Grynpas et al. 1996; Kroes et al. 1977; Morohashi et al. 1994). Similar LOAELs (500–565 mg strontium/kg/day) for abnormal bone mine ralization in weanling rats have been reported (Johnson et al. 1968; Morohashi et al. 1994; Neufeld and Boskey 1994). Slight skeletal effects were noted in mice at 350 mg/kg/day (Marie and Hott 1986). The relevance of the rodent studies to humans is suggested by a Turkish epidemiological study indi cating that excess oral exposure to strontium may contribute to the development of rickets in children (Ögzür et al. 1996).
The skeletal effects of excess strontium are known to be related to its chemical similarity to calcium. Excess strontium adversely affects bone development in several ways. In chickens and rats, excess strontium suppresses the activation of vitamin D3 in the kidney, which severely reduces the expression of calbindin D mRNA and the translation of calbindin D protein in the duodenum (Armbrecht et al. 1979, 1998; Omdahl and DeLuca 1972). As a result, duodenal absorption of calcium is reduced. Strontium also binds directly to hydroxyapatite crystals, which may interfere with the normal crystalline structure of bone in rats (Storey 1961). In addition, excess strontium may prevent the normal maturation of chondrocytes in the epiphyseal plates of long bones of rats (Matsumoto 1976). Excess strontium apparently interferes with the mineralization of co mplexed acidic phospholipids that is thought to helpSTRONTIUM A-5 APPENDIX A
initiate the formation of h ydroxyapatite crystals in developing bone (Neufeld and Boskey 1994). As a result, affected bone contains an excess of comple xed acidic phospholipid and a significantly lower ash weight, reducing its strength.STRONTIUM B-1



### APPENDIX B. USER'S GUIDE Chapter 1
Public Health Statement This chapter of the profile is a health effects su mmary 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 H ealth Statement are useful to find specific topics of concern. The topics are written in a question and answer format. The answer to each questi on includes a sentence that will direct the reader to chapters in the profile th at 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 in formation. This summary is desi gned to present interpretive, weightof-evidence discussions for human health end po ints 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 ar e organized by duration (acute, intermediate, chronic). In vitro data and data from parenteral routes (intramusc ular, 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. Minima l 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 preven t a satisfactory evaluation of the relevance to public health are identified in the Ch apter 3 Data Needs section. Interpretation of Minimal Risk Levels Where sufficient toxicologic information is availabl e, 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 he alth professionals with e xposure levels at which adverse health effects are not expected to occur in humans.STRONTIUM B-2 APPENDIX B

MRLs should help physicians and pu blic health officials determine the safety of a community living near a chemical emission, given the concentration of a contam inant 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 info rmation on which the number is based. Chapter 2, "Relevance to Public Health," contains basic informa tion 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 deri vation 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 developm ental effects. If this information and reliable quantitative data on the chosen end point are availabl e, ATSDR derives an MRL using the most sensitive species (when information from multiple species is availa ble) with the highest no-observed-adverse-effect level (NOAEL) that does not exceed any adverse eff ect levels. When a NOAEL is not available, a lowest-observed-adverse-effect level (LOAEL) can be u sed 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 (peopl e who are most susceptible to the health effects caused by the substance) and for interspecies vari ability (extrapolation from animals to humans). In deriving an MRL, these individual uncertainty fact ors 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 effe cts and illustrate graphica lly levels of exposure associated with those effects. These levels cover health effects observed at increasing dose concentrations and durations, diffe rences 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 appli cation 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.STRONTIUM 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 princi pal routes of exposure, i.e., inhalation, oral, and dermal (LSE Table 3-1, 3-2, and 3-3, respec tively). LSE figures are limited to the inhalation (LSE Figure 3-1) and oral (LSE Figure 3-2) rout es. 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 prese nted within each relevant route of exposure. In this example, an inhalation study of interm ediate exposure duration is reported. For quick reference to health effects occurring from a know n 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 "S ystem" 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 correspondi ng 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 rele vance of animal data to human toxicity and Section 3.4, "Toxicokinetics," contains any available information on comparative toxicokinetics. Although NOAELs and LOAELs are species specific, the levels are extrapolated to equivalent human doses to derive an MRL. (6) Exposure Frequency/Duration . The duration of the study an d 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), ra ts 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 th e 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 numbe r 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").STRONTIUM 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 whic h adverse health effects first appear and the gradation of effects with increasing dose. A brie f 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 associ ated 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 refere nce 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 interm ediate exposure periods are illustrated. (14) Health Effect . These are the categories of health effects for which reliable quantitative data exists. The same health eff ects 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. Exposur e concentration or dose is measured on the log scale "y" axis. Inhalation exposure is reported in mg/m 3 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 inhalati on 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.STRONTIUM 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 (q 1 *). (19) Key to LSE Figure . The Key explains the abbreviations and symbols used in the figure.Reference10↓Nitschke et al. 1981Wong et al. 1982NTP 1982NTP 1982Serious (ppm)(CEL, multipleorgans)(CEL, lung tumors,nasal tumors)(CEL, lung tumors,hemangiosarcomas)11↓201010LOAEL (effect)Less serious(ppm)9↓10 (hyperplasia)SAMPLENOAEL(ppm)8↓3bSystem7↓RespExposurefrequency/duration6↓13 wk5 d/wk6 hr/d18 mo5 d/wk7 hr/d89-104 wk5 d/wk6 hr/d79-103 wk5 d/wk6 hr/dSpecies5↓RatRatRatMouseTABLE 3-1. Levels of Significant Exposure to [Chemical x] – InhalationKey to figureaINTERMEDIATE EXPOSURESystemic18CHRONIC EXPOSURECancer383940a The number corresponds to entries in Figure 3-1.b Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5x10-3 ppm; dose adjusted for intermittent exposure and dividedby an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability).→→→→→123412 STRONTIUM B-6 APPENDIX BSTRONTIUM B-7 APPENDIX BSTRONTIUM C-1



