Health Effects Support 

Document for Strontium
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Health Effects Support Document

For

Strontium

U.S. Environmental Protection Agency

Office of Water (4304T)

Health and Ecological Criteria Division

Washington, DC 20460

www.epa.gov/safewater/ccl/pdf/Strontium.pdf

EPA Document Number: 820-P-14-001

Date: April 2014
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FOREWORD

The Safe Drinking Water Act (SDWA), as amended in 1996, requires the Administrator 

of the U.S. Environmental Protection Agency (U.S. EPA) to establish a list of contaminants to 

aid the Agency in regulatory priority setting for the drinking water program. In addition, the 

SDWA requires U.S. EPA to make regulatory determinations for no fewer than five 

contaminants five years after publication of the Contaminant Candidate List (CCL). The criteria 

used to determine whether or not to regulate a chemical on the CCL are the following: 

 The contaminant may have an adverse effect on the health of persons. 

 The contaminant is known to occur or there is a substantial likelihood that the 

contaminant will occur in public water systems with a frequency and at levels of public 

health concern. 

 In the sole judgment of the Administrator, regulation of such contaminant presents a 

meaningful opportunity for health risk reduction for persons served by public water 

systems.

The agency’s findings for all three criteria are used in making a determination to regulate 

a contaminant. The agency may determine that there is no need for regulation when a 

contaminant fails to meet one of the criteria. The decision not to regulate is considered a final 

Agency action and is subject to judicial review.

This document provides the health effects basis for the regulatory determination for 

strontium and compounds. In arriving at the regulatory determination, data on toxicokinetics, 

human exposure, acute and chronic toxicity to animals and humans, epidemiology, and 

mechanisms of toxicity were evaluated. In order to avoid duplication of effort, information from 

the following risk assessments by the U.S. EPA and other government agencies were used in the 

development of this document.

ATSDR (Agency for Toxic Substances and Disease Registry). 2004. Toxicological 

profile for strontium. United States Department of Health and Human Services, Public 

Health Service, Agency for Toxic Substances and Disease Registry. Available from: 

<http://www.atsdr.cdc.gov/toxprofiles/tp159.html>.

IOM (Institute of Medicine). 2010. Dietary Reference Intakes for Calcium and Vitamin 

D. Institute of Medicine, Food and Nutrition Board. Available from: 

<http://www.nap.edu/catalog.php?record_id=13050>. 

U.S. EPA (United States Environmental Protection Agency). 1992. Strontium (CASRN 

7440-24-6). Integrated Risk Information System (IRIS). Washington, DC, United States 

Environmental Protection Agency. Available from: 

<http://www.epa.gov/ncea/iris/subst/0550.htm>. 
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WHO (World Health Organization). 2010. Concise International Chemical Assessment 

Document 77. Strontium and Strontium Compounds. Available from: 

http://www.who.int/ipcs/publications/cicad/cicad77.pdf.

Information from the published risk assessments was supplemented with information 

from the primary references for key studies and recent studies of strontium and compounds 

identified by a literature search conducted in 2010.

A Reference Dose (RfD) is provided as the assessment of long-term toxic effects other 

than carcinogenicity. RfD determination assumes that thresholds exist for certain toxic effects, 

such as cellular necrosis, significant body or organ weight changes, blood disorders, etc. It is 

expressed in terms of milligrams per kilogram per day (mg/kg/day). In general, the RfD is an 

estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure to 

the human population (including sensitive subgroups) that is likely to be without an appreciable 

risk of deleterious effects during a lifetime. 

The carcinogenicity assessment for strontium and compounds includes a formal hazard 

identification and an estimate of tumorigenic potency when available. Hazard identification is a 

weight-of-evidence judgment of the likelihood that the agent is a human carcinogen via the oral 

route and of the conditions under which the carcinogenic effects may be expressed. 

Development of these hazard identification and dose-response assessments for strontium 

and compounds has followed the general guidelines for risk assessment as set forth by the 

National Research Council (1983). U.S. EPA guidelines that were used in the development of 

this assessment may include the following: Guidelines for the Health Risk Assessment of 

Chemical Mixtures (U.S. EPA, 1986a), Guidelines for Mutagenicity Risk Assessment (U.S. EPA, 

1986b), Recommendations for and Documentation of Biological Values for Use in Risk 

Assessment (U.S. EPA, 1988), Guidelines for Developmental Toxicity Risk Assessment (U.S. 

EPA, 1991), Interim Policy for Particle Size and Limit Concentration Issues in Inhalation 

Toxicity (U.S. EPA, 1994a), Methods for Derivation of Inhalation Reference Concentrations and 

Application of Inhalation Dosimetry (U.S. EPA, 1994b), Use of the Benchmark Dose Approach 

in Health Risk Assessment (U.S. EPA, 1995), Guidelines for Reproductive Toxicity Risk 

Assessment (U.S. EPA, 1996), Guidelines for Neurotoxicity Risk Assessment (U.S. EPA, 1998a), 

Science Policy Council Handbook: Risk Characterization (U.S. EPA, 2000a), Benchmark Dose 

Technical Guidance Document (U.S. EPA, 2000b), Supplementary Guidance for Conducting 

Health Risk Assessment of Chemical Mixtures (U.S. EPA, 2000c), A Review of the Reference 

Dose and Reference Concentration Processes (U.S. EPA, 2002), Guidelines for Carcinogen Risk 

Assessment (U.S. EPA, 2005a), Supplemental Guidance for Assessing Susceptibility from EarlyLife Exposure to Carcinogens (U.S. EPA., 2005b), Science Policy Council Handbook: Peer 

Review (U.S. EPA, 2006a), and A Framework for Assessing Health Risks of Environmental 

Exposures to Children (U.S. EPA, 2006b). 

The chapter on occurrence and exposure to strontium and compounds through potable 

water was developed by the Office of Ground Water and Drinking Water (OGWDW). It is 

based primarily on National Inorganic and Radionuclide Survey (NIRS) data collected under the 
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Safe Drinking Water Act (SDWA). The NIRS data are supplemented with ground water data 

from USGS and States as well as published papers on occurrence in groundwater and drinking 

water.
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ACKNOWLEDGMENT

This document was prepared under the U.S. EPA Contract No EP-C-1-030, Work 

Assignment No. B-02 with ToxServices LLC. The Lead U.S. EPA Scientists is and Joyce M. 

Donohue, Ph.D., Health and Ecological Criteria Division, Office of Science and Technology, 

Office of Water.
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AUTHORS AND CONTRIBUTORS

CHEMICAL MANAGER

Joyce M. Donohue, Ph.D.

Office of Water, Office of Science and Technology

Health and Ecological Criteria Division

U.S. Environmental Protection Agency

Washington, DC 20460

AUTHORS (EPA)

Amal M. Mahfouz, Ph.D.

Office of Water, Office of Science and Technology

Health and Ecological Criteria Division

U.S. Environmental Protection Agency

Washington, DC 20460

Joyce M. Donohue, Ph.D.

Office of Water, Office of Science and Technology

Health and Ecological Criteria Division

U.S. Environmental Protection Agency

Washington, DC 20460

AUTHORS (CONTRACT)

Irene M. Baskerville-Abraham, Ph.D.

Lynne Haber, Ph.D., DABT

Toxicology Excellence for Risk Assessment

2300 Montana Ave, Suite 409

Cincinnati, OH 45211

Contract Number: EP-C-10-030, Work Assignment Number B-02 and 1-02

Under subcontract to 

ToxServices, LLC

1367 Connecticut Ave N.W., Suite 300

Washington, DC 20036

Contract Number: EP-C-10-030, Work Assignment Number B-02
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PEER REVIEWERS1

Marc De Broe, Ph.D. 

University of Antwerp

Antwerp, Belgium

Alan H. Stern, Dr.P.H., DABT

Independent Consultant

Metuchen, NJ

Gensheng Wang, Ph.D., DABT

Lovelace Respiratory Research Institute

Albuquerque, NM

 

1 The Office of Water peer reviewed the assessment for strontium for the chapters on pharmacokinetics, hazard 

identification, and dose response in 2011. 
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TABLE OF CONTENTS

FOREWORD................................................................................................................................ III

ACKNOWLEDGMENT............................................................................................................... VI

AUTHORS AND CONTRIBUTORS .........................................................................................VII

ABBREVIATIONS AND ACRONYMS.................................................................................. XIV

1.0 EXECUTIVE SUMMARY ............................................................................................. 1-1

2.0 IDENTITY: CHEMICAL AND PHYSICAL PROPERTIES ......................................... 2-1

3.0 USES AND ENVIRONMENTAL FATE ....................................................................... 3-1

3.1 Production and Use ...................................................................................................... 3-1

3.2 Environmental Release ................................................................................................ 3-4

3.3 Environmental Fate...................................................................................................... 3-5

3.4 Summary...................................................................................................................... 3-5

4.0 EXPOSURE FROM DRINKING WATER..................................................................... 4-1

4.1 Introduction.................................................................................................................. 4-1

4.2 Ambient Occurrence .................................................................................................... 4-1

4.2.1 Data Sources and Methods....................................................................................... 4-1

4.2.2 Results...................................................................................................................... 4-2

4.3 Drinking Water Occurrences ....................................................................................... 4-3

4.3.1 Data Sources and Methods....................................................................................... 4-4

4.3.2 Derivation of the Health Reference Value............................................................... 4-7

4.3.3 Results...................................................................................................................... 4-8

4.4 Summary.................................................................................................................... 4-17

5.0 EXPOSURE FROM MEDIA OTHER THAN WATER................................................. 5-1

5.1 Exposure from Food .................................................................................................... 5-1

5.1.1 Concentration in Non-Fish Food Items.................................................................... 5-1

5.1.2 Concentrations in Fish and Shellfish ....................................................................... 5-4

5.1.3 Intake of Strontium from Food ................................................................................ 5-4

5.2 Exposure from Air ....................................................................................................... 5-5

5.2.1 Concentration of Strontium in Air........................................................................... 5-5

5.2.2 Intake of Strontium from Air................................................................................... 5-6

5.3 Exposure from Soil ...................................................................................................... 5-6

5.3.1 Concentration of Strontium Soil.............................................................................. 5-7

5.3.2 Intake of Strontium from Soil.................................................................................. 5-7

5.4 Other Residential Exposures........................................................................................ 5-8

5.5 Summary...................................................................................................................... 5-8

6.0 TOXICOKINETICS ........................................................................................................ 6-1

6.1 Absorption.................................................................................................................... 6-1

6.2 Distribution .................................................................................................................. 6-7

6.3 Metabolism ................................................................................................................ 6-11
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6.3.1 Metabolic Rate Constants...................................................................................... 6-11

6.4 Excretion.................................................................................................................... 6-11

6.5 Pharmacokinetic Considerations................................................................................ 6-14

6.6 Summary.................................................................................................................... 6-14

7.0 HAZARD IDENTIFICATION........................................................................................ 7-1

7.1 Overview of Bone Physiology and Development........................................................ 7-1

7.2 Human Effects ............................................................................................................. 7-4

7.2.1 Short-Term Studies and Case Reports..................................................................... 7-5

7.2.2 Long-Term and Epidemiological Studies................................................................ 7-6

7.3 Animal Studies............................................................................................................. 7-8

7.3.1 Acute Toxicity ......................................................................................................... 7-9

7.3.2 Short-Term Studies.................................................................................................. 7-9

7.3.3 Subchronic Studies................................................................................................. 7-14

7.3.4 Neurotoxicity ......................................................................................................... 7-17

7.3.5 Developmental/Reproductive Toxicity.................................................................. 7-18

7.3.6 Chronic Toxicity.................................................................................................... 7-19

7.3.7 Carcinogenicity...................................................................................................... 7-20

7.4 Other Key Data .......................................................................................................... 7-20

7.4.1 Mutagenicity and Genotoxicity.............................................................................. 7-20

7.4.2 Immunotoxicity...................................................................................................... 7-21

7.4.3 Physiological or Mechanistic Studies.................................................................... 7-21

7.4.3.1 Noncancer Effects.......................................................................................... 7-21

7.4.3.2 Cancer Effects................................................................................................ 7-23

7.4.3.3 Interactions with Other Chemicals................................................................. 7-23

7.4.4 Structure-Activity Relationship ............................................................................. 7-24

7.5 Hazard Characterization............................................................................................. 7-24

7.5.1 Synthesis and Evaluation of Major Noncancer Effects ......................................... 7-24

7.5.2 Synthesis and Evaluation of Carcinogenic Effects................................................ 7-26

7.5.3 Mode of Action and Implications in Cancer Assessment...................................... 7-26

7.5.4 Weight of Evidence Evaluation for Carcinogenicity............................................. 7-26

7.5.5 Potentially Sensitive Populations........................................................................... 7-26

8.0 DOSE-RESPONSE ASSESSMENT ............................................................................... 8-1

8.1 Dose-Response for Noncancer Effects ........................................................................ 8-1

8.1.1 RfD Determination................................................................................................... 8-2

8.1.1.1 Benchmark Dose Approach ............................................................................. 8-5

8.1.1.2 NOAEL/LOAEL Approach........................................................................... 8-10

8.1.1.3 Comparison with Current IRIS Assessment .................................................. 8-10

8.1.2 RfC Determination................................................................................................. 8-11

8.2 Dose-Response for Cancer Effects ............................................................................ 8-11

9.0 PRELIMINARY REGULATORY DETERMINATION AND CHARACTERIZATION 

OF RISK FROM DRINKING WATER...................................................................................... 9-1

9.1 Preliminary Regulatory Determination for Chemicals on the CCL............................. 9-1

9.1.1 Criteria for Regulatory Determination..................................................................... 9-1
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9.1.2 National Drinking Water Advisory Council Recommendations............................. 9-2

9.2 Health Effects (Criterion #1) ....................................................................................... 9-2

9.2.1 Hazard Characterization and Mode of Action Implications.................................... 9-2

9.2.2 Dose-Response Characterization ............................................................................. 9-4

9.2.3 Health Criterion Conclusion .................................................................................... 9-4

9.3 Occurrence in Public Water Systems (Criterion #2).................................................... 9-5

9.3.1 Monitoring Data....................................................................................................... 9-5

9.3.2 Occurrence Criterion Conclusion ............................................................................ 9-6

9.4 Risk Reduction (Criterion #3)...................................................................................... 9-6

9.4.1 Exposed Population Estimates................................................................................. 9-7

9.4.2 Relative Sources of Exposure .................................................................................. 9-7

9.4.3 Sensitive Populations............................................................................................... 9-8

9.4.4 Risk Criterion Conclusion........................................................................................ 9-9

9.5 Regulatory Determination Decision ............................................................................ 9-9

10.0 REFERENCES .............................................................................................................. 10-1

APPENDIX A. SUMMARY OF DATA FROM KEY ANIMAL STUDIES............................ A-1

APPENDIX B. HRL DERIVATION WITH AGE-RELATED EXPOSURE FACTORS ........ B-1

APPENDIX C. BENCHMARK DOSE MODELING RESULTS FOR NON-CANCER 

ENDPOINTS .............................................................................................................................. C-1
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LIST OF TABLES

Table 2-1 Chemical and Physical Properties of Strontium......................................................... 2-1

Table 3-1 Strontium Compounds Production in the United States (pounds).............................. 3-2

Table 4-1 STORET Data for Strontium – Summary of Detected Concentrations ..................... 4-2

Table 4-2 STORET Data for Strontium – Summary of Samples, Sites, and States................... 4-3

Table 4-3 Strontium Occurrence Data from the NIRS Database – Summary of Detected 

Concentrations ............................................................................................................................. 4-9

Table 4-4 Strontium Occurrence Data from the NIRS Database – Summary of Ground Water 

System and Population Served Data ............................................................................................ 4-9

Table 4-5 Strontium State Drinking Water Occurrence Data – Summary of Systems............. 4-10

Table 4-6 Strontium State Drinking Water Occurrence Data – Summary of Detected 

Concentrations ........................................................................................................................... 4-11

Table 4-7 Strontium State Drinking Water Occurrence Data – Summary of Samples ............ 4-12

Table 4-8 Strontium STORET Data – PWS Indiana and Ohio Summary of Detected 

Concentrations ........................................................................................................................... 4-12

Table 4-9 Strontium STORET Data – PWS Indiana and Ohio Summary of Samples and Sites . 4-

13

Table 4-10 Summary of EWG Strontium Data, 2004-2009 ..................................................... 4-14

Table 4-11 Strontium Data from Public-Supply Wells – Summary of Detected Concentrations 4-

15

Table 4-12 Strontium Data from Public-Supply Wells – Summary of Samples...................... 4-15

Table 4-13 Strontium Data from Northern United States Glacial Aquifer System – Summary of 

Concentrations ........................................................................................................................... 4-16

Table 5-1 Strontium Levels in Fruits and Vegetables ................................................................ 5-1

Table 5-2 Strontium Levels Measured in Various Foods........................................................... 5-2

Table 5-3 Strontium Levels in Juices.......................................................................................... 5-3

Table 5-4 Dietary Strontium Intakes for Population Subgroups from the 2006 United Kingdom 

Total Diet Study........................................................................................................................... 5-5

Table 5-5 Levels of Strontium in Soils and Other Geologic Materials (ppm)............................ 5-7

Table 6-1 Summary of Estimates of Absorption of Ingested Strontium in Humans.................. 6-2

Table 6-2 Summary of uptake and turnover of 90Sr in bones of children and adolescents......... 6-9

Table 7-1 Genotoxicity of Strontium In Vitro .......................................................................... 7-20

Table 7-2 Genotoxicity of Strontium In Vivo ........................................................................... 7-21

Table 8-1 NOAEL/LOAEL Data for Oral Subchronic and Chronic Studies of Strontium........ 8-1

Table 8-2 Output of Benchmark Dose (BMD) Models using BMR of 1 Standard Deviation ... 8-6
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LIST OF FIGURES

Figure 7-1 Bone anatomy and growth ........................................................................................ 7-3

Figure 8-1 Restricted Polynomial model, BMR = 1 SD............................................................. 8-7
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ABBREVIATIONS AND ACRONYMS

ANL Argonne National Laboratory

atm atmosphere

ATSDR Agency of Toxic Substances and Disease Registry

AUC∞ area under the plasma-concentration time curve at the first intestinal absorption 

loci

AUC2∞ area under the plasma-concentration time curve at the second intestinal absorption 

loci

AUCiv area under the plasma-concentration time curve following intravenous 

administration

AUCoral area under the plasma-concentration time curve following oral administration

AWWA American Water Works Association 

BMD benchmark dose

BMDL benchmark dose – Lower 95th percentile confidence bound 

BMR benchmark response

bw body weight 

C Celsius

Ca Calcium

CAS Chemical Abstracts Service 

CaSR calcium sensing receptor

CCL Contaminant Candidate List 

CCL 2 Contaminant Candidate List 2

CCL 3 Contaminant Candidate List 3

Cmax peak plasma concentration at the first intestinal absorption loci

Cmax2 peak plasma concentration at the second intestinal absorption loci

CSF Cancer Slope Factor

CUS Chemical Update System

CW concentration in water

CWS community water system 

d day

deg degree

DW/kg bw drinking water intake expressed as liters per kg bodyweight

DWI drinking water intake

ERK1/2 extracellular-signal-regulated-kinase 1/2

F The fraction of a 70 year lifetime applicable to the age period

FDA Food and Drug Administration

g gram 

HRL health reference level 

HSDB Hazardous Substances Data Bank

ICRP International Commission on Radiological Protection

IOM Institute of Medicine

IRIS Integrated Risk Information System 

IU international unit

IUR Inventory Update Reporting
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i.v. intravenous

kg kilogram 

Koc organic carbon water partitioning coefficient 

Kow octanol water partitioning coefficient

L liter 

LD50 Lethal dose for 50% (statistical median) of animals

LOAEL lowest observed adverse effect level 

m meter 

MAPK Mitogen-activated protein kinase

Ci microcurie

MCLG Maximum Contaminant Level Goal 

g microgram

mg milligram

min minute

mL milliliter

m micrometer

mmol millimole

mol mole

NAWQA National Water Quality Assessment 

NDWAC National Drinking Water Advisory Council

ng nanogram

NIER National Institute of Environmental Research

NIRS National Inorganics and Radionuclides Survey

NOAEL no observed adverse effect level 

NPDWR National Primary Drinking Water Regulation 

NRC National Research Council

NTNCWS Non-Transient Non-Community Water System

OGWDW Office of Ground Water and Drinking Water

OR observed ratio

OW Office of Water

p38 a class of mitogen-activated protein kinases responsive to stress stimuli

PBPK pharmacologically based pharmacokinetic

PI3K Phosphoinositide 3-kinase

ppm parts per million 

PWS public water system 

Reg Det 2 Regulatory Determinations on the Second CCL

RfC reference concentration 

RfD reference dose 

Riv whole body retention following intravenous administration

Roral whole body retention following oral administration

RSC relative source contribution

SD standard deviation

SDWA Safe Drinking Water Act

Sr Strontium

Sr(C18H36O2)2 Strontium Stearate
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SrCl2 Strontium Chloride

SrCO3 Strontium Carbonate

SrCrO4 Strontium Chromate

Sr(NO3)2 Strontium Nitrate

SrO Strontium Oxide

Sr(OH)2 Strontium Hydroxide

SrSO4 Strontium Sulfate

TDS Total Diet Studies

TNCWS Transient Non-Community Water System

TRI Toxic Release Inventory

TSCA Toxic Substances Control Act

UCMR Unregulated Contaminant Monitoring Rule

UCMR 1 Unregulated Contaminant Monitoring Rule 1

UCMR 2 Unregulated Contaminant Monitoring Rule 2

U.S. EPA U.S. Environmental Protection Agency

USGS U.S. Geological Service 

VOC volatile organic compound 

WHO World Health Organization

WRF Water Research Foundation
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1.0 EXECUTIVE SUMMARY 

Strontium (Sr) is a naturally-occurring element (atomic number 38) and a member of the 

alkaline earth metals. There are several radioactive strontium isotopes formed by nuclear fission 

of uranium or plutonium. The best known is 90Sr, a legacy from above ground testing of the 

atomic bomb (half-life 29 years). Since drinking water contamination by radioactive isotopes, 

including beta particle emitters, is covered under the existing radionuclides rule, this health 

effects source document deals primarily with nonradioactive properties and the occurrence of 

“total” strontium in the environment. The bulk of environmental strontium (83%) is the stable 

88Sr isotope.

Strontium occurs naturally in rocks, soils, and sea water. Strontium was mined in the 

United States until 1959. Historically, the most important commercial use of strontium has been 

in the faceplate glass of cathode-ray tube televisions. As flat panel technology has become 

widespread in the United States, demand for strontium for this application has fallen. Strontium 

compounds are still used for applications such as pyrotechnics, magnets, and pigments. 

Extrapolation from the National Inorganics and Radionuclides Survey (NIRS), conducted 

from 1984 to 1986, indicate that an estimated national population of 10.5 million people served 

by ground water systems was exposed to strontium in drinking water above the health reference 

level (HRL) of 1500 μg/L during the survey period. The mean concentration for the samples 

with detections was 603 mg/L and the median reported level was 178 μg/L. The maximum 

reported level was 43,500 μg/L (a value approximately 30 times the HRL). Approximately 7% 

percent (69 of 989) of the NIRS public water systems (PWSs) detected strontium at a level 

greater than the HRL of 1500 μg/L. Limited data from USGS suggest that sandstone aquifers

may have higher levels of strontium than other types.

 

Although strontium is known to occur in food, air, and soil, data on levels in those media 

are limited, as are estimates of intake from those sources. Estimated strontium intake from air 

and soil is very low compared with that from food and drinking water. The estimated exposure 

for children from air is 0.1 μg Sr/day and the estimated exposure from soil is 24 μg Sr/day. The 

dietary intakes based on an FDA Total Diet Study range from 493 to 685 μg/day for ages 6 

months to 2 years and 928 to 1,388 μg Sr/day for 14 to 16 year old adolescents. 

There are several studies that evaluated the relationship between strontium exposure in 

the environment or the body burden of strontium (as a measure of internal dose) and 

development of disease following either occupational or environmental exposures. These studies 

are of limited utility for characterizing hazard and assessing dose response due to inadequate 

control for other factors potentially contributing to the endpoint being evaluated.

Strontium has low acute toxicity to rodents via the oral and dermal routes; the low 

volatility of strontium compounds makes inhalation exposure unlikely. The chemical similarity

of strontium to calcium allows it to exchange imperfectly for calcium in a variety of biological 

processes; the most important of these is the substitution of calcium in bone, affecting skeletal 

development. Subchronic and chronic studies in rats show that strontium can decrease the 
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calcification of the cartilaginous portion of bone in the young, and at therapeutic doses can 

increase bone formation relative to degradation in the elderly. Due to the mode of action for 

strontium toxicity, strontium uptake into bone and the resulting toxicity is affected by the stage 

of bone development and intake of nutrients related to bone formation, such as calcium, 

magphosphorous and vitamin D. The results of clinical studies in people administered strontium 

ranelate [Sr2(C12H6N2O8)] to treat osteoporosis support the conclusion from animal studies 

that strontium influences bone composition and metabolic processes in ways that can be 

beneficial as well adverse, varying with life-stage and level of exposure. 

There are no standard one- or two-generation reproductive toxicity studies for any

strontium compound, but the available data indicate that strontium does not cause structural or 

functional effects at doses well above those causing bone effects. In a screening test for 

reproductive and developmental toxicity, no effects were observed on mating behavior, fertility, 

gestation period or the histopathology of the reproductive tissues and organs, and no 

developmental or teratogenic effects were observed.

The data relevant to strontium carcinogenicity are very limited. No increase in tumors 

was seen in the single available chronic oral study, but this study used a small sample size and 

was inadequate for evaluation of carcinogenic potential. The weight of evidence from the 

genotoxicity data is that strontium compounds are negative for gene mutation, chromosome 

aberrations and DNA damage. Based on these data, there is inadequate information to assess the 

carcinogenic potential of strontium, due to the lack of adequate chronic duration studies.

The RfD of 0.3 mg Sr/kg-day is based on the critical effect of decreased bone 

calcification during growth and development. In the principal study, male weanling rats 

(8/group) were administered strontium in drinking water for 9 weeks at concentrations of 0, 0.19, 

0.27, 0.34, or 0.40% strontium chloride (estimated by the authors to be equivalent to 0, 316, 425, 

525, and 633 mg Sr/kg-day, respectively). The RfD was calculated using the benchmark dose 

(BMD) method, and based on the lower 95% confidence limit on the benchmark dose (defined as 

a one control standard deviation change in the mean), a BMDL (1 SD) of 328 mg Sr/kg-day was 

derived. This value was divided by an uncertainty factor of 1000, with a factor of 10 each used 

to account for human variability, extrapolation from rats, and database uncertainties. 

The U.S. EPA also evaluated whether health information is available regarding potential 

effects on children and/or other sensitive populations. Because strontium can substitute for 

calcium in growing bone, children and teenagers are expected to be a sensitive population, since 

they are actively growing. Strontium exposure in children and teenagers may result in effects on 

bone structure (poor calcification) with a more severe and/or a long-term impact than similar 

exposures in adults. The RfD was based on changes in bone growth in weanling rats (i.e., the 

sensitive population). Accordingly, strontium at concentrations above the HRL would be 

expected to have the greatest impact during periods of rapid growth in the developing fetus, 

during childhood and adolescence, particularly if calcium intake is insufficient, but exposure at 

the HRL is expected to be protective of the sensitive populations. People with severely impaired 

kidney function or disorders affecting the normal equilibrium between the breakdown of old 

bone and the formation of new bone (such as Paget’s disease) might also be sensitive to 
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strontium exposure.

In summary, strontium has the potential to cause adverse bone effects, based on 

toxicological data from animal studies, and supported by limited human data and an 

understanding of its mode of action. Strontium is known to occur in public water systems with a 

frequency and at levels of public health concern. Due to the large number of people exposed to 

strontium through drinking water and the potentially high concentration of strontium measured in 

some PWSs, regulation of strontium presents a meaningful opportunity for health risk reduction 

especially for those with developing bones (such as infants, children and adolescents), 

individuals deficient in calcium, and persons with kidney conditions.
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2.0 IDENTITY: CHEMICAL AND PHYSICAL PROPERTIES

Strontium is a naturally-occurring element (atomic number 38) and a member of the 

alkaline earth metals (Group 2 of the periodic table), which also include beryllium, magnesium, 

calcium, barium, and radium. Of the many known isotopes of strontium, four are stable and 

found in nature: 84Sr (~0.5%), 86Sr (~9.9%), 87Sr (~7.0%), and 88Sr (~82.6%) (ANL, 2007). 

There are also several radioactive isotopes formed by nuclear fission of uranium or 

plutonium (ATSDR, 2004). Notable among these is 90Sr, a beta particle emitter with a half-life 

of 29 years that was released into the atmosphere from above-ground testing of nuclear weapons 

in the period 1945-1980. Since drinking water contamination by radioactive isotopes, including 

beta particle emitters, is covered under the existing radionuclides rule, this document deals 

primarily with nonradioactive properties and the occurrence of “total” strontium in the 

environment.

Strontium constitutes approximately 0.02-0.03% of the earth’s crust, and is the fifth most 

abundant metallic ion in seawater (Hibbins, 1997). In the earth’s crust strontium occurs 

principally as strontium sulfate (SrSO4) in the mineral celestite (USGS, 2009a). The elemental 

form does not exist in nature (ATSDR, 2004). Two common refining methods for celestite are 

the black ash method (calcining) and the soda method. Both produce strontium carbonate 

(SrCO3) (ATSDR, 2004). Strontium may be present as an impurity in coal, and may be released 

to air as strontium oxide from coal-burning (ATSDR, 2004).

Physical and chemical properties and other reference information for select strontium 

compounds are listed in Table 2-1 below. Table 3-1 in Section 3.1 identifies some additional 

strontium-containing compounds that are produced industrially.

Table 2-1 Chemical and Physical Properties of Strontium

Property

Information

Elemental 

Strontium

Strontium 

Carbonate

Strontium 

Chromate

Strontium 

Nitrate

Strontium 

Hydroxide

Strontium 

Chloride

Chemical 

Abstracts 

Service 

(CAS) 

Registry

No.

7440-24-6 1633-05-2 7789-06-2 10042-76-9 18480-07-4 10476-85-4

Chemical 

Formula Sr SrCO3 SrCrO4 Sr(NO3)2 Sr(OH)2 SrCl2

Molecular 

Weight

87.6 

g/mol

147.63 

g/mol

203.61 

g/mol

211.63 

g/mol

121.64 

g/mol

158.53 

g/mol

Color/ 

Physical 

State

Pale 

yellow 

solid

White solid Yellow 

solid

Colorless 

solid

Colorless 

solid White solid
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Property

Information

Elemental 

Strontium

Strontium 

Carbonate

Strontium 

Chromate

Strontium 

Nitrate

Strontium 

Hydroxide

Strontium 

Chloride

Boiling 

Point

1,390 deg 

C

1,100 deg C, 

decomposes -- 645 deg C -H20, 710 deg C 1,250 deg C

Melting 

Point 777 deg C

1,497 degC 

at 69 atm. 

pressure

-- 570 deg C 375 deg C 875 deg C

Density 2.6 g/cm3

at 4 deg C

3.70 g/cm3

at 4 deg C

3.895 

g/cm3 at 15 

deg C

2.986 g/cm3

at 4 deg C

3.625 g/cm3

at 4 deg C

3.052 g/cm3

at 4 deg C

Kow -- -- -- -- -- --

Koc -- -- -- -- -- --

Solubility

in Water Reactive 11 mg/L at 

18 deg C

1,200 mg/L 

at 15 deg C

709,000 

mg/L at 18 

deg C

4100 mg/L 

at 0 deg C

538,000 

mg/L at 20 

deg C

Solubility

in Other 

Solvents

Alcohol

Acid, 

ammonium 

salts

Acetic acid

Slightly in 

alcohol and 

acetone

Alcohol Alcohol, 

acetone

Conversion 

Factors

(at 25 deg 

C, 1 atm)

NA NA NA NA NA NA

Sources: HSDB (2006b); RAIS (2009); Weast and Astle (1981); ChemIDplus (2011); ATSDR (2004)

Note: “--” indicates that no information was found; “NA” indicates that the property is not applicable to the 

compound.
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3.0 USES AND ENVIRONMENTAL FATE 

This section summarizes information pertaining to the uses, manufacture, and 

environmental fate of strontium and select strontium compounds.

3.1 Production and Use

Strontium mineral mining in the United States ceased in 1959. Imports of strontium 

minerals and compounds stood at approximately 31,000-38,500 metric tons from 1994 to 2001 

(ATSDR, 2004). Since then imports have declined. Total U.S. consumption of strontium 

minerals and compounds was 16,700 metric tons of strontium content in 2004 and approximately

7,750 metric tons in 2008 (USGS, 2009a). 

Historically, the most important commercial use of strontium has been in the faceplate 

glass of cathode-ray tube televisions, to block x-ray emissions. During manufacturing strontium 

carbonate is added to liquid glass and converts to strontium oxide (SrO). Strontium oxide 

constitutes approximately 8% (by weight) of the picture tube glass (ATSDR, 2004). As flat 

panel technology has become widespread in the United States in the last decade, demand for 

strontium for this application has fallen (USGS, 2009a). In 2008, approximately 30% of 

commercial strontium consumption was in pyrotechnics and signals (as strontium nitrate and 

other compounds). Strontium produces a characteristic crimson red flame during combustion 

(Weast and Astle, 1981). Other uses include 30% in ferrite ceramic magnets (as strontium 

ferrite), 10% in master alloys (as strontium metal), 10% in pigments and fillers (as strontium 

chromate), 10% in electrolytic production of zinc (as strontium carbonate), and 10% in other 

applications such as fluorescent lights (strontium phosphate), toothpaste (strontium chloride), 

and medicines (strontium chloride and strontium peroxide). The feed material for most 

applications is strontium carbonate (Hibbins, 1997; USGS, 1999; USGS, 2002; USGS, 2009a). 

Production data from the U.S. EPA Inventory Update Reporting (IUR) program are 

available for several strontium-containing compounds. U.S. EPA collects information on 

chemicals manufactured in or imported into the United States in the Toxic Substances Control 

Act (TSCA) Chemical Substance Inventory. The U.S. EPA IUR regulation of 1986 required 

chemical manufacturers and importers to report to U.S. EPA every four years the identity of, and 

basic manufacturing information for organic chemical substances manufactured and imported 

annually at individual sites in quantities of 10,000 pounds or more (U.S. EPA, 2010a). 

Modifications of the IUR rule in 2003 and 2005 expanded the range of chemicals and plant sites 

reporting, expanded the type of data reported, raised the production volume threshold that 

triggers reporting from 10,000 pounds to 25,000 pounds, and made other adjustments. Because 

of changes in minimum thresholds and other program modifications, the results from 2006 might 

not be directly comparable to results from earlier years. IUR data are stored in the Chemical 

Update System (CUS).

The CUS-IUR assigns one of eight production and importation volume ranges for each 

chemical included in the inventory. Table 3-1 presents the reported production of 17 strontium 

compounds in the United States every four years from 1986 to 2006. Not every compound had 
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data reported in every cycle. Annual production of strontium carbonate varied considerably over 

the periods for which data were reported, reaching into the tens of millions of pounds. There 

was an apparent increase in the production of strontium nitrate between 2002 and 2006. The 

production of seven other strontium compounds with pre-2006 data remained relatively constant 

in years when data were reported, and eight compounds had no data reported until 2006. Three 

compounds, strontium carbonate, strontium chromate, and strontium nitrate, were produced or 

imported in quantities greater than one million pounds in at least one cycle (U.S. EPA, 2010a).

When considering the strontium contribution from complex compounds, such as many of 

those included in Table 3-1, it is important to remember that strontium itself is only a fraction of 

the total poundage reported. For example, strontium distearate is only 13% strontium by weight 

(88 out of 656 g/mol). Dissociation of strontium and various strontium species from degradation 

of the compounds listed in the table may pose health risks, and some of the compounds 

themselves may be of health concern.

