TOXICOLOGICAL PROFILE FOR
 

BORON
 


 


 


 


 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

Agency for Toxic Substances and Disease Registry
 

November 2010 
 

BORON ii 

DISCLAIMER 

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

Agency for Toxic Substances and Disease Registry. 
 


 


 


 


 


 


 

BORON iii 

UPDATE STATEMENT
 

A Toxicological Profile for Boron Draft for Public Comment was released in October 2007. This edition 

supersedes any previously released draft or final profile. 

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

status of previously released profiles, contact ATSDR at: 

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology and Environmental Medicine/Applied Toxicology Branch
 

1600 Clifton Road NE
 

Mailstop F-62
 

Atlanta, Georgia 30333
 
BORON iv 

This page is intentionally blank. 
FOREWORD 


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

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

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

and republished as necessary. 

The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health 

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

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

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

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

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

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

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

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

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

significance to protection of public health are identified by ATSDR. 

Each profile includes the following: 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

and views expressed in this toxicological profile resides with ATSDR. 

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

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


Administrator 


Agency for Toxic Substances and 


Disease Registry 

"Legislative Background 

The toxicological profiles are developed under the Comprehensive Environmental Response, 

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

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

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

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

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

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

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

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

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

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

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

 

 

 

 

 

 

 

 

 

 


 


 


 


 

BORON vii 

QUICK REFERENCE FOR HEALTH CARE PROVIDERS 

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

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

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

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

answers to often-asked questions. 

Primary Chapters/Sections of Interest 

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

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

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

the general health effects observed following exposure. 

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

and assesses the significance of toxicity data to human health. 

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

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

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

reported in this section. 

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

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

following exposure. 

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

issues: 

Section 1.6 How Can (Chemical X) Affect Children?
 

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

Section 3.7 Children’s Susceptibility
 

Section 6.6 Exposures of Children
 

Other Sections of Interest: 

Section 3.8 Biomarkers of Exposure and Effect 

Section 3.11 Methods for Reducing Toxic Effects 

ATSDR Information Center 

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

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

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

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

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

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

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

Toxicity; and numerous chemical-specific case studies. 
 

 

 

 

 

 

 

 

 

 

 

 

BORON viii 

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

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

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

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

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

professionals treating patients exposed to hazardous materials. 

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

Other Agencies and Organizations 

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

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

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

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

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

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

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

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

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

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

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

• Phone: 800-35-NIOSH. 

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

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

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

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

Referrals 

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

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

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

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

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

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

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

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

 

 

 


 


 


 


 


 


 


 


 


 

	 

	 

	 

	 

BORON ix 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHOR(S): 

Malcolm Williams, DVM, Ph.D.
 

Moiz Mumtaz, Ph.D. 

Mike Fay, Ph.D.
 

Franco Scinicariello, M.D.
 

Kim Jenkins
 

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

Mike Lumpkin, Ph.D.
 

Lara Chappell, Ph.D.
 

Peter R. McClure, Ph.D., DABT
 

SRC, Inc., North Syracuse, NY
 

THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS: 

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

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

end points. 

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

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

profile, and makes recommendations for derivation of MRLs. 

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

consistency across profiles and adherence to instructions in the Guidance. 

4.	 Green Border Review. Green Border review assures the consistency with ATSDR policy. 
BORON x 

This page is intentionally blank. 
 

 

 

 

 

 

 

 

	 

	 

	 

BORON xi 

PEER REVIEW 

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

Draft for Public Comment: 

1.	 Michael Dourson, Ph.D., DABT, Toxicological Excellence for Risk Assessment, Cincinnati, 

Ohio; 

2.	 Curtis Eckhert, Ph.D., University of California Los Angeles, Los Angeles, California; and 

3.	 Joseph Landolph, Ph.D., University of Southern California, Los Angeles, California. 

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

key health end points, mechanisms of action, human and animal exposure, and quantification of risk to 

humans. All reviewers were selected in conformity with the conditions for peer review specified in 

Section 104(I)(13) of the Comprehensive Environmental Response, Compensation, and Liability Act, as 

amended. 

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

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

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

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

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

content. The responsibility for the content of this profile lies with the ATSDR. 
BORON xii 

This page is intentionally blank. 
	 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 

 
 


 


 


 

 	 


 

 	 
 

 	 
 


 


 


 


 

 
 

 
 

 
 

 
 

 
 

 
 

 
 

 
 

 
 

 
 

 

 

 

 

 


 


 


 


 


 

CONTENTS
 

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

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

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

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

CONTRIBUTORS.......................................................................................................................................ix
 

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

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

LIST OF FIGURES ..................................................................................................................................xvii
 

LIST OF TABLES.....................................................................................................................................xix
 

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

1.1 WHAT IS BORON?.......................................................................................................................2
 

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

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

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

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

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

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

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

TO BORON?..................................................................................................................................6
 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

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

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

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

2.1	 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO BORON IN THE UNITED 

STATES .........................................................................................................................................9
 

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

2.3	 MINIMAL RISK LEVELS (MRLs) ............................................................................................13
 

2.3.1 Chronic-Duration Oral Studies..............................................................................................20
 

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

3.1 INTRODUCTION........................................................................................................................23
 

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE .....................................23
 

3.2.1 Inhalation Exposure ..............................................................................................................24
 

3.2.1.1 Death..............................................................................................................................24
 

3.2.1.2 Systemic Effects.............................................................................................................25
 

3.2.1.3 Immunological and Lymphoreticular Effects................................................................38
 

3.2.1.4 Neurological Effects ......................................................................................................38
 

3.2.1.5 Reproductive Effects......................................................................................................38
 

3.2.1.6 Developmental Effects...................................................................................................38
 

3.2.1.7 Cancer............................................................................................................................38
 

3.2.2 Oral Exposure........................................................................................................................39
 

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

3.2.2.2 Systemic Effects.............................................................................................................41
 

3.2.2.3 Immunological and Lymphoreticular Effects ................................................................76
 

3.2.2.4 Neurological Effects ......................................................................................................76
 

3.2.2.5 Reproductive Effects......................................................................................................77
 

3.2.2.6 Developmental Effects...................................................................................................82
 

BORON	 xiii 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 

3.2.2.7 Cancer............................................................................................................................85
 

3.2.3 Dermal Exposure...................................................................................................................85
 

3.2.3.1 Death..............................................................................................................................86
 

3.2.3.2 Systemic Effects.............................................................................................................86
 

3.2.3.3 Immunological and Lymphoreticular Effects ................................................................87
 

3.2.3.4 Neurological Effects ......................................................................................................87
 

3.2.3.5 Reproductive Effects......................................................................................................87
 

3.2.3.6 Developmental Effects...................................................................................................87
 

3.2.3.7 Cancer............................................................................................................................87
 

3.2.4 Other Routes of Exposure .....................................................................................................87
 

3.3 GENOTOXICITY........................................................................................................................87
 

3.4 TOXICOKINETICS.....................................................................................................................89
 

3.4.1 Absorption.............................................................................................................................89
 

3.4.1.1 Inhalation Exposure .......................................................................................................89
 

3.4.1.2 Oral Exposure ................................................................................................................89
 

3.4.1.3 Dermal Exposure ...........................................................................................................89
 

3.4.2 Distribution ...........................................................................................................................89
 

3.4.2.1 Inhalation Exposure .......................................................................................................89
 

3.4.2.2 Oral Exposure ................................................................................................................90
 

3.4.2.3 Dermal Exposure ...........................................................................................................90
 

3.4.3 Metabolism............................................................................................................................90
 

3.4.4 Elimination and Excretion.....................................................................................................90
 

3.4.4.1 Inhalation Exposure .......................................................................................................90
 

3.4.4.2 Oral Exposure ................................................................................................................90
 

3.4.4.3 Dermal Exposure ...........................................................................................................91
 

3.4.4.4 Other Routes of Exposure..............................................................................................91
 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models.............92
 

3.5 MECHANISMS OF ACTION .....................................................................................................95
 

3.5.1 Pharmacokinetic Mechanisms...............................................................................................95
 

3.5.2 Mechanisms of Toxicity........................................................................................................96
 

3.5.3 Animal-to-Human Extrapolations.........................................................................................97
 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS.............................97
 

3.7 CHILDREN’S SUSCEPTIBILITY..............................................................................................98
 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT .....................................................................100
 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Boron.............................................101
 

3.8.2 Biomarkers Used to Characterize Effects Caused by Boron...............................................102
 

3.9 INTERACTIONS WITH OTHER CHEMICALS .....................................................................102
 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE ............................................102
 

3.11 METHODS FOR REDUCING TOXIC EFFECTS................................................................103
 

3.11.1 Reducing Peak Absorption Following Exposure.............................................................103
 

3.11.2 Reducing Body Burden ...................................................................................................104
 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects..........................................104
 

3.12 ADEQUACY OF THE DATABASE.....................................................................................104
 

3.12.1 Existing Information on Health Effects of Boron............................................................105
 

3.12.2 Identification of Data Needs............................................................................................107
 

3.12.3 Ongoing Studies ..............................................................................................................116
 

4. CHEMICAL AND PHYSICAL INFORMATION..............................................................................119
 

4.1 CHEMICAL IDENTITY............................................................................................................119
 

4.2 PHYSICAL AND CHEMICAL PROPERTIES.........................................................................119
 

BORON xiv 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL..........................................................127
 

5.1 PRODUCTION ..........................................................................................................................127
 

5.2 IMPORT/EXPORT ....................................................................................................................128
 

5.3 USE ............................................................................................................................................128
 

5.4 DISPOSAL.................................................................................................................................132
 

6. POTENTIAL FOR HUMAN EXPOSURE .........................................................................................135
 

6.1 OVERVIEW...............................................................................................................................135
 

6.2 RELEASES TO THE ENVIRONMENT...................................................................................138
 

6.2.1 Air .......................................................................................................................................138
 

6.2.2 Water...................................................................................................................................141
 

6.2.3 Soil ......................................................................................................................................142
 

6.3 ENVIRONMENTAL FATE ......................................................................................................143
 

6.3.1 Transport and Partitioning...................................................................................................143
 

6.3.2 Transformation and Degradation ........................................................................................144
 

6.3.2.1 Air................................................................................................................................144
 

6.3.2.2 Water............................................................................................................................144
 

6.3.2.3 Sediment and Soil ........................................................................................................145
 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT..................................145
 

6.4.1 Air .......................................................................................................................................145
 

6.4.2 Water...................................................................................................................................146
 

6.4.3 Sediment and Soil ...............................................................................................................146
 

6.4.4 Other Environmental Media................................................................................................147
 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE........................................150
 

6.6 EXPOSURES OF CHILDREN..................................................................................................153
 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES ..............................................154
 

6.8 ADEQUACY OF THE DATABASE ........................................................................................155
 

6.8.1 Identification of Data Needs ...............................................................................................155
 

6.8.2 Ongoing Studies..................................................................................................................158
 

7. ANALYTICAL METHODS................................................................................................................159
 

7.1 BIOLOGICAL MATERIALS....................................................................................................159
 

7.2 ENVIRONMENTAL SAMPLES ..............................................................................................161
 

7.3 ADEQUACY OF THE DATABASE ........................................................................................164
 

7.3.1 Identification of Data Needs ...............................................................................................164
 

7.3.2 Ongoing Studies..................................................................................................................165
 

8. REGULATIONS, ADVISORIES, AND GUIDELINES.....................................................................167
 

9. REFERENCES ....................................................................................................................................173
 

10. GLOSSARY ......................................................................................................................................191
 

APPENDICES 

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

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

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

D. INDEX ................................................................................................................................................D-1
 

BORON xv 
BORON xvi
 

This page is intentionally blank. 
 

 

 


 


 


 


 


 


 


 

BORON xvii 

LIST OF FIGURES
 

3-1. Levels of Significant Exposure to Boron and Compounds - Inhalation ............................................. 31
 

3-2. Levels of Significant Exposure to Boron and Compounds - Oral ...................................................... 66
 

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

Hypothetical Chemical Substance......................................................................................................94
 

3-4. Existing Information on Health Effects of Boron.............................................................................106
 

6-1. Frequency of NPL Sites with Boron and Selected Boron Contamination........................................136
 
BORON xviii
 

This page is intentionally blank. 
 

 

 

 

 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 

BORON xix 

LIST OF TABLES
 

3-1. Levels of Significant Exposure to Boron and Compounds - Inhalation ............................................. 26
 

3-2. Levels of Significant Exposure to Boron and Compounds - Oral ...................................................... 42
 

3-3. Genotoxicity of Boron In Vitro ..........................................................................................................88
 

4-1. Chemical Identity of Boron and Selected Boron Compounds..........................................................120
 

4-2. Physical and Chemical Properties of Boron and Selected Boron Compounds.................................123
 

5-1. Facilities that Produce, Process, or Use Boron Trifluoride ..............................................................129
 

5-2. Facilities that Produce, Process, or Use Boron Trichloride..............................................................130
 

5-3. Current U.S. Manufacturers of Boron and Selected Boron Compounds..........................................131
 

6-1. Releases to the Environment from Facilities that Produce, Process, or Use Boron Trifluoride.......139
 

6-2. Releases to the Environment from Facilities that Produce, Process, or Use Boron Trichloride ......140
 

6-3. Boron Levels in Food .......................................................................................................................148
 

6-4. Dietary Boron Intake ........................................................................................................................152
 

7-1. Analytical Methods for Determining Boron in Biological Materials...............................................160
 

7-2. Analytical Methods for Determining Boron in Environmental Samples..........................................162
 

8-1. Regulations, Advisories and Guidelines Applicable to Boron and Boron Compounds...................169
 
BORON xx
 

This page is intentionally blank. 
 

 

 

 

 

 

 

 

BORON 1 

1. PUBLIC HEALTH STATEMENT 

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

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

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

federal clean-up activities. Boron and boron compounds have been found in at least 164 of the 

1,689 current or former NPL sites, respectively. Although the total number of NPL sites evaluated for 

this substance is not known, the possibility exists that the number of sites at which boron is found may 

increase in the future as more sites are evaluated. This information is important because these sites may 

be sources of exposure and exposure to this substance may be harmful. 

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

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

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

eating, or drinking the substance, or by skin contact. 

If you are exposed to boron, many factors will determine whether you will be harmed. These factors 

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

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

state of health. 
 

 

 

 

BORON 2 

1. PUBLIC HEALTH STATEMENT 

1.1 WHAT IS BORON? 

Naturally 

occurring 

Boron is a widely occurring element in minerals found in the earth’s crust. It 

is the 51st most common element found in the earth’s crust and is found at 

an average concentration of 8 mg/kg (approximately 0.0008%). 

Combines with Boron is found in the environment primarily combined with oxygen in 

oxygen to form compounds called borates. Common borate compounds include: 

borates 

• boric acid 

• sodium tetraborates (also referred to as borax) 

• boron oxide 

Used to Borate-containing minerals are mined and processed to produce borates for 

manufacture several industrial uses in the United States including: 

industrial and 

consumer • glass and ceramics 

products • soaps, bleaches, and detergents 

• fire retardants 

• pesticides 

More information on the properties and uses of boron and boron compounds and how they behave in the 

environment may be found in Chapters 4, 5, and 6. 

1.2 WHAT HAPPENS TO BORON WHEN IT ENTERS THE ENVIRONMENT? 

Released into 

air, water, and 

soil 

Boron can be released into air, water, or soil after natural weathering of soils 

and rocks. 

Smaller amounts of boron can be released from: 

• glass manufacturing plants 

• coal-burning power plants 

• copper smelters 

• agricultural fertilizer and pesticide usage 

Is not broken 

down 

Boron cannot be destroyed in the environment. It can only change its form or 

become attached or separated from particles in soil, sediment, and water. 

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

 

 

 

 

 

 

 

 

 

BORON 3 

1. PUBLIC HEALTH STATEMENT 

1.3 HOW MIGHT I BE EXPOSED TO BORON? 

Food You can be exposed to boron in food, mainly vegetables and fruits, as boron 

is an essential element in plants. The average daily intake of boron for 

adults is 1 milligram. 

Water Boron is widely distributed in surface water and groundwater. 

• the average surface water concentration is about 0.1 mg per liter 

(mg/L) 

• boron concentrations in ground water can be as high as 300 mg/L in 

areas with natural boron-rich deposits 

• concentrations up to 0.4 mg/L have been found in most drinking 

water samples 

Soil Average concentrations of 26 and 33 mg per kilogram (mg/kg) have been 

reported in soil. 

Air The general public is not likely to be exposed to air contaminated with boron. 

The average level of boron in air samples is 0.00005 mg boron per cubic 

meter of air (mg boron/m3

). 

Workplace air In workplaces that mine and process borates, boron concentrations in dusty 

air samples have been reported to range from about 0.5 to 3 mg boron/m3 

. 

Consumer Boric acid, anhydrous sodium tetraborate, and sodium tetraborate 

products decahydrate (borax) are found in consumer products such as: 

• laundry detergent 

• pesticides 

• facial creams and cleaners 

• plant foods 

• household cleaners 

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

 

 

 

 

 

 

 

 

BORON 4 

1. PUBLIC HEALTH STATEMENT 

1.4 HOW CAN BORON ENTER AND LEAVE MY BODY? 

Most ingested 

boron is 

absorbed 

Boron can enter your body when you eat food (fruit and vegetables), drink 

water containing it, when you breathe borate dust in the air, and when 

damaged skin comes in contact with it. 

Typically leaves 

your body within 

4 days 

Most of the boron leaves the body in urine. 

Over half of the boron taken by mouth can be found in urine within 24 hours 

and the other half can be detected in urine for up to 4 days. 

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

1.5 HOW CAN BORON AFFECT MY HEALTH? 

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

One way to learn whether a chemical will harm people is to determine how the body absorbs, uses, and 

releases the chemical. For some chemicals, animal testing may be necessary. Animal testing may also 

help identify health effects such as cancer or birth defects. Without laboratory animals, scientists would 

lose a basic method for getting information needed to make wise decisions that protect public health. 

Scientists have the responsibility to treat research animals with care and compassion. Scientists must 

comply with strict animal care guidelines because laws today protect the welfare of research animals. 

The effect of boron on human health depends on how much boron is present, how you are exposed to it, 

and the length of exposure. 

Exposure in air People working in dusty workplaces where borates are mined and 

processed have reported irritation of the nose, throat, and eyes. The 

irritation does not persist for long periods after leaving the dusty area. 
 

 

 

 

 

 

 

 

 

 

 

 

BORON 5 

1. PUBLIC HEALTH STATEMENT 

Exposure by 

ingestion 

Humans: Exposure to large amounts of boron (about 30 g of boric acid) 

over short periods of time can affect the stomach, intestines, liver, kidney, 

and brain and can eventually lead to death. 

Animals: Studies of dogs, rats, and mice indicate that the male reproductive 

organs, especially the testes, are affected if large amounts of boron are 

ingested for short or long periods of time. The doses that produced these 

effects in animals are more than 1,800 times higher than the average daily 

intake of boron in food by adults in the U.S. population. 

No evidence of cancer was found in a study in which mice were given boric 

acid in the diet throughout their lifetime. 

More information on the health effects of boron in humans and animals can be found in Chapters 2 and 3. 

1.6 HOW CAN BORON AFFECT CHILDREN? 

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

conception to maturity at 18 years of age. 

Children are likely 

to have similar 

effects as adults 

It is likely that children would show the same health effects as adults. We 

do not know whether children differ in their susceptibility to the effects of 

boron. 

Birth defects We do not know whether boron causes birth defects in people. Low birth 

weights, birth defects, and developmental delays have occurred in newborn 

animals whose mothers were orally exposed to high doses of boron (as 

boric acid). The doses that produced these effects in pregnant animals are 

more than 800 times higher than the average daily intake of boron in food 

by adult women in the U.S. population. 

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

If your doctor finds that you have been exposed to substantial amounts of boron, ask whether your 

children might also have been exposed. Your doctor might need to ask your state health department to 

investigate. 
 

 

 

 

 

 

 

 

 

 

 

 

BORON 6 

1. PUBLIC HEALTH STATEMENT 

Boron is part of the natural environment and you will have some exposure from foods and drinking water. 

Limit children’s 

exposure to 

pesticides 

Pesticides containing boron compounds should be used according to their 

directions and should be kept away from children. 

Store household 

chemicals out of 

reach of young 

children 

Always store household chemicals in their original labeled containers out of 

reach of young children to prevent accidental poisonings. Never store 

household chemicals in containers children would find attractive to eat or 

drink from, such as old soda bottles. 

Discourage 

children from 

eating dirt or 

putting hands in 

their mouth while 

playing with dirt 

Children living near waste sites containing boron and boron compounds are 

likely to be exposed to higher than normal environmental levels of boron 

through breathing in boron-containing dust, touching soil, and eating 

contaminated soil. 

Children should be encouraged to wash their hands frequently, especially 

before eating. 

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

BORON? 

Can be measured Blood and urine can be examined to determine whether excessive 

in blood and urine exposure to boron has occurred. 

The detection of boron in the blood or urine cannot be used to predict the 

kind of health effects that might develop from that exposure. 

Further information on how boron can be measured in exposed humans is presented in Chapters 3 and 7. 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? 

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

can be enforced by law. The EPA, the Occupational Safety and Health Administration (OSHA), and the 

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

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

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

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

recommendations for toxic substances. 
 

 

 

 

 

 

 

 

 

BORON 7 

1. PUBLIC HEALTH STATEMENT 

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

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

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

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

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

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

Some regulations and recommendations for boron include the following: 

Levels in drinking 

water set by EPA 

The EPA has determined that exposure to boron in drinking water at 

concentrations of 4 mg/L for one day or 0.9 mg/L for 10 days is not 

expected to cause any adverse effects in a child. 

The EPA has determined that lifetime exposure to 1 mg/L boron is not 

expected to cause any adverse effects. 

Levels in 

workplace air set 

by OSHA 

OSHA set a legal limit of 15 mg/m3 for boron oxide in air averaged over an 

8-hour work day. 

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

1.10 WHERE CAN I GET MORE INFORMATION? 

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

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

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

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

substances. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 8 

1. PUBLIC HEALTH STATEMENT 

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

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

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

to: 

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology and Environmental Medicine
 

1600 Clifton Road NE
 

Mailstop F-62
 

Atlanta, GA 30333
 

Fax: 1-770-488-4178
 

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

National Technical Information Service (NTIS)
 

5285 Port Royal Road
 

Springfield, VA 22161
 

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

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

 

 

 

 

 

 

 

 

 

 

 

BORON 9 

2. RELEVANCE TO PUBLIC HEALTH
 

2.1	 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO BORON IN THE UNITED 

STATES 

Boron is a widely occurring element in minerals found in the earth’s crust. It is the 51st most common 

element found in the earth’s crust and is found at an average concentration of 8 mg/kg (approximately 

0.0008%). It is found in the environment primarily combined with oxygen in compounds called borates. 

Common borate compounds include boric acid, salts of boric acid (e.g., sodium tetraborates, which are 

also referred to as borax), and boron oxide. U.S. borate mining and production mainly occurs in Kern, 

San Bernardino, and Inyo Counties, California. Borate-containing minerals are mined and processed to 

produce borates for several industrial uses in the United States. Industrial uses include glass and ceramics 

(70%), soaps, bleaches, and detergents (4%), fire retardants (2%), and agriculture (2%). Other uses, 

including metallurgy, nuclear applications, sale to distributors, addition to enamels and glazes, and 

ingredients in cosmetics or medical preparations, make up the remaining 19%. There are 189 pesticide 

products registered in the United States that contain boric acid or one of its sodium salts as an active 

ingredient. 

Human exposure to boron, typically as borates or boric acid, may occur through ingestion of food and 

water, or through use of pesticides containing boron compounds, inhalation of boron-containing powders 

or dusts, or the use of boron from cosmetics or medical preparations. The most appreciable boron 

exposure to the general population is likely to be through ingestion of food (as boron is an essential 

element in plants) and, to a lesser extent, water. Mean daily intakes of boron for male and female adults 

were reported to be 1.28 and 1.0 mg boron/day. Consumption of fruits and vegetables contribute largely 

to boron intake in the human diet. Boron levels reported in drinking water generally range from <1 to 

3 mg boron/L. 

Boron concentrations in ambient non-occupational air samples have been reported to range from 

<5x10-7 to 8x10-5 mg boron/m3

, with an average concentration of 2x10-5 mg boron/m3. Workers in other 

industries, including manufacture of fiberglass and other glass products, cleaning and laundry products, 

fertilizers, pesticides, and cosmetics, may also be exposed to boron compounds. Mean dust 

concentrations ranging from 3.3 to 18 mg particulates/m3 were measured in air samples from U.S. 

facilities where borax was packaged and shipped. Dust samples in these facilities were predominantly 

composed of various types of borates and ranged from 11.8 to 15.2% boron by weight. Using the 

midpoint of this range of boron percentages in the dusts (13.5% boron), boron concentrations in air from 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 10 

2. RELEVANCE TO PUBLIC HEALTH 

these workplaces are estimated to have ranged from 0.45 to 2.43 mg boron/m3. In another study of dust 

concentrations in air samples from a U.S. borax production facility, mean total dust concentrations ranged 

from 0.29 to 18.95 mg particulates/m3 (approximately 0.02–1.50 mg boron/m3

, using the midpoint (7.9%) 

of the ranges of average boron content in these dusts). 

The average surface water boron concentration in the United States is about 0.1 mg boron/L, but 

concentrations vary greatly, depending on boron content of local geologic formations and anthropogenic 

sources of boron. Several studies have measured boron concentrations in water in those areas of 

California with boron-rich deposits. Reported high boron concentrations in surface waters ranged from 

15 mg boron/L in coastal drainage waters to 360 mg boron/L in a boron-rich lake. Groundwater boron 

concentrations >100 mg boron/L are common in California. Average concentrations of 26 and 33 mg 

boron/kg soil have been reported in soils in the United States, with concentrations ranging up to 300 mg 

boron/kg. For a more complete discussion of possible exposures to boron, see Chapter 6 of the profile. 

2.2 SUMMARY OF HEALTH EFFECTS 

Most of the inhalation toxicity data for boron involves human or animal exposure to borate dusts such as 

boric acid, boron oxide, or various hydration states of sodium borate salts (anhydrous, pentahydrate, and 

decahydrate, also referred to borax) or other borate salts (e.g., calcium borate). Equivalent boron doses 

have been calculated throughout this assessment by multiplying reported doses by an adjustment factor 

relating the molar mass ratio of boron in a given compound to the total molar mass. Thus, the dose 

adjustment factors are 0.175 for boric acid, 0.113 for disodium borate decahydrate, 0.151 for disodium 

borate pentahydrate, 0.215 for anhydrous borate, and 0.155 for boron oxide. 

The primary health effects associated with inhalation exposure of humans to boron are acute respiratory 

irritation. Sensations of “feel” just below the self-reported threshold for nasal irritation and significant 

increases in mass of nasal secretions have been observed in well-controlled laboratory studies of 

exercising volunteers exposed for short durations (up to 47 minutes) to 1.5 mg boron/m3 as boric acid or 

sodium borate dusts (Cain et al. 2004, 2008). 

Acute-duration exposures of mining and processing workers to 0.44–3.1 mg boron/m3 (5.7–14.6 mg 

particulates/m3

) as sodium borate dusts has been associated with mild irritation of the eyes, throat, and 

nose, as well as cough and breathlessness. No exposure-related changes in lung function were observed 

in nonsmoking workers; a decrease in 1 second forced expiratory volume (FEV1) was observed in 
 

 

 

 

 

 

 

 

 

 

 

 

BORON 11 

2. RELEVANCE TO PUBLIC HEALTH 

workers who smoked and were exposed to higher concentrations of boron. However, a re-examination of 

the workers 7 years later did not result in boron-related alterations in lung function. Animal studies of 

inhalation exposure to boron are restricted to a series of studies that found no histological changes in a 

comprehensive examination of tissues (including the respiratory tract) from rats exposed to aerosols of 

boron oxide (6 hours/day, 5 days/week) at concentrations of 73 mg boron/m3 for 10 weeks, 27 mg 

boron/m3 for 12 weeks, or 12 mg boron/m3 for 24 weeks. There was some indication of local irritation of 

the external nares in rats exposed to 73 mg boron/m3 for 10 weeks. A limited examination of dogs 

exposed to 9 mg boron/m3 did not find hematological alterations or evidence of liver damage, evaluated 

using the sulfobromophthalein retention test. 

In contrast, diborane gas (B2H4) is a potent respiratory tract toxicant. Exposure of mice to diborane gas at 

a concentration of 5 ppm diborane (1.7 mg boron/m3

) for 2 weeks produced severe damage to the lungs 

including pulmonary congestion, bleeding, and edema. Slight changes (infiltration of polymorphous 

neutrophil in peribronchiolar region) were observed at 0.7 ppm diborane (0.2 mg boron/m3

). However, 

diborane gas is expected to have a very short half-life in the environment and is not expected to be a 

significant environmental toxicant, except in workplaces where it might be used or manufactured and 

accidentally released. 

Human case reports have shown that boron can be lethal following short-term oral exposure at high doses, 

although the dose estimation can be quite imprecise and variability in human responses to acute exposure 

is quite large. The minimal lethal dose of ingested boron (as boric acid) was reported to be 2–3 g in 

infants, 5–6 g in children, and 15–20 g in adults. However, a review of 784 human poisonings with boric 

acid (10–88 g) reported no fatalities, with 88% of cases being asymptomatic. Liver, kidney, central 

nervous system, and gastrointestinal effects and skin lesions have been found in lethal cases following 

ingestion of boron, but death has been attributed to respiratory failure. Surveys of Turkish and Chinese 

populations with elevated levels of borate salts in drinking water (9–25 mg boron/L) found no 

associations for chronic-duration exposure with reproductive effects. The essentiality of boron has been 

established for most plants and some animals, but not in humans. The use of boron as a dietary 

supplement has not been endorsed by the Food and Nutrition Board/Institute of Medicine and did not 

result in increased plasma testosterone or strength levels in bodybuilders. 

Oral exposure animal studies have clearly identified the reproductive system and developing fetus as the 

most sensitive targets of boron toxicity. Adverse developmental effects have been identified for acuteand intermediate-duration exposures. Decreases in the number of live fetuses and litters, decreases in 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 12 

2. RELEVANCE TO PUBLIC HEALTH 

body weight, and increases in the occurrence of external, visceral, and cardiovascular malformations were 

observed in the fetuses of rabbits administered 44 mg boron/kg/day on gestation days 6–19; no 

developmental effects were observed at 22 mg boron/kg/day. Following intermediate-duration exposure, 

decreases in body weight and increases in the occurrence of skeletal malformations have been observed in 

the fetuses of rats exposed to 13 mg boron/kg/day on gestation days 0–20; a no-observed-adverse-effect 

level (NOAEL) of 10 mg boron/kg/day was identified. Reproductive effects have been observed at higher 

doses. Histological alterations in the testes and sperm effects have been observed in rats administered 

88 mg boron/kg/day for 2 weeks; the NOAEL was 44–53 mg boron/kg/day. Intermediate-duration 

exposure resulted in histological alterations in the testes and associated effects on spermatogenesis in rats 

exposed to doses of ≥26 mg boron/kg/day. No viable sperm were observed in male rats exposed to 

101 mg boron/kg/day for 14 weeks. Impaired ovulation and failure to conceive was also observed in 

female rats (mated with unexposed males) exposed to 116 mg boron/kg/day for 14 weeks prior to mating. 

A NOAEL of 30 mg boron/kg/day was identified for reproductive effects (testicular atrophy) in males in a 

3-generation rat study. Testicular atrophy has also been observed in rats exposed to 81 mg boron/kg/day 

and mice exposed to 201 mg boron/kg/day for 2 years; no testicular alterations were observed at 24 or 

79 mg boron/kg/day, respectively. 

In addition to the developmental and reproductive effects, several systemic effects have been observed in 

orally exposed animals. Consistently observed effects following intermediate and chronic exposure 

include hematological alterations (decreases in hemoglobin levels and splenic hematopoeisis) and 

desquamated skin on the paw; these effects have been observed at doses of ≥60 mg boron/kg/day. 

Chronic inflammation and coagulative necrosis have also been observed in the livers of mice exposed to 

79 mg boron/kg/day for 2 years. 

The primary health effects associated with dermal exposure are irritation of the eyes and reversible skin 

changes. Case reports of human occupational exposures have suggested that acute dermal exposure to 

boron as borax may cause focal alopecia of the scalp. However, as this effect has been reported in only 

three cases with no estimate of dose and involved co-exposure to high levels of other organic solvents, 

this association is uncertain. In animals, ocular instillation of 50 mg boron oxide (7.8 mg boron) dust 

resulted in conjunctivitis, while instillation of a sodium perborate monohydrate solution containing 

6.3 mg boron into the eyes of rabbits caused mild irritancy of the epithelium and superficial stroma. 

No epidemiology studies have identified an association between boron exposure and development of 

cancer. However, some investigators have suggested that boron exposure in drinking water may be 
 

 

 

 

 

 

 

 

 

 

 

 

BORON	 13 

2. RELEVANCE TO PUBLIC HEALTH 

associated with lower incidences of some types of cancer in humans. Intermediate-duration oral exposure 

of boric acid to mice that had been implanted with prostate tumor cells resulted in significantly reduced 

tumor growth and reduced tumor serum antigen levels. Chronic-duration oral studies in rats, mice, and 

dogs involving dietary exposure to boric acid or borax have not found significant increases in neoplastic 

lesions. In vitro genotoxicity assays have given predominantly negative results. The International 

Agency for Research on Cancer (IARC), the National Toxicology Program (NTP), and EPA have not 

classified boron for human carcinogenicity. 

2.3 MINIMAL RISK LEVELS (MRLs) 

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

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

appreciable risk of adverse effects (noncarcinogenic) over a specified duration of exposure. MRLs are 

derived when reliable and sufficient data exist to identify the target organ(s) of effect or the most sensitive 

health effect(s) for a specific duration within a given route of exposure. MRLs are based on 

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

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

methodology does not exist to develop MRLs for dermal exposure. 

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

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

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

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

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

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

significant human exposure improve, these MRLs will be revised. 

Inhalation MRLs 

•	 An MRL of 0.3 mg/m3 has been derived for acute-duration inhalation exposure (14 days or less) 

to boron. 

The available information on the toxicity of inhaled boron comes from an occupational exposure study 

(Wegman et al. 1994) and two human experimental studies (Cain et al. 2004, 2008). These studies 

identified increases in nasal secretions as the most sensitive effect. Nasal and throat irritation were 
 

 

 

 

 

 

 

 

 

 

 

 

BORON 14 

2. RELEVANCE TO PUBLIC HEALTH 

reported by volunteers exposed to ≥4.5 mg boron/m3 (≥30 mg sodium borate/m3) for 20 minutes while 

exercising (Cain et al. 2004). These investigators identified a minimal lowest-observed-adverse-effect 

level (LOAEL) of 1.5 mg boron/m3 for increased nasal secretions in exercising volunteers exposed for 

47 minutes (Cain et al. 2008). Nose, eye, and throat irritation were self-reported by workers at a borax 

processing facility exposed to a 6-hour time-weighted average (TWA) concentration ranging from 0.44 to 

3.1 mg boron/m3 (5.7–14.6 mg particulates/m3

) (Wegman et al. 1994), although identification of a 

NOAEL or LOAEL in this study is problematic (see next paragraph). The identification of the respiratory 

tract as the most sensitive target of toxicity is supported by longer-term animal studies (Wilding et al. 

1959) that found no adverse systemic effects in rats or dogs exposed to higher concentrations (9–72 mg 

boron/m3

). 

The Cain et al. (2004, 2008) studies were selected over the Wegman et al. (1991, 1994) studies as the 

basis of the acute-duration inhalation MRL for boron because they identified a NOAEL based on 

observations from carefully-controlled exposures of volunteers. The Wegman et al. (1991, 1994) data are 

problematic for identifying a NOAEL or LOAEL because the average irritation intensity level reported 

prior to a work shift was very close to the average intensity level reported for all incidents of nasal 

irritation. Area dust samples taken in the areas in which workers reported respiratory irritation varied 

over 4 orders of magnitude, ranging from 0.12 to 205 mg particulate/m3

. The contribution of non-boroncontaining dusts to the reported irritancy cannot be ascertained. Further, the best 0.25-hour TWA data 

(confirmed by worker response and simultaneous air sampling by a study technician) suggest that the 

probability of workers reporting incidences of nasal irritation occurred when estimated boron 

concentrations reached 0.8–1.2 mg boron/m3

, which is very similar to the laboratory findings of Cain et 

al. (2004, 2008). 

Cain et al. (2004, 2008) trained male and female volunteers to recognize the difference in chemesthetic 

feel (pungency or irritancy) of various levels of CO2 offered to the eyes, nose, and throat. Exposures of 

≥17.7% CO2 resulted in a “feel” described by the volunteers as irritating. Twelve male volunteers were 

exposed to 0, 0.8, 1.5, 3.0, 4.5, or 6.0 mg boron/m3 (0, 5, 10, 20, 30, or 40 mg sodium borate 

pentahydrate/m3

) for 20 minutes while performing light exercise (Cain et al. 2004). At 5-minute 

intervals, they reported the magnitude of “feel” of borate dust in terms of equivalent CO2 irritancy. They 

were also observed for changes in nasal secretions (by mass) and nasal airway resistance. In a similar 

fashion, six male and six female volunteers were exposed to 1.5 mg boron/m3 (10 mg sodium borate/m3

) 

or 0.4 to 1.8 mg boron/m3 (2.5 to 10 mg boric acid/m3

) for 47 minutes while exercising. They reported 

the magnitude of “feel” of boric acid and borate dusts in terms of equivalent CO2 irritancy. They were 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 15 

2. RELEVANCE TO PUBLIC HEALTH 

also observed for changes in nasal secretions (by mass), nasal airway resistance, and respiration 

frequency. 

Male volunteers exposed to ≤3.0 mg boron/m3 (≤20 mg sodium borate/m3

) for 20 minutes reported 

increasingly higher magnitude of feel of the dust in eyes, nose, and throat. However, the mean reported 

level of feel, compared to equivalent CO2 levels, was not considered irritating by the study subjects. The 

mean reported perception of feel at ≥4.5 mg boron/m3 (≥30 sodium borate/m3

) was reported to feel 

irritating to the nose (Cain et al. 2004). Significantly increased nasal secretions (by mass) occurred at 

1.5 mg boron/m3 (10 mg sodium borate/m3

), but not 0.8 mg boron/m3 (5 mg sodium borate/m3) (Cain et 

al. 2004). Similarly, male and female volunteers exposed to 1.5 mg boron/m3 (10 mg sodium borate/m3

) 

or 1.8 mg boron/m3 (10 mg boric acid/m3

) for 47 minutes while exercising reported a mean sense of feel 

that initially increased and peaked at the equivalent of slightly less than 17.7% CO2. These boron 

exposures, with a mean reported feel equivalent to <17.7% CO2, were considered non-irritating by the 

study subjects, although increases in nasal secretions were observed at 1.8 mg boron/mg3 (10 mg boric 

acid/m3

), but not at 0.9 mg boron/mg3 (5 mg boric acid/m3) (Cain et al. 2008). Nasal secretions increased 

above controls for the first 20 minutes (as observed by Cain et al. 2004), but did not accumulate 

thereafter. Nasal airway resistance decreased, then increased as a result of exercise, but did not change in 

a dose-related manner. 

An acute-duration inhalation MRL of 0.3 mg boron/m3 was derived using the NOAEL of 0.8 mg 

boron/m3 associated with a minimal LOAEL of 1.5 mg/m3 for increased nasal secretions in exercising 

volunteers. The NOAEL of 0.8 mg/m3 was divided by an uncertainty factor of 3 (100.5 for human 

variability in the pharmacodynamic response to boron). 

A series of studies conducted by Wilding et al. (1959) examined the toxicity of boron following 

intermediate-duration exposure of rats. No adverse effects, as assessed by a histological examination of a 

comprehensive set of tissues, were observed in rats exposed to aerosols of boron oxide (6 hours/day, 

5 days/week) at concentrations of 73 mg boron/m3 for 10 weeks, 27 mg boron/m3 for 12 weeks, or 12 mg 

boron/m3 for 24 weeks. A reddish exudate from the nose was observed in some of the rats exposed to 

73 mg boron/m3 for 10 weeks; the investigators noted that the rats were covered with dust and there 

probably was local irritation of the external nares and scratching. Another study by this group (Wilding et 

al. 1959) found no hematological alterations or alterations in sulfobromophthalein retention for liver 

damage in dogs exposed to 9 mg boron/m3 for 23 weeks. Because the NOAELs identified in the rat and 

dog studies were higher than concentrations associated with irritation in humans acutely exposed to boron 
 

 

 

 

 

 

 

 

 

 

 

 

 

BORON	 16 

2. RELEVANCE TO PUBLIC HEALTH 

(Cain et al. 2004, 2008; Wegman et al. 1994), the intermediate-duration inhalation database was 

considered inadequate for derivation of an MRL. However, these data do suggest that the acute-duration 

inhalation MRL of 0.01 mg boron/m3 should be health-protective for intermediate-duration exposures. 

There are limited data on the chronic toxicity of boron in humans and no chronic-duration inhalation 

animal studies. Workers exposed to mean boron concentrations of 1.8 and 3.1 mg boron/m3 reported a 

higher frequency of respiratory symptoms such as dryness of the mouth, nose, or throat, dry cough, nose 

bleeds, and sore throat than in workers exposed to low levels of boron (0.9 and 0.2 mg boron/m3

) 

(Garabrant et al. 1984, 1985); this is the same study population examined by Wegman et al. (1994) (see 

acute MRL discussion). No alterations in lung function, as measured by FEV1, were observed in 

nonsmoking workers; a reduced FEV1 was found in a subgroup of smoking workers with estimated boron 

exposure of ≥9 mg boron/m3

. In the Wegman et al. (1994) follow-up study, no alterations in lung 

function were observed 7 years after the initial examination of workers receiving exposures of ≥15 mg

boron/m3

. The cross-sectional design of the Garabrant et al. (1985) study prevents determining whether 

the elevation of respiratory symptoms was a consequence of acute or repeated exposure to sodium borate 

dusts. Tarasenko et al. (1972) reported low sperm counts, reduced sperm motility, and elevated fructose 

content of seminal fluids in workers exposed to 22–80 mg/m3 boron aerosols (boron form uncertain) for 

≥10 years; however, interpretation of these results is limited by the small number of subjects and limited 

data reporting. Another study reported elevated fertility rates, as compared to U.S. national average, in 

workers employed at a borax production facility for at least 9 months (Whorton et al. 1994); no exposure 

data were reported. The uncertainty as to whether the effects observed in the Garabrant et al. (1984) 

study were due to acute or chronic exposure and the limitations in the Tarasenko et al. (1972) study 

preclude deriving a chronic-duration inhalation MRL for boron. However, the lack of chronic effects in 

workers observed by Wegman et al. (1994) 7 years after an assessment by Garabrant et al. (1985) 

suggests that the acute-duration inhalation MRL of 0.01 mg/m3 should be health-protective for chronicduration exposures. 

Oral MRLs 

•	 An MRL of 0.2 mg/kg/day has been derived for acute-duration oral exposure (1–14 days) to 

boron. 

Acute-duration oral exposures of humans to high levels of boron (as boric acid) have resulted in little or 

no observable toxicity, as was seen in accidental poisonings of 10–88 g, of which 88% of cases were 

asymptomatic (Litovitz et al. 1988). However, gastrointestinal, cardiovascular, hepatic, renal, and central 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 17 

2. RELEVANCE TO PUBLIC HEALTH 

nervous system effects, dermatitis, erythema, and death have been observed in children and adults 

exposed to ≥84 mg boron/kg (Ishii et al. 1993; Restuccio et al. 1992; Schillinger et al. 1982; Wong et al. 

1964). 

Most of the available animal studies on the acute toxicity of boron have focused on developmental and 

reproductive toxicity end points. NTP (1987; Dieter 1994) reported gastric hyperplasia and dysplasia in 

mice exposed to 2,251 mg boron/kg/day as boric acid in the diet for 14 days; no gastrointestinal effects 

were observed at 926 mg boron/kg/day. Similarly, Weir and Fisher (1972) reported vomiting in dogs 

receiving a single gavage dose of 1,000 mg boron/kg/day as boric acid. Testicular and spermatogenic 

effects were observed in rats receiving gavage doses of 88 mg boron/kg/day for 2 weeks (Fukuda et al. 

2000; Kudo et al. 2000). No effects were observed at 44 or 53 mg boron/kg/day. 

A series of studies conducted by Cherrington and Chernoff (2002) demonstrate the fetal toxicity of boron 

in mice. A variety of skeletal malformations (e.g., rib agenesis, fused rib, cervical rib, reduced rib length) 

were observed in the fetuses of mice receiving gavage doses of 88 mg boron/kg/day on gestation days 6– 

10, 131 mg boron/kg on gestation day 8, or 70 mg boron/kg administered twice daily on gestation day 

8 or 6–8. Two gavage doses of 131 mg boron/kg on gestation day 8 resulted in multiple thoracic skeletal 

malformations. Reductions in fetal body weights were also observed in these studies and in studies of 

mice receiving two gavage doses of 70 mg boron/kg on gestation days 6, 7, 9, or 10. However, skeletal 

malformations were not observed in studies that did not include exposure on gestation day 8. No 

NOAELs for developmental effects were observed in the Cherrington and Chernoff (2002) studies. A 

study of rabbits (Price et al. 1996b) identified a lower LOAEL for developmental toxicity. At gavage 

doses of 44 mg boron/kg/day as boric acid administered on gestation days 6–19, significant increases in 

resorptions and decreases in the number of live litters and fetuses were observed. This dose was also 

associated with decreases in fetal body weight and increases (on percent fetuses per litter basis) in 

external, visceral, and cardiovascular malformations. Marked decreases in maternal body weight were 

also observed at 44 mg boron/kg/day. No adverse maternal or fetal effects were observed at 22 mg 

boron/kg/day. 

The Price et al. (1996b) study was selected as the principal study for derivation of an acute-duration oral 

MRL because it identified a lower LOAEL than the Cherrington and Chernoff (2002) studies and 

involved a longer duration of exposure (14 days compared to 5 days). In the Price et al. (1996b) study, 

groups of 30 pregnant New Zealand white rabbits were given gavage doses of 0, 62.5, 125, or 250 mg 

boric acid/kg/day (0, 11, 22, or 44 mg boron/kg/day) on gestation days 6–19. Observations were made 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON	 18 

2. RELEVANCE TO PUBLIC HEALTH 

for clinical signs, maternal and fetal body weight, number of implantations, resorptions, number of live 

and dead fetuses, and fetal external, visceral, and skeletal defects. No adverse maternal effects were 

observed in rabbits in the 11 or 22 mg boron/kg/day groups. At 44 mg boron/kg/day, decreases in 

maternal body weight, relative kidney weight, and food consumption were observed. During the 

treatment period, the rabbits lost 137 g body weight compared to a weight gain of 93 g in controls. No 

differences in the number of implantation sites per litter were observed; however, there were significant 

increases in the percent resorptions per litter, percent of litters with one or more resorptions, and percent 

of litters with 100% resorption. The number of live litters was 18, 23, 20, and 6 in the 0, 11, 22, and 

44 mg boron/kg/day groups, respectively, and the number of live fetuses was 159, 175, 153, and 14, 

respectively. A decrease in fetal body weights (92% of controls) was observed at 44 mg boron/kg/day; 

although the body weight was not significantly different from controls, the effect was considered 

biologically significant. Significant increases in the percent of fetuses per litter with external, visceral, 

and cardiovascular malformations and cardiovascular variations were observed. Although the overall 

incidence of external malformations was increased at 44 mg boron/kg/day, there were no increases in a 

specific malformation. The visceral malformations primarily consisted of cardiovascular malformations, 

particularly interventricular septal defect, enlarged aorta, papillary muscle malformation, and double 

outlet right ventricle. The cardiovascular variations consisted of abnormal number of cardiac papillary 

muscles. 

An acute-duration oral MRL of 0.2 mg boron/kg/day was derived using the NOAEL of 22 mg 

boron/kg/day associated with a LOAEL of 44 mg boron/kg/day for increased incidence of external, 

visceral, and cardiovascular malformations and reduced body weight in the fetuses of rabbits administered 

boric acid via gavage on gestation days 6–19. The NOAEL of 22 mg boron/kg/day was divided by an 

uncertainty factor of 100 (10 for interspecies extrapolation and 10 for human variability). 

•	 An MRL of 0.2 mg/kg/day has been derived for intermediate-duration oral exposure (15–
 

364 days) to boron.
 

There are limited data on the intermediate-duration toxicity of boron in humans. Seizure disorders were 

observed in infants orally exposed to approximately 12–120 g of borax for 4–12 weeks (Gordon et al. 

1973; O'Sullivan and Taylor 1983). The possible association between boron exposure and impaired 

fertility was investigated in Turkish subpopulations expected to have intermediate- to chronic-duration 

exposures to boron (Sayli 1998a, 1998b, 2003; Sayli et al. 1998) and boron mining and processing 

workers, which may have included oral exposure to boron (Chang et al. 2006; Whorton et al. 1994). 

These studies did not find significant associations. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 19 

2. RELEVANCE TO PUBLIC HEALTH 

Animal studies have clearly identified reproductive and developmental toxicity as the most sensitive 

effects of oral boron exposure. Intermediate-duration exposure of rats, mice, and dogs to boric acid or 

borax results in histological damage to the testes and the associated impacts on spermatogenesis (sperm 

abnormalities and reduced sperm production) at doses ≥26 mg boron/kg/day as boric acid (Dieter 1994; 

Dixon et al. 1976, 1979; Fail et al. 1991; Fukuda et al. 2000; Harris et al. 1992; Ku et al. 1993a; Kudo et 

al. 2000; Lee et al. 1978; NTP 1987; Nusier and Bataineh 2005; Seal and Weeth 1980; Weir and Fisher 

1972; Yoshizaki et al. 1999). Complete sterility was observed in rats exposed to 101 mg boron/kg/day as 

boric acid or borax for 14 weeks prior to mating (Weir and Fisher 1972); a lack of viable sperm was 

observed at this dose level. Additionally, female rats exposed to similar doses (116 mg boron/kg/day) for 

14 weeks failed to become pregnant when mated with non-exposed males (Weir and Fisher 1972); the 

female sterility response at this dose level was associated with decreased ovulation. The Weir and Fisher 

(1972) 3-generation studies (males and females exposed to boric acid or borax) established a NOAEL of 

30 mg boron/kg/day for reproductive toxicity in rats. 

The developing fetus appears to be a more sensitive target than the reproductive system. Reductions in 

fetal body weights were observed in rats following exposure to 13–13.6 mg boron/kg/day as boric acid on 

gestation days 0–20 (Heindel et al. 1992; Price et al. 1996a); an increase in the occurrence of skeletal 

abnormalities was also observed at this dose level (Price et al. 1996a). At 28.4 mg boron/kg/day, rib cage 

defects, enlargement of the lateral ventricles of the brain, and increased resorptions were observed in rats 

exposed to boric acid on gestation days 0–20 (Heindel et al. 1992). No developmental effects were 

observed in rats exposed to 10 mg boron/kg/day as boric acid on gestation days 0–20 (Price et al. 1996a). 

In mice, gestational exposure on days 0–17 resulted in reduced fetal weights at 79 mg boron/kg/day and 

increased skeletal defects and increased resorptions at 175.3 mg boron/kg/day (Heindel et al. 1992); a 

NOAEL of 43.4 mg boron/kg/day was identified. 

Systemic effects are observed at somewhat higher doses. Hematological alterations (splenic 

extramedullary hematopiesis and decreased hemoglobin levels) were observed at 60.5 and 72 mg 

boron/kg/day in dogs and rats, respectively, exposed to as borax or boric acid (NTP 1987; Weir and 

Fisher 1972), desquamation of paw and tail skin and eye inflammation were observed in rats exposed to 

150 mg boron/kg/day as boric acid or borax (Weir and Fisher 1972), and hyperkeratosis and/or acanthosis 

was observed in rats at 577 mg boron/kg/day as boric acid (NTP 1987). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 20 

2. RELEVANCE TO PUBLIC HEALTH 

The available intermediate-duration oral database clearly identifies the developing fetus as the most 

sensitive target of toxicity. Two studies in rats (Heindel et al. 1992; Price et al. 1996a) identified 

LOAELs of 13–13.6 mg boron/kg/day for decreases in fetal body weight and skeletal malformations 

(only identified in the Price et al. 1996a study). These LOAELs are lower than the NOAEL of 30 mg 

boron/kg/day identified for reproductive toxicity in a 3-generation study (Weir and Fisher 1972) and 

NOAELs of 35 or 45 mg boron/kg/day for hematological and dermal effects (Weir and Fisher 1972). 

Multiple developmental end point data from the Price et al. (1996a) and Heindel et al. (1992) studies were 

pooled and subjected to multiple benchmark dose analyses (Allen et al. 1996); see Appendix A for 

summaries of these two studies and the benchmark dose analysis. The 95% lower confidence limit on the 

benchmark dose associated with a 5% reduction in fetal body weight (BMDL05) was calculated to be 

10.3 mg boron/kg/day. This estimate was similar to the observed NOAEL of 10 mg boron/kg/day (Price 

et al. 1996a) and was used as a point of departure for derivation of the intermediate-duration oral MRL. 

The BMDL05 of 10.3 mg boron/kg/day was divided by a chemical-specific uncertainty factor of 

66 (3.3 for toxicokinetic extrapolation from animals to humans, 3.16 for toxicodynamic extrapolation 

from animals to humans, 2.0 for variability in human toxicokinetics, and 3.16 for variability in human 

toxicodynamics) (see Appendix A for derivation of the chemical-specific uncertainty factor) resulting in 

an intermediate-duration oral MRL of 0.2 mg boron/kg/day. 

2.3.1 Chronic-Duration Oral Studies 

As previously discussed, no significant associations between boron exposure and impaired fertility were 

observed in Turkish subpopulations expected to have intermediate- to chronic-duration exposures to 

boron (Sayli 1998a, 1998b; Sayli et al. 1998, 2003). Chronic-duration studies have been conducted in 

rats and dogs exposed to boric acid or borax in the diet (Weir and Fisher 1972) and mice exposed to boric 

acid in the diet (Dieter 1994; NTP 1987). Systemic effects consisted of hematological alterations 

(decreases in hemoglobin in rats and splenic hematopoeisis in mice), desquamation of footpad skin and 

bloody ocular discharge in rats, decreased body weight gain in rats and mice, lung hemorrhage in mice, 

and hepatic chronic inflammation and coagulative necrosis in mice. The hematological, dermal, ocular, 

and body weight effects were observed in rats exposed to 81 mg boron/kg/day (NOAEL of 24 mg 

boron/kg/day). In mice, the hematological and liver effects were observed at 79 mg boron/kg/day and the 

body weight and lung effects were observed at 201 mg boron/kg/day. The highest dose tested in the dog 

studies (6.8 mg boron/kg/day) was a NOAEL for systemic effects. Testicular atrophy was observed in 

rats exposed to 81 mg boron/kg/day as boric acid or borax (Weir and Fisher 1972) and mice exposed to 
 

 

 

 

 

 

BORON 21 

2. RELEVANCE TO PUBLIC HEALTH 

201 mg boron/kg/day as boric acid (Dieter 1994; NTP 1987); the NOAELs for these effects were 24 and 

79 mg boron/kg/day for the rats and mice, respectively. A chronic-duration oral MRL, based on results 

from the chronic oral toxicity studies in animals, was not derived. However, the intermediate MRL, 

which is based on developmental toxicity, should be protective for chronic exposure because the NOAEL 

(24 mg boron/kg/day) for testicular atrophy and systemic effects in chronically exposed rats (Weir and 

Fisher 1972) was higher than the intermediate-duration LOAELs of 13–13.6 mg boron/kg/day for 

developmental toxicity in rats (Heindel et al. 1992; Price et al. 1996a). 
 

