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TOXICOLOGICAL PROFILE FOR
 

VANADIUM
 


 


 


 


 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

Agency for Toxic Substances and Disease Registry
 

September 2009 
 

 

 


 

VANADIUM ii 

DISCLAIMER

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

Agency for Toxic Substances and Disease Registry. 

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

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

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

agency determination or policy. 

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VANADIUM iii 

UPDATE STATEMENT
 

A Toxicological Profile for Vanadium was released in 1992. This present edition supersedes any 

previously released draft or final profile. 

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

status of previously released profiles, contact ATSDR at: 

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology and Environmental Medicine/Applied Toxicology Branch
 

1600 Clifton Road NE
 

Mailstop F-62
 

Atlanta, Georgia 30333
 

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VANADIUM iv 

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v 

FOREWORD 

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

Toxic Substances and Disease Registry (A TSDR) 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 necesslll)'. 

The A TSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects 

information for these toxic substances described therein. Each peer-reviewed profile identifies and reviews 

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

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

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

The focus ofthe profiles is on health and toxicologic information. Each toxicological profile begins 

with a public health statement that describes, in nontechnical language, a substance's relevant toxicological 

properties. Following the public health statement is information concerning levels ofsignificant human 

exposure and, where known, significant health effects. The adequacy of information to determine a 

substance's health effects is described in a health effects summlll)'. Data needs that are ofsignificance to 

protection ofpublic health are identified by A TSDR and EPA. 

Each profile includes the following: 

(A) The examination, summlll)', and interpretation ofavailable toxicologic information and 

epidemiologic evaluations on a toxic substance to ascertain the levels ofsignificant human 

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

(B) 	 A determination ofwhether adequate information on the health effects ofeach substance is 

available or in the process of development to determine levels of exposure 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 of 

exposure that may present significant risk ofadverse 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. We pIan to 

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

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

Comments should be sent to: 

Agency for Toxic Substances and Disease Registry 

Division of Toxicology and Environmental Medicine 

1600 Clifton Road, N.E. 

Mail Stop F-62 

Atlanta, Georgia 30333 
VI 

The toxicological profiles are developed under the Comprehensive Environmental Response, 

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

I 04(i)(1) directs the Administrator ofATSDR 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) of 

CERCLA, as amended, directs the Administrator ofA TSDR 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 

I 04(i)(1 XB), to respond to requests for consultation under section 104(iX 4), and as otherwise necessary to 

support the site-specific response actions conducted by ATSDR. 

This profile reflects ATSDR's assessment of all relevant toxicologic testing and information 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 is being made available for public review. Final responsibility for the contents 

and views expressed in this toxicological profile resides with ATSDR. 

Howard Frumkin, M.D., Dr. P.H. VThomas R. Frieden, M.D., M.P.H. 

Director, National Center for Environmental Administrator, Agency for Toxic Substances and 

Health/Agency for Toxic Substances and Disease Disease Registry 

Registry 
 

 

 

 

 

 

 


 


 


 


 

VANADIUM 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. 

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VANADIUM 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. 

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VANADIUM ix 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHOR(S): 

Jessilynn Taylor, M.S., CDR USPHS
 

Sam Keith, M.S., CHP
 

Larry Cseh, M.S.A., R.S., CPT USPHS
 

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

Lisa Ingerman, Ph.D., DABT
 

Lara Chappell, Ph.D.
 

Jennifer Rhoades, B.A.
 

Amy Hueber, M.L.S.
 

SRC, Inc., North Syracuse, NY
 

THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS: 

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

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

end points. 

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

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

profile, and makes recommendations for derivation of MRLs. 

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

consistency across profiles and adherence to instructions in the Guidance. 

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

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VANADIUM xi 

PEER REVIEW
 

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

1.	 Janusz Z. Byczkowski, Ph.D., DABT, Independent Consultant, Fairborn, Ohio; 

2.	 David Dorman, Ph.D., D.V.M., DABT, Associate Dean for Research and Graduate Studies, North 

Carolina State University, Raleigh, North Carolina; and 

3.	 Anna Fan, Ph.D., DABT, Chief, Pesticide and Environmental Toxicology Branch, Office of 

Environmental Health Hazard Assessment, California Environmental Protection Agency, 

Oakland/Sacramento, California. 