Table 3-1 Strontium Compounds Production in the United States (pounds)

Chemical Name and 

CASRN in CUS 

Database

Chemical Inventory Update Reporting Cycle

1986 1990 1994 1998 2002 2006

Strontium carbonate

(SrCO3)

1633-05-2

> 1 

million -

10 

million

No 

reports No reports

> 10 

million -

50 million

10000 -

500000

10 million 

–

< 50 

million

Strontium chromate

(SrCrO4)

7789-06-2

> 1 

million -

10 

million

> 1 

million -

10 

million

No 

Reports

No 

Reports

No 

Reports < 500000

Strontium stearate

(Sr(C18H36O2)2)

10196-69-7

10000 -

500000

10000 -

500000

No 

Reports

No 

Reports

No 

Reports

No 

Reports

Strontium nitrate

(Sr(NO3)2)

10042-76-9

No 

Reports

No 

Reports

No 

Reports

No 

Reports

10000 -

500000

1 million 

–

< 10 

million

2-

Naphthalenecarboxylic 

acid, 3-hydroxy-4-[(4-

methylsulfophenyl)azo]-, 

strontium salt (1:1)

73612-29-0

10000 -

500000

10000 -

500000

10000 -

500000

10000 -

500000

10000 -

500000

No 

Reports

1-Naphthalenesulfonic 

acid, 2-[(2-hydroxy-1-

1-napthaleneyl)azo]-

strontium salt (2:1)

No 

Reports

No 

Reports

No 

Reports

No 

Reports

10000 -

500000

No 

Reports
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Chemical Name and 

CASRN in CUS 

Database

Chemical Inventory Update Reporting Cycle

1986 1990 1994 1998 2002 2006

6371-67-1

2-

Napthalenecarboxylic 

acid, 3-hydroxy-4-[(4-

methyl-2-

sulfophenyl)azo]-, 

calcium strontium salt

(2:1:1)

55491-44-6

No 

Reports

No 

Reports

No 

Reports

No 

Reports

10000 -

500000

No 

Reports

2-

Napthalenecarboxylic 

acid, 4-[(5-chloro-4-

methyl-2-

sulfophenyl)azo]-3-

hydroxy-, strontium 

salt (1:1)

15782-05-5

10000 -

500000

10000 -

500000

10000 -

500000

10000 -

500000

10000 -

500000

No 

Reports

2-

Naphthalenecarboxylic 

acid, 4-[(4-chloro-5-

methyl-2-

sulfophenyl)azo]-3-

hydroxy-, strontium 

salt (1:1)

67828-72-2

10000 -

500000

10000 -

500000

No 

Reports

No 

Reports

No 

Reports

No 

Reports

Strontium oxide (SrO)

1314-11-0

No 

Reports

No 

Reports

No 

Reports

No 

Reports

No 

Reports < 500000

Strontium titanium 

oxide (SrTiO3)

12060-59-2

No 

Reports

No 

Reports

No 

Reports

No 

Reports

No 

Reports

500000 to 

- 1 million

Phosphoric acid, 

strontium salt (1:1)

13450-99-2

No 

Reports

No 

Reports

No 

Reports

No 

Reports

No 

Reports < 500000

Phenol, nonyl-, 

strontium salt (2:1)

31291-42-6

No 

Reports

No 

Reports

No 

Reports

No 

Reports

No 

Reports < 500000

Phosphoric acid, 

magnesium strontium 

salt, tin-doped

68784-28-1

No 

Reports

No 

Reports

No 

Reports

No 

Reports

No 

Reports < 500000

Strontium fluoride No No No No No < 500000
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Chemical Name and 

CASRN in CUS 

Database

Chemical Inventory Update Reporting Cycle

1986 1990 1994 1998 2002 2006

phosphate 

(Sr5F(PO4)3), 

antimony and 

manganese-doped

68784-78-1

Reports Reports Reports Reports Reports

Barium calcium 

strontium chloride 

phosphate, europiumdoped

109037-74-3

No 

Reports

No 

Reports

No 

Reports

No 

Reports

No 

Reports < 500000

Silicon sodium 

strontium titanium 

hydroxide oxide

326855-77-0

No 

Reports

No 

Reports

No 

Reports

No 

Reports

No 

Reports < 500000

Source: U.S. EPA (2010a)

3.2 Environmental Release

Naturally occurring strontium in rocks, soils, and sea water can be mobilized by natural 

weathering, wind, and sea spray. Higher concentrations of atmospheric strontium in coastal 

areas relative to inland areas have been attributed to sea spray (Capo et al., 1998). 

Human activities that contribute strontium to environmental media include milling, 

refining, and other industrial activities, plus coal burning and use of phosphate fertilizers and 

pyrotechnic devices (Lee and von Lehmden, 1973; Que Hee et al., 1982; Ondov et al., 1989; 

Raven and Loeppert, 1997; Perry, 1999). 

There are no data on industrial releases of strontium compounds in U.S. EPA’s Toxics 

Release Inventory (TRI). (More precisely: the list of compounds for which TRI reporting is 

required has never included a compound with “strontium” in its name (U.S. EPA, 2010b)).

Strontium concentrations of up to 2718 g/m3have been measured in atmospheric 

emissions from coal-fired power plants in the western United States, and concentrations of 

approximately 9800 g/m

3

have been measured in the eastern U.S (Que Hee et al., 1982; Ondov 

et al., 1989). In phosphate fertilizers, strontium concentrations are reported to range between 20 

g/g and 4000 g/g (Lee and von Lehmden, 1973; Raven and Loeppert, 1997). Local 

atmospheric concentrations of strontium in the range of 0.009 g/m3have been observed 

following pyrotechnic displays (Perry, 1999).
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3.3 Environmental Fate

Strontium can exist in oxidation states 0 and +2; under normal environmental conditions 

it is found primarily in the +2 oxidation state (ATSDR, 2004). 

Strontium enters the atmosphere via natural weathering and sea spray (Capo et al., 1998), 

and as a result of industrial activity, the application of phosphate fertilizers, and the use of 

pyrotechnics (Lee and von Lehmden, 1973; Ondov et al., 1989; Perry, 1999; Que Hee et al., 

1982; Raven and Loeppert, 1997). If strontium is released to air as strontium oxide (e.g., from 

coal-burning), it will react with moisture to form strontium hydroxide (Sr(OH)2) or with carbon 

dioxide to form strontium carbonate. Strontium hydroxide will further interact with moisture to 

release Sr2+ and SrOH+ions. Strontium ions and compounds in the atmosphere are subject to 

wet and dry deposition (ATSDR, 2004).

Strontium is naturally present in most soils, and additional strontium may be added by 

atmospheric deposition and by direct human activity such as application of phosphate fertilizers 

(ATSDR, 2004). Strontium is considered to have moderate or moderate-to-low mobility in soils 

(Hayes and Traina, 1998). Mobility is affected by the type of soil and by the salinity of the soil 

water (ATSDR, 2004). Though strontium is not an essential nutrient for most plants, uptake 

does occur. Strontium uptake decreases as the concentration of calcium in soils increases 

(ATSDR, 2004). 

Strontium enters freshwater resources (surface and ground water) from the natural 

weathering of rocks and soils, from atmospheric deposition, from the leaching of strontium 

compounds from soils, and from direct discharge of contaminated waste water (ATSDR, 2004). 

Strontium may be present in water in an ionic form such as Sr2+ or SrOH+, or in the form of 

compounds such as strontium carbonate and strontium sulfate, both of which are insoluble at 

neutral pH (Cotton and Wilkenson, 1980). The mobility of strontium can increase in water 

bodies with high salt concentrations on account of decreased sorption to sediments (Bunde et al., 

1997, 1998). Source waters that contain elevated levels of strontium can also contain calcium

and other bone forming minerals according to data from the National Inorganic and Radionuclide 

Study (Donohue et al., 2005).

3.4 Summary

Strontium was mined in the United States until 1959. Imports of strontium minerals and 

compounds stood at approximately 31,000-38,500 metric tons from 1994 to 2001 and have since 

declined. Historically, the most important commercial use of strontium has been in the faceplate 

glass of cathode-ray tube televisions. As flat panel technology has become widespread in the 

United States, demand for strontium for this application has fallen. Strontium compounds are 

still used for applications such as pyrotechnics, magnets, and pigments. The feed material for 

most applications is strontium carbonate.

U.S. EPA’s CUS database records production information for 17 industrial compounds 

that contain strontium. No TRI data are available on industrial releases of strontium compounds.
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Strontium compounds in the atmosphere may be subject to wet and dry deposition. 

Strontium is naturally present in most soils, and additional strontium may be added by 

atmospheric deposition and by direct human activity such as application of phosphate fertilizers. 

Strontium has moderate-to-low or moderate mobility in soils and can also be taken up by plants. 

Strontium may be present in water in an ionic form such as Sr2+ or SrOH+, or in the form of 

compounds such as strontium carbonate and strontium sulfate, both of which are insoluble at 

neutral pH. The mobility of strontium can increase in water bodies with high salt concentrations 

on account of decreased sorption to sediments.
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4.0 EXPOSURE FROM DRINKING WATER 

4.1 Introduction

This section presents data on the occurrence of strontium in ambient water and drinking 

water in the United States. As described in 4.3.2, a child-specific health reference level (HRL) 

of 1,500 μg/L was derived based on the demonstrated increased risk for bone development 

effects in growing infants, children, and adults. The HRL is a risk derived concentration against 

which to compare the occurrence data from PWSs to determine if a chemical occurs with a 

frequency and at levels of public health concern. Occurrence data from the sources discussed 

below are analyzed with respect to the HRL and 1⁄2 the HRL. When possible, population 

exposures to the contaminant at concentrations above the HRL and 1⁄2 the HRL are estimated and 

presented.

For general background on occurrence sources and how occurrence and exposure data 

were used to inform CCL 3 and RegDet3 decision-making, see Protocol for the Regulatory 

Determinations 3 (U.S. EPA, 2012a) and the introductory chapters of the Regulatory 

Determinations 3 Support Document (U.S. EPA, 2012b).

4.2 Ambient Occurrence

Lakes, rivers, and aquifers are the ambient sources of most drinking water. Contaminant 

occurrence in ambient water provides information on the potential for contaminants to adversely 

affect drinking water supplies that draw raw water from the ambient sources represented. 

4.2.1 Data Sources and Methods

National Water Quality Assessment Data, 1991-2003 

USGS instituted the National Water Quality Assessment (NAWQA) program in 1991 to 

examine ambient water quality status and trends in the United States. NAWQA is designed to 

apply nationally consistent methods to provide a consistent basis for comparisons among study

basins across the country and over time. These occurrence assessments serve to facilitate 

interpretation of natural and anthropogenic factors affecting national water quality. The USGS 

NAWQA program also reported information on both drinking water source wells and monitoring 

wells; these data are included with the drinking water data in Section 4.3. 

Storage and Retrieval (STORET) Data Warehouse, 1967-2011

The U.S. EPA’s STORET Data Warehouse is a collaborative database that has been 

actively populated with water quality data since 1999. It contains raw biological, chemical, and 

physical data on surface and ground water, and ambient and drinking water collected by federal, 

state and local agencies, Indian Tribes, volunteer groups, academics, and others. A wide variety 

of data relating to water quality from all 50 states as well as multiple territories and jurisdictions 

of the United States are represented in this data system. Most data are post-1999, but some 
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earlier sampling is included. STORET includes strontium records from 1967 to 2011. Few 

records are available in earlier years. 

Many (though not all) sample results are accompanied by information on sample location 

(latitude, longitude, state, county, Hydrologic Unit Code and a brief site identification), sample 

date, the medium sampled (e.g., water, sediment, fish tissue), and the name of the organization 

that sponsored the monitoring. In addition, there can be information on why the data were 

gathered; sampling and analytical methods used; the laboratory used to analyze the samples; the 

quality control checks used when sampling, handling the samples, and analyzing the data; and 

the personnel responsible for the data.

STORET data have quality limitations. Since data submission to STORET is voluntary, 

the extent of national coverage and data completeness can differ from parameter to parameter. 

Data maintained in STORET also reflect a wide range of quality since data contributors can 

range from federal agencies to volunteer groups and there are no restrictions on submission of 

data based on analytical methods, quality assurance (QA) requirements, etc. For more general 

STORET data information, please refer to: http://www.epa.gov/storet/index.html.

4.2.2 Results

Storage and Retrieval (STORET) Database, 1967-2011

The results of the STORET analysis by the OGWDW (U.S. EPA, 2012c) are presented in 

Tables 4-1 and 4-2. Note that ground water data in STORET are from wells and surface water 

data are from lakes, rivers/streams, and reservoirs. There were some Public Water System 

(PWS) data from the State of Indiana and the State of Ohio in STORET. A summary of those 

data is included with the State Drinking Water Monitoring Program data in Section 4.3.3. 

Of 12,433 sites where strontium was monitored, 1,541 (12.39%) had concentrations 

greater than 1⁄2 the HRL, and 653 (5.25%) had concentrations in excess of the HRL of 1,500 

μg/L. Minimum detected concentrations are reported in Table 4-1; these minimum values may

be indicative of reporting levels used. (A minimum value of zero, on the other hand, could 

represent a detection that was entered into the database as a non-numerical value (e.g., 

“Present”).)

Table 4-1 STORET Data for Strontium – Summary of Detected Concentrations

Source Water

Type

Concentration Value of Detections (μg/L)

Minimuma,b Median 90th Percentile Maximum

Ground Water 0

a

240 2,528.40 19,000

Surface Water 0

a

270 1,300 19,034,000

Total 0

a

270 1,344.83 19,034,000
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Source Water

Type

Concentration Value of Detections (μg/L)

Minimuma,b Median 90th Percentile Maximum

aA minimum value of zero may represent a detection that was entered into the database as a non-numerical value 

(e.g., “Present”).

bThe minimum detection level may reflect the minimum reporting level.

Table 4-2 STORET Data for Strontium – Summary of Samples, Sites, and States

Source 

Water Type

Total 

Number 

of 

Samples

Samples with 

Detections

Detections > 1⁄2 HRL 

(750 μg/L)

Detections > HRL 

(1,500 μg/L)

Number Percent Number Percent Number Percent

Ground Water

Samples 2,320 2,179 93.92% 555 23.92% 322 13.88%

Sites 890 865 97.19% 208 23.37% 120 13.48%

States a13 13 100% 7 53.85% 7 53.85%

Surface Water

Samples 41,121 39,780 96.74% 8,866 21.56% 3,170 7.71%

Sites 11,543 11,434 99.06% 1,333 11.55% 533 4.62%

States a31 31 100% 19 61.29% 17 54.84%

Total

Samples 43,441 41,959 96.59% 9,421 21.69% 3,492 8.04%

Sites 12,433 12,299 98.92% 1,541 12.39% 653 5.25%

States a33 33 100.00% 21 63.64% 19 57.58%

The STORET data suggest that strontium is found in both surface water and ground water 

and is widely distributed across the United States. Median concentrations of strontium are low; 

only about 8% of samples exceeded the HRL. Among the STORET samples, the highest 

concentration (19,034,000 μg/L) was found in a surface water sample. The 90th percentile values 

and detection rates in surface and ground water indicate that strontium is not merely a ground 

water problem.

4.3 Drinking Water Occurrences

The Agency reviewed a number of data sources for information on contaminant 

occurrence in drinking water. Data and information on strontium were available from the 

following sources: 

 U.S. EPA’s National Inorganics and Radionuclides Survey (NIRS), 1984-1986

 State drinking water monitoring programs, 1998-2005

 U.S. EPA’s Community Water System Survey (CWSS), 2006

 Consumer Confidence Reports (CCRs) from PWSs, 2006-2007

a

Some states provided information on both surface and ground water and others information on groundwater only or 

surface water only.
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 Environmental Working Group (EWG) Drinking Water Database, 1998-2009

 USGS NAWQA – Drinking Water Studies, 1991-2007

Note that there may be some overlap in the data because sources may have reported the 

same underlying data. The NIRS data were the primary data source for the strontium Regulatory

Determination because the study was designed to be nationally representative. It has limitations, 

however, because it covers only ground water sources. The data are expected to reflect the 

geology of the site to a greater extent than anthropogenic contamination.

4.3.1 Data Sources and Methods

U.S. EPA’s National Inorganics and Radionuclides Survey (NIRS), 1984-1986

NIRS was conducted by the U.S. EPA to provide national data on the occurrence of a 

select set of radionuclides and inorganic chemicals (IOCs). It is the primary source of the 

drinking water data for Regulatory Determination for strontium. The data set includes 

occurrence data from 989 community water systems (CWSs) served by ground water sources. 

Each of these randomly selected PWSs was sampled a single time between 1984 and 1986. 

Selection of the PWSs was designed so that the results from these PWSs would be representative 

of national occurrence of contaminants in ground water systems. Further description of the 

NIRS can be found in Longtin (1988) and U.S. EPA (2008b).

NIRS was structured as a stratified, random sampling of the nation’s community ground 

water supplies as they existed in the mid-1980s. A random selection of systems from each of 

several size categories was included, in proportion to the number of PWSs that existed in those 

size categories nationally. The sampling frame used in NIRS was designed to be representative 

of ground water supplies on a national basis, but not necessarily on a state-by-state, regional, or 

other geographic basis. The resulting sample of systems represents approximately 2% of the 

nation’s community ground water supply in each system size category. Since there are many 

more small than large PWSs in the United States, most of the NIRS data are from smaller 

systems. The data are from 49 states (there are no data from Hawaii), plus Puerto Rico. For 

EPA’s detailed analysis of strontium data from NIRS, see the Regulatory Determinations 3 

Support Document (U.S. EPA, 2012b).

State Drinking Water Monitoring Programs, 1998-2005

Because there is no national database that receives and stores all relevant data regarding 

the occurrence of regulated contaminants in public drinking water systems, the U.S. EPA 

conducted a voluntary data call-in from the states, territories, and tribes to obtain regulated 

contaminant occurrence data in support of national occurrence assessments conducted for the 

second Six-Year Review. The U.S. EPA worked with the states and primacy agencies to receive 

the states’ and agencies’ complete records of compliance monitoring data (public drinking water 

system regulated contaminant occurrence data) for 1998 through 2005. 
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Some states submitted monitoring data for unregulated compounds along with their data 

for regulated compounds. EPA supplemented these data by gathering publicly available data on 

unregulated contaminant occurrence from state websites. The result was a collection of 

unregulated contaminant monitoring data from nine states, representing those states with varying 

degrees of completeness. The collection includes drinking water occurrence data for strontium 

from Illinois, Ohio, and Region 9 Tribes.2

In addition, there were some PWS data from Indiana and Ohio in STORET. These PWS 

data from Indiana and Ohio were not included in the totals calculated in the analysis of ambient 

water data from STORET, above. The Indiana and Ohio PWS monitoring data could not be 

subcategorized as relying on ground water or surface water. 

U.S. EPA’s Community Water System Survey (CWSS), 2006

The 2006 CWSS (U.S. EPA, 2009b) gathered data on the financial and operating 

characteristics of a random sample of CWSs nationwide. All systems serving more than 500,000 

people (94 systems in 2006) received the survey, and systems in that size category were asked 

questions about concentrations of unregulated contaminants in their raw and finished water. Of 

the 94 systems asked about unregulated contaminants, 62 percent (58 systems) responded to the 

survey. Not all systems answered every question. U.S. EPA supplemented the data set by

gathering additional information about contaminant occurrence at the 94 systems from publicly

available sources such as the CCR reports discussed below. 

Consumer Confidence Reports (CCRs) from PWSs, 2006-2007

CCRs are annual water quality reports that CWSs are required to provide to their 

customers. These reports summarize information on water sources, detected contaminants, and 

system compliance with U.S. EPA drinking water standards; they may also include general 

educational material. Under the CCR Rule (40 CFR Subpart O), CWSs with 15 or more 

connections or serving at least 25 year-round residents must prepare and distribute a CCR to all 

billing units or service connections every year. Systems serving 100,000 or more residents are 

also required to post their current CCRs on a publicly accessible Internet site. The U.S. EPA 

(2012a) reviewed CCRs published by the 26 systems that serve over one million customers for 

unregulated contaminant occurrence information. Data on strontium were available from CCRs 

prepared by two CWSs in New York: Suffolk County and New York City. Reporting levels 

were not specified in either of the CCRs.

Environmental Working Group (EWG) Drinking Water Database, 1998-2009

In December 2009, EWG released their “National Drinking Water Database,” which 

includes data on occurrence of drinking water contaminants (regulated and unregulated) 

collected between 2004 and 2009 from 45 states and the District of Columbia. The 2009 EWG

 

2 A small amount of strontium data (37 records) were available for download from the State of Wisconsin, but it was 

unclear if some of the data represented “Total strontium” or “Strontium-90” (the radionuclide). Hence, those data 

are not included in this summary.
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database includes results from approximately 48,000 water systems; data were obtained 

primarily from state water offices.

EWG reviewed the data for inconsistencies, potential outliers, and other errors. It also

invited the American Water Works Association (AWWA) and the Association of Metropolitan 

Water Agencies (AMWA) to review the data and/or have their constituents, the PWSs, review 

the data. Some corrections apparently were made since the public release of the data in 

December, 2009. The data were downloaded on January 10, 2010. U.S. EPA’s analysis is based 

solely on the data made publicly available by EWG on its Web site. Reporting levels are not 

specified in EWG’s database.

USGS NAWQA – Drinking Water Studies, 1991-2007

Public Supply Wells. To assess risks posed by contaminants in public-supply wells, 

water samples were collected from source (untreated) ground water from 932 public-supply

wells located in parts of 40 NAWQA Study Units in 41 states (Toccalino et al., 2010). Each well 

was sampled once between 1993 and 2007. About half of the samples were analyzed for 

strontium; reporting levels were not specified in this study.

Private Wells. USGS also conducted an assessment of the quality of water from 

domestic wells across the United States using NAWQA data (DeSimone, 2009). The program 

included the analysis of major ions, trace elements, nutrients, radon, and organic compounds 

(pesticides and volatile organic compounds (VOCs)) at approximately 2100 domestic wells 

(private drinking water wells) across 48 states, covering 30 regional aquifers, between 1991 and 

2004. As was the case for the Public Wells, not all samples were analyzed for strontium. In 

addition, USGS summarized data from wells sampled for NAWQA agricultural land-use 

assessment studies to provide an indication of the potential effects of agricultural land-use 

practices on the ground water in the aquifers studied. 

DeSimone (2009) reported both Method Reporting Levels as well as Long-Term Method 

Detection Levels (LT-MDLs), but did not differentiate between them in the detection summaries. 

DeSimone censored the strontium data at a common reporting level of 10 μg/L. It is not evident 

whether this value represented the Method Reporting Level or the LT-MDL.

Bartholomay et al. (2007) is an additional USGS study of drinking water from private 

wells that was conducted under the USGS NAWQA programs for the Centers for Disease 

Control’s (CDC) National Environmental Public Health Tracking Program. The study covered 

16 states with sample collection from 1991 to 2006. Half of the states were located in the 

Northeastern part of the country; three states covered the west coast. The remaining states were 

Wisconsin, Florida, Missouri, Utah, and New Mexico. 

As part of the NAWQA program, Lindsey et al. (2008) conducted an assessment of the 

water quality in carbonate aquifers, which account for 22% of the groundwater pumped by the 

country’s PWSs. From 1993 to 2005, the study analyzed 1,042 wells and springs across 12 
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aquifer systems and 20 states for major ions, radon, nutrients, pesticides, and volatile organic 

chemicals (VOCs). Reporting levels for strontium were not specified in this study. 

Groschen et al. (2009) used NAWQA data collected between 1991 and 2003 to conduct 

an assessment of the occurrence and distribution of several contaminants in ground water of the 

glacial aquifer system in the Northern United States, which underlies portions of New England, 

the Midwest, the Pacific Northwest, and Alaska. The study analyzed sample data collected from 

1,590 monitoring wells and water supply wells. The reporting level for strontium used in this 

study ranged from 0.08 μg/L to 1.4 μg/L.

4.3.2 Derivation of the Health Reference Value 

To evaluate the systems and populations exposed to strontium in drinking water from 

PWSs, the monitoring data were analyzed against the reporting level and a concentration in 

drinking water that is termed the Health Reference Level (HRL). The HRL is defined as a 

concentration against which to compare the occurrence data from PWSs to determine if 

strontium occurs with a frequency and at levels of public health concern. Two different 

approaches are used to derive HRLs, one for chemicals that cause cancer and exhibit a linear 

response to dose, and the other for noncarcinogens and carcinogens evaluated using a non-linear 

approach. 

The HRL for strontium is based on the Reference Dose (RfD). As mentioned in the 

introduction, the RfD is an estimate (with uncertainty spanning perhaps an order of magnitude) 

of a daily oral exposure to the human population (including sensitive subgroups) that is likely to 

be without an appreciable risk of deleterious effects during a lifetime. The HRL for Strontium is 

based on the RfD of 0.3 mg/kg/day determined to be protective against a decreased rate of 

calcification in bone, especially during the periods of active growth from conception through 

adolescence. The RfD derivation is provided in Section 8.1 of this report. Age-specific 

exposure factors have been used in the HRL derivation in order to adjust for the increased risk 

associated with early life exposures (Appendix B). The HRL is calculated as follows:

Child specific HRL = (RfD / ∑(DWI/BWR x F)) x RSC

HRL = (0.3 mg/kg/day ÷ 0.040 L/kg/day) x 0.2 = 1.5 mg/L =1,500 μg/L

where:

RfD = 0.3 mg/kg/day

DWI/BWR = Drinking Water Intake Body Weight Ratio (DWI/BWR) expressed as liters 

per kg body weight (L/kg/day)(90th percentile, consumers only) for each 

age-specific period for the first 18 years, the average postnatal duration for 

bone growth in humans3.

 

3 Because the critical health endpoint had dose-response data associated with exposure during a specific period of 

sensitivity (i.e, sensitive population), EPA used age-specific drinking water intake to body weight ratio values from 

the Exposure Factors Handbook (2011) to derive the HRL for strontium (see Appendix B).
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F = The fraction of the 18 year exposure duration for each age-specific period.

RSC = Relative Source Contribution, or the level of exposure believed to result 

from drinking water when compared to other sources (e.g., food, ambient 

air). In all cases a 20 percent RSC is used for HRL derivation because it is 

the lowest and most conservative RSC used in the derivation of an MCLG 

for drinking water.

The monitoring results in Section 4.3.3 report the concentrations that exceed the HRL

and 1⁄2 HRL when the data are available. The number of systems and samples that exceed the 

HRL are indicators suggesting that strontium has the potential to occur in drinking water at 

levels of potential human health concern.

4.3.3 Results 

The data on the levels of strontium in drinking water sources cover a time period from 

1984 to 2009. The primary national data source, NIRS (1984-1986), is the oldest of the data sets. 

NIRS includes ground water data only. Because much of the strontium found in ground water is 

of geochemical origin, the NIRS data retain their value. The NIRS findings are consistent with 

more recent ground water studies such as Toccalino et al. (2010) and DeSimone (2009). The 

available data for strontium in surface waters are more limited. For EPA’s detailed analysis of 

strontium data from NIRS, see the Regulatory Determinations 3 Support Document (U.S. EPA, 

2012b). 

U.S. EPA’s National Inorganics and Radionuclides Survey (NIRS), 1984-1986

The NIRS data set supports analyses to estimate national occurrence in ground water 

PWSs. A total of 989 samples were collected from systems serving a population of 1,482,133. 

Extrapolations from this dataset provide the best available estimate of contaminant occurrence in 

ground water on a nationwide scale. To extrapolate, the percentage of ground water systems 

observed to exceed a specified threshold (or percentage of population served) is multiplied by the 

total national number of ground water systems (or the total national population served). The 

total number of ground water systems (and population served) was calculated in two ways: as the 

total number of CWSs served by ground water, and as the sum of CWSs and non-transient noncommunity water systems (NTNCWSs) served by ground water. NTNCWSs are public water 

systems that regularly supply water to at least 25 of the same people at least six months per year, 

but not year-round. Some examples are schools, factories, office buildings, and hospitals that 

have their own water systems.

Results of the analysis of NIRS data are presented in Table 4-3 and 4-4. Strontium was 

monitored with a reporting level of 1 μg/L. Approximately 99.1% of ground water PWSs had 

detections of strontium (i.e., concentrations at or above the reporting level). These detections 

affected about 99.9% of the population served by the PWSs. Detected concentrations ranged 

from 1.53 μg/L to 43,550 μg/L, with a median reported level of 178 μg/L; the maximum 

reported level was approximately 30 times the HRL. The data support the conclusion that 

occurrence of strontium in groundwater is widespread across the country but is most frequently
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found at levels below the toxicological level of concern. The mean concentration among 

detections (not shown in the table) was 603 μg/L.

Table 4-3 Strontium Occurrence Data from the NIRS Database – Summary of Detected 

Concentrations

Source 

Water 

Type

Total 

Number 

of 

Samples

Number

of 

Detections

Percent 

of 

Detections

Concentration Value of Detections (μg/L)

Minimuma Median

90th

Percentile

99th

Percentile Maximum

Ground 

Water 

Only

989 980 99.09% 1.53 178 1,078 7,339 43,550

a

The reporting level for strontium was 1 μg/L.

Table 4-4 presents strontium occurrence relative to the reporting level, 1⁄2 the HRL (750 

μg/L), and the HRL (1,500 μg/L).

Table 4-4 Strontium Occurrence Data from the NIRS Database – Summary of Ground 

Water System and Population Served Data 

Detections

Number Percent National Extrapolationa

Systems Population Systems Population Systems Population

All 

detections 980 1,480,581 99.09% 99.90%

39,741

(CWS only)

93,035,877

(CWS only)

58,864

(CWS + 

NTNCWS)

98,406,604

(CWS + 

NTNCWS)

>1/2HRL 141 245,870 14.26% 16.59%

5,718

(CWS only)

15,449,834

(CWS only)

8,469

(CWS + 

NTNCWS)

16,341,714

(CWS + 

NTNCWS)

>HRL 69 158,557 6.98% 10.70% 2,798

(CWS only)

9,963,311

(CWS only)
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Detections

Number Percent National Extrapolationa

Systems Population Systems Population Systems Population

4,145

(CWS + 

NTNCWS)

10,538,468

(CWS + 

NTNCWS)

a

National extrapolations are generated by multiplying the NIRS national statistical sample findings of 

system/population percentages and national system/population inventory numbers for ground water-sourced PWSs 

developed from EPA’s SDWIS, the CWSS, and UCMR.

NIRS data indicate that 7% of ground water CWSs (serving an estimated 10 million 

persons) may have strontium present in concentrations that could impact bone development in 

infants, young children, and adolescents. Although only one sample was collected per system, 

the levels in ground water are generally of geochemical origin and subject to minimal variability. 

The NIRS data identify strontium as a contaminant of potential chronic toxicological concern.

For EPA’s detailed analysis of the strontium data from NIRS, see the Regulatory Determinations 

3 Support Document (USEPA, 2012b)

State Drinking Water Monitoring Programs 1998-2005

Only two states and Region 9 Tribes provided strontium data from their State drinking 

water monitoring programs (Table 4-5). In the case of Illinois, data were available from 19

systems representing approximately 1% of CWSs. Results from Ohio (32 systems) came from 

approximately 2.5% of CWSs and less than 1% of NTNCWSs and transient non-community

water systems (TNCWSs4). One CWS from the Region 9 Tribes submitted strontium results for 

a single sample; the contaminant was not detected. The numbers of ground and surface water 

systems are too small to be considered representative of all systems.

Table 4-5 Strontium State Drinking Water Occurrence Data – Summary of Systems

State

(Date Range)

Source

Water

Type

Total 

Number 

of 

Systems

Systems with 

Detections

Systems with 

Detections

> 1⁄2 HRL 

(750 μg/L)

Systems with 

Detections

> HRL (1,500 

μg/L)

Number Percent Number Percent Number Percent

Illinois

(1998-2005)

Ground Water 16 16 100% 4 25.00% 4 25.00%

Surface Water 3 3 100% 1 33.33% 1 33.33%

 

4 TNCWSs are public water systems that provide water in a place such as a gas station or campground where people 

do not remain for long periods of time
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State

(Date Range)

Source

Water

Type

Total 

Number 

of 

Systems

Systems with 

Detections

Systems with 

Detections

> 1⁄2 HRL 

(750 μg/L)

Systems with 

Detections

> HRL (1,500 

μg/L)

Number Percent Number Percent Number Percent

Total 19 19 100% 5 26.32% 5 26.32%

Ohio

(2000-2005)

Ground Water 28 26 92.86% 8 28.57% 5 17.86%

Surface Water 4 4 100% 2 50.00% 2 50.00%

Total 32 30 93.75% 10 31.25% 7 21.88%

In Illinois systems, strontium was detected in 100% of 21 drinking water samples (Table 

4-7). These detections occurred at all 19 CWSs reporting data. Concentrations ranged from 71 

μg/L to 4,600 μg/L (Table 4-6), with 26.32% of systems reporting concentrations greater than 

the HRL of 1,500 μg/L; the same percentage of systems reported concentrations greater than 1⁄2 

the HRL (750 μg/L). Thirty-two Ohio PWSs detected strontium in 75 (97.40%) of 77 drinking 

water samples (Table 4-7). These detections occurred at 30 (93.75%) of the 32 PWSs reporting 

data. Concentrations ranged from 4 μg/L to 40,889 μg/L, with 21.88% of sites reporting 

concentrations greater than the HRL. 

Table 4-6 provides information on the concentrations of strontium reported in the State 

data sets. For both Illinois and Ohio, the concentration at the 90th percentile was greater than the 

HRL: for Ohio, the 90th percentile values in ground and surface water were about 4 times greater 

than the HRL. 

Table 4-6 Strontium State Drinking Water Occurrence Data – Summary of Detected 

Concentrations

State

(Date Range)

Source Water 

Type

Concentration Value of Detections (μg/L)

Minimum Median

90th

Percentile

99th

Percentile Maximum

Illinois

(1998-2005)

Ground Water 71 475 2,360 4,243 4,600

Surface Water 81 270 2,614 3,141 3,200

Total 71 450 2,500 4,320 4,600

Ohio

(2000-2005)

Ground Water 4 262 6,032 40,193 40,889

Surface Water 131 169 7,109 8,863 9,009

Total 4 257 6,950 39,935 40,889

Table 4-7 provides information on the individual sample data provided by the states. In 

the case of Illinois, it does not expand the information found in Table 4-5 to any extent because 

an average of one sample per system was submitted from that state. In Ohio, on the other hand, 
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an average of 2 samples was submitted per groundwater system and 5 samples per surface water 

system. In Ohio, where 50% of the 4 reporting surface water systems exceeded the HRL, 40% of 

the surface water samples exceeded the HRL. 

Table 4-7 Strontium State Drinking Water Occurrence Data – Summary of Samples

State

(Date Range)

Source 

Water

Type

Total 

Number 

of 

Samples

All Detections

Detections > 1⁄2 

HRL (750 μg/L)

Detections > HRL 

(1,500 μg/L)

Number Percent Number Percent Number Percent

Illinois

(1998-2005)

Ground 

Water 18 18 100% 4 22.22% 4 22.22%

Surface 

Water 3 3 100% 1 33.33% 1 33.33%

Total 21 21 100% 5 23.81% 5 23.81%

Ohio

(2000-2005)

Ground 

Water 57 55 96.49% 13 22.81% 10 17.54%

Surface 

Water 20 20 100% 8 40.00% 8 40.00%

Total 77 75 97.40% 21 27.27% 18 23.38%

As noted above, the STORET dataset included strontium data from PWSs in Indiana and 

Ohio. It could not be determined whether the data came from groundwater or surface water 

systems. Tables 4-8 and 4-9 include the STORET PWS monitoring data. The median 

concentration reported for Indiana and Ohio is higher than the corresponding values reported in 

Table 4-6, as is the 90th percentile value. Data submitted to STORET are not necessarily 

representative. 

Table 4-8 Strontium STORET Data – PWS Indiana and Ohio Summary of Detected 

Concentrations

Source Water 

Type

Concentration Value of Detections (μg/L)

Minimum Median 90th Percentile Maximum

PWS (IN, OH)a52 567 18,210 66,200

a It could not be determined from the data in STORET whether the Indiana or Ohio PWS facilities were served by 

ground water or surface water.
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Table 4-9 Strontium STORET Data – PWS Indiana and Ohio Summary of Samples and 

Sites

Source Water

Type

Total 

Number

Detections Detections > 1⁄2 

HRL (750 μg/L)

Detections > HRL 

(1,500 μg/L)

Number Percent Number Percent Number Percent

PWS (IN, OH)a

Samples

3,128 3,110 99.42% 1,345 43.00% 1,039 33.22%

PWS (IN, OH)a

Sites

199 199 100% 99 49.75% 75 37.69%

a

It could not be determined from the data in STORET whether the Indiana or Ohio PWS facilities were served by 

ground water or surface water.