BORON 22
 

2. RELEVANCE TO PUBLIC HEALTH 

This page is intentionally blank. 
 

 

 

 

 

 

 

 

 

 

BORON 23 

3. HEALTH EFFECTS 

3.1 INTRODUCTION 

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

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

descriptions and evaluations of toxicological studies and epidemiological investigations and provides 

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

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

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

 

 

 

 

 

 

 

 

 

 

 

BORON 24 

3. HEALTH EFFECTS 

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

effects to human health. 

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

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

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

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

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

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

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

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

3.2.1 Inhalation Exposure 

Most of the inhalation toxicity data for boron involves human or animal exposure to borate dusts such as 

boric acid, boron oxide, or various hydration states of sodium borate salts (anhydrous; pentahydrate; and 

decahydrate; also referred to as borax) or other borate salts (e.g., calcium borate). In aqueous media, 

boron oxide is rapidly transformed to boric acid and, depending on the pH of the media, to borate salts. 

Equivalent boron doses have been calculated throughout this assessment by multiplying reported doses by 

an adjustment factor relating the molar mass ratio of boron in a given compound to the total molar mass. 

Thus, the dose adjustment factors are 0.175 for boric acid, 0.113 for disodium borate decahydrate, 

0.151 for disodium borate pentahydrate, 0.215 for anhydrous borate, and 0.155 for boron oxide. In 

addition, animal studies were located reporting the effects of inhaled diborane, a flammable boroncontaining gas. Because of the differences in environmental prevalence, industrial uses, likelihood of 

exposure, and respiratory toxicity, the effects of diborane exposure are discussed separately from other 

boron compounds in Section 3.2.1.2, Respiratory Effects. 

3.2.1.1 Death 

No studies were located regarding death in humans after inhalation exposure to boron. The 4-hour 

LC50 for boric acid, borax, and disodium borates is >2 mg boron/m3 (Hubbard 1998). No fatalities were 

observed in rats exposed for 6 hours/day, 5 days/week, to 470 mg boron oxide/m3 (73 mg boron/m3

) for 

10 weeks, 175 mg boron oxide/m3 (27 mg boron/m3

) for 12 weeks, or 77 mg boron oxide/m3 (12 mg 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 25 

3. HEALTH EFFECTS 

boron/m3) for 24 weeks, or dogs exposed to 57 mg boron oxide/m3 (9 mg boron/m3) for 23 weeks 

(Wilding et al. 1959). 

3.2.1.2 Systemic Effects 

No studies were located regarding cardiovascular, gastrointestinal, hematological, musculoskeletal, or 

renal effects in humans after inhalation exposure to boron. No studies were located regarding dermal 

effects after acute inhalation exposure in humans or animals for any duration category, but eye irritation 

has been reported in sodium-borate mining and processing workers. Information on respiratory, 

cardiovascular, gastrointestinal, hematological, musculoskeletal, and renal effects in animals and 

respiratory effects and dermal/ocular effects in humans is discussed below. The highest NOAEL values 

and all reliable LOAEL values for these systemic effects for each species and duration category involving 

exposure to boric acid, borates, or boron oxide are recorded in Table 3-1 and plotted in Figure 3-1. 

Results from a few mouse inhalation studies of diborane gas indicate that it is a potent respiratory 

toxicant, much more potent than borates or boron oxide. Since it is not expected to be as important an 

environmental compound as borates or boron oxide, NOAEL and LOAEL values from these mouse 

studies of diborane gas are not included in Table 3-1 or Figure 3-1. 

Respiratory Effects. Occupational studies of workers exposed to dusts of sodium borates, the most 

important commercial forms of boron, have identified irritation of the respiratory tract and eyes, without 

measurable changes in pulmonary function. In an early cross-sectional surveillance of 629 U.S. workers 

in a sodium borate open-pit mining and production plant, past occurrence of symptoms of respiratory 

irritation such as dryness of the mouth, nose, or throat, dry cough, nose bleeds, and sore throat were 

reported at elevated frequencies in workers in areas with mean dust concentrations of 8.4 and 14.6 mg 

particulates/m3 (1.8 and 3.1 mg boron/m3

, respectively), compared with workers in areas with lower mean 

dust levels of 4.0 and 1.1 mg particulate/m3 (0.9 and 0.2 mg boron/m3

) (Garabrant et al. 1984; 1985). 

These boron concentrations are upper bound estimates, assuming that all of the sampled dust is anhydrous 

borax. A reduction in forced expiratory volume in 1 second (FEV1) was measured in a subgroup of 

smoking workers with estimated high cumulative exposure (≥80 mg particulate/m3

, ≥9 mg boron/m3) to 

sodium borate dusts, but not in groups of less-exposed smoking workers or in nonsmoking workers. 

However, a subsequent surveillance of FEV1 in 303 of the original 629 borax workers, 7 years after the 

original surveillance, , some of whom were exposed to ≥15 mg boron/m3

, found no exposure-related 

changes in FEV1 over this period, when adjustments were made for the effects of age, height, and 

smoking on FEV1 (Wegman et al. 1991, 1994). Although the prevalence of workers reporting acute 
98

0.8

1.5

158

0.9

1.8

1

73

737373737373737373

Table 3-1 Levels of Significant Exposure to Boron - Inhalation 

Exposure/ 

Duration/ 

a 

Key to Species Frequency 

Figure (Strain) (Route) 

ACUTE EXPOSURE Systemic 

1 Human once 

20 min 

2 Human 1 x 47 min 

INTERMEDIATE EXPOSURE Systemic 

3 Rat 10 wk 

5 d/wk 6 hr/d 

System 

Resp Resp Resp 

Cardio Gastro Hemato Musc/skel Hepatic Renal Endocr Ocular Bd Wt 

LOAEL 

NOAEL 

(mg/m3) 

Less Serious 

(mg/m3) 

Serious 

(mg/m3) 

Reference Chemical Form 

b

0.8 M 1.5 M (mild irritation of nose 

and throat; increased nasal secretion) 

Cain et al. 2004 SODIUM BORATE 

0.9 1.8 (increased nasal 

secretions) 

Cain et al. 2008 BORIC ACID 

73 (reddish nasal exudate) Wilding et al. 1959 

BORIC OXIDE 

73 

73 

73 73 73 73 73 73 

73 
100

27272727272727272727

Table 3-1 Levels of Significant Exposure to Boron - Inhalation (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (mg/m3) Less Serious (mg/m3) 

LOAEL 

Serious 

(mg/m3) 

Reference Chemical Form 

4 Rat 12 wk 

5 d/wk 6 hr/d 

Resp 27 Wilding et al. 1959 

BORIC OXIDE 

Cardio Gastro Hemato Musc/skel Hepatic Renal Endocr Ocular Bd Wt 

27 

27 

27 27 27 27 27 27 

27 
106

12121212121212121212

2

99

104

27

Table 3-1 Levels of Significant Exposure to Boron - Inhalation (continued) 

Exposure/ 

Duration/ 

a 

Key to Species Frequency 

Figure (Strain) (Route) 

5 Rat 24 wk 

5 d/wk 6 hr/d 

6 Dog 23 wk 

(NS) 

Immuno/ Lymphoret 

7 Rat 12 wk 

5 d/wk (albino) 6 hr/d 

System 

Resp 

Cardio Gastro Hemato Musc/skel Hepatic Renal Endocr Ocular Bd Wt Hemato 

Hepatic 

LOAEL 

NOAEL 

(mg/m3) 

Less Serious 

(mg/m3) 

Serious 

(mg/m3) 

Reference Chemical Form 

12 Wilding et al. 1959 

BORIC OXIDE 

12 

12 

12 12 12 12 12 12 

12 

9 Wilding et al. 1959 

BORIC OXIDE 

9 

27 Wilding et al. 1959 

BORIC OXIDE 
109

12

110

73

105

73

108

27

3

12

101

27

107

12

Table 3-1 Levels of Significant Exposure to Boron - Inhalation (continued) 

a 

Key to Species 

Figure (Strain) 

8 Rat 

(albino) 

9 Rat 

(albino) 

Neurological 

10 Rat 

(albino) 

11 Rat 

(albino) 

12 Rat 

Reproductive 

13 Rat 14 Rat 

(albino) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (mg/m3) Less Serious (mg/m3) 

LOAEL 

Serious 

(mg/m3) 

Reference Chemical Form 

24 wk 5 d/wk 6 hr/d 

12 Wilding et al. 1959 

BORIC OXIDE 

10 wk 5 d/wk 6 hr/d 

73 Wilding et al. 1959 

BORIC OXIDE 

10 wk 5 d/wk 6 hr/d 12 wk 5 d/wk 6 hr/d 24 wk 5 d/wk 6 hr/d 12 wk 5 d/wk 6 hr/d 24 wk 5 d/wk 6 hr/d 

73 27 12 27 12 

Wilding et al. 1959 BORIC OXIDE Wilding et al. 1959 BORIC OXIDE Wilding et al. 1959 BORIC OXIDE Wilding et al. 1959 BORIC OXIDE Wilding et al. 1959 BORIC OXIDE 
4

37

6

8.1

Table 3-1 Levels of Significant Exposure to Boron - Inhalation (continued) 

a

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/m3) 

Less Serious 

(mg/m3) 

LOAEL 

Serious 

(mg/m3) 

Reference Chemical Form 

15 Rat 10 wk 

5 d/wk 6 hr/d 

73 Wilding et al. 1959 

BORIC OXIDE 

CHRONIC EXPOSURE 

Systemic 

16 Human 11.4 yr (mean) Resp 1.8 (dryness of the mouth, 

nose, or throat, dry cough, nose bleeds, and sore throat) 

Garabrant et al. 1984, 1SODIUM BORATE 

a The number corresponds to entries in Figure 3-1. b Used to derive an acute-duration inhalation MRL of 0.3 mg boron/m3 ; exposure level divided by an uncertainty factor of 3 (100.5 for human pharmacodynamic vari

Bd Wt = body weight; Cardio = cardiovascular; d = day(s); Endocr = endocrine; F = Female; Gastro = gastrointestinal; Hemato = hematological; hr = hour(s); Immunimmunological/lymphoreticular; LOAEL = lowest-observed-adverse-effect level; M = male; min = minute(s); Musc/skel = musculoskeletal; NOAEL = no-observed-adNS = not specified; occup = occupational; Resp = respiratory; TWA = time-weighted average; x = time(s); wk = week(s); yr = year(s) 
Respiratory 


	


	


	 
	


	

Figure 3-1 Levels of Significant Exposure to Boron - Inhalation 

Acute (≤ 14 days) 

Systemic 

mg/m3 

10 

2
	

1
	

1
	 2
	

1
	

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans Minimal Risk Level 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans for effects 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans other than 

q-Cow a-Sheep g-Guinea Pig Cancer 

0.1 

BORON

3. HEALTH EFFECTS

31
3 

piratory 

ular 

mg/m Res 

Car diovascular 

Ga strointestinal 

He matological 

Mu sculoskeletal 

patic 

nal 

ocrine 

y Weight 

He 

Re 

End 

Oc 

Bod 

Im muno/Lymphor 

Ne urological 

Re productive 

100 

3r 3r 3r 3r 3r 3r 3r 3r 3r 3r 9r 10r 15r 

4r 4r 4r 4r 4r 4r 4r 4r 4r 4r 7r 11r 13r 

5r 5r 5r 5r 5r 5r 5r 5r 5r 5r 8r 12r 14r 

10 

6d 6d 

1 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans Minimal Risk Level

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans for effects

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans other than

q-Cow a-Sheep g-Guinea Pig Cancer 

Figure 3-1 Levels of Significant Exposure to Boron - Inhalation (Continued)
 

Intermediate (15-364 days)
	
	

Systemic
	

BORON

3. HEALTH EFFECTS

32
Respiratory 

Chronic (≥ 365 days) 

Systemic 

mg/m3 

10 

16 

1 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans Minimal Risk Level 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans for effects 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans other than 

q-Cow a-Sheep g-Guinea Pig Cancer 

BORON

Figure 3-1 Levels of Significant Exposure to Boron - Inhalation (Continued)

3. HEALTH EFFECTS

33
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 34 

3. HEALTH EFFECTS 

respiratory irritation symptoms increased with the mean dust concentrations for different job categories in 

the plant, the cross-sectional design of the Garabrant et al. (1985) study prevented the determination of 

whether the elevation of acute respiratory symptoms was a consequence of acute or repeated exposure to 

sodium borate dusts. Thus, the effect levels associated with the measured prevalence of acute respiratory 

symptoms in this study are not included in Table 3-1 or Figure 3-1. 

The occurrence of acute respiratory symptoms as a possible consequence of acute exposure to dusts of 

sodium borate (the decahydrate, pentahydrate, and anhydrous tetraborates) was studied in a later study by 

interviewing workers about acute irritation symptoms before the work shift began and at regular hourly 

intervals during the work shift, and by measuring personal air concentrations of particulates at concurrent 

intervals for 4 consecutive days (Hu et al. 1992; Wegman et al. 1991, 1994). Seventy-nine exposed 

production workers and 27 nonexposed workers were included in the study. In the latest analysis of the 

collected data, the incidence rates for irritation symptoms in exposed workers were statistically 

significantly higher than those in nonexposed workers, with exposed workers 9-, 5-, and 3-fold more 

likely to report incidents of nasal, eye, and throat irritation, respectively, than comparison workers (Hu et 

al. 1992; Wegman et al. 1991, 1994). For the unexposed groups, the arithmetic means of the 6-hour 

TWA daily dust concentration was 0.45 mg particulates/m3 (0.02 mg boron/m3

), with 100% of samples 

≤1.0 mg particulates/m3 and about 90% of samples ≤0.5 mg particulates/m3

. The arithmetic mean of the 

6-hour TWA daily dust concentrations for the exposed group was 5.72 mg particulates/m3 (0.44 mg 

boron/m3

), with a majority of air concentrations between 1.0 and 10.0 mg particulates/m3 (Wegman et al. 

1991, 1994). Several factors make it difficult to identify a NOAEL or LOAEL for this study, precluding 

its inclusion in Table and Figure 3-1. Study participants rated their perception of individual episodes of 

eye, throat, and nasal irritancy on a scale of 0 (not at all) to 10 (very, very much), with ratings of 1, 2, and 

3 representing “very little”, “fairly little”, and “moderate” irritation, respectively. Unexposed responders 

to the pre-shift survey reported a mean rating of 1.9 for all symptoms, while the mean rating for nasal 

irritation (the most commonly reported effect) among exposed workers was just slightly higher at 2.2. 

Thus, the cutoff for boron dust-induced effects is likely to be for ratings of ≥3. In the exposed group,

91% of reported symptoms were rated with severity scores ≤3 and 96% of symptoms were rated with 

severity scores of ≤4 (“pretty much”). For incidences in which the workers depressed a counter button to 

record time of symptom onset, and the study surveyor recorded an occurrence of effect, the probability of 

reporting an effect did not change markedly until 0.25-hour TWA exposure levels reached 0.8–1.2 mg 

boron/m3 (Wegman et al. 1991). There was no significant difference in reporting of symptoms based on 

the type of borate dust, which differ in boron content by almost a factor of two (i.e., 4.7 mg anhydrous 

borax/m3 and 8.8 mg/m3 of the decahydrate provide 1 mg boron/m3

). Finally, the data do not indicate a 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 35 

3. HEALTH EFFECTS 

temporal increase in effect intensity, as would be expected for a local irritant. Further, since no chronic 

effects (i.e., reduced FEV1) were observed in workers assessed by Wegman et al. (1994), 7 years after 

being assessed by Garabrant et al. (1985), the acute-duration inhalation MRL of 0.3 mg/m3 should also be 

health-protective for intermediate- and chronic-duration exposures. 

Acute-duration laboratory exposures of volunteers to boric acid and sodium borate (sodium borate 

pentahydrate) dust provide more precise estimates of effect levels than the occupational studies. Male 

and female volunteers were trained to recognize the difference in chemesthetic feel (pungency or 

irritancy) of various levels of CO2 offered to the eyes, nose, and throat (Cain et al. 2004, 2008). 

Exposures of ≥17.7% CO2 resulted in a “feel” described by the volunteers as irritating. Male volunteers 

exposed to ≤3.0 mg boron/m3 (≤20 mg sodium borate/m3

) for 20 minutes reported increasingly higher 

magnitude of feel of the dust in eyes, nose, and throat. However, the mean reported level of feel, 

compared to equivalent CO2 levels, was not considered irritating by the study subjects. The mean 

reported perception of feel at ≥4.5 mg boron/m3 (≥30 sodium borate/m3

) was reported to feel irritating to 

the nose (Cain et al. 2004). Significantly increased nasal secretions (by mass) occurred at 1.5 mg 

boron/m3 (10 mg sodium borate/m3

), but not 0.8 mg boron/m3 (5 mg sodium borate/m3) (Cain et al. 2004). 

In a similar experiment, male and female volunteers exposed to 1.5 mg boron/m3 (10 mg sodium 

borate/m3

) or 1.8 mg boron/m3 (10 mg boric acid/m3) for 47 minutes while exercising reported a mean 

sense of feel that initially increased and peaked at the equivalent of slightly less than 17.7% CO2. These 

boron exposures, with a mean reported feel equivalent to <17.7% CO2, were considered non-irritating by 

the study subjects, although increases in nasal secretions were observed at 1.8 mg boron/mg3 (10 mg boric 

acid/m3

), but not at 0.9 mg boron/mg3 (5 mg boric acid/m3) (Cain et al. 2008). The volume of nasal 

secretions increased above controls for the first 20 minutes of exposure, but did not continue to increase 

thereafter, suggesting that increased secretions resulted from possible dust-induced changes in osmolarity 

rather than an irritation response. No dose-related changes in nasal airway resistance or breathing 

patterns were observed. Together, these studies were used to identify a minimal LOAEL of 1.5 mg 

boron/m3

, with an associated NOAEL of 0.8 mg/m3, for significantly increased mass of nasal secretions, 

from which an acute-duration inhalation MRL of 0.3 mg boron/m3 was derived (see Appendix A). 

Corroborating evidence in animals for the respiratory irritation potential of inhaled boron compounds is 

sparse. Mild respiratory irritation, indicated by a 20% reduction in breathing rate, occurred in mice 

inhaling 53 mg boron/m3 (300 mg boric acid/m3

) for 3 hours (Krystofiak and Schaper 1996). Rats were 

exposed to aerosols of boron oxide (6 hours/day, 5 days/week) at concentrations of 470 mg boron 

oxide/m3 (73 mg boron/m3

) for 10 weeks, 175 mg boron oxide/m3 (27 mg boron/m3) for 12 weeks, or 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 36 

3. HEALTH EFFECTS 

77 mg boron oxide/m3 (12 mg boron/m3) for 24 weeks, and dogs were exposed to 57 mg boron oxide/m3 

(9 mg boron/m3

) for 23 weeks (Wilding et al. 1959). In rats, histological examination of a comprehensive 

set of tissues revealed no differences between the tissues of exposed and control animals. Signs of gross 

toxicity were restricted to the appearance of a reddish exudate from the nose of some of the rats exposed 

to 470 mg boron oxide/m3

. 

Mice (ICR) exposed to 0.7 ppm diborane gas (0.2 mg boron/m3

) for 2 or 4 weeks exhibited slight 

infiltration of polymorphous neutrophil in peribronchiolar regions of the respiratory tract (Nomiyama et 

al. 1995). Mice exposed to 5 ppm diborane gas (1.7 mg boron/m3

) for 2 weeks exhibited increased lung 

weight, nasal cavity changes, diffuse panbrochiolitis-like lesions, cellular infiltration of the bronchioles 

and perivascular area, appearance of alveolar macrophages, perivascular lymphoid hyperplasia, lung 

congestion, bleeding, and edema (Uemura et al. 1995). 

Comparison of the results from the studies of mice exposed to diborane gas (Nomiyama et al. 1995; 

Uemura et al. 1995) and those from studies of rats and dogs exposed to boron oxide (Wilding et al. 1959) 

indicate that diborane gas is much more potent as a respiratory toxicant than boron oxide. Diborane gas is 

expected to have a very short half-life in the environment because of its reactivity. Thus, it is not 

expected to be a significant environmental toxicant, except in workplaces where it might be used and 

accidentally released. 

Cardiovascular Effects. Rats exposed to aerosols of boron oxide at a concentration of 470 mg boron 

oxide/m3 (73 mg boron/m3

) for 10 weeks, 175 mg boron oxide/m3 (27 mg boron/m3) for 12 weeks, or 

77 mg boron oxide/m3 (12 mg boron/m3

) for 24 weeks showed no gross or microscopic effects in the 

cardiovascular system (Wilding et al. 1959). 

Gastrointestinal Effects. No gross or microscopic changes were seen in the gastrointestinal tract of 

rats exposed to aerosols of boron oxide at a concentration of 470 mg boron oxide/m3 (73 mg boron/m3

) 

for 10 weeks, 175 mg boron oxide/m3 (27 mg boron/m3

) for 12 weeks, or 77 mg boron oxide/m3 (12 mg 

boron/m3

) for 24 weeks (Wilding et al. 1959). 

Hematological Effects. Rats exposed to aerosols of boron oxide at concentrations of 470 mg boron 

oxide/m3 (73 mg boron/m3

) for 10 weeks, 175 mg boron oxide/m3 (27 mg boron/m3) for 12 weeks, or 

77 mg boron oxide/m3 (12 mg boron/m3

) for 24 weeks, and dogs exposed to aerosols of boron oxide at 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 37 

3. HEALTH EFFECTS 

concentrations of 57 mg boron oxide/m3 (9 mg boron/m3) for 23 weeks showed no significant changes in 

total red and white blood cell count, hemoglobin, hematocrit, or differential count (Wilding et al. 1959). 

Musculoskeletal Effects. No gross or microscopic effects of exposure were observed in the femur, 

rib, and muscle of rats exposed to concentrations of 470 mg boron oxide/m3 (73 mg boron/m3

) for 

10 weeks, 175 mg boron oxide/m3 (27 mg boron/m3

) for 12 weeks, or 77 mg boron oxide/m3 (12 mg 

boron/m3

) for 24 weeks (Wilding et al. 1959). 

Hepatic Effects. No gross or microscopic hepatic effects were observed in rats exposed to aerosols of 

boron oxide at concentrations of 470 mg boron oxide/m3 (73 mg boron/m3

) for 10 weeks, 175 mg boron 

oxide/m3 (27 mg boron/m3

) for 12 weeks, or 77 mg boron oxide/m3 (12 mg boron/m3) for 24 weeks. No 

hepatic effects were indicated from serum chemistry of dogs exposed to aerosols of boron oxide at 

concentrations of 57 mg boron oxide/m3 (9 mg boron/m3

) for 23 weeks (Wilding et al. 1959). 

Renal Effects. No gross or microscopic renal effects were observed in rats exposed to aerosols of 

boron oxide at concentrations of 470 mg boron oxide/m3 (73 mg boron/m3

) for 10 weeks, 175 mg boron 

oxide/m3 (27 mg boron/m3

) for 12 weeks, or 77 mg boron oxide/m3 (12 mg boron/m3) for 24 weeks. No 

renal effects were indicated from serum chemistry of dogs exposed to aerosols of boron oxide at 

concentrations of 57 mg boron oxide/m3 (9 mg boron/m3

) for 23 weeks (Wilding et al. 1959). 

Ocular Effects. Human occupational exposure to a mean concentration of 0.44 mg boron/m3 (5.72 mg 

particulates/m3

) (Hu et al. 1992; Wegman et al. 1994) and 1.8–3.1 mg boron/m3 (8.4–14.6 mg 

particulates/m3

) (Garabrant et al. 1984, 1985) as sodium borate dust produced eye irritation following 

acute-duration exposures. The cross-sectional study design of Garabrant et al. (1984, 1985) made it 

difficult to determine whether the observed effects were caused by acute or repeated exposures; however, 

the design employed by Wegman et al. (1994), which included 6-hour TWA air samples and worker 

reports of irritancy before the start of the work shift and during the shift, allowed the determination that 

this acute ocular irritation was due to acute exposure. No ocular effects were observed in rats exposed to 

aerosols of boron oxide at concentrations of 470 mg boron oxide/m3 (73 mg boron/m3

) for 10 weeks, 

175 mg boron oxide/m3 (27 mg boron/m3

) for 12 weeks, or 77 mg boron oxide/m3 (12 mg boron/m3) for 

24 weeks (Wilding et al. 1959). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 38 

3. HEALTH EFFECTS 

3.2.1.3 Immunological and Lymphoreticular Effects 

No gross or microscopic effects on immunological or lymphoreticular tissues (lymph nodes and spleens) 

were observed in rats exposed to aerosols of boron oxide at concentrations of 470 mg boron oxide/m3 

(73 mg boron/m3

) for 10 weeks, 175 mg boron oxide/m3 (27 mg boron/m3) for 12 weeks, or 77 mg boron 

oxide/m3 (12 mg boron/m3

) for 24 weeks (Wilding et al. 1959). 

3.2.1.4 Neurological Effects 

No gross or microscopic effects on the brain were observed in rats exposed to aerosols of boron oxide at 

concentrations of 470 mg boron oxide/m3 (73 mg boron/m3

) for 10 weeks, 175 mg boron oxide/m3 (27 mg 

boron/m3

) for 12 weeks, or 77 mg boron oxide/m3 (12 mg boron/m3) for 24 weeks (Wilding et al. 1959). 

3.2.1.5 Reproductive Effects 

A study of 28 male boric acid production workers occupationally exposed to 22–80 mg/m3 boron aerosols 

(boron form uncertain) for ≥10 years (Tarasenko et al. 1972) revealed low sperm counts, reduced sperm 

motility, and elevated fructose content of seminal fluids, compared to controls. These effects are 

consistent with high-dose animal exposures. However, this study is limited by the small number of 

subjects and limited data reporting. Furthermore, a cross-sectional survey of 753 employees working for 

at least 9 months at a borax production facility in California found worker fertility rates to be higher than 

the U.S. national average (Whorton et al. 1994). However, this study is limited by lack of exposure data. 

In animals, no gross or microscopic effects were found on the ovary or testes of rats exposed to aerosols 

of boron oxide at concentrations of 470 mg boron oxide/m3 (73 mg boron/m3

) for 10 weeks, 175 mg 

boron oxide/m3 (27 mg boron/m3

) for 12 weeks, or 77 mg boron oxide/m3 (12 mg boron/m3) for 24 weeks 

(Wilding et al. 1959). 

3.2.1.6 Developmental Effects 

No studies were located regarding developmental effects in humans or animals after inhalation exposure 

to boron. 

3.2.1.7 Cancer 

No studies were located regarding cancer in humans or animals after inhalation exposure to boron. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 39 

3. HEALTH EFFECTS 

3.2.2 Oral Exposure 

Data for boron oral toxicity in humans involves exposure to the borates or boric acid. These boroncontaining compounds are primarily found in food and water and have been implicated in numerous 

accidental or intentional poisonings in human case reports. Similarly, the boron toxicity studies in 

animals have utilized exposures to borates or boric acid. 

3.2.2.1 Death 

Case reports of lethal oral exposure of humans to boron primarily involve accidental or intentional 

exposures to high levels of boric acid. Similar clinical signs have been seen in adults and children. A 

review of 784 primarily acute boric acid exposures in adults and children found that 88% of cases were 

asymptomatic. The reports did not contain information on the dose response for boric acid, as 

symptomatic cases had doses ranging from 100 mg to 55 g boric acid (18 mg–10 g boron), while 

asymptomatic cases had doses ranging from 10 mg to 89 g boric acid (2 mg–16 g boron) (Litovitz et al. 

1988). Nonetheless, death occurred in some children following oral doses in this wide dose range. Five 

infants who ingested formula accidentally prepared with 2.5% aqueous solution of boric acid became 

lethargic, developed vomiting and diarrhea, and died within 3 days after exposure (Wong et al. 1964). 

The estimated boric acid consumption ranged from 4.51 to 14 g (0.8–2.5g boron). In two infants who 

ingested 9.25 g boric acid (505 mg boron/kg/day) and 14 g boric acid (765 mg boron/kg/day), 

degenerative changes were seen in the liver, kidney, and brain (Wong et al. 1964). In a food poisoning 

incident in Malaysia, 13 children died after consuming Chinese noodles contaminated with boric acid 

(Chao et al. 1991a, 1991b). The deaths were determined by the study authors to be caused by unknown 

levels of aflatoxin and boric acid in the noodles. Clinical signs included vomiting, pyrexia, diarrhea, 

abdominal pain, anorexia, giddiness, seizures, and eventual coma. Postmortem examination revealed 

coagulative necrosis of the liver, proliferative metaplasia of the hepatocytes, giant cell formation, central 

vein sclerosis, bile stasis, and steatosis, acute renal tubule necrosis, upper gastrointestinal erosion, and 

encephalopathy. However, the relative contribution of boric acid to these effects could not be determined. 

A common suite of symptoms was presented in case reports of adult oral exposures that resulted in death. 

A 77-year-old man ingested a single dose of 30 g of boric acid (85 mg boron/kg) to cure hiccups (Ishii et 

al. 1993). Effects included vomiting, diarrhea, erythema, cyanotic extremities, acute renal failure, 

cardiopulmonary hypotension, and death from cardiac insufficiency. Almost identical clinical signs and 
 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 40 

3. HEALTH EFFECTS 

death occurred in a 45-year-old man ingesting approximately 49 g of boron (280 g boric acid, 700 mg 

boron/kg assuming a body weight of 70 kg) (Restuccio et al. 1992). 

In animals, rats appear to be more sensitive than dogs or mice to the lethal effects of acute boron 

exposures. Oral LD50 values for respective boron equivalents of boric acid or borax were 898 and 

642 mg/kg in an unspecified rat strain (Smyth et al. 1969), 600 and 510 mg/kg in Sprague-Dawley rats 

(Weir and Fisher 1972), and 550 and 690 mg/kg in Long Evans rats (Weir and Fisher 1972). No deaths 

were reported in dogs exposed to a single dose of 696 mg boron/kg (3,977 mg boric acid/kg) and 738 mg 

boron/kg (5,549 mg borax/kg) (Weir and Fisher 1972). No single-dose LD50 studies in mice were 

available; however, mortality rates of 20 and 60% were observed in males given 14 daily doses of 

2,251 and 3,671 mg boron/kg/day (12.9 or 21.0 g boric acid/kg/day) in the diet, respectively (NTP 1987), 

but not at 926 mg boron/kg/day (5.3 g boric acid/kg/day). These animals were lethargic and exhibited 

discolored spleen, liver, and renal medullae and hyperplasia and dysplasia of the forestomach (NTP 

1987). 

With intermediate-duration oral exposure, rats appear to be slightly more sensitive than mice to the 

lethality of boric acid. There was 100% mortality in Sprague-Dawley rats fed 450 mg boron/kg/day 

within a 6-week period (Weir and Fisher 1972). Congestion of liver and kidneys, small gonads, and brain 

swelling were reported. Eighty percent of male and 60% of female B6C3F1 mice died in a study 

involving exposure to 577 mg boron/kg/day (3,298 mg boric acid/kg/day) in the diet for up to 90 days 

(NTP 1987). Hyperkeratosis and/or acanthosis in the stomach and extramedullary hematopoiesis of the 

spleen in both sexes of mice were observed at the same dose level. 

With chronic exposure to boric acid in the diet, mortality at 103 weeks was ≥40 and ≥30% in male and 

female B6C3F1 mice, respectively, exposed to ≥79 mg boron/kg/day (≥450 mg boric acid/kg/day), 

compared to 18 and 34% in untreated male and female controls, respectively (NTP 1987). No clinical 

signs were reported for either sex; however, boron caused an increased incidence of testicular atrophy and 

interstitial hyperplasia in male mice exposed to doses ≥201mg boron/kg/day (1,150 mg boric 

acid/kg/day). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 41 

3. HEALTH EFFECTS 

LD50 values and, in some cases, the lowest levels at which death was reported in humans and animals and 

the duration categories are recorded in Table 3-2 and plotted in Figure 3-2. 

3.2.2.2 Systemic Effects 

No studies were located regarding respiratory effects in animals or musculoskeletal effects in humans or 

animals after oral exposure to boron. 

Information on respiratory, gastrointestinal, hematological, cardiovascular, hepatic, renal, and 

dermal/ocular effects is discussed below. The highest NOAEL values and all reliable LOAEL values for 

these systemic effects for each species and duration category are recorded in Table 3-2 and plotted in 

Figure 3-2. 

Respiratory Effects. Widespread vascular congestion and hemorrhages in the lungs were reported in 

one infant who ingested an estimated dose of 505 mg boron/kg/day for 3–5 days (Wong et al. 1964). 

Cardiovascular Effects. Ingestion of 85 mg boron/kg (as 30 g of boric acid) by a 77-year-old man 

(Ishii et al. 1993) resulted in cardiopulmonary hypotension and death from cardiac insufficiency. 

Gastrointestinal Effects. Ingestion of boron in humans can cause gastrointestinal effects. Nausea, 

persistent vomiting, diarrhea, and colicky abdominal pain in infants were associated with acute ingestion 

of a total of ≥184 mg boron/kg/day (based on 1.9 kg body weight) as boric acid, which was accidentally 

incorporated in infant formula (Wong et al. 1964). Vomiting and diarrhea occurred following ingestion 

of 85 mg boron/kg (as 30g of boric acid) by a 77-year-old man (Ishii et al. 1993). Vomiting was the only 

sign of boron toxicity in two adult females who ingested 14 g boron (80 g boric acid) in a fungicide and 

52 g boron (297 g boric acid) in a suicide attempt. In the absence of body weight data, doses for these 

cases could not be estimated. The subjects were hospitalized for 24–96 hours and did not develop further 

symptoms following release (Linden et al. 1986). Food poisoning of 13 children with unknown levels of 

aflatoxin and boric acid (Chao et al. 1991a, 1991b) resulted in vomiting, diarrhea, abdominal pain, 

anorexia, and upper gastrointestinal erosion. 
152

642

153

898

111

600

112

550

114

510

115

690

12

2251

Table 3-2 Levels of Significant Exposure to Boron - Oral Exposure/ LOAEL 

Duration/ 

a Frequency Key to Species NOAEL Less Serious Serious (Route) Figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

ACUTE EXPOSURE Death 

1 Rat 1 x/d 642 (LD50) (NS) 

2 Rat 1 x/d 898 (LD50) (NS) 3 Rat 1 d 600 F (LD50) (Sprague- (G)

Dawley)

4 Rat 1 d 550 M (LD50) (Long- Evans) (G) 5 Rat 1 d 510 M (LD50) (Sprague- (G)

Dawley)

6 Rat 1 d 690 M (LD50) (Long- Evans) (G) 7 Mouse 14 d 2251 (20% mortality) (B6C3F1) (F) 

Reference Chemical Form 

Smyth et al. 1969 Borax Smyth et al. 1969 Boric acid Weir and Fisher 1972 Boric acid Weir and Fisher 1972 Boric acid Weir and Fisher 1972 Borax Weir and Fisher 1972 Borax NTP 1987, Dieter 1994 Boric acid 
16

505

184

505765505

19

926

2251

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

Systemic 

8 Human 3-5 d 

Resp 505 (vascular congestion, Wong et al. 1964 (F) 

hemorrage in one infant Boric acid who died) 

Gastro 184 (vomiting, diarrhea in

infants)

Hepatic 505 (parenchymatous 

degeneration, jaundice, fatty changes, congestion in one infant who died) 

Renal 765 (parenchymatous 

degeneration, reduced urine output, protein in urine in one infant who died) 

Dermal 505 (erythema, 

desquamation, extensive shedding of skin in one infant who died) 

9 Mouse 14 d Gastro 926 2251 (gastric hyperplasia and NTP 1987, Dieter 1994 (F) dysplasia) Boric acid 
113

1000

20

505

143

3671

79

53

88

82

44

88

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) 

a 

Key to Species 

Figure (Strain) 

10 Dog 

(Mongrel) 

Neurological 

11 Human 12 Mouse 

(B6C3F1) 

Reproductive 

13 Rat 

(Wistar) 

14 Rat 

(Wistar) 

Exposure/ LOAEL 

Duration/ 

Frequency NOAEL Less Serious Serious Reference (Route) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

1 d Gastro 1000 (vomiting) Weir and Fisher 1972 (G) Boric acid 

3-5 d 505 (perivascular Wong et al. 1964 (F) hemorrhage, congestion, Boric acid 

thrombosis, and edema in brain of one infant) 

14 d 3671 NTP 1987, Dieter 1994 (F) Boric acid 

1 x/d 53 M 88 M (12 and 13% reduction in Fukuda et al. 2000 2 wk absolute and relative Boric acid (G) testes weight; increase in 

residual body-like structures in the testes; increase in cellular debris in the epididymal ducts; exfoliation of round spermatides, retention of step 19 spermatids) 

1 x/d 44 M 88 M (decreased stage XII Kudo et al. 2000 2 wk spermatids and Boric acid (G) spermatogonia; 

increased stage X pacytene spermatocytes) 
154

70

155

131

66

88

67

70

68

70

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

Developmental 

15 Mouse 2 x/d 70 F (reduced fetal weight and Cherrington and Cherno

Gd 8 (CD-1) increased skeletal Boric acid (G) effects– cervical rib, rib 

agenesis, reduced rib length, and fused ribs) 

16 Mouse 1 x/d 131 F (reduced fetal weight and Cherrington and Cherno

Gd 8 (CD-1) increased cervical Boric acid (G) ossification) 

17 Mouse 1 x/d 88 F (increased skeletal Cherrington and Cherno

Gd 6-10 (CD-1) abnormalities) Boric acid (G) 

18 Mouse 2 x/d 70 F (reduced fetal weight and Cherrington and Cherno

Gd 6-8 (CD-1) increased skeletal Boric acid (G) abnormalities) 

19 Mouse 2 x/d 

70 F (reduced fetal weight) Cherrington and Cherno

Gd 6, 7, 9, or (CD-1) 

10 Boric acid (G) 
70

131

64

70 210

74

22

44

122

450

123

450

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

20 Mouse 2 x/d 131 F (reduced fetal weight and Cherrington and Cherno

Gd 8 (CD-1) increased multiple Boric acid (G) skeletal malformations) 

21 Mouse 1 x/d Harris et al. 1992 

70 F 210 F (no littering) Gd 8-14 (CD-1) 

Boric acid (G) 

22 Rabbit 1 x/d b 22 F 44 F (increased resorptions, Price et al. 1996b Gd 6-19 (New decreased number of live Boric acid Zealand) (G) litters and fetuses, 

increased fetal external, visceral, and cardiovascular malformations) 

INTERMEDIATE EXPOSURE Death 

23 Rat 90 d 450 (100% death by 6 weeks) Weir and Fisher 1972 (Sprague- (F) Borax Dawley) 

24 Rat 90 d 450 (100% mortality by 6 Weir and Fisher 1972 (Sprague- (F) weeks) Boric acid Dawley) 
24

577

62

0.03

148

43

86

172

71

52

68

65

61

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

25 Mouse 13 wk 577 (80% males and 60% NTP 1987, Dieter 1994 (B6C3F1) (F) females died) Boric acid 

Systemic 

26 Human 1 d/wk Endocr 0.03 M Ferrando and Green 19

7 wk 

Boron (C) 

27 Rat 30 d Hepatic 43 M 86 M (11% reduction in liver Dixon et al. 1979 (Sprague- (F) weight) Borax Dawley) 

Bd Wt 172 M 

28 Rat 9 wk Bd Wt 52 M 68 M (16% decrease in body Ku et al. 1993a (Fischer- 344) (F) weight gain) Boric acid 

29 Rat 4 wk Endocr 61 M (approximately 60-78% Treinen and Chapin 199

(Fischer- 344) (F) decrease in plasma Boric acid 

testosterone) 
116

45045045045045

150

45045

150

45

150

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

30 Rat 90 d Cardio 450 (Sprague- (F)

Dawley)

Gastro 450 Hemato 450 Musc/skel 450 Hepatic 45 M 150 M Renal 450 Dermal 45 150 Ocular 45 150 

Weir and Fisher 1972 Borax 

(16% decrease in relative 

liver weight without histologic changes) 

(desquamated skin on 

paws and tails) 

(inflammed eyes [clinical 

observation]) 
124

45045045045045

150

45045045

150

45

150

31 

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) 

Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

Rat 90 d Cardio 450 Weir and Fisher 1972 (Sprague- (F) 

Boric acid Dawley) 

Gastro 450 Hemato 450 Musc/skel 450 Hepatic 45 M 150 M (22% reduction in liver

weight without histologicchanges)

Renal 450 Endocr 450 Dermal 45 150 (desquamated skin on

paws and tail)

Ocular 45 150 (inflammed eyes [clinical

observations])
144

577577288

577

35

72

577577577577144

288 577

32 

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) 

Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

Mouse 13 wk Resp 577 NTP 1987, Dieter 1994 (B6C3F1) (F) 

Boric acid 

Cardio 577 Gastro 288 M 577 M (hyperkeratosis and/or

acanthosis of thestomach)

Hemato 35 M 72 M (splenic extramedullary

hematopoiesis)

Hepatic 577 Renal 577 Endocr 577 Dermal 577 Bd Wt 144 M 288 M (17% reduction in body 577 M (23% reduction in body 

weight) weight) 
117

60.560.56

60.5

60.560.560.560.560.560.5

33 

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) 

Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

Dog 90 d Cardio 60.5 Weir and Fisher 1972 (Beagle) (F) 

Borax 

Gastro 60.5 Hemato 6 60.5 (decreased packed cell

volume and hemoglobinvalues)

Musc/skel 60.5Hepatic 60.5Renal 60.5Endocr 60.5Dermal 60.5Ocular 60.5
129

60.560.560.560.560.56

60.5

60.560.560.560.5

118

50

170

125

50

170

150

577

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) 

a 

Key to Species 

Figure (Strain) 

34 Dog 

(Beagle) 

Neurological 

35 Rat 

(SpragueDawley) 

36 Rat 

(SpragueDawley) 

37 Mouse 

(B6C3F1) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

90 d (F) 90 d (F) 90 d (F) 13 wk (F) 

LOAEL 

System 

Resp 

Cardio Gastro Hemato Musc/skel Hepatic Renal Endocr Dermal Ocular 

NOAEL 

(mg/kg/day) 

60.5 

60.5 

60.5 

60.5 

60.5 

6 F 

60.5 60.5 60.5 

60.5 

50 F 50 F 

577 

Less Serious Serious 

(mg/kg/day) (mg/kg/day) 

60.5 F (46% increase in relative 

liver weight with no adverse histologic changes) 

170 F (15% increase in relative 

brain weight) 

170 F (15% increase in relative 

brain weight) 

Reference Chemical Form 

Weir and Fisher 1972 Boric acid Weir and Fisher 1972 Borax Weir and Fisher 1972 Boric acid NTP 1987, Dieter 1994 Boric acid 
128

60.5

39

0.6

149

43

86

41

43

86

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) 

a 

Key to Species 

Figure (Strain) 

38 Dog 

(Beagle) 

Reproductive 

39 Rat 

(SpragueDawley) 

40 Rat 

(SpragueDawley) 

41 Rat 

(SpragueDawley) 

Exposure/ LOAEL 

Duration/ 

Frequency NOAEL Less Serious Serious Reference (Route) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

90 d 60.5 F Weir and Fisher 1972 (F) Borax 

90 d 0.6 Dixon et al. 1976 (W) Borax 30 d 43 M (decreased testicular 86 M (infertility for 3 weeks Dixon et al. 1979 (F) enzyme activities; following exposure) Borax 

increased plasma FSH) 

60 d 43 M (62% decrease in testes 86 M (infertility for 5 weeks Dixon et al. 1979 (F) weight; 37% decrease in following exposure) Borax 

epidiymis weight; increased plasma FSH; reduced diameter of seminiferous tubules) 
80

53

72

26

52

83

22

44

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) Exposure/ LOAEL

Duration/

a Frequency Key to Species NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

42 Rat 1 x/d 53 M (13 and 15% reduction in Fukuda et al. 2000 

(Wistar) 4 wk 

absolute and relative Boric acid (G) testes weight; cellular debris in the testes, cauda and caput epididymis; focal atrophy of the seminiferous tubules; decrease in the number of sperm in the ducta lumina) 

43 Rat 9 wk 

26 M (mildly inhibited 52 M (testicular atrophy by Ku et al. 1993a (Fischer- 344) (F) 

spermiation by week 5) week 9; severe inhibition Boric acid 

of spermiation) 

44 Rat 1 x/d 

22 M 44 M (reduced sperm motility; Kudo et al. 2000 (Wistar) 4 wk 

reduced total sperm in Boric acid (G) caudal epididymis) 
38

50

100

86

136

43

44.7

120

45

150

121

45

150

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) Exposure/ LOAEL

Duration/

a Frequency Reference Key to Species NOAEL Less Serious Serious (Route) Figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

45 Rat 30-60 d 50 100 (testicular atrophy, Lee et al. 1978 (F) decreased enzymes) Borax 

46 Rat 60 d 

136 M (decreased weights of Nusier and Bataineh 20

(Sprague- (F) 

testes and associated Boric acid Dawley) 

tissues; decreased sperm motility, number of spermatocytes, spermatids, Leydig cells, testosterone levels, sexually aggressive behavior, number of females impregnated; increased fetal resorption in impregnated females) 

47 Rat 70 d 44.7 M (impaired Seal and Weeth 1980 (Long- Evans) (W) spermatogenesis) Borax 

48 Rat 90 d 45 M 150 M (53% reduction in Weir and Fisher 1972 (Sprague- (F) testicular weight) Borax Dawley) 

49 Rat 90 d 45 M 150 M (53% decrease in Weir and Fisher 1972 (Sprague- (F) testicular weight; Borax Dawley) testicular atrophy) 
141

30 101

116

142

30 101

116

156

116

157

116

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) 

a 

Key to Species 

Figure (Strain) 

50 Rat 

(SpragueDawley) 

51 Rat 

(SpragueDawley) 

52 Rat 

(SpragueDawley) 

53 Rat 

(SpragueDawley) 

Exposure/ LOAEL 

Duration/ 

Frequency NOAEL Less Serious Serious Reference (Route) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

3 gen c 30 101 M (complete sterility) Weir and Fisher 1972 (F) Borax 

116 F (complete sterility) 

3 gen c 30 101 M (complete sterility) Weir and Fisher 1972 (F) Boric acid 

116 F (complete sterility) 

3 gen 116 F (complete sterility) Weir and Fisher 1972 (F) Borax 

3 gen 116 F (complete sterility) Weir and Fisher 1972 (F) Boric acid 
87

9

26

97

27

111

63

21

70

210

44

288

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) Exposure/ LOAEL 

Duration/ 

a 

Key to Species 

Figure (Strain) 

54 Rat 

(Wistar) 

55 Mouse 

(CD-1) 

56 Mouse 

(CD-1) 

57 Mouse 

(B6C3F1) 

Frequency NOAEL Less Serious Serious (Route) System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

3 wk 9 M 26 M (increased (G) pre-implantation fetal 

loss; decreased sperm motility; morphologically-abnormal 

sperm heads and tails) 

27 wk 27 M 111 M (degeneration of the (F) seminiferous tubules; 

impaired spermatogenesis; decreased sperm motility, litters per mating pair, and live pups per litter) 

M: 17 d (d 3-20) 21 M 70 M (reduced testis weight, 210 M (exfoliation/disruption of F: 20 d (d 0-20) germ cell loss) seminiferous tubules; (G) inhibited spermiation; no 

effect on % females pregnant) 

13 wk 288 M (degeneration or atrophy (F) of seminiferous tubules) 

Reference Chemical Form 

Yoshizaki et al. 1999 Boric acid Fail et al. 1991 Boric acid Harris et al. 1992 Boric acid NTP 1987, Dieter 1994 Boric acid 
126

6

60.5

127

6

60.5

36

13.6

28.4

73

10

13

37

43.4

79

175.3

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) Exposure/ LOAEL 

Duration/ 

a 

Key to Species 

Figure (Strain) 

58 Dog 

(Beagle) 

59 Dog 

(Beagle) 

Developmental 

60 Rat 

(SpragueDawley) 

61 Rat 

(SpragueDawley) 

62 Mouse 

(CD-1) 

Frequency NOAEL Less Serious Serious (Route) System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

90 d 6 M 60.5 M (50% decrease in relative (F) testes weight; severe 

testicular atrophy) 

90 d 6 M 60.5 M (40% decrease in testes (F) weight; severe testicular 

atrophy) 

Gd 0-20 d 13.6 (reduced fetal weight) 28.4 (rib cage defects, (F) enlargement of the lateral 

ventricles of the brain, increased resorptions) 

Gd 0-20 d 10 F 13 F (reduced fetal weight, (F) increase in skeletal 

abnormalities observed on gestation day 20) 

Gd 0-17 43.4 79 (reduced fetal body 175.3 (increased skeletal (F) weight) effects [short rib XIII, 

fused ribs, agenesis of lumbar vertabra], increased resorptions) 

Reference Chemical Form 

Weir and Fisher 1972 Borax Weir and Fisher 1972 Boric acid Heindel et al. 1992 Boric acid Price et al. 1996a, 1998 Boric acid Heindel et al. 1992 Boric acid 
50

79

131

81818124

81

81818124

81

24 8124

81

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

CHRONIC EXPOSURE Death 

63 Mouse 103 wk 79 (40% mortality) NTP 1987, Dieter 1994 (B6C3F1) (F) Boric acid 

Systemic 

64 Rat 2 yr Resp 81 Weir and Fisher 1972 

(Sprague- (F) 

Boric acid Dawley) 

Cardio 81 Gastro 81 Hemato 24 F 81 F (decreased packed cell

volume and hemoglobinlevels)

Hepatic 81 Renal 81 Endocr 81 Dermal 24 81 (scaly tails,

desquamation of skin onfootpads)

Ocular 24 81 (bloody ocular discharge) Bd Wt 24 81 (reduced growth

throughout study)
133

81818124

81

81818124

81

24 8124

81

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

65 Rat 2 yr Resp 81 (Sprague- (F)

Dawley)

Cardio 81 Gastro 81 Hemato 24 81 Hepatic 81 Renal 81 Endocr 81 Dermal 24 81 Ocular 24 81 Bd Wt 24 81 

Weir and Fisher 1972 Borax 

(decreased packed cell volume and hemoglobin levels) (scaly tails, desquamation of skin on footpads) (bloody ocular discharge) (decreased growth throughout study) 
145

79 201201201

7979

20120120179

201

66 

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) 

Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

Mouse 103 wk Resp 79 F 201 F (lung hemorrhage) NTP 1987, Dieter 1994 (B6C3F1) (F) 

Boric acid 

Cardio 201 Gastro 201 Hemato 79 M (spenic hematopoiesis) Hepatic 79 (chronic inflammation; 

coagulative necrosis) 

Renal 201Endocr 201Ocular 201Bd Wt 79 201 (10%-17% decrease in

body weight) 
130

6.86.86.86.86.86.86.86.86.86.86.8

67 

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) 

Exposure/ LOAEL

Duration/

a Frequency Key to Species NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

Dog 2 yr Resp 6.8 Weir and Fisher 1972 (Beagle) (F) 

Boric acid 

Cardio 6.8 Gastro 6.8 Hemato 6.8 Musc/skel 6.8 Hepatic 6.8 Renal 6.8 Endocr 6.8 Dermal 6.8 Ocular 6.8 Bd Wt 6.8 
132

6.86.86.86.86.86.86.86.86.86.86.8

137

24

81

138

24

81

151

201

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) 

a 

Key to Species 

Figure (Strain) 

68 Dog 

(Beagle) 

Neurological 

69 Rat 

(SpragueDawley) 

70 Rat 

(SpragueDawley) 

71 Mouse 

(B6C3F1) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

2 yr (F) 2 yr (F) 2 yr (F) 103 wk (F) 

System 

Resp 

Cardio Gastro Hemato Musc/skel Hepatic Renal Endocr Dermal Ocular Bd Wt 

LOAEL 

NOAEL Less Serious Serious Reference

(mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

6.8 Weir and Fisher 1972 

Borax 

6.8 

6.8 6.8 6.8 6.8 6.8 6.8 6.8 6.8 

6.8 

24 81 (increased relative brain Weir and Fisher 1972

weight) Boric acid

24 81 (increased relative brain Weir and Fisher 1972

weight) Borax

201 NTP 1987, Dieter 1994 

Boric acid 
161

6.1

135

24

81

136

24

81

55

79

201

139

6.8

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

Reproductive 

72 Human NS 6.1 F Liu et al. 2006a (Environ) Borate 

73 Rat 2 yr 24 M 81 M (decreased relative Weir and Fisher 1972 (Sprague- (F) testes weight; testicular Borax Dawley) atrophy; atrophied 

seminiferous epithelium and reduced tubular size) 

74 Rat 2 yr 24 M 81 M (decreased relative Weir and Fisher 1972 (Sprague- (F) testes weight; testicular Boric acid Dawley) atrophy; atrophied 

seminiferous epithelium and reduced tubular size) 

75 Mouse 103 wk 79 201 (testicular atrophy, NTP 1987, Dieter 1994 (B6C3F1) (F) interstitial hyperplasia) Boric acid 

76 Dog 2 yr 6.8 M Weir and Fisher 1972 (Beagle) (F) Borax 
140

6.8

77 

Table 3-2 Levels of Significant Exposure to Boron - Oral (continued) 

Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

Dog 2 yr 6.8 M Weir and Fisher 1972 (Beagle) (F) Boric acid 

Table 3-2 Oral a The number corresponds to entries in Figure 3-2. b Used to derive an acute-duration oral MRL of 0.2 mg/kg/day; dose divided by an uncertainty factor of 100 (10 for interspecies extrapolation and 10 for human varic Differences in levels of health effects and cancer effects between male and females are not indicated in Figure 3-2. Where such differences exist, only the levels most sensitive gender are presented. d Used to derive an intermediate-duration oral MRL of 0.2 mg/kg/day; a point of departure from benchmark dose analysis of 10.3 mg boron/kg/day was divided by a uncertainty factor of 66 (3.3 for toxicokinetic extrapolation from animals to humans, 3.16 for toxicodynamic extrapolation from animals to humans, 2.0 for variability toxicokinetics, and 3.16 for variability in human toxicodynamics). Bd Wt = body weight; (C) = capsule; Cardio = cardiovascular; CEL = cancer effect level; d = day(s); Endocr = endocrine; (F) = feed; F = Female; FSH = follicle stim(G) = gavage; Gastro = gastrointestinal; Gd = gestational day; Hemato = hematological; LD50 = lethal dose, 50% kill; LOAEL = lowest-observed-adverse-effect leveMetab = metabolic; Musc/skel = musculoskeletal; NOAEL = no-observed-adverse-effect level; NS = not specified; Resp = respiratory; x = time(s); (W) = drinking wyr = year(s) 
Death 

Respiratory Gastrointestinal Hepatic Renal Dermal Neurological Reproductive 


	


	

10000 

12m 

7m 9m 

1000 10d 2r 9m 8 1r 6r 3r 4r 5r 8 8 8 11 

8 

100 13r 14r 

13r 14r 

10 

1 

0.1 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

21m 

16m 20m 

17m 

15m 18m 19m 21m 

22h 

22h 

Developmental 


	


	


	

3. HEALTH EFFECTS

Figure 3-2 Levels of Significant Exposure to Boron - Oral

Acute (≤ 14 days)
	 BORON

Systemic 

mg/kg/day 

66
De

ReCaGaHeMuHeRe

1000 

mg/kg/day 

25m 32m 32m 32m 32m 

23r 24r 30r 31r 30r 31r 30r 31r 30r 31r 

32m 

30r 31r 

100 27r 32m 34d 33d 34d 33d 34d 33d 34d 33d 34d 33d 34d 33d 

27r 30r 31r

32m 

10 

33d 34d 

1 

0.1 

0.01 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

ath 

spiratory 

rdiovascular 

strointestinal 

matological 

sculoskeletal 

patic 

nal 


 


	


	

3. HEALTH EFFECTS

Figure 3-2 Levels of Significant Exposure to Boron - Oral (Continued)

Intermediate (15-364 days)
	

Systemic
	

BORON 67
Renal 

Endocrine Dermal Ocular Body Weight Neurological Reproductive 


	

1000 

Systemic

mg/kg/day 

32m 32m 32m 32m 37m 

30r 31r 31r 

32m 57m 

56m

27r 35r 36r 30r 31r 30r 31r 32m 46r

100 55m 45r 40r 41r

28r 56m 34d 33d 34d 29r 33d 34d 33d 34d 38d 58d 59d 28r 35r 36r 42r 43r 45r 30r 31r 30r 31r 40r 41r 44r

55m 43r

56m 44r

10 

58d 59d 

1 

39r 

0.1 

26 

0.01 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 


	


 

3. HEALTH EFFECTS

Figure 3-2 Levels of Significant Exposure to Boron - Oral (Continued)

Intermediate (15-364 days)
	 BORON 68
Reproductive 

Developmental 

mg/kg/day 

1000 

62m 48r 49r 

50r 51r 52r 53r 50r 51r 

62m 

47r 

100 

48r 49r 62m 

50r 51r 60r 54r 

60r 61r 

10 61r 54r 

1 

0.1 

0.01 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans Minimal Risk Level 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans for effects 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans other than 

q-Cow a-Sheep g-Guinea Pig Cancer 


 


	

3. HEALTH EFFECTS

Figure 3-2 Levels of Significant Exposure to Boron - Oral (Continued)

Intermediate (15-364 days)
	 BORON 69
Death 

Respiratory Cardiovascular Gastrointestinal Hematological Musculoskeletal Hepatic 

Systemic 

mg/kg/day 

1000 

66m 66m 66m 

100 

63m 66m 64r 65r 64r 65r 64r 65r 66m 64r 65r 66m 64r

64r 65r 

10 

67d 68d 67d 68d 67d 68d 67d 68d 67d 68d 67d 68d 

1 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 


	


 

3. HEALTH EFFECTS

Figure 3-2 Levels of Significant Exposure to Boron - Oral (Continued)

Chronic (≥ 365 days)
	 BORON 70
Hepatic 

Renal Endocrine Dermal Ocular Body Weight Neurological Reproductive 


	


	

1000 

Chronic (≥ 365 days)
	

Systemic
	

mg/kg/day 

66m 66m 66m 66m 71m 

100 

65r 64r 65r 64r 65r 64r 65r 64r 65r 66m 64r 65r 69r 70r

64r 65r 64r 65r 64r 65r 69r 70r 

10 

67d 68d 67d 68d 67d 68d 67d 68d 67d 68d 76d 

1 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 


 

3. HEALTH EFFECTS

Figure 3-2 Levels of Significant Exposure to Boron - Oral (Continued)

BORON 71
mg/kg/day Reproductive 

1000 

75m 

100 

75m 73r 74r

73r 74r 

10 

77d 72 

1 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 


 


	

3. HEALTH EFFECTS

Figure 3-2 Levels of Significant Exposure to Boron - Oral (Continued)

Chronic (≥ 365 days)
	 BORON 72
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 73 

3. HEALTH EFFECTS 

In B6C3F1 mice, dietary exposure to ≥2,251 mg boron/kg/day as boric acid for 14 days resulted in gastric 

hyperplasia and dysplasia (NTP 1987). Dogs given a single dose of 1,000 mg boron/kg as boric acid 

vomited (Weir and Fisher 1972). 