### APPENDIX C. ACRONYMS, AB BREVIATIONS, AND SYMBOLS Some terms are generic and may not be used in this profile. ACGIH American Conference of Gove rnmental Industrial Hygienists ACOEM American College of Occupa tional 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 Occupationa l 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 Res ponse, 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 DefenseSTRONTIUM 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/Inte rnational Maritime Da ngerous 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 F 1 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, F ungicide, 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 K oc organic carbon partition coefficient K ow octanol-water partition coefficient L liter LC liquid chromatography LC 50 lethal concentration, 50% kill LC Lo lethal concentration, low LD 50 lethal dose, 50% kill LD Lo lethal dose, low LDH lactic dehydrogenase LH luteinizing hormone LOAEL lowest-observed-adverse-effect level LSE Levels of Significant Exposure LT 50 lethal time, 50% kill m meter MA trans,trans -muconic acidSTRONTIUM 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 O ccupational 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 AdministrationSTRONTIUM C-4 APPENDIX C OSW Office of Solid Waste, EPA OTS Office of Toxic Substances OW Office of Water OWRS Office of Water Regula tions 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 TD 50 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 compoundSTRONTIUM C-5

WBC WHO

> ≥ = < ≤ % α β γ δ μm μg q 1 *

– + (+) (–) APPENDIX C
white blood cell 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 resultSTRONTIUM D-1



### APPENDIX D. OVERVIEW OF BASI C RADIATION PHYSICS, CHEMISTRY, AND BIOLOGY

Understanding the basic concepts in radiation physi cs, 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 br ief 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 a nd electrons in a cloud of orbits around the nucleus. Nuclide is the general term referring to any nucleu s 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 num ber 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 at om 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 atom s are called radionuclides; their emissions are called ionizing radiation; and the whole property is called radi oactivity. Transformation or decay results in the formation of new nuclides some of which may them selves 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 s ubsequent products of the transformation are called progeny, daughters, or decay products. In general there are two classifications of radioac tivity and radionuclides: na tural and artificial (manmade). Naturally-occurring radioactive materials (N ORMs) exist in nature and no additional energy is necessary to place them in an unstable state. Natural radioactivity is the pr operty of some naturally occurring, usually heavy elements, that are heavie r than lead. Radionuclides, such as radium and uranium, primarily emit alpha particles. Some li ghter 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 h eavier 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 fo r 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 artificia lly produced radioactive elements usually decay by emission of particles, such as positive or negative be ta particles and one or more high energy photons (gamma rays). Unstable (radioactive) atoms of any element can be produced.STRONTIUM D-2 APPENDIX D