U.S EPA’s Community Water System Survey (CWSS) 2006

In the 2006 CWSS, there was one system from among the 94 PWSs nationwide serving 

more than 500,000 people that reported monitoring data for strontium. This system reported the 

results of one sample only. The concentration of strontium in that sample was 330 μg/L and thus 

did not exceed the HRL (1,500 μg/L) for strontium. Reporting levels were not specified in this 

survey.

Consumer Confidence Reports (CCRs) from PWSs 2006-2007

Data on strontium were available from CCRs prepared by Suffolk County New York and 

New York City. Reporting levels were not specified in either of the CCRs. The highest 

concentrations from both locales (both located in the southern and coastal portion of New York) 

were well below the HRL. The Suffolk County Water Authority included data on strontium-88 

in its 2007 CCR. Samples were collected from 30 distribution areas supplied by both treated and 

untreated ground water from three major aquifers. The number of strontium samples collected in 

each distribution area varied from four to 255. Strontium-88 was detected in 26 of the 30 

distribution areas. The calculated average annual concentrations for these 26 distribution areas 

ranged from non-detections to 150 μg/L. The highest detected concentration was 200 μg/L, 

which is less than the HRL of 1,500 μg/L and less than 1⁄2 the HRL.

New York City included data on strontium in its 2006 and 2007 CCRs. The city is served 

by two distribution systems supplied by surface water from 19 reservoirs and three controlled 

lakes, and one distribution system supplied by treated ground water. In 2006, one of the surface 

water systems was off-line; 319 strontium samples were collected from the other surface water 

system and six samples were collected from the ground water system. The number of samples 

with detections was not reported. The average annual strontium concentration calculated for the 

surface water system was 20 μg/L, while that for the ground water system was 40 μg/L. 

Maximum concentrations of 30 μg/L and 50 μg/L were reported from the surface water and 

ground water systems, respectively. In 2007, strontium monitoring was conducted at the two 

surface water systems, but not at the ground water system. Four samples were collected at one 

system and 332 samples were collected at the other system. The number of samples with detects 

was not reported. Average annual concentrations calculated for the two surface water systems 
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were 20 μg/L and 70 μg/L. The highest detected concentration was 70 μg/L. No detections 

exceeded the HRL (1,500 μg/L) or 1⁄2 the HRL for strontium.

Environmental Working Group (EWG) Drinking Water Database 2004-2009 

EWG data for strontium come from a total of 370 systems and were gathered between 

2004 and 2009. These data showed detections of strontium in 366 PWSs in five states serving 

almost 2.4 million people (Table 4-10). EWG found that 16 PWSs in four states had detections 

of strontium above a threshold of 4,000 μg/L. These detections were therefore also exceedances 

of the HRL of 1,500 μg/L. 

Table 4-10 Summary of EWG Strontium Data, 2004-2009

State

PWSs with Detections of Strontium

PWSs with Detections of Strontium 

> 4,000 μg/L

Number of PWSs Population Served Number of PWSs Population Served

Wisconsin 2 64,500 2 64,500

Illinois 340 2,141,804 12 62,865

Ohio 17 117,126 1 18,135

New York 3 9,668 1 1,500

Minnesota 4 32,955 0 0

Total 366 2,366,053 16 147,000

USGS NAWQA – Drinking Water Studies 1991-2007

The USGS drinking water data collected from public and private wells are semi-national 

in scope. Like the NIRS data, they only reflect the concentrations in groundwater. The private 

well data have been included because, to the extent that the samples are drawn from the same 

aquifers as the public water, they provide an indication of source water quality at nearby PWSs.

Public Wells. Results from this study are presented in Table 4-11 and Table 4-12. The 

public well data come from 41 states; samples reflect untreated water and each site was only 

sampled once. Not every sample collected as part of the program was analyzed for strontium. 

Based on a total of 503 samples (Table 4-12), 126 (25.05%) exceeded 1⁄2 the HRL and 61 

(12.13%) exceeded the HRL (USGS, 2009). The lowest level reported in Table 4-11 may be 

indicative of reporting levels used. The median value is generally consistent with the NIRS data, 

as is the 90th percentile. Thus, the USGS data are supportive of the NIRS results. The percent of 

systems that exceeded the HRL is slightly higher than that observed in the NIRS data.
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Table 4-11 Strontium Data from Public-Supply Wells – Summary of Detected 

Concentrations

Source Water Type

Concentration Value of Detections (μg/L)

Minimuma Median

90th

Percentile

99th

Percentile Maximum

Ground Water Only 5.61 385 1,810 7,080 43,950

Source: Toccalino et al. (2010)

a

The minimum detection level may reflect the minimum reporting level.

Table 4-12 Strontium Data from Public-Supply Wells – Summary of Samples 

Source Water 

Type

Number 

of 

Samples

All Detections

Detections > 1⁄2 HRL 

(750 μg/L)

Detections > HRL 

(1,500 μg/L)

Number Percent Number Percent Number Percent

Ground Water 

Only 503 503 100% 126 25.05% 61 12.13%

Source: Toccalino et al. (2010)

The Lindsey et al. (2008) study examines water quality in carbonate aquifers utilized as 

sources by many PWSs. The authors reported 425 “observations” of strontium, but did not 

specify how many of the 1,042 samples collected for the study were tested for strontium and did 

not specify a reporting level for strontium. From the 425 observations, the 25th percentile 

concentration was 92.3 μg/L, the 50th percentile concentration was 220 μg/L, the 75th percentile 

concentration was 606.1 μg/L, and the maximum concentration was 43,950 μg/L. Unfortunately

data for the 90th percentile were not reported, preventing a comparison with the other 

groundwater data sets.

Strontium was detected in 551 (99.8%) of a total of 552 samples included in the 

Groschen et al. (2009) analysis of ground water in the glacial aquifer system in the Northern 

portions of the United States. The mean concentration was 390 μg/L and the 50th percentile 

value was 185 μg/L, indicating a distribution skewed towards high rather than low 

concentrations (Table 4-13). Less than 5% of the samples exceeded the HRL, with about 10% 

exceeding the 1⁄2 HRL. 
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Table 4-13 Strontium Data from Northern United States Glacial Aquifer System –

Summary of Concentrations

Element

Minimuma,b

Concentration 

(μg/L)

Mean

Concentration

(μg/L)

Maximum

Concentration

(μg/L)

Percentile Concentrations (μg/L) 

Estimated from ROS

5

th 10th 25th 50th 75th 90th 95th

Strontium 1.47 390 9,120 28 37 84 185 438 800 1,300

Source: Groschen et al. (2009)

a The reporting levels for strontium used in this study ranged from 0.08 μg/L to 1.4 μg/L. 

bThe minimum detection level may reflect the minimum reporting level.

Note: the minimum, mean, and maximum concentrations are measured values. The percentile concentrations in Table 

4-13 are estimated statistically using regression on ordered statistics (ROS) techniques. 

Private Wells. In the USGS private well study (DeSimone, 2009) there were a total of 

570 samples analyzed for strontium. The samples came from 48 states and covered 30 aquifers. 

The 570 analyses for strontium were conducted in a subset of the total samples. In 6.49% of 

wells, detected concentrations of strontium exceeded a threshold of 4,000 μg/L.

In the USGS/CDC study reported by Bartholomay et al. (2007), strontium was detected 

in 100 percent of the 446 wells sampled in 16 states, and found in excess of 4,000 μg/L in 2.2% 

of the wells. Reporting levels varied. The data in the report are inadequate to support an 

estimation of the number of wells that exceed the HRL.

Regional Patterns

Review of the NIRS data shows that strontium was detected in all 50 states/entities in 

which it was sampled (i.e., in 49 states (all except Hawaii) as well as Puerto Rico). It was 

detected at levels greater than half the HRL (750 μg/L) in 34 states and at levels greater than the 

HRL (1,500 μg/L) in 26 states, including states in all regions of the country.

The USGS survey of water from public wells (Toccalino et al., 2010) found the highest 

concentrations of strontium in sandstone aquifers, especially those in the Cambrian–Ordovician 

system found in Illinois, Iowa, and Wisconsin. High levels were also found in the EdwardsTrinity aquifer system in Texas. The USGS private well study (DeSimone, 2009) identified 

similar areas of vulnerability south-western and south-central areas of the United States. The 

State data set add Ohio to the list of states with high background levels of strontium.

Temporal Patterns

The available data do not support analysis of temporal pattern of exposure. Most of the 

data reflect a single sample per site and thus cannot be used to evaluate seasonal trends. In the 

case of ground water from public and private wells, the concentrations would be expected to 

increase during periods of low rainfall and low groundwater recharge. A comparison of the 

median and 90th percentile vales for groundwater from NIRS to the more recent USGS public 
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well data suggests that the concentrations in ground water have been fairly stable over the last 30 

years.

4.4 Summary

Strontium was detected in 980 of 989 samples collected from 989 CWSs served by

ground water sources between 1984 and 1986 as part of NIRS; surface water systems were not 

evaluated in NIRS. Of the 989 systems sampled, 141 systems serving 245,870 persons exceeded 

half the HRL, and 69 systems serving 158,557 persons exceeded the HRL. The mean for the 

samples with detection was 603 mg/L. Although only one sample was collected per system, the 

levels in ground water are generally of geochemical origin and subject to minimal variability. 

When extrapolated to a national basis, the population exposed to an exceedance of half the HRL 

in drinking water is approximately 15.4 million persons (or 16.3 million if NTNCWSs are 

included), while the population exposed to an exceedance of the HRL is approximately 10.0 

million persons (or 10.5 million if NTNCWSs are included). Based on USGS public and private 

well data, higher levels of strontium from geochemical sources occur in the CambrianOrdovician aquifer system (found in Illinois, Iowa, and Wisconsin) and similar areas of 

vulnerability in the southwestern and south-central areas of the United States. More limited 

monitoring data show that strontium has been detected in PWSs in Wisconsin, Illinois, New 

York, Minnesota, and Ohio. However, the scope of the information from the State and EWG 

monitoring programs is too limited to support inferences regarding the risks within individual 

states.

Monitoring information for ambient water is reported by the STORET database and by

Groschen et al. (2009) using USGS NAWQA data collected between 1991 and 2003 during a 

study of the ground water of the glacial aquifer system in the Northern United States. Strontium 

was detected in 551 (99.8%) samples analyzed for strontium by the USGS. Due to wide 

variations in concentrations detected and the large geographic area covered in the NAWQA data 

set, these data are not informative as to the expected population risk. Within the STORET data, 

strontium was detected in at 1,541 (12.39%) sites (including groundwater and surface water) at 

concentrations greater than half the HRL and at 653 (5.25%) sites in excess of the HRL. 

However, the STORET data have quality limitations that prevent them from being used for 

estimating population risk. Much of the strontium found in groundwater is of geochemical 

origin. Human activities that may contribute strontium to the environment (and potentially

groundwater) include milling, refining, other industrial activities, direct discharge of 

contaminated waste water, and use of phosphate fertilizers (see Chapter 3).
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5.0 EXPOSURE FROM MEDIA OTHER THAN WATER 

This chapter presents information on human exposure to strontium from food, air, soil, 

and other residential exposures. Note that the available information addresses strontium 

concentrations and intakes as the element Sr, and does not provide any information on the 

speciation of strontium compounds in these media.

5.1 Exposure from Food

5.1.1 Concentration in Non-Fish Food Items

There is limited information available on measured levels of strontium in non-fish food 

items. 

The USGS (1980) included strontium among elements analyzed for in fruits and 

vegetables in the US. Their results, as summarized in ATSDR (2004), are presented in Table 5-

1.

Table 5-1 Strontium Levels in Fruits and Vegetables 

Fruit or Vegetable Average Solid Concentration (g/100g)*

Apple 1358

Bean (Dry) 663

Bean (Snap) 2170

Cabbage 6417

Corn 41.6

Cucumber 2400

Grape (American) 2560

Grape (European) 3840

Lettuce 2226

Orange 2556

Peach 3082

Potato 2562

Tomato 996

Source: USGS (1980)

*Values were presented as ppm (g/g) in ATSDR (2004), but converted here to g/100g to facilitate comparison 

with Total Diet Study data

Pennington and Jones (1987) reported strontium levels for 234 foods collected in 1994 as 

part of the FDA’s Total Diet Study. Their results, which include both adult foods and infant 

foods, are summarized in Table 5-2. Strontium concentrations in 84% of the individual food 

samples were ≤149 μg/100g. 
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Table 5-2 Strontium Levels Measured in Various Foods

Food Category

Number of Foods in 

Category Mean (g/100g) Range (g/100g)

Adult Foods

Milk, yogurt and 

cheese 11 104 22 – 418

Meat, fish and 

poultry* 23 135 3 – 2420

Eggs 3 123 101 – 135

Nuts 3 329 181 – 588

Legumes 7 101 68 – 169

Grains and grain 

prods 25 112 9 – 465

Fruits and fruit 

juices 28 83 0 – 403

Vegetables 42 171 2 – 893

Mixed dishes and 

soups

16 108 40 – 326

Desserts 14 94 31 – 195

Sweeteners 9 92 3 – 367

Fats and sauces 9 24 0 – 46

Beverages 11 16 0 – 64

Infant Foods

Formulas 2 46 39 – 52

Meat and poultry 3 13 3 – 30

Cereals 2 44 26 – 62

Fruit and juices 9 28 10 – 57

Vegetables 7 96 20 – 216

Mixed dishes 9 71 45 – 89

Custard 1 25 -

Source: Pennington and Jones (1987)

*Note that excluding shrimp from the meat, fish and poultry group results in a mean of 31 and a range of 3 - 81 

g/100g.

Barnes (1997) included strontium among several trace elements for which she measured 

concentrations in a variety of fruit juices that were prepared for this study from the raw fruit and 

diluted to single strength. Note that the primary purpose of the paper was to demonstrate the 

improved sensitivity of the “Spectroscopic” method used for multiple element analyses. The 

results for strontium are summarized in Table 5-3.
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Table 5-3 Strontium Levels in Juices

Juice Product Sub-product Concentration (g/mL)*

Apple Juice

Apple Juice 1

Apple Juice 2

Apple Juice 3

Apple Juice 4

0.1549

ND (< 0.01 g/L)

0.1176

0.1087

Orange Juice

Brazilian

California

FL Valencia

Navel Orange

Pineapple Orange

0.0417

0.5368

0.0933

0.5209

0.1612

Lemon Products

CA Lemon

Bottled Lemon

Lemonade

0.0986

0.5334

0.1653

Other Citrus Fruits

Ruby Red Grapefruit

Lime

Tangerine

2.577

0.3464

0.0828

Stone Fruit Cultivars

Apricot

Sour Cherry

Peach

Plum

Prune

0.1566

0.0338

0.0128

0.1052

0.8805

Grape Cultivars

Concord Grape

Red Grape

White Grape

0.3661

0.1086

0.6318

Berry Juices

Blackberry

Blueberry

Boysenberry

Raspberry

Strawberry

0.2619

0.0406

0.9523

2.232

0.3001

Tropical Fruit Juice

Banana

Kiwi

Mango

Pineapple

0.1297

1.744

0.5121

0.0604

Papaya

Papaya 1

Papaya 2

Papaya 3

1.448

2.130

1.493

Tomato Tomato Sauce 1

Tomato Sauce 2

0.9390

0.8397

Other Fruits Red Currant

Pear

1.251

0.5912

Source: Barnes (1997)

*Note: These values are shown in ATSDR (2004) as g/L; however, the original study gives them as g/mL.
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Tautkus et al. (2007) reported on the strontium levels in milk as determined by flame 

atomic adsorption spectrometry. Cow’s milk samples were collected from 5 different dairies for 

analysis. The average strontium concentration was 0.036 mg/L with a range of from 0.024 mg/L 

to 0.055 mg/L.

Iyengar et al. (2000) evaluated the levels of a number of trace elements, including 

strontium and calcium, in freeze dried mixed total diet composites from samples collected

between 1985 and 1989. Their composite diet was based on the 201 food items consumed by

adults and adolescents as used by FDA in its Total Diet Studies (TDS) for various age-sex 

groups. The authors did not report the levels of strontium or other elements in the individual 

food items making up the freeze-dried composite, but only an average for 10 diet composites 

representing various US regions. The mean strontium concentration was reported as 3.45 mg/kg 

dry weight (s.d. = 0.5). (To compare with the other data shown above, this would be 345 g/100 

g.) The value for calcium was 1823 ± 150 mg/kg or 182.3 mg/100 g, a calcium:strontium ratio 

of about 500 mg to 1mg.

A recent study of strontium dietary intake was conducted in Ireland between 2001 and 

2005 (FSAI, 2011). Cereal grains accounted for the largest percentage of the total daily intake

(33.1%) followed by bottled water (22.3%). Dairy products accounted for 7.7%, vegetables for 

12.0% and fruits and preserves 8%. The United Kingdom (2009) conducted a comparable study

in 2006 with similar results: Cereal grains 34%; vegetables 23%, fruits and fruit products 16%; 

milk and dairy products 12%, and beverages 7%.

5.1.2 Concentrations in Fish and Shellfish

Fish and fish-products contained the highest levels of strontium among the food groups 

evaluated by Millour et al. (2012). The average concentration from 83 samples was 7.7 mg/kg in 

the fish shellfish category compared with an average concentration of < 2 mg/kg for the other 

food groups. Among the fish and shellfish examined shrimp had the highest average 

concentration (25.4 mg/kg). The high levels in fish and shellfish likely reflect the fact that 

strontium is the fifth most abundant metallic cation present in ocean water (Hibbins, 1997).

5.1.3 Intake of Strontium from Food

Pennington and Jones (1987) estimated that strontium intakes ranged from 493 to 1489 

g/day for eight groups of various ages and both sexes. These estimates were based on the 

measured levels of strontium in the various food products as reported above and the intakes for 

the eight groups developed as part of the Total Diet Study, as shown below: 

6 to 11 months: 493 g/day

2 years: 685 g/day

14 - 16 years, female: 928 g/day

14 - 16 years, male: 1388 g/day

25 - 30 years, female: 999 g/day

25 - 30 years, male: 1489 g/day
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60 - 65 years, female: 979 g/day

60 - 65 years, male: 1265 g/day

If the strontium level reported by Tautkus et al. (2007) for strontium levels in milk is 

applicable to infant formula, an infant would be exposed to 22 to 28 μg Sr/day from formula 

prepared with distilled water. This estimate is based on the IOM (1997) estimate that average 

breast milk or formula intake is780 mL/day through the first six months of life, and 600 mL/day

for the second six months. These exposures are calculated below:

Birth to six months: 0.036 mg/L x 0.780 L/day = 0.028 mg/day = 28 μg/day

Six months to one year: 0.036 mg/L x 0.6 L/day = 0.0216 mg/day = rounded to 22 μg/day

Iyengar et al. (2000) provided an estimate of 1620 g/day (s.d. = 240) for strontium 

intake from the composite diet of the 25 - 30 year old adult males group based on samples 

collected during the 1985-1989 time period. This was the only age/sex group that these authors 

considered, noting that it was the group with the “highest daily intake.” For the same age group 

the calcium intake was 860 ± 150 mg/day (Ca:Sr ratio = ~500 mg Ca:1 mg Sr). The current 

recommended calcium intake for this age group is 1000 mg/day (IOM, 2010).

The mean daily dietary intake for the Irish population (958 individuals) was 1,580 μg/day

(0.20 μg/kg/day) with a 97.5 percentile value of 2,790 μg/day (40 μg/kg/day). The highest 

intake reported was.60 μg/kg/day (FSAI, 2011). The mean daily intake from the 2006 United 

Kingdom (2009) study was lower than that for the Irish study, 1,200 μg/day. The study included 

19 food categories divided into 20 food groups. When intakes were evaluated for population 

subgroups, young children and adolescents had the highest intakes per unit body weight (Table 

5-4).

Table 5-4 Dietary Strontium Intakes for Population Subgroups from the 2006 United 

Kingdom Total Diet Study.

Population group Descriptor

Mean

(μg/kg/day)

High

(μg/kg/day)

Toddlers 1.5-4.5 years 42.8 71.1

Young People 4 -18 years 25.9 51.0

Adults Not Defined 15.6 30.6

Elderly Free living 14.0 26.6

Vegetarians Not defined 20.5 35.9

5.2 Exposure from Air

5.2.1 Concentration of Strontium in Air 

WHO (2010) noted that strontium enters the atmosphere, mainly as particulate strontium 

oxide, as a result of both natural processes (weathering of rocks, particle entrainment, wind 
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resuspension, and sea spray), and from human activity (notably milling, coal burning, and use of 

phosphate fertilizers). Very limited data could be found, however, on measured levels of 

strontium in that atmosphere. 

Both ATSDR (2004) and WHO (2010) noted data from studies conducted in the 1970s 

and 1980s that reported strontium levels observed in air. Strontium in urban air in an 

unidentified city in the 1970’s ranged from 4 to 100 ng/m3averaging 20 ng/m3(Dzubay and 

Stevens, 1975). Strontium in the Los Angeles basin in 1985 was measured at 29.1 ng/m3and 

averaged 0.9 - 4.8 ng/m3in urban Illinois air between 1985 and 1988 (Witz et al., 1986; Sweet et 

al., 1993). 

Atmospheric concentrations of strontium associated with emissions from coal fired plants 

range from 17 to 2718 g/m3in the western states and approximately 9,800 g/m3for eastern 

states (Que Hee et al., 1982; Ondov et al., 1989). Emissions are influenced by the strontium in 

the coal, the amounts of coal burned, and the efficacy of fly-ash recovery.

Perry (1999) noted a strontium concentration of 9 ng/m3in the proximity of a pyrotechnic 

display.

5.2.2 Intake of Strontium from Air

Using the average urban air concentration for strontium of 20 ng/m3noted above, and an 

estimated 20 m3/day air breathed by an adult (Dzubay and Stevens, 1975; Witz et al., 1986), 

ATSDR (2004) calculated an inhalation exposure of 400 ng/day (0.4 g/day) of strontium from 

air. Note that these air data are from the early 1970s. WHO (2010) did not calculate an intake 

value from air but noted that the contribution from air to be “insignificant by comparison” with 

food and drinking water intakes.

Estimates of non-occupational exposures to strontium in ambient air for adults can be 

derived from the arithmetic mean ambient air concentration 20 ng/m3using the assumption that 

adult humans breathe 15.8 m

3

of air per day (U.S. EPA, 2011). The estimated adult exposure is:

20 ng/m3× 15.8 m

3

/day = 316 ng/day, rounded to 300 ng/day (= 0.3 g/day)

For a children (birth to one year), the average respiratory rate is 5.4 m

3

/day (U S. EPA, 

2011) resulting in an exposure of 100 ng/day (0.1 g/day). 

20 ng/m3× 5.4 m

3

/day = 108 ng/day, rounded to 100 ng/day (= 0.1 g/day)

Individual intakes vary depending on factors including activity, geographic location, and 

inhalation rate.

5.3 Exposure from Soil
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5.3.1 Concentration of Strontium Soil

As discussed in Chapter 3, strontium is a naturally occurring element present in nearly all 

rocks and soils. Shacklette and Boerngen (1984) provided estimates of the mean concentration 

of strontium in soils and other geologic materials in the continental US. The values they 

reported are summarized in Table 5-4.

Table 5-5 Levels of Strontium in Soils and Other Geologic Materials (ppm)

Area Geometric Mean Arithmetic Mean Range

Eastern US 53 120 <5 – 700

Western US 200 270 10 – 3000

Overall US 120 240 --

Source: Shacklette and Boerngen (1984)

Note: “--” indicates that no information was found.

5.3.2 Intake of Strontium from Soil

No published estimates of strontium intake from soil were found.

Human exposure to contaminants in soils is usually from dust that infiltrates homes, 

automobiles, etc. in adults, and from dust and incidental soil ingestion in children. Infants and 

toddlers ingest soil and household dust by hand-to-mouth transfer during everyday activities. 

They may therefore be exposed to higher levels than adults living in the same contaminated 

environment. 

Estimates of intake for soil and dust assume an ingestion rate of 60 mg/day (0.00006 

kg/day) for children < 1 year and 100 mg/day (0.0001 kg/day) for children ages 1 to 21 years 

(U.S. EPA, 2011). The estimate is 50 mg/day (0.00005 kg/day) for adults (U.S. EPA, 2011). 

Using the overall US arithmetic mean for strontium in soils of 240 ppm (= 240 mg/kg), 

soil/dust estimates of the exposures for infants are 14 g/day and for children < age 21 are 24 

g/day. The estimate for adult exposures is 12 g/day. 

Infants: 240 mg/kg × 0.00006 kg/day = 0.014 mg/day (14 g/day)

Children: 240 mg/kg × 0.0001 kg/day = 0.024 mg/day (24 g/day)

Adults: 240 mg/kg × 0.00005 kg/day = 0.012 mg/day (12 g/day)
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5.4 Other Residential Exposures

As noted in Chapter 3, strontium has a number of commercial uses (notably in 

electronics), but no estimates of exposure from these uses was found. It is also used in some 

toothpastes to treat tooth sensitivity (USGS, 2009b), but no exposure estimates related to this use 

were found in the literature.

5.5 Summary

Although strontium is known to occur in food, air, and soil, data on levels in those media 

are limited as are estimates of intake from those sources. Food appears to be a more significant 

source than air and soil. Dietary intakes based on an FDA Total Diet Study by Pennington and 

Jones (1987) indicated dietary intakes to range from 493 to 685 g/day for children 6 months to 

2 years old; 928 to 1388 g/day for 14 to 16 year old adolescents; and 979 to 1489 g/day for 

adults. Another estimate of dietary intake for 25 - 30 year old males by Iyengar et al. (2000) was 

reported to be 1620 g/day. Recent studies from Ireland and England provided estimates of 

1,580 μg/day and 1,200 μg/day, respectively for the general population. Both means are 

consistent with the results from the U.S. studies.

Estimated strontium intakes from air and soil are very low compared with those from 

food. Exposure from air has been estimated from data for levels of strontium in nonoccupational air to be 0.1 g/day for children and 0.3 g/day for adults, while an inhalation 

exposure for adults of 0.4 g/day has been estimated based on the average urban air 

concentration of strontium. The estimates of intake from soil are 14 g/day for infants, 24 

g/day for children, and 12 g/day for adults.
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6.0 TOXICOKINETICS

The human strontium data reported in this section come from stable isotope and 

radioactive isotope studies. Stable (nonradioactive) isotopes of metals can be found in nature in 

fixed abundances. Those found in low abundance can be isolated and enriched, and are often 

used as tracers in studies to follow the kinetics and metabolism of metals in a specific diet or at a 

specific dose. Strontium has four stable, naturally occurring isotopes with the following natural 

abundances: 84Sr (0.56%), 86Sr (9.86%), 87Sr (7.00%), and 88Sr (82.58%) (WHO, 2010). 

There are 16 known radioactive isotopes of strontium, but only two, 85Sr and 90Sr, are 

mentioned in papers relevant to drinking water exposure and toxicokinetics. 85Sr is synthetic, 

meaning it is not found in nature. Its relatively short half-life makes it convenient for use in 

metabolism studies, thus it is used as a tracer in the studies described in this section. 90Sr is a byproduct of nuclear fission is found in nuclear fallout, and has a half-life of approximately 29 

years (ATSDR, 2004). The radioactive strontium (90Sr) exposures used in the studies described 

in this section are via diet, drinking water or accidental inhalation only. 

For toxicokinetics studies, both types of isotopes are of use. Both stable tracers and 

radioactive isotopes can be differentiated from endogenous forms of the element and those 

consumed at other times. Radioactive isotopes have the additional advantage of being easily

tracked as they move within the body. 

6.1 Absorption

Human studies show that approximately 20% of ingested strontium or SrCl2 is absorbed 

via the gastrointestinal tract (see Table 6-1), with more efficient absorption occurring from 

aqueous solutions (Li et al., 2006). 

No age- or gender-related differences in absorption were observed in human studies 

(Harrison et al., 1965; Kahn et al., 1969); in contrast, animal studies report age-dependent 

changes in absorption following ingestion (Forbes and Reina, 1972). Increased strontium 

absorption has been reported during lactation in rats (Kostial et al., 1969), due to the strontium’s 

common absorption pathway with calcium (Reid et al., 1986; Milsom et al., 1987; Blumsohn et 

al., 1994; Sips et al., 1994; Bianchi et al., 1999). Although similar studies have not been 

conducted in humans, there is the potential that absorption is also increased during lactation and 

pregnancy in humans. 

Very limited information is available regarding absorption following inhalation or dermal 

exposure to strontium. 
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Oral Exposure 

Humans

Numerous studies have evaluated the fractional absorption of ingested strontium in 

healthy human subjects or hospital patients who received an oral dose of strontium chloride 

(SrCl2) or ingested strontium in the diet (see Table 6-1). Tracer studies found that absorption of 

85Sr in cancer patients ranged between 14 to 50% of the administered oral dose; doses ranged 

from 0.1 to 0.3 μCi/kg (i.e., trace amounts of carrier-free 85Sr; Comar et al., 1957 did not provide 

body weights, thus the 20 μCi dose was converted using an assumption of 70 kg body weight) 

(Harrison et al., 1955; Comar et al., 1957; Spencer et al., 1960; Lengemann, 1963). Collectively, 

these studies indicate that, following oral exposure, approximately 20% of ingested strontium is 

absorbed from the gastrointestinal tract. 

Table 6-1 Summary of Estimates of Absorption of Ingested Strontium in Humans

Dose and 

mediaa

Subjects 

(N)b

Absorption

(% of dose)c Comment Reference

Tracerg Adults

(9M) 28±3

Healthy adults. Absorption 

estimate based on whole body

retention (R): Roral/Riv.

Likhtarev et al. 

(1975)

44 mg, 

SrCl2

Adults

(8M) 25±7

Healthy, fasted subjects adults. 

Absorption estimate based on 

plasma AUCoral/AUCiv.

d

Sips et al. (1995)

44 mg, 

SrCl2

Adults

(8M) 25±6

Healthy fasted subjects. 

Absorption estimate based on 

plasma AUCoral/AUCiv.

Sips et al. (1996)

88 mg, 

SrCl2

Adults

(8M) 19±5

Healthy subjects. Dose 

administered with meal. 

Absorption estimate based on 

plasma AUCoral/AUCiv.

Sips et al. (1996)

219 mg,

SrCl2

Adults

(6M, 11F) 20

Patients with osteoporosis or 

chronic renal failure. Dose 

administered with meal. 

Absorption estimate based on 

plasma AUCoral/AUCiv.

Blumsohn et al. 

(1994)

Tracerg Adults

(3M)

21

(18-24)

Patients with osteoporosis. Dose 

administered with meal. 

Absorption estimate based on 

plasma AUCoral/AUCiv.

Hart and Spencer 

(1967)

1.45 

mg/kg,

SrCl2

Adults

(6M, 4F) 22±2

Healthy fasted subjects. 

Absorption estimate based on 

fraction of dose in plasma at 3 

hours.

Bianchi et al. 

(1999)

Tracerg Adults 17 Healthy subjects without a pre- LeRoy et al. 
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Dose and 

mediaa

Subjects 

(N)b

Absorption

(% of dose)c Comment Reference

(12) (8-34) dosing fast. Absorption estimate 

based on whole body counting.

(1966)

44 mg, 

SrCl2

Adults

(43M, 

20F)

13

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.

Sips et al. (1994)

219 mg,

SrCl2

Adults

(6M)

20

Healthy fasted subjects. 

Absorption estimated from 

cumulative urinary excretion.

Leeuwenkamp

et al. (1990)

Tracer in 

milkg

Adults

(5) 11

Healthy subjects. Dose 

administered in milk, daily for 

21-32 days. Absorption 

estimated from whole body

retention kinetics.

Rundo and 

Lillegraven 

(1966)

Tracerg Adults

(4F)

42

(25-59)

Two healthy subjects, two 

patients with osteoporosis. 

Absorption estimated from intake 

minus 20-day fecal excretion, 

corrected for fecal excretion after 

an intravenous dose.

Uchiyama et al. 

(1973)

0.8 

mg/day

Diet

Adults

(11M)

18

(-17-42)

Patients with various disorders, 

including osteoporosis. 

Absorption estimate based on 6-

day balance; dietary intake minus 

fecal excretion.e

Warren and 

Spencer (1976)

Tracerg Adults

(11M)

18

(-17-42)

Patients with various disorders, 

including osteoporosis. 

Absorption estimate based on 

estimated from 6-day balance; 

dietary intake minus fecal 

excretion.e

Warren and 

Spencer (1976)

1500 

mg/day

Adults

(5F, 1M)

22

(20-28)

Patients with various illnesses. 

Absorption estimated from 

dietary intake minus fecal 

excretion minus fecal excretion 

after an I.V. dose (endogenous 

fecal excretion).

Spencer et al. 

(1960)

Diet Adults

(9)

12

(0-48)

Patients with various illnesses. 

Absorption estimate based on 

Spencer et al. 

(1972)
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Dose and 

mediaa

Subjects 

(N)b

Absorption

(% of dose)c Comment Reference

estimated from 6-day balance; 

dietary intake minus fecal 

excretion.e

5-100 mg,

SrCl2

Children

(5)

4-14 years

22

Patients with various illnesses. 

Dose administered for 24-28 

days. Absorption estimated from 

dose minus 14-day fecal 

excretion.

Sutton et al. 

(1971b)

100 μg,

breast 

milk

Infants

(12)

6-8 days

15

(-47f-59)

Healthy breast-feeding subjects. 

Absorption estimate based on 

estimated from 3-day balance 

intake minus fecal excretion.e

Harrison et al. 

(1965)

600 μg

Diet

Infants

(21)

20 days-1 

year

28

(12-43)

Healthy subjects. Absorption 

estimate based on estimated from 

seven sequential 28-day balances; 

dietary intake minus fecal 

excretion.e

Kahn et al. 

(1969)

aDoses are in mass of strontium.

bNumber of males (M) or females (F) is presented if reported.

cValues are reported means ± standard deviation; values in parentheses are reported ranges.

dAUC refers to the area under the plasma strontium concentration-time curve.

eCalculated from reported individual subject data.

f

Sic. Apparent error in ATSDR (2004).

g Tracer used is 85Sr (specific dose unavailable but is toxicologically small)

Data in humans suggest there are no age-dependent differences in strontium absorption in 

contrast to age-related changes that have been observed in animal studies. Similar ranges of 

strontium absorption (15-35%) were observed in infants, children and adults in several studies 

(Harrison et al., 1965; Kahn et al., 1969; Sutton et al., 1971a; Alexander et al., 1974). Most of 

the studies in Table 6.1 reported absorption of 20-30% over a wide range of conditions and doses 

(healthy and osteoporotic adults, healthy infants, sick children, fed and fasted adults, and doses 

of <1-1500 mg). Although there are some outliers, the data are not sufficient to determine 

whether these outliers represent true differences, and do not support categorization of levels of 

absorption by different groups. Differences by gender were not observed in a study of the area 

under the curve (AUC) for plasma strontium in adult healthy age-matched subjects versus 

patients who had calcium-oxalate urinary tract stones but normal levels of calcium in urine (10.6 

± 0.6 mmol/L-min male; 9.3 ± 0.6 mmol/L-min female; Vezzoli et al., 1998). 

The main route of entry of strontium into the body is the gastrointestinal tract. 

Leeuwenkamp et al. (1990) reported that two dominant intestinal absorption loci were present in 

the intestines, with the first locus having a higher uptake capacity than the second. In this study, 

six healthy male volunteers were orally administered 2.5 mmol SrCl2 (in water). For these 

subjects, two absorption phases were observed in the overall plasma concentration time curve, 

due to two dominant intestinal absorption loci. The overall peak plasma concentration (Cmax) 
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and area under the curve plasma concentration-time curve (AUC ∞) were 33.55 ± 1.22 μg/mL

and 9138 ± 1930 μg*min/mL, respectively. For the first locus the terminal plasma elimination 

half-life time and Cmax were 47.3 ± 7.9 hours and 3.09 ± 0.95 μg/mL, respectively. The limited 

pharmacokinetic parameters for the second locus could only be attained for 3 of the 6 subjects. 