Hematological Effects. In animals orally exposed for intermediate or chronic durations, effects on 

hematological end points have been observed sporadically in dogs and consistently in mice; they did not 

occur in rats exposed for 90 days. Mongrel dogs fed 60.5 mg boron/kg/day for 90 days in the diet as 

borax (but not as boric acid) had decreased packed cell volume and hemoglobin values, but no 

hematological effects were seen in dogs fed 81 mg boron/kg/day as borax or boric acid for 2 years (Weir 

and Fisher 1972). Erythrocyte count and total and differential leukocyte counts were comparable to 

control levels (Weir and Fisher 1972). Splenic extramedullary hematopoiesis occurred in mice fed 72 mg 

boron/kg/day as boric acid for 90 days and 79 mg boron/kg/day for 2 years (Dieter 1994; NTP 1987), 

while no hematological effects were observed in rats fed 450 mg boron/kg/day as borax or boric acid for 

90 days (Weir and Fisher 1972). Decreased packed cell volume and hemoglobin values were seen in rats 

fed 81 mg boron/kg/day as borax for 2 years (Weir and Fisher 1972). 

Hepatic Effects. Case reports in humans suggest that the liver is susceptible to boron toxicity at high 

dose levels (Wong et al. 1964). Jaundice has been reported, and there were mild alterations at histological 

examination in infants who ingested 505 or 765 mg boron/kg/day as boric acid (accidentally incorporated 

in infant formula) for 3–5 days (Wong et al. 1964). In the same incident, congestion and fatty changes 

were observed, and there was parenchymatous degeneration in newborn infants who ingested 505 or 

765 mg boron/kg as boric acid for 3–5 days (Wong et al. 1964). Coagulative necrosis of the liver, 

proliferative metaplasia of the hepatocytes, giant cell formation, central vein sclerosis, bile stasis, and 

hepatic steatosis were observed in children ingesting unknown levels of aflatoxin and boric acid in 

Chinese noodles (Chao et al. 1991a, 1991b). 

In mice, the liver appears to be a toxicity target of repeated oral exposure to boric acid, but it is not a 

target in rats and dogs repeatedly exposed to boric acid or borates. Two-year dietary exposures of 

≥79 mg boron/kg/day as boric acid to B6C3F1 mice resulted in chronic inflammation and coagulative 

necrosis in the liver (NTP 1987; Dieter 1994), but no exposure-related hepatic lesions were found in 

Sprague-Dawley rats fed 81 mg boron/kg/day as boric acid or borax in the diet for 2 years or in mongrel 

dogs fed 6.8 mg boron/kg/day as boric acid or borax in the diet for 2 years (Weir and Fisher 1972). No 

exposure-related liver lesions were seen in mice fed 577 mg boron/kg/day as boric acid for 13 weeks 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 74 

3. HEALTH EFFECTS 

(Dieter 1994; NTP 1987); in Sprague-Dawley rats fed 450 mg boron/kg/day as boric acid or borax for 

90 days (Weir and Fisher 1972); or in mongrel dogs fed 60.5 mg boron/kg/day as boric acid or borax for 

90 days (Weir and Fisher 1972). 

Boron-related changes in liver weights have not been consistently observed in animal studies. Reduced 

liver weights were observed in rats fed 86 mg boron/kg/day as borax for 30 days (Dixon et al. 1979) and 

fed 150 mg boron/kg/day as borax or boric acid for 90 days (Weir and Fisher 1972), while increased 

relative liver weights were seen in mongrel dogs fed 60.5 mg boron/kg/day as boric acid for 90 days 

(Weir and Fisher 1972). 

In liver microsomal fractions from rats given approximately 20.8 mg boron/kg/day as borax in drinking 

water, NADPH-cytochrome C reductase activity and cytochrome b5 content decreased in the liver 

microsomal fraction after 10 and 14 weeks of exposure (Settimi et al. 1982). There was also a reduction 

in the cytochrome P-450 concentration detected at 14 weeks (Settimi et al. 1982). The toxicological 

significance of these biochemical changes is not clear, especially since intermediate- and chronic-duration 

feeding studies with Sprague-Dawley rats fed boric acid or borax did not report exposure-related hepatic 

lesions (Weir and Fisher 1972). 

Renal Effects. Human case reports involving high accidental ingestion levels show that boron can 

cause injury to the kidney. Acute renal failure was observed in a 77-year-old man ingesting 85 mg 

boron/kg (as 30 g of boric acid) (Ishii et al. 1993). Degenerative changes in parenchymal cells with 

oliguria and albuminuria have been demonstrated in two newborn infants after ingestion of 505 and 

765 mg boron/kg/day as boric acid in an evaporated milk formula over a period of 3–5 days (Wong et al. 

1964). Acute renal tubule necrosis was seen in children dying from ingestion of unknown levels of 

aflatoxin and boric acid in Chinese noodles (Chao et al. 1991a, 1991b). 

No exposure-related renal lesions were observed in Sprague-Dawley rats fed up to 450 mg boron/kg/day 

as borax or boric acid for 90 days (Weir and Fisher 1972), in mice fed 577 mg boron/kg/day as boric acid 

for 13 weeks (NTP 1987; Dieter 1994), or in dogs fed up to 60.5 mg boron/kg/day as borax or boric acid 

for 90 days (Weir and Fisher 1972). With 2 years of dietary exposure, no exposure-related renal lesions 

were observed in Sprague-Dawley rats fed 81 mg boron/kg/day as borax or boric acid (Weir and Fisher 

1972), in B6C3F1 mice fed up to 201 mg boron/kg/day as boric acid (Dieter 1994; NTP 1987), or in 

mongrel dogs fed 6.8 mg boron/kg/day as borax or boric acid (Weir and Fisher 1972). The available data 

indicate that the kidney is not a sensitive toxicity target of oral exposure to boric acid or borates. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 75 

3. HEALTH EFFECTS 

Endocrine Effects. Human data for endocrine effects from orally ingested boron are limited to 

studies of low-dose boron nutritional supplementation. Postmenopausal women ingesting 0.4 mg 

boron/day (as 3.25 mg sodium borate/day) in the diet had a 3-fold increase in plasma testosterone levels 

compared to those ingesting 0.03 mg boron/day (as 0.25 mg sodium borate/day) (Nielsen et al. 1987). 

However, bodybuilders taking daily supplements of 2.5 mg boron (approximately 0.03 mg/kg; calculated 

using mean body weights from study data) for 7 weeks did not exhibit differences from controls in free or 

total plasma testosterone levels (Ferrando and Green 1993). 

Rats fed diets with 61 mg boron/kg/day as boric acid (9000 ppm) for 28 days had decreases of 

approximately 60–78% in plasma testosterone levels beginning on day 4 of exposure (Treinen and Chapin 

1991). Follicle stimulating hormone (FSH) and leutenizing hormone (LH) levels in the blood of rats fed 

26–68 mg boron/kg/day as boric acid (3,000–9,000 ppm; doses estimated by study authors) in the diet 

were increased, possibly in response to testicular atrophy observed in the 52 and 68 mg boron/kg/day 

groups (Ku et al. 1993a). No histologic lesions were observed in thyroid, adrenals, or pituitary tissues of 

Sprague-Dawley rats fed 450 or 81 mg boron/kg/day as boric acid or borax in the diet for 90 days or 

2 years, respectively, or in mongrel dogs fed 60.5 or 6.8 mg boron/kg/day as boric acid or borax in the 

diet for 90 days or 2 years, respectively (Weir and Fisher 1972) or in pituitary tissues of mice fed 577 or 

201 mg boron/kg day as boric acid for 90 days or 2 years, respectively (Dieter 1994; NTP 1987). 

Dermal Effects. Skin effects can occur following ingestion of boron (as boric acid) in humans. 

Extensive exfoliative dermatitis began in infants as an erythema involving palms, soles, and buttocks. It 

eventually became generalized with subsequent bulbous formation, massive desquamation, and sloughing 

(Wong et al. 1964). These changes were associated with ingestion of 505 mg boron/kg/day; however, 

skin lesions were lacking following ingestion of 765 mg boron/kg/day. Similarly, extensive erythema 

with desquamation was observed in an adult who ingested single doses of boric acid powder (Schillinger 

et al. 1982). The exact amount ingested was not stated. However, 14 g (equivalent to 22.5 mg boron/kg 

based on 109 kg body weight) was measured as missing from a container from which the patient admitted 

consuming half its contents. 

In animals studies, skin lesions were observed in Sprague-Dawley rats fed 150 mg boron/kg/day as borax 

or boric acid in the diet for 90 days (skin desquamations on the paws and tails) or 81 mg boron/kg/day for 

2 years (scaly tails and desquamation on footpads) (Weir and Fisher 1972), but dermal lesions were not 

observed in B6C3F1 mice exposed to boric acid in the diet for 13 weeks or 2 years (Dieter 1994; NTP 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 76 

3. HEALTH EFFECTS 

1987) or in mongrel dogs exposed to boric acid or borax in the diet for 90 days or 2 years (Weir and 

Fisher 1972). 

Ocular Effects. There are no reports of ocular effects in humans following oral exposure to humans. 

Sprague-Dawley rats fed 150 mg boron/kg/day as borax or boric acid for 90 days exhibited inflammation 

of the eyes, while 81 mg boron/kg/day as borax or boric acid in the diet for 2 years resulted in bloody 

ocular discharge (Weir and Fisher 1972). No ocular effects were seen in dogs fed 60.5 mg boron/kg/day 

as borax or boric acid for 90 days or 6.8 mg boron/kg/day borax or boric acid for 2 years (Weir and Fisher 

1972). Likewise, mice fed 201 mg boron/kg/day as boric acid for 2 years exhibited no ocular effects. 

Body Weight Effects. Fisher 344 rats fed 68 mg boron/kg/day as boric acid (9,000 ppm) for 9 weeks 

had 6% lower body weight gain than controls (Ku et al. 1993a). Male and female B6C3F1 mice fed 

288 and 577 mg boron/kg/day as boric acid (0.5% of diet) for 13 weeks had 17 and 23% decreased weight 

gains, respectively, while 2-year exposures to 201 mg boron/kg/day as boric acid resulted in 19% lower 

weight gains in both sexes (NTP 1987, Dieter 1994). 

3.2.2.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological effects in humans or animals after oral exposure to 

boron. 

3.2.2.4 Neurological Effects 

Case reports in humans have indicated neurological effects after accidental ingestion of high levels of 

boron (as boric acid). Newborn infants who ingested 4.5–14 g boric acid showed central nervous system 

involvement manifested by headache, tremors, restlessness, and convulsions followed by weakness and 

coma (Wong et al. 1964). Histological examination of 2 of 11 infants revealed congestion and edema of 

brain and meninges with perivascular hemorrhage and intravascular thrombosis at a dose ≥505mg 

boron/kg/day (Wong et al. 1964). Seizure disorders have been associated with boron exposures (as 

borax) in infants who ingested 12–120 g borax for 4–10 weeks (O'Sullivan and Taylor 1983) and 9–125 g 

borax over a period of 5–12 weeks (Gordon et al. 1973). Estimates of boron dose could not be 

determined since the authors did not provide body weight data. Blood boron levels in the infants exposed 

who ingested borax ranged from 2.6 to 8.5 μg/mL (O'Sullivan and Taylor 1983). In one infant with a 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 77 

3. HEALTH EFFECTS 

seizure disorder who ingested (via pacifier dipped in honey and borax mixture) approximately 125 g 

borax over 3 months, the blood boron level was 1.64 mg/100 mL (Gordon et al. 1973). 

Existing animal studies do not provide evidence that the nervous system is a toxicity target of repeated 

oral exposure to boric acid or borates, but no studies have examined batteries of neurological end points 

in animals following exposure to boron compounds. Relative brain weights were increased in mongrel 

dogs fed 60.5 mg boron/kg/day as borax, but not boric acid, for 90 days and in rats fed 170 or 81 mg 

boron/kg/day as borax or boric acid for 90 days or 2 years, respectively (Weir and Fisher 1972). No 

histological lesions were observed in these animals or in the brain or spinal cord of mice fed 577 or 

201 mg boron/kg/day as boric acid for 13 weeks or 2 years, respectively (NTP 1987; Dieter 1994). 

In Wistar rats, exposure to approximately 20.8 mg boron/kg/day as borax (based on weight of 0.35 kg and 

average water consumption of 20.7 mL) in drinking water for up to 14 weeks caused increased cerebral 

succinate dehydrogenase activity after 10 and 14 weeks of exposure (Settimi et al. 1982). Increased 

ribonucleic acid (RNA) concentration and increased acid proteinase activity in brain occurred after 

14 weeks (Settimi et al. 1982). The neurological significance of these biochemical changes is unclear. 

All LOAEL values for neurological effects in humans and animals are recorded in Table 3-2 and plotted 

in Figure 3-2. 

3.2.2.5 Reproductive Effects 

A survey of Turkish subpopulations compared fertility rates of 1,068 families living in two Turkish 

villages having drinking water boron levels of 2–29 mg/liter (from nearby geological deposits of calcium 

borate) with 610 families living in three other villages having drinking water boron levels of 0.03– 

0.4 mg/liter (Sayli 1998a, 1998b; Sayli et al. 1998). Assuming 70-kg body weights and 2-L/day drinking 

water consumption, these boron levels would results in an estimated range of daily doses of 0.06– 

0.8 mg/kg/day. Three generations of families were represented. No significant differences in frequencies 

of infertility were observed between high- (2.34% infertility) and low-exposure (2.62% infertility) village 

groups. A separate analysis of the same subpopulation found no association of higher drinking water 

borate concentrations with increased rates of spontaneous abortions, stillbirths, or infant death (Tuccar et 

al. 1998). A follow-up study of this population reported no significant differences in infertility 

frequencies between the two populations (Sayli 2003). 
 

 

 

 

 

 

 

 

 

 

 

 

BORON 78 

3. HEALTH EFFECTS 

A questionnaire was administered to 542 male workers at a borax and boric acid production facility in 

California inquiring about the ability to conceive a child after at least 9 months of employment at the 

facility (Whorton et al. 1994). The worker population was categorized as having low, mid, or high 

exposures to borax or boric acid (exposure levels were not reported). A standardized birth ratio (SBR) 

was calculated as the number of children born to wives compared to the number of births expected in the 

same fraction of the U.S. population. The calculated SBR of 113 indicated higher birth rates among the 

borate workers relative to the U.S. population. Thus, this survey provided no evidence for association 

between occupational exposure to borax or boric acid and impaired fertility; however, the study is limited 

by non-rigorous survey design, lack of quantitative exposure data, and lack of a comparable comparison 

(control) group. 

A cross-sectional survey of 1,187 Chinese boron mining and processing workers examined the 

association of boron exposure and various lifestyle factors to multiple reproductive indices (Chang et al. 

2006). No exposure estimates were reported, but boron levels in drinking water and staple foodstuffs 

were significantly higher for surveyed workers compared to a comparison population. After correcting 

for age, race, diet, alcohol consumption, smoking, and education, there were no statistically significant 

differences between workers and the comparison population for ability to sire offspring, delayed 

pregnancy, multiple births, miscarriages, induced abortions, stillbirths, or tubal or ectopic pregnancies. 

Liu et al. reported two studies of 176 (2006a) and 195 (2006b) Chinese men exposed to between 13 and 

430 mg boron/day. The investigators found no significant difference in semen quality and sperm motility, 

speed, or departure from a straight-line path in groups of borate workers, non-occupationally exposed 

men from a nearby community with high environmental levels of borates, and men from a community 

with low environmental levels of borates. However, data for estimated boron exposures for each group 

were not available. 

A study of 146 Chinese men comprising borate workers, a community group, and controls were assessed 

for chromosomal shifts in the ratio of Y:X chromosomes in sperm (Robbins et al. 2008). A significant 

correlation was found for Y:X ratios and internal boron doses in blood, semen, and urine. Estimated daily 

boron exposures of 41.2, 4.3, and 2.3 mg/day in the borate workers, community group, and controls were 

associated with mean Y:X sperm ratios of 0.93, 0.96, and 0.99, respectively. However, no dose-response 

relationship was observed in the reported percentage of men who had fathered “more boys than girls”, 

which was 57.7, 42.3, and 76.7% in the borate workers, community group, and controls, respectively. 

There were several possible confounding factors in this study, including (1) the exclusion of men who had 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 79 

3. HEALTH EFFECTS 

fathered equal numbers of boys and girls, (2) the average number of children/subject was 

<2 (approximately 1.3), and (3) a high rate of elective abortions across groups (49.2, 28.2, and 50.0% for 

borate workers, community group, and controls, respectively), in which some men may have favored 

raising male offspring while complying with China’s one-child-only policy. Thus, it cannot be 

determined from these data if a boron-associated shift in the Y:X sperm ratio resulted in a change in sex 

of offspring. 

While the human survey database is extensive in that large populations with chronic exposure durations 

were sampled from multiple locations (Chang et al. 2006; Liu et al. 2006a, 2006b; Robbins et al. 2008; 

Sayli 1998a, 1998b, 2003; Sayli et al. 1998; Whorton et al. 1994), they are limited for informing dose 

response relationships for reproductive effects. Specifically, the reliance on questionnaires and lack of 

clinical observations, absence of an appropriate comparison population (Robbins et al. 2008; Whorton et 

al. 1994), or low confidence in estimates of personal or group boron exposure (Liu et al. 2006a, 2006b) 

preclude these data from providing a basis for deriving an oral MRL. 

Animal studies of acute-, intermediate-, and chronic- oral exposure to boric acid or borax consistently 

identified testicular atrophy and histological lesions and the associated impacts on spermatogenesis as the 

most sensitive reproductive effect. The majority of studies were performed in rats; however, the effects 

observed in rats were also observed in mice and dogs. The effects of boron on animal testes appear to be 

dose- and duration-related. 

Acute-duration (2-week) oral gavage or dietary exposures of Wistar rats to 88 mg boron/kg/day as boric 

acid produced significant damage to male reproductive tissues, but doses of 53 or 44 mg boron/kg/day 

were without effect (Fukuda et al. 2000; Ku et al. 1993a; Kudo et al. 2000). Exposure to 88 mg 

boron/kg/day resulted in 12 and 13% reduction in absolute and relative testes weights, respectively, 

multinucleated giant cell formation, increased residual body-like structures in the testes, 

degeneration/necrosis of germ cells, increased cellular debris in the epididymal ducts, exfoliation of round 

spermatids, and mild inhibition of spermiation (retention of step 19 spermatids at stages IX–XI) (Fukuda 

et al. 2000; Kudo et al. 2000). 

Intermediate-duration gavage studies in rats resulted in similar effects as observed in the acute studies, but 

at lower exposure levels. Wistar rats given gavage doses of 26 mg boron/kg/day as boric acid for 3 weeks 

exhibited decreased sperm motility, morphologically-abnormal sperm heads and tails, and increased 

preimplantation fetal loss when treated males were mated with untreated females; no reproductive effects 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 80 

3. HEALTH EFFECTS 

occurred in this study with exposure to 9 mg boron/kg/day (Yoshizaki et al. 1999). Four-week daily 

gavage doses of 44 mg boron/kg/day as boric acid resulted in exfoliation of testicular and epididymal 

germ cells in Wistar rats (Kudo et al. 2000). Fukuda et al. (2000) gave gavage doses of 53 mg 

boron/kg/day to Wistar rats for 4 weeks and observed 13 and 15% reductions in absolute and relative 

testes weights, respectively, cellular debris in the testes, caudal and caput epididymis, focal atrophy of the 

seminiferous tubules, and decreased number of sperm in the ducta lumina. Rats given 4-week daily 

gavage doses of 88 mg boron/kg/day group exhibited reduced sperm motility, reduced total sperm in 

caudal epididymis, atrophy of seminiferous tubules, atypical residual bodies, multinucleated giant cell 

formation, and the inability to impregnate females (Yoshizaki et al. 1999). 

Intermediate-duration feeding studies in rats reported effects similar to those of the gavage studies. Rats 

fed 100 mg boron/kg/day as borax in the diet, but not 50 mg boron/kg/day, for 30 and 60 days showed 

testicular atrophy (Lee et al. 1978). Sprague-Dawley rats fed 86 mg boron/kg/day as borax in the diet for 

30 or 60 days were infertile for 3 or 5 weeks after exposure, respectively (Dixon et al. 1979). Exposure to 

43 mg boron/kg/day as borax for 60 days produced reduced testicular and epididymal weights and 

diameter of seminiferous tubules occurred, and reduced testicular levels of hyaluronidase, sorbitol 

dehydrogenase, and lactic acid dehydrogenase (isoenzyme-X) at 30 days (Dixon et al. 1979). Mildly 

inhibited spermiation was observed in Fischer 344 rats exposed to 26 mg boron/kg/day in the diet for 5– 

9 weeks (Ku et al. 1993a). Fischer 344 rats fed 61 mg boron/kg/day as boric acid for 4 weeks showed 

inhibited spermiation, appearance of peripheral spermatid nuclei, and spermatocyte sloughing/epithelial 

disorganization (Treinen and Chapin 1991), while severe inhibition of spermiation and testicular atrophy 

were observed in Fischer 344 rats exposed to 68 or 52 mg boron/kg/day as boric acid in the diet for 6 or 

9 weeks (Ku et al. 1993a). Full recovery from inhibition of spermiation was observed in a 38 mg 

boron/kg/day group by 16 weeks after cessation of exposure for 9 weeks, but no recovery from testicular 

atrophy was observed in the 52 and 68 mg boron/kg/day groups up to 32 weeks after exposure ended (Ku 

et al. 1993a). Dose-related elevations of FSH and LH suggested that boron exposure did not affect the 

compensatory response to atrophy (Ku et al. 1993a). In a recent study, Sprague-Dawley rats fed 136 mg 

boron/kg/day as boric acid for 60 days exhibited decreased weights of testes, epididymes, seminal 

vesicles, prostate, and vas deferens; decreased sperm motility, spermatocyte, spermatid, and Leydig cell 

numbers; decreased testosterone levels, sexually aggressive behavior, sexual mounts, number of females 

impregnated, and viable pups/impregnated female; and increased cellular degeneration, ejaculation time, 

postejaculatory interval, and fetal resorptions in impregnated females (Nusier and Bataineh 2005). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 81 

3. HEALTH EFFECTS 

In intermediate-duration drinking water studies in rats, no reproductive effects (reproductive organ weight 

or histolopathology) were evident in Sprague-Dawley rats following exposure to 0.6 mg boron/kg/day as 

borax for 90 days (Dixon et al. 1976). In another study, impaired spermatogenesis was observed in LongEvans rats given 44.7 mg boron/kg/day as borax in drinking water for 70 days (Seal and Weeth 1980). 

Complete sterility was observed in Sprague-Dawley rats fed 1,170 ppm boron equivalents in the diet as 

boric acid or borax (at an estimated dose level of 101 and 116 mg boron /kg/day for males and females); 

sterility was associated with a lack of viable sperm in atrophied testes in males and decreased ovulation in 

females (Weir and Fisher 1972). Rats were exposed for 14 weeks before mating in this study. No 

pregnancies occurred when female rats exposed to this dose level were mated with non-exposed male rats. 

At lower exposure levels (10 or 30 mg boron/kg/day for males and 12 or 35 mg boron/kg/day for 

females), no exposure-related adverse effects were found on overall fertility indices in three successive 

generations (Weir and Fisher 1972). 

Studies in mice and dogs support the observations of reproductive effects seen in rats. In a study in which 

male CD-1 mice were exposed to gavage doses of boric acid of 0, 21, 70, or 210 mg boron/kg/day for 

21 days (5 days before mating, during 5 days of mating, and extending to 21 total days of exposure), 

average testes weights were decreased at doses ≥70mg boron/kg/day, and exfoliation/disruption of 

seminiferous tubules and inhibited spermiation were observed at 210 mg boron/kg/day (Harris et al. 

1992). Exposed male mice were mated to similarly exposed female mice (except that females were 

exposed for 8 days before mating), but no exposure-related effects were found on the percentage of 

females who became pregnant, the number of live pups per litter, or the weight of pups at birth (Harris et 

al. 1992). Degeneration of the seminiferous tubules was seen in mice exposed to 288 mg boron/kg/day as 

boric acid in the diet for 13 weeks, while 103-week dietary exposure to 201 mg boron/kg/day as boric 

acid resulted in testicular atrophy, degeneration of the seminiferous tubules, and interstitial hyperplasia 

(Dieter 1994; NTP 1987). 

In a 2-generation (27-week) feeding study in CD-1 mice using a continuous breeding protocol, 

seminiferous tubule degeneration, impaired spermatogenesis, and reduced sperm motility resulted from 

≥111 mg boron/kg/day as boric acid (Fail et al. 1991). These doses were also associated with reduced 

litter size and fetal body weight. No effects were observed in a 27 mg boron/kg/day dose group. 

In mongrel dogs fed boric acid or borax for 90 days, severe testicular atrophy was seen at 60.5, but not at 

6 mg boron/kg/day (Weir and Fisher 1972). With 2 years of exposure, testicular atrophy and 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 82 

3. HEALTH EFFECTS 

spermatogenic arrest were observed in dogs exposed to 22.8, but not in dogs exposed to 6.8 mg 

boron/kg/day (Weir and Fisher 1972). 

Effects of boric acid or borates on female reproductive organs and their functions are less clearly 

identified and studied in animals than effects on male reproductive organs. When pregnant CD-1 mice 

were exposed to gavage doses of 210 mg boron/kg/day on gestation days 8–14, all dams failed to deliver 

litters (Harris et al. 1992). Exposure to 21 or 70 mg boron/kg/day during the same period did not affect 

littering ability, average litter weight, or the number of live neonates at postnatal days 0, 1, and 4 (Harris 

et al. 1992). Mechanistic aspects of this effect of gestational exposure on littering capability of pregnant 

rats are unstudied. As discussed earlier, female Sprague Dawley rats exposed for 14 weeks to 1,170 ppm 

boron equivalents in the diet as boric acid or borax (estimated dose level of 116 mg boron/kg/day) did not 

become pregnant when mated with non-exposed males (Weir and Fisher 1972). The female sterility 

response at this dose level was associated with decreased ovulation. 

The highest NOAEL values and all reliable LOAEL values for reproductive effects in animals and 

duration category are recorded in Table 3-2 and plotted in Figure 3-2. 

3.2.2.6 Developmental Effects 

No studies were available identifying developmental toxicity in humans from exposure to boron. 

However, several types of developmental effects (e.g., decreased fetal body weight, increased incidence 

of skeletal abnormalities) in animals were observed in standard developmental toxicity studies involving 

oral exposure of pregnant mice, rats, and rabbits to boric acid of borate salts. In addition, reduced pup 

weight at birth has been observed in animals receiving intermediate-duration exposures. 

In mice, reduced fetal body weight and skeletal malformations were seen following acute- and 

intermediate-duration maternal oral exposures to boric acid. 

Pregnant CD-1 mice fed 79 mg boron/kg/day as boric acid on gestation days 0–17 had fetuses with 33% 

lower body weight compared with controls, while fetal skeletal effects (e.g., short rib XIII, agenesis of 

lumbar vertabra, fused ribs) were reported at 175.3 mg boron/kg/day on gestation days 0–17 (Heindel et 

al. 1992, 1994). No effects on fetal development were observed in the 43.4 mg boron/kg/day dose group 

(Heindel et al. 1992, 1994). 
 

 

 

 

 

 

 

 

 

 

BORON 83 

3. HEALTH EFFECTS 

No effects on implantation sites, littering, number of live pups per litter, or postnatal pup weight were 

observed following gavage exposure of pregnant CD-1 mice to 70 mg boron/kg/day as boric acid on 

gestation days 8–14 (Harris et al. 1992). 

In an acute-duration study, pregnant CD-1 mice were given gavage doses of boric acid on various 

gestation days to examine the influence of stage of fetal development on skeletal malformations caused 

by boric acid (Cherrington and Chernoff 2002). When two gavage doses of 70 mg boron/kg as boric acid 

were given on gestation day 6, 7, 8, 9, or 10, increased incidence of fetuses with cervical rib and rib 

agenesis were observed in the groups treated on gestation day 8, but not with exposure on gestation days 

6, 7, 9, or 10 (Cherrington and Chernoff 2002). Similarly, increased incidences of fetuses with cervical 

rib, rib agenesis, reduced rib length, and fused ribs were seen after twice daily doses of 70 mg boron/kg 

on gestation days 6–8. Reduction in length of fetal rib XIII was seen in groups dosed once daily with 

88 mg boron/kg/day on gestation days 6–10. A single dose of 131 mg boron/kg on gestation day 

8 resulted in increased incidence of fetuses with cervical ossification, while two doses of 131 mg 

boron/kg on gestation day 8 caused multiple thoracic skeletal malformations. Reduced fetal weight was 

observed in all treated groups (Cherrington and Chernoff 2002). This study did not identify acute 

NOAELs for fetal skeletal effects in mice. The study authors suggested that boric acid may alter 

gastrulation and presomitic mesoderm formation in CD-1 mice, which are key gestational milestones for 

axial skeletal development. 

In rats, acute-duration developmental toxicity data were not available. However, intermediate-duration 

oral exposure of pregnant rats exhibited effects on fetal skeletal development and fetal weight, similar to 

those observed in mice. Pregnant Sprague-Dawley rats fed 13.6 boron/kg/day as boric acid in the diet on 

gestation days 0–20 had reduced fetal body weight, and increased incidence of fetuses with skeletal 

abnormalities at gestation day 20 occurred in groups of dams fed 28.4 mg boron/kg/day (Heindel et al. 

1992). Skeletal abnormalities observed in groups fed 28.4 mg boron/kg/day included agenesis or 

shortening of rib XIII, increased incidence of fetuses with enlargement of the lateral ventricles of the fetal 

brain, and increased resorptions (Heindel et al. 1992). Pregnant Sprague-Dawley rats fed 10 mg 

boron/kg/day as boric acid on gestation days 0–20 exhibited no developmental effects, but exposures of 

13 mg boron/kg/day as boric acid resulted in decreased fetal body weight and skeletal abnormalities seen 

on gestation day 0. However, in a second phase of this study, identically treated dams were allowed to 

litter and pups were observed through postnatal day 21. Upon necropsy, these pups did not exhibit 

significantly different body weights or incidences of skeletal abnormalities seen and fetuses examined on 

gestation day 0 (Price et al. 1996a, 1998). 
 

 

 

 

 

 

 

 

 

BORON 84 

3. HEALTH EFFECTS 

Developmental toxicity data in rabbits are available only for acute-duration oral exposures (Price et al. 

1996b). Pregnant New Zealand white rabbits given gavage doses of 44 mg boron/kg/day as boric acid on 

gestation days 6–19 exhibited increased maternal body weight (corrected for gestation) and reduced 

maternal kidney weight, gravid uterine weight, fetal body weight, number of ovarian corpora lutea, 

number of implantation sites, and live fetuses, compared with controls. Resorptions and fetal external 

(cleft palate), visceral (enlarged lateral ventricle of the brain), skeletal (cleft sternum, fused sternebrae), 

and cardiovascular (enlarged aorta, interventricular septal defect) malformations were increased, 

compared with controls. No significant maternal or fetal effects were observed following gavage doses of 

22 mg boron/kg/day as boric acid. The observed effects are consistent with those seen in acute-, 

intermediate-, and chronic-duration oral exposures in other animals. These data represent the most 

sensitive adverse effects observed in any species following acute-duration oral exposures. Thus, an acuteduration MRL of 0.2 mg boron/kg/day was derived based on a NOAEL of 22 mg boron/kg/day and a 

LOAEL of 44 mg boron/kg/day for developmental effects in New Zealand white rabbits (Price et al. 

1996b). 

With intermediate-duration oral exposure to boric acid, reduced fetal body weight and skeletal 

abnormalities were consistently observed in developmental toxicity assays of mice, rats, and rabbits. 

Skeletal malformations increased in variety and severity with dose. However, reductions in fetal body 

weight appear to occur at lower exposure levels than those associated with skeletal abnormalities. With 

intermediate-duration exposure during gestation, the most sensitive developmental effect identified across 

all three species was reduced fetal weight in pregnant Sprague-Dawley rats fed 13.6 mg boron/kg/day in 

the diet on gestation days 0–20. This effect was seen at lower intermediate-duration exposure levels than 

the lowest intermediate-duration oral dose associated with reproductive effects in rats (i.e., a LOAEL of 

26 mg boron/kg/day was identified for inhibition of spermiation in rats) (Ku et al. 1993a). An 

intermediate oral MRL of 0.2 mg boron/kg/day was calculated as described in the footnote on Table 3-2, 

based on a benchmark dose analysis (Allen et al. 1996) of combined data sets (Heindel et al. 1992; Price 

et al. 1996a) for reduced fetal body weight in rats. 

The highest NOAEL values and all reliable LOAEL values for developmental effects in animals and 

duration category are recorded in Table 3-2 and plotted in Figure 3-2. 
 

 

 

 

 

 

 

 

 

 

BORON 85 

3. HEALTH EFFECTS 

3.2.2.7 Cancer 

Three epidemiological studies have associated increased boron intake in drinking water with decreased 

incidences of prostate and vaginal cancer. Cui et al. (2004) used the cross-sectional data from the 

NHANES III study, conducted from 1988 to 1994, which contained health and diet information for the 

non-institutionalized U.S. population. These investigators reported that men with mean intakes of 

≥1.54 mg boron/day had significantly less risk of developing prostate cancer than men ingesting 

≤0.52 mg/day. This study was limited by its cross-sectional design and reliance on 1-day recall of diet 

information to estimate boron exposure. A second study (Barranco et al. 2007) on a Texas population 

correlated increased boron in groundwater with reduced prostate cancer incidence rates. However, the 

observed correlation appeared to be driven primarily by 2–3 specific cases. Korkmaz et al. (2007) studied 

1,059 rural Turkish women and associated higher boron intake (as evidenced by approximately 8-fold 

higher urinary boron concentration) with lower incidences of cervical cytopathology (0 findings in the 

high-boron group, 15 cases in the low-boron group). While this study did attempt to correct for lifestyle 

factors and other genotoxic confounders, it was cross-sectional in design. The hypotheses drawn from 

these studies are interesting; however, no clinical studies in humans or animals are available to 

substantiate effects of anti-tumor protection offered by boron. 

No evidence of exposure-related cancer was observed in rats exposed to 81 mg boron/kg/day as boric acid 

or borax for 2 years (Weir and Fisher 1972), dogs exposed to 6.8 mg boron/kg/day as boric acid or borax 

for 2 years (Weir and Fisher 1972), or mice exposed to 201 mg boron/kg/day as boric acid for 2 years 

(Dieter 1994; NTP 1987). In nude mice subcutaneously injected with human LNCaP cells (prostate 

tumor clones), oral gavage doses of boric acid were given for 8 weeks (Gallardo-Williams et al. 2004) to 

determine if boron offered protection against prostate tumor growth. Although there was no significant 

difference between control and boron-treated mice in tumor incidences, the tumor sizes in mice given 

1.7 mg boron/kg/day were significantly smaller and the serum level of tumor specific antigen (PSA) was 

significantly less than controls. 

3.2.3 Dermal Exposure 

Information on dermal toxicity in humans involves exposure to the borates (as boric acid or borax), while 

the animal data involves exposure to boron oxide, which easily converts to boric acid in humid air or 

upon entering the mucosal layer of tissues. 
 

 

 

 

 

 

 

 

 

 

 

BORON 86 

3. HEALTH EFFECTS 

3.2.3.1 Death 

No studies were located regarding death in humans or animals after dermal exposure to boron. 

3.2.3.2 Systemic Effects 

No studies were located regarding hematological and dermal/ocular effects in humans or regarding 

respiratory, cardiovascular, gastrointestinal, musculoskeletal, hepatic, or renal effects in humans or 

animals after dermal exposure to boron. 

Hematological Effects. Draize and Kelley (1959) reported the application of 25–200 mg/kg/day 

boric acid in aqueous solution did not produce hematological changes when rubbed onto intact skin 

during a 90-day rabbit study. No quantitative data were provided; therefore, these results could not be 

evaluated. 

Dermal Effects. Human data are limited to case reports of accidental exposure of the head. Three 

male workers (59-year-old waste handler and 34- and 36-year-old automotive mechanics) presented with 

general or focal alopecia of the scalp, presumably from spillage or wiping of boric acid or borax, 

respectively, onto the head (Beckett et al. 2001). In the case of the waste handler, the concentration of 

boric acid in the milieu of other known solvents in the waste tank was unknown. In the cases of the 

automotive workers, exposure was determined to arise from under-the-chassis flushing of automobile 

radiators which contained coolant solutions of ethylene glycol and 1–5% borax. Actual exposures could 

not be determined. Blood sample analysis revealed no elevated blood boron levels in any of the subjects. 

Gradual and full hair re-growth occurred. 

In animals, application of 1 g boron oxide dust to a 25 cm2 area of the skin of four rabbits produced 

erythema that lasted for 2–3 days (Wilding et al. 1959). 

Ocular Effects. Instillation of boron oxide dust (50 mg) into the eyes of four rabbits produced 

conjunctivitis (Wilding et al. 1959). 
 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 87 

3. HEALTH EFFECTS 

No studies were located regarding the following effects in humans or animals after dermal exposure to 

boron: 

3.2.3.3 Immunological and Lymphoreticular Effects 

3.2.3.4 Neurological Effects 

3.2.3.5 Reproductive Effects 

3.2.3.6 Developmental Effects 

3.2.3.7 Cancer 

3.2.4 Other Routes of Exposure 

Direct application of a solution containing 6.3 mg boron (as sodium perborate monohydrate) onto the 

cornea of rabbits resulted in mild irritancy of the epithelium and superficial stroma (Maurer et al. 2001). 

3.3 GENOTOXICITY 

No studies were located regarding genotoxic effects of boron by inhalation, oral, or dermal exposure in 

humans. 

Results were predominantly negative in bacterial assays and in in vitro (Table 3-3) mammalian assays, 

including tests for chromosomal aberrations, gene mutation (Benson et al. 1984; Demerec et al. 1951; 

Haworth et al. 1983; Landolph 1985; NTP 1987), and cell transformation (Landolph 1985). Induction of 

β-galactosidase as part of the SOS response was observed in Escherichia coli PQ37, both with and 

without S-9 metabolic activation (Odunola 1997). Structural chromosomal aberrations, but not sister 

chromatid exchanges, were observed in cultured human lymphocytes exposed to boric acid (Arslan et al. 

2008). 
 

 

BORON 88 

3. HEALTH EFFECTS 

Table 3-3. Genotoxicity of Boron In Vitro 

Results 

With Without 

Species (test system) End point activation activation Reference 

Prokaryotic organisms: 

Salmonella typhimurium Gene mutation – – Haworth et al. 1983 

Gene mutation – – Benson et al. 1984 

Gene mutation – – NTP 1987 

Escherichia coli Gene mutation – – Demerec et al. 1951 

Mammalian cells: 

Mouse lymphoma Gene mutation – – NTP 1987 

Mouse embryo fibroblast Gene mutation NA – Landolph 1985 

Human foreskin fibroblast Gene mutation NA – Landolph 1985 

Chinese hamster ovary Gene mutation NA – Landolph 1985 

Chinese hamster ovary Chromosomal – – NTP 1987 

aberration 

Human lymphocytes Sister chromatid NA – Arslan et al. 2008 

exchange 

Human lymphocytes Chromosomal NA + Arslan et al. 2008 

aberrations 

– = negative result; NA = not applicable 
 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 89 

3. HEALTH EFFECTS 

3.4 TOXICOKINETICS 

3.4.1 Absorption 

3.4.1.1 Inhalation Exposure 

Reports of upper respiratory tract symptoms of irritation following exposure to boron oxide and boric acid 

dusts suggest that boron can deposit in the upper airway (Garabrant et al. 1984, 1985). Borax production 

workers were found to have approximately an order of magnitude higher blood and urine concentrations 

of boron at the end of a work shift compared to the beginning, suggesting that inhaled boron is absorbed 

and systemically distributed (Culver et al. 1994a). 

3.4.1.2 Oral Exposure 

Near-complete gastrointestinal absorption was indicated in humans as evidenced by the urinary recovery 

of 93.9% of the ingested dose of boric acid over a 96-hour collection period (Jansen et al. 1984a). 

Dourson et al. (1998) reviewed data from the literature to estimate oral absorption fractions of 81–92% 

for humans and 95% for animals (rats). 

3.4.1.3 Dermal Exposure 

Volunteers exhibited 0.23 and 0.21% percutaneous absorption of 1.8 mL of 5% solutions of boric acid 

and borax (Wester et al. 1998). Urinary excretion studies in humans (Section 3.4.4.3) suggest there is 

very little absorption of boron through intact skin. Excretion studies (Section 3.4.4.3) in rabbits suggest 

that boron is readily absorbed following contact with damaged skin (Draize and Kelley 1959). 

3.4.2 Distribution 

No quantitative studies were located regarding distribution in humans. 

3.4.2.1 Inhalation Exposure 

No studies were located regarding distribution of boron in animals after inhalation exposure. 
 

 

 

 

 

 

 

 

 

 

 

 

BORON 90 

3. HEALTH EFFECTS 

3.4.2.2 Oral Exposure 

Boron evenly distributed to liver, kidney, brain, muscle, adrenals, epididymis, testes, seminal vesicles, 

and blood, but not fat, of male rats fed 61 mg boron/kg/day as boric acid (9,000 ppm) for 1–28 days (Ku 

et al. 1991; Moseman 1994; Treinen and Chapin 1991), reaching steady-state by 4 days. Blood and testes 

boron levels were similar in rats fed 26–68 mg boron/kg/day as boric acid (3,000–9,000) for 9 weeks (Ku 

et al. 1991). However, boron accumulated in bone in male rats fed 61 mg boron/kg/day (as boric acid) for 

9 weeks, with achievement of steady-state at 4 weeks. Bone levels were approximately 3-fold higher than 

soft tissue levels (Moseman 1994). 

3.4.2.3 Dermal Exposure 

No studies were located regarding distribution of boron in animals after dermal exposure. 

3.4.3 Metabolism 

As an inorganic chemical, boron is not expected to be metabolized by humans or animals. Studies of 

inhalation and oral exposure of animals and humans to borates have consistently reported recovery of the 

parent borate only in the blood, tissues, and urine (Culver et al. 1994a; Draize and Kelley 1959; Jansen et 

al. 1984a; Ku et al. 1991; Moseman 1994; Treinen and Chapin 1991). 

3.4.4 Elimination and Excretion 

3.4.4.1 Inhalation Exposure 

Over 94% of estimated total boric acid (mean 11.84 mg boron/day) inhaled and ingested by Chinese 

borate workers was eliminated 24 hours later in the urine (Xing et al. 2005) as determined by the percent 

estimated daily dose recovered in the urine. In rats that inhaled average concentrations of 

77 mg/m3 boron oxide aerosols over a 22-week period, an average of 11.90 mg boron/kg/day was 

detected in the urine compared to 0.24 mg/kg/day in untreated control groups (Wilding et al. 1959). 

3.4.4.2 Oral Exposure 

Over 93% of the administered dose was excreted in the urine of six male volunteers 96 hours after 

administration of a single oral dose of 1.9 mg boron/kg (as boric acid) (Jansen et al. 1984a). An analysis 

of nine cases involving boric acid poisoning revealed a mean half-life of 13.4 hours (range 4–27.8 hours). 
 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 91 

3. HEALTH EFFECTS 

There was no correlation between half-life and calculated serum boric acid level at to (r=0.08, p=0.84) 

(Litovitz et al. 1988). Boric acid was detected in urine of patients 23 days after a single ingestion (Wong 

et al. 1964). Renal clearance of dietary boron from fifteen pregnant women was calculated to be 

1.02 mL/minute/kg, or 66.1 mL/minute (Pahl et al. 2001). 

In rabbits, 50–66% of the administered dose was recovered in urine after ingestion of 17.1–119.9 mg 

boron/kg/day as boric acid (Draize and Kelley 1959). In rats fed 26–68 mg boron/kg/day as boric acid 

(3,000–6,000 ppm) for 9 weeks, boron concentrations in bone began decreasing after cessation of 

exposure; however, bone levels remained approximately 3-fold higher than controls for up to 32 weeks 

(Chapin et al. 1997; Moseman 1994). Blood levels in these same animals returned to control levels 

within 7 days of exposure cessation (Ku et al. 1991). Using literature data, Dourson et al. (1998) 

estimated the fraction eliminated of absorbed boron to be 67–98% in humans and 99% in rats. These 

investigators also calculated clearance values of 40 mg/kg/hour in humans, 163 mg/kg/hour in rats, and 

397 mg/kg/hour in pregnant rats. Pregnancy did not affect renal clearance (0.2 L/hour/kg or 

1.0 mL/minute) or elimination half-life (3.2 hours) in rats given gavage doses of 0.05–5 mg boron/kg/day 

(as boric acid) on gestation day 16 (Vaziri et al. 2001). 

3.4.4.3 Dermal Exposure 

Limited data in humans suggest that very little absorption of boron occurs through intact skin. There was 

no increase in the urinary excretion of boron in one human subject following the application of 15 g boric 

acid (37.5 mg boron/kg body weight) on the forearm for 4 hours (Draize and Kelley 1959). In volunteers 

having 1.8 mL of 5% boric acid or borax solutions applied to the back and left for 24 hours, urinary boron 

levels increased to peak values of <0.1% above background levels at 14 days following exposure (Wester 

et al. 1998). 

Animal studies support human findings. Draize and Kelley (1959) applied 200 mg/kg as boric acid to 

intact, abraded or burnt, and partially denuded skin of rabbits. Net urinary excretion of boric acid per 

24 hours during 4 consecutive days of compound treatment was 1.4, 7.6, and 21.4 mg/kg, respectively 

(0.25, 1.3, and 3.7 mg boron/kg, respectively). 

3.4.4.4 Other Routes of Exposure 

In eight adult volunteers administered a single dose of boric acid (562–611 mg) by intravenous infusion, 

98.7% of the administered dose was recovered in urine 120 hours after injection (Jansen et al. 1984b). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 92 

3. HEALTH EFFECTS 

Renal blood clearance averaged 39.1 mL/minute per 1.73 m2 surface area in eight adult human subjects 

administered intravenous injections of 35 mg boron/kg (as sodium pentaborate). Urine boron 

concentrations on the day of administration averaged 1.19 mg/mL (Farr and Konikowski 1963). In rats 

administered an intravenous infusion of 86 mg boron/kg (as borax) (Tagawa et al. 2000), boron 

distributed rapidly to the extravascular tissues, giving a steady state volume of distribution of 1.19 L/kg. 

Excretion of boron was rapid, with 87.6% eliminated in the urine by 2 hours after infusion. 

Pharmacokinetic analysis of the blood time course data resulted in an estimated elimination rate constant 

(Kel) of 0.15 hour-1 and a clearance rate of 0.11 L/hour/kg. The elimination half-life was 8.43 hours. 

Guinea pigs given intra-tympanic doses of 0.2 mL/day of 4% boric acid in saline did not exhibit changes 

in hearing level (Oztukcan et al. 2008). 

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

Physiologically based pharmacokinetic (PBPK) models use mathematical descriptions of the uptake and 

disposition of chemical substances to quantitatively describe the relationships among critical biological 

processes (Krishnan et al. 1994). PBPK models are also called biologically based tissue dosimetry 

models. PBPK models are increasingly used in risk assessments, primarily to predict the concentration of 

potentially toxic moieties of a chemical that will be delivered to any given target tissue following various 

combinations of route, dose level, and test species (Clewell and Andersen 1985). Physiologically based 

pharmacodynamic (PBPD) models use mathematical descriptions of the dose-response function to 

quantitatively describe the relationship between target tissue dose and toxic end points. 

PBPK/PD models refine our understanding of complex quantitative dose behaviors by helping to 

delineate and characterize the relationships between: (1) the external/exposure concentration and target 

tissue dose of the toxic moiety, and (2) the target tissue dose and observed responses (Andersen and 

Krishnan 1994; Andersen et al. 1987). These models are biologically and mechanistically based and can 

be used to extrapolate the pharmacokinetic behavior of chemical substances from high to low dose, from 

route to route, between species, and between subpopulations within a species. The biological basis of 

PBPK models results in more meaningful extrapolations than those generated with the more conventional 

use of uncertainty factors. 

The PBPK model for a chemical substance is developed in four interconnected steps: (1) model 

representation, (2) model parameterization, (3) model simulation, and (4) model validation (Krishnan and 

Andersen 1994). In the early 1990s, validated PBPK models were developed for a number of 
 

 

 

 

 

 

 

 

 

BORON 93 

3. HEALTH EFFECTS 

toxicologically important chemical substances, both volatile and nonvolatile (Krishnan and Andersen 

1994; Leung 1993). PBPK models for a particular substance require estimates of the chemical substancespecific physicochemical parameters, and species-specific physiological and biological parameters. The 

numerical estimates of these model parameters are incorporated within a set of differential and algebraic 

equations that describe the pharmacokinetic processes. Solving these differential and algebraic equations 

provides the predictions of tissue dose. Computers then provide process simulations based on these 

solutions. 

The structure and mathematical expressions used in PBPK models significantly simplify the true 

complexities of biological systems. If the uptake and disposition of the chemical substance(s) are 

adequately described, however, this simplification is desirable because data are often unavailable for 

many biological processes. A simplified scheme reduces the magnitude of cumulative uncertainty. The 

adequacy of the model is, therefore, of great importance, and model validation is essential to the use of 

PBPK models in risk assessment. 

PBPK models improve the pharmacokinetic extrapolations used in risk assessments that identify the 

maximal (i.e., the safe) levels for human exposure to chemical substances (Andersen and Krishnan 1994). 

PBPK models provide a scientifically sound means to predict the target tissue dose of chemicals in 

humans who are exposed to environmental levels (for example, levels that might occur at hazardous waste 

sites) based on the results of studies where doses were higher or were administered in different species. 

Figure 3-3 shows a conceptualized representation of a PBPK model. 

If PBPK models for boron exist, the overall results and individual models are discussed in this section in 

terms of their use in risk assessment, tissue dosimetry, and dose, route, and species extrapolations. 

There are no PBPK models available for boron. 
 

 

BORON 94 

3. HEALTH EFFECTS 

Figure 3-3. Conceptual Representation of a Physiologically Based
 

Pharmacokinetic (PBPK) Model for a Hypothetical
 

Chemical Substance
 

Inhaled chem ical Exhaled chem ical 

Ing es tion 

L un gs 

Liv er 

F at 

S lo w ly 

p erfus ed 

tissue s 

R ic h ly 

p erfus ed 

tissue s 

K idn ey 

S k in 

V 

E 

N 

O 

U 

S 

B 

L 

O 

O 

D 

A 

R 

T 

E 

R 

I 

A 

L 

B 

L 

O 

O 

D 

V m a x 

K m G I 

T ra ct 

F ec es 

U rin e

 C he m ic als 

co nta ctin g skin 

Note: This is a conceptual representation of a physiologically based pharmacokinetic (PBPK) model for a 

hypothetical chemical substance. The chemical substance is shown to be absorbed via the skin, by inhalation, or by 

ingestion, metabolized in the liver, and excreted in the urine or by exhalation. 

Source: adapted from Krishnan and Andersen 1994 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 95 

3. HEALTH EFFECTS 

3.5 MECHANISMS OF ACTION 

3.5.1 Pharmacokinetic Mechanisms 

Absorption. Boron is absorbed across pulmonary tissues into the blood, as seen in workers exposed to 

borate dusts, who were found to have higher blood and urine boron concentrations at the end of a work 

shift compared to the beginning of the shift (Culver et al. 1994a). Boron is almost completely absorbed in 

the gastrointestinal tract, with up to 92 and 95% of ingested dose being recovered in the urine (Dourson et 

al. 1998). No data are available to indicate whether boron is actively transported or passively diffused 

across pulmonary or gastrointestinal tissues. Diet may influence the rate of boron absorption in the gut, 

as higher initial boron levels were found in the urine of humans given boron in an ointment vehicle, 

compared to administration via a water vehicle (Schou et al. 1984). Boron was found to be minimally 

absorbed across intact human or animal skin (Draize and Kelley 1959; Wester et al. 1998). 