Both naturally occurring and artificial radioisotopes find application in medici ne, 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 daught ers, 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 chai n of daughter decay produc ts may be produced until stable atoms are formed. Radionuclides can be charact erized 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 ch arged 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 charac teristics 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 fi rst-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 combin ations 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 (transforma tions) 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) = 3.7x10 10 disintegrations (transforma tions)/second (dps) or 2.22x10 12 disintegrations (transformations)/minute (dpm). The SI unit of activity is the becquerel (Bq); 1 Bq = th at 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 radioac tive nuclei is a random process, and the number of transformations is directly proportional to the num ber of radioactive atoms present. For any pure radioactive substance, the rate of decay is usually described by its radiological half-life, T R , i.e., the time it takes for a specified source material to decay to ha lf 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.STRONTIUM D-3 APPENDIX D

The activity of a radionuclide at time t may be calculated by:

-0.693t/Trad A = A o e where A is the activity in dps or curies or becquerels, A o is the activity at time zero, t is the time at which measured, and T rad is the radiological half-life of the radionuclide (T rad and t must be in the same units of time). The time when the activity of a sample of radi oactivity 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 length b Radiation Rest mass a Charge energy range Air Solid Comments Alpha ( α ) 4.00 amu +2 4–10 MeV 5–10 cm 25–80 μm Identical to ionized He nucleus Negatron ( β
– ) 5.48x10 -4 amu; –1 0–4 MeV 0–10 m 0–1 cm Identical to electron 0.51 MeV Positron ( β + ) 5.48x10 -4 amu; +1 0-4 MeV 0–10 m 0–1 cm Identical to electron 0.51 MeV except for sign of charge Neutron 1.0086 amu; 0 0–15 MeV b b Free half-life: 16 939.55 MeV min X ray (e.m. – 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=mc 2 , where 1 amu = 932 MeV. b Path lengths are not applicable to x- a nd gamma rays since their intensities decrea se exponentially; path lengths in solid tis sue are variable, depending on particle energy, elec tron density of materi al, 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 = 1.3x10 8 / (T rad ) (atomic weight) or [3.577 x 10 5 x mass(g)] / [T rad x atomic weight] where T rad 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 pro cesses of elimination of the respective chemical or biochemical substance from the organism. This intr oduces a rate constant called the biological half-life (T biol ) 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.STRONTIUM 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 elimin ation is the effective clearance half-time:
T eff = (T biol x T rad ) / (T biol + T rad ). Table D-2 presents representative effective half-lives of particular interest.

Table D-2. Half-Lives of Some Radionuclides in Adult Body Organs
Half-life a Radionuclide Critical organ Physical Biological Effective Uranium 238 Hydrogen 3 b 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 w ith materials; that is, radiation will lose kinetic energy to any solid, liquid or gas through which it pa sses 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 radiat ion 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 mo lecules, 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 mol ecules, 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 ionizati on. Heavy, highly charged particles, such as alphaSTRONTIUM 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 sl owing down of any incide nt 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 par ticle 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 tw o 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 travel s 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 nega tively 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 proton s 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 maxi mum 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 th ought 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 leve l. 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 negativ e beta particles and positron emissionsSTRONTIUM D-6 APPENDIX D energy released is in the form of gamma radiation (h igh energy photons) and has an energy equal to the change in the energy state of the nucleus. Gamma an d 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 oc curs 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 th e 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 wh en radionuclides, which have entered the body (e.g., through the inhalation, ingestion, or dermal pa thways), undergo radioactive decay resulting in the deposition of energy to internal organs. External e xposures occur when radiation enters the body directly from sources located outside the body, such as radi ation 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 an d 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 ga mma-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 radia tion, 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 whic h is equivalent to 100 rad or 1 J/kg. Internal and external exposures from radiation sources are not usua lly 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 (thr ough polonium-214), per liter of air, that will result in the emission of 1.3x10 5 MeV of alpha energy. An activity concentrati on 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, 1.3x10 5 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 th e unit Working Level Month (WLM). One WLMSTRONTIUM 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 in ternally 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 fro m 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 worker s, inhalation of radioactive particles with pulmonary deposition and puncture wounds with subcutaneous deposition have b een the most frequent. The general population has been exposed via ingestion and in halation of low levels of naturally occurring radionuclides as well as radionuclides from nuclear weapons testing. The models for external dosimetry consider only th e 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 inhale d 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 passag e 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 absorpti on 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 be ing 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 abso rption. 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 ma ss 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 th e 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 ti ssue) of reference. Gamma-emitting radionuclide emissions are penetrating radiation, and a substantial fraction of ga mma energy may be absorbed inSTRONTIUM 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 radiati on, 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 mo lecules in cells and to explain the resulting damage to biological systems from those interactions. Ma ny factors may modify the response of a living organism to a given dose of radiation. Factors relate d to the exposure include the dose rate, the energy of the radiation, and the temporal pattern of the exposur e. 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 19 84; 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-strande d DNA breaks are likely, resulting in cellular reproductive death after one or more divisions of the i rradiated parent cell. At large doses of radiation, usually greater than 500 rad (5 Gy), direct cell d eath 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. Accordi ng 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 in dividual. 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 underlyi ng 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 or gan 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 ra diosensitive cells, such as the stem cells in the bone marrow. Injury may also result from constric tion of the microcirculation and from edema and inflammation of the basement membrane, designated as the histohematic barrier, which may progress toSTRONTIUM D-9 APPENDIX D
fibrosis. In slow renewal and nonr enewal systems, the radiation may ha ve little effect on the parenchymal cells, but ultimate parenchymal atr ophy 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 ab ility of alpha, beta, and gamma radiation to produce cancer in virtually every tissue and organ in labor atory 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 i onizing 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 ionizi ng radiation, including cancer. Damage to genetic material is basic to developmental or teratogenic eff ects, as well. However, for effects other than cancer, there is little evidence of human eff ects 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 pr oduct of the absorbed dose, D, and the quality factor, Q, at the point of interest in biological ti ssue. 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 wei ghting factor is a dimensionless quan tity 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 bi ological 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 vari ous 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.STRONTIUM D-10 APPENDIX D