For the second locus, the Cmax2 and AUC2∞ were 0.9 ± 0.4 μg/mL and 1204 ± 565 

μg*min/mL, respectively. The AUC2∞/AUC∞ was 0.14, which indicates that 14% of the 

absorbed dose was absorbed through the second locus with the remaining 86% being absorbed 

through the first locus. The estimated strontium bioavailability was 20%. 

Li et al. (2006) studied the intestinal absorption of strontium carbonate in 13 healthy

adult volunteers using simultaneous administration of oral 86Sr (0.1 to 5 mg) and intravenous 84Sr 

(0.4 mg) in order to understand the effect that various foodstuffs have on strontium absorption. 

The oral 86Sr was administered either via an aqueous solution or added to a variety of food stuffs 

at the following doses: green/black tea (1 mg), water (0.1 to 5 mg), cress (0.72 mg), milk with or 

without alginate (1 mg), salad (1.39 mg), calcium solution (1 mg) and baby food (0.384 to 1 mg). 

Strontium ingested with black tea had the highest absorption rate (61%), while strontium 

ingested with alginate in milk had the lowest absorption rate (27%). The 86Sr tracer was 

absorbed by the intestinal wall and reached maximum value in the plasma within 80-160 minutes 

before being cleared from the plasma. Peak strontium absorption occurred between 40 and 120 

min, based upon the ICRP GI tract model. The authors stated that this implies that the 

absorption process occurs mostly in the small intestinal wall. Overall, the authors concluded that 

strontium carbonate is more efficiently absorbed when dissolved in aqueous solutions than 

intrinsically labeled food. 

Zittermann et al. (2000) determined that fractional absorption of 2.27 mmol (200 mg) 

strontium chloride hexahydrate administered with a meal, dissolved in apple juice, to healthy

adults was 12%. No significant difference in absorption was observed when strontium was coadministered with either lactose or glucose/galactose. 

During pregnancy and lactation there is an increased demand for calcium (Kostial et al., 

1969; ATSDR, 2004). This suggests that pregnant and lactating women would have increased 

strontium absorption (for a given level of calcium intake), since strontium and calcium 

absorption share a common mechanism (Reid et al., 1986; Milsom et al., 1987; Blumsohn et al., 

1994; Sips et al., 1994; Bianchi et al., 1999).

Animals

Limited data on strontium absorption following oral exposure are available in animals. 

These studies show that calcium and phosphate decrease absorption in rats (Comar et al., 1961; 

Kostial et al., 1963, 1964, 1967; Slat et al., 1971), and there are substantial age-related 

differences in absorption of strontium by rats (Forbes and Reina, 1972).

Strontium absorption is influenced by dietary factors. For example, increased dietary

concentrations of calcium and phosphate have been shown to decrease strontium absorption in 

rats (Comar et al., 1961; Kostial et al., 1963, 1964, 1967; Slat et al., 1971). A diet that mimicked 
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the normal human diet and one containing high levels (75 to 100%) of meat products (type of 

meat unspecified) resulted in a greater absorption of strontium (Kostial et al., 1980; Kargacin and 

Kostial, 1982, 1984) than the grain-based rat chow diet. 

Animal studies suggest that strontium is absorbed from both stomach and small intestine. 

Ex-vivo studies using isolated rat intestine in vitro or in situ provide direct evidence for 

strontium absorption in the small intestine (ATSDR, 2004). In vivo hamster studies using tracer 

doses of 85SrCl2 found that strontium absorption was decreased from 37% to 20% when hamsters 

had their pyloric sphincters (located at the base of the stomach) ligated (Cuddihy and Ozog, 

1973). Since the stomach contents could not enter the intestine, this supports the conclusion that 

both the stomach and intestine can absorb strontium. 

Data in animals suggest that lactating dams absorb more strontium than non-lactating 

control rats (Kostial et al., 1969). Lactating rats that received a tracer dose of 85Sr as SrCl2 in 

drinking water between 14 and 16 days after the start of lactation absorbed 11% of the dose 

compared to 5% absorption in non-lactating rats (Kostial et al., 1969). Forbes and Reina (1972) 

found that 85% of orally-administered strontium chloride (further information on route not 

available) was absorbed by 15-day-old rats, while only 8% of the dose was absorbed by 89-dayold rats. Sips et al. (1997) reported that 19% of orally-administered strontium chloride was 

absorbed by adult rats. ATSDR (2004) suggested that the difference between the two studies in 

estimates of absorption by the adult rats was due to differences in method. 

Inhalation Exposure

Humans

Data from humans and animals suggest that strontium is readily absorbed following 

inhalation. Radiologically-active strontium has been detected in the urine of workers 

accidentally exposed to airborne 90Sr, demonstrating that inhaled aerosolized strontium can be 

absorbed (Rundo and Williams, 1961; Petkau and Pleskach, 1972). However, definitive 

quantitative information is not available for these exposures. Furthermore, inhalation is not a 

relevant route of exposure via drinking water except if it is aerosolized and inhaled during 

showering.

Animals

Animals studies using direct exposure and intratracheal instillation show that the rate of 

absorption following inhalation is dependent upon the chemical form of the strontium aerosol, 

with compounds of greater solubility having more rapid absorption. Willard and Snyder (1966) 

exposed rats to various compounds of aerosolized strontium, showing 99% of the 85Sr carbonate, 

phosphate, fluoride or oxide cleared within 5 days, while 60% of the 85Sr titanate remained in the 

lung. 
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Dermal Exposure

Humans

Ilyin et al. (1975) found that less than 1% of 85SrCl2 (aqueous solution with pH of 7) 

applied to intact forearm skin (average area of 8 cm2) was absorbed after 6 hours, while 38% and 

57% of the applied dose was absorbed through scratched and abraded skin after 30 min and 6 

hours, respectively. No information was available on the administered dose.

Animals

No data were identified on dermal absorption in laboratory animals. 

6.2 Distribution

In general, once absorbed strontium is preferentially (>95%) and uniformly distributed in 

the bones and teeth (Comar et al., 1957; Sowden and Stitch, 1957; Tipton and Cook, 1963; 

Schroeder et al., 1972; Underwood, 1977; Skoryna, 1981; Rosenthal, 1981; Cabrera et al., 1999). 

The skeletal uptake and distribution of strontium is influenced by dietary calcium, but a study of 

maternal-fetal transfer of strontium suggests it likely undergoes transport via a concentration 

gradient while calcium transport occurs via active transport (Rossipal et al., 2000). Animal 

studies report tissue concentrations for strontium to be 1,000-fold higher in the bone than in other 

tissues following supplementation via drinking water (Skoryna, 1981). Strontium has been 

shown to transfer to the fetus during pregnancy and neonates during lactation (Harrison et al., 

1965; Underwood, 1977; Olsen and Jonsen, 1979; Tolstykh et al., 1998, 2001; Rossipal et al., 

2000). 

Oral Exposure

Humans

Strontium distribution via the blood plasma has been well studied, but there is limited 

information regarding the partitioning of strontium in the blood. Leeuwenkamp et al. (1990) 

reported a peak plasma concentration of 3.55 μg/mL approximately 2.5 hours after oral 

administration of 2.5 mmol SrCl2. Further analysis of the plasma concentrations relative to time 

suggested that two dominant intestinal absorption loci were present, with peak plasma 

concentrations of 3.09 and 0.9 μg/mL for the first and second loci, respectively.

Measurements of 7.2 μg/L strontium in the erythrocyte fraction and 44 μg/L strontium in 

the plasma fraction were obtained using blood from blood banks (Olehy et al., 1966), and a 

similar total value (53 μg Sr/L) was reported in serum from 100 human subjects receiving a 

normal diet (Skoryna, 1981). An in vitro study (Alda and Escanero, 1985) and an intravenous 

study (Harrison et al., 1955) determined that 45% and 60%, respectively, of the strontium in 

serum was ultrafilterable (or able to pass through biologic membranes), unlike protein-bound 

strontium, which is not diffusible. The remainder was apparently protein bound, although the 
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specific serum proteins to which strontium binds have not been characterized. The strontium 

concentrations used in these studies were 300 to 1,000 times higher than those in the general 

population dietary studies performed by Olehy et al. (1966) and Skoryna (1981). Since 

strontium plasma binding is believed to be saturable, the lower concentrations measured in the 

dietary studies may have resulted in a larger bound fraction of serum strontium (Berg et al., 

1973; Alda and Escanero, 1985).

Greater than 95% of the total human body burden of absorbed strontium accumulates in 

the skeleton (Comar et al., 1957; Sowden and Stitch, 1957; Tipton and Cook, 1963; Schroeder et 

al., 1972; Underwood, 1977; Skoryna, 1981; Rosenthal, 1981). The remaining < 5% of absorbed 

strontium is found in most of the body’s soft tissues (Skoryna, 1981; Rosenthal, 1981). Data 

suggest that strontium uptake and distribution are influenced by dietary calcium. Based on the 

results of an unpublished study, Storey (1961) reported that serum strontium levels increased in 

rats without corresponding changes in the serum level of calcium following 200-300 mg/day

doses of strontium carbonate over a 20 day period. No information was given on the level of 

calcium intake in these subjects. 

Analysis of bone samples from human autopsies provides information on the skeletal 

burden of stable strontium (Herring and Keefer, 1971; O’Connor et al., 1980; Papworth and 

Vennart, 1984; Tanaka et al., 1981). For example, Tanaka et al. (1981) reported skeletal burdens 

of 440 mg strontium and 850 g calcium in Japanese adult males. To determine the amount of 

strontium taken up into the skeleton following customary dietary intakes, Papworth and Vennart 

(1984) analyzed published data on 90Sr and calcium concentrations in human bone tissues and 

diets of people in the United Kingdom during the period from 1955 to 1970. They concluded 

that approximately 5% of the dietary intake was distributed to the adult skeleton and 10% was 

distributed to the infant/adolescent skeleton. The greater skeletal uptake of strontium in infants 

and during adolescence is likely attributable to the higher bone growth rates during childhood. 

Papworth and Vennart (1984) studied uptake and turnover of 90Sr in bone in response to 

concerns about human health following dietary exposure to 90Sr (~29 year half-life) as a result of 

nuclear weapons testing in the 1950s. The data gathered and modeled suggests that uptake and 

turnover of strontium in bone appears to be a function of age-related bone growth and 

remodeling. In adults, approximately 4% of dietary intake of 90Sr reached the skeleton, with 

about 7% and 28% of the 90Sr burden lost each year from cortical and trabecular bone, 

respectively. Uptake and turnover varied with age in children and adolescents (See Table 6-2). 

Assuming an intake of 1 g of calcium per day at all ages, infants had the highest bone uptake of 

90Sr at 10% (reported as picocuries of 90Sr per gram calcium). Uptake then fell to about 5% by 

age 5, remained constant until age 10, after which uptake began to increase. Strontium uptake 

increased to 10% until age 15 after which it fell to and remained at about 5% throughout 

adulthood. In terms of 90Sr turnover, the low rate in newborns rapidly rose to a yearly maximum 

of approximately 38% in 4- to 5-year-old children, after which the rate of turnover rapidly

decreased to almost zero by age 10 and then steadily increased to 12% by age 15, remaining 

constant throughout adulthood. 
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Table 6-2 Summary of uptake and turnover of 90Sr in bones of children and adolescents

Age Range (in years) Rate of 90Sr uptake (%) Rate of 90Sr Turnover (%)

0-4  10 to 5 ↑ 0 to 38

5-10 5  38 to 0

11-15 ↑ 5 to 10 ↑ 0 to 12

16-adult 5 12

Source: Papworth and Vennart (1984)

*When an increase (↑) or decrease () is specified, it occurs from the lowest age to the highest age in the specified 

range.

Distribution of strontium in the bone is relatively uniform, where it replaces the calcium 

moiety of hydroxyapatite. The concentration ratio of strontium to calcium (Sr:Ca) in bone has 

been reported to increase from 0.3 mg Sr/g Ca at birth to 0.5 mg Sr/g Ca in adults (Papworth and 

Vennart, 1984; Tanaka et al., 1981). It has also been shown that Sr:Ca ratios differ by bone type, 

with 10-20% higher ratios in the cortical bone than the trabecular bone (Tanaka et al., 1981).

Strontium has been shown to transfer to the fetus during pregnancy and to neonates 

during breastfeeding (Harrison et al., 1965; Underwood, 1977; Rossipal et al., 2000; Tolstykh et 

al., 1998, 2001). A study of bone ash from human fetuses and adults reported approximately 160 

and 240 ppm strontium, respectively (Underwood, 1977). A study of people living near the 

Techa River who were exposed to 90Sr following releases from a plutonium production plant 

reported 90Sr fetal:maternal transfer coefficient of 0.012 to 0.24 becquerels per gram of calcium 

(Tolstykh et al., 1998, 2001). In cases where exposure occurred prior to pregnancy the 

variability in this transfer coefficient was not related to the maternal strontium burden at 

pregnancy. Overall, the 90Sr fetal:maternal ratios on the high end of the range correlated with 

maternal exposure during adulthood, while those on the lower end correlated with maternal 

exposures during childhood or adolescence. 

During breastfeeding, an average concentration of 74 μg/L (this is higher than reported 

for cow’s milk; see Chapter 5) with a Sr:Ca ratio of 0.24 μg strontium/mg Ca was found in breast 

milk (Harrison et al., 1965). The strontium concentration in colostrum was reported to be similar 

to that of serum blood taken 20 minutes before delivery, while in the same women calcium in 

colostrum was significantly increased over serum blood (Rossipal et al., 2000). Based on these 

findings the authors concluded that the transfer of strontium was based upon a concentration 

gradient, while calcium transfer occurred by active transport. 

Animals

Animal studies of distribution following oral exposure provide information about serum 

blood binding, distribution in soft tissues, and maternal transfer of strontium. Guinea pigs and 

rabbits are reported to have similar values of strontium bound to proteins in the blood plasma 

(40%) or serum (60%) (Lloyd, 1968; Twardock et al., 1971). Rats exposed to 3.4 mg SrCl2 in 

drinking water had a serum concentration of 8.7 mg/L strontium (Skoryna, 1981). The 

tissue:serum strontium concentration ratios were ≤ 1.3 for liver, heart, muscle, adrenal, and 

brain, whereas for bone it was > 1000. The strontium:calcium ratio ranged from 0.05 to 0.1 in all 
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of the tissues. Rats exposed to 1.9 mg Sr/L in the same study had 5-fold higher strontium in the 

mitochondrial, lysosomal and microsomal fractions of liver than in the cytosol.

A study by Kshirsagar (1977) reported that a major fraction of the strontium in 

noncalcified tissues, possibly as much as 50-80%, appears to be bound to protein, thus making 

this portion of strontium unable to pass through biologic membranes and be further distributed 

through the body. 

Similarly to humans, studies in animals report the transfer of strontium through the 

placenta to the fetus, causing the fetus to accumulate strontium as the fetal skeleton develops 

(Olsen and Jonsen, 1979). 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. A skeletal:soft 

tissue strontium concentration ratio was approximately 40 in mouse fetuses and dams (Jacobsen 

et al., 1978).

As in humans, data from animal studies support the likely transfer of strontium from 

breast milk to newborns during lactation (Hopkins, 1967; Jacobsen et al., 1978; Kostial et al., 

1969; Rönnbäck et al., 1968). In lactating rats that received an oral exposure to 0.3 microcuries 

of 85Sr per 10 mL drinking water during the 14th through 16th days of lactation (Kostial et al., 

1969), approximately 5% of the ingested dose was recovered in the nursing pups 24 hours after 

the end of the 2-day exposure. The tracer 85Sr recovery rates in the pups following lactation are 

consistent with the data from the dams, if one assumes that approximately 25% of the oral dose 

was absorbed by the dam.

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. 

Distribution of strontium following inhalation exposure of experimental animals has been 

reported to occur in a similar fashion to that absorbed after ingestion (Willard and Snyder, 1966; 

Fission Product Inhalation Project, 1967a,b). 

Dermal Exposure

Ilyin et al. (1975) tracked distribution using dermally applied 85SrCl2 on the left forearm 

as compared to external counting of 85Sr of the untreated areas. At 3 and 6 hours after exposure 

85Sr was detected at the patella and the right forearm; therefore it was concluded that the 

absorbed strontium had been taken up by bone. No other studies were located regarding dermal 

exposure to strontium; however, it is probable that distribution would be similar to strontium 

absorbed via the oral route (i.e., most of the body burden in the skeleton). 
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Other Routes of Exposure

In human subjects following the intravenous administration of strontium gluconate, the 

rapidly miscible pool of stable strontium was equivalent to 42.7 ± 1.1 L of serum. Daily 

turnover rate was 13.5 ±0.6 L (30.9%); of this, 3.9 ±0.2 L was excreted by the kidneys, and the 

equivalent of 9.6 ±0.4 L of serum was deposited in bone (Eisenberg and Gordan, 1961).

An exchangeable pool of approximately 64 L of serum for stable strontium was estimated 

in male volunteers following intravenous infusion of 5 mmol strontium gluconate over 1 hour 

(Moraes et al., 1991). The renal clearance of strontium was determined to be 57.5% of the total 

clearance. 

6.3 Metabolism

Because strontium is a divalent metal, its ions do not undergo metabolic conversion. 

However, strontium does undergo interactions with cellular components, such as protein. 

Because of similar chemical and physical characteristics, many of the kinetic studies of 

strontium have been conducted in conjunction with calcium. It has been suggested that 

strontium and calcium share similar involvement in several biological processes (Sips et al. 

1994). Strontium has been shown to mimic the actions of calcium in in vitro experiments of (1) 

insulin secretion, (2) contractions of the coronary artery and (3) parathyroid hormone regulation; 

the response in these studies is reported to be weaker than that caused by calcium (Hellman et 

al., 1997; Pors Nielsen, 2004; Ohashi et al., 1995). In addition to the observed functional 

mimicry, it is likely that strontium binds to carboxylic acids (e.g., citrate and lactate), based on 

the chemical similarity to calcium. 

6.3.1 Metabolic Rate Constants

Kinetic data on strontium interactions with proteins or tissues were not identified.

6.4 Excretion 

Urinary excretion is the major route of elimination for absorbed strontium (Harrison et 

al., 1955; Spencer et al., 1956; Eisenberg and Gordan, 1961; Comar and Wasserman, 1964). A 

urinary:feces excretion ratio of 3:1 has been reported in humans following several routes of 

exposure (oral, inhalation and intravenous) (Petkau and Pleskach, 1972; Wenger and Soucas, 

1975). Fecal strontium reflects both unabsorbed strontium plus any absorbed strontium lost with 

gastrointestinal secretions. 
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Oral Exposure

Humans

Elimination of ingested strontium primarily occurs through urine and feces. Strontium 

appears to have both a long-term and a short-term elimination half-life (Müller et al., 1966; 

Uchiyama et al., 1973; Likhtarev et al., 1975; Tolstykh et al., 1997). Short-term losses after 

exposure reflect soft-tissue elimination as well as elimination from a more rapidly exchangeable 

pool of strontium in bone. Long-term elimination half-times reflect primarily the storage and 

release of stable strontium in bone. There is evidence for tubular resorption during renal 

excretion (Leeuwenkamp et al., 1990). 

Long-term whole body elimination half-times of strontium (estimated at 28 years in 

males and 16 years in females) have been determined in people exposed to a release of 

plutonium fission products for decades in the Techa River area of Russia (Tolstykh et al., 1997). 

The longer elimination half-time in the males is attributed to increased bone resorption in 

females over the age of 50, which was likely after menopause. In a study of radium dial painters, 

a similar long-term elimination half-life of 25 years was reported (Muller et al., 1966). In studies 

using 85Sr tracer or SrCl2 doses with time periods of 13-108 days after exposure, whole body

elimination half-lives ranged from 2 to 91 days, reflecting the faster initial elimination phase 

(Uchiyama et al., 1973; Likhtarev et al., 1975). 

Warren and Spencer (1976) found that patients on a low calcium diet given a daily dose 

of 600 mg strontium gluconate transiently retained about half of the strontium dose, and urinary 

calcium excretion increased. Once the treatment was stopped, strontium was excreted via urine 

and feces within 6 days. 

A urinary: fecal strontium excretion ratio of 3 was reported in radium dial painters 

(Wenger and Soucas, 1975); this observation is consistent with ratios observed following 

intravenous injections of SrCl2 (ATSDR, 2004). Other studies reported urinary excretion of 

strontium to be approximately 0.25 mg/day (18% of the daily dietary intake) (Harrison et al., 

1955; Comar and Wasserman, 1964) and renal plasma clearance of strontium to be 9.7 L/day in 

adults and 4.0 L/day in children (Sutton et al., 1971b). In other studies, only 4% of the oral dose 

was found in urine (Spencer et al., 1960; Bronner et al., 1963).

Urinary excretion of ingested or parenterally administered strontium in humans was 

maximal on the day of administration and was directly proportional to the plasma concentration 

at levels up to 100-fold the naturally occurring levels (Spencer et al., 1956; Harrison et al., 1955; 

Eisenberg and Gordan, 1961). No information was available about the administered dose. 

Harrison et al. (1955) reported excretion of strontium was mainly in the feces following oral 

administration, reflecting unabsorbed strontium. Overall, these studies support the conclusion 

that urine is likely the major route of excretion for absorbed strontium.
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Animals

No data were identified on excretion in laboratory animals after oral exposures. 

Inhalation Exposure

Human

Studies following accidental exposures to radioactive strontium (90SrCl2, inspired

quantity not known) found that strontium absorbed after deposition in the respiratory tract is 

excreted in feces and urine, with a urinary:fecal excretion ratio of 3:1 over 800 days (Petkau and 

Pleskach, 1972). This ratio is similar to the ratios reported following oral (Wenger and Soucas, 

1975) and intravenous (ATSDR, 2004) exposures. Humans accidentally exposed to airborne 

radioactive strontium had a lower urinary: fecal ratio (<1-1.4) after shorter observation periods 

(24 days) (Rundo and Williams, 1961). This lower ratio may reflect the fecal excretion of 

strontium that is cleared from the lungs via the mucociliary escalator, but not absorbed from the 

gastrointestinal tract 

Because human data for excretion of strontium following inhalation exposure is limited 

to case reports of measuring 90Sr in the urine and feces after an accidental exposure to 

aerosolized 90SrCl2, it is not conclusively known how Sr gets from the lungs to feces in humans. 

However, as noted, mechanical clearance via the mucociliary escalator is likely to play some 

role. 

Animal

A whole body elimination study was performed in dogs following inhalation exposures to 

85SrCl2 (Fission Product Inhalation Project, 1967a). Three phases of elimination were reported, 

with elimination half-lives of 0.6 (59%), 9 (12%) and 300 days (29%). While the slower 

elimination time reflects skeletal elimination of strontium, the rapid early phase (0.6 day) reflects 

mechanical clearance of strontium in the tracheobronchial region, which is then transferred to the 

gastrointestinal tract and feces. 

In rats and dogs, urinary: fecal excretion ratios are time-dependent following inhalation 

strontium exposure (Fission Product Inhalation Project, 1967a,b). In dogs, a large fecal 

component of excretion during the initial 22 minute observation period after 85SrCl2 exposure 

was followed later by lower fecal excretion and higher urinary: fecal ratios of <1-1.4 (Fission 

Product Inhalation Project, 1967a). In rats, the urinary: fecal excretion ratios increased over time 

from <1 to 2-4 after intratracheal instillation of SrCl2 (Fission Product Inhalation Project, 1967b; 

Naményi et al., 1986). 

Dermal Exposure

Ilyin et al. (1975) reported strontium urinary excretion in volunteers exposed to 85SrCl2 

via dermal application to their left forearm. Fecal excretion was not measured in this study.
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Other Exposure Routes

Following intravenous injection in humans, 60% of the dose was found in the urine after 

14 to 50 days (McCance and Widdowson, 1939; Harrison et al., 1955; Spencer et al., 1960; 

Bronner et al., 1963; Warren and Spencer, 1976), while 12 to 13% of the dose was eliminated in 

the feces (Bronner et al., 1963; Spencer et al., 1960). No information was available about the 

administered dose.

6.5 Pharmacokinetic Considerations

ICRP (1993) developed a compartmental model of the kinetics of alkaline earth elements, 

including strontium that is applicable to humans of all ages for inhalation, gastrointestinal, or 

injection exposures to radioactive strontium (89Sr and 90Sr). This model has been used by ICRP 

(1994a, b) and U.S. EPA (2000d) to calculate inhalation, food and water risk coefficients for 

several strontium radionuclides (i.e., Sr 80, 81, 82, 83, 85, 85m, 87m, 89, 90, 91, 92). 

Overall, the model assumes that 99% of the absorbed strontium is transferred to the 

bones, and the remaining 1% enters the soft tissues. The model assumes that the fractional 

absorption of ingested strontium decreases from 0.6 in infants to 0.3 in adulthood. Absorbed 

strontium in the plasma is described as distributing to the bones, liver and other tissues. 

Excretion is modeled as going from plasma to urine, plasma to feces, and liver to feces.

No other PBPK models for strontium were located.

6.6 Summary

Strontium is toxicokinetically similar to calcium. In humans, it is moderately absorbed 

(20%) after ingestion but poorly absorbed (<1%) through intact skin. Dietary strontium is more 

readily absorbed when present as a soluble compound (e.g., SrCl2) and in individuals with low 

intakes of dietary calcium. A substantial amount of absorbed strontium is deposited in the tissue. 

The vast majority (>95%) of the retained strontium is distributed to the bone and excretion of 

absorbed strontium occurs primarily via the urine. Strontium has been shown to transfer to the 

fetus during pregnancy and neonates during lactation (Harrison et al., 1965; Underwood, 1977; 

Olsen and Jonsen, 1979; Tolstykh et al., 1998, 2001; Rossipal et al., 2000). Urinary excretion is 

the major route of elimination for absorbed strontium (Harrison et al., 1955; Spencer et al., 1956; 

Eisenberg and Gordan, 1961; Comar and Wasserman, 1964). 

Strontium has been shown to have generally similar absorption, distribution, and 

excretion in humans and rodents following ingestion, with some differences. For example, a 

substantial age-related difference in absorption of strontium has been observed in rats (Forbes 

and Reina, 1972), but no such differences have been seen in humans (Harrison et al., 1965; Kahn 

et al., 1969). 
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7.0 HAZARD IDENTIFICATION 

7.1 Overview of Bone Physiology and Development 

Because an understanding of bone physiology and development is key to understanding 

the effects of strontium, this section begins with a brief review of the topic. As described by 

several reviews of bone physiology and development (Cabrera et al., 1999; Javaid and Cooper, 

2002; Clarke et al., 2008; Cooper et al., 2008), bone tissue is composed of collagen fibers, 

noncollagenous proteins, and deposited minerals (50 to 70%), primarily hydroxyapatite. Crystals 

of hydroxyapatite (a complex calcium salt with phosphate and hydroxide ions) are located in and 

on the collagen fibers and in the ground substance (contains glycoproteins and proteoglycans 

such as elastin) of bone. There are four general categories of bones: long, short, flat and 

irregular. This discussion focuses upon long bone growth and development. 

Long bones can be divided into cortical and trabecular bone tissue, with the different 

types predominating in different portions of the bone. Long bones are comprised of a hollow 

shaft (diaphysis), a flared region (metaphyses) and two rounded heads (epiphyses) (see Figure 7-

1). The diaphysis is mostly dense compact (cortical) bone tissue, while the other portions of the 

long bone are spongy cancellous (trabecular) bone tissue with a shell of cortical bone tissue. 

Cortical bone comprises approximately 80% of the total skeletal mass and has a slow rate of 

turnover and high resistance to bending and torsion. Trabecular bone comprises the remaining 

20% of the total skeletal mass, but makes up 80% of the total bone surface area, as it forms the 

interior scaffolding. The primary functional unit of both cortical and trabecular bone tissue is the 

osteon. Cortical osteons (Haversian systems) are made of concentric layers of mineralized bone 

matrix, called concentric lamellae. The concentric lamellae form around the Haversian canal 

containing a blood and nerve supply. Trabecular osteons (packets) also form concentric 

lamellae, but are arranged in a pattern such that the bone tissue appears spongy but is rigid, and 

this is integral in bones maintaining their shape. 

Most of the fetal skeleton is made of cartilage, which is composed ground substance and 

chondrocytes (which produce collagen and maintain the cartilaginous matrix). There are three 

types of cartilage, elastic cartilage, hyaline cartilage and fibrocartilage, which differ in the 

relative amount of chondrocytes and ground substance. For the purposes of this discussion, only

hyaline cartilage will be discussed. Longitudinal bone growth begins just after birth and 

continues until closure of the epiphyses during adolescence. Elongation of the long bones occurs 

in a region made of hyaline cartilage between the diaphysis and the epiphysis at either end; this 

region is called the epiphyseal plate. The chondrocytes in the epiphyseal plates produce new 

cartilage cells, which form a template as they migrate towards the diaphysis. Osteoblasts then 

move into these areas and begin the process of bone remodeling over this cartilage template. 

Throughout life, longitudinal and radial bone growth, modeling and remodeling occurs. 

Longitudinal bone growth ends following puberty, with the closure of the epiphyseal plates. 

Bone modeling occurs throughout life and involves the change of the shape of bones in response 

to biomechanical stress (i.e., weight bearing movements). In adults, bone modeling is usually

less frequent than bone remodeling. Following puberty, continued increase in bone density is 
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linked to bone modeling (due to weight bearing stressors). Bone mineral density increases until 

it reaches a peak level at about 30 years of age (Wood, 2000). The process of bone remodeling 

enables bone strength and mineral homeostasis to be maintained by renewal of old or damaged 

bone. 

Several cell types are involved in bone remodeling and communication. Osteoblasts are 

responsible for bone formation and osteoclasts for the degradation of bone tissue during 

remodeling. Osteocytes maintain intercellular communication in stable sections of bone 

(Saladin, 2003). In early life, activity of the osteoblasts is greater than that for the osteoclasts 

(consistent with bone growth predominating). In healthy young adults, the amount of new bone 

formation is balanced with the amount of bone destruction (resorption); however with increasing 

age bone resorption is more favored. The rate of remodeling varies greatly among specific 

bones, with the lumbar vertebral bone turning over most rapidly (Wood, 2000). It is estimated 

that the adult skeleton completely regenerates every 10 years through this process (Manolagas, 

2000). The entire bone calcium pool turns over on average every 5 to 6 years. 

Bone remodeling occurs at localized sites in both cortical and trabecular bone via four 

sequential steps: activation, resorption, reversal and formation. During activation, cytokines and 

growth factors (IGF-1; hormones: thyroid, androgens) act on preosteoclasts, stimulating them, 

and causing them to differentiate and mature into active osteoclasts. During resorption, the 

osteoclasts digest the old mineral matrix as regulated by receptor activator of NF-κB ligand 

(RANKL), osteoprotegerin, interleukins, parathyroid hormone, vitamin D and calcitonin (Clarke, 

2008). In the reversal step, the remodeling process shifts from bone resorption to bone formation 

and preosteoblasts begin infiltrating to the site in preparation for the final phase of remodeling. 

Serum vitamin D levels are involved in the differentiation of osteoblasts and stimulate the 

osteoblast to express bone-specific proteins associated with mineralization. Finally, during the 

formation step, osteoblasts synthesize new cartilage-based organic bone matrix and regulate the 

incorporation of minerals such as calcium and phosphorus into the matrix. Bone matrix 

mineralization is associated with calcium and phosphate binding proteins (i.e., alkaline 

phosphatase, osteocalcin, oestopontin and sialoprotein), which are believed to regulate 

deposition through controlling the formation (size and quantity) of hydroxyapatite crystals 

(Clarke, 2008). Serum vitamin D levels are also involved in bone matrix mineralization by 

stimulating intestinal absorption of calcium and phosphorus, which results in adequate serum 

levels of calcium and phosphorus for passive mineralization of unmineralized (or newly formed) 

bone matrix.

Several pathophysiological conditions exist for the bone, such as osteomalacia, 

osteopenia and osteoporosis, which are described in more detail in the following text. 

Osteomalacia occurs when the incorporation of minerals into the bone matrix is disrupted, 

leading to accumulation of unmineralized bone matrix as the osteoblasts continue to secrete 

osteoid. Due to the decreased mineral content of the bone matrix, the bone is soft. Structurally

(i.e., on a radiograph), osteomalacia can be observed as trabeculae with a washed-out appearance 

due to decreased bone mineral density and content. A similar defect in the mineralization of 

cartilage in growth plates is observed clinically as “rickets”. Structurally, this can be observed as 

an irregular border between growth cartilage and the bony metaphysis, and increased width of 
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the epiphyseal plate. These two conditions (osteomalacia and rickets) often coexist while 

epiphyseal plates are open prior to the end of puberty. These conditions are biochemically 

identified by an increase in serum levels of alkaline phosphatase and are generally linked with a 

deficient supply or uptake of mineral (calcium or phosphorus). 

Osteopenia is a decreased amount of bone tissue caused by either insufficient deposition, 

decreased bone synthesis or increased resorption of the osteoid. It differs from osteomalacia and 

rickets in that the incorporation of calcium and phosphate into both osteoid and cartilage of the 

growth plate are unaffected. However, bone mineral density and content are decreased as they

are in osteomalacia. Structurally it is observed as a decreased thickness of the bone cortex and/ 

or thickness and number of trabeculae. This condition is usually linked with severe systemic 

disease, drug side effect (i.e., corticosteroids), or lack of mechanical stimulation known 

commonly as “disuse osteoporosis”. Thus, this condition can be caused by a signal that more 

bone formation is unnecessary. 

Osteoporosis is diagnosed when bone mineral density is below -2.5 standard deviations 

from the mean of young healthy adults (Rauch and Schoenau, 2001). Bone mineral 

(hydroxyapatite) provides rigidity and load bearing strength to bone. Thus, bone mineral density 

is linked with bone strength. Adequate bone calcification at maturity is a protective factor for 

bone health later in life (Javaid and Cooper, 2002; Cooper et al., 2008). As discussed earlier, 

there is a shift towards more bone resorption via increased osteoclast activity with increasing

age; thus, high bone turnover with more resorption than formation leads to microarchitectural 

deterioration and reduced bone strength. However, in some cases the development of 

osteoporosis is due to abnormal bone matrix (Clarke, 2008). 

Figure 7-1 Bone anatomy and growth

(a)
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(b)

(c)

Source: http://training.seer.cancer.gov/anatomy/skeletal/tissue.html

The figures show compact (dense) and trabecular (cancellous) bone anatomy (a), anatomy of the long bone (b), and 

bone growth (c). 

7.2 Human Effects

The database on short-term effects of strontium is limited to an oral metabolic balance 

study of approximately one month that did not include detailed evaluation of bone, a case report 

of inhalation exposure to strontium and other compounds, and a study on dermal exposure to 

strontium reducing sensory irritation. Long-term studies include studies of general population 

exposures to strontium through drinking water or soil (and food grown on that soil), 
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occupationally-exposed workers, and patients administered “low dose” strontium for bone 

disorders.

7.2.1 Short-Term Studies and Case Reports 

One oral short-term study was located for strontium, but it was not designed to evaluate 

systemic toxicity or bone effects. Also, a case report documenting health effects in humans 

following an acute inhalation exposure to strontium was identified. Finally, some data are 

available on the response to single dermal applications. 

Intentional and Accidental Acute Ingestion

No studies were identified regarding the intentional or accidental acute ingestion of 

strontium.

Acute and Short-Term Oral Exposure

A study by Warren and Spencer (1976) found no adverse effects following oral 

administration of 1537 mg per day as strontium lactate (corresponding to 507 mg Sr per day, or 

about 7.2 mg Sr/kg-day, assuming a body weight of 70 kg) for 24-36 days as part of a metabolic 

balance study; this study was not designed to evaluate toxicity and did not include detailed 

evaluation of the bone.