Distribution. Boron is distributed readily to all body tissues. Tissue levels from daily doses were 

observed to achieve steady-state with plasma in all tissues examined, including neurological and 

reproductive tissues, with the exception of bone and adipose tissues (Ku et al. 1991. Bone serves as a 

storage depot for boron, while adipose tissue has a lower affinity for boron than other soft tissues. The 

mechanism(s) of transport across tissue membranes and into bone are not known. No data were available 

identifying binding of boron to a carrier protein in the blood or plasma membranes. 

Metabolism. Boron is a trace element and is not metabolized in the body. Borates exist in the body as 

boric acid, the only form of boron recovered in the urine. 

Excretion. Excretion of systemically absorbed born is accomplished primarily through renal 

elimination, with minor fractions excreted in the saliva, sweat, and feces (Jansen et al. 1984a). No data are 

available regarding the contribution of tubular absorption of boron in the kidney. Glomerular filtration rate 

is likely the dominant factor in renal elimination of boron. As such, the systemic elimination of boron may 

be compromised in populations with reduced glomerular filtration rates (Dourson et al. 1998), such as 

preeclamptic women. This assumption is used in deriving chemical-specific uncertainty factors, which 

themselves are used for deriving the intermediate-duration oral MRL (Appendix A). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 96 

3. HEALTH EFFECTS 

3.5.2 Mechanisms of Toxicity 

No studies were available in humans describing a mechanism of toxicity for neurological, gastrointestinal, 

hepatic, or renal effects observed in case reports of high-dose poisoning incidents. In animals, 

reproductive and developmental effects have been the most sensitive toxic end points observed. 

Although several studies have examined possible mechanisms for reproductive toxicity, the actual toxic 

mechanism remains unknown. In rats, delayed spermiation (inhibited release of mature sperm) appears to be 

the hallmark event in testicular toxicity, followed by exfoliation of germ epithelium and atrophy at higher 

doses (Treinen and Chapin 1991). Leydig and Sertoli cell cultures exposed to 10 mM boric acid did not 

exhibit reduced responsiveness to induction of testosterone production, but exhibited reduced intracellular 

cAMP levels following FSH stimulation (Ku et al. 1993b). Further, lactate and pyruvate (the primary energy 

sources for Sertoli cells) production (possibly from boronation of NAD cofactors [Ku et al. 1993b]) and 

deoxyribonucleic acid (DNA) synthesis were significantly reduced, suggesting that germ epithelial sloughing 

and testicular atrophy may result from impaired energy production and mitosis/meiosis in the Sertoli cells 

(Fail et al. 1998). However, in vivo delayed spermiation appears to occur at lower Sertoli cell exposure levels 

than disruption of energy production and DNA synthesis, making it difficult to conclude whether reproductive 

effects are hormonally or metabolically-mediated (Fail et al. 1998; Ku et al. 1993a). 

The mechanism of toxicity for developmental effects is also unknown. Fail et al. (1998) suggest that the 

reduction in fetal body weight (the most sensitive end point observed in rats [Heindel et al. 1992]) may be 

due to mitotic inhibition observed in viruses, bacteria, insects, yeasts, and animals. Hyperacetylation of 

embryonic mouse tissues is highly associated with skeletal malformations following exposure to histone 

deacetylase inhibitors such as valproic acid and trichostatin A. Mice given intraperitoneal doses of 

175 mg boron/kg (as boric acid) on gestation day 8 exhibited hyperacetylation of embryonic somites, 

inhibition of histone deacetylase, and increased incidences of skeletal malformations (fused ribs and 

vertebra, changes in the typical number of axial segments in different axial districts). The association of 

these biochemical and morphological effects suggest that boric acid-induced skeletal malformations may 

result from inhibition of histone deacetylase. Wery et al. (2003) reported a cranial shift in the anterior 

limits of the hoxa6 and hoxc6 genes in the fetuses of pregnant rats given two gavage doses of 

88 mg/boron/kg/day (as boric acid) on gestation day 9. The control of position and development of the 

fetal vertebrae have been associated with the activity of these genes (see Section 3.3). It is not known 

whether inhibition of histone deacetylase, as suggested by Fail et al. (1998) is involved with the response 

of the hoxa6 and hoxc6 genes to in utero exposure to high doses of boron. 
 

 

 

 

 

 

 

 

 

 

BORON 97 

3. HEALTH EFFECTS 

3.5.3 Animal-to-Human Extrapolations 

Similarities in rodents and humans for boron toxicokinetics and reproductive physiology suggest that the 

animal toxicity data are relevant for human risk assessment. Animal and rodents studies indicate that 

boron is readily absorbed (particularly via the oral route), not metabolized, and extensively eliminated via 

urinary excretion (Section 3.4). Male humans and rodents share similar physiological structures and 

hormonal control mechanisms of the reproductive system, suggesting a similar target of toxicity for 

reproductive effects. Similarly, the sequence of fetal developmental steps is similar between the species. 

Lack of human data, particularly reproductive and developmental data, for effects observed in animal 

studies introduce uncertainty into the extrapolation of animals data to humans. 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS 

Recently, attention has focused on the potential hazardous effects of certain chemicals on the endocrine 

system because of the ability of these chemicals to mimic or block endogenous hormones. Chemicals 

with this type of activity are most commonly referred to as endocrine disruptors. However, appropriate 

terminology to describe such effects remains controversial. The terminology endocrine disruptors, 

initially used by Thomas and Colborn (1992), was also used in 1996 when Congress mandated the EPA to 

develop a screening program for “...certain substances [which] may have an effect produced by a 

naturally occurring estrogen, or other such endocrine effect[s]...”. To meet this mandate, EPA convened a 

panel called the Endocrine Disruptors Screening and Testing Advisory Committee (EDSTAC), and in 

1998, the EDSTAC completed its deliberations and made recommendations to EPA concerning endocrine 

disruptors. In 1999, the National Academy of Sciences released a report that referred to these same types 

of chemicals as hormonally active agents. The terminology endocrine modulators has also been used to 

convey the fact that effects caused by such chemicals may not necessarily be adverse. Many scientists 

agree that chemicals with the ability to disrupt or modulate the endocrine system are a potential threat to 

the health of humans, aquatic animals, and wildlife. However, others think that endocrine-active 

chemicals do not pose a significant health risk, particularly in view of the fact that hormone mimics exist 

in the natural environment. Examples of natural hormone mimics are the isoflavinoid phytoestrogens 

(Adlercreutz 1995; Livingston 1978; Mayr et al. 1992). These chemicals are derived from plants and are 

similar in structure and action to endogenous estrogen. Although the public health significance and 

descriptive terminology of substances capable of affecting the endocrine system remains controversial, 

scientists agree that these chemicals may affect the synthesis, secretion, transport, binding, action, or 

elimination of natural hormones in the body responsible for maintaining homeostasis, reproduction, 
 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 98 

3. HEALTH EFFECTS 

development, and/or behavior (EPA 1997). Stated differently, such compounds may cause toxicities that 

are mediated through the neuroendocrine axis. As a result, these chemicals may play a role in altering, 

for example, metabolic, sexual, immune, and neurobehavioral function. Such chemicals are also thought 

to be involved in inducing breast, testicular, and prostate cancers, as well as endometriosis (Berger 1994; 

Giwercman et al. 1993; Hoel et al. 1992). 

No studies were located regarding endocrine disruption in humans after exposure to boron. 

While depressed testosterone blood levels was observed in rats fed diets with 61 mg boron/kg/day as 

boric acid (Treinen and Chapin 1991), GnRH challenge in boron-fed rats (Fail et al. 1998) resulted in LH 

responses similar to controls and an exacerbated FSH response relative to controls, suggesting that 

peripheral hormonal changes were not due to neuroendocrine toxicity, but possibly to Leydig and Sertoli 

cell-specific effects (Fail et al. 1998). 

No in vitro studies were located regarding endocrine disruption of boron. 

3.7 CHILDREN’S SUSCEPTIBILITY 

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

maturity at 18 years of age in humans, when all biological systems will have fully developed. Potential 

effects on offspring resulting from exposures of parental germ cells are considered, as well as any indirect 

effects on the fetus and neonate resulting from maternal exposure during gestation and lactation. 

Relevant animal and in vitro models are also discussed. 

Children are not small adults. They differ from adults in their exposures and may differ in their 

susceptibility to hazardous chemicals. Children’s unique physiology and behavior can influence the 

extent of their exposure. Exposures of children are discussed in Section 6.6, Exposures of Children. 

Children sometimes differ from adults in their susceptibility to hazardous chemicals, but whether there is 

a difference depends on the chemical (Guzelian et al. 1992; NRC 1993). Children may be more or less 

susceptible than adults to health effects, and the relationship may change with developmental age 

(Guzelian et al. 1992; NRC 1993). Vulnerability often depends on developmental stage. There are 

critical periods of structural and functional development during both prenatal and postnatal life, and a 

particular structure or function will be most sensitive to disruption during its critical period(s). Damage 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 99 

3. HEALTH EFFECTS 

may not be evident until a later stage of development. There are often differences in pharmacokinetics 

and metabolism between children and adults. For example, absorption may be different in neonates 

because of the immaturity of their gastrointestinal tract and their larger skin surface area in proportion to 

body weight (Morselli et al. 1980; NRC 1993); the gastrointestinal absorption of lead is greatest in infants 

and young children (Ziegler et al. 1978). Distribution of xenobiotics may be different; for example, 

infants have a larger proportion of their bodies as extracellular water, and their brains and livers are 

proportionately larger than adults (Altman and Dittmer 1974; Fomon 1966; Fomon et al. 1982; Owen and 

Brozek 1966; Widdowson and Dickerson 1964). The infant also has an immature blood-brain barrier 

(Adinolfi 1985; Johanson 1980) and probably an immature blood-testis barrier (Setchell and Waites 

1975). Many xenobiotic metabolizing enzymes have distinctive developmental patterns. At various 

stages of growth and development, levels of particular enzymes may be higher or lower than those of 

adults, and sometimes unique enzymes may exist at particular developmental stages (Komori et al. 1990; 

Leeder and Kearns 1997; NRC 1993; Vieira et al. 1996). Whether differences in xenobiotic metabolism 

make the child more or less susceptible also depends on whether the relevant enzymes are involved in 

activation of the parent compound to its toxic form or in detoxification. There may also be differences in 

excretion, particularly in newborns who all have a low glomerular filtration rate and have not developed 

efficient tubular secretion and resorption capacities (Altman and Dittmer 1974; NRC 1993; West et al. 

1948). Children and adults may differ in their capacity to repair damage from chemical insults. Children 

also have a longer remaining lifetime in which to express damage from chemicals; this potential is 

particularly relevant to cancer. 

Certain characteristics of the developing human may increase exposure or susceptibility, whereas others 

may decrease susceptibility to the same chemical. For example, although infants breathe more air per 

kilogram of body weight than adults breathe, this difference might be somewhat counterbalanced by their 

alveoli being less developed, which results in a disproportionately smaller surface area for alveolar 

absorption (NRC 1993). 

Human data of boron toxicity in children and humans due to high-dose exposures are not adequate to 

identify the presence or lack of children’s susceptibility. Normal boron blood levels in children and 

infants range from 0 to 1.25 μg/mL (Fisher and Freimuth 1958; O'Sullivan and Taylor 1983). Infants

exhibiting adverse effects after ingestion of boric acid in infant formula had boron blood levels (reported 

as borate) of 20–150 μg/mL, with fatal cases having blood levels of 200–1,600 μg/mL (Wong et al. 1964).

Comparatively, adult serum boron level (as boric acid) of 2,320 μg/mL was not associated with

significant toxicity (Linden et al. 1986). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 100 

3. HEALTH EFFECTS 

No animal studies were located regarding susceptibility of immature animals to boron toxicity. However, 

oral exposure studies in pregnant animals have identified developmental effects in fetus exposed to boron 

(as borax or boric acid) in utero. No developmental effects were observed in animals following 

inhalation exposures. The observed effects from oral exposure include skeletal malformations and 

cardiovascular abnormalities. The most sensitive effect identified was reduced fetal body weight, which 

consistently occurred in animals at lower doses than required for skeletal malformations or other effects. 

The acute- and intermediate-duration oral MRLs are based on reduced fetal body weight in rats and 

should be protective of children developing in the womb. 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT 

Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility (NAS/NRC 

1989). 

A biomarker of exposure is a xenobiotic substance or its metabolite(s) or the product of an interaction 

between a xenobiotic agent and some target molecule(s) or cell(s) that is measured within a compartment 

of an organism (NAS/NRC 1989). The preferred biomarkers of exposure are generally the substance 

itself, substance-specific metabolites in readily obtainable body fluid(s), or excreta. However, several 

factors can confound the use and interpretation of biomarkers of exposure. The body burden of a 

substance may be the result of exposures from more than one source. The substance being measured may 

be a metabolite of another xenobiotic substance (e.g., high urinary levels of phenol can result from 

exposure to several different aromatic compounds). Depending on the properties of the substance (e.g., 

biologic half-life) and environmental conditions (e.g., duration and route of exposure), the substance and 

all of its metabolites may have left the body by the time samples can be taken. It may be difficult to 

identify individuals exposed to hazardous substances that are commonly found in body tissues and fluids 

(e.g., essential mineral nutrients such as copper, zinc, and selenium). Biomarkers of exposure to boron 

are discussed in Section 3.8.1. 

Biomarkers of effect are defined as any measurable biochemical, physiologic, or other alteration within an 

organism that, depending on magnitude, can be recognized as an established or potential health 

impairment or disease (NAS/NRC 1989). This definition encompasses biochemical or cellular signals of 

tissue dysfunction (e.g., increased liver enzyme activity or pathologic changes in female genital epithelial 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 101 

3. HEALTH EFFECTS 

cells), as well as physiologic signs of dysfunction such as increased blood pressure or decreased lung 

capacity. Note that these markers are not often substance specific. They also may not be directly 

adverse, but can indicate potential health impairment (e.g., DNA adducts). Biomarkers of effects caused 

by boron are discussed in Section 3.8.2. 

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism's ability 

to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic or 

other characteristic or a preexisting disease that results in an increase in absorbed dose, a decrease in the 

biologically effective dose, or a target tissue response. If biomarkers of susceptibility exist, they are 

discussed in Section 3.10, Populations That Are Unusually Susceptible. 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Boron 

Boron in blood and urine can be used as an indicator of exposure to boron. Normal dietary concentrations 

of boron in the blood of humans range from 0 to 1.25 μg/mL in children and infants (Fisher and Freimuth 

1958; O'Sullivan and Taylor 1983). Boron blood levels (reported as borate) of 20–150 μg/mL have been 

associated with adverse systemic effects in infants who ingested boric acid in infant formula (Wong et al. 

1964). Boron concentrations, expressed as borate, reported in fatal cases vary from 200 to 1,600 μg/mL

in infants (Wong et al. 1964). In adults, a serum boron level (as boric acid) of 2,320 μg/mL was not

associated with significant toxicity (Linden et al. 1986). 

Urinary excretion levels can also be useful indicators of elevated total body burden of boron. 

Concentrations of boron in the normal population range from 0.07 to 0.15 mg/100 mL (Vignec and Ellis 

1954) and from 0.004 to 0.66 mg/100 mL (Imbus et al. 1963). In one infant, the urine contained 13.9 mg 

boron/liter as borax or 1.38 mg boron/mL of boric acid following ingestion of a borax and honey mixture 

over a period of 12 weeks (Gordon et al. 1973). Virtually complete urinary excretion was indicated by 

the recovery of 93.9% (over a 96-hour collection period) of a boric acid solution ingested by three 

volunteers (Jansen et al. 1984a). 

Neurological, dermal, gastrointestinal, liver, and kidney effects in humans have been associated with 

exposure to boron. Studies in animals have demonstrated gonadal injury. Various clinical and 

biochemical tests exist that may provide useful information on exposure. However, similar effects are 

caused by a variety of other substances and are, therefore, not specific for boron exposure. 
 

 

 

 

 

 

 

 

 

 

BORON 102 

3. HEALTH EFFECTS 

3.8.2 Biomarkers Used to Characterize Effects Caused by Boron 

Central nervous system injury, gastrointestinal effects, and skin damage are characteristic manifestations 

of boron toxicity in humans. Liver and kidneys in humans and testes in animals can also be affected. 

Various clinical and biochemical changes associated with these effects may be measured to detect the 

extent of exposure to boron. There is no single biological indicator of boron exposure; consequently, 

several parameters must be measured including boron levels in urine and blood and biochemical changes 

for systemic and neurological effects. 

Neurological damage has been reported in humans. Neurological effects reported in humans have 

focused primarily on histopathological alterations. No data were provided on biochemical changes. In 

animals, testicular atrophy and reduced sperm production have been demonstrated following chronic 

boron exposure. There are clinical and biochemical tests to detect neurological and gonadal injury, but 

these are not specific for boron exposure. Sparse data in animals suggest some biochemical changes; for 

instance, cerebral succinate dehydrogenase was increased in rats after boron exposure. Animal data 

further demonstrate biochemical alterations following gonadal injury. Dose-dependent reduction in 

hyaluronidase, sorbitol dehydrogenase, and lactic acid dehydrogenase (isoenzyme-X) were observed in 

rats following boron exposure. 

3.9 INTERACTIONS WITH OTHER CHEMICALS 

No studies were located regarding the influence of other chemicals on the toxicity of boron. 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to boron than will most persons 

exposed to the same level of boron in the environment. Reasons may include genetic makeup, age, health 

and nutritional status, and exposure to other toxic substances (e.g., cigarette smoke). These parameters 

result in reduced detoxification or excretion of boron, or compromised function of organs affected by 

boron. Populations who are at greater risk due to their unusually high exposure to boron are discussed in 

Section 6.7, Populations with Potentially High Exposures. 

No data were located identifying a population that is unusually susceptible to boron toxicity. Case reports 

in humans suggest that large variability exists with the human population to the lethal effect of boron. 

However, there are no data to suggest which segment of the population is more susceptible to boron. 
 

 

 

 

 

 

 

 

 

 

BORON 103 

3. HEALTH EFFECTS 

3.11 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to boron. However, because some of the treatments discussed may be experimental and 

unproven, this section should not be used as a guide for treatment of exposures to boron. When specific 

exposures have occurred, poison control centers and medical toxicologists should be consulted for 

medical advice. The following texts provide specific information about treatment following exposures to 

boron: 

Ellenhorn MJ, Schonwald S, Ordog G, et al., eds. 1997. Ellenhorn's medical toxicology. Diagnosis 

and treatment of human poisoning. 2nd ed. Baltimore, MA: Williams & Wilkins, 1098-1100, 160t, 

162t. 

Goldfrank LR, Flomenbaum NE, Lewin NA, et al., eds. 2002. Goldfrank's toxicologic emergencies. 7th 

ed. New York, NY: McGraw-Hill, 1282, 1289-1290, 1134. 

Viccellio P, Bania T, Brent J, et al., eds. 1998. Emergency toxicology. 2nd ed. Philadelphia, PA: 

Lippincott-Raven, 448-449, 470, 1141. 

Human exposure to boron may occur by inhalation, ingestion, or dermal contact (see Chapter 6). Boron 

in the form of boric acid or borate dust is an upper respiratory tract irritant following inhalation and may 

also irritate the eyes and skin. Ingestion of boron may cause gastrointestinal, neurological, hepatic, renal, 

and dermal effects (see Section 3.2). General recommendations for reducing absorption of boron 

following exposure have included removing the exposed individual from the contaminated area and 

removing the contaminated clothing. If the eyes and skin were exposed, then they should be flushed with 

water. 

3.11.1 Reducing Peak Absorption Following Exposure 

Nausea, vomiting, and diarrhea have been induced by ingestion of boron in humans. Some authors 

recommend reducing absorption of boron from the gastrointestinal tract by administration of emetics 

(e.g., syrup of ipecac) and cathartics (e.g., magnesium sulfate) (Stewart and McHugh 1990). Caution 

should be taken, however, not to induce further damage to the esophageal mucosa or to cause aspiration 

of the vomit into the lungs during emesis. There is disagreement regarding the efficiency of activated 

charcoal in preventing absorption of boron from the gastrointestinal tract following oral exposure 

(Ellenhorn and Barceloux 1988; Stewart and McHugh 1990). It has been suggested that activated 

charcoal be administered following gastric evacuation, but its effectiveness has not been established 
 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 104 

3. HEALTH EFFECTS 

(Ellenhorn and Barceloux 1988). Administration of intravenous fluids may be required if severe 

dehydration or shock develop and local skin care may be necessary if skin desquamation occurs (Stewart 

and McHugh 1990). In addition, the treatment of boron poisoning may require a control for convulsions. 

3.11.2 Reducing Body Burden 

Elemental boron is not metabolized (see Section 3.4). Studies in volunteers indicated that most of the 

administered dose is excreted in the urine within few days (Jansen et al. 1984a). Saline diuresis has been 

suggested to enhance urinary excretion of boron (Goldfrank et al. 1990). Exchange transfusions, 

peritoneal dialysis, or hemodialysis may be employed to lower plasma boron levels following either acute 

or chronic intoxication. There are indications that hemodialysis is the most effective of these procedures 

(Goldfrank et al. 1990; Naderi and Palmer 2006; Stewart and McHugh 1990). 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects 

No studies were available to support measures to interfere with the mechanism of action for boron once it 

has been absorbed. 

3.12 ADEQUACY OF THE DATABASE 

Section 104(I)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of boron is available. Where adequate information is not 

available, ATSDR, in conjunction with the National Toxicology Program (NTP), is required to assure the 

initiation of a program of research designed to determine the health effects (and techniques for developing 

methods to determine such health effects) of boron. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 
 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 105 

3. HEALTH EFFECTS 

3.12.1 Existing Information on Health Effects of Boron 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

boron are summarized in Figure 3-4. The purpose of this figure is to illustrate the existing information 

concerning the health effects of boron. Each dot in the figure indicates that one or more studies provide 

information associated with that particular effect. The dot does not necessarily imply anything about the 

quality of the study or studies, nor should missing information in this figure be interpreted as a “data 

need”. A data need, as defined in ATSDR’s Decision Guide for Identifying Substance-Specific Data 

Needs Related to Toxicological Profiles (Agency for Toxic Substances and Disease Registry 1989), is 

substance-specific information necessary to conduct comprehensive public health assessments. 

Generally, ATSDR defines a data gap more broadly as any substance-specific information missing from 

the scientific literature. 

Most of the information concerning health effects of oral exposure to boron in humans is found in case 

reports of accidental acute and intermediate ingestion of boron. Controlled-exposure studies of volunteers 

and cross-sectional surveys of borate mining and production workers have identified acute upper 

respiratory and ocular irritation as an effect of concern from acute inhalation exposure. Epidemiology 

studies of intermediate- to chronic-duration exposures (involving repeated occupational exposure to dusts 

of borates or repeated exposure to boron in drinking water) have not clearly identified a toxic effect in 

humans, but have found no associations between boron exposure and impaired pulmonary function or 

impaired fertility. Information on acute dermal exposure exists, but none was found on effects after 

intermediate- and chronic-duration exposure. 

In animals, information exists on health effects following acute, intermediate, and chronic oral exposure 

to boric acid or borax. Comprehensive acute toxicity studies involving inhalation exposure to boron 

compounds are not available, with the exception of a study of mice exposed by inhalation to diborane gas 

for 2 or 4 weeks. Diborane gas is expected to have a very short half-life in the environment because of its 

reactivity. Thus, it is not expected to be a significant environmental toxicant, except in workplaces where 

it might be used and accidentally released. Health effects have been examined in rats and dogs exposed 

by inhalation to boric oxide aerosols for intermediate durations. Studies of health effects in animals 

exposed by inhalation to boron compounds for chronic durations are not available. Health effects have 

been observed in animals following acute dermal exposure, but no toxicity studies of animals dermally 

exposed for intermediate and chronic durations are available. 
 

BORON 106 

3. HEALTH EFFECTS 

Figure 3-4. Existing Information on Health Effects of Boron 

Death

Acute 

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

Inhalation 

Oral 

Dermal 

Human 

Death

Acute 

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

Inhalation 

Oral 

Dermal 

Animal 

Existing Studies 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 107 

3. HEALTH EFFECTS 

3.12.2 Identification of Data Needs 

Acute-Duration Exposure. Associations between acute inhalation exposure to borate dusts and 

increased prevalence of self-reported symptoms of irritation of the eyes, nose, and throat of volunteers 

under controlled exposure conditions (Cain et al. 2004, 2008) form the basis of an acute-duration 

inhalation MRL. These data are supported by self-reported data for mild upper respiratory tract irritation 

in workers under workplace conditions (Garabrant et al. 1984, 1985; Hu et al. 1992; Wegman et al. 1991, 

1994). Dose-response relationships for mild respiratory and ocular irritation from studies of animals 

exposed by inhalation for acute durations are not available. 

Case reports of acute oral poisonings with boric acid do not clearly identify toxicity targets and doseresponse relationships in humans, but reported effects in fatal cases include degenerative changes in the 

liver, kidney, and brain (Chao et al. 1991a, 1991b; Wong et al. 1964). In animal studies, acute-duration 

oral exposure to boric acid or borates has been associated with effects on the male reproductive organs 

(e.g., decreased testicular weight and altered sperm morphology) in Wistar rats exposed to gavage boric 

acid doses of 88 mg boron/kg/day for 2 weeks (Fukuda et al. 2000; Kudo et al. 2000) and 

developmentally toxic effects (including reduced fetal weight and increased skeletal variations or 

malformations) in CD-1 mice exposed during gestation to boric acid doses as low as 70 mg boron/kg 

(2 times/day) (Cherrington and Chernoff 2002) and in New Zealand rabbits exposed during gestation 

(days 6–19) to doses of 44 mg boron/kg/day (Price et al. 1996b). A NOAEL of 22 mg boron/kg/day for 

developmental effects in rabbits (Price et al. 1996b) serves as the basis of the acute-duration oral MRL for 

boron. 

Dermal/ocular effects have been associated with dermal exposure in humans (Beckett et al. 2001) and 

animals (Wilding et al. 1959). The irritation effects observed in animals may have been due to the 

exothermic rehydration reaction of the anhydride boron oxide. 

No further acute-duration health effect studies are recommended at this time. 

Intermediate-Duration Exposure. No studies are available that establish associations between 

intermediate-duration oral exposures to boron compounds and health effects in humans. Case reports of 

intermediate-duration exposure to humans are limited to reports on infants exhibiting neurological effects 

after ingestion of high levels of boron as boric acid. Seizure disorders occurred during oral exposures of 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 108 

3. HEALTH EFFECTS 

infants to borax lasting 4–12 weeks, with cumulative approximate doses of 12–120 g (Gordon et al. 1973; 

O'Sullivan and Taylor 1983). No associations were found between elevated levels of borates in drinking 

water and fertility rates in surveys of Turkish subpopulations expected to have intermediate- to chronicduration exposures to boron (Sayli 1998a, 1998b, 2003; Sayli et al. 1998). Likewise, cross-sectional 

surveys of boron mining and processing workers in California (Whorton et al. 1994) and China (Chang et 

al. 2006; Liu et al. 2006a, 2006b) failed to find associations between boron exposure (which may have 

included oral exposure to boron) and adverse effects on indices of fertility. Robbins et al. (2008) 

associated a shift in Y:X sperm and male:female offspring ratios with boron exposure; however, this 

study had multiple confounders limiting the interpretation of reported results. 

Studies in animals indicate that reproductive and developmental effects are the most sensitive effects 

associated with intermediate-duration oral exposures to boric acid or borates. Testicular atrophy and 

histopathology, sperm abnormalities, and reduced sperm production have been observed in mice, rats and 

dogs after intermediate-duration ingestion of doses ≥26 mg boron/kg/day as boric acid (Dieter 1994; 

Dixon et al. 1976, 1979; Fail et al. 1991; Fukuda et al. 2000; Harris et al. 1992; Ku et al. 1993a; Kudo et 

al. 2000; Lee et al. 1978; NTP 1987; Nusier and Bataineh 2005; Seal and Weeth 1980; Weir and Fisher 

1972; Yoshizaki et al. 1999). Complete sterility was observed in Sprague-Dawley rats fed boric acid or 

borax in the diet (101 and 116 mg boron/kg/day for males and females, respectively) for 14 weeks before 

mating; sterility was associated with a lack of viable sperm in atrophied testes in males and decreased 

ovulation in females (Weir and Fisher 1972). No pregnancies occurred, when female rats exposed to this 

dose level were mated with non-exposed male rats. At lower exposure levels (10 or 30 mg boron/kg/day 

for males and 12 or 35 mg boron/kg/day for females), no exposure-related adverse effects were found on 

overall fertility indices in three successive generations (Weir and Fisher 1972). Developmental effects 

(including decreased fetal weight, increased incidence of skeletal variations and malformations, and 

increased resorptions) have been observed in offspring of rat and mouse dams exposed to 13–79 mg 

boron/kg/day as boric acid during gestation (Heindel et al. 1992, 1994; Price et al. 1996a). Multiple 

developmental end point data from the rat studies by Heindel et al. (1992) and Price et al. (1996a) were 

pooled and subjected to benchmark dose analyses (Allen et al. 1996) to derive a benchmark-dose point of 

departure of 10.3 mg boron/kg/day for the intermediate-duration oral MRL for boron. 

Studies of Chinese borate workers have evaluated specific clinical end points of semen quality, but do not 

provide adequate estimation of magnitude or duration of boron exposure. Additional cross-sectional or 

prospective surveys of reproductive health end points in populations exposed to elevated levels of boron 

compounds in drinking water may help to better identify reproductive toxicity and developmental toxicity 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 109 

3. HEALTH EFFECTS 

as potential health effects in humans with elevated oral exposure to boron for intermediate or chronic 

durations. 

Increased frequencies of symptoms of acute upper respiratory and ocular irritation have been reported in 

workers exposed repeatedly by inhalation to boron oxide and borate dusts at average concentrations of 

1.8 and 3.1 mg boron/m3

, and employed in the borax industry for a mean duration of 11.4 years 

(SD 8.1 years), compared with a reference population (Garabrant et al. 1984, 1985); however, it is 

uncertain if these acute symptoms were due to acute or repeated exposure. Later studies of a different 

design indicated that acute irritation symptoms in these workers are due to acute exposures, and that 

pulmonary function variables (e.g., FEV1) were not significantly influenced by exposure over a 7-year 

period of employment (Hu et al. 1992; Wegman et al. 1994). These results are adequate to form the basis 

of an acute inhalation MRL for boron, but do not clearly indicate whether the dose-response relationships 

for acute boron-induced upper respiratory and ocular irritation symptoms are changed with intermediate 

or chronic durations of exposure. Because exposure-related effects on pulmonary function variables were 

not evident during a 7-year period between the studies of Garabrant et al. (1984, 1985) and Wegman et al. 

(1994), the results provide some confidence that the acute-duration inhalation MRL may by protective for 

intermediate- and chronic-duration exposures. 

Intermediate-duration inhalation exposure studies in animals are restricted to a series of studies in which 

albino rats were exposed to boric oxide aerosols for 6 hours/day, 5 days/week for 10 weeks at an average 

concentration of 73 mg boron/m3 (n=20 rats), 12 weeks at 27 mg boron/m3 (n=4), or 24 weeks at 12 mg 

boron/m3 (n=70) (Wilding et al. 1959). Histopathologic examination of a comprehensive set of tissues 

(lung, trachea, pancreas, thyroid, adrenal, eye, femur, rib, bone marrow, liver, heart, spleen, kidney, brain, 

stomach, intestine, ovary, testis, lymph node, and muscle) in exposed and control rats revealed no 

exposure-related lesions, with the exception that some rats exposed to the highest concentration (73 mg 

boron/m3

) showed a reddish nasal exudate. Although dogs were included in this study (three dogs were 

exposed to 9 mg boron/m3 for 23 weeks), end points were restricted to clinical signs of toxicity, body 

weight, hematological end points, and sulfobromophthalein retention, a measure of liver function 

(Wilding et al. 1959). No exposure-related effects on these end points were found in exposed dogs, 

compared with controls. Because the NOAELs identified in the rat and dog studies were higher than 

concentrations associated with acute respiratory and ocular irritation in humans acutely exposed to boron 

(Cain et al. 2004; Wegman et al. 1994), the intermediate-duration inhalation database was considered 

inadequate for derivation of an MRL. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 110 

3. HEALTH EFFECTS 

Additional prospective health evaluations of respiratory function and reproductive and developmental 

variables in borate mining and processing workers with intermediate- and chronic-duration exposures 

may help to better identify impaired respiratory function, impaired reproductive performance, and 

developmental effects as critical effects in humans from intermediate- or chronic duration exposure to 

boron compounds. 

Chronic-Duration Exposure and Cancer. No studies are available that establish associations 

between chronic-duration oral exposures to boron compounds and noncancer or cancer effects in humans. 

As discussed in the previous section, no associations were found between exposure to borates or boric 

oxide and indices of fertility in surveys of Turkish subpopulations expected to have intermediate- to 

chronic-duration oral exposures to boron (Sayli 1998a, 1998b, 2003; Sayli et al. 1998), or in surveys of 

boron mining and processing workers in California (Whorton et al. 1994) and China (Chang et al. 2006; 

Liu et al. 2006a, 2006b). Chronic-duration oral toxicity studies in animals include 2-year toxicity studies 

in Sprague-Dawley rats and beagle dogs exposed to boric acid or borax in the diet (Weir and Fisher 

1972), and a 2-year toxicity and cancer bioassay in B6C3F1 mice (Dieter 1994; NTP 1987). 

Histopathological examination of a comprehensive set of tissues from exposed and control rats and dogs 

(brain, pituitary, thyroids, lung, heart, liver spleen, kidneys, adrenals, pancreas, intestines, urinary bladder 

testes, ovary (rat only), bone, and bone marrow) found no exposure-related non-neoplastic or neoplastic 

lesions at dose levels up to 6.8 mg boron/kg/day in dogs or 81 mg boron/kg/day in rats, with the exception 

that rats exposed to 81 mg boron/kg/day, but not 24 mg boron/kg/day, showed testicular atrophy, 

decreased growth, decreased packed blood cell and hemoglobin levels, and scaly tails and desquamated 

footpad skin (Weir and Fisher 1972). In the mouse bioassay, no cancer responses were observed at dose 

levels up to 201 mg boron/kg/day (Dieter 1994; NTP 1987). Noncancer effects in mice included 

testicular atrophy and interstitial hyperplasia, lung hemorrhage, and 10–17% decreased body weight at 

201 mg boron/kg/day and splenic hematopoiesis and chronic hepatic inflammation and coagulative 

necrosis at 79 and 201 mg boron/kg/day, the only dose levels included in the study. 

Although data are sufficient to develop a chronic oral MRL, a value was not derived. Because 

intermediate-duration LOAELs for developmental toxicity in rats (13.6 and 13 mg boron/kg/day [Heindel 

et al. 1992; Price et al. 1996a, 1998]) were lower than the NOAEL (24 mg boron/kg/day) for testicular 

atrophy and other non-cancer effects in chronically exposed rats (Weir and Fisher 1972), the intermediate 

MRL, which is based on developmental toxicity, should be protective against reproductive toxicity 

following chronic exposure. In mice, the intermediate-duration oral NOAEL (43.4 mg boron/kg/day) and 

LOAEL (79 mg boron/kg/day) for developmental toxicity in CD-1 mice (Heindel et al. 1992) were lower 
 

 

 

 

 

 

 

 

 

 

BORON 111 

3. HEALTH EFFECTS 

than the chronic-duration LOAEL for testicular atrophy and decreased body weight in B6C3F1 mice 

(201 mg boron/kg/day) and overlapped with the LOAEL (79 mg boron/kg/day) for splenic hematopoiesis 

and chronic hepatic inflammation and necrosis (Dieter 1994; NTP 1987). Additional studies may be 

useful in assessing the level of confidence in existing intermediate-duration NOAEL and LOAEL values 

for developmental toxicity in rats and mice. Additional chronic-duration oral exposure studies in animals 

do not seem necessary at this time. 

As discussed in the previous section, symptoms of acute upper respiratory and ocular irritation have been 

reported in workers employed in the borax industry for an average of >10 years, but pulmonary function 

variables were not significantly influenced by exposure over a 7-year period of employment (Garabrant et 

al. 1984, 1985; Hu et al. 1992; Wegman et al. 1994). These results are the basis of an acute inhalation 

MRL for boron, but do not clearly indicate whether the dose-response relationships for acute boroninduced upper respiratory and ocular irritation effects are changed with intermediate or chronic durations 

of exposure. Because exposure-related effects on pulmonary function variables were not evident during a 

7-year period of employment, the results provide some confidence that the acute-duration inhalation MRL 

may by protective for intermediate- and chronic-duration exposures. Additional prospective health 

evaluations of respiratory function and reproductive and developmental variables in borate mining and 

processing workers with intermediate- and chronic-duration exposures may help to better identify 

impaired respiratory function, impaired reproductive performance, and developmental effects as critical 

effects in humans from intermediate- or chronic-duration inhalation exposure to boron compounds. 

The available chronic oral bioassays in rats and dogs exposed to boric acid or borax (Weir and Fisher 

1972) and mice exposed to boric acid (Dieter 1994; NTP 1987) found no evidence for exposure-related 

cancer. Although no epidemiological studies have been conducted to examine possible associations 

between boron exposure and cancer, the results from the animal studies provide no strong impetus to 

conduct such studies. 

Genotoxicity. No in vivo human data were located. Bacterial and limited mammalian assays were 

negative for mutagenicity (Benson et al. 1984; Landolph 1985; Demerec et al. 1951; Haworth et al. 1983; 

NTP 1987) or cell transformation (Landolph 1985). However, the in vivo animal study of Wery et al. 

(2003) reported specific alterations in gene expression in embryos at critical points of development that 

may be associated with skeletal malformations seen in several animal species. Thus, additional in vivo 

studies may be useful to establish whether direct genetic changes or indirect factors are responsible for the 

observed changes in gene expression associated with observed skeletal effects in animals. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 112 

3. HEALTH EFFECTS 

Reproductive Toxicity. No associations were found between exposure to borates or boric oxide and 

indices of fertility in surveys of Turkish subpopulations expected to have intermediate- to chronicduration oral exposures to boron (Sayli 1998a, 1998b, 2003; Sayli et al. 1998), or in surveys of boron 

mining and processing workers in California (Whorton et al. 1994) and China (Chang et al. 2006). 

Studies of Chinese borate workers and populations living in environments with high boron exposure did 

not find effects on semen quality (Liu et al. 2006a, 2006b); however, adequate estimation magnitude or 

duration of boron exposure for each study group was not available. One study of Chinese borate workers 

associated high boron exposure with a shift toward males in the ratio the sex of offspring (Robbins et al. 

2008); however, several confounding factors in this study limit the interpretation of study data. 

Effects on the male and female reproductive organs have been clearly demonstrated in rats orally exposed 

to boric acid or borax; supporting evidence for effects on the male reproductive organs from oral exposure 

to boron has been reported in mice and dogs. Testicular atrophy and histopathology, sperm abnormalities, 

and reduced sperm production have been observed in mice, rats, and dogs after intermediate-duration 

ingestion of doses ≥26 mg boron/kg/day as boric acid (Dieter 1994; Dixon et al. 1976, 1979; Fail et al. 

1991; Fukuda et al. 2000; Harris et al. 1992; Ku et al. 1993a; Kudo et al. 2000; Lee et al. 1978; NTP 

1987; Nusier and Bataineh 2005; Seal and Weeth 1980; Weir and Fisher 1972; Yoshizaki et al. 1999). 

Complete sterility was observed in male and female Sprague-Dawley rats fed boric acid or borax in the 

diet for 14 weeks before mating at 101 and 116 mg boron/kg/day for males and females, respectively 

(Weir and Fisher 1972). Sterility was associated with a lack of viable sperm in males and decreased 

ovulation in females, and no pregnancies occurred when female rats exposed to this dose level were 

mated with non-exposed male rats. At lower exposure levels (10 or 30 mg boron/kg/day for males and 

12 or 35 mg boron/kg/day for females), no exposure-related adverse effects were found on fertility indices 

in three successive generations (Weir and Fisher 1972). With chronic-duration oral exposure, testicular 

atrophy occurred at 201, but not 79, mg boron/kg/day in B6C3F1 mice (Dieter 1994; NTP 1987) and at 

81, but not 24, mg boron/kg/day in Sprague-Dawley rats (Weir and Fisher 1972). No testicular atrophy 

was found in dogs exposed for 2 years to dietary doses of boric acid or borax at levels up to 6.8 mg 

boron/kg/day (Weir and Fisher 1972). In the chronic-duration oral exposure studies, no histologic effects 

on the ovaries were found in rats (Weir and Fisher 1972) or mice (Dieter 1994; NTP 1987), but the 

ovaries of chronically exposed female dogs were not examined (Weir and Fisher 1972). 

With inhalation exposure to boron compounds, reproductive effects do not appear to be an effect of 

concern. In intermediate-duration inhalation studies with rats, no histologic effects on the testes or 

ovaries were found in albino rats exposed to boric oxide aerosols for 6 hours/day, 5 days/week for 
 

 

 

 

 

 

 

 

 

BORON 113 

3. HEALTH EFFECTS 

10 weeks at an average concentration of 73 mg boron/m3, 12 weeks at 27 mg boron/m3, or 24 weeks at 

12 mg boron/m3 (Wilding et al. 1959). 

Additional prospective health evaluations of reproductive variables in borate mining and processing 

workers with intermediate- and chronic-duration exposures may help to better identify impaired 

reproductive performance as a critical effects in humans from intermediate- or chronic-duration inhalation 

exposure to boron compounds. 

Developmental Toxicity. No studies were found on the developmental effects of boron and 

compounds in humans following inhalation, oral, or dermal exposure. In acute-duration oral exposure 

animal studies, developmentally toxic effects (including reduced fetal weight and increased skeletal 

variations or malformations) have been reported in CD-1 mice exposed during gestation to boric acid 

doses as low as 70 mg boron/kg (2 times/day) (Cherrington and Chernoff 2002) and in New Zealand 

rabbits exposed during gestation (days 6–19) to doses of 44 mg boron/kg/day (Price et al. 1996b). 

Developmental effects (including decreased fetal weight, increased incidence of skeletal variations and 

malformations, and increased resorptions) have been observed in offspring of rat and mouse dams 

exposed to 13–79 mg boron/kg/day as boric acid during gestation for intermediate durations (Heindel et 

al. 1992, 1994; Price et al. 1996a). Developmental effects observed in these animal studies are the critical 

effects for the acute- and intermediate-duration oral MRLs for boron. 

Developmental toxicity studies in animals exposed to boron compounds by inhalation are not available. 

Such studies may be useful to determine if developmental effects are a critical effect from inhalation 

exposure to boron compounds. 

Immunotoxicity. No studies were found in humans or animals on the effects of boron on the immune 

system by any route of exposure. Results of chronic studies do not suggest that the immune system is a 

potential target for boron toxicity. Additional studies are not needed at this time. 

Neurotoxicity. Case reports in humans, primarily infants, indicate that neurological effects occur after 

ingestion of boron at high dose levels (Wong et al. 1964). Degenerative changes in brain cells, 

perivascular hemorrhage, and intravascular thrombosis have been reported in fatal case reports in infants, 

but neurochemical or neurophysiological changes have not been reported (Settimi et al. 1982; Wong et al. 

1964). No studies are available on neurotoxic effects of boron following inhalation or dermal exposure in 

humans. Animal data are limited to increased brain enzyme activity (Settimi et al. 1982), but no 
 

 

 

 

 

 

 

 

 

 

 

 

BORON 114 

3. HEALTH EFFECTS 

histopathological data are available. Since data on effects are limited primarily to acute oral exposures at 

high dose levels, additional studies in animals evaluating other dose levels and exposure routes and 

durations may be useful in evaluating potential risk to humans who may be exposed to low levels of 

boron compounds near hazardous waste sites. 

Epidemiological and Human Dosimetry Studies. Information exists on the adverse health 

effects of boron compounds in humans. Symptoms of acute upper respiratory and ocular irritation have 

been reported in workers employed in the borax industry for an average of >10 years, but pulmonary 

function variables were not significantly influenced by exposure over a 7-year period of employment 

(Garabrant et al. 1984, 1985; Hu et al. 1992; Wegman et al. 1991, 1994). More precise quantitation of the 

irritation potential of airborne boron compounds comes from controlled exposure studies of human 

volunteers (Cain et al. 2004, 2008). No associations were found between exposure to borates or boric 

oxide and indices of fertility in surveys of Turkish subpopulations expected to have intermediate- to 

chronic-duration oral exposures to boron (Sayli 1998a, 1998b, 2003; Sayli et al. 1998), or in surveys of 

boron mining and processing workers in California (Whorton et al. 1994) and China (Chang et al. 2006). 

Studies of Chinese borate workers and populations living in environments with high boron exposure did 

not find effects on semen quality (Liu et al. 2006a, 2006b). Other human studies involve case reports of 

accidental or intentional ingestion of large quantities of boron compounds (Wong et al. 1964; Litovitz et 

al. 1988; Locatelli et al. 1987). The case report studies identified key health effects (gastrointestinal, 

respiratory, renal, neurological, hepatic) associated with boron exposure (Wong et al. 1964). 

Results from animal studies indicate that the testes and developing fetus as the most sensitive targets 

following acute, intermediate, or chronic oral exposure to boron. Epidemiological studies that look for 

associations between boron exposure and reproductive and/or developmental toxicity end points would be 

useful to better identify impaired reproductive performance and developmental effects as critical effects 

in humans from intermediate- or chronic-duration exposure to boron compounds. 

Biomarkers of Exposure and Effect. 

Exposure. Blood and urine borate concentrations may be useful biomarkers of exposure (Jansen et al. 

1984a; Litovitz et al. 1988). Normal dietary concentrations of boron in the blood of humans range from 

0 to 1.25 μg/mL in children and infants (Fisher and Freimuth 1958; O'Sullivan and Taylor 1983). 

Elevated blood levels of boron have been reported in cases of acute ingestion of boric acid (Linden et al. 

1986; Wong et al. 1964). Urinary concentrations of boron in the normal population range from 0.07 to 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 115 

3. HEALTH EFFECTS 

0.15 mg/100 mL (Vignec and Ellis 1954) and from 0.004 to 0.66 mg/100 mL (Imbus et al. 1963), whereas 

elevated concentrations have been measured in humans orally exposed to borax or boric acid (Gordon et 

al. 1973; Jansen et al. 1984a). Additional studies of exposure levels and blood or urinary levels of boron 

in borate mining and production workers may help to better characterize quantitative relationships 

between occupational exposure levels and blood or urinary levels of boron. 

Effect. The most clearly identified effects in humans exposed to boron compounds are acute respiratory 

and ocular irritation from acute inhalation exposure to boron compounds. Several other types of effects, 

including degenerative changes in brain cells, gastrointestinal irritation, degenerative liver or kidney 

lesions, and skin changes (erythema involving palms, soles, and buttocks), have been observed in some, 

but not all, cases of acute- or intermediate-duration oral poisoning with boric acid or borax. In orally 

exposed animals, effects include testicular atrophy in males and decreased ovulation in females, and 

developmental effects (fetal body weight deficits and skeletal malformations) with gestational exposure. 

None of these effects, however, are necessarily specific to boron. To date, a specific biomarker of effect 

for boron has not been developed for humans or animals. 

Absorption, Distribution, Metabolism, and Excretion. Limited quantitative information is 

available on the absorption, distribution, metabolism, and elimination of boron compounds following oral 

(Dourson et al. 1998; Ku et al. 1991; Moseman 1994; Treinen and Chapin 1991), inhalation (Wilding et 

al. 1959), and dermal (Draize and Kelley 1959; Wester et al. 1998) exposure. Since data on 

toxicokinetics of boron are limited, additional studies are needed by all routes of exposure that will 

provide data on absorption rates, amount and rate of accumulation in various tissues, and clearance rates. 

Limited data from oral and dermal studies suggest that boron is primarily excreted in urine. Since boron 

can deposit in the upper respiratory tract, additional excretion studies by this route would be useful in 

determining if excretion patterns are similar across all routes of exposure. 

Comparative Toxicokinetics. Existing evidence from human and animal studies do not indicate 

whether or not boron compounds affect the same target tissues. Animal studies indicate the testes as a 

target tissue (Dieter 1994; Dixon et al. 1979; Fukuda et al. 2000; Ku et al. 1993a; Kudo et al. 2000; Lee et 

al. 1978; NTP 1990; Price et al. 1998; Seal and Weeth 1980; Weir and Fisher 1972). However, studies of 

Chinese borate workers found no effect of boron exposure on multiple indices of semen quality (Lui et al. 

2006a, 2006b). Data exist on excretion of boron compounds. Based on excretion studies, boron 

compounds are absorbed by the gastrointestinal tract. There are no available quantitative toxicokinetics 
 

 

 

 

 

 

 

 

 

BORON 116 

3. HEALTH EFFECTS 

data on absorption, distribution, and metabolism. Additional toxicokinetics studies may provide a better 

basis for extrapolation of animal data to human exposure risk. 

Methods for Reducing Toxic Effects. Methods for the mitigation of acute effects of boron 

poisoning include prevention of absorption of boron from the gastrointestinal tract and standard 

procedures used to prevent convulsions, severe dehydration, or shock (Stewart and McHugh 1990). 

Saline diuresis, exchange transfusions, peritoneal dialysis, or hemodialysis may be employed to enhance 

removal of absorbed boron from the body (Goldfrank et al. 1990; Stewart and McHugh 1990). No 

additional information was located concerning mitigation of effects of lower-level or longer-term 

exposure to boron. Further information on techniques to mitigate such effects may be useful in 

determining the safety and effectiveness of possible methods for treating boron-exposed populations in 

the vicinity of hazardous waste sites. 

Children’s Susceptibility. Data needs relating to both prenatal and childhood exposures, and 

developmental effects expressed either prenatally or during childhood, are discussed in detail in the 

Developmental Toxicity subsection above. 

The comparative susceptibility of children to the acute respiratory and ocular irritation potential of 

aerosols of boric acid or other boron compounds has not been examined. Results from animal studies 

indicate that developmental effects associated with gestational exposure are the most sensitive effects 

associated with acute- or intermediate-duration oral exposures. Degenerative changes in the male (e.g., 

testicular atrophy and altered spermiation) and female (decreased ovulation) have also been identified as a 

sensitive effect from boron, but no studies were located that examined the relative susceptibility of young 

animals (or children) to these effects. 

Child health data needs relating to exposure are discussed in Section 6.8.1, Identification of Data Needs: 

Exposures of Children. 

3.12.3 Ongoing Studies 

Wendie A. Robbins of the University of California Los Angeles is being funded by the NIOSH to 

perform an epidemiologic study investigating the relationship between workplace exposure to boroncontaining compounds (including boric acid, borax) and adverse male reproductive effects. Two 

published human studies on reproductive effects of occupational boron exposure found no effect on 
 

 

 

 

BORON 117 

3. HEALTH EFFECTS 

fertility or development, while one study reported positive testicular atrophy and sterility and another 

associated a shift in the ratio of offspring sex with boron exposure. All of these studies have been 

criticized for inadequacies in study design exposure assessment. The specific aims of this research are to: 

(1) describe the relationship between boron exposure and direct measures of toxicity on male 

reproduction, (2) describe the relationship between boron exposure and indirect measures of toxicity on 

male reproduction, and (3) describe the relationship between workplace, environmental, and dietary 

sources of boron with biomarkers of exposure and reproductive effect. The goal is to contribute critical 

information on the exposure level at which boron causes adverse effects on human male reproduction. 

 

 

BORON 118
 

3. HEALTH EFFECTS 

This page is intentionally blank. 
 

 

 

 

 

 

 

BORON 119 

4. CHEMICAL AND PHYSICAL INFORMATION 

4.1 CHEMICAL IDENTITY 

Boron appears in Group 13 (IIIA) of the periodic table and is the only nonmetal of this group (Jansen 

2003). Table 4-1 lists common synonyms, trade names, and other pertinent information to identify boron 

and selected compounds. 

4.2 PHYSICAL AND CHEMICAL PROPERTIES 

Boron is a nonmetal and is typically found in nature bound to oxygen. It is never found as the free 

element (Cotton et al. 1999). Boron has two stable isotopes, 10B and 11B, which are naturally present at 

19.10–20.31 and 79.69–80.90%, respectively (Jansen 2003). There are ten other known non-radioactive 

isotopes of boron (Lide 2008). Elemental boron exists in several allotropic forms (Jansen 2003). In 

addition to being an amphorous powder, boron has four crystalline forms: α-rhombohedral, 

β-rhombohedral, α-tetragonal, and β-tetragonal (Jansen 2003). 

The chemical properties of boron are more similar to carbon and silicon than elements of its own group, 

although boron is more electron deficient. Boron has a high affinity for oxygen-forming borates, and 

reacts with water at temperatures above 100 °C to form boric acid and other boron compounds. The 

electron deficiency of boron does not allow conventional two-electron bonds, but rather multicenter bonds 

that are exclusively covalent (Jansen 2003; Schubert and Brotherton 2006). Boron hydrides consequently 

have structures quite different from hydrocarbons (Jansen 2003). The multi-center nature of boron allows 

the formation of a diverse array of covalent networks, rings, cages, and clusters. Boron forms strong 

covalent bonds with electronegative elements such as fluorine and oxygen (Schubert and Brotherton 

2006). 

Table 4-2 lists important physical and chemical properties of boron and selected compounds. 
 