Table D-3. Quality Factors (Q) and Absorbed Dose Equivalencies
Type of radiation Quality factor (Q) Radiation weighting factor (w r )* 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 th e protection against radiati on, table 1004(b).1. 10 CFR 20.1004. U.S. Nuclear Regulatory Commission, Wash ington, 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 require d 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 calculati ons 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, H E , is
H E = (the sum of) W t H tSTRONTIUM D-11 APPENDIX D
where H t is the dose equivalent (or equivalent dose) in the tissue t, W t 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 Pr otection and Measurements. 1993. Risk Estimates for Radiation Protection, Report 115. Bethesda, Maryland USNRC = Nuclear Regulatory Commission, Title 10, Code of Federal Regulations, Part 20STRONTIUM D-12 APPENDIX D

Table D-5. Comparison of Common a nd SI Units for Radiation Quantities Customary Quantity units Definition SI units Definition Activity (A) curie (Ci) 3.7x10 10 becquerel (Bq) s -1 transformations s 1 Absorbed dose (D) rad 10 -2 Jkg -1 gray (Gy) Jkg -1 -1 -1 Absorbed dose rate rad per second 10 -2 Jkg -1 s 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 -1 s 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 -1 s -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 exposu re 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 in ternally 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.STRONTIUM D-13 APPENDIX D Brodsky A. 1996. Review of radiation risks and uranium toxicity with application to decisions associated with decommissioning clean-up crite ria. 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. Radia tion 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 Radiol ogical 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 Radiolog ical Protection 1990 Recommendations of the ICRP ICRU. 1980. International Commission on Radiation Units and Measureme nts. ICRU Report No. 33. Washington, DC. James A. 1987. A reconsideration of cells at risk a nd other key factors in radon daughter dosimetry. In: Hopke P, ed. Radon and its decay products: Occurren ce, 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 Univer sity 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 i onizing radiation. New York: Grune and Stratton. NCRP. 1971. Basic radiation protection criteri a. National Council on Radiation Protection and Measurements. Report No. 39. Washington, DC.STRONTIUM D-14 APPENDIX D NCRP. 1985. A handbook of radioactivity meas urements procedures. 2nd ed. National Council on Radiation Protection and Measurements. Report No. 58. Bethesda, MD: NCRP. 1993. Risk estimates for radiation protec tion. National Council on Ra diation 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 pat hology. 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.STRONTIUM E-1