Acute and Short-Term Inhalation Exposure

Federman and Sachter (1997) reported a sudden anaphylactic reaction in a 35-year-old 

female paramedic following the inhalation of fumes from a flare that contained about 75% 

strontium nitrate, 10% potassium perchlorate, 10% sulfur and 10% sawdust/oil binder. The 

initial symptoms included coughing, wheezing, severe tachycardia and shortness of breath, and 

could not be controlled by administration of albuterol, epinephrine or steroids. The paramedic 

recovered completely after sedation, intubation and several days of intensive care. The role of 

strontium in the anaphylactic response in this report is uncertain. Each component of the flare 

could yield products that would be irritating to the respiratory tract during combustion. 

Acute and Short-Term Dermal Exposure

Two studies involving dermal application of strontium compounds to humans were 

located (Zhai et al., 2000a,b). However, the endpoint for these studies was not toxicity, but 

rather a beneficial suppression of sensory irritation. Therefore, the studies are discussed briefly 

in Section 7.3.3.
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7.2.2 Long-Term and Epidemiological Studies 

Epidemiological Studies

Several studies examined the relationship between strontium exposure in the environment 

or the body burden of strontium (as a measure of internal dose) and development of disease 

following either occupational or environmental exposures. These studies are limited 

quantitatively because they may not have adequately controlled for other factors potentially 

contributing to the endpoint being evaluated. 

The relationship between strontium levels in workers hair and myocardial infarction was 

examined by Zerbino and Solomenchuk (2007). In this study, strontium content of hair in 

myocardial infarction patients was compared with that of healthy individuals, all of whom 

worked in occupations associated with “xenobiotic” exposures (presumably industrial 

chemicals). The hair of the myocardial infarction patients all contained high amounts of various 

metals, including strontium. Two-thirds of the patients had strontium and potassium levels 

considerably exceeding levels that were described as “maximally allowable values”. 

Özgür et al. (1996) evaluated whether the prevalence of childhood rickets in the Ulaş 

Health Region of Sivas, Turkey was related to high soil levels of strontium. The prevalence of 

clinical signs of rickets among 2,140 children ages 6 months to 5 years in this area was 32%, 

based on craniotabs, rachitic rib cage rosary, bulging at the wrist, delayed closure of the 

fontanels, and/or deformities of the legs compared with a national prevalence of 4.4%. The 

regional diet was largely based on locally-grown grains. The children were divided into two 

groups based on soil strontium (>350 mg/kg Sr and <350 mg/kg Sr). There was a greater 

proportion of signs and severity of rickets in the group with high soil strontium (31.5%) versus 

the group with lower soil strontium (19.5%); the differences were statistically significant 

(p<0.001). Factors including age, duration of breastfeeding, height and weight of the children 

had a significant effect on the odds ratio for developing rickets for most of the age groups 

evaluated. Heights were less than the population third centile for 38.6 % of the children in the 

high soil strontium area compared to 24.85% of children in the lower-soil strontium region

(p<0.01). This study is consistent with the observations from animals that elevated strontium 

exposures during bone growth can lead to altered bone structure.

Several studies evaluated the impact of elevated strontium exposure in drinking water on 

targets besides bone, resulting from strontium substituting for calcium. Dawson et al. (1978) 

evaluated families (subjects aged 5-97 years) who had resided for at least 10 years within low 

socioeconomic Texas communities. The authors reported that there was no correlation between 

strontium concentration (0.4 to 37.8 mg/L) in the drinking water and mortality from 

arteriosclerotic and degenerative heart disease, or other vascular/heart diseases. 

Studies conducted by Longerich et al. (1991) and St. Leger et al. (1980) in Canada (56 

participants) and the UK (80 participants), respectively, explored the correlation of strontium 

levels in tap water with the development of infant neural tube defects. In both studies, the mean 

concentration of strontium was not significantly lower in the tap water of mothers who gave birth 
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to normal infants versus those with neural tube defects. St. Leger et al. (1980) compared 

strontium levels in the drinking water of 36 women in Cardiff, UK who gave birth to an infant 

with a neural tube defect (mean 0.09 mg/L; range 0.02-0.13 mg/L) and 44 matched women 

whose babies had no such defects (mean 0.08 mg/L; range 0.03-0.15 mg/L). Longerich et al. 

(1991) reported slightly, but not significantly, higher strontium levels in the tap water of 28 

mothers in Newfoundland, Canada, who gave birth to babies with neural tube defects. A similar 

pattern was observed for 12 of the 13 elements evaluated; thus the data are inadequate to 

implicate any single metal or combination of metals. 

Curzon and Spector (1977) studied 1,313 children aged 12-14 years living in Wisconsin 

and found that lifelong residents, but not immigrants, experienced increased tooth enamel 

mottling as the average drinking water concentration increased from 0.02 to 34 mg Sr/L. 

Another study by the same group investigated the prevalence of dental caries in Ohio using 539 

children of the same age range, and found that caries decreased as the average drinking water 

concentration increased from 0.2 to 15.3 mg Sr/L (Curzon, 1981). Though fluoride exposure can 

cause increased tooth enamel mottling (fluorosis) and decreases in dental caries, in both studies, 

these effects were found to have no association with fluoride concentration.

Cancer Studies

Wang et al. (1990) performed a study of the relationship between strontium exposure (as 

measured by the strontium concentration in hair) and the incidence of liver cancer mortality in 

communities on Chongming Island, China with high (41-58 per 100,000) versus low (17-18 per 

100,000) liver cancer mortality incidence. There was no correlation between mean strontium 

concentration in hair and the liver cancer mortality. A case-control analysis of liver cancer 

included in this study found similar mean strontium hair concentrations in cases and controls (3.0 

vs. 3.7 mg/kg in hair, respectively). 

An increase in lung cancer mortality was reported in workers in British chromate pigment 

manufacturing plants between the years of 1950 to 1976 (Davies, 1979; 1984). For workers 

exposed to high and medium levels of chromates before industrial hygiene improvements were 

introduced in 1961, the observed/expected ratio (O/E) was 6/1.61, with a standardized mortality

ratio (SMR) of 373 (p < 0.01) for lung cancer deaths. While strontium chromate was implicated 

as a factor for the observed increase in these workers, the carcinogenicity of strontium chromate 

is attributed to ions in which chromium is present in the 6+ oxidation state and requires 

transformation to become a genotoxic agent (ATSDR, 2004). 

Long-term Clinical Studies

Administration of “low doses” of strontium (usually as the lactate, gluconate, carbonate 

or ranelate) over several years has been used to treat patients with disorders of bone 

mineralization, such as osteoporosis (ATSDR, 2004). The term “low dose” was not further 

defined by ATSDR, but clearly includes doses up to at least 24 mg Sr/kg-day, based on the 

available data. Although strontium is not recognized in the U.S. as a standard therapy for 

osteoporosis (Krane, 1977), strontium ranelate is prescribed in Europe for treatment of 
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osteoporosis. Strontium ranelate (CAS RN 13549-90-4) is the strontium salt of ranelic acid, 

which has the following chemical formula [C12H6N2O8S] 4-2Sr2+. Because calcium and vitamin 

D also play key roles in bone formation, these supplements are often are co-administered with 

strontium, meaning that the doses in these studies cannot be used to identify nontoxic doses of 

strontium, even for adults. Studies have been conducted in post-menopausal women with signs 

of osteoporosis using exposures ranging from 3-4 mg Sr/kg-day (as either strontium lactate or 

chloride) for at least 3 months to 24 mg Sr/kg-day for 0.25-3 years (McCaslin and James, 1959; 

Skoryna, 1981; Skoryna and Fuskova, 1981). 

7.3 Animal Studies

Strontium has low acute oral toxicity, with an LD50 above 2,000 mg/kg (Llobet et al., 

1991; Ghosh et al., 1990; Woodard and Calvery, 1941). Strontium can substitute for calcium, 

and studies in rats and mice show that the bone is the primary target of strontium exposure. 

Short-term and subchronic studies in rats indicate that ingestion of strontium results in more 

severe skeletal effects in young animals than in adults (Storey, 1961, 1962), although direct 

comparison is difficult, due to the higher feed intake of young animals per unit body weight. 

Limited data on reproductive and developmental toxicity (Kroes et al., 1977; Skoryna, 1981; 

Skoryna and Fuskova, 1981; NIER, 2006c; Shibata and Yamashita, 2001) indicate that strontium 

does not cause structural or functional reproductive effects at doses well above those causing 

bone effects, and that bone development is the key developmental endpoint of concern. Because 

bone growth and development is affected by levels of multiple nutrients, including levels of 

calcium, phosphorous and vitamin D, these levels are reported when provided by the study

authors. Many suppliers list the normal level of (calcium), (phosphorus) and (vitamin D) for rat 

chow. For example, the “laboratory rodent diet 5001,” a common laboratory rodent diet from 

PMI Feeds Inc., is listed as containing 0.95% calcium, 0.66% phosphorous, and providing 4.5 

IU/g of vitamin D3 (www.labdiet.com).

For most studies, there is some uncertainty in the actual doses of strontium, since 

reporting was in terms of concentration in food or water, rather than strontium intake. In those 

cases, strontium intake was estimated using as much study-specific information as possible and 

feasible, with greater emphasis placed on studies testing multiple doses with effects at lower 

doses. Actual body weights were used when available, and body weights from U.S. EPA (1988) 

were used when the study authors did not provide a needed body weight. When possible, body

weight was estimated as the average of the initial and final body weight. If strontium intake was 

not reported, food intake was estimated using the allometric equation from U.S. EPA (1988)5. 

An exception to this approach was the study of Marie et al. (1985), for which the study authors 

estimated strontium intake based on body weight and water consumption. 

A summary table of relevant animal toxicity studies can be found in Appendix A.

 

5

F = 0.056*(BW)0.6611 where F = food consumption in kg/day and BW = body weight in kg.
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7.3.1 Acute Toxicity

Oral Exposure

Oral median lethal doses of strontium have been reported to be between 2.35 and 3.1 g 

Sr/kg in rodents using the nitrate or chloride salts of strontium (Woodard and Calvery, 1941; 

Ghosh et al., 1990; Llobet et al., 1991). However, Zyuzyukin and Makolkina (1979) reported no 

signs of overt toxicity following administration of 14 g Sr/kg (as the carbonate) via stomach tube 

to rats and mice. In light of the low water solubility of strontium carbonate (0.11 g/L, compared 

with 538 g/L for strontium chloride; Merck, 1989), the low toxicity of strontium carbonate may

reflect low bioavailability, particularly at high lethal doses. Administration of 950 mg Sr/kg as 

strontium sulfate (water solubility 0.14 g/L) by gavage to six female rats showed no toxic effects 

or histologic changes (NIER, 2006a). Because all of these doses are above 1,000 mg Sr/kg, they

indicate that acute oral toxicity is low, and further indicate that water solubility is related to the 

lethal dose of strontium compounds.

Inhalation Exposure

No studies were located on the acute inhalation toxicity of strontium to animals. Lack of 

inhalation data is not a concern based on the low volatility of strontium compounds, which are 

solids at room temperature (ATSDR, 2004); therefore, there is little likelihood of exposure via 

volatilization from tap water.

Dermal/Ocular Exposure

The equivalent of a 950 mg Sr/kg (2 g/kg strontium sulfate) was applied for 24 hours 

(covered) to the skin of 10 male and female rats. No overt toxicity or histological changes were 

observed during the 14-day observation period (NIER, 2006b). No LD50 values for the dermal 

route or other data related to eye or skin irritation were identified.

7.3.2 Short-Term Studies

Oral Exposure

No signs of toxicity were seen in monkeys administered 1100 mg Sr/kg-day as strontium 

chloride by capsule for 7 days. However local irritation of the gastrointestinal tract (leading to 

hemorrhage and erosive lesions of the esophagus and upper duodenum) was observed (Fisch et 

al., 2006). Since effects were seen only at the portal-of-entry, the results are consistent with the 

effects being due to the high local concentration resulting from the capsule administration.

No effects on behavior, growth, food intake, liver and kidney weight, liver and kidney

histopathology, or hematology were seen in Wistar rats (3/sex/group) fed diets containing up to 

3,000 ppm strontium chloride hexahydrate for 2 weeks (about 110 mg Sr/kg-day, based on an 

average initial body weight of 0.15 kg and consumption of 0.016 kg food/day, based on an 
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allometric equation6) (Kroes et al., 1977). This was a range-finding study; effects on bone were 

not evaluated. Other doses tested were reported as 0 (control), 0.11, 1.1, and 11 mg Sr/kg-day

(ATSDR, 2004). 

Bone and cartilage are important targets of strontium toxicity, as shown in several shortterm repeated oral dose studies. Storey (1961) investigated the impact of strontium on bone 

structure in groups of young (40-60 g) and adult (200-250 g) female rats (strain not specified) fed 

strontium at 0%, 0.19%, 0.38%, 0.75%, 1% (young rats only), 1.5%, or 3% of the diet as 

strontium carbonate for 20 days. These concentrations correspond to about 0, 190, 380, 750, 

1000, 1500, and 3000 mg Sr/kg-day for young rats (assuming that young rats consume food 

equivalent to 10% of their body weight per day) and 0, 95, 190, 375, 750, and 1500 mg Sr/kgday for adult rats assuming food consumption at 5% of body weight. The dose groups 

apparently contained 10/dose for young rats and 3/dose for adult rats, but the number of young 

rats evaluated ranged from 3 to 10, depending on the endpoint. The diets also contained 1.6% 

calcium and 0.9% phosphorus, which were considered adequate amounts by the study authors 

and are consistent with amounts provided in a normal rat diet (PMI Feeds Inc., Laboratory

Rodent Diet 5001). Young rats were affected more severely and at lower doses than the adults. 

In the young rats, there was no effect at the low dose, but bone structure was altered at 

0.38%. Changes observed at 0.38% and higher included inhibition of calcification, as evidenced 

by increasing width of epiphyseal cartilage (the cartilage plate at the end of long bones7), the 

presence of uncalcified bone matrix and decreased ash weight of bone. Taken together these 

changes suggest early development of osteomalacia and/or strontium “rickets”. Higher dietary

concentrations resulted in more severe effects, including irregularities in the organization of the 

hypertrophic zone cells (distorting the usual parallel arrangement of intercellular matrix 

columns), in the pattern of calcification and in deposition of osteoid, as well as bands of 

uncalcified cartilage matrix isolated between areas of osteoid tissue. These more severe effects 

suggest progression of the osteomalacia-like effects observed at lower strontium concentrations. 

Growth was reduced at 1.5% and above. The calcium level in the diet in this study was severalfold higher than in that in many of the other studies (e.g., compare with 0.5% calcium in Marie et 

al., 1985). This high level of calcium may have provided some protection from the bone effects 

of strontium. 

In the adult rats, the first obvious bone change occurred at the 1.5% dietary strontium 

level (estimated as 750 mg Sr/kg-day by U.S. EPA, 1992) and included histological changes in 

the tibia (slightly wider epiphyseal cartilage plate, increased width of metaphyseal osteoid seams 

[i.e., the seams at the wider portion of the long bone adjacent to the epiphyseal line]). These 

increased widths of the epiphyseal plate and metaphyseal seam together suggest progression 

towards strontium “rickets”. More severe effects observed at a dietary concentration of 3% 

included reduced growth, the deposition of osteoid tissue near vascular canals, a reduction in the 

area of bone resorptions, and reductions in the dry weight, ash weight, ash percentage and 

calcium in ash of bone. Taken together these effects suggest that bone remodeling was disrupted 

 

6 Allometrically-scaled food intake for rats throughout this document was calculated using the equation of U.S. EPA 

(1988), F = 0.056*(BW)0.6611 where F = food consumption in kg/day and BW = body weight in kg.

7

In adults that have stopped growing, the epiphyseal plate is replaced by the epiphyseal line.
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by increased strontium exposure as evidenced by less formation and resorption with decreased 

mineralization. In young rats, the dietary level of 0.19% strontium (estimated as 190 mg Sr/kgday by U.S. EPA, 1992) was a NOAEL and 0.38% strontium (estimated as 380 mg Sr/kg-day) 

was a LOAEL, based on inhibition of calcification. 

For adult rats, the dietary level of 0.75% strontium (estimated as 375 mg Sr/kg-day) was 

a NOAEL and 1.5% strontium (estimated as 750 mg Sr/kg-day) was a LOAEL, based on 

histological changes of the bone. Both effect levels were based on changes in bone structure. 

This study is limited by the small sample size and by the lack of dose reporting as mass per unit 

body weight. The lack of dose reporting is a common weakness in many of the studies of effects 

on bone.

Effects comparable to those observed by Storey (1961) were seen in a study of female 

weanling Wistar rats (6-8/group) (Morohashi et al., 1994). This study tested diets containing 

0%, 0.05%, 0.1%, or 0.5% strontium carbonate (estimated as doses of 0, 50, 100, and 500 mg 

Sr/kg-day), and was designed to distinguish therapeutic and toxic doses of strontium, based on 

the kinetics of bone remodeling (formation and resorption), by studying the effects of strontium 

on calcium balance following injection of radiolabeled calcium. In 36-day-old rats that ingested 

0.1% strontium carbonate in the diet (100 mg Sr/kg-day, based on the authors’ reported Sr intake 

and an average body weight of 0.15 kg) for 27 days, calcium absorption and rates of bone 

formation and resorption were normal. The diet contained 0.5% calcium, 0.35% phosphorus, 

and vitamin D3 (supplementation concentration not specified), which are low concentrations of 

calcium and phosphorus based on a normal rat diet (PMI Feeds Inc., Laboratory Rodent Diet 

5001). Disruption of bone remodeling as evidenced by decreases in bone formation rate (24%), 

serum calcium (13%), bone resorption rate (28%), and a significant reduction in the calcium 

content of ashed femurs were observed at an estimated strontium dose of 500 mg/kg body weight 

per day. 

Higher doses of strontium have been observed to affect bone formation and structure in a 

number of other studies. Bone abnormalities, including large areas of non-mineralized bone 

(osteoid) in epiphyseal bone and secondary spongiosa, abnormally wide epiphyseal plates with 

abnormally long and dense metaphyses, longer primary spongiosa of the proximal tibia, and 

disorganized trabeculae disconnected from the overlying calcified cartilage, were seen in 

“young” (100-125 g) male Sprague-Dawley rats (18/group) ingesting 500 mg Sr/kg-day in diet 

(estimated based on average body weight and the allometric food intake equation of U.S. EPA, 

1988) as strontium carbonate for 3 weeks (Neufeld and Boskey, 1994). Other effects at this dose 

included reduced ash weight (mineral content) of metaphyseal bone, increased complexed acidic 

phospholipid content (lipid nucleator of bone mineral) and lower bone density areas in the 

diaphyses (shafts of the long bones). These effects suggest defects in bone mineralization 

(osteomalacia/ strontium “rickets”). There was no information provided on dietary calcium, 

phosphorus or vitamin D; however the strontium fed rats were found to have normal serum 

calcium levels and there was no evidence of vitamin D deficiency. The investigators suggested 

that strontium binds to the surface of initial hydroxyapatite crystallites, reducing their further 

proliferation and resulting in a smaller crystal size.
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Growth was reduced in male weanling Sprague-Dawley rats (10/group) ingesting 1.6% 

strontium in their diets in an unspecified form (1,520 mg Sr/kg-day, based on estimated average 

body weight and the allometric food intake equation of U.S. EPA, 1988) for 26 days (Svensson 

et al., 1985, 1987). The authors noted that epiphyseal growth plates had abnormally thick 

hypertrophic zones and impaired calcification and resorption at the metaphyseal side, and 

cartilage contained 75% less calcium and had a 60% lower rate of synthesis of 

glycosaminoglycans and collagen, all signs of strontium rickets. Serum concentrations of 

calcium, phosphorus and parathyroid hormone were reported to be normal, but the method used 

to measure the parathyroid hormone could not distinguish between the active and inactive form 

of the hormone. A stereological analysis found no changes in volumes of parathyroid tissue 

components relative to body weight. The study authors concluded that the mechanism of 

strontium rickets did not involve the parathyroid gland.

Similar effects of reduced growth and thickened epiphyseal growth plate were seen in 

weanling (21-day-old) male England Wright Y rats (5/group) ingesting 1,850 mg Sr/kg-day

(form unspecified) for 20 days in a diet sufficient in calcium (1.2%), phosphorus (1%) and 

vitamin D (1500 IU/kg) (Reinholt et al., 1984). Other effects at this dose included larger zones 

in the epiphyseal regions of long bones (as well as smaller proportional volumes of the resting, 

proliferative and calcifying zones, and a larger volume of the hypertrophic zone) and an increase 

in the volume of extracellular matrix in bone, possibly associated with a reduced rate of 

extracellular matrix vesicle degradation. The epiphyseal cartilage of these rats had alterations in 

proteoglycan composition, which the authors (Reinholt et al., 1985) suggested might affect the 

process of mineralization. 

Bone hypomineralization and increased bone mass, compared to controls given the same 

low-calcium diet, were reported in weanling male Sprague-Dawley rats ingesting 0.4% of 

strontium chloride while on a low calcium diet (Grynpas and Marie, 1990) for 4 or 8 weeks. 

This suggests an osteomalacia type of effect during bone remodeling, where bone growth was 

not halted, but softer bones were formed. Rats were divided into groups (5/group/exposure 

duration) receiving 0, 0.19, or 0.40% of strontium chloride in distilled water for 4 or 8 weeks. 

These concentrations correspond to doses of 0, 222, and 466 mg Sr/kg-day during the 4-week 

study, and 0, 146, and 307 mg Sr/kg-day during the 8-week study, assuming ingestion of 0.211 

L/kg-day by a weanling Sprague-Dawley rat and 0.139 L/kg-day by a Sprague-Dawley rat during 

a subchronic study (U.S. EPA, 1988) and based on the average reported body weights for the two 

durations. The diet contained 0.5% calcium, 0.54% phosphorus, 0.16% magnesium, and 2,000 

IU/kg vitamin D. No effect was seen at the low dose of 0.19% strontium chloride in water for 

either study duration. 

Reduced growth and bone mineralization, compared both to controls given 0.67% in the 

diet and to controls fed the same low-calcium (0.04% calcium) diet were observed in 4-week-old 

male Wistar rats (50-60 g, 30/group) given low-calcium (0.04% calcium) diets providing 1970 

mg Sr/kg-day in the form of strontium carbonate for 4 weeks (Matsumoto, 1976). Tibia length 

was decreased by 33% and epiphyseal plate width was increased by 5-fold. Rats treated with 

strontium also had no detectable mineralization in the tibial proximal heads. Thus, rats exposed 

to strontium, when compared to rats on an identical low-calcium diet, developed effects 
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consistent with osteomalacia and strontium rickets.

In a study by Kshirsagar (1976), decreased body weight gain compared to controls was 

observed in male weanling (21-day-old, 5-6 per group) Wistar rats fed for 2 weeks with diets 

containing 2% strontium as strontium phosphate, 5000 IU vitamin D per kg diet, 0.4% calcium 

and 0.4% phosphate (corresponding to a dose of about 3,000 mg Sr/kg-day, based on the 

reported body weight and the allometric equation of U.S. EPA, 1988) (Kshirsagar, 1976). The 

study also reported decreased acid phosphatase in the small intestine and liver; alkaline 

phosphatase was decreased in the small intestine, increased in the bone and unchanged in the 

liver. The changes in enzyme levels were reversed after two weeks on the control diet, which 

contained 0.001% strontium (corresponding to about 1.5 mg Sr/kg-day). The author suggested 

that strontium may have stimulated osteoblasts, which secrete osteoid and have a high alkaline 

phosphatase activity. As mentioned in Section 7.1, osteomalacia and rickets are biochemically

identified by an increase in serum levels of alkaline phosphatase and are often associated with a 

deficient supply or uptake of mineral. 

Administration of strontium carbonate in diet to young (50-70 g) rats of both sexes (strain 

not specified, 12-50 per group) at a dose of 2160 mg Sr/kg-day for up to 7 months resulted in the 

rats developing an altered gait characteristic of rickets (Storey, 1962). A few young rats that 

were more severely affected died following 3 weeks of exposure. Histological abnormalities in 

long bone differentiation included reduced calcification, excess growth of epiphyseal cartilage, 

abnormal deposition of osteoid in the metaphysis, fragmentation of the epiphyseal plates and 

isolated nodules of cartilage. The diet also contained 1.5% calcium and 0.9% phosphorus. 

No effects on exploratory motor activity were seen in rats that ingested 2,000 mg Sr/L 

(corresponding to 1,105 mg Sr/kg-day) in drinking water as strontium chloride for 15 days 

(Escanero et al., 1985). Other effects were apparently not evaluated.

Only one subacute study that evaluated the effects of strontium in mice was identified 

(Marie and Hott, 1986). As in rats, it showed that strontium had effects on bone. Exposure to 

0.27% strontium chloride in drinking water (350 mg Sr/kg-day, or 640 mg strontium chloride/kgday, based on actual water consumption and estimated average body weight) for 29 days caused 

minor bone effects in 21-day-old male C57BL/6J mice (11-13/group), including a 10% increase 

in osteoid surface (percentage of the endosteal surface covered by an osteoid seam) and an 11% 

reduction in the number of active osteoclasts. These minor effects are suggestive of early stage 

rickets and less bone resorption compared to control (due to less osteoclasts available to digest 

the bone matrix). The authors also suggested that some bone resorbing surfaces may have been 

converted to bone forming surfaces. Only one dose was tested and compared with an unexposed 

control group. The diet also contained 0.5% calcium, 0.74% phosphorus, and 2,000 IU vitamin 

D/kg. There were no effects on tibial length, bone mineral content (percent ash, calcium or 

phosphorus), the osteoblastic surface of the vertebrae (percentage of the endosteal surface 

showing plump osteoblasts), bone matrix apposition rate, osteoid seam thickness (average width 

of all endosteal osteoid seams) or calcified bone volume. 

Inhalation Exposure
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One study involving repeated inhalation of a strontium salt was identified. A study from 

the former Soviet Union (Zyuzyukin, 1974) reported that rats were exposed to strontium nitrate 

at 45 mg/m3 for 4 hours/day for 1 month (83% of particles <5 μm). Reported toxic effects were 

functional changes in the liver and kidney plus histological changes in the lungs, heart, liver, 

kidneys and spleen. The authors apparently did not conduct histopathological evaluation of the 

bone.

7.3.3 Subchronic Studies

Oral Exposure

Kroes et al. (1977) exposed weanling Wistar rats (10/sex/dose) to strontium chloride 

hexahydrate at dietary concentrations of 0, 75, 300, 1,200, or 4,800 ppm for 90 days. Based on 

reference body weights for males and females, and the U.S. EPA (1988) allometric equation for 

food intake, these concentrations correspond to estimated doses of 0, 2, 9, 36, and 146 mg Sr/kgday for males and 0, 3, 10, 42, or 166 mg Sr/kg-day for females; the corresponding estimated 

doses of strontium chloride hexahydrate are 0, 7, 27, 109, and 443 mg/kg-day for males and 0, 8, 

31, 127, and 505 mg/kg-day for females8. The authors described the semi-purified diet as 

containing “adequate” levels of calcium (0.85%), magnesium (0.05%), phosphorus (0.75%), and 

vitamin D3 (1,800 IU/kg); however the levels of calcium provided were relatively high (ATSDR, 

2004) as compared with other strontium studies, which may have reduced the effects of 

strontium exposure. 

There was no effect on behavior, appearance, growth, food intake, survival, hematology, 

serum chemistry, blood calcium or phosphorus, liver glycogen, urinalysis, weights of the major 

organs or histopathology of a wide range of tissues (including bone) at doses up to 300 ppm (9-

10 mg Sr/kg-day). At 1,200 ppm (36-42 mg Sr/kg-day), relative thyroid weight was statistically

significantly increased in males, but the effect was not clearly dose-related. At 4,800 ppm (146-

166 mg Sr/kg-day) relative thyroid weight was increased (although not by as much as at the 

lower dose) and there were histological signs of “moderate thyroid activation.” No further 

histological details were provided, and no supporting information was provided on thyroid 

hormone levels and or effects on the parathyroid. It is difficult to evaluate the implications of the 

observed changes in the absence of additional information. The thyroid takes up iodide anions; a 

cation such as strontium would not be expected to have a direct effect on the thyroid. The study

authors reported that the diet provided adequate iodine, but did not provide additional details. 

Strontium stimulation of the extracellular calcium-sensing receptor (CaSR) found in 

thyroid C-cells has been studied by Coulombe et al. (2004). CaSR activity modulates the 

secretions of calciotropic hormones in the thyroid, parathyroid, and kidney. It is possible that 

increased C-Cell activity could be associated with the thyroid changes observed by Kroes et al. 

(1977) but no data were provided that would support this hypothesis. The Kroes et al. (1977) 

 

8

Strontium chloride hexahydrate doses calculated based on unrounded strontium doses. WHO (2010) presented the 

doses for males and females as 0, 2.5, 10, 40, and 160 mg Sr/kg-day, based on average body weight and ingestion of 

10% of their body weight per day. 
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study provided minimal detail regarding the histological features that were suggestive of thyroid 

activation. Thus, it is difficult to determine whether the observed the thyroid changes should be 

classified as adverse or adaptive. 

Other statistically significant effects at the high dose included decreased relative pituitary

weights in females (without microscopic changes), and decreased liver glycogen levels in 

females; there was also a nonsignificant decrease in liver glycogen in males. Although strontium 

levels of bone were increased, there was no evidence of histological changes in the bone. Based 

on undefined histological signs of thyroid activation and increased relative thyroid weight, the 

LOAEL for the Kroes et al. (1977) study was 146 mg Sr/kg-day; the corresponding NOAEL was 

36 mg Sr/kg-day.

The South Korean National Institute of Environmental Research (NIER, 2006c) reported 

on a study of rats (strain not available) administered strontium sulfate by gavage for 40-54 days. 

There was no effect on survival, growth, sensory and motor functions, urinalysis, or the 

microscopic appearance of the tissues and organs evaluated (including bone) at doses up to 950 

mg Sr/kg-day. Decreased spleen weights were seen in female rats at doses of 500 mg/kg-day

strontium sulfate (about 240 mg Sr/kg-day) and higher, and males had increased epididymis and 

testis weights at 480 mg/kg-day strontium sulfate (corresponding to 229 mg Sr/kg-day). 

Decreased reticulocyte counts and decreased activity of aspartate aminotransferase (AST) were 

also seen in females at 980 mg/kg-day strontium sulfate (corresponding to 467 Sr /kg-day). 

Marie et al. (1985) administered strontium to weanling male Sprague-Dawley rats. The 

purpose of this study was to determine the effect of low doses of strontium on mineral 

homeostasis and bone histology. Rats (8/group) received 0, 0.19, 0.27, 0.34, or 0.40% strontium 

chloride in distilled water for 9 weeks. The diet contained 0.5% calcium, 0.54% phosphorus, 

0.16% magnesium and 2,000 IU/kg vitamin D. Based on body weight and water consumption 

data, the authors estimated average strontium intakes of 0, 316, 425, 525, and 633 mg Sr/kg-day. 

A dose-related, statistically significant decrease in the bone calcification rate was 

reported at doses of 525 mg Sr/kg-day and higher, with no significant change at the next lower 

dose of 425 mg Sr/kg-day. Rats in the 0.40% (633 mg Sr/kg-day) dose group showed signs of 

increased mineralization lag time; excessive osteoid thickness associated with a decline in the 

rate of calcification, which resulted in slow growth rate; and a decreased double-labeled osteoid 

surface, which frequently resulted in defective long bone growth. These effects are consistent 

with the development of osteomalacia, which is disruption of incorporation of minerals into the 

bone matrix. This leads to accumulation of unmineralized bone matrix as osteoid continues to be 

secreted by osteoblasts, causing development of soft bone. The osteoid volume and percent 

osteoid surface in relation to bone tissue or endosteal surface increased with dose. These effects 

likely reflect the continued secretion of osteoid without the mineralization necessary to increase 

bone tissue/endosteal surface. Appendix A, Table A-2 shows primary data from Marie et al. 

(1985). The study authors identified a NOAEL of 525 mg Sr/kg-day and a LOAEL of 633 mg 

Sr/kg-day based upon body growth and bone mineralization. However, based upon the 

observation of decreased calcification, a LOAEL of 525 mg Sr/kg-day and a NOAEL of 424 mg 

Sr/kg-day has been identified for this assessment. 
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Grynpas and Marie (1990) reported bone hypomineralization and increased bone mass in 

weanling male Sprague-Dawley rats administered 0.4% strontium chloride in distilled water 

while on a low calcium (0.5%) diet for 8 weeks. This suggests an osteomalacia type of effect 

during bone remodeling, where bone growth was not halted, but softer bones were formed. The 

full study description can be found in Section 7.3.2. 

A limited drinking water study was described by Skoryna (1981) and Skoryna and 

Fuskova (1981), in which adult male RVH hooded rats (10/group) were given strontium chloride 

in drinking water at 0%9, 0.09%, 0.19%, or 0.34% for 3 months. These concentrations 

correspond to doses of 0, 70, 147, and 263 mg Sr/kg-day, assuming water consumption of 0.14 

L/kg-day for an adult rat. Microscopic examination showed that the tissues (bone, heart, liver, 

muscle, lung, brain, adrenal and kidney) were unaffected by treatment. Adequate amounts of 

calcium (35 mg/L) and magnesium (6.8 mg/L) were given in the drinking water.

Johnson et al. (1968) reported respiratory difficulties, hindlimb paralysis, rickets, 

osteomalacia and deaths in weanling Sprague-Dawley rats (15/group) administered 0.45% 

strontium in feed (form not specified) for 43 days (corresponding to 565 mg Sr/kg-day, based on 

average body weight of 0.092 kg and allometric food intake equation). While the paralysis could 

have been related to abnormal calcium signaling, it was not known whether the paralysis had a 

neurological or muscular etiology. The paper’s authors noted that it was unlikely that the 

paralysis was due to femoral deformation, since even severely rachitic and osteomalacic rodents 

are not usually paralyzed. ATSDR (2004) suggested that the effects may have been due to 

compression of the hypertrophic epiphyseal cartilage, which was insufficiently mineralized to 

support the weight of the body. A study limitation is that only one dose level was tested. 

Comparable effects were not observed at similar doses in rats of the same strain and sex in other 

studies (e.g. Marie et al., 1985) with longer exposure durations. 

In contrast with the results of Johnson et al. (1968), Kshirsagar (1976) did not find 

treatment-related effects in weanling male Wistar rats (5-6 per group) exposed under similar 

conditions and at the same exposure level, but did report effects at higher doses. The Kshirsagar 

(1976) study treated with the rats for 4-6 weeks with 0, 0.5, 1, or 2% strontium in the diet as 

strontium phosphate (approximately 0, 580, 1270, or 2820 mg Sr/kg-day, based on a reference 

body weight for Wistar rats of 0.046 kg and allometrically scaled dietary intake). There were no 

treatment-related effects at the lowest dose, which was similar to the Johnson et al. (1968) 

LOAEL. Kshirsagar (1976) did report slowed growth and altered alkaline phosphatase activity

starting at 1270 mg Sr/kg-day. Hemorrhage, paralysis, abnormally thick epiphyseal cartilage 

plates in the long bones and 30% mortality were reported at 2820 mg Sr/kg-day.

In addition to the information presented in Storey (1961), the greater sensitivity of young 

animals was also demonstrated by Storey (1962). Both young (50-70 g) and adult (200-250 g) 

rats of both sexes (strain not specified) were provided a diet containing 1.8% strontium as 

strontium carbonate. The exposure continued for up to 7 months with several interim sacrifices. 

 

9The control group actually had 0.02 mg Sr/dL, corresponding to a negligible dose of 0.015 mg Sr/kg-day.
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After only 3 weeks of exposure, the young rats exhibited a "rachitic gait" with the most obvious 

changes occurring in the distal end of the femur and the proximal end of the tibia. The 

epiphyseal plate was reported to be “grossly widened” and the metaphysis was “a mass of soft 

white tissue.” Conversely, it was 3 months before change was observed in the adult rats, in the 

form of fine traverse lines in the upper tibial metaphysis. The tooth enamel of the adults was 

abnormally white and pitted. The author noted that the abnormal deposition of osteoid in long 

bones and the skull was less extensive in adults than in the young rats, and that the epiphyseal 

plates were fragmented in the young rats, but not the adults. 