 

BORON 120 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Boron and Selected Boron Compoundsa 

Characteristic Boron Boron oxide Boric acid 

Synonym(s) Boron, metallic Boric anhydride; boric 

acid, anhydride; boron 

sesquioxide; boron 

trioxide; diboron trioxide; 

fused boric acid 

Orthoboric acid; boron 

hydroxide; boron 

trihydroxide 

Registered trade 

name(s) 

No data No data Optiborb 

Chemical formula 

Chemical structure 

B 

Amphorous powder, as 

well as four crystalline 

forms: α-rhombohedral, 

β-rhombohedral, 

α-tetragonal, and 

β-tetragonalc 

B2O3 

Randomly oriented B3O3 

rings with bridging 

oxygen atomsd 

B(OH)3 

Planar BO3 

3­

units linked by 

asymmetrical hydrogen 

bondsd 

Identification numbers: 

CAS registry 7440-42-8 1303-86-2 10043-35-3 

NIOSH RTECSe ED7350000 ED7900000 ED4550000 

EPA hazardous waste No data No data No data 

EPA/OPP pesticide 

Code 

128945 011002 011001 

OHM/TADS No data No data No data 

DOT/UN/NA/IMDG 

shipping 

No data No data No data 

HSDB 4482 1609 1432 

EINECS 231-151-2 215-125-8 233-139-2 

NCI No data No data C56417 
 

BORON 121 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Boron and Selected Boron Compoundsa 

Characteristic Borax Sodium tetraborate Boron tribromide 

Synonym(s) Sodium borate; sodium Sodium borate; sodium Boron bromide; tribromotetraborate; borax borate anhydrous; borane; tribromoboron 

decahydrate; disodium disodium tetraborate; 

tetraborate decahydrate sodium biborate; sodium 

pyroborate; boric acid, 

disodium salt 

Registered trade 

name(s) 

Jaikin, Pyrobor, Three 

Elephant, V-Borb 

Dehybor 65b No data 

Chemical formula B4Na2O7•10H2O Na2B4O7 BBr3 

Chemical structure Anhydrous borates have 

polymeric assemblies of 2­ planar BO3 and/or 

tetrahedral BO4 units HO OH linked by shared oxygen 

atomsd 

Br Br 

Tetraborate anion in 

solutiond 

Identification numbers: 

CAS registry 1303-96-4 1330-43-4 10294-33-4 

NIOSH RTECSe VZ2275000 ED4588000 ED7400000 

EPA hazardous waste No data No data No data 

EPA/OPP Pesticide 029601 011112 No data 

Code 

OHM/TADS No data No data No data 

DOT/UN/NA/IMDG No data No data UN 2692; IMDG 8.1 

shipping 

HSDB 328 5025 327 

EINECS 233-139-2 215-540-4 233-657-9 

NCI No data No data No data 

Br 

B 

O 

B 

O 

B 

O 

B 

O 

B 

O 

OH 

OH 
 

 

 

BORON	 122 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Boron and Selected Boron Compoundsa 

Characteristic Boron trifluoride Boron trichloride 

Synonym(s)	 Anca 1040; boron fluoride; Trichloroborane; 

trifluoroborane trichloroboron 

Registered trade No data No data 

name(s) 

Chemical formula BF3 BCl3 

Chemical structure 

F

F

B

F Cl 

Cl 

B

Cl 

Identification numbers: 

CAS registry 7637-07-2 10294-34-5 

NIOSH RTECSe ED2275000 ED1925000 

EPA hazardous waste No data No data 

EPA/OPP Pesticide No data No data 

Code 

OHM/TADS No data No data 

DOT/UN/NA/IMDG UN 1008; IMDG 6.1 UN 1741; IMDG 2.2 

shipping	 (boron trifluoride); UN 

2851; IMDG 8.2 (boron 

trifluoride dihydrate) 

HSDB 325 326 

EINECS 231-569-5 233-658-4 

NCI No data No data 

a

All information obtained from HSDB 2009 and ChemIDplus 2009, except where noted. b

NIOSH 2005 c

Jansen 2003 

d

Cotton et al. 1999 

e

RTECS 2007 

CAS = Chemical Abstracts Service; DOT/UN/NA/IMDG = Department of Transportation/United Nations/North 

America/Intergovernmental Maritime Dangerous Goods Code; EINECS = European Inventory of Existing Chemical 

Substances; EPA = Environmental Protection Agency; HSDB = Hazardous Substances Data Bank; NCI = National 

Cancer Institute; NIOSH = National Institute for Occupational Safety and Health; OHM/TADS = Oil and Hazardous 

Materials/Technical Assistance Data System; RTECS = Registry of Toxic Effects of Chemical Substances 
 

 

 

 

 

 

 

 

 

BORON 123 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Boron and Selected Boron 

Compoundsa
 

Property Boron Boron oxide Boric acid 

Molecular weight 10.811 69.620 61.833 

Physical Black or dark brown powder Colorless, glassy or Colorless, transparent 

description (amorphous form); clear red hexagonal crystals, crystals; white granules or 

crystals (α-rhombohedral hygroscopic powder 

form); black, opaque 

crystals with metallic luster 

(α-tetragonal form); black 

(β-rhombohedral form) 

Melting point 2,075 °C 450 °C (crystal) 170.9 °C 

Boiling point 4,000 °C 1,500 °C (crystal) No data 

Density 2.350 g/cm3 (amorphous); 

2.46 g/cm3 

1.8 g/cm3 (amorphous); 

2.46 g/cm3 (crystal) 

1.435 g/cm3 at 15 °C 

(α-rhombohedral); 

2.31 g/cm3 (α-tetragonal); 

2.35 g/cm3 

(β-rhombohedral) 

Odor No data Odorless Odorless 

Solubility: 

Water Insoluble 4.0% at 20 °C 50 g/L at 25 °C 

Organic Insoluble alcohol, ether Soluble in alcohol, 17.5% in glycerol; 18.5% in 

solvent(s) glycerol ethylene glycol; 173.9 g/L in 

methanol; 94.4 g/L in ethanol; 

0.6% in acetone; 1.5% in ethyl 

acetate (all at 25 °C) 

Other Soluble in concentrated No data No data 

nitric and sulfuric acids 

pKa No data No data 9.42 

Log Kow No data No data 0.175 

Vapor pressure 0.0119 mm Hg at 2,140 °C Negligible at 20 °C Negligible at 20 °C 

Autoignition 580 °C No data No data 

temperature 

Flashpoint No data No data No data 

Flammability Dust ignites spontaneously Noncombustible Not flammable 

limits in air in air 

Conversion No data No data No data 

factors 

Explosive limits No data No data No data 
 

 

 

 

 

BORON 124 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Boron and Selected Boron 

Compoundsa
 

Property Borax Sodium tetraborate Boron tribromide 

Molecular weight 381.373 201.220 250.52 

Physical White, monoclinic crystals Colorless glassy solid; Colorless, fuming liquid 

Description hygroscopic 

Melting point 75 °C (decomposes) 743 °C -46.0 °C 

Boiling point No data 1,575 °C (decomposes) 90 °C 

Density 1.73 g/cm3 2.367 g/cm3 2.698 g/cm3 at 0 °C 

Odor Odorless Odorless Sharp, irritating odor, pungent 

Solubility: 

Water 59.3 g/L at 25 °C 3.1% at 25 °C Decomposes in water
 

Organic 1 g/1 mL in glycerol; 16.7% in methanol; 30% Decomposes in alcohol;
 

solvents insoluble in alcohol in ethylene glycol; soluble in carbon 

40.6 g/L in formamide (all tetrachloride, sulfur dioxide 

at 25 °C) (liquid), carbon disulfide 

Other Insoluble in acid No data No data 

pKa No data No data No data 

Log Kow No data No data No data 

Vapor pressure Negligible Negligible at 20 °C 100 mm Hg at 33.5 °C 

Autoignition No data No data No data 

temperature 

Flashpoint No data No data No data 

Flammability Not flammable Noncombustible Nonflammable 

limits in air 

Conversion No data No data 1 ppm=10.25 mg/m3b 

factors 

Explosive limits No data No data No data 
 

BORON	 125 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Boron and Selected Boron 

Compoundsa
 

Property Boron trifluoride	 Boron trichloride 

Molecular weight 67.81	 117.17 

Physical Colorless gas Colorless fuming liquid at low temperature 

Description 

Melting point -126.8 °C -107 °C 

Boiling point -101 °C 12.5 °C 

Density 3.07666 g/L at 1 atm, 0 °C 1.3728 g/cm3 at 0 °C 

Odor Pungent, suffocating odor, irritatingc Pungent, suffocating odor, irritating, sharp 

Solubility: 

Water	 332 g/100 g water at 0 °C with some Decomposes in water, hydrolyzed easily 

hydrolysis forming fluoboric and boric 

acids 

Organic	 Soluble in benzene, dichlorobenzene, Decomposes in alcohol 

solvents	 chloroform, carbon tetrachloride, carbon
 

sulfide; soluble in most saturated and 

halogenated hydrocarbons and in 

aromatic compounds
 

Other 1.94 g/100 g in anhydrous sulfuric acid, No data 

soluble in concentrated nitric acid 

pKa No data No data 

Log Kow No data No data 

Vapor pressure 3.656x104 mm Hg at -13.2 °C 1 mm Hg at 25 °C (extrapolated) 

Autoignition No data No data 

temperature 

Flashpoint No data	 No data 

Flammability Nonflammable Nonflammable 

limits in air 

Conversion 1 ppm=2.77 mg/m3b No data 

factors 

Explosive limits No data No data 

a

All information from HSDB 2009, except where noted. b

NIOSH 2009
 c

Odor threshold 4.50 mg/m3 (Ruth 1986)
 
BORON 126
 
 

4. CHEMICAL AND PHYSICAL INFORMATION 

This page is intentionally blank. 
 

 

 

 

 

 

 

 

BORON 127 

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

5.1 PRODUCTION 

Boron is the 51st most common element found in the earth’s crust and is found at an average 

concentration of 8 mg/kg (Cotton et al. 1999; Jansen 2003). Boron is a nonmetal and is typically found in 

nature bound to oxygen. It is never found as the free element (Cotton et al. 1999). There are over 

200 minerals containing boron oxide; however, only four boron-containing minerals (borax, kernite, 

colemite, and ulexite) comprise the majority, nearly 90%, of the borates used by industry worldwide. 

These minerals are extracted mainly from California and Turkey. The majority of domestic boron 

production is from Kern County, California, with the remainder from San Bernardino and Inyo Counties 

in California (USGS 2008). 

The most widely used commercial process for producing boron is the Moissan process, which involves 

the reduction of boric oxide with magnesium (Jansen 2003). This process yields 90–92% pure boron, 

which is then leached with acid to separate it from the magnesium oxide formed during the process, 

followed by multiple washes and drying. The purity of the boron can be increased to 95–97% by further 

chemical processing (Jansen 2003). Due to boron’s tendency to bind to electron-rich elements (carbon, 

nitrogen, and oxygen) it can be very difficult to isolate boron in high purity (Cotton et al. 1999). High 

purity boron (>99.9%) is prepared by the reduction of boron trihalides or by the decomposition of boron 

triiodide or boron hydrides at high temperatures. Other methods include electrolytic reduction of 

potassium tetrafluoroborate (KBF4) in molten potassium chloride-potassium fluoride mixtures. High 

purity boron can generally only be obtained in kilogram quantities (Cotton et al. 1999). 

In 2005, 1.15 million metric tons of boron ore were produced in the United States, with a boron oxide 

(B2O3) content of 612,000 metric tons. Colemanite, kernite, tincal (natural borax), and ulexite were the 

most common mineral of commercial importance in the United States. Boron compounds and minerals 

are produced both by surface and underground mining, as well as from brine (USGS 2008). 

Boron trifluoride is prepared by the reaction of a boron-containing material and a fluorine-containing 

substance in the presence of an acid (e.g., borax, fluorspar, and sulfuric acid) (Alam et al. 2003). It can 

also be produced by the treatment of fluorosulfonic acid with boric acid. Large-scale production of boron 

trichloride involves the reaction of chlorine with a mixture of borax and crude oil residue heated in a 

rotary kiln. On a smaller-scale, boron trichloride can be prepared by reacting chlorine and a mixture of 

boron oxide, petroleum coke, and lampblack (carbon black) in a fluidized bed. Large-scale production of 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 128 

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

boron tribromide involves reaction of bromine and granulated boron carbide (B4C) at 850–1,000 °C or by 

reaction of hydrogen bromide with calcium boride (CaB6) at high temperatures (Alam et al. 2003). 

Tables 5-1 and 5-2 list facilities in each state that manufacture or process boron trifluoride and boron 

trichloride, respectively, as well as the intended use and the range of maximum amounts of these boron 

compounds that are stored onsite. In 2006, there were 50 and 19 reporting facilities that produced, 

processed, or used boron trifluoride and boron trichloride, respectively, in the United States. The data 

listed in Tables 5-1 and 5-2 are derived from the Toxics Release Inventory (TRI06 2008). Only certain 

types of facilities were required to report. Therefore, this is not an exhaustive list. Current U.S. 

manufacturers of boron and selected boron compounds are given in Table 5-3. 

5.2 IMPORT/EXPORT 

Turkey was a major import source in 2004–2007 for boric acid, supplying 55%, followed by Chile (24%), 

Bolivia (8%), Peru (5%), and other (8%) (USGS 2009). In 2008, U.S. imports of borax, boric acid, 

colemanite, and ulexite were 1x103

, 65x103, 27x103, and 90x103 metric tons, respectively. In 2008, U.S. 

exports of boric acid and refined sodium borates were 260x103 and 470x103 metric tons, respectively 

(USGS 2009). 

5.3 USE 

In 2008, the estimated use distribution pattern for boron compounds in the United States was 74% for 

glass and ceramics, 6% for soaps and detergents and bleaches, 3% for agriculture, 3% for enamels and 

glazes, and 14% remaining for other (USGS 2009). Boric acid is used in cosmetics, pharmaceuticals, and 

toiletries. It is also used to reduce the flammability of cellulose insulation, cotton batting in mattresses, 

and wood composites. Boron oxide is incorporated into cellulose materials to inhibit combustion. 

Borates are used in the manufacture of adhesives and are added to lubricants, brake fluids, metalworking 

fluids, water treatment chemicals, and fuel additives (USGS 2008). 

Pesticide products containing boric acid and its sodium salts (sodium tetraborate decahydrate, sodium 

tetraborate pentahydrate, anhydrous sodium tetraborate, disodium octaborate tetrahydrate, anhydrous 

disodium octaborate, and sodium metaborate) are registered in the United States for use as insecticides, 

fungicides, and herbicides. There are 189 pesticide products registered that contain boric acid or its 
 

 

BORON 129 

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

Table 5-1. Facilities that Produce, Process, or Use Boron Trifluoride 

Minimum Maximum 

Number of amount on site amount on site 

Statea facilities in poundsb in poundsb Activities and usesc 

AL 4 1,000 99,999 2, 3, 6, 10 

AR 3 1,000 99,999 2, 3, 6 

DE 2 100,000 999,999 1, 4, 8 

FL 3 0 99,999 6, 10 

KY 2 10,000 99,999 10, 12 

LA 5 0 999,999 2, 3, 10, 11 

MD 2 1,000 99,999 6 

NJ 2 0 9,999 6 

NY 3 1,000 999,999 6 

OH 1 10,000 99,999 6 

OK 3 10,000 999,999 1, 3, 6 

PA 8 0 999,999 6, 7, 9, 10, 12 

SC 6 1,000 99,999 2, 3, 6, 12 

TN 1 10,000 99,999 10 

TX 13 0 999,999 2, 3, 4, 6, 9, 10, 11, 12 

a

Post office state abbreviations used 

b

Amounts on site reported by facilities in each state 

c

Activities/Uses: 

1. Produce 6. Impurity 11. Chemical Processing Aid 

2. Import 7. Reactant 12. Manufacturing Aid 

3. Onsite use/processing 8. Formulation Component 13. Ancillary/Other Uses 

4. Sale/Distribution 9. Article Component 14. Process Impurity 

5. Byproduct 10. Repackaging 

Source: TRI07 2009 (Data are from 2007) 
 

BORON 130 

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

Table 5-2. Facilities that Produce, Process, or Use Boron Trichloride 

Minimum Maximum 

Number of amount on site amount on site 

Statea facilities in poundsb in poundsb Activities and usesc 

AZ 1 100 999 11, 12 

CA 2 1,000 99,999 1, 2, 3, 4, 9 

IN 3 10,000 999,999 6, 7, 10, 11 

MA 2 1,000 9,999 2, 3, 6 

MI 1 1,000 9,999 10 

NM 2 100 9,999 11 

NV 1 0 0 0 

OH 1 1,000 9,999 6 

PA 4 0 99,999 2, 4, 9 

SC 2 1,000 9,999 2, 3, 6, 7, 10, 11, 12 

WI 2 1,000 99,999 6 

WV 1 10,000 99,999 6 

a

Post office state abbreviations used 

b

Amounts on site reported by facilities in each state 

c

Activities/Uses: 

1. Produce 6. Impurity 11. Chemical Processing Aid 

2. Import 7. Reactant 12. Manufacturing Aid 

3. Onsite use/processing 8. Formulation Component 13. Ancillary/Other Uses 

4. Sale/Distribution 9. Article Component 14. Process Impurity 

5. Byproduct 10. Repackaging 

Source: TRI07 2009 (Data are from 2007) 
 

 

BORON 131 

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

Table 5-3. Current U.S. Manufacturers of Boron and Selected Boron Compounds 

Company Location 

Boron 

Eagle-Picher Incoroporated, Eagle-Pitcher Boron LLC Quapaw, Oklahoma 

SB Boron Corporation Franklin Park, Illinois 

TETRA Micronutrients Fairbury, Nebraska 

Tronox Incorporated Henderson, Nevada 

Boron oxide 

Johnson Matthey, Inc., Alfa Aesar Ward Hill, Massachusetts 

Boric acid 

InCide Technologies, Inc. Phoenix, Arizona 

Searles Valley Minerals, Argus-Trona-Westend Complex Trona, California 

Rio Tinto Minerals Boron, California 

Sodium tetraborate pentahydrate (borax pentahydrate) 

Searles Valley Minerals, Argus-Trona-Westend Complex Westend, California 

Rio Tinto Minerals Boron, California 

Sodium tetraborate decahydrate (borax decahydrate) 

Searles Valley Minerals, Argus-Trona-Westend Complex Westend, California 

Rio Tinto Minerals Boron, California 

Sodium tetraborate (Borax) 

Searles Valley Minerals, Argus-Trona-Westend Complex Trona, California 

Westend, California 

Rio Tinto Minerals Boron, California 

Boron tribromide 

Air Liquide America L.P., Air Liquide Electronics Division Dallas, Texas 

EP Scientific Products, LLC Miami, Oklahoma 

Schumacher Carlsbad, California 

Boron trifluoride dihydrate 

Atotech USA, Inc. Rock Hill, South Carolina 

Boron trichloride 

Tronox Incorporated Henderson, Nevada 

Source: Stanford Research Institute (SRI 2008), except where otherwise noted. SRI reports production of 

chemicals produced in commercial quantities (defined as exceeding 5,000 pounds or $10,000 in value annually) by 

the companies listed. 
 

 

 

 

 

 

 

 

 

 

 

 

BORON 132 

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

sodium salt as an active ingredient. Boric acid and its sodium salts are used on several agricultural and 

many non-agricultural sites including residential, commercial, medical, veterinary, industrial, forestry, 

and food/feed handling areas. Various formulations are available, including liquids, soluble and 

emulsifiable concentrates, granulars, powders, dusts, pellets, tablets, solids, paste, baits, and crystalline 

rods (EPA 1993). 

Boron halides are important industrial chemicals. Their Lewis acid properties make them useful as 

catalysts. Boron trichloride is widely used to prepare boron filaments by chemical vapor deposition 

(CVD). Much of the boron tribromide produced in the United States is used in the manufacture of 

proprietary pharmaceuticals (Alam et al. 2003). 

Boron isotopes have also found several medical and analytical uses. BNCT, a biologically targeted form 

of radiotherapy, offers the potential use of the non-radioactive, stable 10B isotope for cancer imaging. 

This technique may allow selective delivery of 10B to tumors and, as a result, better targeted irradiation of 

the tumor (Schubert and Brotherton 2006; Wittig et al. 2008). The measured ratio of 10B to 11B is 

frequently used as a hydrologic and geochemical tracer (Chetelat and Gaillardet 2005; Moore et al. 2008). 

The natural abundance of 10B and 11B is specific to location, making anthropogenic boron isotopic ratios 

from a mined location distinctly different than that found in most groundwater and soil ratios (Davidson 

and Bassett 1993). This allows utilization of the boron isotopic ratio to determine potential contamination 

in groundwater (Vengosh et al. 1994), river water (Chetelat and Gaillardet 2005), marine water (Xiao et 

al. 2007), and effluent (Kloppmann et al. 2008). 

5.4 DISPOSAL 

Boron trifluoride and boron trichloride are classified as extremely hazardous substances under the 

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

commonly known as Superfund, and the Superfund Amendments and Reauthorization Act (SARA) of 

1986 and the Emergency Planning and Community Right-to-Know Act (EPCRA), also known as Title III 

of SARA. Under CERCLA, spills or discharges into the environment of more than 500 pounds of boron 

trifluoride or boron trichloride must be reported immediately to the National Response Center (EPA 

2008b). 

Boron trifluoride and boron trichloride are also regulated under the chemical accident prevention 

provisions of the Clean Air Act (CAA) amendments of 1990. Owners and operators of stationary sources 
 

 

BORON 133 

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

who produce, process, handle, or store boron trifluoride in excess of 5,000 pounds are required to initiate 

specific activities to prevent and mitigate accidental releases (i.e., hazard assessment, a prevention 

program, and an emergency response program) (EPA 2008a). 

Boron recycling in the United States during 2008 was insignificant (USGS 2009). No other information 

regarding disposal of boron or other boron compounds was located. 
 

BORON 134
 

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

This page is intentionally blank. 
 

 

 

 

 

 

 

 

 

 

 

BORON 135 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.1 OVERVIEW 

Boron and boron compounds have been identified in at least 164 of the 1,689 hazardous waste sites that 

have been proposed for inclusion on the EPA National Priorities List (NPL) (HazDat 2007). However, 

the number of sites evaluated for boron and boron compounds is not known. The frequency of these sites 

can be seen in Figure 6-1. Of these sites containing boron and boron compounds, 163 are located within 

the United States and 1 is located in Guam (not shown). 

Boron is the 51st most common element found in the earth’s crust and is found in an average 

concentration of 8 mg/kg (approximately 0.0008%) (Cotton et al. 1999; Jansen 2003). Boron is a 

nonmetal and is typically found in nature bound to oxygen. It is never found as the free element (Cotton 

et al. 1999). There are over 200 minerals containing boron oxide; the four most important boroncontaining minerals are borax, kernite, colemite, and ulexite (USGS 2008). Boron is an essential 

micronutrient for most plants and there is evidence that it is also essential for animals, including humans 

(Rainey et al. 1999, 2002). 

In 2008, the primary use of boron compounds in the United States was for glass and ceramics, followed 

by soaps and detergents, bleaches, agriculture, and enamels and glazes (USGS 2009). Boric acid is used 

in cosmetics, pharmaceuticals, and toiletries. It is also used to reduce the flammability of cellulose 

insulation, cotton batting in mattresses, and wood composites. Boron oxide is also incorporated into 

cellulose materials to inhibit combustion. Borates are used in the manufacture of adhesives and are added 

to lubricants, brake fluids, metalworking fluids, water treatment chemicals, and fuel additives (USGS 

2008). There are 189 pesticide products registered in the United States that contain boric acid or its 

sodium salt as an active ingredient (EPA 1993). 

Borates are widespread, naturally-occurring substance found mainly as inorganic compounds in sediments 

and sedimentary rock. Boron is released to the environment slowly in low concentrations by weathering 

processes. Although few data are available quantifying boron releases from industrial sources, it is 

estimated that natural weathering releases more boron to the environment worldwide than do these 

industrial sources (Butterwick et al. 1989). 
BORON 136 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-1. Frequency of NPL Sites with Boron and Selected Boron 

Contamination 
 

 

 

 

 

 

 

 

 

 

BORON 137 

6. POTENTIAL FOR HUMAN EXPOSURE 

Boron can be released from municipal sewage waste water, coal-burning power plants, copper smelters, 

and industries using boron compounds. Boron can also be released from runoff where boron-containing 

fertilizers and herbicides are used (Butterwick et al. 1989; Fox et al. 2002; Nolte 1988; Waggott 1969). 

Adsorption-desorption reactions are expected to be the only significant mechanism that will influence the 

fate of boron in water (Rai et al. 1986). The extent of boron adsorption depends on the pH of the water 

and the chemical composition of the soil. The greatest adsorption is generally observed at pH 7.5– 

9.0 (Keren and Mezuman 1981; Keren et al. 1981; Waggott 1969). The abundance of amorphous 

aluminum oxide in soil is the single-most important property of soil that will influence the mobility of 

boron (Bingham et al. 1971). 

Rainey et al. (2002) reported mean daily intakes of boron for male and female adults to be 1.28 and 

1.00 mg, respectively, from food and beverages. Daily dietary boron intakes were 0.75 mg for infants 

aged 0–6 months and 0.99 mg for infants aged 7–11 months. Daily boron intakes were 0.86 mg for 

children aged 1–3 years, 0.80 mg for children aged 4–8 years, 0.90 and 1.02 mg, respectively, for 

adolescent males aged 9–13 and 14–18 years, and 0.83 and 0.78 mg, respectively, for adolescent females 

aged 9–13 and 14–18 years. 

Ingestion of boron from food (primarily fruits and vegetables) and water is the most frequent route of 

human exposure, but occupational exposures to boron dusts may be significant. Boron is also a 

component of several consumer products, including cosmetics medicines and insecticides. Populations 

residing in areas of the western United States with natural boron-rich deposits may be exposed to higherthan-average levels of boron. 

Boron is widely distributed in surface water and groundwater. An average surface water boron 

concentration in the United States is about 0.1 mg/L (Butterwick et al. 1989; EPA 1986b), but 

concentrations vary greatly, depending on boron content of local geologic formations and anthropogenic 

sources of boron (Butterwick et al. 1989). A survey of U.S. surface waters detected boron in 98% of 

1,577 samples at concentrations ranging from 0.001 to 5 mg/L (Butterwick et al. 1989). Concentrations 

of boron in tap water have been reported in a range of 0.007–0.2 mg/L in the United States, Canada, and 

England (Choi and Chen 1979; Davies 1990; Waggott 1969). In a 1987 survey of 989 public water 

supplies, boron concentrations ranged from <0.005 to >2 mg/L (NIRS 1987). Mean boron concentrations 

in soil in the United States are about 30 mg/kg, with concentrations ranging up to 300 mg/kg (Eckel and 

Langley 1988; USGS 1984). 
 

 

 

 

 

 

 

 

 

 

 

BORON 138 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.2 RELEASES TO THE ENVIRONMENT 

The Toxics Release Inventory (TRI) data should be used with caution because only certain types of 

facilities are required to report (EPA 2005). This is not an exhaustive list. Manufacturing and processing 

facilities are required to report information to the TRI only if they employ 10 or more full-time 

employees; if their facility is included in Standard Industrial Classification (SIC) Codes 10 (except 1011, 

1081, and 1094), 12 (except 1241), 20–39, 4911 (limited to facilities that combust coal and/or oil for the 

purpose of generating electricity for distribution in commerce), 4931 (limited to facilities that combust 

coal and/or oil for the purpose of generating electricity for distribution in commerce), 4939 (limited to 

facilities that combust coal and/or oil for the purpose of generating electricity for distribution in 

commerce), 4953 (limited to facilities regulated under RCRA Subtitle C, 42 U.S.C. section 6921 et seq.), 

5169, 5171, and 7389 (limited S.C. section 6921 et seq.), 5169, 5171, and 7389 (limited to facilities 

primarily engaged in solvents recovery services on a contract or fee basis); and if their facility produces, 

imports, or processes ≥25,000 pounds of any TRI chemical or otherwise uses >10,000 pounds of a TRI 

chemical in a calendar year (EPA 2005). 

6.2.1 Air 

Estimated releases of 3,600 pounds (~1.6 metric tons) of boron trifluoride to the atmosphere from 

21 domestic manufacturing and processing facilities in 2006, accounted for about 100% of the estimated 

total environmental releases from facilities required to report to the TRI (TRI06 2008). Estimated 

releases of 520 pounds (~0.24 metric tons) of boron trichloride to the atmosphere from five domestic 

manufacturing and processing facilities in 2006, accounted for about 100% of the estimated total 

environmental releases from facilities required to report to the TRI (TRI06 2008). These releases for 

boron trifluoride and boron trichloride are summarized in Tables 6-1 and 6-2, respectively. There is no 

information on releases of other boron compounds to the atmosphere from manufacturing and processing 

facilities because these releases are not required to be reported (EPA 1997). 

Borates are released to air from natural and industrial sources. Natural sources include oceans, volcanoes, 

and geothermal steam (Graedel 1978). Boron compounds are released from anthropogenic sources such 

as coal-fired and geothermal steam power plants, chemical plants, and rockets as well as manufacturing 
 

 

BORON 139 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Releases to the Environment from Facilities that Produce, Process, or
 

Use Boron Trifluoridea
 

Reported amounts released in pounds per yearb 

Total release 

Statec RFd Aire Waterf UI

g Landh Otheri On-sitej Off-sitek On- and off-site 

AR 1 10 0 0 0 0 10 0 10 

DE 1 500 0 0 0 3,770 500 3,770 4,270 

FL 1 0 0 0 0 0 0 0 0 

LA 3 6 0 0 0 0 6 0 6 

MD 1 55 0 0 0 0 55 0 55 

NJ 1 0 0 0 0 0 0 0 0 

OK 1 1,750 0 0 0 0 1,750 0 1,750 

PA 3 0 0 0 0 0 0 0 0 

SC 2 11 0 0 4,983 0 11 4,983 4,994 

TX 7 2,306 0 0 0 0 2,306 0 2,306 

Total 21 4,638 0 0 4,983 3,770 4,638 8,753 13,391 

a

The TRI data should be used with caution since only certain types of facilities are required to report. This is not an 

exhaustive list. Data are rounded to nearest whole number.
 b

Data in TRI are maximum amounts released by each facility.
 c

Post office state abbreviations are used.
 d

Number of reporting facilities.
 e

The sum of fugitive and point source releases are included in releases to air by a given facility.
 f

Surface water discharges, waste water treatment-(metals only), and publicly owned treatment works (POTWs) (metal
 

and metal compounds).
 g

Class I wells, Class II-V wells, and underground injection. h

Resource Conservation and Recovery Act (RCRA) subtitle C landfills; other on-site landfills, land treatment, surface 

impoundments, other land disposal, other landfills.

i

Storage only, solidification/stabilization (metals only), other off-site management, transfers to waste broker for
 

disposal, unknown

j

The sum of all releases of the chemical to air, land, water, and underground injection wells.

k

Total amount of chemical transferred off-site, including to POTWs.
 

RF = reporting facilities; UI = underground injection 

Source: TRI07 2009 (Data are from 2007) 
 

 

BORON 140 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-2. Releases to the Environment from Facilities that Produce, Process, or
 

Use Boron Trichloridea
 

Reported amounts released in pounds per yearb 

Total release 

Statec RFd Aire Waterf UI

g Landh Otheri On-sitej Off-sitek On- and off-site 

CA 1 0 0 0 0 0 0 0 0 

MA 1 0 0 0 0 0 0 0 0 

NV 1 0 0 0 0 0 0 0 0 

OH 1 0 0 0 0 0 0 0 0 

PA 1 0 0 0 0 0 0 0 0 

SC 1 35 0 0 2,422 0 2,422 35 2,422 

WI 1 35 0 0 0 0 0 35 0 

WV 1 0 0 0 0 0 0 0 0 

Total 8 70 0 0 2,422 0 2,422 70 2,422 

a

The TRI data should be used with caution since only certain types of facilities are required to report. This is not an 

exhaustive list. Data are rounded to nearest whole number.
 b

Data in TRI are maximum amounts released by each facility.
 c

Post office state abbreviations are used.
 d

Number of reporting facilities.
 e

The sum of fugitive and point source releases are included in releases to air by a given facility.
 f

Surface water discharges, waste water treatment-(metals only), and publicly owned treatment works (POTWs) (metal
 

and metal compounds).
 g

Class I wells, Class II-V wells, and underground injection. h

Resource Conservation and Recovery Act (RCRA) subtitle C landfills; other on-site landfills, land treatment, surface 

impoundments, other land disposal, other landfills.

i

Storage only, solidification/stabilization (metals only), other off-site management, transfers to waste broker for
 

disposal, unknown

j

The sum of all releases of the chemical to air, land, water, and underground injection wells.

k

Total amount of chemical transferred off-site, including to POTWs.
 

RF = reporting facilities; UI = underground injection 

Source: TRI07 2009 (Data are from 2007) 
 

 

 

 

 

 

 

 

 

 

BORON 141 

6. POTENTIAL FOR HUMAN EXPOSURE 

facilities producing fiberglass and other products (EPA 1987; Graedel 1978; Hollis et al. 1988; Lang et al. 

1986; Rope et al. 1988; Stokinger 1981). 

Boron or boron compounds have been identified in 1 air sample collected from 1,689 current or former 

NPL hazardous waste sites where it was detected in some environmental media (HazDat 2007). 

6.2.2 Water 

No releases of boron trifluoride or boron trichloride to surface water were reported from 21 and 

5 domestic manufacturing and processing facilities, respectively, in 2006 (TRI06 2008). Releases for 

boron trifluoride and boron trichloride are summarized in Tables 6-1 and 6-2, respectively. There is no 

information on releases of other boron compounds to surface water from manufacturing and processing 

facilities because these releases are not required to be reported (EPA 1997). 

Boron compounds are released to water in municipal sewage from perborates in detergents and in waste 

waters from coal-burning power plants, copper smelters, and industries using boron. Borate levels above 

background may be present in runoff waters from areas where boron-containing fertilizers or herbicides 

were used (Butterwick et al. 1989; Nolte 1988; Waggott 1969). An average boron concentration of 

1 mg/L was reported in sewage effluents in California (Butterwick et al. 1989). Waggott (1969) reported 

that boron concentrations in municipal sewage in a treatment plant in England ranged from 2.5 to 

6.5 mg/L, releasing between 130 and 240 kg boron/day. Matthijs et al. (1999) reported boron 

concentrations of 0.41–1.2, 0.39–0.96, and 0.44–1.0 mg/L in raw sewage, settled sewage, and effluent, 

respectively, collected in 1994 from seven Dutch sewage treatment plants. These data demonstrate that 

boron passes through the sewage treatment process virtually unchanged. Since boron cannot be degraded 

and is not substantially absorbed during processing, there is almost no removal during the sewage 

treatment process (Fox et al. 2002). 

Boron is also found in water produced from coal bed natural gas produced water (Jackson and Reddy 

2007), irrigation, geothermal waste water, and thermal springs (Koç 2007) used for power generation and 

heating. In the Powder River Basin, Wyoming, boron was detected in coal natural gas waste water outfall 

and disposal ponds at 5.89−13.08 (0.064−0.14) and 7.72−15.20 μM (0.083−0.16 mg/L), respectively 

(Jackson and Reddy 2007). In the Great Menderes Basin, Turkey, boron is brought to the surface and 

released from natural borate mineral deposits into local rivers via geothermal waste waters and crop 
 

 

 

 

 

 

 

 

 

 

BORON 142 

6. POTENTIAL FOR HUMAN EXPOSURE 

irrigation canals (Koç 2007). The hot waste waters of a geothermal power plant released into the Buyuk 

Menderes River contained approximately 25–30 mg/L boron (Akar 2007). 

Boron or boron compounds have been identified in 100 groundwater and 57 surface water samples 

collected from 1,689 NPL hazardous waste sites, where it was detected in some environmental media 

(HazDat 2007). 

6.2.3 Soil 

Estimated releases of 1,300 pounds (~0.59 metric tons) of boron trifluoride to soil and 6 pounds 

(3 kilograms) by underground injection from 21 domestic manufacturing and processing facilities in 

2006, accounted for about 100% of the estimated total environmental releases from facilities required to 

report to the TRI (TRI06 2008). Estimated releases of 136 pounds (61.7 kg) of boron trichlorideto soil 

and 18 pounds (8.2 kilograms) by underground injection from five domestic manufacturing and 

processing facilities in 2006, accounted for about 100% of the estimated total environmental releases 

from facilities required to report to the TRI (TRI06 2008). These releases for boron trifluoride and boron 

trichloride are summarized in Tables 6-1 and 6-2, respectively. There is no information on releases of 

other boron compounds to soil or by underground injection from manufacturing and processing facilities 

because these releases are not required to be reported (EPA 1997). 

Boron is naturally released to soil and water by rainfall, weathering of boron-containing minerals, 

desorption from clays, and decomposition of boron-containing organic matter. Human-made sources 

include application of boron-containing fertilizers or herbicides, application of fly ash or sewage sludge 

as a soil amendment, the use of waste water for irrigation, or land disposal of boron-containing industrial 

wastes (Butterwick et al. 1989; Hollis et al. 1988; Mumma et al. 1984; Nolte 1988; Rope et al. 1988). In 

the Great Menderes Basin, Turkey, the hot waste waters of a geothermal power plant contained high 

levels of boron (~25–30 mg/L). This water becomes part of the irrigation systems and is thus deposited in 

sediments and soils. The boron concentrations of surrounding irrigated soils before the waste water 

discharges began were 0.15 ppm (0–20 cm depth) and 0.19 ppm (80–100 cm depth), while after the 

discharges, the boron concentrations were 13.90 ppm (0–20 cm depth) and 3.66 ppm (80–100 cm depth) 

(Akar 2007). Barber et al. (2006) reported that daily loads of boron in the Boulder Creek, Colorado of 0– 

55 kg/day are mostly due to the effluent of the Boulder waste water treatment plant. Mumma et al. (1984) 

reported that the boron concentration in sewage sludges from 23 U.S. cities ranged from 7.1 to 

53.3 mg/kg. Landfilling or land application is a common disposal method for these sludges. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 143 

6. POTENTIAL FOR HUMAN EXPOSURE 

Boron or boron compounds have been identified in 37 soil and 21 sediment samples collected from 

1,689 NPL hazardous waste sites, where it was detected in some environmental media (HazDat 2007). 

6.3 ENVIRONMENTAL FATE 

6.3.1 Transport and Partitioning 

Boron is generally found in nature bound to oxygen and is never found as the free element (Cotton et al. 

1999). Atmospheric boron may be in the form of particulate matter or aerosols as borides, boron oxides, 

borates, boranes, organoboron compounds, trihalide boron compounds, or borazines. Borates are 

relatively soluble in water, and will probably be removed from the atmosphere by precipitation and dry 

deposition (EPA 1987). The half-life of airborne particles is usually on the order of days, depending on 

the size of the particle and atmospheric conditions (Nriagu 1979). No specific information on the fate of 

atmospheric boron was located. 

Boron readily hydrolyzes in water to form the electrically neutral, weak monobasic acid, boric acid 

(H3BO3), and the monovalent ion, B(OH)4

-

. In concentrated solutions, boron may polymerize, leading to 

the formation of complex and diverse molecular arrangements. Rai et al. (1986) concluded that because 

most environmentally relevant boron minerals are highly soluble in water, it is unlikely that mineral 

equilibria will control the fate of boron in water. Boron was found to not be significantly removed during 

the conventional treatment of waste water (Matthijs et al. 1999; Pahl et al. 2001; Waggott 1969). Boron 

may, however, be co-precipitated with aluminum, silicon, or iron to form hydroxyborate compounds on 

the surfaces of minerals (Biggar and Fireman 1960). 

Waterborne boron may be adsorbed by soils and sediments. Adsorption-desorption reactions are expected 

to be the only significant mechanism that will influence the fate of boron in water (Rai et al. 1986). The 

extent of boron adsorption depends on the pH of the water and the chemical composition of the soil. The 

greatest adsorption is generally observed at pH 7.5–9.0 (Keren and Mezuman 1981; Keren et al. 1981; 

Waggott 1969). Bingham et al. (1971) concluded that the single most important property of soil that will 

influence the mobility of boron is the abundance of amorphous aluminum oxide. The extent of boron 

adsorption has also been attributed to the levels of iron oxide (Sakata 1987), and to a lesser extent, the 

organic matter present in the soil (Parks and White 1952), although other studies (Mezuman and Keren 

1981) found that the amount of organic matter present was not important. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 144 

6. POTENTIAL FOR HUMAN EXPOSURE 

The adsorption of boron may not be reversible in some soils. The lack of reversibility may be the result 

of solid-phase formation on mineral surfaces (Rai et al. 1986) and/or the slow release of boron by 

diffusion from the interior of clay minerals (Griffin and Burau 1974). 

Partition coefficients such as adsorption constants describe the tendency of a chemical to partition from 

water to solid phases. Adsorption constants for inorganic constituents such as boron cannot be predicted 

a priori, but must be measured for each soil-water combination. Compilations of available data for boron 

are given elsewhere (Rai et al. 1986). In general, boron adsorption will be most significant in soils that 

contain high concentrations of amorphous aluminum and iron oxides and hydroxides such as the reddish 

Ultisols in the southeastern United States. 

It is unlikely that boron is bioconcentrated significantly by organisms from water. A bioconcentration 

factor (BCF) relates the concentration of a chemical in the tissues of aquatic and terrestrial animals or 

plants to the concentration of the chemical in water or soil. The BCFs of boron in marine and freshwater 

plants, fish, and invertebrates were estimated to be <100 (Thompson et al. 1972). Experimentally 

measured BCFs for fish have ranged from 52 to 198 (Tsui and McCart 1981). These BCFs suggest that 

boron is not significantly bioconcentrated. 

6.3.2 Transformation and Degradation 

6.3.2.1 Air 

There is no information available that suggests that particulate boron compounds are transformed or 

degraded in the atmosphere. Particulate-phase boron compounds would be removed from the atmosphere 

by wet and dry deposition. Volatile boron trihalides are moisture sensitive and will hydrolyze to boric 

acid and their corresponding halogen acid (Culver et al. 1994b). 

6.3.2.2 Water 

As an element, boron itself cannot be degraded in the environment; however, it may undergo various 

reactions that change the form of boron (e.g., precipitation, polymerization, and acid-base reactions) 

depending on conditions such as its concentration in water and pH. In nature, boron is generally found in 

its oxygenated form (Cotton et al. 1999). In aqueous solution, boron is normally present as boric acid and 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 145 

6. POTENTIAL FOR HUMAN EXPOSURE 

borate ions, with the dominant form of inorganic boron in natural aqueous systems as undissociated boric 

acid (Choi and Chen 1979). Boric acid acts as an electron acceptor in aqueous solution, accepting an 

hydroxide ion from water to form (B(OH)4)

- ion. In dilute solution, the favored form of boron is B(OH)4

­

(Cotton et al. 1999). In more concentrated solutions (>0.1 M boric acid) and at neutral to alkaline pH (6– 

11), polymeric species are formed (e.g., B3O3(OH)4

-

, B5O6(OH)4

-

, B3O3(OH)5

2-, and B4O5(OH)42-) (Choi 

and Chen 1979; Cotton et al. 1999). 

6.3.2.3 Sediment and Soil 

Most boron compounds are transformed to borates in soil due to the presence of moisture. Borates 

themselves are not further degraded in soil. However, borates can exist in a variety of forms in soil (see 

Section 6.2.3). Borates are removed from soils by water leaching and by assimilation by plants. 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

Reliable evaluation of the potential for human exposure to boron depends in part on the reliability of 

supporting analytical data from environmental samples and biological specimens. Concentrations of 

boron in unpolluted atmospheres and in pristine surface waters are often so low as to be near the limits of 

current analytical methods. In reviewing data on boron levels monitored or estimated in the environment, 

it should also be noted that the amount of chemical identified analytically is not necessarily equivalent to 

the amount that is bioavailable. The analytical methods available for monitoring boron in a variety of 

environmental media are detailed in Chapter 7. 

6.4.1 Air 

Boron concentrations in ambient air samples have been reported to range from <5x10-7 to 8x10-5 mg/m3

, 

with an average concentration of 2x10-5 mg/m3 (Howe 1998). Bertine and Goldberg (1971) estimated that 

approximately 11,600 tons of boron are injected into the atmosphere as a component of fly ash produced 

by coal combustion, which was estimated to contain an average boron concentration of about 75 mg/kg. 

Mean dust concentrations ranging from 3.3 to 18 mg particulates/m3 were measured in air samples from 

U.S. facilities where borax was packaged and shipped (Culver et al. 1994a). Dust samples in these 

facilities were predominantly composed of various types of borates and ranged from 11.8 to 15.2% boron 

by weight. 
 

 

 

 

 

 

 

 

 

 

 

 

BORON 146 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.4.2 Water 

Boron is widely distributed in surface water and groundwater. The average surface water boron 

concentration in the United States is about 0.1 mg/L (Butterwick et al. 1989; EPA 1986b), but 

concentrations vary greatly, depending on boron content of local geologic formations and anthropogenic 

sources of boron (Butterwick et al. 1989). A survey of U.S. surface waters detected boron in 98% of 

1,577 samples at concentrations ranging from 0.001 to 5 mg/L. Mean boron concentrations calculated for 

the 15 drainage basins in the continental United States ranged from 0.019 mg/L in the Western Great 

Lakes Basin to 0.289 mg/L in the Western Gulf Basin (Butterwick et al. 1989). Mean boron 

concentration ranging from 0.28 to 7.8 mg/L were reported in samples collected during 1985–2002 from 

26 sites in the San Joaquin River, California (Hall et al. 2004). The concentration of boron in sea water is 

about 4.5 mg/L (Butterwick et al. 1989; EPA 1986b). 

Several studies have measured boron concentrations in water in those areas of California with boron-rich 

deposits. Reported high boron concentrations in surface waters ranged from 15 mg/L in coastal drainage 

waters to 360 mg/L in a boron-rich lake (Butterwick et al. 1989; Deverel and Millard 1988). Mean boron 

concentration in a California river ranged from 0.30 to 0.50 mg/L over a 20-year period (Butterwick et al. 

1989). Reported boron concentrations in groundwater in the San Joaquin Valley ranged from 0.14 to 

120 mg/L with a median concentration of about 4 mg/L (Butterwick et al. 1989; Deverel and Millard 

1988). Waggott (1969) reported that groundwater boron concentrations >100 mg/L are common in 

California. 

Drinking water surveys generally do not report boron concentration. Concentrations of boron in tap water 

have been reported in a range of 0.007–0.2 mg/L in the United States and England (Choi and Chen 1979; 

Waggott 1969), and the National Inorganics and Radionuclides Survey completed in 1987 reported 

relatively widespread occurrence of boron in 989 public water supplies (NIRS 1987). Boron 

concentrations ranged from <0.005 to >2 mg/L, with concentrations of up to 0.4 mg/L in 90% of systems 

(NIRS 1987). A survey of 969 public water supply systems showed that 99% contained boron at 

<1 mg/L. The maximum level measured was 3.28 mg/L (McCabe et al. 1970). Davies (1990) reported 

an average boron concentration of 0.0258 mg/L in drinking water from Toronto, Canada (1978–1984). 

6.4.3 Sediment and Soil 

Background boron levels in U.S. soils were reported at a geometric mean concentration of 26 mg/kg with 

a maximum concentration of 300 mg/kg (Eckel and Langley 1988). Similar concentrations were reported 
 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 147 

6. POTENTIAL FOR HUMAN EXPOSURE 

in a U.S. Geological Survey report (USGS 1984), with an average boron concentration of 33 mg/kg 

(range <20–300 mg/kg) in surface soils from the conterminous United States. Mean boron 

concentrations in soil collected in the summer of 1981 from the Idaho National Engineering Laboratory 

and a reference site were 10.1 and 4.7 mg/kg dry weight, respectively (Rope et al. 1988). A geometric 

mean boron concentration of 8.98 mg/kg (range 2.90–38.0 mg/kg) was reported in soil collected from 

Aviles, northern Spain (Ordonez et al. 2003). 

Boron is an essential nutrient for plants. Boron soil concentrations for optimum plant growth reportedly 

range from 0.1 to 0.5 mg/kg for several plant species (Butterwick et al. 1989). 

Geometric mean boron concentration in sediment collected in 1993 and 1994 from 16 Great Lake 

embayments and riverine environments of eastern Lake Erie, southern Lake Ontario, and the Niagara 

River ranged from 0.5 to 7.9 mg/kg dry weight (Lowe and Day 2002). Boron concentrations in sediments 

collected in 1992 from the Neosho River Basin in Kansas ranged from 2 to 6.5 mg/kg dry weight (Allen 

et al. 2001). 

6.4.4 Other Environmental Media 

Boron concentrations in various foods are summarized in Table 6-3. Rainey et al. (1999, 2002) reported 

the highest content of boron in foods such as raisins, peanut butter, peanuts, dried fruits, and avocados 

with concentrations of 2.20, 1.45, 1.70, 1.87, and 1.22 mg/100 g food, respectively. The top two items 

that contribute to boron intake were coffee and milk, due to the volume with which they are consumed 

(Rainey et al. 1999, 2002). Hunt et al. (1991) determined boron concentrations various foods. In general, 

boron concentrations were lowest in foods such as meats, cereal and grain products, and confections, 

ranging from ≤0.015 mg/kg in many of these foods to 1.470 mg/kg in grape jelly. Fruits, vegetables, 

herbs, and spices contained the highest concentrations of boron, including parsley flakes (26.878 mg/kg), 

ground cinnamon (10.370 mg/kg); dried onion flakes (6.573 mg/kg), and applesauce (2.828 mg/kg). 

Meacham and Hunt (1994) studied the boron content in infant (6–11 months) foods. Foods containing 

fruit typically had the highest concentrations of boron: prunes with tapioca (2.6 mg/kg); apples with ham 

(2.5 mg/kg); applesauce with apricot (2.5 mg/kg); pears (1.9 mg/kg); and applesauce (1.8 mg/kg). Boron 
 

BORON 148 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-3. Boron Levels in Food 

Food item Level (μg/100 g)a 

Fruits and vegetables 

Apples, raw 360 

Applesauce, unsweetened 280 

Avacado, guacamole 1,222b 

Bananas, raw 135 

Beans, string, cooked 120 

Broccoli, boiled 250 

Cantaloupe, raw 180 

Carrots, raw or frozen 140 

Coleslaw with dressing 120 

Corn, yellow, cooked 46 

Fruit cocktail, canned in heavy syrup 240 

Fruit, dried 1,870 

Grapes, raw 490 

Lettuce, raw 105 

Onions, raw 190 

Oranges, raw 260 

Peaches, raw 530 

Pears, raw 280 

Peas, green, cooked 130 

Potatoes, not fried 62b 

Raisins 2,200 

Spinach, boiled 180 

Tomatoes, raw 63 

Beverages 

Apple juice 180 

Beer 12 

Coffee, from ground beans 29 

Fruit-flavored drink from powder 16 

Grape juice unsweetened 300 

Milk, whole 18 

Orange juice 72 

Soft drink, cola-type 13 

Tea, leaf, brewed 9 

Wine, table, dry 610 
 

BORON 149 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-3. Boron Levels in Food 

Food item Level (μg/100 g)a 

Meat/fish products 

Beef and vegetable stew 120 

Beef, burgers 23b 

Beef vegetable soup with potato, stew type 140 

Chicken breast, broiled, without skin 27 

Chili con carne, with beans 170 

Hamburger, with tomato and/or ketchup 51 

Tuna, canned, water packed 54 

Other 

Beans, lima, dry cooked, fat added 370 

Beans, refried 400 

Bran flakes with raisins 450 

Bread, white 46 

Cakes 100b 

Cereal, ready to eat 128b 

Cookies, brownies 112b 

French fries, from frozen, deep fried 110 

Donuts, sweet rolls, etc. 69 

Ice cream, regular, not chocolate 22 

Nuts/seeds, whole 1214b 

Pasta 44b 

Peanut butter 1,450 

Peanuts, roasted, salted 1,700 

Peas, black-eyed, cooked, fat added 65 

Pizza with meat, thin crust 490 

Potato chips 325 

Rice, white, cooked 32 

Spaghetti sauce 120 

Spaghetti with meat sauce 65 

Tomato sauce 132b 

a

Rainey et al. 1999 (CSFII 1989–1991), unless otherwise noted. b

Rainey et al. 2002 (CSFII 1994–1996) 
 

 

 

 

 

 

 

 

 

 

BORON 150 

6. POTENTIAL FOR HUMAN EXPOSURE 

is also found in infant formula (120 μg/L) and expressed human breast milk (10–100 μg/L) (Hunt and 

Meacham 2001; Hunt et al. 2004, 2005; Lopez-Garcia et al. 2009). 

Minoia et al. (1994) determined the concentrations of various elements in beverages available in Italy. 

Mean boron concentrations in wine, mineral water, beer, ready-to-drink-infusion of tea, and instant 

coffees were 1.164, 0.112, 0.166, 0.219, and 0.085 mg/L, respectively. In this study, it was estimated that 

beverages contributed 34% to the estimated weekly total dietary intake of 9 mg of boron (Minoia et al. 

1994). Red and white Australian wine samples that were analyzed contained boron concentrations of 

approximately 2.5 mg/L (Cozzolino et al. 2008). 

Boric acid, anhydrous sodium tetraborate, and sodium tetraborate decahydrate (borax) are found in 

various commercial products including pesticides, plant foods, household cleaners, laundry detergents, 

facial creams and cleaners, shampoo, diaper rash ointments, and pet products. Typical amounts of borax 

in detergents range from 1 to 5%. Boric acid concentrations in various ant and roach pesticide products 

range from 5 to 100% (NIH 2004). 

Gonzales et al. (2004) determined elements found in dust collected from homes of Native Americans in 

Zuni Pueblo, New Mexico where jewelry was produced. Surface dust samples were collected from work 

and living areas of jewelers’ homes and from control homes. A surface area of 715 cm2 was wiped at 

each location. Mean boron concentrations were found to be significantly higher in work areas 

(0.87 μg/sample) than in living areas (0.28 μg/sample) of homes where jewelry was made. The geometric 

mean boron concentration was 0.19 μg/sample in living areas of homes in which no jewelry was made 

(Gonzales et al. 2004). 

The geometric mean boron concentration in soft tissues of zebra mussels collected in 1993 and 1994 from 

16 Great Lake embayments and riverine environments of eastern Lake Erie, southern Lake Ontario, and 

the Niagara River ranged from 0.92 to 6.89 μg/g dry weight (Lowe and Day 2002). Boron was not 

detected (detection limit 2–4 μg/g dry weight) in the soft tissues of mussels collected in 1991 or in fish 

composites collected in 1990–1992 from the Neosho River Basin in Kansas (Allen et al. 2001). 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

Human exposure to borates may occur through ingestion of food and water or insecticides used to control 

cockroaches, inhalation of boron-containing powders or dusts, or the use of boron from cosmetics or 
 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 151 

6. POTENTIAL FOR HUMAN EXPOSURE 

medical preparations. The most appreciable boron exposure to the general population is likely to be 

ingestion of food and to a lesser extent in water (Beyer et al. 1983; Waggott 1969). As boron is a natural 

component of the environment, individuals will have some exposure from foods and drinking water. 

Dietary intakes of boron in children and adults in the United States are summarized in Table 6-4. Rainey 

et al. (1999) reported mean daily intakes of boron for male and female adults to be 1.17 and 0.96 mg/day, 

respectively (range 0.02–>9 mg/day). The highest median boron intake of 1.30 mg/day was found for 

adult male vegetarians, and the lowest median boron intake of 0.72 mg/day was found for women aged 

19–30 years. Median boron intakes were higher in adult male and female vegetarians, 1.47 and 

1.29 mg/day, respectively, than for all adult males and females, 1.17 and 0.96 mg/day, respectively 

(Rainey et al. 1999). Consumption of fruits and vegetables contribute largely to boron intake in the 

human diet. An average daily intake of 1 mg was reported for boron for individuals in the United States. 

Consumption of wine may contribute an additional 3–4 mg/day of boron (Pahl et al. 2001). 

Concentrations of various elements were determined in hair samples from women in two areas (acid and 

alkaline) of southern Sweden (Rosborg et al. 2003). Median boron concentrations were 281 and 

<1 mg/kg in hair samples from the acid and alkaline areas, respectively. In this study, the boron levels in 

drinking water were similar, 10.6 and 9.3 μg/L, in the acid and alkaline areas, respectively, and the 

authors noted that drinking water did not explain the significantly higher concentrations of boron in the 

individuals living in the acid area (Rosborg et al. 2003). A mean boron concentration of 0.50 mg/kg wet 

weight was reported in lung tissue collected from 26 nonsmoking individuals, aged >50 years with no 

history of occupational exposure to elements living in Terni, central Italy (Alimonti et al. 1992). Boron 

was not detected in a national survey of human adipose tissue (EPA 1986a). 