### APPENDIX E. INDEX acetylcho line.................................................................................................................. ..............................................61 acute inhalatio n exposure ............................................................................................................................................73 adenocarcinoma................................................................................................................. ..........................................75 adsorption ..................................................................................................................... .....................................169, 254 air...................................2, 3, 4, 11, 12, 15, 30, 135, 138, 157, 177, 195, 205, 209, 213, 214, 217, 219, 220, 222, 236, 239, 243, 244, 252, 255, 257, 259, 260, 262, 270, 272, 274 ambient air.................................................................................................................... .............................................237 Arctic ......................................................................................................................... ................................................241 bass ............................................................................................................................................................................217 BCF (see bioconcentration factor).............................................................................................. ...............................217 bioaccumulation ................................................................................................................ ................................217, 243 bioavaila bility

................................................................................................................ ....120, 169, 176, 186, 187, 243 bioconcentration f actor (see BCF).............................................................................................. .......................217, 218 biodegradation ................................................................................................................. ..................................217, 243 biomarker...................................................................................................................... .....162, 163, 164, 184, 186, 187 birds.............................................................................................................................................................................55 birth weight................................................................................................................... .................................95, 96, 180 blood............................................7, 10, 22, 60, 61, 72, 73, 99, 110, 115, 117, 127, 128, 135, 143, 144, 146, 14 7, 149, 156, 163, 164, 184, 187, 240, 251, 255 body weight effects............................................................................................................ ........................25, 55, 73, 92 breast milk ..................................................................................................... 9, 122, 128, 13 2, 159, 161, 239, 240, 245 cancer...........................................3, 6, 7, 8, 9, 15, 20, 21, 27, 28, 32, 33, 35, 59, 62, 74 , 75, 76, 77, 93, 95, 96, 97, 98, 100, 109, 110, 116, 153, 157, 159, 178, 179, 180, 181, 182, 183, 186, 188, 201, 257, 267, 268, 269, 272, 274, 276 carcinogen..................................................................................................................... .7, 8, 16, 21, 153, 257, 259, 272 carcinogenic............................................................................................... 8, 16, 22, 27, 31, 3 2, 62, 100, 178, 259, 274 carcinoge nicity ................................................................................................................ ............35, 117, 176, 257, 259 carcinoma ...................................................................................................................... ..............22, 35, 65, 75, 98, 100 cardiovascular effects ........................................................................................................................33, 48, 70 , 80, 101 deoxyribonucleic acid (see DNA)................................................................................................ ......................114, 115 Department of Health and Human Services........................................................................................ ...........................7 dermal effects ................................................................................................................. ...........................................107 DNA (see deoxyribonucleic acid).................................. 8, 113, 114, 115, 116, 117, 153, 163, 164, 179, 184, 187, 255 dog............................................................................................................................ ...................71, 73, 74, 76, 99, 182 endocrine effects.............................................................................................................. ....................................55, 101 estrogen receptor.............................................................................................................. ..........................................150 FDA (see Food and Drug Administrati on) ..................................................................................11, 261 , 267, 272, 275 Federal Research in Progress (see FEDRIP) ...................................................................................... ...............246, 255 FEDRIP (see Federal Re search in Progress) ...................................................................................... .......246, 247, 255 fetus ................................................................. 9, 76, 126, 1 27, 128, 156, 158, 161, 180, 181, 185, 186, 261, 265, 267 fish........................................................................................................................... ..........4, 5, 217, 218, 229, 232, 241 Food and Drug Admini stration (see FDA) ......................................................................................... .11, 229, 272, 275 fruits......................................................................................................................... ......................15, 27, 229, 232, 242 gastrointestin al effects ....................................................................................................... ....................................48, 89 general populatio n ......................................................................... 8, 15, 16, 18, 60 , 110, 162, 165, 18 2, 183, 239, 275 groundwater................................................................................................... 4, 205, 213, 215, 222, 223, 247, 264, 270 half-life ................................................................................ 2, 15, 18, 28, 142, 152, 160, 162, 189 , 197, 205, 216, 275 hematological effects.......................................................................................................... .....................26, 50, 71, 110 hepatic effects................................................................................................................ ..................................54, 72, 91 hydrol ysis ..................................................................................................................... .....................................217, 243 immune system.................................................................................................................. ......21, 29, 73, 110, 178, 181 immunological effects .......................................................................................................... .............23, 34, 73 , 93, 177 insects ........................................................................................................................ ................................................217STRONTIUM E-2 APPENDIX E Integrated Risk In formation System............................................................................................. .....................257, 259 intermediate or al exposure..................................................................................................... ......................................92 kidney .......................................................................... 