Because young rats consume more food per kg body weight that adults, it is difficult to 

determine how much of the difference in effects is due to a higher dose in the young rats, and 

how much (if any) is due to greater sensitivity in the young rats. ATSDR (2004) calculated that 

the average intake was 2160 mg Sr/kg-day in the young rats and 1570 mg Sr/kg-day in the adult 

rats, based on body weights estimated from the study and reference body weights (average of 

0.152 kg for the young rats and 0.304 kg for the adult rats) and an allometric equation for food 

intake. 

In contrast to the adverse effects on bone at higher doses, low doses of strontium in the 

presence of adequate calcium have beneficial effects on bone mineralization. Grynpas et al. 

(1996) found that exposure of 28-day-old male Sprague-Dawley rats (8/group) to 0.2% strontium 

(form unspecified, reported by the authors to correspond to 168 mg Sr/kg-day) in drinking water 

containing 0.15% calcium for 8 weeks resulted in a 17% increase in mineral bone volume and a 

70% increase in the number of bone-forming sites and no adverse effect on the hydroxyapatite 

mineral particle size. The rats’ diets contained 0.5% calcium, 0.54% phosphorus, 0.16% 

magnesium and 2,000 IU/kg vitamin D. There were also no effects on mineral apposition rate, 

osteoid thickness, indicating no deleterious effect. No studies investigating beneficial effects of 

strontium on young animals were located.

Inhalation Exposure

No subchronic studies regarding the toxicity of strontium following inhalation exposure 

were identified.

7.3.4 Neurotoxicity

No studies designed to evaluate neurotoxic effects of strontium were located. As noted in 

Section 7.3.3, Johnson et al. (1968) reported hindlimb paralysis in weanling Sprague-Dawley rats 

(15/group) administered 0.45% strontium in feed (form not specified) for 43 days (dose 

estimated as 565 mg Sr/kg-day).
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7.3.5 Developmental/Reproductive Toxicity 

Reproductive Effects

The only available studies investigating reproductive effects of strontium were conducted 

in rats. No standard one- or two-generation reproductive toxicity studies exist for any strontium 

compound, but the available data indicate that strontium does not cause structural or functional 

reproductive effects at doses well above those causing bone effects. In a screening test for 

reproductive and developmental toxicity, NIER (2006c) found no effects on mating behavior, 

fertility, gestation period or histopathology of the reproductive tissues and organs. In this study, 

rats (16/sex/dose; strain not available) were given strontium sulfate by gavage at up to 2000 

mg/kg-day (corresponding to doses up to 950 mg Sr/kg-day), from 2 weeks before mating until 

day 4 of lactation. The total dosing period was 42 days for males and 40-54 days for females. 

There was no effect on the weights or histopathology of reproductive organs (testes, 

ovaries, uterus or prostate) in weanling Wistar rats (10/sex/dose) exposed to strontium chloride 

hexahydrate in the diet at doses up to 4800 ppm in the Kroes et al. (1977) study of systemic 

toxicity. As documented above in Section 7.3.3, this corresponds to a dose of about 146-166 mg 

Sr/kg-day. 

The review article by Skoryna (1981) mentions a study in RVH hooded rats that were 

given strontium supplements of 0, 0.09%, 0.19% or 0.34% in drinking water during a 3-

generation breeding period without adverse effects. However, no information was provided on 

the parameters evaluated, dietary concentrations of calcium or phosphorus, and the basis for the 

author’s conclusion. The highest concentration is equivalent to a dose of about 260 mg Sr/kgday (U.S. EPA, 1992). 

Developmental Effects

The database on the potential developmental toxicity of strontium is limited, with studies 

focusing primarily on bone effects. Some limited studies (Shibata and Yamashita, 2001; NIER, 

2006c) evaluated other developmental endpoints. Overall, there was no indication of fetotoxicity

or developmental effects on targets other than bone. Several studies conducted of in utero or 

postnatal effects on bone development found inhibition of calcification, but it is difficult to 

evaluate the relative susceptibility of developing fetuses and young animals to the bone effects of 

strontium, because most of the studies cited tested only a single, high-dose exposure level. 

There were no adverse effects on fetal development (implantations, litter size, live births, 

viability, sex ratio, body weight and length, overt malformations on external examination) in the 

NIER (2006c) screening tests. However, there was no microscopic examination for skeletal or 

visceral alterations. Rats (16/sex/dose; strain not available) were given strontium sulfate by

gavage at doses of 500 to 2000 mg/kg-day (corresponding to doses of 240 to 950 mg Sr/kg-day), 

from 2 weeks before mating until day 4 of lactation. The total dosing period was 42 days for 

males and 40-54 days for females. 
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Other studies evaluated the effects of strontium on postnatal bone formation, particularly 

endochondral ossification (bone formation from centers in the cartilage). As discussed further in 

Section 7.5.1, bone growth in rats continues throughout life. Studies on weanlings were 

discussed in Sections 7.3.2 and 7.3.3., and found that weanlings exhibited more severe skeletal 

effects than adults exposed at the same level in diet or drinking water (Storey, 1961, 1962; 

Grynpas and Marie, 1990). 

Several developmental toxicity studies focused on potential bone effects of perinatal 

strontium exposure. In a limited study conducted with a very small sample size (4 pregnant 

dams/dose; strain not available), mice were exposed throughout pregnancy to diets containing 0 

or 2% strontium carbonate (corresponding to doses of 0 or about 1500 mg Sr/kg-day), and bone 

and cartilage development were assessed in the newborn pups (Shibata and Yamashita, 2001). 

There was no effect on maintenance of pregnancy, fetal numbers or fetal viability. However, 

extensive inhibition of calcification of mandibular bone and cartilage was observed. 

Ultrastructural changes in the osteoclasts (on the mandibular alveolar bone) and chondroclasts 

(in the resorption area of the condylar cartilage) were also present. Increased phagocytic activity

in osteoclasts and chondroclasts was indicative of functional changes in these cells. In another 

study of female rats (strain and number/group not available) exposed to 2,000 ppm strontium 

carbonate in diet throughout pregnancy (equivalent to 1187 mg Sr/kg-day), the only reported 

effects were on fetal bone (Miki and Miyamoto, 1968). Observed effects included vertebral 

kyphosis (convex curvature of the spine), reduced vertebral calcification and an irregular 

arrangement and appearance of the chondrocytes. These studies are insufficient to identify an 

threshold effect level for bone effects of perinatal strontium exposure. 

7.3.6 Chronic Toxicity

Oral Exposure

The reports by Skoryna (1981) and Skoryna and Fuskova (1981) discuss a study in which 

small numbers of animals were exposed for longer than the standard duration (increasing the 

potential for age-related lesions and decreasing study sensitivity); the reports provide inadequate 

documentation of the methods and results. Based on the available information, male RVH 

hooded rats (12/dose10) were given strontium chloride in their drinking water at a concentration 

of 0,11 900, 1900, or 3400 mg/L for 3 years. Assuming that an adult rat consumes 0.14 L/kg-day, 

these concentrations correspond to strontium doses of 0, 70, 147, and 263 mg Sr/kg-day as 

estimated by U.S. EPA (1992). The rats received adequate amounts of calcium (35 ppm) and 

magnesium (6.8 ppm) in the drinking water. No adverse effects on body weight or on the 

microscopic appearance of the bone, kidney, lung, adrenal, brain, heart or muscle were reported. 

Organ weights were not determined and there was no mention of tumors. Based on the absence 

of effects, this study identified the high dose of 263 mg Sr/kg-day as the study NOAEL. 

 

10 The secondary sources are not clear on the number treated, and the reporting in Skoryna (1981) is vague, although 

it appears that different numbers of animals were evaluated for different endpoints. Some endpoints apparently 

evaluated only a subset of the total exposed animals. The reported number of animals/dose is from WHO (2010).

11The control group actually had 0.02 mg Sr/dL, corresponding to a negligible dose of 0.015 mg Sr/kg-day.
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7.3.7 Carcinogenicity

No studies designed to evaluate the carcinogenicity of strontium compounds by any route 

were located. As noted in Section 7.3.6, the 3-year study reported by Skoryna (1981) and 

Skoryna and Fuskova (1981) did not mention tumors.

7.4 Other Key Data

7.4.1 Mutagenicity and Genotoxicity

The only form of strontium that is consistently genotoxic is strontium chromate. The 

observed effects are attributed to the chromate ion rather than the strontium and are not included 

in this assessment. Other strontium compounds were negative in tests for gene mutation in 

bacterial cells (Kanematsu et al., 1980; Yang, 1984; NIER, 2006e) and chromosome aberrations 

in mammalian cells (Tateno and Kamiguchi, 1997; NIER, 2006d) (Table 7-1), although not all of 

the tests were conducted using standard test systems. No studies of gene mutation of strontium 

compounds in mammalian cells were identified. Strontium compounds were also negative for 

cell transformation in vitro (Heidelberger et al., 1983) and DNA damage in vitro (Loeb et al., 

1977; Casto and DiPaolo, 1983).

Thus, overall the data are negative for strontium genotoxicity in vitro. 

Table 7-1 Genotoxicity of Strontium In Vitro

Species 

(test system) End-point

With 

activation

Without 

activation Reference

Bacillus subtilis Rec-

(strontium chloride) Gene mutation - -

Kanematsu et al. 

(1980)

Ames test (strontium 

carbonate)

Salmonella typhimurium 

strains TA98, TA100, 

TA1535, TA1537 or 

TA1538

Gene mutation - - Yang (1984)

Ames test (strontium 

sulfate) Salmonella 

typhimurium strains TA98, 

TA100, TA1535 or 

TA1537 or in Escherichia 

coli strain WP2uvrA

Gene mutation - - NIER (2006e)

Chinese hamster oocytes 

(strontium chloride)

Chromosomal 

aberrations, changes 

in chromosome 

number

N/Ab-

Tateno and 

Kamiguchi 

(1997)
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Species 

(test system) End-point

With 

activation

Without 

activation Reference

Chinese hamster lung cells 

(strontium sulfate)

Chromosomal 

aberrations or 

polyploidy

- - NIER (2006d)

Syrian hamster embryo 

cells (strontium chloride) Cell transformation (?)a

-

Heidelberger et 

al. (1983)

Syrian hamster embryo 

cells (strontium chloride) DNA strand breaks (?)a

-

Casto and 

DiPaolo (1983)

DNA synthesis reaction 

(strontium chloride)

Lack of fidelity in 

DNA synthesis - -

Loeb et al. 

(1977)

aOnly one set of results was reported. It is unclear whether the chemical was tested both +/- S9, and if so, whether 

the results in the presence of S9 were the same as in the absence.

bN/A - not available 

Only a single in vivo genotoxicity study is available (Table 7-2). In this study, Swiss 

albino mice were treated with strontium chloride (apparently as a single dose) at 240-2,400 

mg/kg (females) or 260-2,600 mg/kg (males) (Ghosh et al., 1990). The corresponding strontium 

doses were 130-1326 mg Sr/kg for females and 140 - 1437 mg Sr/kg for males. There was a 

dose-related increase in chromosome aberrations in bone marrow cells at 6, 12, and 24 hours “of 

treatment” (apparently time after dosing). The response in females was higher than that in males 

at the lowest dose. However, it is difficult to fully interpret the reported values, due to 

inconsistencies in the reporting of the number of animals/dose per time point. In addition, no 

information was provided on the nature of the aberrations, and it appears that polyploidy was 

included together with structural aberrations. If five animals per dose per time point were used, 

then the reported results are consistent with possible genotoxicity, but the reporting limitations 

raise questions about the overall study quality. It is not clear why the results of this study

apparently differed from those of the in vitro chromosome aberration studies.

Table 7-2 Genotoxicity of Strontium In Vivo

Species

(test system) End-point Results Reference

Strontium chloride: Mouse 

(bone marrow)

Chromosomal aberrations 

polyploidy + Ghosh et al. (1990)

7.4.2 Immunotoxicity 

No studies designed to evaluate the immunotoxicity of strontium compounds by any 

route were located.

7.4.3 Physiological or Mechanistic Studies

7.4.3.1 Noncancer Effects
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There has been considerable interest in potential physiological effects of strontium due to 

its potential impact on calcium uptake, transport and function. Strontium treatment has been 

shown to increase the formation of bone nodules in vitro, while increased osteoblast number, 

bone volume and trabecular thickness have been reported in vivo (Lymperi et al., 2008). As 

reviewed by Dahl et al. (2001), strontium at doses of 316 to 634 mg Sr/kg-day, administered as 

strontium chloride or strontium ranelate for 9-26 weeks, increases bone formation in adult 

rodents and humans by increasing the number of osteoblasts (increasing bone formation) and 

decreasing the activity of osteoclasts (decreasing bone resorption). This results in increased bone 

volume. Because the increased bone formation results in increased mechanical resistance, 

strontium, generally as the ranelate salt, has been evaluated as a treatment for osteoporosis. 

Strontium may exert its effects on osteoblasts and osteoclasts in part via the extracellular 

calcium sensing receptor (CaSR) (Marie, 2010). The CaSR is a member of the G-protein 

coupled receptor family, and is found in bone cells, thyroid (C-cells), kidney, brain, and the 

parathyroid (Coulombe et al., 2004). The CaSR is a low affinity receptor that requires mMol 

concentrations of the agonist, 3 mM for calcium, for activation. Strontium binds to the CaSR as 

a full agonist, but with lower affinity than calcium. Numerous divalent or trivalent cations can 

activate the CaSR, with the following order of potency: La3> Gd3> Be2 > Ca2 > Ba2 > Sr2 > 

Mg2. CaSR activation stimulates the activity of phospholipase C and A2, mitogen–activated 

protein kinase (MAPK), and phosphoinositide kinase 3, inducing the production of a series of 

second messengers that modulate calcium homeostasis through the calciotropic hormones from 

thyroid C-cells and the parathyroid (Coulombe et al., 2004). The activation of CaSR in thyroid 

C cells increases calcitonin synthesis, storage and secretion, which can then lead to reduction in 

serum calcium (Henley et al., 2011). In vitro studies of the CaSR in transfected Chinese hamster 

ovary (CHO) cells demonstrated receptor activation by strontium ranelate but not ranelic acid 

(Coulombe et al., 2004). 

Strontium activated apoptosis in cultured osteoclasts through activation of CaSR, 

suggesting a mechanism for the decrease in bone resorptions in the presence of strontium. 

Conversely, strontium ranelate increased osteoblastic cell replication through the activation of 

CaSR-mediated ERK1/2 signaling. Furthermore, the addition of strontium to parathyroid cells 

(which regulate bone formation and resorption) results in increased levels of intracellular 

calcium, presumably due to interaction with parathyroid calcium receptors (Shoback et al., 

1995). Marie (2010) noted, however, that it has not yet been determined whether CaSR mediates 

the response to strontium in bone cells in vivo. 

The in vitro studies referenced above use strontium concentrations in excess of 4 to 5 

mM. Normal serum or blood levels of strontium are in the range of 10-50 μg Sr/L, or 0.1-0.6 μM 

(depending on the blood fraction evaluated (Olehy et al., 1966; Skoryna, 1981). Higher levels, in 

the range of 7 μM have been reported in dialysis patients receiving contaminated dialysate, and 

up to 0.1 mM in people treated with strontium ranelate. Therefore the highest identified serum 

strontium concentration in humans is 40 to 50 fold lower than those used in vitro that were 

associated with calcimimetic effects. In addition, considering that Sr has a lower affinity for the 

CaSR receptor than five other elements including calcium, it seems unlikely that a calcimimetic 

effect would occur in humans.
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Calcium also acts as a second messenger for signal transduction pathways and plays a 

critical role in regulating neurotransmitter release and in muscle contraction. For example, the 

Ras/MAPK signaling pathway was altered in mesenchymal stem cells exposed to strontium 

(Peng et al., 2009) and strontium can partially substitute for calcium in regulating the signaling 

and insulin release from pancreatic beta cells (Hellman et al., 1997). Thus, there has been some 

research on potential effects of strontium on the nervous and neuromuscular systems. Strontium 

was observed to alter evoked neurotransmitter release in chick ganglions (Yawo, 1999), alter 

neurotransmission in rat hippocampal cells (Morishita and Alger, 1997), and alter the function of 

voltage-gated calcium channels (Wakamori et al., 1998). Most of these studies were mechanistic 

studies that were conducted in vitro, often at a single concentration, with no correlation to in vivo

concentrations of strontium. Therefore, these studies can contribute to the overall weight of 

evidence for hazard identification, suggesting potential targets of strontium toxicity, but their 

biological and risk assessment significance is unclear in the absence of in vivo studies at multiple 

doses. The biological significance of these studies is unclear in the absence of reported clinical 

signs of neurotoxicity at high strontium doses in repeated dosing animal studies and the absence 

of neurotoxicity studies evaluating sensitive endpoints and lifestages. 

7.4.3.2 Cancer Effects 

No studies evaluating the carcinogenic potential of strontium compounds by any route are 

available. Genotoxicity studies of strontium salts, other than chromate salts, were negative with 

the exception of a single chromosome aberration study that gave positive results. 

7.4.3.3 Interactions with Other Chemicals 

Few studies have been conducted on the interaction of strontium with other chemicals. 

As noted in Sections 7.4.3 and 7.5.1, strontium can act as a mimic of calcium, but calcium is 

preferentially absorbed and preferentially binds to relevant targets. As noted in Section 6.1.1, 

phosphate decreases strontium absorption. Two subacute studies in chicks administered 

strontium as part of their diet indicate that strontium inhibits vitamin D-induced calcium binding 

proteins, intestinal calcium absorption and interferes with the metabolism of vitamin D to its 

functional metabolite (i.e., 1,25-dihydroxycholecalciferol), leading to strontium “rickets” 

(Corradino and Wasserman, 1970; Omdahl and DeLuca, 1972). No similar studies performed in 

mammals were identified that specifically evaluated vitamin D as it relates to strontium; thus it is 

unknown whether similar inhibition of vitamin D functionality following strontium exposure 

occurs in mammalian species.

Other interaction studies have found a benefit of strontium in inhibiting effects of some 

other chemical exposures. The application of 20% strontium nitrate upon the volar forearm 

(inside, or palm-side, forearm) for 35 minutes suppressed sensory irritation in response to a 

challenge with histamine or when mixed with 70% glycolic acid (Zhai et al., 2000a,b). This 

suggests that dermal exposure to strontium may decrease the irritant effects of other chemicals. 
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7.4.4 Structure-Activity Relationship

As noted, strontium is structurally-related to calcium because the two ions have the same 

ionic charge (2+) and ionic radii that are not substantially different (Ca 114 pm vs. 132 pm for 

Sr; Weast and Astle, 1981). Accordingly strontium can partially substitute for calcium in some 

physiological processes. When it displaces calcium during bone formation alterations to bone 

histology and structure can result. The implications of these substitutions were discussed in the 

Sections 7.3 and 7.4.3.

7.5 Hazard Characterization

7.5.1 Synthesis and Evaluation of Major Noncancer Effects 

The primary target of strontium exposure is the bone. The chemical similarity of 

strontium to calcium allows it to exchange imperfectly for calcium in a variety of biological 

processes; the most important of these is the substitution of calcium in the bone, affecting 

skeletal development. Those with low or deficient calcium intake are more likely to have 

increased strontium uptake and bone effects following ingestion. Sufficiently high doses of 

strontium can lead to the development of rickets in young animals and possibly in children 

(Özgür et al., 1996), but insufficient information is available to determine the doses associated 

with this effect. Animal studies show that strontium can decrease the calcification of the 

cartilaginous portion of bone at doses to weanlings of 525 mg Sr/kg-day and above, and can 

increase bone formation at 633 mg Sr/kg-day and above (Marie et al., 1985). The decreased 

calcification results in increased width of the epiphyseal cartilage in growing rats, changes in the 

pattern of calcification, and abnormally long metaphyses, effects that were reported by Neufeld 

and Boskey (1994) in “young” rats at 500 mg Sr/kg-day. Due to this effect on growing bones, 

infants, children and teenagers are of particular concern as potentially susceptible populations. 

There are three studies in which mortality is reported following subacute or subchronic 

strontium exposure (Storey, 1962; Johnson et al, 1968; Kshirsagar, 1976). The mortality (and 

other adverse effects) observed in the Johnson et al. (1968) study following exposure to 565 mg 

Sr/kg-day is surprising as comparable effects were not observed at similar doses in rats of the 

same strain and sex in other studies (e.g. Marie et al., 1985) with longer exposure durations. For 

the other two studies, mortality is reported following 2150 mg Sr/kg-day for 3 weeks (Storey, 

1962) or 2820 mg Sr/kg-day for 4 to 6 weeks; these exposures are 4-5 times the LOAEL from 

Marie et al. (1985) and near the beginning of the lethal dose range. The oral median LD50s for 

strontium are between 2.35 and 3.1g Sr/kg in rodents (Woodard and Calvery, 1941; Ghosh et al., 

1990; Llobet et al., 1991). Thus, there is a potentially steep slope from the LOAEL to frank 

effects.

The effects of strontium at low doses (400-500 mg Sr/kg-day) include small changes in 

bone structure and inhibition of calcification (Storey, 1961; Marie and Hott, 1986), consistent 

with early development of osteomalacia and/or strontium “rickets.” Decreased levels of 

osteoclasts and associated decreases in bone resorption may also occur at low doses (Marie and 

Hott, 1986). Higher doses (over about 1500 mg Sr/kg-day in rats) result in more severe bone 
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effects including reduced growth, large areas of unmineralized bone, and bone softening (rickets 

in young animals and possibly children, and osteomalacia in adults), excess growth of epiphyseal 

cartilage and abnormal deposition of osteoid in the metaphyses (Storey, 1962). Because children 

and young animals are growing rapidly, they are more sensitive than adults, with effects of 

strontium exposure occurring at lower doses and higher severity than in adults. Physiological 

differences between rats and other mammals (including humans) may make rats more sensitive 

to the bone effects of strontium. In rats, (unlike most mammals, including humans), the 

epiphyseal cartilage growth plate of the long bones never transforms completely into bone, and 

so bone growth continues throughout life, although it slows down after 12 months of age. This 

difference may make rats more sensitive over longer periods of life due to higher incorporation 

of strontium into the skeleton of adult rats than adults of other mammals. 

No standard one- or two-generation reproductive toxicity studies exist for any strontium 

compound, but the available data indicate that strontium does not cause structural or functional 

effects at doses well above those causing bone effects. No effects on mating behavior, fertility, 

gestation period or the histopathology of the reproductive tissues and organs were observed in a 

screening test for reproductive and developmental toxicity (NIER, 2006c). There were no 

adverse effects on fetal development in this study (implantations, litter size, live births, viability, 

sex ratio, body weight and length, overt malformations on external examination). However, 

since this was a screening study, there was no microscopic examination for skeletal or visceral 

alterations. There was also no effect on organ weight or histopathology of reproductive organs 

(testes, ovaries, uterus or prostate) in weanling rats (10/sex/dose) exposed to strontium chloride 

hexahydrate in the diet at doses up to 4800 mg/kg (equivalent to about 146 mg Sr/kg-day; Kroes 

et al., 1977).

In the (NIER, 2006c) reproductive and developmental toxicity screening tests , there were 

no adverse effects on fetal development (implantations, litter size, live births, viability, sex ratio, 

body weight and length, overt malformations on external examination). However, since this was 

a screening study, there was no microscopic examination for skeletal or visceral alterations. 

Several developmental toxicity studies focused on potential bone effects of perinatal strontium 

exposure (e.g., Miki and Miyamoto, 1968; Shibata and Yamashita, 2001). Overall, there was no 

indication of fetotoxicity or developmental effects on targets other than bone. Several studies 

conducted on in utero or postnatal effects on bone development found inhibition of calcification. 

However, it is difficult to evaluate the relative susceptibility of developing fetuses and young 

animals to the bone effects of strontium because almost all of the available studies tested only a 

single, high-dose exposure level. 

Strontium can also substitute imperfectly in other cellular processes that require calcium, 

including signaling pathways (e.g., the mitogen-activated protein kinase pathway), and 

secondary messenger (e.g., inositol triphosphate) and transporter (calmodulin) systems that 

usually involve calcium. Strontium has been reported to activate several calcium-sensitive 

signaling pathways in vitro, including pathways mediated by ERK1/2, PI3K, protein kinase D, 

p38, MAPK and protein kinase B. Strontium has also been shown to bind and activate the 

calcium-sensing receptor (CaSR) as a full agonist, but with a lower affinity than calcium. The 

extracellular calcium-induced activation of the calcium-sensing receptor (CaSR) in bone cells 
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has been shown in vitro to induce several intracellular signaling pathways that regulate osteoclast 

and osteoblast activity (Marie, 2010). However, while effects have been seen in in vitro studies, 

these effects have either not been seen in in vivo studies, or occur at doses higher than those that 

affect the bone.

7.5.2 Synthesis and Evaluation of Carcinogenic Effects

No studies are available that evaluated tumor formation in an adequate number of 

animals treated with strontium for an adequate duration. Only a single chronic study is available 

for oral strontium exposure (Skoryna, 1981; Skoryna and Fuskova, 1981), and this study

evaluated small numbers of animals for longer than the standard exposure duration (increasing 

the potential for age-related lesions and decreasing study sensitivity). Together, the small 

sample size and late sacrifice date decreased the study sensitivity, and mean that the study was 

inadequate for evaluation of carcinogenic potential. In humans, there is no evidence for a 

carcinogenic effect of strontium. Strontium chromate was implicated as a cause of increased 

lung cancer risk in a study of British chromate pigment manufacturing workers (Davies, 1979, 

1984), but the effects are attributed to the chromium (VI) oxidation state. Chromium (VI) 

compounds and ions are known human carcinogens via the inhalation route (U.S. EPA, 1998b). 

Strontium compounds other than strontium chromate are negative in genotoxicity studies, with 

the exception of one in vivo chromosome aberration assay that had several limitations in the 

reporting of study design and results (Ghosh et al., 1990).

7.5.3 Mode of Action and Implications in Cancer Assessment

Strontium has not been observed to cause cancer; thus, a mode of action evaluation is not 

relevant.

7.5.4 Weight of Evidence Evaluation for Carcinogenicity

Based on the evidence, the human carcinogenic potential of strontium cannot be 

determined because the data relevant to strontium carcinogenicity are very limited. No increase 

in tumors was seen in the single available chronic oral study (Skoryna, 1981; Skoryna and 

Fuskova, 1981), but this study used a small sample size and was inadequate for evaluation of 

carcinogenic potential. Increased lung tumors were seen in British chromate pigment workers 

exposed to strontium chromate, but the effects are attributable to the chromate (VI) moiety in the 

chromate; chromium (VI) is a known human carcinogen via the inhalation route. The weight of 

evidence from the genotoxicity data is that strontium is negative for gene mutation and 

chromosomal damage; positive results were seen with strontium chromate. 

7.5.5 Potentially Sensitive Populations

Because strontium can substitute for calcium in growing bone, children and young adults 

are expected to be a sensitive population, since they are actively growing. This means that 

changes in bone structure and homeostasis may have more severe and/or a long-term impact than 

similar changes in adults. These effects would be expected to have the greatest impact during 
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periods of rapid growth in the developing fetus, during childhood and adolescence, although 

Recker et al. (1992) reported that bone mineral accretion continues slowly into the third decade 

of life, with different skeletal sites reaching peak bone mass at different ages. The expected 

increased sensitivity of children and adolescents is consistent with the results of Storey (1961), 

who found that weanling rats were more sensitive than young adult rats to the bone effects of 

ingested strontium. There are some data from studies in humans that demonstrate a positive 

association between the incidence of low trauma fractures in children and low bone density or 

low calcium intakes (Farr et al. 2014; Matkovic et al., 2007). A recent study in embryonic

zebrafish found that the relative ratio of calcium to strontium in water was an important factor 

influencing strontium’s impact on embryonic bone development (Psqualetti et al., 2013); 

inhibition of bone mineralization increased as the strontium:calcium ratio increased.

In addition to the toxicodynamic sensitivity of young animals, toxicokinetic differences 

may also apply. Increased strontium absorption has been reported during lactation in rats, due to 

the strontium’s common absorption pathway with calcium. Although it has not been directly 

studied in humans, similar increased absorption is likely during lactation and pregnancy in 

humans. 

Strontium’s mode of action suggests other related sensitive populations. Because many 

of the toxic effects of strontium result from strontium ions substituting for calcium ions, calcium 

deficiency would be expected to result in increased sensitivity. According to the NIH Office of 

Dietary Supplements (NIH, 2011), hypocalcemia results primarily from medical problems or 

treatments, including renal failure, surgical removal of the stomach, and use of certain 

medications (such as diuretics). Groups with higher risks of becoming calcium deficient include: 

postmenopausal women, amenorrheic women, female athletes, vegans, and individuals with 

lactose intolerance or cow’s milk allergies. Frank calcium deficiency is uncommon, but longterm intake of calcium below recommended levels might have negative health consequences. 

The potential for calcium deficiency is of particular importance immediately prior to and 

during puberty. Pubertal development is associated with marked increases in calcium utilization, 

with calcium supplementation in the prepubertal and pubertal periods resulting in increased bone 

accretion (Abrams et al., 2000; Lee et al., 1996; Matkovic et al., 2005). IOM (2010) concluded 

that increased calcium intake during the peripubertal period is associated with increased bone 

accretion, although the data do not consistently show long-term retention of increased bone 

mineral content, particularly after supplementation is withdrawn. Median calcium intakes for 

girls ages 14 to 18 years (826 mg/day) are below their recommended intake of 1100 mg/day

(IOM, 2010). Together, these studies indicate that pre-teenagers and teenagers (and perhaps 

particularly teenage girls) are a sensitive population for strontium exposure, due to the rapid 

bone growth and importance of calcium levels during this period. Since calcium can help to 

protect against bone effects of strontium, the below-recommended intake of calcium may make 

this population more sensitive to the effects of strontium. Although it is not clear if there is a 

link between decreased pubertal bone mass and later sensitivity to osteoporosis, the finding of 

such a link would also indicate that the teenage sensitivity to strontium would be related to 

osteoporosis later in life. 
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Based on the potential link between potential effects on pubertal bone mass formation 

and osteoporosis, one might expect that the elderly, particularly osteoporotic women, would also 

be sensitive populations. However, strontium at doses well above the RfD derived in Chapter 8 

have been administered to osteoporotic women for months to years to treat osteoporosis. 

Therefore, while strontium at sufficiently high doses would alter the bone structure in the elderly, 

it is not expected that the effects would be more adverse in the elderly than in the general 

population.

Paget’s disease of bone is a disorder in which the normal equilibrium between the

breakdown of old bone and the formation of new bone is disturbed, resulting in the formation of 

abnormal, dense, and brittle bone. The prevalence of Paget’s disease increases with age; juvenile 

Paget’s disease is very rare. Because Paget’s disease affects bone metabolism, people with the 

disease might be expected to be have increased incorporation of strontium into the bone, and 

might be more affected by strontium exposure. The first supposition is supported by the data of 

Tothill et al. (1983), who found increased uptake and removal from bone of radiolabeled 

strontium in 12 adult patients with Paget’s disease, compared with 7 normal controls; no studies 

on potential health effects associated with the increased bone uptake were located.

There is substantial literature indicating that renal dialysis patients and people with renal 

failure are more sensitive to strontium, based on human data, and supported by animal data 

(Schrooten et al., 1998, 2003 (rats); D’Haese et al., 1999, 2000 (humans); Vanholder et al., 2002 

(humans); Cohen-Solal et al., 2002 (humans); De Broe and D’Haese, 2003 (humans); Oste et al., 

2005 (rats)). This phenomenon is likely due to the potential for strontium to accumulate to a 

larger extent in the bones of those with disorders of the kidney, as the kidney is one of the main 

organs involved in elimination of strontium from the body. In animal studies, the development of 

osteomalacia in rats with chronic renal failure was dose dependent and rapidly reversed after 

strontium treatment ended. In humans, D’Haese et al. (2000) found that renal dialysis patients 

with osteomalacia had higher strontium: calcium ratios than in dialysis patients with other types 

of osteodystrophy, supporting the hypothesis that increased strontium exposure may be 

associated with the osteomalacia. Thus, strontium levels are increased in people with renal 

failure, possibly because renal failure patients have impaired strontium clearance. Regardless of 

the reason, the increased strontium levels in the body may lead to increased susceptibility to bone 

effects.

Because strontium can weakly mimic the actions of calcium in in vitro experiments, it 

may have an impact on contractions of the coronary artery, pancreatic insulin secretion, and/or 

parathyroid hormone regulation (Hellman et al., 1997; Pors Nielsen, 2004; Ohashi et al., 1995). 

Individuals with alterations in these physiological functions (e.g., insulin-dependent diabetics) 

may be sensitive to strontium. However, since these effects lack in vivo confirmation and seem 

to occur at higher doses than the bone effects of strontium, the limits that protect children from 

the bone effects would also be expected to protect these populations. 
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8.0 DOSE-RESPONSE ASSESSMENT

8.1 Dose-Response for Noncancer Effects

The derivation of the reference dose (RfD) for strontium is described below. The RfD is 

an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure 

to the human population (including sensitive subgroups) that is likely to be without an 

appreciable risk of deleterious effects during a lifetime. Table 8-1 summarizes the available 

dose-response data for oral subchronic and chronic animal studies for strontium. Table 8-1 also 

includes shorter-term studies when they are co-critical studies or specifically address the relative 

sensitivity of weanling and adult animals. 

Table 8-1 NOAEL/LOAEL Data for Oral Subchronic and Chronic Studies of Strontium

Species, 

Sex

Form, 

Dietary 

Calcium

Study 

Duration

/ Route

NOAEL

(mg Sr/kgday)a

LOAEL

(mg Sr/kgday)a Critical Effect(s) Reference

Mouse, 

male 

Strontium 

Chloride, 

0.5% Ca

29 days

Drinking 

water

-- 350

10% increase in 

osteoid surface and 

an 11% reduction 

in the number of 

active osteoclasts

Marie and 

Hott (1986)

Rat, 

“young” 

female

Strontium 

Carbonate, 

1.6% Ca

20 days

Diet 190 380 Inhibition of calcification

Storey

(1961)

Rat, 

adult 

female

Strontium 

Carbonate, 

1.6% Ca

20 days

Diet 375 750 Changes in bone structure

Storey

(1961)

Rat, 

weanling 

male

Strontium 

Chloride, 

0.5% Ca

4 weeks

Drinking 

water

222 466

Bone 

hypomineralization 

and increased bone 

mass

Grynpas and 

Marie (1990)

Rat, 

weanling 

male

Unspecified 43 days

Diet -- 565

Respiratory

difficulties, 

hindlimb paralysis, 

rickets and 

osteomalacia and 

40% mortality

Johnson et 

al. (1968)

Rat, 

weanling 

male

Strontium 

Chloride, 

0.5% Ca

8 weeks

Drinking 

water

146 307

Bone 

hypomineralization 

and increased bone 

mass

Grynpas and 

Marie (1990)

Rat,

Male

Strontium 

Chloride, 

9 weeks

Drinking 425b

525b Decreased 

calcification rate

Marie et al. 

(1985)
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Species, 

Sex

Form, 

Dietary 

Calcium

Study 

Duration

/ Route

NOAEL

(mg Sr/kgday)a

LOAEL

(mg Sr/kgday)a Critical Effect(s) Reference

0.5% Ca water

Rat, 

weanling 

male and 

female

Strontium 

Chloride 

hexahydrate, 

0.75% Ca

90 days

Diet 36 146

Histological signs 

of thyroid 

activation in males 

and non-dose 

related increase in 

thyroid weight

Kroes et al. 

(1977)

Rat,

Male

Strontium 

Chloride,

0.35% Ca

3 months

Drinking 

water

263 --

No effect as 

confirmed by 

histological 

examination; 

Presented in a 

review article with 

limited primary

data.