Occupational exposure to boron compounds may be higher. Workers in other industries, including 

manufacture of glass wool (Jensen 2009), fiberglass and other glass products, cleaning and laundry 

products, fertilizers, pesticides, and cosmetics, may also be exposed to boron compounds (Stokinger 

1981). Culver et al. (1994a) reported average end-of-shift boron concentrations in blood and urine of 

0.11–0.26 μg/g and 3.16–10.72 μg/mg creatinine, respectively, collected from workers at a facility where 

borax is packaged and shipped. Average boron concentrations in blood and urine collected Monday 

morning prior to the first shift of the week were 0.09 μg/g and 2.75 μg/mg creatinine, respectively 

(Culver et al. 1994a). In 2004, workers from Kuandian City, China with occupations in boron mines or 

processing plants producing borax or boric acid were monitored over a 24-hour period for boron 
 

 

BORON 152 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. Dietary Boron Intake 

1989–1991a 1994–1996b 

Age group Mean±standard deviation (mg/day) 

School aged male and female children 

4–8 years (n=993a, 1,650b) 0.85±0.040 0.80±0.01 

9–13 years (n=943a, 552b males) 0.91±0.45 0.90±0.03 (m) 

(n=560b females) 0.83±0.03 (f) 

14–18 years (n=759a, 446b males) 0.88±0.47 1.02±0.04 (m) 

(n= 436b, females) 0.078±0.04 (f) 

Adult males (≥19 years ) (n=3,433a, 4,817b) 1.17±0.65 1.28±0.02 

19–30 years (n=878a, 853b) 1.07±0.64 1.15±0.03 

31–50 years (n=1,297a, 1,684b) 1.17±0.64 1.33±0.03 

51–70 years (n=884a, 1,606b) 1.28±0.67 1.34±0.02 

>70 years (n=374a, 674b) 1.19±0.61 1.25±0.03 

Vegetarian (n=49a) 1.47±0.70 No data 

Adult females (≥19 years ) (n=4,881a, 4,536b) 0.96±0.55 1.00±0.01 

19–30 years (n=1,199a, 760b) 0.86±0.55 0.87±0.03 

31–50 years (n=1,734a, 1,614b) 0.96±0.55 1.00±0.02 

51–70 years (n=1,220a, 1,539b) 1.05±0.55 1.11±0.02 

>70 years (n=728a, 623b) 0.97±0.52 0.98±0.03 

Vegetarian (n=130a) 1.29±1.12 No data 

Pregnant women (n=130a, 70b) 1.01±0.72 1.16±0.09 

a

Rainey et al. 1999 (CSFII 1989–1991) b

Rainey et al. 2002 (CSFII 1994–1996) 
 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 153 

6. POTENTIAL FOR HUMAN EXPOSURE 

exposure. Total daily boron measured in food, fluids, and personal air averaged 41.2 mg/day for workers 

in the boron industry, 4.3 mg/day in the surrounding community, and 2.3 mg/day for the comparison 

group. Blood, post-shift urine, and semen levels of boron determined for the boron industry workers were 

19.3, 499.2, and 793.9 mg/day, respectively while the comparison group only had 1.7, 48.0, and 

215.0 mg/day, respectively (Xing et al. 2008). 

Workers in other industries, including manufacture of fiberglass and other glass products, cleaning and 

laundry products, fertilizers, pesticides, and cosmetics, may also be exposed to boron compounds 

(Stokinger 1981). Reported concentrations of borax dust in different areas of a large borax mining and 

refining plant ranged from 1.1 to 14.6 mg/m3 for total particulate (Garabrant et al. 1985) and the mean 

boric acid/boron oxide dust concentration in a boric acid manufacturing plant was 4.1 mg/m3 for total 

particulate (Garabrant et al. 1984). Mean dust concentrations ranging from 3.3 to 18 mg particulates/m3 

were measured in air samples from U.S. facilities where borax was packaged and shipped (Culver et al. 

1994a). Dust samples in these facilities were predominantly composed of various types of borates and 

ranged from 11.8 to 15.2% boron by weight. In another study of dust concentrations in air samples from 

a U.S. borax production facility, mean total dust concentrations ranged from 0.29 to 18.95 mg 

particulates/m3

, with average percent boron contents in dust ranging from 5.6 to 10.1% (Woskie et al. 

1994). 

NIOSH estimated that the number of workers potentially exposed to boron increased from 6,500 in the 

early 1970s (NOHS 1989) to 35,600 in the early 1980s (NOES 1989). Neither the National Occupational 

Hazard Survey (NOHS) nor the National Occupational Exposure Survey (NOES) databases contain 

information on the frequency, concentration, or duration of exposures of workers to any of the chemicals 

listed therein. These surveys provide only estimates of the number of workers potentially exposed to 

chemicals in the workplace. Sittig (1985) reports that NIOSH estimated that the numbers of workers 

potentially exposed to borax, boron oxide, and boron trifluoride are 2,490,000, 21,000, and 50,000, 

respectively. 

6.6 EXPOSURES OF CHILDREN 

This section focuses on exposures from conception to maturity at 18 years in humans. Differences from 

adults in susceptibility to hazardous substances are discussed in Section 3.7, Children’s Susceptibility. 
 

 

 

 

 

 

 

 

 

 

 

 

BORON 154 

6. POTENTIAL FOR HUMAN EXPOSURE 

Children are not small adults. A child’s exposure may differ from an adult’s exposure in many ways. 

Children drink more fluids, eat more food, breathe more air per kilogram of body weight, and have a 

larger skin surface in proportion to their body volume. A child’s diet often differs from that of adults. 

The developing human’s source of nutrition changes with age: from placental nourishment to breast milk 

or formula to the diet of older children who eat more of certain types of foods than adults. A child’s 

behavior and lifestyle also influence exposure. Children crawl on the floor, put things in their mouths, 

sometimes eat inappropriate things (such as dirt or paint chips), and spend more time outdoors. Children 

also are closer to the ground, and they do not use the judgment of adults to avoid hazards (NRC 1993). 

Exposure to boron for children will be similar to adults and will occur primarily through the diet. As 

boron is a natural component of the environment, children, as with the general population, will have some 

exposure from foods and drinking water. Rainey et al. (2002) reported that average daily boron intakes 

ranged from 0.75 to 0.99 mg in infants and children aged 0–8 years. In adolescent males and females 

aged 9–18 years, average daily boron intakes were 0.9–1.02 and 0.78–0.83 mg, respectively. A daily 

boron intake of 1.16 mg was reported for pregnant women. Dietary intake of boron in children in the 

United States is summarized in Table 6-4. Meacham and Hunt (1994) reported a daily intake of 0.333 mg 

for infants (6–11 months) from baby foods and beverages. 

Children and infants may be exposed to boric acid or its sodium salts in homes where pesticide products 

containing boric acid or its sodium salts are used. Individuals applying these products in residential 

setting should take appropriate precautions to avoid exposing children. 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

The populations living in areas of California and other western states with boron-rich geological deposits 

have potentially high exposure to boron from drinking water and locally grown foods (Butterwick et al. 

1989). Individuals using boron-containing cosmetics or medicines extensively, especially on damaged 

skin, may be exposed to higher-than-normal levels of boron (Beyer et al. 1983). Workers in industries 

producing or using boron-containing materials also have potentially high exposure as noted above 

(Section 6.5). People living in the vicinity of waste sites are also at risk of higher-than-normal exposure 

levels. 
 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 155 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.8 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of boron is available. Where adequate information is not 

available, ATSDR, in conjunction with NTP, is required to assure the initiation of a program of research 

designed to determine the health effects (and techniques for developing methods to determine such health 

effects) of boron. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

6.8.1 Identification of Data Needs 

Physical and Chemical Properties. Table 4-2 summarizes many of the relevant physical and 

chemical properties of boron and selected boron compounds. There are adequate data for the physical 

and chemical properties of boron and boron compounds. No data needs are identified. 

Production, Import/Export, Use, Release, and Disposal. According to the Emergency 

Planning and Community Right-to-Know Act of 1986, 42 U.S.C. Section 11023, industries are required 

to submit substance release and off-site transfer information to the EPA. The TRI, which contains this 

information for 2006, became available in May of 2008. This database is updated yearly and should 

provide a list of industrial production facilities and emissions. 

Current data on the production volume and uses of boron and boron compounds are available and no 

further production data are necessary at this time (Alam et al. 2003; USGS 2008, 2009); however, a data 

need exists for disposal methods of boron-containing wastes. 

Environmental Fate. The only quantifiable mechanism that influences the fate of boron is soil 

adsorption (Rai et al. 1986). A data need exists for the adsorption and mobility of boron in soils low in 

aluminum oxide, since aluminum oxide content of soils is an important property of soil that will influence 

the mobility of boron (Bingham et al. 1971). 
 

 

 

 

 

 

 

 

 

 

 

 

BORON 156 

6. POTENTIAL FOR HUMAN EXPOSURE 

Bioavailability from Environmental Media. Boron compounds can be absorbed following 

inhalation of contaminated workplace air, ingestion of contaminated food, or through damaged skin 

(Draize and Kelley 1959; Wong et al. 1964). The most significant routes of exposure near hazardous 

waste sites are likely to be through drinking boron-contaminated water and ingestion of locally grown 

food (Beyer et al. 1983; Butterwick et al. 1989). A data need exists for the amount of boron that is 

bioavailable from environmentally relevant media, such as drinking water, food, and soil. 

Food Chain Bioaccumulation. Only one study was located where boron bioconcentration was 

actually measured (Tsui and McCart 1981). Future research may be helpful, but it appears that boron is 

not significantly bioconcentrated. There are no data on the biomagnification of boron in the food chain, 

but it is not likely that bioaccumulation is a major environmental concern. Therefore, there are no data 

needs at this time. 

Exposure Levels in Environmental Media. Reliable monitoring data for the levels of boron in 

contaminated media at hazardous waste sites are needed so that the information obtained on levels of 

boron in the environment can be used in combination with the known body burden of boron to assess the 

potential risk of adverse health effects in populations living in the vicinity of hazardous waste sites. 

Data on boron levels in surface water and soil are available (Butterwick et al. 1989; Eckel and Langley 

1988; EPA 1986b; Hall et al. 2004; Ordonez et al. 2003; Rope et al. 1988; USGS 1984). Data on boron 

concentration in drinking water are limited (Choi and Chen 1979; Davies 1990; McCabe et al. 1970; 

NIRS 1987; Waggott 1969). Boron concentrations in foods and beverages have been reported (Hunt et al. 

1991; Minoia et al. 1994; Rainey et al. 1999, 2002). Additional data on boron concentrations in air and 

food, and more recent data on boron concentrations in drinking water would be useful in estimating the 

exposure of humans to boron. 

Exposure Levels in Humans. Background levels of boron in human blood, urine, and hair have 

been reported (Alimonti et al. 1992; Culver et al. 1994a; Rosborg et al. 2003; Stokinger 1981). 

Additional data on blood and/or urine concentrations in individuals with potentially high exposure to 

boron would be useful in assessing the magnitude of human exposure. 

This information is necessary for assessing the need to conduct health studies on these populations. 
 

 

 

 

 

 

 

 

 

BORON 157 

6. POTENTIAL FOR HUMAN EXPOSURE 

Exposures of Children. Children are exposed to boron by the same routes as adults. Rainey et al. 

(2002) reported daily boron intakes of 0.75 and 0.99 mg for infants aged 0–6 and 7–11 months 

respectively. In children, 0.86 and 0.80 mg daily boron intakes were reported for 1–3 and 4–8 year olds, 

respectively. In male adolescents, 0.90 and 1.02 mg were reported for 9–13 and 14–18 year olds, 

respectively. In female adolescents, 0.83 and 0.78 mg were reported for 9–13 and 14–18 year olds, 

respectively. Meacham and Hunt (1994) reported a daily intake of 0.333 mg for infants (6–11 months) 

from baby foods and beverages. There do not appear to be any childhood-specific means to decrease 

exposure to boron. 

Boron intake from infant food was estimated to supply 47% of the 0.55 mg of daily boron to infants aged 

6–11 months and toddlers aged 2 years 0.54 mg; 38% from fruits and juices and 19% from milk and 

cheese (Hunt and Meacham 2001). Children may also be exposed to boron by breastfeeding mothers. 

Boron has been detected in breast milk with concentrations ranging from 10 to 100 μg/L, although higher

levels have been found in infant formulas (120 μg/L) and whole cow milk (280 μg/L) (Lopez-Garcia et al. 

2009). Another study from St. John’s, Newfoundland measured boron concentrations of lactating 

mothers’ milk for full-term infants to be 30 and 28 μg/L at 1 and 12 weeks postpartum, respectively. In 

lactating mothers’ milk for preterm infants boron concentrations were found to be 37 and 27 μg/L at 

1 and 12 weeks, respectively (Hunt et al. 2004). The concentration of boron was determined in archived 

milk collected (1980–1984) from lactating mothers of full-term, exclusively breastfed infants living in 

Houston, Texas. The results indicated that infants were supplied average concentrations of 42±6.5 μg/L 

at 1 month old and 35±6.5 μg/L at 4 months old via breast milk (Hunt et al 2005). Hunt et al. (2004, 

2005) indicated that boron concentrations over the first 4 months of lactating did not vary widely and 

were stable over time. The highest concentrations of boron detected in each study were 88 μg/L (Hunt et 

al. 2005) and 100 μg/L (Hunt et al. 2004). 

Child health data needs relating to susceptibility are discussed in Section 3.12.2, Identification of Data 

Needs: Children’s Susceptibility. 

Exposure Registries. No exposure registries for boron were located. This substance is not currently 

one of the compounds for which a sub-registry has been established in the National Exposure Registry. 

The substance will be considered in the future when chemical selection is made for sub-registries to be 

established. The information that is amassed in the National Exposure Registry facilitates the 

epidemiological research needed to assess adverse health outcomes that may be related to exposure to this 

substance. 
 

 

 

 

 

 

 

 

BORON 158 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.8.2 Ongoing Studies 

Ongoing studies pertaining to boron or boron compounds were identified in a search of the Federal 

Research in Progress database (FEDRIP 2009). A large comprehensive study on boron by C. Hunt at the 

United States Department of Agriculture in Grand Forks, North Dakota is collecting and analyzing dietary 

data and biochemical indices aimed at enhancing the quality of life through establishing mineral intakes, 

which support optimal bone health as well as general micronutrient roles in physiology and health. 

D. Evans at Columbia University Health Sciences, New York, New York is sponsored by the Institute of 

Environmental Health Sciences to investigate the use of low-toxicity pesticides such as baits, gels, and 

boric acid. The USDA Water Management Research Unit in Parlier, California is attempting to develop 

strategies for sustainable agronomic systems for water reuse and bioremediation of soils impacted by the 

use of saline water containing high concentrations of boron and trace elements. B. Hoenisch at Colombia 

University is funded by the National Science Foundation to investigate validation of the boron/calcium 

proxy for surface seawater pH and application to measure anthropogenic ocean acidification (FEDRIP 

2009). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 159 

7. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting, 

measuring, and/or monitoring boron, its metabolites, and other biomarkers of exposure and effect to 

boron. The intent is not to provide an exhaustive list of analytical methods. Rather, the intention is to 

identify well-established methods that are used as the standard methods of analysis. Many of the 

analytical methods used for environmental samples are the methods approved by federal agencies and 

organizations such as EPA and the National Institute for Occupational Safety and Health (NIOSH). Other 

methods presented in this chapter are those that are approved by groups such as the Association of 

Official Analytical Chemists (AOAC) and the American Public Health Association (APHA). 

Additionally, analytical methods are included that modify previously used methods to obtain lower 

detection limits and/or to improve accuracy and precision. 

7.1 BIOLOGICAL MATERIALS 

Methods for the determination of boron in biological materials are summarized in Table 7-1. Methods for 

the determination of boron in samples of toxicological interest have been summarized (Stokinger 1981; 

Van Ormer 1975). Total boron is usually determined after the material is digested or ashed. No 

techniques are available to quantitatively analyze for specific boron compounds in biological matrices 

(Culver et al. 1994a). The most common analytical procedure to analyze boron in biological materials 

involves digestion of the sample in hot acid or base, followed by analysis of the resulting solution by 

inductively coupled plasma-atomic emission spectrometry (ICP-AES) (Culver et al. 2001). 

Goullé et al. (2005) assessed inductively coupled plasma–mass spectrometry (ICP-MS) for detecting 

metals and metalloids in whole blood, plasma, urine, and hair. ICP-MS is a fast, sensitive method that 

requires a small sample size. Analysis required 0.4 mL of blood, plasma, or urine and 25 mg of hair. 

Usuda et al. (1998) noted that boron levels in urine can be influenced by dietary intake of boron and 

recommended that the intake of large amounts of boron-rich foods or drinks should be avoided if the 

boron status is being evaluated for possible environmental- or labor-related exposure. Xing et al (2008) 

suggested that creatinine-corrected, post-shift urine boron concentration can be used as a biomarker of 

human boron exposure in worker populations when monitored by ICP-MS. 

Colorimetric analysis can also be used to determine boron concentrations in biological samples; however, 

colorimetric procedures are more time-consuming and require more laboratory care and technical skill 
 

 

 

 

 

BORON 160 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Boron in Biological Materials 

Analytical Sample detection Percent 

Sample matrix Preparation method method limit recovery Reference 

Urine Dilution; direct analysis ICP-AES 6.24 μg/L 100.8– Usuda et al. 

104.2% 1998 

Whole blood, Dilution with purified ICP-MS 1.33 μg/L (blood) No data Goullé et al. 

plasma, urine water, acid, buffer, and 

butanol 

1.26 μg/L (plasma)

0.25 μg/L (urine) 

2005 

Hair Mineralization after ICP-MS 0.14 ng/mg No data Goullé et al. 

decontamination with 2005 

water/acetone 

Blood Ashed by oxygen in a Colorimetric <100 μg/L 84% at Hill and 

Parr bomb, dissolved carmine 5 μg/mL Smith 1959 

method 

Serum (borate) Deproteinized, allowed to Colorimetric Greater than 92–104% Baselt 1988 

react with reagent carmine endogenous levels, 

method which are 

<20 mg/L 

ICP-AES = inductively coupled plasma-atomic emission spectroscopy; ICP-MS = inductively coupled plasma-mass 

spectrometry 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 161 

7. ANALYTICAL METHODS 

(Culver et al. 2001). Spectrophotometric methods suffer from interferences from other elements (e.g., Al, 

Cu, Fe, Zn, and Mo), as well as pH (Sah and Brown 1997). 

Neutron activation analysis (NAA) is another analytical technique used to determine boron in biological 

samples. In NAA, the sample is bombarded with neutrons, and the element of interest is made 

radioactive. The amount of the element present in the sample is then determined by measurement of the 

radioactivity or radioactive decay products. This process involves 10B, which is a naturally occurring, 

stable isotope of boron that occurs with about 20% abundance. When 10B is bombarded with neutrons, it 

does not become radioactive, but results in a neutron-capture reaction, resulting in the emission of a 

α-particle and γ-photon. NAA methods for boron determination are based on the measurement of one of 

more of the products (α-particle and γ-photon), using techniques such as neutron activation mass 

spectrometry (NA-MS) or prompt γ-ray spectroscopy. An advantage of NAA is that it is a nondestructive 

method. However, the requirements of a neutron source and the abundance of 10B restrict its use (Culver 

et al. 2001; Sah and Brown 1997). 

7.2 ENVIRONMENTAL SAMPLES 

Methods for the determination of boron in environmental samples are summarized in Table 7-2. 

Boron is readily measured in multielement analyses of air, water, and solid waste samples by ICP-AES 

atomic emission spectroscopy, the method of choice for the determination of boron in modern practice. 

Although not multielement procedures, colorimetric cucumin and colorimetric carmine methods are still 

reliable methods for the determination of boron in water, air, and solid waste samples (APHA 1998b; 

1998c; EPA 1983). These colorimetric procedures provide adequate methods when ICP instrumentation 

is not available. Alkali fusion or wet digestion with hydrofluoric acid or a mixture of hydrofluoric acid 

and other acids are used to digest soils and other geological and silica-rich materials (Sah and Brown 

1997). A highly sensitive and selective method for determining boron at ng/dm3 levels was developed by 

Takahashi et al. (2008) by derivatization reaction of boron with reversed-phase partition highperformance liquid chromatography (HPLC) separation and ultraviolet spectrophotometric detection. A 

detection limit as low as 22 ng/dm3 was achieved without any preconcentration. No significant 

interference was observed in the determination of 16 μmol/dm3 of boron with the addition of nine metal 

ions (Al3+, CuI2+, Co2+, Fe2+, Fe3+, Ni2+, Mn2+, V5+, and Zn2+) at concentrations 100 times greater than that 

of boron (Takahashi et al. 2008). 
 

 

 

 

 

 

 

 

BORON 162 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Boron in Environmental Samples 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Air Collection on filter, hot NIOSH 0.0094 μg/L No data NIOSH 2003 

block/HCl/HNO3 digestion Method 7303 0.71 μg/sample

followed by dilution with water ICP-AES 

Air (boron Collection on filter, ashed, NIOSH 0.05 mg/ No data NIOSH 1994 

carbide) suspended in 2-propanol, Method 7506 sample 

redeposited on silver X-ray powder 

membrane filter diffraction 

Air (boron A known volume of air is OSHA 10 μg or No data OSHA 1989b 

trifluoride) drawn through a solution of Method 0.4 μg/mL of

ammonium fluoride; ID216SG solution 

fluoroborate ion is measured Fluoroborate 

using an ion specific electrode ion specific 

electrode 

Water Acidify, inject APHA 5 μg/L 115.46%a APHA 1998a 

Method 3120 27% RDSa 

ICP-AES 

Water Direct analysis APHA 0.2 μg 22.8% APHA 1998b 

Method 4500­ RSD 

B Colorimetric 

curcumin 

Water Ash, dissolve in acid APHA 2 μg 35.5% APHA 1998c 

Method 4500­ RSD 

B Colorimetric 

carmine 

Water Direct analysis EPA Method 0.1–1.0 mg/L 22.8% EPA 1983 

212.3 Colori­ (optimal range) RSD 

metric 

curcuminb 

Water Filter, acidify EPA Method 3 μg/L 115%a EPA 1994 

200.7 ICP­ 27% RSDa 

AES 

Water, Aqueous and solid matrices EPA Method 3.8 μg/L No data EPA 2000 

sediments, require acid digestion prior to 6010C ICPsolid wastes, analysis; pre-filtered, acidified AES 

sludges groundwater samples do not 

need acid digestion 

Water Direct analysis USGS-NWQL Applicable 5.8% RSD USGS 1989 

Method I- range: 10– 

1114 DCP­ 1,000 μg/L

AES 

Aquatic Nitric acid digestion followed USGS-NWQL Not calculable 95–96% USGS 1996a 

biological by treatment with 30% Method Bmaterial hydrogen peroxide 9001-95 ICPAES 
 

 

 

 

 

 

 

 

BORON 163 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Boron in Environmental Samples 

Sample 

matrix Preparation method 

Analytical 

method 

Sample 

detection limit 

Percent 

recovery Reference 

Water Acidify to a pH <2.0 with nitric 

acid 

USGS-NWQL 

Method I1472-95 ICPAES 

Method 

reporting limit: 

4 μg/L

91.6–109% USGS 1996b 

Water Filter, acidify USGS-NWQL 

Method I0.5 μg/L 70–103% USGS 1999 

2477-92 ICPAES 

Water Acidify, filter USGS-NWQL 

Method I4471-97 ICP13 μg/L 98% (average) 

USGS 1998 

OES 

a

Percent recovery and relative standard deviation were reported by NEMI (2007). b

Same method as APHA (1998b). 

APHA = American Public Health Association; DCP = direct current plasma; EPA = U.S. Environmental Protection 

Agency; ICP-AES = inductively coupled plasma-atomic emission spectroscopy; ICP-OES = inductively coupled 

plasma-optical emission spectroscopy; NIOSH = National Institute for Occupational Safety and Health; 

NWQL = National Water Quality Laboratory; OSHA = Occupational Safety and Health Administration; RSD = relative 

standard deviation; USGS = U.S. Geological Survey 
 

 

 

 

 

 

 

 

 

BORON 164 

7. ANALYTICAL METHODS 

Anthropogenic-derived boron concentrations can be effectively distinguished by the the measurement of 

the 10B to 11B isotopic ratio (Chetelat and Gaillardet 2005; Moore et al. 2008). The natural abundance of 

10B and 11B is specific to location, making anthropogenic boron isotopic ratios distinctly different than 

groundwater (Davidson and Bassett 1993). This allows utilization of the boron isotopic ratio to determine 

potential contamination in groundwater (Vengosh et al. 1994), river water (Chetelat and Gaillardet 2005), 

marine water (Xiao et al. 2007), and effluent (Kloppmann et al. 2008). 

7.3 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of boron is available. Where adequate information is not 

available, ATSDR, in conjunction with NTP, is required to assure the initiation of a program of research 

designed to determine the health effects (and techniques for developing methods to determine such health 

effects) of boron. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

7.3.1 Identification of Data Needs 

Analytical methods are available and are adequately sensitive to detect boron in biological materials (e.g., 

blood and urine) and in environmental samples (e.g., water, sediments, and air). No data needs are 

identified at this time. 
 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 165 

7. ANALYTICAL METHODS 

Methods for Determining Biomarkers of Exposure and Effect. 

Exposure. Boron can be determined sensitively and selectively by ICP-AES and ICP-MS in urine and 

blood (Goullé et al. 2005; Sah and Brown 1997; Usuda et al. 1998). Analytical methods with satisfactory 

sensitivity and precision are available to determine levels of boron in human tissues and body fluids. 

Effect. Existing methods are sensitive enough to measure background levels for boron in the population 

and levels at which biological effects occur. 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. ICP-AES is a satisfactory multielement method available for the determination of boron in 

water, air, and solid waste samples (APHA 1998a; EPA 1994; 2000; NIOSH 2003; USGS 1989, 1996a, 

1996b, 1999). Colorimetric procedures are as sensitive and precise, but are more labor intensive. 

Colorimetric procedures do provide adequate methods for those laboratories that do not have ICP 

instrumentation. An alternative method to the expensive and highly skill-dependent ICP-MS has been 

developed by boron derivatization and analysis by standard reverse-phase HPLC without sacrificing 

sensitivity (Takahashi et al. 2008). 

Sampling methodologies for very low level elemental substances like boron continue to pose problems 

such as nonrepresentative samples, insufficient sample volumes, contamination, and labor-intensive, 

tedious extraction and purification procedures (Green and Le Pape 1987). 

7.3.2 Ongoing Studies 

No ongoing studies pertaining to analytical methods for boron were identified in a search of the Federal 

Research in Progress database (FEDRIP 2009). 
 

BORON 166
 

7. ANALYTICAL METHODS 

This page is intentionally blank. 
 

 

 

 

 

 

 

 

 

 

 

 

BORON 167 

8. REGULATIONS, ADVISORIES, AND GUIDELINES
 

MRLs are substance specific estimates, which are intended to serve as screening levels, are used by 

ATSDR health assessors and other responders to identify contaminants and potential health effects that 

may be of concern at hazardous waste sites. 

ATSDR has derived an acute-duration inhalation MRL of 0.3 mg boron/m3 for boron. This MRL is based 

on a NOAEL of 0.8 mg boron/m3 for significantly increased nasal secretions in volunteers (Cain et al. 

2004) and an uncertainty factor of 3 (100.5 for human variability in the pharmacodynamic response to 

boron). 

ATSDR has derived an acute-duration oral MRL of 0.2 mg boron/kg/day for boron. This MRL is based 

on a NOAEL of 22 mg boron/kg/day associated with a LOAEL of 44 mg boron/kg/day for increased 

incidence of external, visceral, and cardiovascular malformations and reduced body weight in the fetuses 

of rabbits administered boric acid via gavage on gestation days 6–19 (Price et al. 1996b) and an 

uncertainty factor of 100 (10 for interspecies extrapolation and 10 for human variability). 

ATSDR has derived an intermediate-duration oral MRL of 0.2 mg boron/kg/day for boron. This MRL is 

based on a BMDL05 of 10.3 mg boron/kg/day estimated from fetal body weight data from two studies in 

which pregnant rats were exposed to boron in the diet on gestation days 0–20 (Heindel et al. 1992; Price 

et al. 1996a) and chemical-specific uncertainty factor of 66 (3.3 for toxicokinetic extrapolation from 

animals to humans, 3.16 for toxicodynamic extrapolation from animals to humans, 2.0 for variability in 

human toxicokinetics, and 3.16 for variability in human toxicodynamics). 

EPA has established an oral reference dose (RfD) of 0.2 mg/kg/day based on decreased fetal weight in a 

developmental study in Sprague-Dawley rats orally exposed to boric acid from gestation days 0 to 

20 (IRIS 2007). EPA has not established an inhalation reference concentration (RfC) for boron and 

compounds. 

Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), boron oxide, boric acid, borax, 

and sodium tetraborate are exempt from tolerances for pesticide chemicals in food (EPA 2007b); they are 

also listed as inerts of unknown toxicity (List 3) in EPA’s Categorized List of Inert Pesticide Ingredients 

(EPA 2004). 
 

BORON 168 

8. REGULATIONS, ADVISORIES, AND GUIDELINES 

The international and national regulations, advisories, and guidelines regarding boron in air, water, and 

other media are summarized in Table 8-1. 
 

 

 

 

 

 

 

BORON 169 

8. REGULATIONS, ADVISORIES, AND GUIDELINES 

Table 8-1. Regulations, Advisories and Guidelines Applicable to Boron and 

Boron Compounds
 

Agency Description Information Reference 

INTERNATIONAL 

Guidelines: 

IARC Carcinogenicity classification No data IARC 2006 

WHO Air quality guidelines No data WHO 2000 

Drinking water quality guidelines (boron) 0.5 mg/La WHO 2004 

NATIONAL 

Regulations and 

Guidelines: 

a. Air 

ACGIH TLV (8-hour TWA) ACGIH 2006 

Borate compounds, inorganic (borax, 2 mg/m3 

boric acid, and sodium tetraborate) 

Boron oxide 10 mg/m3 

TLV (ceiling) 

Boron tribromide 10 mg/m3 

Boron trifluoride 3 mg/m3 

STEL (15-minute TWA) 

Borate compounds, inorganic (borax, 6 mg/m3 

boric acid, and sodium tetraborate) 

AIHA Boron trifluoride AIHA 1999 

ERPG-1b 2 mg/m3 

ERPG-2b 30 mg/m3 

ERPG-3b 100 mg/m3 

EPA AEGL-1c (boron trifluoride) EPA 2007a 

10 minutes 2.5 mg/m3 

30 minutes 2.5 mg/m3 

60 minutes 2.5 mg/m3 

4 hours 2.5 mg/m3 

8 hours 2.5 mg/m3 

AEGL-2c (boron trifluoride) 

10 minutes 47 mg/m3 

30 minutes 47 mg/m3 

60 minutes 37 mg/m3 

4 hours 24 mg/m3 

8 hours 12 mg/m3 

AEGL-3c (boron trifluoride) 

10 minutes 140 mg/m3 

30 minutes 140 mg/m3 
 

 

 

 

 

 

 

 

 

BORON 170 

8. REGULATIONS, ADVISORIES, AND GUIDELINES 

Table 8-1. Regulations, Advisories and Guidelines Applicable to Boron and 

Boron Compounds
 

Agency Description Information Reference 

60 minutes 110 mg/m3 

4 hours 72 mg/m3 

8 hours 36 mg/m3 

NATIONAL (cont.) 

EPA Regulated toxic substances and threshold EPA 2008a 

quantities for accidental release prevention 40 CFR 68.130 

pursuant to Section 112(r) of the Clean Air 

Act 

Boron trichloride 5,000 pounds 

Boron trifluoride 5,000 pounds 

NIOSH REL NIOSH 2005 

Borax (10-hour TWA) 5 mg/m3 

Boron oxide (10-hour TWA) 10 mg/m3 

Boron tribromide (ceiling) 10 mg/m3 

Boron trifluoride (ceiling) 3 mg/m3 

Sodium tetraborate (10-hour TWA) 1 mg/m3 

IDLH (30-minute exposure) 

Borax No data 

Boron oxide 2,0000 mg/m3 

Boron tribromide No data 

Boron trifluoride 70 mg/m3 

Sodium tetraborate No data 

OSHA PEL for general industry OSHA 2006c 

Boron oxide, total dust (8-hour TWA) 15 mg/m3 29 CFR 1910.1000 

Boron trifluoride (ceiling) 3 mg/m3 

PEL for shipyard industry OSHA 2006a 

Boron oxide, total dust (8-hour TWA) 15 mg/m3 29 CFR 1915.1000 

Boron tribromide (8-hour TWA) 10 mg/m3 

Boron trifluoride (ceiling) 3 mg/m3 

PEL for construction industry OSHA 2006b 

Boron oxide, total dust (8-hour TWA) 

Boron tribromide (8-hour TWA) 

15 mg/m3 

10 mg/m3 

29 CFR 1926.55, 

Appendix A 

Boron trifluoride (ceiling) 3 mg/m3 

Threshold quantity of highly hazardous OSHA 2006d 

chemicals, toxics, and reactives 29 CFR 1910.119 

Boron trichloride 2,500 pounds 

Boron trifluoride 250 pounds 

b. Water 

EPA Drinking water contaminant candidate list EPA 1998 

Boron Yes 63 FR 10274 
 

 

 

 

 

 

BORON 171 

8. REGULATIONS, ADVISORIES, AND GUIDELINES 

Table 8-1. Regulations, Advisories and Guidelines Applicable to Boron and 

Boron Compounds
 

Agency Description Information Reference 

NATIONAL (cont.) 

EPA Drinking water standards and health 

advisories for boron 

EPA 2006 

1-day health advisory for a 10-kg child 4 mg/L 

10-day health advisory for a 10-kg child 0.9 mg/L 

DWEL 7 mg/L 

Lifetime 

10-4 Cancer risk 

1 mg/L 

No data 

National primary drinking water standards No data EPA 2003 

c. Food 

EPA Inert pesticide ingredients in pesticide 

products 

Borax, boric oxide, boric acid, and 

sodium tetraborate 

List 3d 

EPA 2004 

Tolerances and exemptions from 

tolerances for pesticide chemicals in food 

EPA 2007c 

40 CFR 180.101 

Borax, boron oxide, boric acid, and 

sodium tetraborate 

Yes 

FDA EAFUS FDA 2007 

Borax, boric acid, and sodium 

tetraborate 

Yese 

Indirect food additives: adhesives and 

components of coatings 

FDA 2006 

21 CFR 175.105 

Borax and boric acid Yes 

d. Other 

ACGIH 

EPA 

Carcinogenicity classification 

Borate compounds, inorganic (borax, 

boric acid, and sodium tetraborate) 

Carcinogenicity classification (boron and 

boron compounds) 

A4f 

No datag 

ACGIH 2006 

IRIS 2007 

RfC (boron and boron compounds) Not recommended 

RfD (boron and boron compounds) 0.2 mg/kg/day 

Superfund, emergency planning, and 

community right-to-know; effective date of 

toxic chemical release reporting 

EPA 2007b 

40 CFR 372.65 

Boron tribromide, boron trichloride, and 

boron trifluoride 

01/01/95 

Extremely hazardous substances and their 

threshold planning quantities 

Boron trichloride 500 pounds 

EPA 2008b 

40 CFR 355, 

Appendix A 

Boron trifluoride 500 pounds 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 172 

8. REGULATIONS, ADVISORIES, AND GUIDELINES 

Table 8-1. Regulations, Advisories and Guidelines Applicable to Boron and 

Boron Compounds
 

Agency Description Information Reference 

NATIONAL (cont.) 

NTP Carcinogenicity classification No data NTP 2005 

a

Provisional guideline value because calculated guideline value is below the level that can be achieved 

through practical treatment methods, source protection, etc.

b

ERPG-1 is the maximum airborne concentration below which nearly all individuals could be exposed for up to 1 hour 

without experiencing other than mild, transient health effects; ERPG-2 is the maximum airborne concentration below 

which nearly all individuals could be exposed for up to 1 hour without experiencing irreversible or other serious 

adverse effects; and ERPG-3 is the maximum airborne concentration below which nearly all individuals could be 

exposed for up to 1 hour without life-threatening health effects (AIHA 1999). c

AEGL-1 is the airborne concentration of a substance above which it is predicted that the general population, 

including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic nonsensory 

effects; AEGL-2 is the airborne concentration of a substance above which it is predicted that the general population, 

including susceptible individuals, could experience irreversible or other serious, long-lasting adverse health effects or 

an impaired ability to escape; and AEGL-3 is the airborne concentration of a substance above which it is predicted 

that the general population, including susceptible individuals, could experience life-threatening health effects or death 

(EPA 2007c). d

List 3: inerts of unknown toxicity 

e

The EAFUS list of substances contains ingredients added directly to food that FDA has either approved as food 

additives or listed or affirmed as GRAS. 

f

A4: not classifiable as a human carcinogen 

g

Data are inadequate for an assessment of human carcinogenic potential. 

ACGIH = American Conference of Governmental Industrial Hygienists; AEGL = Acute Exposure Guideline Levels; 

AIHA = American Industrial Hygiene Association; CFR = Code of Federal Regulations; DWEL = drinking water 

equivalent level; EAFUS = Everything Added to Food in the United States; EPA = Environmental Protection Agency; 

ERPG = Emergency Response Planning Guidelines; FDA = Food and Drug Administration; FR = Federal Register; 

GRAS = Generally Recognized As Safe; IARC = International Agency for Research on Cancer; IDLH = immediately 

dangerous to life or health; IRIS = Integrated Risk Information System; NIOSH = National Institute for Occupational 

Safety and Health; NTP = National Toxicology Program; OSHA = Occupational Safety and Health Administration; 

PEL = permissible exposure limit; REL = recommended exposure limit; RfC = inhalation reference concentration; 

RfD = oral reference dose; STEL = short-term expsoure limit; TLV = threshold limit values; TWA = time-weighted 

average; WHO = World Health Organization 
 

 

 

 

 

BORON 173 

9. REFERENCES
 

ACGIH. 2006. Boron. Threshold limit values for chemical substances and physical agents and 

biological exposure indices. Cincinnati, OH: American Conference of Governmental Industrial 

Hygienists, 14-15. 

Adinolfi M. 1985. The development of the human blood-CSF-brain barrier. Dev Med Child Neurol 

27(4):532-537. 

Adlercreutz H. 1995. Phytoestrogens: Epidemiology and a possible role in cancer protection. Environ 

Health Perspect Suppl 103(7):103-112. 

Agency for Toxic Substances and Disease Registry. 1989. Decision guide for identifying substancespecific data needs related to toxicological profiles; Notice. Agency for Toxic Substances and Disease 

Registry, Division of Toxicology. Fed Regist 54(174):37618-37634. 

AIHA. 1999. Boron trifluoride. Emergency response planning guidelines (ERPG). Fairfax, VA: 

American Industrial Hygiene Association. 

Akar D. 2007. Potential boron pollution in surface water, crop, and soil in the lower Buyuk Menderes 

Basin. Environ Eng Sci 24(9):1273-1279. 

Alam F, Evans F, Mani G, et al. 2003. Boron halides. Kirk-Othmer encyclopedia of chemical 

technology. John Wiley & Sons, Inc. 

http://www.mrw.interscience.wiley.com/emrw/9780471238966/kirk/article/boroalam.a01/current/pdf. 

March 11, 2009. 

Alimonti A, Fornarelli L, Coni E, et al. 1992. Assessment of trace element concentrations in human 

lungs of urban subjects. Microchem J 46(2):191-198. 

Allen BC, Strong PL, Price CJ, et al. 1996. Benchmark dose analysis of developmental toxicity in rats 

exposed to boric acid. Fundam Appl Toxicol 32(2):194-204. 

Allen GT, Blackford SH, Tabor VM, et al. 2001. Metals, boron, and selenium in Neosho madtom 

habitats in the Neosho River in Kansas, USA. Environ Monit Assess 66(1):1-21. 

Altman PL, Dittmer DS. 1974. Biological handbooks: Biology data book. Vol. III. 2nd ed. Bethesda, 

MD: Federation of American Societies for Experimental Biology, 1987-2008, 2041. 

Andersen ME, Krishnan K. 1994. Relating in vitro to in vivo exposures with physiologically based 

tissue dosimetry and tissue response models. In: Salem H, ed. Animal test alternatives: Refinement, 

reduction, replacement. New York: Marcel Dekker, Inc., 9-25. 

Andersen ME, Clewell HJ, Gargas ML, et al. 1987. Physiologically based pharmacokinetics and the risk 

assessment process for methylene chloride. Toxicol Appl Pharmacol 87(2):185-205 

APHA. 1998a. Method 3120 A. Introduction. Method 3120 B. Inductively coupled plasma (ICP) 

method. In: Clesceri LS, Greenberg AE, Eaton AD, eds. Standard methods for the examination of water 

and wastewater. 20th ed. Washington, DC: American Public Health Association. American Water 

Works Association. Water Environmental Federation, 3-37 to 3-43. 
 

 

 

 

 

 

 

 

BORON 174 

9. REFERENCES 

APHA. 1998b. Method 4500 BB. Curcumin method. In: Clesceri LS, Greenberg AE, Eaton AD, eds. 

Standard methods for the examination of water and wastewater. 20th ed. Washington, DC: American 

Public Health Association. American Water Works Association. Water Environmental Federation, 4-21 

to 4-22. 

APHA. 1998c. Method 4500 BC. Carmine method. In: Clesceri LS, Greenberg AE, Eaton AD, eds. 

Standard methods for the examination of water and wastewater. 20th ed. Washington, DC: American 

Public Health Association. American Water Works Association. Water Environmental Federation, 4-23. 

Arslan M, Topaktas M, Rencuzogullari E. 2008. The effects of boric acid on sister chromatid exchanges 

and chromosome aberrations in cultured human lymphocytes. Cytotechnology 56(2):91-96. 

Barber LB, Murphy SF, Verplanck PL, et al. 2006. Chemical loading into surface water along a 

hydrological, biogeochemical, and land use gradient: A holistic watershed approach. Environ Sci 

Technol 40(2):476-486. 

Barnes DG, Dourson M. 1988. Reference dose (RfD): Description and use in health risk assessments. 

Regul Toxicol Pharmacol 8(4):471-486. 

Barranco WT, Hudak PF, Eckhert CD. 2007. Evaluation of ecological and in vitro effects of boron on 

prostate cancer risk (United States). Cancer Causes Control 18:71-77. 

Baselt RC. 1988. Borate. In: Biological monitoring methods for industrial chemicals. 2nd ed. 

Littleton, MA: PSG Publishing Company, Inc., 48-50. 

Beckett WS, Oskvig R, Gaynor ME, et al. 2001. Association of reversible alopecia with occupational 

topical exposure to common borax-containing solutions (Comment in J Am Acad Dermatol 47(4):636­

637). J Am Acad Dermatol 44(4):599-602. 

Benson WH, Birge WJ, Dorough HW. 1984. Absence of mutagenic activity of sodium borate (borax) 

and boric acid in the Salmonella preincubation test. Environ Toxicol Chem 3:209-214. 

Berger GS, ed. 1994. Epidemiology of endometriosis. In: Endometriosis: Advanced management and 

surgical techniques. New York, NY: Springer-Verlag, 3-7. 

Bertine KK, Goldberg ED. 1971. Fossil fuel combustion and the major sedimentary cycle. Science 

173:233-235. 

Beyer KH, Bergfeld WF, Berndt WO, et al. 1983. Final report on the safety assessment of sodium borate 

and boric acid. J Am Coll Toxicol 2(7):87-125. 

Biggar JW, Fireman M. 1960. Boron adsorption and release by soils. Soil Sci Soc Proc 115-120. 

Bingham FT, Page AL, Coleman NT, et al. 1971. Boron adsorption characteristics of selected 

amorphous soils from Mexico and Hawaii. Soil Sci Am Proc 35:546-550. 

Butterwick L, de Oude N, Raymond K. 1989. Safety assessment of boron in aquatic and terrestrial 

environments. Ecotoxicol Environ Safety 17:339-371. 

Cain WS, Jalowayski AA, Kleinman M, et al. 2004. Sensory and associated reactions to mineral dusts: 

Sodium borate, calcium oxide, and calcium sulfate. J Occup Environ Hyg 1:222-236. 
 

 

 

 

 

 

 

 

 

 

BORON 175 

9. REFERENCES 

Cain WS, Jalowayski AA, Schmidt R, et al. 2008. Chemesthetic responses to airborne mineral dusts: 

Boric acid compared to alkaline materials. Int Arch Occup Environ Health 81:337-345. 

Chang BL, Robbins WA, Wei F, et al. 2006. Boron exposure in China: Exploring work and lifestyle 

factors to boron exposure. AAOHN J 54(10):435-443. 

Chao TC, Maxwell SM, Lyen K, et al. 1991a. Mass poisoning in Perak, Malaysia or the Tale of the Nine 

Emperor Gods and rat tail noodles. J Forensic Sci Soc 31(2):283-288. 

Chao TC, Maxwell SM, Wong SY. 1991b. An outbreak of aflatoxicosis and boric acid poisoning in 

Malaysia: A clinicopathological study. J Pathol 164(3):225-233. 

Chapin RE, Ku WW, Kenney MA, et al. 1997. The effects of dietary boron on bone strength in rats. 

Fundam Appl Toxicol 35(2):205-215. 

ChemIDplus. 2009. Boron and selected boron chemicals. ChemIDplus. Bethesda, MD: U.S. National 

Library of Medicine. http://sis.nlm.nih.gov/chemical.html. April 01, 2009. 

Cherrington JW, Chernoff N. 2002. Periods of vertebral column sensitivity to boric acid treatment in 

CD-1 mice in utero. Reprod Toxicol 16(3):237-243. 

Chetelat B, Gaillardet J. 2005. Boron isotopes in the Seine River, France: A probe of anthropogenic 

contamination. Environ Sci Technol 39(8):2486-2493. 

Choi WW, Chen KY. 1979. Evaluation of boron removal by adsorption on solids. Environ Sci Technol 

13(2):189-196. 

Clewell HJ, Andersen ME. 1985. Risk assessment extrapolations and physiological modeling. Toxicol 

Ind Health 1(4):111-131. 

Cotton FA, Wilkinson G, Murillo CA, et al., eds. 1999. Boron. In: Advanced inorganic chemistry. 6th 

ed. New York, NY: John Wiley & Sons, Inc., 131-174. 

Cozzolino D, Kwiatkowski MJ, Dambergs RG, et al. 2008. Analysis of elements in wine using near 

infrared spectroscopy and partial least squares regression. Talanta 74(4):711-716. 

Cui Y, Winton MI, Zhang Z, et al. 2004. Dietary boron intake and prostate cancer risk. Oncol Rep 

11:887-892. 

Culver BD, Shen PT, Taylor TH, et al. 1994a. The relationship of blood- and urine-boron exposure in 

borax-workers and usefulness of urine-boron as an exposure marker. Environ Health Perspect 102:133­

137. 

Culver BD, Smith RG, Brotherton RJ, et al. 1994b. Boron. In: Clayton GD, Clayton FE, eds. Patty's 

industrial hygiene and toxicology. Vol. II. Part F. 4th ed. New York, NY: John Wiley & Sons, Inc., 

4411-4448. 

Culver BD, Strong PL, Murray JF. 2001. Boron. In: Bingham E, Cohrssen B, Powell CH, eds. Patty's 

toxicology. Vol. 3. 5th ed. New York, NY: John Wiley & Sons, Inc., 519-582. 
 

 

 

 

 

 

 

BORON 176 

9. REFERENCES 

Davidson GR, Bassett RL. 1993. Application of boron isotopes for identifying contaminants such as fly 

ash leachate in groundwater. Environ Sci Technol 27(1):172-176. 

Davies K. 1990. Human exposure pathways to selected organochlorines and PCBs in Toronto and 

Southern Ontario. Adv Environ Sci Technol 23:525-540. 

Demerec M, Bertani G, Flint J. 1951. A survey of chemicals for mutagenic action on E. coli. American 

Naturalist 85:119-136. 

Deverel SJ, Millard SP. 1988. Distribution and mobility of selenium and other trace elements in shallow 

groundwater of the western San Joaquin Valley, California. Environ Sci Technol 22:697-702. 

Dieter MP. 1994. Toxicity and carcinogenicity studies of boric acid in male and female B6C3F1 mice. 

Environ Health Perspect Suppl 102(7):93-97. 

Dixon RL, Lee IP, Sherins RJ. 1976. Methods to assess reproductive effects of environmental 

chemicals: Studies of cadmium and boron administered orally. Environ Health Perspect 13:59-67. 

Dixon RL, Sherins RJ, Lee IP. 1979. Assessment of environmental factors affecting male fertility. 

Environ Health Perspect 30:53-68. 

Dourson M, Maier A, Meek B, et al. 1998. Boron tolerable intake: Re-evaluation of toxicokinetics for 

data-derived uncertainty factors. Biol Trace Elem Res 66:453-463. 

Draize JH, Kelley EA. 1959. The urinary excretion of boric acid preparations following oral 

administration and topical applications to intact and damaged skin of rabbits. Toxicol Appl Pharmacol 

1:267-276. 

Dunlop W. 1981. Serial changes in renal haemodynamics during normal human pregnancy. Br J Obstet 

Gynaecol 88(1):1-9. 

Eckel W, Langley WD. 1988. A background-based ranking technique for assessment of elemental 

enrichment in soils at hazardous waste sites. In: Superfund '88: Proceedings of the 9th National 

Conference, November 28-30, 1988, Washington, D.C. Silver Spring, MD: The Hazardous Materials 

Control Research Institute, 282-286. 

Ellenhorn MJ, Schonwald S, Ordog G, et al., eds. 1997. Ellenhorn's medical toxicology: Diagnosis and 

treatment of human poisoning. 2nd ed. Baltimore, MA: Williams & Wilkins, 106t, 162t, 1098-1100. 

Ellenhorn MJ, Barceloux DG. 1988. Medical toxicology: Diagnosis and treatment of human poisoning. 

New York, NY: Elsevier, 921-924. 

EPA. 1983. Method 212.3. Boron (colorimetric, curcumin). In: EPA methods and guidance for 

analysis of water. U.S. Environmental Protection Agency. 

http://web1.er.usgs.gov/nemi/method_pdf/5279.pdf. March 22, 2007. 

EPA. 1986a. Broad scan analysis of the FY82 national human adipose tissue survey specimens: Vol. I. 

Executive summary. Washington, DC: U.S. Environmental Protection Agency, Office of Toxic 

Substances. EPA560586035. 
 

 

 

 

 

 

 

 

 

 

BORON 177 

9. REFERENCES 

EPA. 1986b. Quality criteria for water. Washington, DC: U.S. Environmental Protection Agency, 

Office of Water Planning and Standards. EPA440586001. 

EPA. 1987. Toxic air pollutant/source crosswalk: A screening tool for locating possible sources 

emitting toxic air pollutants. Research Triangle Park, NC: U.S. Environmental Protection Agency, 

Office of Air Quality Planning and Standards. EPA450487023a. PB88161146. 

EPA. 1990. Interim methods for development of inhalation reference concentrations. Washington, DC: 

U.S. Environmental Protection Agency, Office of Health and Environmental Assessment, Office of 

Research and Development, Environmental Criteria and Assessment Office. EPA600890066A. 

EPA. 1993. Reregistration Eligibility Decision (RED). Boric acid and its sodium salts. Washington, 

DC: U.S. Environmental Protection Agency. EPA738F93006. 

EPA. 1994. Method 200.7. Determination of metals and trace elements in water and wastes by 

inductively coupled plasma-atomic emission spectrometry. In: EPA methods and guidance for analysis 

of water. U.S. Environmental Protection Agency. http://web1.er.usgs.gov/nemi/method_pdf/4690.pdf. 

March 22, 2007. 

EPA. 1997. Special report on environmental endocrine disruption: An effects assessment and analysis. 

Washington, DC: U.S. Environmental Protection Agency, Risk Assessment Forum. EPA630R96012. 

EPA. 1998. The drinking water contaminant candidate list. Washington, DC: U.S. Environmental 

Protection Agency. Fed Regist 63:10274. http://www.gpoaccess.gov/fr/index.html. April 11, 2007. 

EPA. 2000. Method 6010C. Inductively coupled plasma-atomic emission spectrometry. In: EPA 

methods and guidance for analysis of water. U.S. Environmental Protection Agency. 

http://web1.er.usgs.gov/nemi/method_pdf/4712.pdf. March 21, 2007. 

EPA. 2003. National primary drinking water regulations. Washington, DC: U.S. Environmental 

Protection Agency, Office of Ground Water and Drinking Water. EPA816F03016. 

http://www.epa.gov/safewater/mcl.html. March 07, 2006. 

EPA. 2004. Inert pesticide ingredients in pesticide products. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/opprd001/inerts/lists.html. April 11, 2007. 

EPA. 2005. Toxic chemical release inventory reporting forms and instructions: Revised 2004 version. 

Section 313 of the Emergency Planning and Community Right-to-Know Act (Title III of the Superfund 

Amendments and Reauthorization Act of 1986). U.S. Environmental Protection Agency. Office of 

Environmental Information. EPA260B05001. 

EPA. 2006. Drinking water standards and health advisories. Washington, DC: Office of Water, U.S. 

Environmental Protection Agency. EPA822R04005. http://epa.gov/waterscience/criteria/drinking/. 

April 11, 2007. 

EPA. 2007a. Boron trifluoride. Acute exposure guideline levels (AEGLs). Washington, DC: Office of 

Pollution Prevention and Toxics, U.S. Environmental Protection Agency. 

http://www.epa.gov/oppt/aegl/pubs/compiled.pdf. April 11, 2007. 
 

 

 

 

 

 

 

 

BORON 178 

9. REFERENCES 

EPA. 2007b. Tolerances and exemptions from tolerances for pesticide chemicals in food. Washington, 

DC: U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 180.101. 

http://www.epa.gov/epacfr40/chapt-I.info/chi-toc.htm. March 12, 2009. 

EPA. 2008a. Regulated toxic substances and threshold quantities for accidental release prevention. 

Washington, DC: U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 

68.130. http://edocket.access.gpo.gov/cfr_2008/julqtr/pdf/40cfr68.130.pdf. March 31, 2009.. 

EPA. 2008b. Superfund, emergency planning, and community right-to-know programs. Extremely 

hazardous substances and their threshold planning quantities. Washington, DC: U.S. Environmental 

Protection Agency. Code of Federal Regulations. 40 CFR 355, Appendix A. 

http://edocket.access.gpo.gov/cfr_2008/julqtr/pdf/40cfr355AppA.pdf. March 31, 2009. 

Fail PA, Chapin RE, Price CJ, et al. 1998. General, reproductive, developmental, and endocrine toxicity 

of boronated compounds. Reprod Toxicol 12(1):1-18. 

Fail PA, George JD, Seely JC, et al. 1991. Reproductive toxicity of boric acid in Swiss (CD-1) mice: 

Assessment using the continuous breeding protocol. Fundam Appl Toxicol 17(2):225-239. 

Farr LE, Konikowski T. 1963. The renal clearance of sodium pentaborate in mice and men. Clin Chem 

9(6):717-726. 

FDA. 2006. Indirect food additives: adhesives and components of coatings. Washington, DC: U.S. 

Food and Drug Administration. Code of Federal Regulations. 21 CFR 175.105. 

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm. April 11, 2007. 

FDA. 2007. Everything added to food in the United States (EAFUS). Washington, DC: U.S. Food and 

Drug Administration. http://vm.cfsan.fda.gov/~dms/eafus.html. April 11, 2007. 

FEDRIP. 2009. Boron and selected boron compounds. Federal Research in Progress database. 

Springfield, VA: National Technical Information Service. 

Ferrando AA, Green NR. 1993. The effect of boron supplementation on lean body mass, plasma 

testosterone levels, and strength in male bodybuilders. Int J Sport Nutr 3(2):140-149. 

Fisher RS, Freimuth HC. 1958. Blood boron levels in human infants. J Invest Dermatol 30:85-86. 

FNB/IOM. 2001. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, 

iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc (2000). A Report of the Panel 

on Micronutrients, subcommittees on upper reference levels of nutrients and of interpretation and uses of 

dietary reference intakes, and the standing committee on the scientific evaluation of dietary reference 

intakes. Food and Nutrition Board. Institute of Medicine. Washington, DC: National Academy Press, 

510-520. http://books.nap.edu/openbook.php?record_id=10026&page=R2. August 06, 2007. 

Fomon SJ. 1966. Body composition of the infant: Part I: The male reference infant. In: Falkner F, ed. 

Human development. Philadelphia, PA: WB Saunders, 239-246. 

Fomon SJ, Haschke F, Ziegler EE, et al. 1982. Body composition of reference children from birth to age 

10 years. Am J Clin Nutr 35(Suppl 5):1169-1175. 
 

 

 

 

 

 

BORON 179 

9. REFERENCES 

Fox KK, Cassani G, Facchi A, et al. 2002. Measured variation in boron loads reaching European sewage 

treatment works. Chemosphere 47(5):499-505. 

Fukuda R, Hirode M, Mori I, et al. 2000. Collaborative work to evaluate toxicity on male reproductive 

organs by repeated dose studies in rats. 24). Testicular toxicity of boric acid after 2- and 4-week 

administration periods. J Toxicol Sci 25:233-239. 