55, 119, 125, 126, 12 7, 129, 148, 149, 151, 158 , 163, 165, 167 K ow ............................................................................................................................... ..............................193, 194, 195 lake ............................................................................................................................................................................222 LD 50 ............................................................................................................................... ........................................25, 36 leukemia ........................................................................ 8, 9, 21, 26, 28, 65, 75, 76, 77, 93, 97, 98, 1 00, 116, 178, 183 liver...................................................................... 20, 59, 63, 72 , 76, 119, 125, 126, 127, 129, 134, 14 4, 146, 163, 182 LOAEL (see lowest-observed-adverse-effect level).......... 24, 31 , 36, 58, 62, 65, 74 , 76, 80, 94, 95, 97, 101, 107, 108 lowest-observed-adverse-ef fect level (see LOAEL)............................................................................... ...............24, 31 lung........................................5, 8, 12, 18, 20, 21, 22, 23, 33, 35, 63, 64, 65, 70, 71, 72, 73, 75, 76, 80, 118, 119, 125, 126, 127, 135, 163, 185, 262 lymph......................................................................................................... 19, 63, 73, 76, 1 12, 114, 117, 142, 143, 147 lymphatic ...................................................................................................................... .............................................135 lymphoreticular effects ........................................................................................................ ..................................58, 94 marine......................................................................................................................... .......................214, 216, 228, 241 mass spectroscopy .............................................................................................................. .......................................184 mast cell...................................................................................................................... .................................61, 152, 181 melanoma ....................................................................................................................................................................92 milk................................................................ 8, 9, 19, 96, 112, 121, 128, 132, 161, 168, 169, 229, 239, 240, 244, 275 Minimal Risk Le vel (see MRL)................................................................................................... ................................32 miscarriages................................................................................................................... ......................................95, 159 MRL (see Minimal Risk Level) ........................................................................... 23, 24, 25, 26, 32, 160, 176, 177, 257 musculoskeleta l effects........................................................................................................ ..................................50, 51 National Priorities List (see NPL) ............................................................................................. ............................1, 205 neurobehavioral .........................................................................................................................................................155 neurophysiologi cal............................................................................................................. ..........................................17 neurotrans mitter............................................................................................................... ............................................61 NIOSH......................................................................................... 11, 190, 191, 192, 237, 249, 250, 258, 259, 267, 272 NOAEL (see no-observed-adverse-effect level)........................... 24, 25, 31, 32, 36, 58 , 62, 65, 74, 76, 80, 94, 95, 97, 101, 107, 108, 257 NOES.........................................................................................................................................................................239 non-Hodgkin’s lymphoma......................................................................................................... ..........................97, 183 no-observed-adverse-eff ect level (s ee NOAEL)................................................................................... .................24, 31 NPL (see National Prioritie s List) .................................................................................1, 205, 206, 207, 209, 213, 214 ocular effects ................................................................................................................. ....................33, 36, 65 , 92, 108 odds ratio (see OR)............................................................................................................ ..........................................50 OR (see odds ratio)............................................................................................................ ................212, 220, 225, 234 particulate .................................................................................................................... ................................63, 135, 147 particul ates................................................................................................................... ........................34, 144, 147, 244 PBPD (see physiologically based pharm acodynamic)............................................................................... ................132 PBPK (see physiologically based pharmacokinetic) .................................................................132, 133, 134, 185, 186 PEL (see permissible exposure limit) ........................................................................................... .....................258, 259 permissible exposur e limit (s ee PEL) ........................................................................................... .............................259 pharmacodynamic......................................................................................................................................................132 pharmacokinetic................................................................................................................ .................................132, 133 physiologically based pha rmacodynamic (see PBPD)............................................................................... ................132 physiologically based pharm acokinetic (see PBPK) ............................................................................... ..................134 plankt on ....................................................................................................................... ..............................................218 precipitatio n............................................................................................................... 214 , 215, 219, 223, 247, 250, 253 public health .................................................................................................................. .. 1, 6, 11, 27, 31, 155, 176, 276 pulmonary fibros is............................................................................................................. ..............................18, 65, 70 RCRA (see Resource Conserva tion and Rec overy Act).............................................................................. ..............202 reference dose (see RfD) ....................................................................................................... ............................257, 259 regulations ............................................................................................. 11, 12 , 201, 243, 257, 260, 265, 274, 275, 276 renal effects .................................................................................................................. ...................................55, 72, 92