Skoryna and 

Fuskova 

(1981)

Rat, 

adult 

male

Strontium 

Chloride, 

0.35% Ca

3 years

Drinking 

water

263 --

Presented in a 

review article with 

limited primary

data. No reported 

adverse effects on 

growth

Skoryna, 

(1981); 

Skoryna and 

Fuskova(198

1)

aUnless otherwise specified, doses were calculated for this assessment from concentrations in diet or drinking water, 

using U.S. EPA (1988) allometric equations, as described in Chapter 7.

bDoses calculated by the authors

8.1.1 RfD Determination

The selection of an endpoint of concern is based on exposure of healthy populations, 

including pregnant women and children, to strontium. People with impaired health are 

considered as part of the human variability, but the RfD is not based on those who require 

medical assistance to sustain life, such as individuals in chronic renal failure. The animal data 

suggest that adult animals are less sensitive than young animals to bone effects following 

strontium exposure. However no robust studies were located that would allow focused 

evaluation regarding the sensitivity of animals during fetal development, perinatal or lactation 

stages following strontium exposure. Two studies are considered co-critical for development of 

the strontium RfD. In the first co-critical study, Marie et al. (1985) exposed weanling male 

Sprague-Dawley rats (8/group) to 0, 0.19, 0.27, 0.34 or 0.4% strontium chloride in distilled water 

for 9 weeks. The diet contained 0.5% calcium, which is somewhat lower than typical rodent 

diets. Based on body weight and water consumption data, the authors estimated average 

strontium intakes of 0, 316, 425, 525 and 633 mg Sr/kg-day. A dose-related, statistically

significant decrease in the bone calcification rate was reported at doses of 525 mg Sr/kg bw-day
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and higher, with no significant change at the next lower dose of 425 mg Sr/kg bw-day; thus the 

LOAEL was 525 mg Sr/kg bw-day and the NOAEL was 425 mg Sr/kg bw-day. Based on 

decreased calcification rate and a BMR of 1 SD change from the mean, a BMDL of 328 mg 

Sr/kg-day was calculated. This was a well-conducted study with extensive quantitative 

documentation of the effect data. Although the number of animals/group is somewhat smaller 

than that recommended for a subchronic study (10/sex/group), the number evaluated (8 

males/group) is larger than those in the comparable studies (Storey, 1961: 3-10 females, Grynpas 

and Marie, 1990: 5 males). The use of a low-calcium diet in this study and in the other cocritical study (Grynpas and Marie, 1990) may provide an additional measure of protection, since 

the lower calcium may have increased the sensitivity of the test animals. 

In the second co-critical study, Grynpas and Marie (1990) exposed weanling male 

Sprague-Dawley rats (5/group/exposure duration) to 0, 0.19, or 0.40% strontium chloride in 

distilled water for 4 or 8 weeks. This diet also contained 0.5% calcium, which was reported by

the authors as a relatively low level of calcium, and is somewhat lower than typical rodent diets. 

Bone hypomineralization and increased bone mass were reported in rats exposed to 0.40% for 4 

or 8 weeks. No effect was seen at the low dose of 0.19% strontium chloride in water for either 

study duration. The tested concentrations correspond to doses of 0, 222, and 446 mg Sr/kg-day

during the 4-week study, and 0, 145, and 307 mg Sr/kg-day during the 8-week study, assuming 

ingestion of 0.211 L/kg-day by a weanling Sprague-Dawley rat or 0.139 L/kg-day by a SpragueDawley rat during a subchronic study (U.S. EPA, 1988). Thus, the NOAEL in this study is 145 

mg Sr/kg-day and the LOAEL is 307 mg Sr/kg-day, based on the 8-week study. This study is 

limited by the lack of experimentally-determined doses, the absence of an intermediate dose 

between the 0.19 and 0.4% dose groups, and the use of only 5 rats/group. 

In another study, Storey (1961) exposed young (40-60 gram) (specific age not reported) 

and adult (200-250 gram) female rats (3-10/dose group; strain not reported) to 0, 0.19, 0.38, 0.75, 

1 (young only), 1.5 or 3.0% strontium in the diet as strontium carbonate for 20 days. Assuming 

young rats consume 10% and adult rats consume 5% of their body weight in food per day, these 

doses correspond to 0, 190, 380, 750, 1000, 1500 and 3000 mg Sr/kg-day for young rats and 0, 

95, 190, 375, 750 and 1500 mg Sr/kg-day for adult rats (U.S. EPA, 1992). The dose groups 

apparently contained 10/dose for young rats and 3/dose for adult rats, but the number of young 

rats evaluated ranged from 3 to 10, depending on the endpoint. The diet was reported to contain 

1.6% calcium and 0.9% phosphorous. Young rats were more sensitive than adults. Inhibition of 

calcification, as evidenced by increasing width of the epiphyseal cartilage and uncalcified bone 

matrix was observed in young rats at the LOAEL of 380 mg Sr/kg-day; the NOAEL was 190 mg 

Sr/kg-day.

In adult rats, the LOAEL was 750 mg Sr/kg-day, based on histological changes of the 

bone, and the NOAEL was 375 mg Sr/kg-day. This study is limited by the small sample size, 

short exposure duration, lack of information on the animals’ age or strain, and the absence of 

experimentally-determined doses. Due to these limitations and considerations, the Storey (1961) 

study is considered closely supporting, unlike the U.S. EPA (1992) approach of considering this 

study co-critical. The point of departure is based on the Marie et al. (1985) study because of the 

uncertainties in the dose estimate from the Storey (1961) study and the longer exposure duration 
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in the Marie et al. (1985) study. The Storey (1961) study does provide perspective, on an 

additional time point to supplement the two critical studies. 

Appendix A, Table A-3 provides additional information on the Storey (1961) and Marie 

et al. (1985) studies, supporting the preference for the latter study as the basis for the RfD. In 

addition to the points noted above, the levels of dietary calcium were higher in the Storey (1961) 

study, as was reflected in higher Ca:Sr ratios in serum and bone. Furthermore, the serum levels 

of strontium at the NOAEL in the Storey (1961) study were higher than those at the dose below 

the NOAEL in the Marie et al. (1985) study. These points suggest that the doses in the Storey

(1961) study as estimated using factors not specific to strain because the authors did not identify

the strain of rat studies may not be accurate. In addition, the higher calcium levels in the diet may

have more protective than the levels in the Marie et al. (1985) study. These observations raise 

questions about whether the NOAEL in the Storey (1961) study for young rats is really lower 

than that in Marie et al. (1985), and/or whether the estimates Storey (1961) doses are accurate. 

The current IRIS summary (U.S. EPA, 1992) lists information from reports by Skoryna 

(1981) and Skoryna and Fuskova(1981) on a study with male RVH hooded rats (12/group) 

administered strontium chloride (55% strontium) in drinking water at 0, 900, 1,900 or 3,400 ppm 

for 3 years as a co-critical study. Assuming that an adult rat consumes water at a rate of 0.14 

L/kg-day, and adjusting to dose of strontium, the experimental doses correspond to 0,70, 147 and 

263 mg Sr/kg-day. Based on an observation of bone histology, histologic evaluation of selected 

organs (kidney, lungs, adrenal, brain, heart and muscle), and evaluation of body weight, no 

effects were reported; the NOAEL was the highest dose tested, 263 mgSr/kg-day.

The information from Skoryna (1981) and Skoryna and Fuskova(1981) is considered 

supporting rather than co-critical, as described by U.S. EPA (1992), for several reasons. The 

publications that mention the study lack important details regarding the study design. In 

addition, study sensitivity was decreased by the small sample size and long study duration, which 

results in increased age-related lesions in the control group. The initial starting weight of 250 

grams indicates that exposure did not occur during the sensitive period of active bone growth and 

calcium accretion. However, recognizing these caveats, this study indicates that a lower effect 

level is unlikely to be identified in a chronic study evaluating a broader array of tissues and 

endpoints than the single target (bone) evaluated in the co-critical studies by Marie et al. (1985), 

Grynpas and Marie (1990) and Storey (1961). Thus, this study supports the choice of co-critical 

studies. 

One study in Table 8-1 had a lower NOAEL and LOAEL, but the results did not support 

use of this study as the basis for the RfD because of lack of confirmation of the results in other 

studies. Kroes et al. (1977) reported histological signs of what they described as moderate 

thyroid activation in male rats and a non-dose-related increase in thyroid weight, with a NOAEL 

of 40 mg Sr/kg-day and a LOAEL of 160 mg Sr/kg-day. (No definition was provided for the 

term activation.) It is difficult to evaluate the implications of the observed changes because the 

study reported only thyroid weight and unspecified histological changes, with no supporting 

information on thyroid’s calciotropic and/or thyroxin-related hormone levels. No other study 

reported effects on the thyroid, and even the more recent studies of the CaSR (e.g., Coulombe et 
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al., 2004) have not focused on thyroid C-cell responses or hormones.

Johnson et al. (1968) reported respiratory difficulties and hindlimb paralysis in weanling 

Sprague Dawley rats administered 565 mg Sr/kg-day in feed for 43 days as an unspecified form 

of strontium. This study apparently tested only one dose level. Although this effect level is 

consistent with the co-critical studies, the severity of the effects suggests that the NOAEL might 

be lower than in the co-critical studies. This study was not used as co-critical or as the basis for 

the POD, because of a lack of support for the observed effects, even in studies at much higher 

doses, and because of the lack of experimental data that could support a mode of action for these 

effects. While it has been hypothesized that the paralysis could have been related to abnormal 

calcium signaling in muscle or nerve, paralysis was not reported at higher doses in other studies. 

It is unlikely that the paralysis was due to femoral deformation, as even severely rachitic rodents

and those with osteomalacia are not generally paralyzed. Instead, ATSDR (2004) suggested that 

the effects may have been due to compression of the hypertrophic epiphyseal cartilage, which 

was insufficiently mineralized to support the weight of the body. 

8.1.1.1 Benchmark Dose Approach

The calcification rate in Marie et al. (1985) was modeled using EPA’s Benchmark Dose 

Software, version 2.1, using benchmark response (BMR) definitions of 1 SD and 0.5 SD (one 

standard deviation and 1⁄2 standard deviation change from the mean, respectively). All of the 

standard continuous models were run and the data were modeled using both homogeneous and 

non-homogenous variance (See Appendix C). Neither approach was able to fit the variance well. 

Because the variance showed no clear pattern (both increasing and decreasing with dose), it is 

not surprising that neither approach was successful. However, the standard deviation estimated 

by the chosen model (0.11, for the restricted polynomial model) closely approximates the control 

SD (0.12), and so the BMD and the BMDL (the lower 95% confidence limit on the BMD) based 

on the SD are reliable. Because the BMR is defined in terms of the estimated control SD, a 

wrong estimate of the control SD will result in a mis-estimate of the BMR, and therefore of the 

BMDL. Therefore, it is much more important to have a good estimate of the control SD than of 

the SD at other doses, and the model with a homogenous variance is preferred over the model 

with a non-homogeneous variance, even though the latter model results in a slightly lower 

BMDL (317 mg Sr/kg-day). Both models would result in the same ultimate RfD.

Of the acceptable fits, the best fits are for the Hill, polynomial, and power models (all 

with goodness of fit p values well over 0.1). The unrestricted polynomial model resulted in a 

slightly U-shaped curve, and so the restricted polynomial model was used instead. Based only 

on the AIC

12 (i.e., not considering other fit measures, such as the p value, local fit or visual fit), 

the restricted polynomial model clearly has the best fit. The BMDL for this model is 328 mg 

Sr/kg-day. Although the value estimated by the Hill model at the dose closest to the BMD (the 

scaled residual, Table 8-2) is closer to the value reported in the study (a measure of “local fit” 

 

12 The AIC, or Akaike Information Criterion, is a measure of fit that takes into account the number of parameters in 

the model. For the same goodness of fit, models with fewer parameters are preferred. The Hill model has four 

parameters, or variables, that can be estimated by the model to provide flexibility in the curve fitting the data. Only 

three parameters were estimated for the polynomial model, meaning that it is a simpler model. 
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near the BMR), the “local fit” was also good for the restricted polynomial model, and the AIC 

for the Hill model is substantially larger. When selecting the appropriate BMD from a variety of 

model results, BMDs with smaller AICs (i.e., to the left on the number line) are preferred. 

Therefore, although both models have acceptable fit, the restricted polynomial model is 

preferred. Thus, the recommended BMDL based on a BMR of 1 SD is from the restricted 

polynomial model, 328 mg Sr/kg-day (BMD is 434 mg Sr/kg-day); other BMDLs were 355 (Hill 

model) and 348 (power model) mg Sr/kg-day (Table 8-2). In the absence of information about 

what degree of change is adverse, the default BMR of 1 SD was used.

BMDs were also calculated using a BMR of 0.5 SD for the sake of comparison. These 

BMDLs were in the range of 186-216 mg Sr/kg-day, with a BMDL of 186 mg Sr/kg-day for the 

restricted polynomial model. This BMDL is below the corresponding NOAEL for the decreased 

calcification rate, and based on a response that has not been quantified with respect to the degree 

of change that constitutes an adverse effect. Accordingly, the BMDL for a one standard 

deviation change is used for the RfD derivation. 

Table 8-2 Output of Benchmark Dose (BMD) Models using BMR of 1 Standard Deviation

Model Name BMD BMDL p-value AIC

Scaled 

Residual of 

Interesta

Hill 480.06 355.23 0.85 -127.51 0.07

Exponential2 -280.51 NA 0.11 -125.53 2.29

Exponential3 -280.51 NA 0.11* -125.53 2.29

Exponential4 NA 0 0.00* -111.24 0

Exponential5 NA 0 <0.0001* -109.24 0

Linear 347.55 238.75 0.16 -126.43 1.38

Polynomial 490.47 352.75 0.95 -129.45 -0.20

Polynomial 

(Restricted) 434.07 328.36 0.82 -130.61 0.30

Power 485.26 347.71 0.86 -129.25 -0.28

aThe scaled residual is a measure of the local fit, how close the modeled response is to the observed response at 

a specified dose, in this case, the dose closest to the BMR.

*Indicates that these results are from p-value tests 5a, 6a, and 7a, as reported in BMDS for exponential models 

3, 4, and 5, respectively.

NA = not available
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Figure 8-1 Restricted Polynomial model, BMR = 1 SD

As discussed above, the RfD is derived from the BMDL (1 SD) of 328 mg Sr/kg-day, for 

decreased bone calcification rate in male weanling rats (Marie et al., 1985), divided by a 

composite UF of 1000, resulting in a value of 0.3 mg Sr/kg-day.

RfD = BMDL = 328 mg/kg/day= 0.328 mg/kg/day (rounded to 0.3 mg/kg/day)

UF 1000

where:

BMDL = The 95% lower confidence bound on the BMD for a significant decrease

in bone calcification rate

UF = A composite uncertainty factor for intraspecies uncertainty, interspecies

uncertainty and database deficiencies.

The net uncertainty factor was derived as follows:

Human intraspecies variability - UFH - 10 

The critical effect was observed in young/weanling animals, the sensitive population. 

However, it is not clear if the window of vulnerability was adequately captured, since the 

weanling rats were exposed only for 28-63 days, a period that did not include exposure during 

gestation, lactation, and through young adulthood. In particular, fetuses exposed during bone 

development may be a sensitive population. As noted in Section 7.5.5, pre-teenagers and 

teenagers (particularly teenage girls) may be a sensitive population for strontium exposure, due 

 1

 1.1

 1.2

 1.3

 1.4

 0 100 200 300 400 500 600

Mean Response

dose

Polynomial Model with 0.95 Confidence Level

11:37 11/19 2010

BMDL BMD

 

Polynomial

BMD Lower Bound
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to the rapid bone growth and limited calcium intakes relative to need during this period. As 

discussed in Section 7.5.5, it is likely that sensitivity to strontium is affected by whether the 

individual has sufficient calcium intake. In addition, the data from the critical study demonstrate 

considerable heterogeneity among the small group of 8 males, suggesting the potential for a 

broad range of intraspecies variability. Because of these considerations, and the impact of 

inadequate calcification in bone at the end of the human adolescent growth period on the risk of 

bone fracture later in life, the full factor of 10 is used.

Animal to human variability - UFA– 10

Data are not available to develop a data-derived UFA, due to the lack of adequate 

information on toxicokinetic and toxicodynamic differences between rats and humans. 

Physiological differences between rats and humans indicate that adult rats may be more sensitive 

than adult humans to effects of strontium, since bone growth in rats continues throughout 

adulthood. However, this does not mitigate the differences for the critical effect, which occurs in 

young/weanling rats.

Extrapolation from LOAEL to NOAEL - UFL– 1

The Point of Departure (POD) for the RfD determination is a BMDL1 SD supported by a 

NOAEL. Therefore, no uncertainty factor is necessary to adjust from a lowest observed effect 

level. 

Extrapolation from subchronic to chronic exposure - UFS– 1

Exposure for a longer duration through adulthood than in the Marie et al. (1985) study is 

unlikely to be of concern for strontium, since that study was for a subchronic duration, and adults 

are less sensitive than the young rats that were exposed. Bone development in humans extends 

through adolescence, after which dietary calcium requirements, although still important, decrease 

(IOM, 2010). However, as noted in the context of the intraspecies factor, the critical studies did 

not include exposure during the entirety of the expected sensitive window (i.e., no exposure 

during gestation and lactation). An additional factor of 3 could be applied, but this concern was 

much of the rationale for the use of the full factor of 10 for intraspecies variability; thus, it is not 

necessary to include an additional UF to account for extrapolation from subchronic to chronic 

exposure. 

Database uncertainty/insufficiency - UFD– 10

Most of the database is from studies conducted in rats. However, a study of strontium 

chloride in weanling mice (Marie and Hott, 1986) reported effects in the same dose range as the 

Storey (1961) study, indicating that mice are not more sensitive than rats. Developmental 

toxicity studies suggest that the effects on bone development are of greatest concern. No 

standard reproductive studies are available, but several screening studies (NIER, 2006c; Skoryna, 

1981) found no toxic effects at doses higher than or comparable to those causing bone effects. 

As screening studies, these studies did not include complete evaluation of histopathology; the 
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absence of information on bone histopathology in the exposed fetuses is an important data gap. 

The review article by Skoryna (1981) provided very limited information regarding the 3-

generation study design and results.

Countering these considerations, there are a number of uncertainties in the database. The 

first relates to overall study sensitivity. The overall number of animals used in both of the 

critical studies is small, ranging from 5 to 8 per group, limiting the sensitivity of the studies, 

although the number of animals in the Marie et al. (1985) study was only slightly less than the 

10/group recommended for subchronic studies. The 20-day study by Storey (1961) apparently 

exposed 10 rats/group, however, it seems that as few as 3 were evaluated for the critical 

endpoint. 

Concerns about the strontium’s interaction with the thyroid were raised, based upon the 

data from Kroes et al. (1977) (see Table 8-1); however, the implications of the observed effects 

are unclear in light of the minimal reporting of the effects and the absence of data on the 

thyroid’s thyroxin-related and/or calciotropic hormone levels. An additional uncertainty relates 

to the potential for other effects not monitored in the Marie et al. (1985) study. Strontium’s 

chemical similarity with calcium allows it to exchange for calcium. Therefore, it is possible that 

exposure could affect synaptic signaling. While further neurotoxicity testing of adult animals is 

not likely necessary, based on the results of Johnson et al. (1968), ATSDR (2004) noted the lack 

of developmental neurotoxicity studies and the failure to include exposures during gestation and 

lactation as a data gap. 

Differences in the solubility of strontium carbonate (used by Storey, 1961) and strontium 

chloride were identified as a source of an uncertainty by U.S. EPA (1992). Strontium carbonate 

is much less soluble in water than strontium chloride, with solubilities of 110 mg/L and 538,000 

mg/L, respectively. No information was located on the bioavailability of strontium carbonate, 

but the lower solubility of the carbonate (solubility product constant 5.6 x 10 -10) would lead to 

lower bioavailability at sufficiently high doses. However, the implications of this lower 

solubility cannot be determined, due to many other differences between the studies using 

strontium chloride (Marie et al., 1985; Grynpas and Marie, 1990) and the study using strontium 

carbonate (Storey, 1961). These studies used different dosing protocols (in drinking water and 

food, respectively), different durations, and had differing uncertainties in the actual ingested 

doses. In addition, the calcium in the diet in the Storey (1961) study was more than three times 

higher than that in the Marie et al. (1985) study, with the Storey (1961) study providing a more 

protective calcium:strontium ratio. Despite these differences, there are not large quantitative 

differences in the LOAELs identified by these studies. These uncertainties about how to 

quantitatively account for differences in calcium intake and in the amount of absorbed strontium 

support the application of a10-fold factor for UFD. In addition, the use of a diet that is somewhat 

lower in calcium than standard rodent diets may have increased the sensitivity of the critical 

studies, providing some additional measure of protection. 
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8.1.1.2 NOAEL/LOAEL Approach

The NOAEL/LOAEL approach was not considered for determining an RfD for strontium 

because the data were amenable to benchmark modeling of dose-response.

8.1.1.3 Comparison with Current IRIS Assessment

The on-line IRIS RfD assessment of strontium was verified in 1992. It was based on the 

studies by Storey (1961) and Marie et al. (1985) with support from Skoryna (1981). The point of 

departure for the analysis was the estimated NOAEL (190 mg Sr/kg-day) from the Storey (1961) 

study using a 300-fold uncertainty factor. A factor of 10 was used for interspecies extrapolation, 

and a factor of 10 for an incomplete database (including a lack of developmental and 

reproductive data) and to account for uncertainties in using data for strontium carbonate to derive 

a risk estimate that may apply to other salts of strontium. An uncertainty factor of 3 was applied 

for sensitive subpopulations; a factor of 10 was not considered warranted because the critical 

study was performed in young animals, a recognized sensitive subpopulation. 

The OW has chosen the BMDL of 328 mg Sr/kg-day from the Marie et al (1985) study in 

establishing the point of departure for their analysis for the following reasons:

 The doses were reported by the authors rather than estimated,

 The duration of exposure was longer (63 days versus 20 days),

 The monitoring of the bone effects was more quantitative than the photomicrographs 

evaluated by Storey (1961),

 The dosing was via drinking water, the medium of interest for the OW,

 The strain of rats and the age of the animals at the time that dosing was initiated and 

completed were reported, and

 The data were amenable to dose-response modeling to identify the BMD and BMDL.

The RfD (0.3 mg Sr/kg-day) determined by the OW differs only slightly (2-fold) from 

that determined by IRIS (1992) (0.6 mg Sr/kg-day). The 1000-fold uncertainty factor utilized in 

the OW assessment reflects concern for impacts of strontium on developing bone and the 

nervous system because of its competitive interactions with calcium.

As described in Section 4.3.2, the concentrations of strontium in drinking water from 

national monitoring studies were compared to a Health Reference Level (HRL) to determine the 

frequency at which the HRL and half the HRL were exceeded. The HRL for strontium was 

derived from the RfD. Age-specific exposure factors were applied in order to adjust for the risk 

associated with exposures during infancy, childhood and adolescence, periods of active bone 

growth and calcification (Appendix B). The HRL is calculated as follows:

HRL = (RfD / ∑(DWI/BWR x F)) x RSC

HRL = (0.3 mg/kg/day ÷ 0.040 L/kg/day) x 0.2 = 1.5 mg/L =1,500 μg/L
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where:

RfD = 0.3 mg/kg/day

DWI/BWR = Drinking Water Intake Body Weight Ratio (DWI/BWR) expressed as liters 

per kg body weight (L/kg/day)(90th percentile, consumers only) for each 

age-specific period for the first 18 years, the average postnatal duration for 

bone growth in humans.

8.1.2 RfC Determination

The OW does not generally develop an RfC for drinking water contaminants but does 

adopt those that are provided in the IRIS database. The 1992 IRIS assessment of strontium did 

not determine an RfC. Strontium is not volatile, thus inhalation exposure is not likely. No data 

were identified that would support derivation of an RfC. 

8.2 Dose-Response for Cancer Effects

As described in Section 7.5.4, there is inadequate information to assess the carcinogenic 

potential (I) of strontium, due to the lack of adequate studies of chronic duration. The only

reports of a study that involved a chronic duration (Skoryna, 1981; Skoryna and Fuskova, 1981) 

included minimal reporting of the study design and outcomes. Although the study did not 

identify any tumors, the sensitivity was decreased by the small sample size for a chronic study

(12/dose group) and the likely increased background response resulting from the long study

duration. Therefore, no quantitative cancer assessment is appropriate. The on-line IRIS 

assessment of strontium did not evaluate the carcinogenicity of strontium.
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9.0 PRELIMINARY REGULATORY DETERMINATION AND 

CHARACTERIZATION OF RISK FROM DRINKING WATER

9.1 Preliminary Regulatory Determination for Chemicals on the CCL

The SDWA, as amended in 1996, required the U.S. EPA to establish a list of 

contaminants to aid the agency in regulatory priority setting for the drinking water program. The 

list of contaminants is called the Contaminant Candidate List (CCL). U.S. EPA has thus far 

published three CCLs in 1998, 2005, and 2009, respectively. The final CCL 3 was published in 

the Federal Register on October 8, 2009 (USEPA, 2009c; 74 FR 51850-51862).

The SDWA requires U.S. EPA to make regulatory determinations for no fewer than five 

contaminants from each CCL. In cases where the agency determines that a regulation is 

necessary, the regulation should be proposed and then promulgated. The agency is given the 

freedom to determine that there is no need for a regulation if a chemical on the CCL fails to meet 

one or more of three criteria established by the SDWA as described in Section 9.1.1. The 

agency’s preliminary regulatory determination for strontium is presented formally in the Federal 

Register. This section summarizes the preliminary Regulatory Determination 3 decision for 

strontium.

9.1.1 Criteria for Regulatory Determination

These are the three criteria used to determine whether or not to regulate a chemical on the 

CCL:

 The contaminant may have an adverse effect on the health of persons.

 The contaminant is known to occur or there is a substantial likelihood that the 

contaminant will occur in public water systems with a frequency and at levels of 

public health concern.

 In the sole judgment of the Administrator, regulation of such contaminant presents a 

meaningful opportunity for health risk reduction for persons served by public water 

systems.

The findings for all criteria are used in making a determination to regulate a contaminant. 

As required by the SDWA, a decision to regulate commits the agency to publication of a 

Maximum Contaminant Level Goal (MCLG) and promulgation of a National Primary Drinking 

Water Regulation (NPDWR) for that contaminant. The agency may determine that there is no 

need for a regulation when a contaminant fails to meet one or more of the criteria. A decision 

not to regulate is considered a final agency action and is subject to judicial review. The agency

can choose to publish a Health Advisory (a nonregulatory action) or other guidance for any

contaminant on the CCL, independent of the regulatory determination.
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9.1.2 National Drinking Water Advisory Council Recommendations

In March 2000, the U.S. EPA convened a Working Group under the National Drinking 

Water Advisory Council (NDWAC) to help develop an approach for making regulatory

determinations. The Working Group developed a protocol for analyzing and presenting the 

available scientific data and recommended methods to identify and document the rationale 

supporting a regulatory determination decision. The NDWAC Working Group report was 

presented to and accepted by the entire NDWAC in July 2000.

The Working Group developed separate but similar protocols for microorganisms and 

chemicals. The approach for chemicals was based on an assessment of the impact of acute, 

chronic, and lifetime exposures, as well as a risk assessment that includes evaluation of 

occurrence, fate, and dose-response. The NDWAC protocol for chemicals provided a semiquantitative, systematic approach to addressing each of the three Regulatory Determination 

criteria. The U.S. EPA utilized NDWAC suggestions for Regulatory Determinations 1, 2, and 3.

Because the process used in developing CCL 3 was more data-driven than that used for 

CCL 1 and CCL 2, the process used to select the chemicals for Regulatory Determination 3 

differed from the earlier Regulatory Determinations. The Regulatory Determination 3 process 

was formalized in a protocol document that was reviewed by an expert panel in October, 2011 

and revised in response to reviewer suggestions (U.S. EPA, 2012b). Strontium was selected for 

Regulatory Determination 3 based on the criteria outlined in the Protocol document. The 

quantitative and qualitative factors considered for each of the three criteria in making the 

Regulatory Determination for strontium are presented in the sections that follow.

9.2 Health Effects (Criterion #1)

The first criterion asks if the contaminant may have an adverse effect on the health of 

persons. Because all chemicals have adverse effects at some level of exposure, the challenge is 

to identify a health reference level (HRL), a dose below which adverse health effects are 

considered unlikely to occur (threshold toxicant), or below which adverse effects have a defined 

low probability of occurrence (non-threshold toxicant). The key elements that must be 

considered in evaluating the first criterion are the mode of action, the critical effect(s), the doseresponse for critical effect(s), the RfD for threshold effects, and the slope factor for nonthreshold effects.

A full description of the health effects associated with exposure to strontium is presented 

in Chapter 7 of this document and summarized below in Section 9.2.2. Chapter 8 and Section 

9.2.3 present dose-response information. 

9.2.1 Hazard Characterization and Mode of Action Implications

Several studies evaluated the relationship between strontium exposure or the body burden 

of strontium (as a measure of internal dose) and development of human disease following either 

occupational or environmental exposures (Curzon and Spector, 1977; Dawson et al., 1978; 
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Davies, 1979; 1984; St. Leger et al., 1980; Wang et al., 1990; Longerich et al., 1991; Özgür et 

al., 1996). In these studies, the hypothesis that strontium exposure might be correlated with 

effects other than those related to bone or teeth (i.e., neural tube defects, cancer mortality, or 

heart disease) was not supported (Dawson et al., 1978; Davies, 1979; 1984; St. Leger et al., 

1980; Wang et al., 1990; Longerich et al., 1991), although these studies are limited by inadequate 

control for other factors potentially contributing to the endpoint being evaluated. 

Two studies evaluating the effect of environmental strontium exposure on bone (Özgür et 

al., 1996) or teeth (Curzon and Spector, 1977) reported increased signs and severity of rickets 

with increasing strontium exposure and enamel mottling plus decreased dental caries, 

respectively. Several studies show that strontium levels are increased in people with renal 

failure, possibly because renal failure patients have impaired strontium clearance (D’Haese et al., 

1999, 2000; Vanholder et al., 2002; Cohen-Solal et al., 2002; De Broe and D’Haese, 2003). In 

European clinics, “low dose” strontium as strontium ranelate is used as a therapy for 

osteoporosis because of its inhibition of bone resorption without reducing bone formation in 

adults (McClasin and James, 1959; Krane, 1977; ATSDR, 2004). 

Experimental animal studies indicate that strontium has low acute oral toxicity via 

ingestion (Llobet et al., 1991; Ghosh et al., 1990; Woodard and Calvery, 1941). The primary

target of strontium exposure is the bone. The chemical similarity of strontium to calcium allows 

it to exchange imperfectly for calcium in a variety of biological processes; the most important of 

these is its substitution for calcium in bone, affecting skeletal development and causing effects in 

animal studies similar to osteomalacia and rickets (Storey, 1961, 1962; Kshirsagar, 1976; 

Johnson et al, 1968; Marie et al., 1985; Marie and Hott, 1986; Grynpas and Marie, 1990; Neufeld 

and Boskey, 1994). Concerns have been raised about strontium’s interaction with the thyroid, 

based upon the data from Kroes et al. (1977) (see Table 8-1); however, the implications of the 

observed effects are unclear in light of the minimal reporting by Kroes et al. (1977) and the 

absence of other studies reporting thyroid effects or supporting data on the thyroid’s thyroxinrelated and/or calciotropic hormone levels. 

Available data from limited reproductive/ developmental studies at strontium doses well 

above those causing bone effects indicate that strontium does not cause fetotoxicity or 

developmental effects on targets other than bone (Miki and Miyamota, 1968; Kroes et al., 1977; 

Skoryna, 1981; Shibata and Yamashita, 2001; NIER, 2006c). The animal data suggest that adult 

animals are less sensitive than young animals to bone effects following strontium exposure. 

However no robust studies were located that provided good dose-response information for bone 

effects in animals exposed to strontium during fetal development or perinatally.

No studies are available that evaluated tumor formation in an adequate number of 

animals treated with strontium for an adequate duration. Only a single chronic study is available 

for oral strontium exposure (Skoryna, 1981; Skoryna and Fuskova, 1981), and this study

evaluated small numbers of animals for longer than the standard exposure duration (increasing 

the potential for age-related lesions and decreasing study sensitivity). Therefore, the study was 

inadequate for evaluation of carcinogenic potential. In humans, there is no evidence for

strontium carcinogenicity. Strontium compounds other than strontium chromate are negative in 
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genotoxicity studies, with the exception of one in vivo chromosome aberration assay that had 

several limitations in the reporting of study design and results (Ghosh et al., 1990). Therefore, 

the agency determined that there is inadequate information to assess the carcinogenic potential 

of strontium, due to the lack of adequate studies of chronic duration. 

9.2.2 Dose-Response Characterization 

Two studies were considered co-critical for development of the strontium RfD (Marie et 

al., 1985; Grynpas and Marie, 1990). The LOAELs in the co-critical studies were 525 and 307 

mg Sr/kg-day, respectively, based on effects such as hypomineralization, increased bone mass or 

decreased calcification. These studies used diets containing 0.5% calcium, which is somewhat 

lower than typical rodent diets; the lower calcium intake may have increased the sensitivity of 

the test animals. Benchmark dose modeling was performed using EPA’s Benchmark Dose 

Software, version 2.1, to derive the RfD. The model with the best overall fit was used. The RfD 

is derived from the BMDL (1 SD) of 328 mg Sr/kg-day, for decreased bone calcification rate in 

male weanling rats (Marie et al., 1985), divided by a composite UF of 1000. The composite UF 

is based on a factor of 10 for interspecies differences, a factor of 10 for protection of sensitive 

populations, and a factor of 10 for database uncertainties and deficiencies, including the small 

sample size in the critical studies, the absence of standard developmental or reproductive toxicity 

studies, and uncertainties regarding differences in strontium uptake from different strontium 

compounds, somewhat countered by the added sensitivity due to the low calcium diets in the 

critical studies. An RfD of 0.3 mg Sr/kg-day results. 

EPA calculated a non-cancer HRL of 1,500 μg/L for strontium using the RfD of 0.3 

mg/kg/day, an RSC of 20%, and age-specific exposure factors (i.e., drinking water intake 

expressed as liters per kg of body weight) for the sensitive population of birth through 18 years 

to reflect the most active period of bone growth and development.

There is inadequate information to assess the carcinogenic potential of strontium. Due to 

the lack of adequate studies of chronic duration no cancer slope factor was calculated. 

9.2.3 Health Criterion Conclusion

The available toxicological data indicate that exposure to strontium has the potential to 

cause adverse health effects in humans and animals; bone is the primary target. A potential link 

between high strontium exposures and rickets in Turkish children was reported by Özgür et al. 

(1996), but the data were insufficient for identifying the doses associated with this effect. No 

other epidemiology study was located that evaluated bone effects following strontium exposure. 

Clinical studies are available (McClasin and James, 1959; Krane, 1977; D’Haese et al., 1999, 

2000; Vanholder et al., 2002; Cohen-Solal et al., 2002; De Broe and D’Haese, 2003). However,

these studies are limited to patients with bone disorders or chronic renal failure; thus, they are 

considered as part of human variability but are not appropriate for the basis of the RfD. 

Disruption of normal skeletal development, causing effects similar to osteomalacia and 

rickets in rats (young and adult) and mice has been reported following subchronic and chronic 
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oral strontium exposure (Storey, 1961, 1962; Kshirsagar, 1976; Johnson et al, 1968; Marie et al., 

1985; Marie and Hott, 1986; Grynpas and Marie, 1990; Neufeld and Boskey, 1994). Data to 

support the potential for effects on systems other than the skeleton are limited.

Toxicological data from human and animal studies indicate that bone is a target of 

strontium toxicity. Data on decreased bone calcification in rats support the development of an 

HRL of 1,500 μg/L for human exposure via drinking water. Based on these considerations, EPA 

concludes that strontium meets the SDWA statutory criterion #1 for regulatory determinations; it 

may have an adverse effect on the health of persons.

9.3 Occurrence in Public Water Systems (Criterion #2)

The second criterion asks if the contaminant is known to occur or if there is a substantial 

likelihood that the contaminant will occur in public water systems with a frequency and at levels 

of public health concern. In order to address this question, the U.S. EPA consulted a variety of 

information sources, including data from the National Inorganics and Radionuclides Survey

(NIRS), a nationally representative survey of ground water systems conducted from 1984 to 

1986. The U.S. EPA looked at the total number of systems that reported detections of strontium, 

as well as those that reported concentrations of strontium above the drinking water health 

reference level (HRL) of 1500 μg/L. 

The available monitoring data, including data that shed light on regional and national 

occurrence, are presented in Chapter 4 of this document and in Chapter 5 of the Regulatory

Determinations 3 Support Document (USEPA, 2012b), and are summarized below. Additional 

information on production, use, and fate are found in Chapters 2 and 3 of this document and in 

Chapter 5 of the Regulatory Determinations 3 Support Document (USEPA, 2012b).