Gallardo-Williams MT, Chapin RE, King PE, et al. 2004. Boron supplementation inhibits the growth 

and local expression of IGF-1 in human prostate adenocarcinoma (LNCaP) tumors in nude mice. Toxicol 

Pathol 32:73-78. 

Garabrant DH, Bernstein L, Peters JM, et al. 1984. Respiratory and eye irritation from boron oxide and 

boric acid dusts. J Occup Med 26(8):584-586. 

Garabrant DH, Bernstein L, Peters JM, et al. 1985. Respiratory effects of borax dust. Br J Ind Med 

42:831-837. 

Giwercman A, Carlsen E, Keiding N, et al. 1993. Evidence for increasing incidence of abnormalities of 

the human testis: A review. Environ Health Perspect Suppl 101(2):65-71. 

Goldfrank LR, Flomenbaum NE, Lewin NA, et al. 1990. Goldfrank's toxicologic emergencies. 4th ed. 

Norwalk, CT: Appleton & Lange, 664-665. 

Goldfrank LR, Flomenbaum NE, Lewin NA, et al., eds. 2002. Goldfrank's toxicologic emergencies. 7th 

ed. New York, NY: McGraw-Hill, 1282, 1289-1290, 1134. 

Gonzales M, Shah V, Bobelu A, et al. 2004. Concentrations of surface-dust metals in Native American 

jewelry-making homes in Zuni Pueblo, New Mexico. Arch Environ Health 59(5):245-249. 

Gordon AS, Prichard JS, Freedman MH. 1973. Seizure disorders and anemia associated with chronic 

borax intoxication. Can Med Assoc J 108:719-721, 724. 

Goullé JP, Mahieu L, Castermant J, et al. 2005. Metal and metalloid multi-elementary ICP-MS 

validation in whole blood, plasma, urine and hair. Forensic Sci Int 153(1):39-44. 

Graedel TE. 1978. Inorganic elements, hydrides, oxides and carbonates. In: Chemical compounds in 

the atmosphere. New York, NY: Academic Press, 35-49. 

Green DR, Le Pape D. 1987. Stability of hydrocarbon samples on solid-phase extraction columns. Anal 

Chem 59:699-703. 

Griffin RA, Burau RG. 1974. Kinetic and equilibrium studies of boron desorption from soil. Soil Sci 

Soc Am Proc 38:892-897. 

Guzelian PS, Henry CJ, Olin SS, eds. 1992. Similarities and differences between children and adults: 

Implications for risk assessment. Washington, DC: International Life Sciences Institute Press. 

Hall LW, Killen WD, Anderson RD, et al. 2004. Analysis of historical salinity and boron surface water 

monitoring data from the San Joaquin river watershed: 1985-2002. Environ Monit Assess 95(1-3):125­

151. 
 

 

 

 

 

 

BORON 180 

9. REFERENCES 

Harris MA, Chapin RE, Lockhart AC, et al. 1992. Assessment of short-term reproductive and 

developmental toxicity screen. Fundam Appl Toxicol 19(2):186-196. 

Haworth S, Lawlor T, Mortelmans K, et al. 1983. Salmonella mutagenicity test results for 250 

chemicals. Environ Mutagen 5(Suppl 1):3-142. 

HazDat. 2007. Boron. HazDat Database: ATSDR’s Hazardous Substance Release and Health Effects 

Database. Atlanta, GA: Agency for Toxic Substances and Disease Registry. 

http://www.atsdr.cdc.gov/hazdat.html. April 23, 2007. 

Heindel JJ, Price CJ, Field EA, et al. 1992. Developmental toxicity of boric acid in mice and rats. 

Fundam Appl Toxicol 18(2):266-277. 

Heindel JJ, Price CJ, Schwetz BA. 1994. The developmental toxicity of boric acid in mice, rats, and 

rabbits. Environ Health Perspect Suppl 102(7):107-112. 

Hill WH, Smith RC. 1959. Analysis of blood for boron. Am Ind Hyg Assoc J 20:131-133. 

Hoel DG, Davis DL, Miller AB, et al. 1992. Trends in cancer mortality in 15 industrialized countries, 

1969-1986. J Natl Cancer Inst 84(5):313-320. 

Hollis JF, Keren R, Gal M. 1988. Boron release and sorption by fly ash as affected by pH and particle 

size. J Environ Qual 17:181-184. 

Howe PD. 1998. A review of boron effects in the environment. Biol Trace Elem Res 66(1-3):153-166. 

HSDB. 2009. Boron and selected boron chemicals. Hazardous Substances Data Bank. National Library 

of Medicine. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB. April 01, 2009. 

Hu X, Wegman DH, Eisen EA, et al. 1992. Dose related acute irritant symptom responses to 

occupational exposure to sodium borate dusts. Br J Ind Med 49(10):706-713. 

Hubbard SA. 1998. Comparative toxicology of borates. Biol Trace Elem Res 66:343-357. 

Hunt CD, Meacham SL. 2001. Aluminum, boron, calcium, copper, iron, magnesium, manganese, 

molybdenum, phosphorus, potassium, sodium, and zinc: Concentrations in common Western food and 

estimated daily intakes by infants, toddlers, and male and female adolescents, adults, and seniors in the 

United States. J Am Diet Assoc 101:1058-1060. 

Hunt CD, Butte NF, Johnson, LK. 2005. Boron concentrations in milk from mothers of exclusively 

breast-fed healthy full-term infants are stable during the first four months of lactation. J Nutr 

135(10):2383-2386. 

Hunt CD, Friel JK, Johnson LK. 2004. Boron concentrations in milk from mothers of full-term and 

premature infants. Am J Clin Nutr 80(5):1327-1333. 

Hunt CD, Shuler TR, Mullen LM. 1991. Concentration of boron and other elements in human foods and 

personal-care products. J Am Diet Assoc 91(5):558-568. 
 

 

 

 

 

 

BORON 181 

9. REFERENCES 

IARC. 2006. Agents reviewed by the IARC monographs. Volumes 1–96. Lyon, France: International 

Agency for Research on Cancer. http://monographs.iarc.fr/ENG/Classification/index.php. April 11, 

2007. 

Imbus HR, Cholak J, Miller LH, et al. 1963. Boron, cadmium, chromium, and nickel in blood and urine. 

Arch Environ Health 6:286-295. 

IRIS. 2007. Boron and boron compounds. Washington, DC: Integrated Risk Information System. U.S. 

Environmental Protection Agency. http://www.epa.gov/iris/subst/index.html. April 11, 2007. 

Ishii Y, Fujizuka N, Takahashi T, et al. 1993. A fatal case of acute boron poisoning. J Toxicol Clin 

Toxicol 31(2):345-352. 

Jackson RE, Reddy KJ. 2007. Trace element chemistry of coal bed natural gas produced water in the 

Powder River Basin, Wyoming. Environ Sci Technol 41(17):5953-5959. 

Jansen JA, Anderson J, Schou JS. 1984b. Boric acid single dose pharmacokinetics after intravenous 

administration to man. Arch Toxicol 55:64-67. 

Jansen JA, Schou JS, Aggerback B. 1984a. Gastro-intestinal absorption and in vitro release of boric acid 

from water-emulsifying ointments. Food Chem Toxicol 22:49-53. 

Jansen LH. 2003. Boron, elemental. In: Kirk-Othmer encyclopedia of chemical technology. John 

Wiley & Sons, Inc. 

http://www.mrw.interscience.wiley.com/emrw/9780471238966/kirk/article/borojans.a01/current/pdf. 

March 11, 2009. 

Jensen AA. 2009. Risk assessment of boron in glass wool insulation. Environ Sci Pollut Res 16:73-78. 

Johanson CE. 1980. Permeability and vascularity of the developing brain: Cerebellum vs cerebral 

cortex. Brain Res 190(1):3-16. 

Keren R, Mezuman U. 1981. Boron adsorption by clay minerals using a phenomenological equation. 

Clays Clay Miner 29:198-204. 

Keren R, Gast RG, Bar-Yosef B. 1981. pH-dependent boron adsorption by Na-montmorillonite. Soil Sci 

Soc Am J 45:45-48. 

Kloppmann W, Van Houtte E, Picot G, et al. 2008. Monitoring reverse osmosis treated wastewater 

recharge into a coastal aquifer by environmental isotopes (B, Li, O, H). Environ Sci Technol 

14(23):8759-8765. 

Koc C. 2007. Effects on environment and agriculture of geothermal wastewater and boron pollution in 

Great Menderes Basin. Environ Monit Assess 125(1-3):377-388. 

Komori M, Nishio K, Kitada M, et al. 1990. Fetus-specific expression of a form of cytochrome P-450 in 

human livers. Biochemistry 29(18):4430-4433. 

Korkmaz M, Uzgoren E, Bakirdere S, et al. 2007. Effects of dietary boron on cervical cytopathology and 

on micronucleus frequency in exfoliated buccal cells. Environ Toxicol 22(1):17-25. 
 

 

 

 

 

 

 

 

 

BORON 182 

9. REFERENCES 

Krishnan K, Andersen ME. 1994. Physiologically based pharmacokinetic modeling in toxicology. In: 

Hayes AW, ed. Principles and methods of toxicology. 3rd ed. New York, NY: Raven Press, Ltd., 149­

188. 

Krishnan K, Anderson ME, Clewell HJ, et al. 1994. Physiologically based pharmacokinetic modeling of 

chemical mixtures. In: Yang RSH, eds. Toxicology of chemical mixtures. New York, NY: Academic 

Press, 399-437. 

Krutzen E, Olofsson P, Back SE, et al. 1992. Glomerular filtration rate in pregnancy: a study in normal 

subjects and in patients with hypertension, preeclampsia and diabetes. Scand J Clin Lab Invest 

52(5):387-392. 

Krystofiak SP, Schaper MM. 1996. Prediction of an occupational exposure limit for a mixture on the 

basis of its components: Application to metalworking fluids. Am Ind Hyg Assoc J 57(3):239-244. 

Ku WW, Chapin RE, Moseman RF, et al. 1991. Tissue disposition of boron in male Fischer rats. 

Toxicol Appl Pharmacol 111:145-151. 

Ku WW, Chapin RE, Wine RN, et al. 1993a. Testicular toxicity of boric acid (BA): Relationship of 

dose to lesion development and recovery in the F344 rat. Reprod Toxicol 7(4):305-319. 

Ku WW, Shih LM, Chapin RE. 1993b. The effects of boric acid (BA) on testicular cells in culture. 

Reprod Toxicol 7:321-331. 

Kudo S, Tanase H, Yamasaki M, et al. 2000. Collaborative work to evaluate toxicity on male 

reproductive organs by repeated dose studies in rats. A comparative 2- and 4-week repeated oral dose 

testicular toxicity study of boric acid in rats. J Toxicol Sci 25:223-232. 

Landolph JR. 1985. Cytotoxicity and negligible genotoxicity of borax and borax ores to cultured 

mammalian cells. Am J Ind Med 7:31-43. 

Lang FJ, Bingham FT, Hendrix FF, et al. 1986. Boron deposition on soil and native vegetation from 

geothermal emissions. J Environ Qual 15(3):260-265. 

Lee IP, Sherins RJ, Dixon RL. 1978. Evidence for induction of germinal aplasia in male rats by 

environmental exposure to boron. Toxicol Appl Pharmacol 45:577-590. 

Leeder JS, Kearns GL. 1997. Pharmcogenetics in pediatrics: Implications for practice. Pediatr Clin 

North Am 44(1):55-77. 

Leung H. 1993. Physiologically-based pharmacokinetic modeling. In: Ballentyne B, Marrs T, Turner P, 

eds. General and applied toxicology. Vol. 1. New York, NY: Stockton Press, 153-164. 

Lide DR. 2008. CRC handbook of chemistry and physics. 2007-2008. 86th ed. Boca Raton, FL: CRC 

Press. Taylor & Francis Group, 4-6 to 4-7. 

Linden CH, Hall AH, Kulig KW, et al. 1986. Acute ingestions of boric acid. Clin Toxicol 24:269-279. 

Litovitz TL, Klein-Schwartz W, Oderda GM, et al. 1988. Clinical manifestations of toxicity in a series 

of 784 boric acid ingestions. Am J Emerg Med 6:209-213. 
 

 

 

 

 

 

 

 

BORON 183 

9. REFERENCES 

Liu P, Hu W, Wei FS, et al. 2006a. Effect of boron on human semen quality. Chin J Public Health 

22:940-942. 

Liu P, Hu W, Gooping W, et al. 2006b. Effect of occupational exposure to boron on the sperm quality of 

males. Chin J Ind Occup Dis 24:167-169. 

Livingston AL. 1978. Forage plant estrogens. J Toxicol Environ Health 4(2-3):301-324. 

Locatelli C, Minoia C, Tonini M, et al. 1987. Human toxicology of boron with special reference to boric 

acid poisoning. G Ital Med Lav 9:141-146. 

Lopez-Garcia I, Vinas P, Romero-Romero R, et al. 2009. Preconcentration and determination of boron 

in milk, infant formula, and honey samples by solid phase extraction-electrothermal atomic absorption 

spectrometry. Spectrochim Acta Part B 64B(2):179-183. 

Lowe TP, Day DD. 2002. Metal concentrations in zebra mussels and sediments from embayments and 

riverine environments of eastern Lake Erie, southern Lake Ontario, and the Niagara River. Arch Environ 

Contam Toxicol 43(3):301-308. 

Matthijs E, Holt MS, Kiewiet A, et al. 1999. Environmental monitoring for linear alkylbenzene 

sulfonate, alcohol ethoxylate, alcohol ethoxy sulfate, alcohol sulfate, and soap. Environ Toxicol Chem 

18(11):2634-2644. 

Maurer JK, Molai A, Parker RD, et al. 2001. Pathology of ocular irritation with bleaching agents in the 

rabbit low-volume eye test. Toxicol Pathol 29(3):308-319. 

Mayr U, Butsch A, Schneider S. 1992. Validation of two in vitro test systems for estrogenic activities 

with zearalenone, phytoestrogens and cereal extracts. Toxicology 74(2-3):135-149. 

McCabe LJ, Symons JM, Lee RD, et al. 1970. Survey of community water supply systems. J Am Water 

Work Assoc 62:670-687. 

Meacham S, Hunt CD. 1994. Boron content of commercial baby foods and beverages typically 

consumed by infants. FASEB J 8(4-5):A430. 

Mezuman U, Keren R. 1981. Boron adsorption by soils using a phenomenological equation. Soil Sci 

Soc Am J 45:722-726. 

Minoia C, Sabbioni E, Ronchi A, et al. 1994. Trace element reference values in tissues from inhabitants 

of the European Community. IV. Influence of dietary factors. Sci Total Environ 141:181-195. 

Moore SJ, Bassett RL, Liu B, et al. 2008. Geochemical tracers to evaluate hydrogeologic controls on 

river salination. Ground Water 46(3):489-501. 

Morselli PL, Franco-Morselli R, Bossi L. 1980. Clinical pharmacokinetics in newborns and infants: 

Age-related differences and therapeutic implications. Clin Pharmacokin 5(6):485-527. 

Moseman RF. 1994. Chemical disposition of boron in animals and humans. Environ Health Perspect 

102:113-117. 
 

 

 

 

BORON 184 

9. REFERENCES 

Mumma RO, Raupach DC, Waldman JP, et al. 1984. National survey of elements and other constituents 

in municipal sewage sludges. Arch Environ Contam Toxicol 13:75-83. 

Naderi AS, Palmer BF. 2006. Successful treatment of a rare case of boric acid overdose with 

hemodialysis. Am J Kidney Dis 48(6):95-97. 

NAS/NRC. 1989. Report of the oversight committee. In: Biologic markers in reproductive toxicology. 

Washington, DC: National Academy of Sciences, National Research Council, National Academy Press, 

15-35. 

NEMI. 2007. Boron and selected boron compounds. National Environmental Methods Index. U.S. 

Environmental Protection Agency. U.S. Geological Survey. http://www.nemi.gov. August 06, 2007. 

Nielsen FH, Hunt CD, Muller LM, et al. 1987. Effect of dietary boron on mineral, estrogen, and 

testosterone metabolism in postmenopausal women. FASEB Monogr 1:394-397. 

NIH. 2004. Boric acid, sodium borate decahydrate (borax), and sodium tetraborate anhydrous. 

Household products database. National Institutes of Health. U.S. National Library of Medicine. 

http://hpd.nlm.nih.gov/ingredients.htm. March 13, 2009. 

NIOSH. 1994. Boron carbide. Method 7506. NIOSH manual of analytical methods (NMAM). 4th ed. 

National Institute for Occupational Safety and Health. http://www.cdc.gov/niosh/nmam/pdfs/7506.pdf. 

March 14, 2007. 

NIOSH. 2003. Method 7303. Elements by ICP. (Hot block/HCl/HNO3 digestion). In: NIOSH manual 

of analytical manual. (NMAM). National Institute for Occupational Safety and Health. 

http://www.cdc.gov.niosh/nmam/pdfs/7303.pdf. March 14, 2007. 

NIOSH. 2005. NIOSH pocket guide to chemical hazards. Boron oxide. Atlanta, GA: National Institute 

for Occupational Safety and Health, Centers for Disease Control and Prevention. 

http://www.cdc.gov/niosh/npg/. April 11, 2007. 

NIOSH. 2007. Boron compounds. International chemical safety cards (ICSCs): U.S. National Version. 

National Institute for Occupational Safety and Health. http://www.cdc.gov/niosh/ipcs/nicstart.html. 

March 14, 2007. 

NIRS. 1987. National inorganics and radionuclides survey. Distribution tables. Cincinnati, OH: U.S. 

Environmental Protection Agency, Office of Drinking Water. 

NOES. 1989. National Occupational Exposure Survey. Cincinnati, OH: National Institute of 

Occupational Safety and Health. October 18, 1989. 

NOHS. 1989. National Occupational Hazard Survey. National Institute of Occupational Safety and 

Health, Cincinnati, OH. October 18, 1989. 

Nolte J. 1988. Pollution source analysis of river water and sewage sludge. Environ Technol Lett 9:857­

868. 

Nomiyama T, Omae K, Uemura T, et al. 1995. No-observed-effect level of diborane on the respiratory 

organs of male mice in acute and subacute inhalation experiments. Sangyo Eiseigaku Zasshi 37(3):157­

160. 
 

 

 

 

 

 

 

 

 

 

BORON 185 

9. REFERENCES 

Nriagu JO. 1979. Copper in the atmosphere and precipitation. In: Nriagu JO, ed. Copper in the 

environment. Part I: Ecological cycling. New York, NY: John Wiley and Sons, Inc., 43-67. 

NRC. 1993. Pesticides in the diets of infants and children. Washington, DC: National Research 

Council. National Academy Press. PB93216091. 

NTP. 1987. National Toxicology Program--technical report series no. TR324 on the toxicology and 

carcinogenesis studies of boric acid (CAS No. 10043-35-3) in B6C3F1 mice (feed studies). Research 

Triangle Park, NC: U.S. Department of Health and Human Services, Public Health Service, National 

Institutes of Health. NIH Publication No. 88-2580. 

NTP. 1990. National Toxicology Program. Final report on the reproductive toxicity of boric acid in CD1-Swiss mice. National Institute of Environmental Health Sciences. NTP Report No. 90-105. 

NTP. 1991. Final report on the developmental toxicity of boric acid (CAS No. 10043-35-3) in New 

Zealand white rabbits. Research Triangle Park, NC: U.S. Department of Health and Human Services, 

Public Health Service, National Toxicology Program. PB92129550. 

NTP. 2005. Report on carcinogens. 11th ed. Research Triangle Park, NC: U.S. Department of Health 

and Human Services, Public Health Service, National Toxicology Program. http://ntpserver.niehs.nih.gov/ntp/roc/toc11.html. March 08, 2006. 

Nusier M, Bataineh HN. 2005. Effect of boric acid on fertility, aggressiveness and sex behaviour in male 

rats. Asian J Chem 17(4):2579-2588. 

Odunola OA. 1997. Individual and combined genotoxic response to boric acid and aflatoxin B1 in 

Escherichia coli PQ37. East Afr Med J 74(8):499-502. 

Ordonez A, Loredo J, De Miguel E, et al. 2003. Distribution of heavy metals in the street dusts and soils 

of an industrial city in northern Spain. Arch Environ Contam Toxicol 44:160-170. 

OSHA. 1989. Method ID216SG. Boron trifluoride (BF3). Occupational Safety and Health 

Administration. http://www.osha.gov/dts/sltc/methods/partial/id216sg/id216sg.html. March 14, 2007. 

OSHA. 2006a. Air contaminants. Occupational safety and health standards for shipyard employment. 

Washington, DC: Occupational Safety and Health Administration. Code of Federal Regulations. 29 

CFR 1915.1000. http://www.osha.gov/comp-links.html. April 11, 2007. 

OSHA. 2006b. Gases, vapors, fumes, dusts, and mists. Safety and health regulations for construction. 

Washington, DC: Occupational Safety and Health Administration. Code of Federal Regulations. 29 

CFR 1926.55, Appendix A. http://www.osha.gov/comp-links.html. April 11, 2007. 

OSHA. 2006c. Limits for air contaminants. Occupational safety and health standards. Washington, DC: 

Occupational Safety and Health Administration. Code of Federal Regulations. 29 CFR 1910.1000. 

http://www.osha.gov/comp-links.html. April 11, 2007. 

OSHA. 2006d. List of highly hazardous chemicals, toxics, and reactives. Occupational safety and health 

standards. Washington, DC: Occupational Safety and Health Administration. Code of Federal 

Regulations. 29 CFR 1910.119. http://www.osha.gov/comp-links.html. April 11, 2007. 
 

 

 

 

 

BORON 186 

9. REFERENCES 

O'Sullivan K, Taylor M. 1983. Chronic boric acid poisoning in infants. Arch Dis Child 58:737-739. 

Owen GM, Brozek J. 1966. Influence of age, sex and nutrition on body composition during childhood 

and adolescence. In: Falkner F, ed. Human development. Philadelphia, PA: WB Saunders, 222-238. 

Ozturkcan S, Dundar R, Katilmus H, et al. 2008. The ototoxic effect of boric acid solutions applied into 

the middle ear of guinea pigs. Eur Arch Otorhinolaryngol [epub ahead of print]. 

Pahl MV, Culver BD, Strong PL, et al. 2001. The effect of pregnancy on renal clearance of boron in 

humans: A study based on normal dietary intake of boron. Toxicol Sci 60(2):252-256. 

Parks WL, White JL. 1952. Boron retention by clay and humus systems saturated with various cations. 

Soil Sci Soc Proc 16:298-300. 

Price CJ, Marr MC, Myers CB, et al. 1996b. The developmental toxicity of boric acid in rabbits. 

Fundam Appl Toxicol 34(2):176-187. 

Price CJ, Strong PL, Marr MC, et al. 1996a. Developmental toxicity NOAEL and postnatal recovery in 

rats fed boric acid during gestation. Fundam Appl Toxicol 32:179-193. 

Price CJ, Strong PL, Murray FJ, et al. 1998. Developmental effects of boric acid in rats related to 

maternal blood boron concentrations. Biol Trace Elem Res 66:359-372. 

Rai D, Zachara JM, Schwab AP, et al. 1986. Chemical attenuation rates, coefficients, and constants in 

leachate migration. Vol. 1. A critical review. Palo Alto, CA: Electric Power Research Institute, 

Research Project 2198-1. 

Rainey CJ, Nyquist LA, Christensen RE, et al. 1999. Daily boron intake from the American diet. J Am 

Diet Assoc 99(3):335-340. 

Rainey CJ, Nyquist LA, Coughlin JR, et al. 2002. Dietary boron intake in the United States: CSFII 

1994-1996. J Food Comp Anal 15:237-250. 

Restuccio A, Mortensen ME, Kelley MT. 1992. Fatal ingestion of boric acid in an adult. Am J Emerg 

Med 10(6):545-547. 

Rope SK, Arthur WJ, Craig TH, et al. 1988. Nutrient and trace elements in soil and desert vegetation of 

southern Idaho. Environ Monit Assess 10:1-24. 

Rosborg I, Nihlgard B, Gerhardsson L. 2003. Hair element concentrations in females in one acid and one 

alkaline area in southern Sweden. Ambio 32(7):440-446. 

RTECS. 2007. Boron. Registry of Toxic Effects on Chemical Substances. National Institute of 

Occupational Safety and Health. MDL Information Systems, Inc. May 7, 2007. 

Ruth JH. 1986. Odor threshold and irritation levels of several chemical substances: A review. Am Ind 

Hyg Assoc J 47:142-151. 

Sah RN, Brown PH. 1997. Boron determination: A review of analytical methods. Microchem J 56:285­

304. 
 

 

 

 

 

 

BORON 187 

9. REFERENCES 

Sakata M. 1987. Relationship between adsorption of arsenic (III) and boron by soil and soil properties. 

Environ Sci Technol 21:1126-1130. 

Sayli BS. 1998a. An assessment of fertility in boron-exposed Turkish subpopulations. Evidence that 

boron has no effect on human reproduction. Biol Trace Elem Res 66:409-422. 

Sayli BS. 1998b. The sex ratio of offspring of people exposed to boron. Reprod Toxicol 12(6):673-674. 

Sayli BS. 2003. Low frequency of infertility among workers in a borate processing facility. Biol Trace 

Elem Res 93:19-29. 

Sayli BS, Tuccar E, Elhan AH. 1998. An assessment of fertility in boron-exposed Turkish 

subpopulations. Reprod Toxicol 12(3):297-304. 

Schillinger BM, Berstein M, Goldberg LA, et al. 1982. Boric acid poisoning. J Am Acad Dermatol 

7:667-673. 

Schou JS, Jansen JA, Aggerbeck B. 1984. Human pharmacokinetics and safety of boric acid. Arch 

Toxicol Suppl 7:232-235. 

Schubert DM, Brotherton, RJ. 2006. Boron: Inorganic chemistry. In: Encyclopedia of inorganic 

chemistry. John Wiley & Sons, Inc. 

http://mrw.interscience.wiley.com/emrw/9780470862100/eic/article/ia025/current/pdf. March 11, 2009. 

Seal BS, Weeth HJ. 1980. Effect of boron in drinking water on the male laboratory rat. Bull Environ 

Contam Toxicol 25:782-789. 

Setchell BP, Waites GMH. 1975. The blood-testis barrier. In: Creep RO, Astwood EB, Geiger SR, eds. 

Handbook of physiology: Endocrinology V. Washington, DC: American Physiological Society, 143­

172. 

Settimi L, Elovaara E, Savolainen H. 1982. Effects of extended peroral borate ingestion on rat liver and 

brain. Toxicol Lett 10:219-223. 

Sittig M. 1985. Handbook of toxic and hazardous chemicals and carcinogens. 2nd ed. Park Ridge, NJ: 

Noyes Publications, 137-142. 

Smyth HF, Carpenter CP, Weil CS, et al. 1969. Range-finding toxicity data: List VII. Am Ind Hyg 

Assoc J 30:470-476. 

SRI. 2008. 2008 Directory of chemical producers. Menlo Park, CA: SRI Consulting, 453, 851. 

Stewart NJ, McHugh TP. 1990. B. Borates. In: Haddad LM, Winchester JF, eds. Clinical management 

of poisoning and drug overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Company, 1447-1451. 

Stokinger HE. 1981. Boron. In: Clayton GD, Clayton FE, eds. Patty's industrial hygiene and 

toxicology. Vol. 2B. Toxicology. 3rd ed. New York, NY: John Wiley and Sons, 2978-3005. 

Sturgiss SN, Wilkinson R, Davison JM. 1996. Renal reserve during human pregnancy. Am J Physiol 

271(40):F16-F20. 
 

 

 

 

 

 

 

 

 

 

BORON 188 

9. REFERENCES 

Tagawa T, Kono K, Dote T, et al. 2000. Pharmacokinetics and effects after intravenous administration of 

high-dose boron to rat. Int Arch Occup Environ Health 73:S98-S100. 

Takahashi T, Yawata S, Hoshino H. 2008. Determination of boron in water samples at nanograms per 

cubic decimeter levels by reversed-phase partition high performance liquid chromatography with 

pecolumn complexation reaction using salicylaldehyde and 1-amino-8-naphthol-3,6-disulfonate. Anal 

Bioanal Chem 391:1101-1106. 

Tarasenko NY, Kaspurov AA, Strongina OM. 1972. [Effect of boric acid on the generative function in 

males.] Gigirna Truda i Professionalyne Zabolevaniya 11:13-16. (Russian) 

Thomas K, Colborn T. 1992. Organochlorine endocrine disruptors in human tissue. In: Colborn T, 

Clement C, eds. Chemically induced alterations in sexual and functional development: The 

wildlife/human connection. Princeton, NJ: Princeton Scientific Publishing, 365-394. 

Thompson SE, Burton CA, Quinn DJ, et al. 1972. Concentration factors of chemical elements in edible 

aquatic organisms. Livermore, CA: Lawrence Livermore Laboratory, Bio-Medical Division, University 

of California. UCRL50564REV1. 

Treinen KA, Chapin RE. 1991. Development of testicular lesions in F344 rats after treatment with boric 

acid. Toxicol Appl Pharmacol 107:325-335. 

TRI06. 2008. TRI explorer: Providing access to EPA’s toxics release inventory data. Washington, DC: 

Office of Information Analysis and Access. Office of Environmental Information. U.S. Environmental 

Protection Agency. Toxics Release Inventory. http://www.epa.gov/triexplorer/. February 12, 2009. 

Tsui PT, McCart PJ. 1981. Chlorinated hydrocarbon residues and heavy metals in several fish species 

from the Cold Lake area in Alberta, Canada. Intern J Environ Anal Chem 10:277-285. 

Tuccar E, Elhan AH, Yaduz Y, et al. 1998. Comparison of infertility rates in communities from boronrich and boron-poor territories. Biol Trace Elem Res 66:401-407. 

Uemura T, Omae K, Nakashima H, et al. 1995. Acute and subacute inhalation toxicity of diborane in 

male ICR mice. Arch Toxicol 69(6):397-404. 

USGS. 1984. Element concentrations in soils and other surficial materials of the conterminous United 

States. Alexandria, VA: U.S. Geological Survey. Geological Survey Professional Paper 1270. 

USGS. 1989. In: Fishman MJ, Friedman LC, eds. Techniques of water-resources investigations, Book 

5, Chapter A1. Methods for determination of inorganic substances in water and fluvial sediments. 

Washington, DC: U.S. Geological Survey. http://pubs.usgs.gov/twri/twri5-a1/pdf/TWRI_5-A1.pdf. 

April 12, 2007. 

USGS. 1996a. Methods of analysis by the U.S. Geological Survey National Water Quality LaboratoryPreparation procedure for aquatic biological material determined for trace metals. Denver, CO: U.S. 

Geological Survey. Open-File Report 96-362. http://pubs.er.usgs.gov/usgspubs/ofr/ofr96362. March 26, 

2007. 

USGS. 1996b. Methods of analysis by the U.S. Geological Survey National Water Quality LaboratoryDetermination of dissolved aluminum and boron in water by inductively coupled plasma-atomic emission 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 189 

9. REFERENCES 

spectrometry. Denver, CO: U.S. Geological Survey. Open-File Report 96-149. 

http://pubs.er.usgs.gov/usgspubs/ofr/ofr96149. March 26, 2007. 

USGS. 1998. Methods of analysis by the U.S. Geological Survey National Water Quality LaboratoryDetermination of elements in whole-water digests using inductively coupled plasma-optical emission 

spectrometry and inductively coupled plasma-mass spectrometry. Denver, CO: U.S. Geological Survey. 

Open-File Report 98-165. http://pubs.er.usgs.gov/usgspubs/ofr/ofr98165. March 26, 2007. 

USGS. 1999. Methods of analysis by the U.S. Geological Survey National Water Quality LaboratoryDetermination of dissolved arsenic, boron, lithium, selenium, strontium, thallium, and vanadium using 

inductively coupled plasma-mass spectrometry. Denver, CO: U.S. Geological Survey. Open-File Report 

99-093. http://pubs.er.usgs.gov/usgspubs/ofr/ofr99093. March 26, 2007. 

USGS. 2008. Boron. 2007 minerals yearbook. U.S. Geological Survey, 13-1 to 13-10. 

http://minerals.usgs.gov/minerals/pubs/commodity/boron/boronmyb05.pdf. March 31, 2009. 

USGS. 2009. Boron. Mineral commodity studies. U.S. Geological Survey, 34-35. 

http://minerals.usgs.gov/minerals/pubs/commodity/boron/mcs-2009-boron.pdf. March 31, 2009. 

Usuda K, Kono K, Dote T, et al. 1998. Study on urine boron reference values of Japanese men: Use of 

confidence intervals as an indicator of exposure to boron compounds. Sci Total Environ 220(1):45-53. 

Vanderpool RA, Hoff D, Johnson PE. 1994. Use of inductively coupled plasma-mass spectrometry in 

boron-10 stable isotope experiments with plants, rats, and humans. Environ Health Perspect 102(Suppl 

7):13-20. 

Van Ormer DG. 1975. Atomic absorption analysis of some trace elements of toxicological interest. J 

Forensic Sci 20:595-623. 

Vaziri ND, Oveisi F, Culver BD, et al. 2001. The effect of pregnancy on renal clearance of boron in rats 

given boric acid orally. Toxicol Sci 60:257-263. 

Vengosh A, Heumann KG, Juraske S, et al. 1994. Boron isotope applications for tracing sources of 

contamination in groundwater. Environ Sci Technol 28(11):1968-1974. 

Viccellio P, Bania T, Brent J, et al., eds. 1998. Emergency toxicology. 2nd ed. Philadelphia, PA: 

Lippincott-Raven, 448-449, 470, 1141. 

Vieira I, Sonnier M, Cresteil T. 1996. Developmental expression of CYP2E1 in the human liver: 

Hypermethylation control of gene expression during the neonatal period. Eur J Biochem 238(2):476-483. 

Vignec AJ, Ellis R. 1954. Inabsorbability of boric acid in infant powder. Am J Dis Child 88:72-80. 

Waggott A. 1969. An investigation of the potential problem of increasing boron concentrations in rivers 

and water courses. Water Res 3:749-765. 

Wegman DH, Eisen EA, Hu X, et al. 1994. Acute and chronic respiratory effects of sodium borate 

particulate exposures. Environ Health Perspect (Suppl 7):102:119-128. 

Weir RJ, Fisher RS. 1972. Toxicologic studies on borax and boric acid. Toxicol Appl Pharmacol 

23:351-364. 
 

 

 

 

 

 

 

BORON 190 

9. REFERENCES 

Wery N, Narotsky MG, Pacico N, et al. 2003. Defects in cervical vertebrae in boric acid-exposed rat 

embryos are associated with anterior shifts of hox gene expression domains. Birth Defects Res A Clin 

Mol Teratol 67(1):59-67. 

West JR, Smith HW, Chasis H. 1948. Glomerular filtration rate, effective renal blood flow, and maximal 

tubular excretory capacity in infancy. J Pediatr 32:10-18. 

Wester RC, Hui X, Hartway T, et al. 1998. In vivo percutaneous absorption of boric acid, borax, and 

disodium octaborate tetrahydrate in humans compared to in vitro absoption in human skin from infinite 

and finite doses. Toxicol Sci 45:42-51. 

WHO. 2000. Air quality guidelines. 2nd ed. Geneva, Switzerland: World Health Organization. 

http://www.euro.who.int/Document/AIQ/AirQualRepMtg.pdf. March 08, 2006. 

WHO. 2004. Guidelines for drinking-water quality. Vol. 1. Recommendations. 3rd ed. Geneva, 

Switzerland: World Health Organization. http://www.who.int/water_sanitation_health/dwq/gdwq3/en/. 

March 08, 2006. 

Whorton D, Haas J, Trent L. 1994. Reproductive effects of inorganic borates on male employees: Birth 

rate assessment. Environ Health Perspect Suppl 102(7):129-132. 

Widdowson EM, Dickerson JWT. 1964. Chemical composition of the body. In: Comar CL, Bronner F, 

eds. Mineral metabolism: An advanced treatise. Vol. II: The elements. Part A. New York, NY: 

Academic Press, 1-247. 

Wilding JL, Smith WJ, Yevich P, et al. 1959. The toxicity of boron oxide. Am Ind Hyg Assoc J 20:284­

289. 

Wittig A, Michel J, Moss RL, et al. 2008. Boron analysis and boron imaging in biological materials for 

Boron Neutron Capture Therapy (BNCT). Crit Rev Oncol Hematol 68(1):66-90. 

Wong LC, Heimbach MD, Truscott DR, et al. 1964. Boric acid poisoning: Report of 11 cases. Can 

Med Assoc J 90:1018-1023. 

Woskie SR, Shen P, Eisen EA, et al. 1994. The real-time dust exposure of sodium borate workers: 

Examination of exposure variability. Am Ind Hyg Assoc J 55(3):207-217. 

Xiao YK, Li SZ, Wei HZ, et al. 2007. Boron isotopic fractionation during seawater evaporation. Mar 

Chem 103(3-4):382-392. 

Xing X, Wu G, Wei F, et al. 2008. Biomarkers of environmental and workplace boron exposure. J 

Occup Environ Hyg 5:141-147. 

Yoshizaki H, Izumi Y, Hirayama C, et al. 1999. Availability of sperm examination for male reproductive 

toxicities in rats treated with boric acid. J Toxicol Sci 24(3):199-208. 

Ziegler EE, Edwards BB, Jensen RL, et al. 1978. Absorption and retention of lead by infants. Pediatr 

Res 12(1):29-34. 
 

 

 

 

 

 

 

 

 

 

 

BORON 191 

10. GLOSSARY 

Absorption—The taking up of liquids by solids, or of gases by solids or liquids. 

Acute Exposure—Exposure to a chemical for a duration of 14 days or less, as specified in the 

Toxicological Profiles. 

Adsorption—The adhesion in an extremely thin layer of molecules (as of gases, solutes, or liquids) to the 

surfaces of solid bodies or liquids with which they are in contact. 

Adsorption Coefficient (Koc)—The ratio of the amount of a chemical adsorbed per unit weight of 

organic carbon in the soil or sediment to the concentration of the chemical in solution at equilibrium. 

Adsorption Ratio (Kd)—The amount of a chemical adsorbed by sediment or soil (i.e., the solid phase) 

divided by the amount of chemical in the solution phase, which is in equilibrium with the solid phase, at a 

fixed solid/solution ratio. It is generally expressed in micrograms of chemical sorbed per gram of soil or 

sediment. 

Benchmark Dose (BMD)—The dose expected to result in a specified change of a biological effect (the 

benchmark response, or BMR), generally 1% to 10% from the untreated population. The BMD is 

determined by modeling the dose response data in the region of the dose response relationship where 

biologically observable data are feasible. 

Benchmark Dose, Lower Limit (BMDL)—The lower confidence limit on the benchmark dose. For 

example, a BMDL10 would be the dose at the 95% lower confidence limit on a 10% response, and the 

benchmark response (BMR) would be 10%. 

Benchmark Dose Model—A statistical dose-response model applied to either experimental toxicological 

or epidemiological data to calculate a BMD. 

Bioconcentration Factor (BCF)—The quotient of the concentration of a chemical in aquatic organisms 

at a specific time or during a discrete time period of exposure divided by the concentration in the 

surrounding water at the same time or during the same period. 

Biomarkers—Broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility. 

Cancer Effect Level (CEL)—The lowest dose of chemical in a study, or group of studies, that produces 

significant increases in the incidence of cancer (or tumors) between the exposed population and its 

appropriate control. 

Carcinogen—A chemical capable of inducing cancer. 

Case-Control Study—A type of epidemiological study that examines the relationship between a 

particular outcome (disease or condition) and a variety of potential causative agents (such as toxic 

chemicals). In a case-controlled study, a group of people with a specified and well-defined outcome is 

identified and compared to a similar group of people without outcome. 

Case Report—Describes a single individual with a particular disease or exposure. These may suggest 

some potential topics for scientific research, but are not actual research studies. 
 

 

 

 

 

 

 

 

 

 

 

BORON 192 

10. GLOSSARY 

Case Series—Describes the experience of a small number of individuals with the same disease or 

exposure. These may suggest potential topics for scientific research, but are not actual research studies. 

Ceiling Value—A concentration of a substance that should not be exceeded, even instantaneously. 

Chronic Exposure—Exposure to a chemical for 365 days or more, as specified in the Toxicological 

Profiles. 

Cohort Study—A type of epidemiological study of a specific group or groups of people who have had a 

common insult (e.g., exposure to an agent suspected of causing disease or a common disease) and are 

followed forward from exposure to outcome. At least one exposed group is compared to one unexposed 

group. 

Cross-sectional Study—A type of epidemiological study of a group or groups of people that examines 

the relationship between exposure and outcome to a chemical or to chemicals at one point in time. 

Data Needs—Substance-specific informational needs that if met would reduce the uncertainties of human 

health assessment. 

Developmental Toxicity—The occurrence of adverse effects on the developing organism that may result 

from exposure to a chemical prior to conception (either parent), during prenatal development, or 

postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any point 

in the life span of the organism. 

Dose-Response Relationship—The quantitative relationship between the amount of exposure to a 

toxicant and the incidence of the adverse effects. 

Embryotoxicity and Fetotoxicity—Any toxic effect on the conceptus as a result of prenatal exposure to 

a chemical; the distinguishing feature between the two terms is the stage of development during which the 

insult occurs. The terms, as used here, include malformations and variations, altered growth, and in utero 

death. 

Environmental Protection Agency (EPA) Health Advisory—An estimate of acceptable drinking water 

levels for a chemical substance based on health effects information. A health advisory is not a legally 

enforceable federal standard, but serves as technical guidance to assist federal, state, and local officials. 

Epidemiology—Refers to the investigation of factors that determine the frequency and distribution of 

disease or other health-related conditions within a defined human population during a specified period. 

Genotoxicity—A specific adverse effect on the genome of living cells that, upon the duplication of 

affected cells, can be expressed as a mutagenic, clastogenic, or carcinogenic event because of specific 

alteration of the molecular structure of the genome. 

Half-life—A measure of rate for the time required to eliminate one half of a quantity of a chemical from 

the body or environmental media. 

Immediately Dangerous to Life or Health (IDLH)—The maximum environmental concentration of a 

contaminant from which one could escape within 30 minutes without any escape-impairing symptoms or 

irreversible health effects. 
 

 

 

 

 

 

 

 

 

 

BORON 193 

10. GLOSSARY 

Immunologic Toxicity—The occurrence of adverse effects on the immune system that may result from 

exposure to environmental agents such as chemicals. 

Immunological Effects—Functional changes in the immune response. 

Incidence—The ratio of individuals in a population who develop a specified condition to the total 

number of individuals in that population who could have developed that condition in a specified time 

period. 

Intermediate Exposure—Exposure to a chemical for a duration of 15–364 days, as specified in the 

Toxicological Profiles. 

In Vitro—Isolated from the living organism and artificially maintained, as in a test tube. 

In Vivo—Occurring within the living organism. 

Lethal Concentration(LO) (LCLO)—The lowest concentration of a chemical in air that has been reported 

to have caused death in humans or animals. 

Lethal Concentration(50) (LC50)—A calculated concentration of a chemical in air to which exposure for 

a specific length of time is expected to cause death in 50% of a defined experimental animal population. 

Lethal Dose(LO) (LDLo)—The lowest dose of a chemical introduced by a route other than inhalation that 

has been reported to have caused death in humans or animals. 

Lethal Dose(50) (LD50)—The dose of a chemical that has been calculated to cause death in 50% of a 

defined experimental animal population. 

Lethal Time(50) (LT50)—A calculated period of time within which a specific concentration of a chemical 

is expected to cause death in 50% of a defined experimental animal population. 

Lowest-Observed-Adverse-Effect Level (LOAEL)—The lowest exposure level of chemical in a study, 

or group of studies, that produces statistically or biologically significant increases in frequency or severity 

of adverse effects between the exposed population and its appropriate control. 

Lymphoreticular Effects—Represent morphological effects involving lymphatic tissues such as the 

lymph nodes, spleen, and thymus. 

Malformations—Permanent structural changes that may adversely affect survival, development, or 

function. 

Minimal Risk Level (MRL)—An estimate of daily human exposure to a hazardous substance that is 

likely to be without an appreciable risk of adverse noncancer health effects over a specified route and 

duration of exposure. 

Modifying Factor (MF)—A value (greater than zero) that is applied to the derivation of a Minimal Risk 

Level (MRL) to reflect additional concerns about the database that are not covered by the uncertainty 

factors. The default value for a MF is 1. 

Morbidity—State of being diseased; morbidity rate is the incidence or prevalence of disease in a specific 

population. 
 

 

 

 

 

 

 

 

 

 

BORON 194 

10. GLOSSARY 

Mortality—Death; mortality rate is a measure of the number of deaths in a population during a specified 

interval of time. 

Mutagen—A substance that causes mutations. A mutation is a change in the DNA sequence of a cell’s 

DNA. Mutations can lead to birth defects, miscarriages, or cancer. 

Necropsy—The gross examination of the organs and tissues of a dead body to determine the cause of 

death or pathological conditions. 

Neurotoxicity—The occurrence of adverse effects on the nervous system following exposure to a 

chemical. 

No-Observed-Adverse-Effect Level (NOAEL)—The dose of a chemical at which there were no 

statistically or biologically significant increases in frequency or severity of adverse effects seen between 

the exposed population and its appropriate control. Effects may be produced at this dose, but they are not 

considered to be adverse. 

Octanol-Water Partition Coefficient (Kow)—The equilibrium ratio of the concentrations of a chemical 

in n-octanol and water, in dilute solution. 

Odds Ratio (OR)—A means of measuring the association between an exposure (such as toxic substances 

and a disease or condition) that represents the best estimate of relative risk (risk as a ratio of the incidence 

among subjects exposed to a particular risk factor divided by the incidence among subjects who were not 

exposed to the risk factor). An OR of greater than 1 is considered to indicate greater risk of disease in the 

exposed group compared to the unexposed group. 

Organophosphate or Organophosphorus Compound—A phosphorus-containing organic compound 

and especially a pesticide that acts by inhibiting cholinesterase. 

Permissible Exposure Limit (PEL)—An Occupational Safety and Health Administration (OSHA) 

allowable exposure level in workplace air averaged over an 8-hour shift of a 40-hour workweek. 

Pesticide—General classification of chemicals specifically developed and produced for use in the control 

of agricultural and public health pests. 

Pharmacokinetics—The dynamic behavior of a material in the body, used to predict the fate 

(disposition) of an exogenous substance in an organism. Utilizing computational techniques, it provides 

the means of studying the absorption, distribution, metabolism, and excretion of chemicals by the body. 

Pharmacokinetic Model—A set of equations that can be used to describe the time course of a parent 

chemical or metabolite in an animal system. There are two types of pharmacokinetic models: data-based 

and physiologically-based. A data-based model divides the animal system into a series of compartments, 

which, in general, do not represent real, identifiable anatomic regions of the body, whereas the 

physiologically-based model compartments represent real anatomic regions of the body. 

Physiologically Based Pharmacodynamic (PBPD) Model—A type of physiologically based doseresponse model that quantitatively describes the relationship between target tissue dose and toxic end 

points. These models advance the importance of physiologically based models in that they clearly 

describe the biological effect (response) produced by the system following exposure to an exogenous 

substance. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON 195 

10. GLOSSARY 

Physiologically Based Pharmacokinetic (PBPK) Model—Comprised of a series of compartments 

representing organs or tissue groups with realistic weights and blood flows. These models require a 

variety of physiological information: tissue volumes, blood flow rates to tissues, cardiac output, alveolar 

ventilation rates, and possibly membrane permeabilities. The models also utilize biochemical 

information, such as air/blood partition coefficients, and metabolic parameters. PBPK models are also 

called biologically based tissue dosimetry models. 

Prevalence—The number of cases of a disease or condition in a population at one point in time. 

Prospective Study—A type of cohort study in which the pertinent observations are made on events 

occurring after the start of the study. A group is followed over time. 

q1*—The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the 

multistage procedure. The q1* can be used to calculate an estimate of carcinogenic potency, the 

incremental excess cancer risk per unit of exposure (usually μg/L for water, mg/kg/day for food, and 

μg/m3 for air). 

Recommended Exposure Limit (REL)—A National Institute for Occupational Safety and Health 

(NIOSH) time-weighted average (TWA) concentration for up to a 10-hour workday during a 40-hour 

workweek. 

Reference Concentration (RfC)—An estimate (with uncertainty spanning perhaps an order of 

magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) 

that is likely to be without an appreciable risk of deleterious noncancer health effects during a lifetime. 

The inhalation reference concentration is for continuous inhalation exposures and is appropriately 

expressed in units of mg/m3 or ppm. 

Reference Dose (RfD)—An estimate (with uncertainty spanning perhaps an order of magnitude) of the 

daily exposure of the human population to a potential hazard that is likely to be without risk of deleterious 

effects during a lifetime. The RfD is operationally derived from the no-observed-adverse-effect level 

(NOAEL, from animal and human studies) by a consistent application of uncertainty factors that reflect 

various types of data used to estimate RfDs and an additional modifying factor, which is based on a 

professional judgment of the entire database on the chemical. The RfDs are not applicable to 

nonthreshold effects such as cancer. 

Reportable Quantity (RQ)—The quantity of a hazardous substance that is considered reportable under 

the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). Reportable 

quantities are (1) 1 pound or greater or (2) for selected substances, an amount established by regulation 

either under CERCLA or under Section 311 of the Clean Water Act. Quantities are measured over a 

24-hour period. 

Reproductive Toxicity—The occurrence of adverse effects on the reproductive system that may result 

from exposure to a chemical. The toxicity may be directed to the reproductive organs and/or the related 

endocrine system. The manifestation of such toxicity may be noted as alterations in sexual behavior, 

fertility, pregnancy outcomes, or modifications in other functions that are dependent on the integrity of 

this system. 
 

 

 

 

 

BORON 196 

10. GLOSSARY 

Retrospective Study—A type of cohort study based on a group of persons known to have been exposed 

at some time in the past. Data are collected from routinely recorded events, up to the time the study is 

undertaken. Retrospective studies are limited to causal factors that can be ascertained from existing 

records and/or examining survivors of the cohort. 

Risk—The possibility or chance that some adverse effect will result from a given exposure to a chemical. 

Risk Factor—An aspect of personal behavior or lifestyle, an environmental exposure, or an inborn or 

inherited characteristic that is associated with an increased occurrence of disease or other health-related 

event or condition. 

Risk Ratio—The ratio of the risk among persons with specific risk factors compared to the risk among 

persons without risk factors. A risk ratio greater than 1 indicates greater risk of disease in the exposed 

group compared to the unexposed group. 

Short-Term Exposure Limit (STEL)—The American Conference of Governmental Industrial 

Hygienists (ACGIH) maximum concentration to which workers can be exposed for up to 15 minutes 

continually. No more than four excursions are allowed per day, and there must be at least 60 minutes 

between exposure periods. The daily Threshold Limit Value-Time Weighted Average (TLV-TWA) may 

not be exceeded. 

Standardized Mortality Ratio (SMR)—A ratio of the observed number of deaths and the expected 

number of deaths in a specific standard population. 

Target Organ Toxicity—This term covers a broad range of adverse effects on target organs or 

physiological systems (e.g., renal, cardiovascular) extending from those arising through a single limited 

exposure to those assumed over a lifetime of exposure to a chemical. 

Teratogen—A chemical that causes structural defects that affect the development of an organism. 

Threshold Limit Value (TLV)—An American Conference of Governmental Industrial Hygienists 

(ACGIH) concentration of a substance to which most workers can be exposed without adverse effect. 

The TLV may be expressed as a Time Weighted Average (TWA), as a Short-Term Exposure Limit 

(STEL), or as a ceiling limit (CL). 

Time-Weighted Average (TWA)—An allowable exposure concentration averaged over a normal 8-hour 

workday or 40-hour workweek. 

Toxic Dose(50) (TD50)—A calculated dose of a chemical, introduced by a route other than inhalation, 

which is expected to cause a specific toxic effect in 50% of a defined experimental animal population. 

Toxicokinetic—The absorption, distribution, and elimination of toxic compounds in the living organism. 
 

 

 

 

 

BORON 197 

10. GLOSSARY 

Uncertainty Factor (UF)—A factor used in operationally deriving the Minimal Risk Level (MRL) or 

Reference Dose (RfD) or Reference Concentration (RfC) from experimental data. UFs are intended to 

account for (1) the variation in sensitivity among the members of the human population, (2) the 

uncertainty in extrapolating animal data to the case of human, (3) the uncertainty in extrapolating from 

data obtained in a study that is of less than lifetime exposure, and (4) the uncertainty in using lowestobserved-adverse-effect level (LOAEL) data rather than no-observed-adverse-effect level (NOAEL) data. 

A default for each individual UF is 10; if complete certainty in data exists, a value of 1 can be used; 

however, a reduced UF of 3 may be used on a case-by-case basis, 3 being the approximate logarithmic 

average of 10 and 1 (see for example, Dourson, 1994). 

Xenobiotic—Any chemical that is foreign to the biological system. 
 

 

 

 

 

 

 

 

 

 

 

 

 

BORON A-1 

APPENDIX A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS 

The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) [42 U.S.C. 

9601 et seq.], as amended by the Superfund Amendments and Reauthorization Act (SARA) [Pub. L. 99– 

499], requires that the Agency for Toxic Substances and Disease Registry (ATSDR) develop jointly with 

the U.S. Environmental Protection Agency (EPA), in order of priority, a list of hazardous substances most 

commonly found at facilities on the CERCLA National Priorities List (NPL); prepare toxicological 

profiles for each substance included on the priority list of hazardous substances; and assure the initiation 

of a research program to fill identified data needs associated with the substances. 

The toxicological profiles include an examination, summary, and interpretation of available toxicological 

information and epidemiologic evaluations of a hazardous substance. During the development of 

toxicological profiles, Minimal Risk Levels (MRLs) are derived when reliable and sufficient data exist to 

identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration for a 

given route of exposure. An MRL is an estimate of the daily human exposure to a hazardous substance 

that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration 

of exposure. MRLs are based on noncancer health effects only and are not based on a consideration of 

cancer effects. These substance-specific estimates, which are intended to serve as screening levels, are 

used by ATSDR health assessors to identify contaminants and potential health effects that may be of 

concern at hazardous waste sites. It is important to note that MRLs are not intended to define clean-up or 

action levels. 

MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty factor 

approach. They are below levels that might cause adverse health effects in the people most sensitive to 

such chemical-induced effects. MRLs are derived for acute (1–14 days), intermediate (15–364 days), and 

chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. Currently, 

MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified a method 

suitable for this route of exposure. MRLs are generally based on the most sensitive chemical-induced end 

point considered to be of relevance to humans. Serious health effects (such as irreparable damage to the 

liver or kidneys, or birth defects) are not used as a basis for establishing MRLs. Exposure to a level 

above the MRL does not mean that adverse health effects will occur. 

MRLs are intended only to serve as a screening tool to help public health professionals decide where to 

look more closely. They may also be viewed as a mechanism to identify those hazardous waste sites that 
 

 

 

 

 

 

BORON A-2 

APPENDIX A 

are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of 

the lack of precise toxicological information on the people who might be most sensitive (e.g., infants, 

elderly, nutritionally or immunologically compromised) to the effects of hazardous substances. ATSDR 

uses a conservative (i.e., protective) approach to address this uncertainty consistent with the public health 

principle of prevention. Although human data are preferred, MRLs often must be based on animal studies 

because relevant human studies are lacking. In the absence of evidence to the contrary, ATSDR assumes 

that humans are more sensitive to the effects of hazardous substance than animals and that certain persons 

may be particularly sensitive. Thus, the resulting MRL may be as much as 100-fold below levels that 

have been shown to be nontoxic in laboratory animals. 