9.3.1 Monitoring Data

Concentrations of strontium from CWSs supplied from ground water sources were 

obtained from the NIRS, a nationally representative survey conducted from 1984 to 

1986. Strontium was monitored with a reporting level of 1 μg/L. The mean reported level was 

603 μg/L, the mean for the detection was 603 mg/L and the maximum reported level was 43,500 

μg/L (a value approximately 30 times the HRL). Sixty-nine of 989 systems (6.98%) reported 

detections greater than the HRL. The national extrapolation from these findings suggests an 

estimated 2,798 ground water CWSs serving 10.0 million people nationally will have strontium 

concentrations exceeding the HRL. 

Review of the NIRS data shows that strontium was detected in all 50 states/entities in 

which it was sampled (i.e., in 49 states (all except Hawaii) as well as Puerto Rico). It was 

detected at levels greater than 1/2 the HRL (750 μg/L) in 34 states and at levels greater than the 

HRL (1,500 μg/L) in 26 states, including states in all regions of the country.

Finished water data for strontium from Ohio and Illinois are consistent with the NIRS 

data. The State of Illinois reported results from testing 21 drinking water samples from 19 
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PWSs; strontium was detected in all 21 samples (100%). Approximately 23.8% (5 of 21) of 

samples from five systems (26.3%) had strontium at levels greater than or equal 1⁄2 HRL (750 

μg/L), and approximately 23.8% (5 of 21) of samples from five systems (26.3%) had strontium 

at levels greater than or equal the HRL (1,500 μg/L). The State of Ohio reported results from 

testing 77 samples from 32 PWSs; strontium was detected in 75 samples (97.4%) from 30 

systems (93.8%). Approximately 27.3% (21 of 77) of samples from 31.3% (10 of 30) of systems

had strontium at levels greater than or equal 1⁄2 HRL, and approximately 23.4% (18 of 77) of 

samples from 21.9% (7 of 30) of systems had strontium at levels greater than or equal to the 

HRL (USEPA, 2012b). Finished water data from Ohio and Illinois come from both surface 

water and ground water systems; rates of strontium detection and HRL exceedance from the two 

source water types are comparable. More limited monitoring data gathered from states by the 

Environmental Working Group confirm that strontium has been detected in PWSs within 

Wisconsin, Illinois, New York, Minnesota, and Ohio.

Ambient water data also show high levels of occurrence, which is expected since 

strontium is a naturally occurring element. The NAWQA Quality of Public Supply Wells 

(Toccalino et al., 2010) study collected water samples from source (untreated) groundwater 

public supply wells in 41 states. Each well was sampled once from 1993-2007, and strontium 

was detected in 100% of samples (503 of 503). Of the detections, 25.8% (130 of 503) were 

above the 1⁄2 HRL (750 μg/L) and 12.3% (62 of 503) were above the HRL (1,500 μg/L). 

STORET, which includes data on ambient water, records strontium concentrations over 12,000 

times greater than the HRL. 

9.3.2 Occurrence Criterion Conclusion

NIRS, a nationally representative survey of ground water, indicates that strontium 

concentrations exceed the HRL of 1,500 μg/L in 6.98% of PWSs, and in some cases the 

measured concentrations exceed the HRL by large margins. The national extrapolation from

these findings suggests an estimated 2,789 ground water CWSs serving 10.0 million people 

nationally will have strontium concentrations exceeding the HRL. In addition, the supplemental 

surface water data for strontium are consistent with the groundwater findings and demonstrate 

the potential for high levels of occurrence in surface waters. 

Based on these considerations, the U.S. EPA concludes that strontium meets the SDWA 

statutory criterion #2 for regulatory determinations; it is known or likely to occur with a 

frequency and at levels of public health concern in PWSs.

9.4 Risk Reduction (Criterion #3)

The third criterion asks if, in the sole judgment of the Administrator, regulation presents a 

meaningful opportunity for health risk reduction for persons served by public water systems. In 

evaluating this criterion, the U.S. EPA looked at several factors. 

Using the monitoring results, the U.S. EPA estimated the total exposed population and 

the population exposed to levels above the HRL. These estimates are included in Chapter 4 of 
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this document and summarized in Section 9.4.2 below.

The U.S. EPA also evaluated the relative contribution of drinking water exposure and 

other routes of exposure (e.g., in food, via air, etc.) to overall risk. For example, if exposure to a 

contaminant occurs primarily through ambient air, regulation of emissions to air may provide a 

more meaningful opportunity for the U.S. EPA to reduce risk than regulation of the contaminant 

in drinking water. In making the preliminary regulatory determination, the available information 

on exposure through drinking water (Chapter 4) and information on exposure through other 

media (Chapter 5) were used to estimate the fraction that drinking water contributes to the total 

exposure. These findings are discussed in Section 9.4.3 below.

In evaluating the third criterion, the U.S. EPA also considered effects on potentially

sensitive populations, including the fetus, infants, and children. Sensitive population 

considerations are discussed in Chapter 7 and in Section 9.4.4 below. 

9.4.1 Exposed Population Estimates 

The U.S. EPA estimated the populations served by CWSs with water containing 

strontium at any level, and at levels in excess of the HRL or 1⁄2 the HRL, based on extrapolation 

from stratified, random sampling of the nation’s community ground water supplies as they

existed in the mid-1980s, recorded in the NIRS database.

According to NIRS data, among the population served nationally by CWSs relying on 

ground water, a total of 93.0 million people (99.9%) may be exposed to strontium in drinking 

water. A subset of 15.4 million (16.6%) may be exposed to concentrations in excess of 1⁄2 the 

HRL, and 10.0 million (10.7%) may be exposed to concentrations in excess of the HRL. These 

estimates do not include people who may be exposed to strontium from CWSs relying on surface 

water, or from public water supplies other than CWSs.

9.4.2 Relative Sources of Exposure

The contribution of drinking water to total strontium exposure can be estimated by

comparing the exposure expected via drinking water to the exposure from intake of strontium in 

other media, such as food, air, and soil (See Chapter 5).

The intake of strontium from drinking water can be calculated from the NIRS ground 

water data, where the mean concentration among the detections was 603 μg/L. Using a 90th

percentile daily intake of 2 L/day for an adult, the daily exposure would be 1,206 μg/day. For 

formula-fed infants, assuming a water intake of 1 L/day, the intake would be 603 μg/day.

Although strontium is known to occur in food, air, and soil, data on levels in those media 

are limited, as are estimates of exposures from those sources. Food appears to be a more 

significant source than air and soil although the presence of strontium in both agricultural soils 

and drinking water can influence the levels in the diet. Dietary intakes based on an FDA Total 

Diet Study by Pennington and Jones (1987) range from 493 to 685 μg/day for children 6 months 
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to 2 years old, 928 to 1,388 μg/day for 14- to 16-year-old adolescents, and 979 to 1,489 μg/day

for adults (ages 25-30 and 60-65). In another study, Iyengar et al. (2000) estimated dietary intake 

for 25 - 30 year old males to be 1,620 μg/day. Note that there is considerable variability in the 

strontium intake from both diet and water, and the data presented here are only estimates. 

Estimated strontium intakes from air and soil are very low compared with those from 

food. Exposure from air has been estimated from data for levels of strontium in non-occupational 

air to be 0.1 μg/day for children and 0.3 μg/day for adults. The estimates of intake from soil are 

14 μg/day for infants, 24 μg/day for children, and 12 μg/day for adults. 

It is possible to estimate the approximate contribution of drinking water from PWSs to 

total strontium exposure using the data presented in Chapter 5 and OW general policies for body 

weight and drinking water intakes. However, many of these data are dated and some aspects of 

strontium exposure may have changed. No data were identified on consumer products, such as 

toothpaste that contain strontium as an ingredient or impurity. Development of a MCLG in 

response to a positive Regulatory Determination will require an updated and more refined 

exposure assessment to determine the RSC. 

9.4.3 Sensitive Populations

Because strontium can substitute for calcium in growing bone, the fetus, newborns, 

infants, children and young adults are a sensitive population. The estimated populations of 

pregnant women (and thus fetuses) and of children (<17 years old) in the United States are 6 and 

75 million, respectively (U.S. EPA, 1998c). Because many of the toxic effects of strontium 

result from strontium ions substituting for calcium ions, calcium deficiency would be expected to 

result in increased sensitivity. Frank calcium deficiency is uncommon, but long-term intake of 

calcium below recommended levels might have negative health consequences. Groups with 

higher risks of becoming calcium deficient include: teenage and postmenopausal women, 

amenorrheic women, female athletes, vegans, and individuals with lactose intolerance or cow’s 

milk allergies (IOM, 2010; NIH, 2011a). Less than 1% of the population has an allergy to cow’s 

milk and approximately 25% of U.S. adults have a limited ability to digest lactose, including 

85% of Asians, 50% of African Americans, and 10% of Caucasians (NIH, 2011a).

Because the major route of elimination of strontium is via the kidneys, individuals with 

impaired renal function are another sensitive population. This population may potentially have 

impaired strontium clearance, as has been shown in renal failure patients. There are 

approximately 20,000,000 people (10%) above the age of 20 with chronic kidney disease (CDC, 

2010) and 547,982 people with kidney end-stage renal disease (USRDS, 2010), who may thus be 

at an increased risk.

People with disorders affecting the normal equilibrium between the breakdown of old 

bone and the formation of new bone (such as Paget’s disease) might also be sensitive to 

strontium exposure. According to the National Institute of Arthritis and Musculoskeletal

Diseases, there are approximately 1 million people (1.2 people per 100 men and women age 45 

to 74) diagnosed with Paget’s disease of the bone (NIH, 2011b). The disease is more common in 
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older people and those of northern European heritage. Men are about twice as likely as women 

to have this disorder. 

9.4.4 Risk Criterion Conclusion 

Based on data from NIRS, an estimated 10.0 million people are exposed nationally to 

levels of strontium greater than the HRL (1500 μg/L). The measured concentrations in NIRS 

exceed the HRL by large margins in some water systems. STORET, which includes data on 

ambient water, records strontium concentrations up to 13,000 times greater than the HRL. 

Approximately 40-90% of strontium exposure is estimated to come from drinking water; food is 

the second-most-significant source of exposure. Potentially sensitive populations include fetuses, 

infants and children, as well as calcium-deficient individuals and those with impaired renal 

function and Paget’s disease. 

The U.S. EPA finds that strontium meets the SDWA statutory criterion #3 for regulatory

determinations; regulation of strontium presents a meaningful opportunity for health risk 

reduction in drinking water based on the estimated exposed population and potential impacts on 

sensitive populations.

9.5 Regulatory Determination Decision

As stated in Section 9.1.1, a positive finding for all three criteria is required in order to 

make a determination to regulate a contaminant. The U.S. EPA has made a preliminary

determination that strontium meets all three criteria. 

Strontium has the potential to cause adverse health effects to the bone, based on 

toxicological data from animal studies, limited human data and an understanding of its mode of 

action. Strontium is known to occur in PWSs with a frequency and at levels of public health 

concern. Data from NIRS indicate that strontium concentrations exceed the HRL of 1,500 μg/L 

in 6.98% of ground water CWSs, and suggest that an estimated 10.0 million people nationally 

may be exposed to strontium in drinking water from PWSs at levels of health concern. Due to 

the large number of people exposed to strontium through drinking water and the potentially high 

concentration of strontium measured in these PWSs, regulation of strontium presents a 

meaningful opportunity for health risk reduction for persons served by PWSs, especially for 

those with developing bones (such as infants, children, and adolescents), individuals deficient in 

calcium, and persons with kidney conditions.

Additional information about the preliminary regulatory determination can be found in 

the Federal Register Notice.
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APPENDIX A. Summary of Data from Key Animal Studies

Table A-1 Summary of Relevant Animal Toxicity Studies

Species, Strain, 

Sex, Age

Form of 

Strontium 

and Dosing 

Medium

Doses

(mg Sr/kgbw/day)

Animals 

per sex per 

dose

Exposure 

Duration

NOAEL

mg/kg-day

LOAEL

mg/kg-day Critical Effect Comment Reference

Monkey, NS Chloride, oral 

capsule

1100 NA 7 days -- 1100 Local irritation of 

the GI tract

Effects observed occurred at 

the portal of entry, do not 

appear to be systemic effects 

associated with high dose 

exposure.

Irritation caused hemorrhage 

and erosive lesions of the 

esophagus and upper 

duodenum 

Fisch et al. (2006)

Rat,

Wistar, M/F, 

Weanling

Chloride hexahydrate, Diet0, 0.1, 1.1, 11, 

110

3 14 days 110 -- No reported effect 

on bone histology, 

but effects on bone 

were not specifically 

evaluated.

No effects on 

clinical signs, organ 

weight, tissue 

histopathology, or 

hematology. 

The diet contained 0.85%

Ca, 0.75% P, 0.05% Mg and 

1.8 IU Vitamin D3 /g. These 

amounts were said to be 

“adequate” levels by the study 

author.

Assuming young rats consume 

feed at an amount equivalent 

to about 10% of their body 

weight per day.

Kroes et al. (1977)
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Species, Strain, 

Sex, Age

Form of 

Strontium 

and Dosing 

Medium

Doses

(mg Sr/kgbw/day)

Animals 

per sex per 

dose

Exposure 

Duration

NOAEL

mg/kg-day

LOAEL

mg/kg-day Critical Effect Comment Reference

Rat, Wistar, 

Male, Weanling

Phosphate, 

Diet

0, 3000 5-6 2 weeks -- 3000 Decreased growth The diet contained 0.4% Ca, 

0.4% P, and, per kg of diet, 

5000 IU of vitamin D.

The control diet also contained 

0.001% strontium 

(corresponding to about 1.5 

mg Sr/kg-day).

Effects caused by strontium 

exposure were reversed by 2 

weeks on the control diet.

Kshirsagar (1976)

Rat, NS, 

Female, Young

Carbonate, 

Diet

0, 190, 380, 750, 

1000, 1500, 

3000

3-10 20 days 190 380 Inhibition of 

calcification 

(increased width of 

epiphyseal cartilage, 

uncalcified bone 

matrix)

Diet contained 1.6% calcium 

and 0.9% phosphorus.

Assuming 10% ingestion of 

bw-day. Conversions done by 

EPA (1992).

Apparently 10 exposed, but 

number evaluated ranged from 

3 to 10 depending on 

endpoint.

Storey (1961)

Rat, NS, 

Female, Adult

Carbonate, 

Diet

0, 95, 190, 375, 

750 and 1500 

3 20 days 375 750 Changes in bone 

structure; inc width 

of epiphyseal 

cartilage plate

Diet contained 1.6% calcium 

and 0.9% phosphorus.

Assuming 5% ingestion of 

bw-day. Conversions done by 

U.S. EPA (1992).

Storey (1961)

Rat, England 

Wright Y, Male, 

Weanling

NS, Diet 0, 1850 5 20 days -- 1850 Reduced growth, 

thickened epiphyseal 

growth plate

The basic diet contained 1.2% 

Ca, 1% P, and 1500 IU of 

vitamin D per kg, and was 

described as sufficient in these 

nutrients

Reinholt et al. 

(1984)
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Species, Strain, 

Sex, Age

Form of 

Strontium 

and Dosing 

Medium

Doses

(mg Sr/kgbw/day)

Animals 

per sex per 

dose

Exposure 

Duration

NOAEL

mg/kg-day

LOAEL

mg/kg-day Critical Effect Comment Reference

Rat, SpragueDawley, 

Male, Weanling

Carbonate, 

Diet

0, 500 18 3 weeks -- 500 Numerous bone 

abnormalities

No evidence of Vitamin D 

abnormality

Neufeld and Boskey 

(1994)

Rat, SpragueDawley, Male, 

Weanling

NS, Diet 0, 1520 10 26 days -- 1520 Numerous bone 

abnormalities

Serum concentrations of 

calcium, phosphorus and 

parathyroid hormone were 

reported to be normal, but the 

method used to measure the 

parathyroid hormone could 

not distinguish between the 

active and inactive form of the 

hormone.

Svensson et al. 

(1985,1987)

Rat, Wistar, 

Female, 

Weanling (36 

day old)

Carbonate, 

Diet

0, 50,

100, 500 

6-8 27 days 100 500 Decreased bone 

formation rate

0.5% calcium, 0.35% 

phosphorus, and

supplemented with vitamin 

D3.

Morohashi et al. 

(1994)

Mouse,

C57BL/6J, 

Male, 

Weanling

Chloride,

Drinking water

0, 350 11-13 29 days -- 350 10% increase in 

osteoid surface and 

an 11% reduction in 

the number of active 

osteoclasts

The diet contained 0.5% Ca, 

0.74% P, and 2,000 IU of 

vitamin D/kg

Marie and Hott 

(1986)

Rat, Wistar, 

Male, Adult

Carbonate, 

Diet

0, 1970 30 4 weeks -- 1970 Reduced growth and 

bone mineralization

Diet contained 0.04% Ca 

(described as low calcium)

Matsumoto (1976)

Rat, SpragueDawley, Male, 

Weanling

Chloride, 

Drinking 

Water

0, 222, and 466 5 4 weeks 222 466 Bone 

hypomineralization 

and increased bone 

mass

Diet contained 0.5% calcium, 

0.54% phosphorous, 0.16% 

magnesium, and 2000 IU/kg 

vitamin D. A low calcium diet 

was used in order to magnify 

the effects of strontium.

Grynpas and Marie 

(1990)
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Species, Strain, 

Sex, Age

Form of 

Strontium 

and Dosing 

Medium

Doses

(mg Sr/kgbw/day)

Animals 

per sex per 

dose

Exposure 

Duration

NOAEL

mg/kg-day

LOAEL

mg/kg-day Critical Effect Comment Reference

Rat, Wistar, 

Male, Weanling

Phosphate, 

Diet

0, 580, 1270and 

2820

5-6 4-6 weeks 580 1270 Slowed growth and 

altered alkaline 

phosphatase activity.

The diet contained 0.4% Ca, 

0.4% P, and, per kg of diet, 

5000 IU of vitamin D.

The control diet also contained 

0.001% strontium 

(corresponding to about 1.5 

mg Sr/kg-day).

Kshirsagar (1976)

Rat, SpragueDawley, Male, 

Weanling

NS, Diet 0, 565 15 43 days -- 565 Respiratory 

difficulties, 

hindlimb paralysis, 

rickets and 

osteomalacia and 

40% mortality.

Cause of the paralysis is 

unclear. 

Johnson et al. (1968)

Rat, SpragueDawley, Male, 

Weanling

Chloride, 

Drinking 

Water

0, 146, 307 5 8 weeks 146 307 Bone 

hypomineralization 

and increased bone 

mass

Diet contained 0.5% calcium, 

0.54% phosphorous, 0.16% 

magnesium, and 2000 IU/kg 

vitamin D. A low calcium diet 

was used in order to magnify 

the effects of strontium.

Grynpas and Marie 

(1990)

Rat, SpragueDawley, Male, 

28-day old

NS, Drinking 

Water

0, 168 8 8 weeks -- 168 Increase in mineral 

bone volume (17%) 

and an increase in 

the number of boneforming sites (70%).

Diets containing 0.5% 

calcium, 0.54% phosphorus, 

0.16% magnesium and 2,000 

IU/kg vitamin D, in order to 

support adequate bone 

mineralization. 

Drinking water also contained 

0.15% calcium.

Grynpas et al. 

(1996)
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Species, Strain, 

Sex, Age

Form of 

Strontium 

and Dosing 

Medium

Doses

(mg Sr/kgbw/day)

Animals 

per sex per 

dose

Exposure 

Duration

NOAEL

mg/kg-day

LOAEL

mg/kg-day Critical Effect Comment Reference

Rat

SpragueDawley, male, 

weanling

Chloride, 

Drinking water

0, 316, 425, 525, 

633 

8 9 weeks 425 525 Decreased 

calcification rate 

Diet contained 0.5% calcium, 

0.54 phosphorous, 0.16% 

magnesium, and 2000 IU/kg 

vitamin D.

Doses calculated by authors

BMDL = 328 mg Sr/kg-day, 

based on a BMR of 1 SD 

change in the mean

Marie et al. (1985)

Rat,

Wistar, M/F, 

Weanling

Chloride 

hexahydrate, 

Diet

0, 2, 9, 36, 146 

(M); 

0, 3, 10, 42, 166 

(F)

10 90 days 36 (M) 146 (M) Histological signs of 

thyroid activation in 

males and non-doserelated increase in 

thyroid wt. 

The diet contained 0.85%

Ca, 0.75% P, 0.05% Mg and 

1.8 IU Vitamin D3 /g. These 

amounts were said to be 

“adequate” levels by the study 

author.

Assuming young rats consume 

feed at an amount equivalent 

to about 10% of their body 

weight per day.

No reported effect on bone 

histology

Kroes et al. (1977)
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Species, Strain, 

Sex, Age

Form of 

Strontium 

and Dosing 

Medium

Doses

(mg Sr/kgbw/day)

Animals 

per sex per 

dose

Exposure 

Duration

NOAEL

mg/kg-day

LOAEL

mg/kg-day Critical Effect Comment Reference

Rat, 

RVH hooded , 

Male

NS

Chloride, 

Drinking 

Water

0, 70, 147, 263 10 3 months 263 -- No effect on 

microscopic 

appearance of 

organs or bone.

The study authors indicate that 

“Adequate” amounts of 

calcium (35 mg/L) and 

magnesium (6.8 mg/L) ppm) 

were given in the drinkingwater. 

Control drinking water also 

contained 0.2 mg/dL 

strontium, corresponding to a 

dose of 0.015 mg Sr/kg-day

Presented in a review article 

with limited primary data. 

Assumes that an adult rat 

consumes 0.14 L water/kg bw 

per day (U.S. EPA 1992)

Skoryna (1981); 

Skoryna and 

Fuskova (1981)

Rat, NS, M/F, 

Young 

Carbonate, 

Diet

0, 2160 12-50 7 months -- 2160 Rachitic gait within 

3 weeks in young 

rats; histological 

abnormalities of 

long bone 

differentiation; 

changes in adult rats 

were observed after 

3 months of 

exposure.

Diet containing 1.5% calcium, 

0.9% phosphorus.

Strontium effects seen in 

young rats were more severe 

than in older animals. 

Storey (1962)
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Species, Strain, 

Sex, Age

Form of 

Strontium 

and Dosing 

Medium

Doses

(mg Sr/kgbw/day)

Animals 

per sex per 

dose

Exposure 

Duration

NOAEL

mg/kg-day

LOAEL

mg/kg-day Critical Effect Comment Reference

Rat, 

RVH hooded, 

Male, Adult

Chloride, 

Drinking 

Water

0, 70, 147 and 

263 

12 3 years 263 -- No adverse effects 

on growth or on 

microscopic 

appearance of 

organs or bone.

The study authors indicate that 

“Adequate” amounts of 

calcium (35 mg/l) and 

magnesium (6.8 mg/l) were 

given in the drinking-water.

Control drinking water also 

contained 0.2 mg/dL 

strontium, corresponding to a 

dose of 0.015 mg Sr/kg-day

Presented in a review article 

with limited primary data. 

Assumes that an adult rat 

consumes 0.14 L water/kg bw 

per day. 

Skoryna (1981); 

Skoryna & Fuskova 

(1981); U.S. EPA, 

(1992)

Rat, NS, Male, 

Adult

Sulfate, 

Gavage

240, 480, 950 16 42 days, 

including 2 

weeks prior 

to mating

240 480 Increased 

epididymis and 

testis weights

Authors reported no effects on 

mating behavior, fertility, 

gestation period or 

histopathology of the 

reproductive tissues and 

organs.

NIER, (2006c)
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Species, Strain, 

Sex, Age

Form of 

Strontium 

and Dosing 

Medium

Doses

(mg Sr/kgbw/day)

Animals 

per sex per 

dose

Exposure 

Duration

NOAEL

mg/kg-day

LOAEL

mg/kg-day Critical Effect Comment Reference

Rat, NS, 

Female, Adult

Sulfate, 

Gavage

240, 480, 950 16 40-54 days, 

including 2 

weeks prior 

to mating 

through day 

4 of lactation

950 -- There was no effect 

on survival, growth, 

sensory and motor 

functions, urinalysis, 

or the microscopic 

appearance of the 

tissues and organs 

evaluated (including 

bone) at doses up to 

950 mg Sr/kg-day.

There were no adverse effects 

on fetal development. 

However, there was no 

microscopic examination for 

skeletal or visceral alterations.

Decreased spleen weight 

observed at 240 mg Sr/kg-day

and higher, but no information 

was available on degree of 

change or on related 

hematological measures.

No effects on mating 

behavior, fertility, gestation 

period or histopathology of the 

reproductive tissues and 

organs. 

NIER (2006c)

Mice, NS, 

Female, Adult

Carbonate, 

Diet

0, 1500 4 dams Gestational 

day 1 - birth 

-- 1500 In newborn pups, 

extensive inhibition 

of calcification of 

mandibular bone 

and cartilage

No effect on maintenance of 

pregnancy, fetal numbers or 

fetal viability.

Sr-exposed group received a 

diet “deficient in vitamin D3” 

(not further described) with 

low calcium (0.003%) 

content.” The control group 

got “normal food”, which 

apparently not vitamin D 

deficient or low in calcium

Shibata and 

Yamashita (2001)

Bw = body weight; GI = gastrointestinal; inc = increased; NA=not applicable; NS=not stated
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Table A-2 Primary Data Table from Marie et al. (1985), Table V

Effects of strontium supplementation on bone growth and on bone formation and resorption

Controls 0.19% SrCl2 0.27% SrCl2 0.34% SrCl2 0.40% SrCl2

Tibia length, cm 3.84±0.16 3.77±0.10 3.80±0.09 3.77±0.13 3.75±0.09

Calcified bone volume, % bone tissue 19.1±2.1 22.8±3.6a21.7±3.3 22.9±2.6c17.6±2.4

Osteoblastic surface, % osteoid surface 69.9±6.7 64. 3±8.9 61.2±12.5 62.2±10.7 52.5±10.7c

Double-labeled surface, % total endosteal surface 16.7±3.0 21.4±6.8 22.3±7.2 23.1±4.7c22.4±3.2c

% osteoid surface 89.9±6.8 83.6±9.4 82.7±9.6 90.3±5.1 65.6±6.6d

Calcification rate, μm/day 1.32±0.12 1.31±0.05 1.25±0.16 1.18±0.09b1.10±0.13c

Osteoclastic surface, % total endosteal surface 3.4±0.5 3.2±0.5 3.5±0.7 3.3±0.8 3.5±0.6

Chrondroclast and osteoclast, number/mm226.1±3.6 22.6±4.3 23.3±7.2 25.1±5.1 23.9±3.2

Data are the mean ±SD of 8 values. A significant difference with controls is indicated by: ap<0.05; bp<0.02; cp<0.01; dp<0.001.
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Table A-3 Comparison of Key Parameters from Marie et al. (1985) and Storey (1961)

Parameter Marie et al. (1985) Storey (1961)

Initial BW 45-60 g 40-60 g

Dietary Ca 0.5% 1.6%

Dietary P 0.54% 0.9%

Vitamin D 2,000 IU/kg ND

Dose medium Drinking Water Diet

Food Sr ND ND

Water Distilled Distilled

Sr Salt SrCl2 SrCO3

Number of animals

n=8

5 exposed at 0.19%; analysis for 

n=3 (serum) or 5 (bone)

8 exposed at 0.38%; analysis of n= 

5 (serum) or 8 (bone)

Dosing Duration 4

a

and 9 weeks 20 days

Concentrations in Medium and Corresponding Doses

0.19% 316 ± 97.4b mg Sr/kg-day 190d mg Sr/kg-day (NOAEL)

0.27% 425 ± 149.3b mg Sr/kg-day

(NOAEL) No study dose given

0.34% 524 ±193.6b mg/kg-day

(LOAEL) No study dose given

0.38% No study dose given 380d mg Sr/kg-day (LOAEL)

0.4% 633 ± 264.3b mg Sr/kg-day No study dose given

Parameter Comparisons

Serum Sr (0.19%) 2.73e mg/dL (4 weeks)

1.34e mg/dL (9 weeks) 0.63 ± 0.4b mg/dL

Serum Sr (0.38% or 

0.4%*)

3.31e mg/dL (4 weeks)

2.59e mg/dL (9 weeks) 1.2 ± 0.1b mg/dL

Serum Ca:Sr ratio 

(0.19%)

3.09 ± 0.87 b(4 weeks)

7.08 ± 2.53 b(9 weeks) 16.8e

Serum Ca:Sr ratio 

(0.38% or 0.4%*)

2.53 ± 0.46 b(4 weeks)

3.55 ± 0.83 b(9 weeks) 8.75e

Bone ash Sr (0.19%) 40 mg/gc(9 weeks) 15e mg/g

Bone ash Sr (0.4%*) 61 mg/gc(9 weeks) 31e mg/g

ND=no data; BW = body weight *Presents results from the high dose in the study – 0.4% in Marie et al. (1985), or 

0.38% in Storey (1961). a No sacrifice at 4 weeks; b As reported by study author; c Estimated from Figure 1 of 

Marie et al. (1985); d Sr dose estimate as reported by EPA 1992; e Calculated for this report
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APPENDIX B. HRL Derivation with Age-Related Exposure Factors

Table B-1. Derivation of the Health Reference Level (HRL) for Strontium using AgeSpecific Exposure Factors for the First 18 years

Age Range

DWI/BWR

(L/kg/day)

Age-Specific 

Fractions of a 19-

Year Exposure 

Duration

Time-Weighted 

DWI/BWR

(L/kg/day)

Birth to < 1 month 0.235 0.004 0.001

1 to <3 months 0.228 0.009 0.002

3 to <6 months 0.148 0.013 0.002

6 to <12 months 0.112 0.026 0.003

1 to <2 years 0.056 0.053 0.003

2 to <3 years 0.052 0.053 0.003

3 to <6 years 0.043 0.158 0.007

6 to <11 years 0.035 0.263 0.009

11 to <16 years 0.026 0.263 0.007

16 to <18 years 0.023 0.105 0.002

18 to <21 years#0.026 0.053 0.001

Summation of the Time-Weighted DWI/BWRs = 0.040 L/kg/day*

Reference Dose= 0.3 mg/kg/day

RSC= 20%

+HRL = (0.3 mg/kg/day ÷ 0.040 L/kg/day) x .20 = 1.500 mg/L

Final child specific HRL: 1500 μg/L

*Rounded; #includes 18th year; DWI/BWR = drinking water intake to body weight ratio; HRL= health reference 

level; RSC = relative source contribution

+ HRL = (RfD / ∑(DWI/BWR x F)) x RSC

The age-specific data on drinking water intakes in units of L/kg/day from birth through age 3 are 

from Table 3-19 in the EPA (2011) Exposures Factors Handbook and from Table 3-38 for ages 

3 to <19 . The exposure duration adjustment was calculated by dividing the age-specific fraction 

of a 19 year exposure by the total exposure in months or years as appropriate (e.g., birth to <1 

month = (1/12)/19 years = 0.00439; 6 to <11 years = 5/19 years = 0.26316). The time-weighted 

DWI/BWR values are the product of the age-specific DWI/BWR multiplied by the age–specific 

fraction of a 19 year exposure. The time-weighted DWI/BWRs are summed to obtain the 

normalized value.
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APPENDIX C. Benchmark Dose Modeling Results for Non-Cancer Endpoints

==================================================================== 

 Polynomial Model. (Version: 2.16; Date: 05/26/2010) 

 Input Data File: C:/USEPA/BMDS212/Data/ply_toxstratstrontium_Opt.(d) 

 Gnuplot Plotting File: C:/USEPA/BMDS212/Data/ply_toxstratstrontium_Opt.plt

Mon Apr 04 11:28:59 2011

==================================================================== 

BMDS Model Run 

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

 The form of the response function is: 

 Y[dose] = beta_0 + beta_1*dose + beta_2*dose^2 + ...

 Dependent variable = calcrate

 Independent variable = mgkgday

 rho is set to 0

 The polynomial coefficients are restricted to be negative

 A constant variance model is fit

 Total number of dose groups = 5

 1

 1.1

 1.2

 1.3

 1.4

 0 100 200 300 400 500 600

Mean Response

dose

Polynomial Model with 0.95 Confidence Level

11:28 04/04 2011

BMDL BMD

 

Polynomial

BMD Lower Bound
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 Total number of records with missing values = 0

 Maximum number of iterations = 250

 Relative Function Convergence has been set to: 1e-008

 Parameter Convergence has been set to: 1e-008

 Default Initial Parameter Values 

 alpha = 0.0135

 rho = 0 Specified

 beta_0 = 1.32123

beta_1 = 0

beta_2 = -9.39201e-007

 Asymptotic Correlation Matrix of Parameter Estimates

 ( *** The model parameter(s) -rho -beta_1 

 have been estimated at a boundary point, or have been specified by 

the user,

 and do not appear in the correlation matrix )

 alpha beta_0 beta_2

 alpha 1 -2.7e-009 -1.2e-008

 beta_0 -2.7e-009 1 -0.81

 beta_2 -1.2e-008 -0.81 1

 Parameter Estimates

 95.0% Wald Confidence 

Interval

 Variable Estimate Std. Err. Lower Conf. Limit Upper Conf. 

Limit

 alpha 0.0120913 0.0027037 0.00679215 

0.0173905

 beta_0 1.34382 0.0296139 1.28578 

1.40187

 beta_1 0 NA

 beta_2 -5.83595e-007 1.25112e-007 -8.2881e-007 -3.38381e007

NA - Indicates that this parameter has hit a bound

 implied by some inequality constraint and thus

 has no standard error.

 Table of Data and Estimated Values of Interest

Dose N Obs Mean Est Mean Obs Std Dev Est Std Dev Scaled Res.

------ --- -------- -------- ----------- ----------- ----------

 0 8 1.32 1.34 0.12 0.11 -0.613

 316 8 1.31 1.29 0.05 0.11 0.629

 425 8 1.25 1.24 0.16 0.11 0.298

 525 8 1.18 1.18 0.09 0.11 -0.0764
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 634 8 1.1 1.11 0.13 0.11 -0.238

Model Descriptions for likelihoods calculated

Model A1: Yij = Mu(i) + e(ij)

 Var{e(ij)} = Sigma^2

Model A2: Yij = Mu(i) + e(ij)

 Var{e(ij)} = Sigma(i)^2

Model A3: Yij = Mu(i) + e(ij)

 Var{e(ij)} = Sigma^2

 Model A3 uses any fixed variance parameters that

 were specified by the user

Model R: Yi = Mu + e(i)

 Var{e(i)} = Sigma^2

 Likelihoods of Interest

 Model Log(likelihood) # Param's AIC

 A1 68.771940 6 -125.543879

 A2 73.844578 10 -127.689155

 A3 68.771940 6 -125.543879

 fitted 68.305375 3 -130.610750

 R 59.618353 2 -115.236707

 Explanation of Tests 

Test 1: Do responses and/or variances differ among Dose levels? 

 (A2 vs. R)

Test 2: Are Variances Homogeneous? (A1 vs A2)

Test 3: Are variances adequately modeled? (A2 vs. A3)

Test 4: Does the Model for the Mean Fit? (A3 vs. fitted)

(Note: When rho=0 the results of Test 3 and Test 2 will be the same.)

 Tests of Interest 

 Test -2*log(Likelihood Ratio) Test df p-value 

 Test 1 28.4524 8 0.0003954

 Test 2 10.1453 4 0.03805

 Test 3 10.1453 4 0.03805

 Test 4 0.933129 3 0.8174

The p-value for Test 1 is less than .05. There appears to be a

difference between response and/or variances among the dose levels

It seems appropriate to model the data

The p-value for Test 2 is less than .1. Consider running a 

non-homogeneous variance model

The p-value for Test 3 is less than .1. You may want to consider a 

different variance model

The p-value for Test 4 is greater than .1. The model chosen seems 
EPA-OST Preliminary Health Effects Support Document for Strontium April 2014

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to adequately describe the data

 Benchmark Dose Computation

Specified effect = 1

Risk Type = Estimated standard deviations from the control mean

Confidence level = 0.95

 BMD = 434.073

 BMDL = 328.358