Proposed MRLs undergo a rigorous review process: Health Effects/MRL Workgroup reviews within the 

Division of Toxicology, expert panel peer reviews, and agency-wide MRL Workgroup reviews, with 

participation from other federal agencies and comments from the public. They are subject to change as 

new information becomes available concomitant with updating the toxicological profiles. Thus, MRLs in 

the most recent toxicological profiles supersede previously published levels. For additional information 

regarding MRLs, please contact the Division of Toxicology and Environmental Medicine, Agency for 

Toxic Substances and Disease Registry, 1600 Clifton Road NE, Mailstop F-62, Atlanta, Georgia 30333. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON A-3 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Boron and Compounds 

CAS Number: 7440-42-8 

Date: August 2009 

Profile Status: Final Draft Post-Public Comment 

Route: [X] Inhalation [ ] Oral 

Duration: [X] Acute [ ] Intermediate [ ] Chronic 

Graph Key: 2 

Species: Human 

Minimal Risk Level: 0.3 [X] mg/m3 [ ] ppm 

Reference: Cain WS, Jalowayski AA, Kleinman M, et al. 2004. Sensory and associated reactions to 

mineral dusts: Sodium borate, calcium oxide, and calcium sulfate. J Occup Environ Hyg 1:222-236. 

Cain WS, Jalowayski AA, Schmidt R, et al. 2008. Chemesthetic responses to airborne mineral dusts: 

boric acid compared to alkaline materials. Int Arch Occup Environ Health 81:337-345. 

Experimental design: Male and female volunteers were trained to recognize the difference in 

chemesthetic feel (pungency or irritancy) of various levels of CO2 offered to the eyes, nose, and throat. 

Exposures of ≥17.7% CO2 resulted in a “feel” described by the volunteers as irritating. Twelve male 

volunteers were exposed to 0, 0.8, 1.5, 3.0, 4.5, or 6.0 mg boron/m3 (0, 5, 10, 20, 30, or 40 mg sodium 

borate pentahydrate/m3

) for 20 minutes while performing light exercise (Cain et al. 2004). At 5-minute 

intervals, they reported the magnitude of “feel” of borate dust in terms of equivalent CO2 irritancy. They 

were also observed for changes in nasal secretions (by mass) and nasal airway resistance relative to preexposure measurements. Data were reported as means of all responses at each concentration and time 

point. 

In a similar fashion, six male and six female volunteers were exposed to 1.5 mg boron/m3 (10 mg sodium 

borate/m3

) or 1.8 mg boron/m3 (10 mg boric acid/m3) for 47 minutes while exercising. They reported the 

magnitude of “feel” of boric acid and borate dusts in terms of equivalent CO2 irritancy. They were also 

observed for changes in nasal secretions (by mass), nasal airway resistance, and respiration frequency. 

Effects noted in study and corresponding doses: Male volunteers exposed to ≤3.0 mg boron/m3 (≤20 mg

sodium borate/m3

) for 20 minutes reported increasingly higher magnitude of feel of the dust in eyes, nose, 

and throat. However, the mean reported level of feel, compared to equivalent CO2 levels, was not 

considered irritating by the study subjects. The mean reported perception of feel at ≥4.5 mg boron/m3 

(≥30 sodium borate/m3) was reported to feel irritating to the nose (Cain et al. 2004). Significantly 

increased nasal secretions (by mass) occurred at 1.5 mg boron/m3 (10 mg sodium borate/m3

), but not 

0.8 mg boron/m3 (5 mg sodium borate/m3

) (Cain et al. 2004). Similarly, male and female volunteers 

exposed to 1.5 mg boron/m3 (10 mg sodium borate/m3

) or 1.8 mg boron/m3 (10 mg boric acid/m3) for 

47 minutes while exercising reported a mean sense of feel that initially increased and peaked at the 

equivalent of slightly <17.7% CO2. Boron exposures with a mean reported feel equivalent to less than 

17.7% CO2 are considered non-irritating, although increases in nasal secretions were observed at 1.8 mg 

boron/mg3 (10 mg boric acid/m3

), but not at 0.9 mg boron/mg3 (5 mg boric acid/m3) (Cain et al. 2008). 

Nasal airway resistance decreased, then increased, as a result of exercise, but did not change in a doserelated manner. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON A-4 

APPENDIX A 

Dose and end point used for MRL derivation: A NOAEL of 0.8 mg/m3 associated with a minimal 

LOAEL of 1.5 mg/m3 for significantly increased volume of nasal secretions. 

[ X] NOAEL [ ] LOAEL 

Uncertainty Factors used in MRL derivation: 

[ ] 10 for use of a LOAEL
 

[ ] 10 for extrapolation from animals to humans
 

[X] 3 for human variability 

Was a conversion used from ppm in food or water to a mg/body weight dose? No. 

If an inhalation study in animals, list the conversion factors used in determining human equivalent dose: 

Not applicable. 

Other additional studies or pertinent information that lend support to this MRL: In an early crosssectional study of sodium borate workers, past occurrence of symptoms of respiratory irritation such as 

dryness of the mouth, nose, or throat, dry cough, nose bleeds, and sore throat were reported at elevated 

frequencies in workers in areas with mean dust concentrations of 8.4 and 14.6 mg particulates/m3 (1.8 and 

3.1 mg boron/m3

, respectively), compared with workers in areas with lower mean dust levels of 4.0 and 

1.1 mg particulate/m3 (0.9 and 0.2 mg boron/m3

) (Garabrant et al. 1984, 1985). In addition, a reduction in 

forced expiratory volume in 1 second (FEV1) was measured in a subgroup of smoking workers with 

estimated high cumulative exposure (≥80 mg particulate/m3

, ≥9 mg boron/m3) to sodium borate dusts, but 

not in groups of less-exposed smoking workers or in nonsmoking workers. However, a subsequent 

survey of FEV1 in 303 of the original 629 borax workers, 7 years after the original survey, found no 

exposure-related changes in FEV1 over this period, when adjustments were made for the effects of age, 

height, and smoking on FEV1 (Wegman et al. 1994). Acute-duration laboratory exposures of volunteers 

to sodium borate dust support the findings of respiratory irritation reported in the occupational studies. 

The occurrence of acute respiratory symptoms as a possible consequence of acute exposure to dusts of 

sodium borate (the decahydrate, pentahydrate, and anhydrous tetraborates) was studied in a later study by 

interviewing workers about acute irritation symptoms before the work shift began and at regular hourly 

intervals during the work shift, and by measuring personal air concentrations of particulates at concurrent 

intervals for 4 consecutive days (Hu et al. 1992; Wegman et al. 1991, 1994). Seventy-nine exposed 

production workers and 27 nonexposed workers were included in the study. In the latest analysis of the 

collected data, the incidence rates for irritation symptoms in exposed workers were statistically 

significantly higher than those in nonexposed workers, with exposed workers 9-, 5-, and 3-fold more 

likely to report incidents of nasal, eye, and throat irritation, respectively, than comparison workers (Hu et 

al. 1992; Wegman et al. 1991, 1994). For the unexposed groups, the arithmetic means of the 6-hour 

TWA daily dust concentration was 0.45 mg particulates/m3 (0.02 mg boron/m3

), with 100% of samples 

≤1.0 mg particulates/m3 and about 90% of samples ≤0.5 mg particulates/m3

. The arithmetic mean of the 

6-hour TWA daily dust concentrations for the exposed group was 5.72 mg particulates/m3 (0.44 mg 

boron/m3

), with a majority of air concentrations between 1.0 and 10.0 mg particulates/m3 (Wegman et al. 

1991, 1994). Several factors make it difficult to identify a NOAEL or LOAEL for this study, precluding 

inclusion of this study in Figure and Table 3-1. Study participants rated their perception of individual 

episodes of eye, throat, and nasal irritancy on a scale of 0 (not at all) to 10 (very, very much), with ratings 

of 1, 2, and 3 representing “very little”, “fairly little”, and “moderate” irritation, respectively. Unexposed 

responders to the pre-shift survey reported a mean rating of 1.9 for all symptoms, while the mean rating 

for nasal irritation (the most commonly reported effect) among exposed workers was just slightly higher 

at 2.2. Thus, the cutoff for boron dust-induced effects is likely to be for ratings of ≥3. In the exposed 
 

 

 

 

 

 

BORON A-5 

APPENDIX A 

group, 91% of reported symptoms were rated with severity scores ≤3 and 96% of symptoms were rated 

with severity scores of ≤4 (“pretty much”). For incidences in which the workers depressed a counter 

button to record time of symptom onset, and the study surveyor recorded an occurrence of effect, the 

probability of reporting an effect did not change markedly until 0.25-hour TWA exposure levels reached 

0.8–1.2 mg boron/m3 (Wegman et al. 1991). There was no significant difference in reporting of 

symptoms based on the type of borate dust, which differ in boron content by almost a factor of two (i.e., 

4.7 mg anhydrous borax/m3 and 8.8 mg/m3 of the decahydrate provide 1 mg boron/m3

). Finally, the data 

do not indicate a temporal increase in effect intensity, as would be expected for a local irritant. 

An uncertainty factor of 3 for human variability was based on the fact that inhaled borates and boric acid 

exert their adverse effects on respiratory tract tissues as portal-of-entry irritants. For portal-of-entry 

inhalation toxicants, the variability between humans in pharmacokinetics (i.e., toxicant deposition in the 

respiratory tract) is minimal. Thus, half (100.5, or 3) of the composite uncertainty factor for 

pharmacokinetic and pharmacodynamic variability in humans should be applied to the identified NOAEL. 

Agency Contacts (Chemical Managers): Malcolm Williams 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON A-6 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Boron and Compounds 

CAS Number: 7440-42-8 

Date: August 2009 

Profile Status: Final Draft Post-Public Comment 

Route: [ ] Inhalation [X] Oral 

Duration: [X] Acute [ ] Intermediate [ ] Chronic 

Graph Key: 22 

Species: Rabbit 

Minimal Risk Level: 0.2 [X] mg/kg/day [ ] ppm 

Reference: Price CJ, Marr MC, Myers CB, et al. 1996b. The developmental toxicity of boric acid in 

rabbits. Fundam Appl Toxicol 34:176-187. 

The results of this study have also been reported in the following references: 

Heindel JJ, Price CJ, Schwetz BA. 1994. The developmental toxicity of boric acid in mice, rats, and 

rabbits. Environ Health Perspect Suppl 102(7):107-112. 

NTP. 1991. Final report on the developmental toxicity of boric acid (CAS No. 10043-35-3) in New 

Zealand white rabbits. Research Triangle Park, NC: U.S. Department of Health and Human Services, 

Public Health Service, National Toxicology Program. PB92129550. 

Experimental design: Groups of 30 pregnant New Zealand white rabbits were given gavage doses of 0, 

62.5, 125, or 250 mg boric acid/kg/day (0, 11, 22, or 44 mg boron/kg/day) on gestation days 6–19. 

Observations were made for clinical signs, maternal and fetal body weight, number of implantations, 

resorptions, number of live and dead fetuses, and fetal external, visceral, and skeletal defects. 

Effects noted in study and corresponding doses: No adverse maternal effects were observed in the 11 or 

22 mg boron/kg/day groups. At 44 mg boron/kg/day, decreases in maternal body weight, relative kidney 

weight, and food consumption were observed. During the treatment period, the rabbits lost 137 g body 

weight compared to a weight gain of 93 g in controls. No differences in the number of implantation sites 

per litter were observed; however, there were significant increases in the percent resorptions per litter 

(6.3, 5.9, 7.7, and 89.9% in the 0, 11, 22, and 44 mg boron/kg/day groups, respectively), percent of litters 

with one or more resorptions (39, 39, 45, and 95%), and percent of litters with 100% resorption (0, 0, 0, 

and 73%). The number of live litters was 18, 23, 20, and 6 in the 0, 11, 22, and 44 mg boron/kg/day 

groups, respectively, and the number of live fetuses was 159, 175, 153, and 14, respectively. A decrease 

in fetal body weights (92% of controls) was observed at 44 mg boron/kg/day; although the body weight 

was not significantly different from controls, the effect was considered biologically significant. 

Significant increases in the percent of fetuses per litter with external (0.8, 1.4, 1.0, and 11.1% in the 0, 11, 

22, and 44 mg boron/kg/day groups, respectively), visceral (7.3, 5.9, 7.4, and 80.6%), cardiovascular 

malformations (2.7, 3.1, 4.2, and 72.2%) and cardiovascular variations (10.6, 5.7, 7.2, and 63.9%) were 

observed. Although the overall incidence of external malformations was increased at 44 mg 

boron/kg/day, there were no increases in a specific malformation. The visceral malformations primarily 

consisted of cardiovascular malformations, particularly interventricular septal defect, enlarged aorta, 

papillary muscle malformation, and double outlet right ventricle. The cardiovascular variations consisted 

of abnormal number of cardiac papillary muscles. 
 

 

 

 

 

 

 

 

 

 

BORON A-7 

APPENDIX A 

Dose and end point used for MRL derivation: NOAEL of 22 mg boron/kg/day as boric acid associated 

with a LOAEL of 44 mg boron/kg/day as boric acid for developmental effects 

[X] NOAEL [ ] LOAEL 

Uncertainty Factors used in MRL derivation: 

[ ] 10 for use of a LOAEL 

[X] 10 for extrapolation from animals to humans 

[X] 10 for human variability 

Was a conversion used from ppm in food or water to a mg/body weight dose? No. 

If an inhalation study in animals, list the conversion factors used in determining human equivalent dose: 

Not applicable. 

Other additional studies or pertinent information that lend support to this MRL: A series of studies 

conducted by Cherrington and Chernoff (2002) also examined the developmental toxicity of boron. A 

variety of skeletal malformations (including rib agenesis, cervical rib, and fused ribs) were observed in 

the fetuses of mice receiving two gavage doses of 70 mg boron/kg on gestation day 8 or gestation days 6– 

8, once daily dose of 88 mg boron/kg/day on gestation days 6–10, or one dose of 131 mg boron/kg on 

gestation day 8. Multiple thoracic skeletal malformations were observed in the fetuses of mice receiving 

two doses of 131 mg boron/kg on gestation day 8. Decreases in fetal body weight were also observed in 

these studies and in studies of mice receiving two gavage doses of 70 mg boron/kg on gestation day 6, 7, 

9, or 10. 

Developmental effects have also been observed in intermediate-duration studies. Decreases in fetal body 

weight were observed in rats exposed to 13 or 13.6 mg boron/kg/day on gestation days 0–20 (Heindel et 

al. 1992; Price et al. 1996a), increases in skeletal abnormalities were observed in rats exposed to 13 mg 

boron/kg/day on gestation days 0–20 (Price et al. 1996a), and rib cage defects and enlargement of the 

brain lateral ventricles were observed in rats exposed to 28.4 mg boron/kg/day on gestation days 0– 

20 (Heindel et al. 1992). In mice exposed to boric acid on gestation days 0–17, reduced fetal body weight 

and increased skeletal defects were observed at 79 and 175.3 mg boron/kg/day, respectively. 

Agency Contacts (Chemical Managers): Malcolm Williams 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON A-8 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Boron and Compounds 

CAS Number: 7440-42-8 

Date: August 2009 

Profile Status: Final Draft Post-Public Comment 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [X] Intermediate [ ] Chronic 

Graph Key: 60, 61 

Species: Rat 

Minimal Risk Level: 0.2 [X] mg/kg/day [ ] ppm 

Reference: Heindel JJ, Price CJ, Field EA, et al. 1992. Developmental toxicity of boric acid in mice and 

rats. Fundam Appl Toxicol 18:266-277. 

Experimental design: Groups of 26–28 pregnant Sprague-Dawley rats and Swiss mice were exposed to 0, 

0.1, 0.2, or 0.4% boric acid in the diet on gestation days 0–20. Estimated boron doses are 0, 13.6, 28.5, or 

57.7 mg boron/kg/day (0, 78, 163, or 330 mg boric acid/kg/day) for rats and 0, 43, 79, or 176 mg 

boron/kg/day (0, 248, 452, or 1,003 mg boric acid/kg/day) for mice. Daily observations were made for 

clinical signs and food and water consumption. At death, body and organ weights were recorded. 

Maternal kidneys were examined microscopically. Live fetuses were excised, anesthetized, weighed, and 

examined for skeletal malformations. 

Effects noted in study and corresponding doses: Decreased maternal weight gain was observed in the 

57.7 mg boron /kg/day group of rats, but not when corrected for gravid uterine weight. Decreased relative 

kidney and liver weights were seen in the 28.4 mg boron/kg/day group. The incidence and severity of the 

minimal maternal nephropathy was not dose-related. Mean fetal body weight per litter was significantly 

reduced (7–15%) in all treated groups. Significant increases in the percentage of malformed fetuses/litter 

or litter with one or more malformed fetuses was observed at doses ≥28.5mg boron/kg/day. Noted 

malformations included anomalies of the eye, central nervous system, cardiovascular system, and axial 

skeleton. Enlarged lateral ventricles of the brain and agenesis or shortening of the 13th rib were seen in 

the 57.7 mg boron/kg/day group. 

Reference: Price PJ, Strong PL, Marr MC, et al. 1996a. Developmental toxicity NOAEL and postnatal 

recovery in rats fed boric acid during gestation. Fundam Appl Toxicol 32:179-193. 

Experimental design: Groups of 60 female Sprague-Dawley rats were exposed to 0, 0.025, 0.050, 0.075, 

0.100, or 0.200% boric acid in the diet on gestation days 0–20. Observations were made for body weight, 

clinical signs, and food and water consumption. The study was performed in two phases; offspring were 

evaluated in both phases for post-implantation mortality, body weight, and external, visceral, and skeletal 

morphology. Phase I was terminated on gestation day 20. The calculated average maternal dose of boron 

was 0, 3.3, 6.3, 10, 13, or 25 mg boron/kg/day (0, 19, 36, 55, 76, or 143 mg boric acid/kg/day). Phase II 

dams were allowed to litter and rear their pups until postnatal day (pnd) 21. For these dams, the 

calculated average doses of boron were 0, 0.2, 6.5, 9.7, 12.9, and 25.3 mg/kg/day (0, 19, 37, 56, 74, and 

145 mg boric acid/kg/day). During this phase, the incidence of skeletal defects in control and exposed 

pups was evaluated at the end of the first 21 postnatal days. 

Effects noted in study and corresponding doses: During Phase I of the study, no maternal deaths or 

clinical signs were associated with boric acid treatment. When corrected for gravid uterine weight, 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON A-9 

APPENDIX A 

maternal weight gain was not affected. However, reduced gravid uterine weight resulted in significant 

trend tests for decreased maternal body weight (gestation days19 and 20) and decreased maternal body 

weight gain (gestation days 15–18 and 0–20). Dams in the 25 mg boron/kg/day group had a 10% 

reduction (statistically significant in the trend test, p<0.05) in gravid uterine weight compared with 

controls. Fetal body weights were significantly decreased in the 13 and 25 mg boron/kg/day groups 

(6 and 12% less than controls) on gestation day 20. Incidences of external or visceral malformations or 

variations were not treatment-related. However, a significant increase was observed for percentage of 

fetuses with skeletal malformations (short rib XIII) per litter and variations (wavy rib or wavy rib 

cartilage) in the 13 and 25 mg boron/kg/day groups. A significant trend test (p<0.05) resulted for 

decrease in rudimentary extra rib on lumbar I (a variation). The LOAEL for Phase I of this study was 

identified as 13 mg boron/kg/day, based on decreased fetal body weight and skeletal malformations. The 

NOAEL for this phase was identified as 10 mg boron/kg/day. 

In the Phase II study, a significant trend for increased number and percent of dead pups was seen between 

pnd 0 and 4, but not between pnd 4 and 21. This appeared to be due to the non-significant early postnatal 

mortality in the 25.3 mg boron/kg/day group. There were no effects of boric acid on the pup body weight 

from pnd 0 to 21; therefore, fetal body weight deficits (identified in Phase I) did not continue into the 

postnatal period (Phase II). The percentage of pups per litter with short rib XIII was increased on pnd 

21 in the 25.3 mg boron/kg/day group. A LOAEL of 25.3 mg boron/kg/day, with an associated NOAEL 

of 12.9 mg boron/kg/day, was identified for skeletal malformations in Phase II of this study. 

Dose and end point used for MRL derivation: BMDL05 of 10.3 mg/kg/day for reduced fetal body weight 

[ ] NOAEL [ ] LOAEL [X] BMDL05 

Allen et al. (1996) performed multiple benchmark dose (BMD) analyses on single-study or combined data 

from Heindel et al. (1992) and Price et al. (1996a) for all statistically significant developmental end points 

(Table A-1). Fetal body weight changes were analyzed using the average fetal weight for each litter with 

live fetuses. The modeling of rib effects aimed to differentiate whether treatment-related differences in 

the lumbar rib were variations or malformations. Thus, a weighting scheme was applied to represent 

three possible interpretations of severity of this effect; that is, a missing rib is: (a) trivially different from 

“normal” (1/6 weighting), (b) intermediate between a trivial or frank malformation (1/2 weighting), or 

(c) considered a frank malformation (5/6 weighting). Rib count analysis involved adjusting up (if 

rudimentary or full lumbar ribs present) or down (shortened rib XIII or rib agenesis) the base count of 

13 rib pairs for each fetus analyzed. Benchmark responses (BMRs) were chosen for each end point. The 

BMD expected to result in the BMR, while the BMDL05 was defined as the 95% lower bound on the 

BMD. The data were modeled with a continuous power model using an F-test evaluation of goodness of 

fit. 
 

 

 

 

BORON A-10
 

APPENDIX A
 

Table A-1. Benchmark Dose Modeling of Developmental Effects of Oral Boric 

Acid Exposure to Rats
 

Lower bound 

BMDb on BMDc 

Goodness-of-fit (mg boron/ (mg boron/ 

End point Study data p-valuea kg/day) kg/day) 

Fetal body weight as Heindel et al. 1994 0.24 14.0 9.8 

continuous data Price et al. 1996a 0.89 11.9 8.2 

(BMR=5% reduction) Combined 0.58 13.7 10.3 

Fetal body weight as Heindel et al. 1994 0.24 12.8 8.4 

continuous data Price et al. 1996a 0.89 8.6 5.4 

(BMR=1/2 standard deviation 

below control) Combined 0.58 11.4 8.4 

Fetal body weight as Heindel et al. 1994 0.44 22.6 20.1 

dichotomous incidence data Price et al. 1996a 0.01 8.2 5.4 

(BMR=5% reduction) Combined NA NA NA 

Shortening or agenesis of rib Heindel et al. 1994 0.07 24.9 18.6 

XIII Price et al. 1996a 0.64 29.9 21.5 

Combined 0.42 24.5 21.0 

Missing lumbar ribs Heindel et al. 1994 0.99 1.2 0.3 

Price et al. 1996a 0.78 1.5 0.6 

Combined 0.99 2.1 0.9 

Rib effects analysis: Heindel et al. 1994 0.27 21.2 16.5 

1/6 weighting for absence of Price et al. 1996a 0.78 32.9 25.7 

lumbar rib Combined NA NA NA 

Rib effects analysis: Heindel et al. 1994 0.02 13.5 10.2 

1/2 weighting for absence of Price et al. 1996a 0.64 45.3 30.3 

lumbar rib Combined NA NA NA 

Rib effects analysis: Heindel et al. 1994 <0.001 24.9 20.5 

5/6 weighting for absence of Price et al. 1996a 0.53 53.7 31.2 

lumbar rib Combined NA NA NA 

Rib effects analysis: Heindel et al. 1994 0.002 16.5 12.8 

rib count for absence of Price et al. 1996a 0.08 25.6 16.5 

lumbar rib Combined NA NA NA 

a

p-values for assessing adequacy of the models for predicting the observed data of Heindel et al. (1992) and Price et 

al. (1996a)

b

Benchmark dose: model estimated dose expected to result in the BMR 

c

95% lower bound on the BMD 

BMR = benchmark response; NA = not applicable 

Source: Heindel et al. 1992; Price et al. 1996a 
 

 

 

 

 

 

 

 

 

 

 

 

BORON A-11 

APPENDIX A 

A likelihood ratio test indicated that the response data from both studies could be modeled as a single 

dose-response function. Of the developmental end points modeled, the lowest resulting BMDL05 was 

10.3 mg boron/kg/day for fetal body weight (litter weight averages), which was similar to the NOAEL of 

10 mg boron/kg/day from the Price et al. (1996a) study. 

Uncertainty Factors used in MRL derivation: A total uncertainty factor of 66 was used. 

[ ] 10 for use of a LOAEL 

[X] 3.3 for extrapolation of toxicokinetics from animals to humans 

[X] 3.16 for extrapolation of toxicodynamics from animals to humans 

[X] 2.0 for human toxicokinetic variability 

[X] 3.16 for human toxicodynamic variability 

In deriving a reference dose (RfD) for chronic oral exposures to boron, the U.S. EPA applied chemicalspecific uncertainty factors to the BMDL05 of 10.3 mg boron/kg/day reported by Allen et al. (1996) (EPA 

2004). Rather than using the default uncertainty factors of 10 for interspecies extrapolation and 10 for 

interindividual human variability, each uncertainty factor was further delineated into toxicokinetic and 

toxicodynamic components specific to boron. Since the critical effect (reduced fetal body weight in 

animals) and point of departure (BMDL05 of 10.3 mg/kg/day) for intermediate oral exposure to boron are 

the same as those for chronic oral exposures, as identified by EPA (2004), the chemical-specific 

uncertainty factors derived by U.S. EPA to derive a chronic RfD are appropriate for use in deriving the 

intermediate-duration MRL. 

Briefly, each uncertainty factor of 10 for extrapolation from animals to humans and human variability was 

initially separated into default toxicokinetic and toxicodynamic adjustment factors of 3.16 (100.5) each to 

account for species differences in toxicokinetic disposition and toxicodymanic responses to orallyingested boron. The same division was made for the uncertainty factor of 10 for human variability. Thus, 

the composite uncertainty factor (UFTOTAL) for the intermediate-duration oral MRL is defined as given by 

EPA (2004) as: 

UFTOTAL = (AFAK x AFAD x AFHK x AFHD x UF) 

where: 

AFAK = interspecies toxicokinetic adjustment factor 

AFAD = interspecies toxicodynamic adjustment factor 

AFHK = interindividual toxicokinetic adjustment factor 

AFHD = interindividual toxicodynamic adjustment factor 

UF = other uncertainty factors (e.g., use of a LOAEL instead of a NOAEL) 

Since no data were available to adequately describe the mode(s) or mechanism(s) of action for boron 

toxicity in animals or humans, the default toxicodynamic adjustment factor of 3.16 was used to account 

for inter- and intraspecies uncertainties in toxicodynamics. 

The pregnant female is considered to be a sensitive population for boron exposure, as fetal effects in rats 

are the most sensitive end point identified for boron toxicity. Since boron exhibits near first-order 

toxicokinetics, distributing freely between total body water and tissues (except for bone, in which it 

accumulates to approximately 4-fold that of plasma [Chapin et al. 1997]), variability between maternal 

and fetal kinetics should be essentially equal. Thus, maternal boron plasma concentration is an 

appropriate surrogate for fetal plasma levels. No data are available to relate rat and human plasma boron 

concentration. However, boron is not metabolized, but almost completely eliminated in the urine, making 

renal clearance an appropriate kinetic factor for comparison of toxicokinetic differences between rats and 

humans. Given the known distribution of boron to total body water and bone, two-compartment 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON A-12 

APPENDIX A 

pharmacokinetic models for boron in rats and humans can describe plasma concentration in terms of renal 

clearance. Boron’s toxicity is likely to be related to a continuous exposure over an extended portion of 

fetal development in which a steady state of circulating boron is achieved. Under the assumption of 

steady-state plasma boron levels, and assuming approximately complete clearance of born to urine, the 

two-compartment model can be simplified to the following expression: 

CSS = (De x fa x BW) / Cl 

where: 

De = external dose of ingested boron (mg boron/kg body weight/day) 

fa = fraction of ingested boron absorbed from the gut 

BW = body weight (kg) 

Cl = renal clearance (mL/minute) 

Assuming that the ratio of 1 for internal, steady-state doses in rats and humans results in equivalent 

responses, the expressions for the plasma boron concentration in rats and humans can be expressed as the 

following ratio, which serves as the AFAK: 

AFAK = (ClR x fAH x BWH) / (ClH x fAR x BWR) 

where the subscripts R and H represent rats and humans. Values for mean renal clearance of 1.0 and 

66.1 mL/minute in pregnant rats and humans, respectively, were derived from the studies of Vaziri et al. 

(2001), and Pahl et al. (2001), which also provided pregnant rat and human body weights of 0.303 and 

67.6 kg, respectively. Using gastrointestinal absorption fractions of 0.92 (Schou et al. 1984) and 

0.95 (Vanderpool et al. 1994) for fAH and fAR, respectively, AFAK is derived as follows: 

AFAK = (1.00 x 0.92 x 67.6) / (66.1 x 0.95 x 0.303) 

= 62.2 / 19.0 

= 3.3 

The assessment of human variability in boron toxicokinetics utilized glomerular filtration rate (GFR) as a 

surrogate for renal clearance. Pregnant women were considered the sensitive population, particularly 

those women with compromised renal function (3–5% preeclamptic women in the U.S. population). 

Using a modification of Dourson et al. (1998), data from women with normal renal function were used to 

define an AFHK as: 

AFHK = GFRAVG / (GFRAVG – (3 x SDGFR)) 

where GFRAVG and SDGFR are mean and standard deviation of the GFR for healthy women. Three 

standard deviations below the mean GFR was chosen to account for the women with very low GFR. 

From the studies of Dunlop (1981), Krutzen et al. (1992), and Sturgiss et al. (1996), a mean GFR of 

161.5 mL/minute and a mean GFR-3SDGFR of 85.8 mL/minute resulted in an AFHK of 1.93. This number 

was rounded to 2.0 to account for uncertainties in human GFR. 

Based on these analyses, the total uncertainty factor applied to the BMDL05 of 10.3 mg boron/kg is 

derived as: 

UFTOTAL = (AFAK x AFAD x AFHK x AFHD x UF) 

= (3.3 x 3.16 x 2.0 x 3.16 x 1) 

= 66 

Was a conversion used from ppm in food or water to a mg/body weight dose? No. 
 

 

 

 

 

BORON A-13 

APPENDIX A 

If an inhalation study in animals, list the conversion factors used in determining human equivalent dose: 

Not applicable. 

Other additional studies or pertinent information that lend support to this MRL: Reproductive effects, 

including testicular atrophy and histopathology, sperm abnormalities, and reduced sperm production have 

been observed in mice, rats, and dogs after intermediate-duration ingestion of doses of 26 mg 

boron/kg/day (as boric acid or borax) and higher (Dixon et al. 1979; Fukuda et al. 2000; Harris et al. 

1992; Ku et al. 1993a; Kudo et al. 2000; Seal and Weeth 1980; Treinen and Chapin 1991; Weir and 

Fisher 1972; Yoshizaki et al. 1999). Systemic effects have been observed in rats and dogs at higher 

doses. Hematological alterations (splenic extramedullary hematopoiesis and decreased hemoglobin 

levels) have been observed at 60.5 or 72 mg boron/kg/day (NTP 1987; Weir and Fisher 1972), 

desquamation of skin on paws and tail and inflamed eyes have been observed in rats exposed to 150 mg 

boron/kg/day (Weir and Fisher 1972), and hyperkeratosis and/or acanthosis of the stomach has been 

observed at 577 mg boron/kg/day (NTP 1987). 

Agency Contacts (Chemical Managers): Malcolm Williams 
BORON A-14
 

APPENDIX A 

This page is intentionally blank. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON	 B-1 

APPENDIX B. USER'S GUIDE 

Chapter 1 

Public Health Statement 

This chapter of the profile is a health effects summary written in non-technical language. Its intended 

audience is the general public, especially people living in the vicinity of a hazardous waste site or 

chemical release. If the Public Health Statement were removed from the rest of the document, it would 

still communicate to the lay public essential information about the chemical. 

The major headings in the Public Health Statement are useful to find specific topics of concern. The 

topics are written in a question and answer format. The answer to each question includes a sentence that 

will direct the reader to chapters in the profile that will provide more information on the given topic. 

Chapter 2 

Relevance to Public Health 

This chapter provides a health effects summary based on evaluations of existing toxicologic, 

epidemiologic, and toxicokinetic information. This summary is designed to present interpretive, weightof-evidence discussions for human health end points by addressing the following questions: 

1.	 What effects are known to occur in humans? 

2.	 What effects observed in animals are likely to be of concern to humans? 

3.	 What exposure conditions are likely to be of concern to humans, especially around hazardous 

waste sites? 

The chapter covers end points in the same order that they appear within the Discussion of Health Effects 

by Route of Exposure section, by route (inhalation, oral, and dermal) and within route by effect. Human 

data are presented first, then animal data. Both are organized by duration (acute, intermediate, chronic). 

In vitro data and data from parenteral routes (intramuscular, intravenous, subcutaneous, etc.) are also 

considered in this chapter. 

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using 

existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer 

potency or perform cancer risk assessments. Minimal Risk Levels (MRLs) for noncancer end points (if 

derived) and the end points from which they were derived are indicated and discussed. 

Limitations to existing scientific literature that prevent a satisfactory evaluation of the relevance to public 

health are identified in the Chapter 3 Data Needs section. 

Interpretation of Minimal Risk Levels 

Where sufficient toxicologic information is available, ATSDR has derived MRLs for inhalation and oral 

routes of entry at each duration of exposure (acute, intermediate, and chronic). These MRLs are not 

meant to support regulatory action, but to acquaint health professionals with exposure levels at which 

adverse health effects are not expected to occur in humans. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON B-2 

APPENDIX B 

MRLs should help physicians and public health officials determine the safety of a community living near 

a chemical emission, given the concentration of a contaminant in air or the estimated daily dose in water. 

MRLs are based largely on toxicological studies in animals and on reports of human occupational 

exposure. 

MRL users should be familiar with the toxicologic information on which the number is based. Chapter 2, 

"Relevance to Public Health," contains basic information known about the substance. Other sections such 

as Chapter 3 Section 3.9, "Interactions with Other Substances,” and Section 3.10, "Populations that are 

Unusually Susceptible" provide important supplemental information. 

MRL users should also understand the MRL derivation methodology. MRLs are derived using a 

modified version of the risk assessment methodology that the Environmental Protection Agency (EPA) 

provides (Barnes and Dourson 1988) to determine reference doses (RfDs) for lifetime exposure. 

To derive an MRL, ATSDR generally selects the most sensitive end point which, in its best judgement, 

represents the most sensitive human health effect for a given exposure route and duration. ATSDR 

cannot make this judgement or derive an MRL unless information (quantitative or qualitative) is available 

for all potential systemic, neurological, and developmental effects. If this information and reliable 

quantitative data on the chosen end point are available, ATSDR derives an MRL using the most sensitive 

species (when information from multiple species is available) with the highest no-observed-adverse-effect 

level (NOAEL) that does not exceed any adverse effect levels. When a NOAEL is not available, a 

lowest-observed-adverse-effect level (LOAEL) can be used to derive an MRL, and an uncertainty factor 

(UF) of 10 must be employed. Additional uncertainty factors of 10 must be used both for human 

variability to protect sensitive subpopulations (people who are most susceptible to the health effects 

caused by the substance) and for interspecies variability (extrapolation from animals to humans). In 

deriving an MRL, these individual uncertainty factors are multiplied together. The product is then 

divided into the inhalation concentration or oral dosage selected from the study. Uncertainty factors used 

in developing a substance-specific MRL are provided in the footnotes of the levels of significant exposure 

(LSE) tables. 

Chapter 3 

Health Effects 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables and figures are used to summarize health effects and illustrate graphically levels of exposure 

associated with those effects. These levels cover health effects observed at increasing dose 

concentrations and durations, differences in response by species, MRLs to humans for noncancer end 

points, and EPA's estimated range associated with an upper- bound individual lifetime cancer risk of 1 in 

10,000 to 1 in 10,000,000. Use the LSE tables and figures for a quick review of the health effects and to 

locate data for a specific exposure scenario. The LSE tables and figures should always be used in 

conjunction with the text. All entries in these tables and figures represent studies that provide reliable, 

quantitative estimates of NOAELs, LOAELs, or Cancer Effect Levels (CELs). 

The legends presented below demonstrate the application of these tables and figures. Representative 

examples of LSE Table 3-1 and Figure 3-1 are shown. The numbers in the left column of the legends 

correspond to the numbers in the example table and figure. 
 

 

 

 

 

 

 

 

 

 

 

BORON	 B-3 

APPENDIX B 

LEGEND 

See Sample LSE Table 3-1 (page B-6) 

(1)	 Route of Exposure. One of the first considerations when reviewing the toxicity of a substance 

using these tables and figures should be the relevant and appropriate route of exposure. Typically 

when sufficient data exist, three LSE tables and two LSE figures are presented in the document. 

The three LSE tables present data on the three principal routes of exposure, i.e., inhalation, oral, 

and dermal (LSE Tables 3-1, 3-2, and 3-3, respectively). LSE figures are limited to the inhalation 

(LSE Figure 3-1) and oral (LSE Figure 3-2) routes. Not all substances will have data on each 

route of exposure and will not, therefore, have all five of the tables and figures. 

(2)	 Exposure Period. Three exposure periods—acute (less than 15 days), intermediate (15– 

364 days), and chronic (365 days or more)—are presented within each relevant route of exposure. 

In this example, an inhalation study of intermediate exposure duration is reported. For quick 

reference to health effects occurring from a known length of exposure, locate the applicable 

exposure period within the LSE table and figure. 

(3)	 Health Effect. The major categories of health effects included in LSE tables and figures are 

death, systemic, immunological, neurological, developmental, reproductive, and cancer. 

NOAELs and LOAELs can be reported in the tables and figures for all effects but cancer. 

Systemic effects are further defined in the "System" column of the LSE table (see key number 

18). 

(4)	 Key to Figure. Each key number in the LSE table links study information to one or more data 

points using the same key number in the corresponding LSE figure. In this example, the study 

represented by key number 18 has been used to derive a NOAEL and a Less Serious LOAEL 

(also see the two "18r" data points in sample Figure 3-1). 

(5)	 Species. The test species, whether animal or human, are identified in this column. Chapter 2, 

"Relevance to Public Health," covers the relevance of animal data to human toxicity and 

Section 3.4, "Toxicokinetics," contains any available information on comparative toxicokinetics. 

Although NOAELs and LOAELs are species specific, the levels are extrapolated to equivalent 

human doses to derive an MRL. 

(6)	 Exposure Frequency/Duration. The duration of the study and the weekly and daily exposure 

regimens are provided in this column. This permits comparison of NOAELs and LOAELs from 

different studies. In this case (key number 18), rats were exposed to “Chemical x” via inhalation 

for 6 hours/day, 5 days/week, for 13 weeks. For a more complete review of the dosing regimen, 

refer to the appropriate sections of the text or the original reference paper (i.e., Nitschke et al. 

1981). 

(7)	 System. This column further defines the systemic effects. These systems include respiratory, 

cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, and 

dermal/ocular. "Other" refers to any systemic effect (e.g., a decrease in body weight) not covered 

in these systems. In the example of key number 18, one systemic effect (respiratory) was 

investigated. 

(8)	 NOAEL. A NOAEL is the highest exposure level at which no harmful effects were seen in the 

organ system studied. Key number 18 reports a NOAEL of 3 ppm for the respiratory system, 

which was used to derive an intermediate exposure, inhalation MRL of 0.005 ppm (see 

footnote "b"). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON	 B-4 

APPENDIX B 

(9)	 LOAEL. A LOAEL is the lowest dose used in the study that caused a harmful health effect. 

LOAELs have been classified into "Less Serious" and "Serious" effects. These distinctions help 

readers identify the levels of exposure at which adverse health effects first appear and the 

gradation of effects with increasing dose. A brief description of the specific end point used to 

quantify the adverse effect accompanies the LOAEL. The respiratory effect reported in key 

number 18 (hyperplasia) is a Less Serious LOAEL of 10 ppm. MRLs are not derived from 

Serious LOAELs. 

(10)	 Reference. The complete reference citation is given in Chapter 9 of the profile. 

(11)	 CEL. A CEL is the lowest exposure level associated with the onset of carcinogenesis in 

experimental or epidemiologic studies. CELs are always considered serious effects. The LSE 

tables and figures do not contain NOAELs for cancer, but the text may report doses not causing 

measurable cancer increases. 

(12)	 Footnotes. Explanations of abbreviations or reference notes for data in the LSE tables are found 

in the footnotes. Footnote "b" indicates that the NOAEL of 3 ppm in key number 18 was used to 

derive an MRL of 0.005 ppm. 

LEGEND 

See Sample Figure 3-1 (page B-7) 

LSE figures graphically illustrate the data presented in the corresponding LSE tables. Figures help the 

reader quickly compare health effects according to exposure concentrations for particular exposure 

periods. 

(13)	 Exposure Period. The same exposure periods appear as in the LSE table. In this example, health 

effects observed within the acute and intermediate exposure periods are illustrated. 

(14)	 Health Effect. These are the categories of health effects for which reliable quantitative data 

exists. The same health effects appear in the LSE table. 

(15)	 Levels of Exposure. Concentrations or doses for each health effect in the LSE tables are 

graphically displayed in the LSE figures. Exposure concentration or dose is measured on the log 

scale "y" axis. Inhalation exposure is reported in mg/m3 or ppm and oral exposure is reported in 

mg/kg/day. 

(16)	 NOAEL. In this example, the open circle designated 18r identifies a NOAEL critical end point in 

the rat upon which an intermediate inhalation exposure MRL is based. The key number 18 

corresponds to the entry in the LSE table. The dashed descending arrow indicates the 

extrapolation from the exposure level of 3 ppm (see entry 18 in the table) to the MRL of 

0.005 ppm (see footnote "b" in the LSE table). 

(17)	 CEL. Key number 38m is one of three studies for which CELs were derived. The diamond 

symbol refers to a CEL for the test species-mouse. The number 38 corresponds to the entry in the 

LSE table. 
 

 

BORON	 B-5 

APPENDIX B 

(18)	 Estimated Upper-Bound Human Cancer Risk Levels. This is the range associated with the upperbound for lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. These risk levels are derived 

from the EPA's Human Health Assessment Group's upper-bound estimates of the slope of the 

cancer dose response curve at low dose levels (q1*). 

(19)	 Key to LSE Figure. The Key explains the abbreviations and symbols used in the figure. 
SAMPLE

1 → Table 3-1. Levels of Significant Exposure to [Chemical x] – Inhalat

LOAEL (effect) Exposure 

Key to frequency/ NOAEL Less serious Serious (ppm) 

figurea Species duration System (ppm) (ppm) 

2 3 4 

→ INTERMEDIATE EXPOSURE 

5 6 7 8 9 

→ Systemic ↓ ↓ ↓ ↓ ↓ 

18 Rat 13 wk Resp 3b 10 (hyperplasia) 

→ 5 d/wk 

6 hr/d 

CHRONIC EXPOSURE 

Cancer 11 

↓

38 Rat 18 mo 20 (CEL, multiple 

5 d/wk organs) 7 hr/d 

39 Rat 89–104 wk 10 (CEL, lung tumors, 

5 d/wk nasal tumors) 6 hr/d 

40 Mouse 79–103 wk 10 (CEL, lung tumors, 

5 d/wk hemangiosarcomas) 6 hr/d 

12 → a The number corresponds to entries in Figure 3-1. b Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5x10-3 ppm; dose adjusted for intermittent 

by an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability). 

BORON B-8
 

APPENDIX B 

This page is intentionally blank. 
 

 

BORON C-1 

APPENDIX C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS 

ACGIH American Conference of Governmental Industrial Hygienists 

ACOEM American College of Occupational and Environmental Medicine 

ADI acceptable daily intake 

ADME absorption, distribution, metabolism, and excretion 

AED atomic emission detection 

AFID alkali flame ionization detector 

AFOSH Air Force Office of Safety and Health 

ALT alanine aminotransferase 

AML acute myeloid leukemia 

AOAC Association of Official Analytical Chemists 

AOEC Association of Occupational and Environmental Clinics 

AP alkaline phosphatase 

APHA American Public Health Association 

AST aspartate aminotransferase 

atm atmosphere 

ATSDR Agency for Toxic Substances and Disease Registry 

AWQC Ambient Water Quality Criteria 

BAT best available technology 

BCF bioconcentration factor 

BEI Biological Exposure Index 

BMD/C benchmark dose or benchmark concentration 

BMDX dose that produces a X% change in response rate of an adverse effect 

BMDLX 95% lower confidence limit on the BMDX 

BMDS Benchmark Dose Software 

BMR benchmark response 

BSC Board of Scientific Counselors 

C centigrade 

CAA Clean Air Act 

CAG Cancer Assessment Group of the U.S. Environmental Protection Agency 

CAS Chemical Abstract Services 

CDC Centers for Disease Control and Prevention 

CEL cancer effect level 

CELDS Computer-Environmental Legislative Data System 

CERCLA Comprehensive Environmental Response, Compensation, and Liability Act 

CFR Code of Federal Regulations 

Ci curie 

CI confidence interval 

CL ceiling limit value 

CLP Contract Laboratory Program 

cm centimeter 

CML chronic myeloid leukemia 

CPSC Consumer Products Safety Commission 

CWA Clean Water Act 

DHEW Department of Health, Education, and Welfare 

DHHS Department of Health and Human Services 

DNA deoxyribonucleic acid 

DOD Department of Defense 

DOE Department of Energy 

DOL Department of Labor 
 

 

BORON C-2 

APPENDIX C 

DOT Department of Transportation 

DOT/UN/ Department of Transportation/United Nations/ 

NA/IMDG North America/Intergovernmental Maritime Dangerous Goods Code 

DWEL drinking water exposure level 

ECD electron capture detection 

ECG/EKG electrocardiogram 

EEG electroencephalogram 

EEGL Emergency Exposure Guidance Level 

EPA Environmental Protection Agency 

F Fahrenheit 

F1 first-filial generation 

FAO Food and Agricultural Organization of the United Nations 

FDA Food and Drug Administration 

FEMA Federal Emergency Management Agency 

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act 

FPD flame photometric detection 

fpm feet per minute 

FR Federal Register 

FSH follicle stimulating hormone 

g gram 

GC gas chromatography 

gd gestational day 

GLC gas liquid chromatography 

GPC gel permeation chromatography 

HPLC high-performance liquid chromatography 

HRGC high resolution gas chromatography 

HSDB Hazardous Substance Data Bank 

IARC International Agency for Research on Cancer 

IDLH immediately dangerous to life and health 

ILO International Labor Organization 

IRIS Integrated Risk Information System 

Kd adsorption ratio 

kg kilogram 

kkg metric ton 

Koc organic carbon partition coefficient 

Kow octanol-water partition coefficient 

L liter 

LC liquid chromatography 

LC50 lethal concentration, 50% kill 

LCLo lethal concentration, low 

LD50 lethal dose, 50% kill 

LDLo lethal dose, low 

LDH lactic dehydrogenase 

LH luteinizing hormone 

LOAEL lowest-observed-adverse-effect level 

LSE Levels of Significant Exposure 

LT50 lethal time, 50% kill 

m meter 

MA trans,trans-muconic acid 

MAL maximum allowable level 

mCi millicurie 
 

 

BORON C-3 

APPENDIX C 

MCL maximum contaminant level 

MCLG maximum contaminant level goal 

MF modifying factor 

MFO mixed function oxidase 

mg milligram 

mL milliliter 

mm millimeter 

mmHg millimeters of mercury 

mmol millimole 

mppcf millions of particles per cubic foot 

MRL Minimal Risk Level 

MS mass spectrometry 

NAAQS National Ambient Air Quality Standard 

NAS National Academy of Science 

NATICH National Air Toxics Information Clearinghouse 

NATO North Atlantic Treaty Organization 

NCE normochromatic erythrocytes 

NCEH National Center for Environmental Health 

NCI National Cancer Institute 

ND not detected 

NFPA National Fire Protection Association 

ng nanogram 

NHANES National Health and Nutrition Examination Survey 

NIEHS National Institute of Environmental Health Sciences 

NIOSH National Institute for Occupational Safety and Health 

NIOSHTIC NIOSH's Computerized Information Retrieval System 

NLM National Library of Medicine 

nm nanometer 

nmol nanomole 

NOAEL no-observed-adverse-effect level 

NOES National Occupational Exposure Survey 

NOHS National Occupational Hazard Survey 

NPD nitrogen phosphorus detection 

NPDES National Pollutant Discharge Elimination System 

NPL National Priorities List 

NR not reported 

NRC National Research Council 

NS not specified 

NSPS New Source Performance Standards 

NTIS National Technical Information Service 

NTP National Toxicology Program 

ODW Office of Drinking Water, EPA 

OERR Office of Emergency and Remedial Response, EPA 

OHM/TADS Oil and Hazardous Materials/Technical Assistance Data System 

OPP Office of Pesticide Programs, EPA 

OPPT Office of Pollution Prevention and Toxics, EPA 

OPPTS Office of Prevention, Pesticides and Toxic Substances, EPA 

OR odds ratio 

OSHA Occupational Safety and Health Administration 

OSW Office of Solid Waste, EPA 

OTS Office of Toxic Substances 
 

 

BORON C-4 

APPENDIX C 

OW Office of Water 

OWRS Office of Water Regulations and Standards, EPA 

PAH polycyclic aromatic hydrocarbon 

PBPD physiologically based pharmacodynamic 

PBPK physiologically based pharmacokinetic 

PCE polychromatic erythrocytes 

PEL permissible exposure limit 

pg picogram 

PHS Public Health Service 

PID photo ionization detector 

pmol picomole 

PMR proportionate mortality ratio 

ppb parts per billion 

ppm parts per million 

ppt parts per trillion 

PSNS pretreatment standards for new sources 

RBC red blood cell 

REL recommended exposure level/limit 

RfC reference concentration 

RfD reference dose 

RNA ribonucleic acid 

RQ reportable quantity 

RTECS Registry of Toxic Effects of Chemical Substances 

SARA Superfund Amendments and Reauthorization Act 

SCE sister chromatid exchange 

SGOT serum glutamic oxaloacetic transaminase 

SGPT serum glutamic pyruvic transaminase 

SIC standard industrial classification 

SIM selected ion monitoring 

SMCL secondary maximum contaminant level 

SMR standardized mortality ratio 

SNARL suggested no adverse response level 

SPEGL Short-Term Public Emergency Guidance Level 

STEL short term exposure limit 

STORET Storage and Retrieval 

TD50 toxic dose, 50% specific toxic effect 

TLV threshold limit value 

TOC total organic carbon 

TPQ threshold planning quantity 

TRI Toxics Release Inventory 

TSCA Toxic Substances Control Act 

TWA time-weighted average 

UF uncertainty factor 

U.S. United States 

USDA United States Department of Agriculture 

USGS United States Geological Survey 

VOC volatile organic compound 

WBC white blood cell 

WHO World Health Organization 
 

BORON C-5 

APPENDIX C 

> greater than ≥ greater than or equal to 

= equal to 

< less than ≤ less than or equal to 

% percent α alpha β beta γ gamma δ delta 

μm micrometer 

μg microgram q1

* cancer slope factor 

– negative 

+ positive 

(+) weakly positive result 

(–) weakly negative result 
BORON C-6
 

APPENDIX C 

This page is intentionally blank. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BORON D-1 

APPENDIX D. INDEX
 

absorbed dose............................................................................................................................................101
 

adipose tissue ...................................................................................................................................... 95, 148
 

adrenals ......................................................................................................................................... 75, 90, 110
 

adsorbed....................................................................................................................................................140
 

adsorption.......................................................................................................................... 134, 140, 141, 152
 

ambient air ................................................................................................................................................142
 

bioaccumulation........................................................................................................................................153
 

bioconcentration factor .............................................................................................................................141
 

biomarker .................................................................................................................. 100, 101, 115, 117, 156
 

blood cell count...........................................................................................................................................36
 

body weight effects............................................................................................................................... 21, 76
 

breast milk................................................................................................................................. 147, 151, 154
 

cancer........................................................................................................ 4, 5, 13, 38, 85, 99, 110, 111, 130
 

carcinogen.................................................................................................................................................170
 

carcinogenic .................................................................................................................................. 14, 22, 170
 

carcinogenicity............................................................................................................................................13
 

cardiovascular ............................................................................. 12, 17, 18, 19, 24, 35, 40, 84, 86, 100, 163
 

Cardiovascular Effects.......................................................................................................................... 35, 40
 

chromosomal aberrations............................................................................................................................87
 

clearance ....................................................................................................................................... 91, 92, 115
 

death................................................................................................ 5, 11, 17, 22, 23, 38, 39, 40, 78, 86, 170
 

deoxyribonucleic acid (see DNA)...............................................................................................................96
 

dermal effects.................................................................................................................... 20, 24, 75, 86, 103
 

developmental effects ................. 12, 18, 20, 37, 82, 84, 85, 87, 96, 100, 107, 108, 110, 111, 113, 115, 116
 

DNA (see deoxyribonucleic acid)....................................................................................................... 96, 101
 

elimination rate ...........................................................................................................................................92
 

endocrine......................................................................................................................................... 75, 97, 98
 

endocrine effects.........................................................................................................................................75
 

erythema............................................................................................................................ 17, 39, 75, 86, 115
 

fetus................................................................................................................................. 12, 20, 98, 100, 114
 

follicle stimulating hormone (see FSH)......................................................................................................75
 

FSH (see follicle stimulating hormone).................................................................................... 75, 80, 96, 98
 

gastrointestinal effects ...................................................................................................... 11, 17, 35, 40, 102
 

general population................................................................................................................. 9, 148, 151, 170
 

genotoxic......................................................................................................................................... 22, 85, 87
 

genotoxicity.................................................................................................................................................13
 

groundwater ............................................................................................ 3, 85, 130, 134, 139, 143, 159, 161
 

half-life.............................................................................................................. 11, 35, 91, 92, 100, 105, 140
 

hematological effects ...................................................................................................................... 36, 73, 86
 

hepatic effects ....................................................................................................................................... 36, 73
 

hydrolysis..................................................................................................................................................124
 

immune system .........................................................................................................................................114
 

immunological ................................................................................................................................ 22, 37, 76
 

immunological effects.................................................................................................................................76
 

Kow ............................................................................................................................................ 122, 123, 124
 

LD50....................................................................................................................................................... 39, 40
 

lymphoreticular...........................................................................................................................................37
 

milk ............................................................................................................................................. 74, 144, 154
 
 

 

 

 

 

 

 

 

 

 

 

BORON D-2 

APPENDIX D 

musculoskeletal effects ......................................................................................................................... 36, 40
 

neoplastic ............................................................................................................................................ 13, 110
 

neurobehavioral...........................................................................................................................................98
 

neurochemical...........................................................................................................................................114
 

neurological effects........................................................................................... 37, 76, 77, 87, 102, 108, 114
 

neurophysiological....................................................................................................................................114
 

nuclear...........................................................................................................................................................9
 

ocular effects......................................................................................................... 24, 36, 40, 76, 86, 87, 107
 

pharmacodynamic......................................................................................................................... 16, 92, 163
 

pharmacokinetic........................................................................................................................ 92, 93, 94, 99
 

renal effects......................................................................................................................... 24, 36, 74, 86, 96
 

reproductive effects......................................................... 12, 37, 77, 79, 80, 81, 82, 84, 87, 96, 97, 113, 117
 

respiratory effects............................................................................................................................ 23, 24, 40
 

retention .................................................................................................................................. 11, 16, 80, 109
 

systemic effects..................................................................................................... 12, 14, 21, 24, 40, 86, 101
 

thyroid................................................................................................................................................. 75, 109
 

toxicokinetic............................................................................................................ 21, 22, 97, 115, 116, 163
 

tremors ........................................................................................................................................................76
 

tumors .......................................................................................................................................................130