These experts collectively have knowledge of vanadium's physical and chemical properties, 

toxicokinetics, key health end points, mechanisms of action, human and animal exposure, and 

quantification of risk to humans. All reviewers were selected in conformity with the conditions for peer 

review specified in Section 104(I)(13) of the Comprehensive Environmental Response, Compensation, 

and Liability Act, as amended. 

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

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

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

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

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

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

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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 VANADIUM? .............................................................................................................1
 

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

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

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

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

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

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

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

EXPOSED TO VANADIUM? .....................................................................................................7
 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

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

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

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

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO VANADIUM IN THE
 

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

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

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

3. HEALTH EFFECTS..............................................................................................................................25
 

3.1 INTRODUCTION ......................................................................................................................25
 

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE....................................25
 

3.2.1 Inhalation Exposure ............................................................................................................26
 

3.2.1.1 Death...............................................................................................................................26
 

3.2.1.2 Systemic Effects..............................................................................................................27
 

3.2.1.3 Immunological and Lymphoreticular Effects .................................................................41
 

3.2.1.4 Neurological Effects .......................................................................................................41
 

3.2.1.5 Reproductive Effects.......................................................................................................41
 

3.2.1.6 Developmental Effects....................................................................................................42
 

3.2.1.7 Cancer.............................................................................................................................42
 

3.2.2 Oral Exposure .....................................................................................................................44
 

3.2.2.1 Death...............................................................................................................................44
 

3.2.2.2 Systemic Effects..............................................................................................................44
 

3.2.2.3 Immunological and Lymphoreticular Effects.................................................................64
 

3.2.2.4 Neurological Effects .......................................................................................................64
 

3.2.2.5 Reproductive Effects.......................................................................................................65
 

3.2.2.6 Developmental Effects....................................................................................................65
 

3.2.2.7 Cancer.............................................................................................................................66
 

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3.2.3 Dermal Exposure.................................................................................................................66
 

3.2.3.1 Death...............................................................................................................................66
 

3.2.3.2 Systemic Effects..............................................................................................................66
 

3.2.3.3 Immunological and Lymphoreticular Effects .................................................................66
 

3.2.3.4 Neurological Effects .......................................................................................................66
 

3.2.3.5 Reproductive Effects.......................................................................................................66
 

3.2.3.6 Developmental Effects....................................................................................................66
 

3.2.3.7 Cancer.............................................................................................................................66
 

3.3 GENOTOXICITY.......................................................................................................................66
 

3.4 TOXICOKINETICS ...................................................................................................................72
 

3.4.1 Absorption...........................................................................................................................72
 

3.4.1.1 Inhalation Exposure ........................................................................................................72
 

3.4.1.2 Oral Exposure .................................................................................................................73
 

3.4.1.3 Dermal Exposure.............................................................................................................73
 

3.4.2 Distribution .........................................................................................................................73
 

3.4.2.1 Inhalation Exposure ........................................................................................................73
 

3.4.2.2 Oral Exposure .................................................................................................................74
 

3.4.2.3 Dermal Exposure.............................................................................................................77
 

3.4.2.4 Other Routes of Exposure...............................................................................................77
 

3.4.3 Metabolism .........................................................................................................................77
 

3.4.4 Elimination and Excretion ..................................................................................................77
 

3.4.4.1 Inhalation Exposure ........................................................................................................77
 

3.4.4.2 Oral Exposure ................................................................................................................. 78
 

3.4.4.3 Dermal Exposure.............................................................................................................78
 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models...........78
 

3.5 MECHANISMS OF ACTION....................................................................................................80
 

3.5.1 Pharmacokinetic Mechanisms.............................................................................................80
 

3.5.2 Mechanisms of Toxicity......................................................................................................82
 

3.5.3 Animal-to-Human Extrapolations.......................................................................................82
 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS ...........................82
 

3.7 CHILDREN’S SUSCEPTIBILITY ............................................................................................83
 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT......................................................................85
 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Vanadium......................................86
 

3.8.2 Biomarkers Used to Characterize Effects Caused by Vanadium........................................87
 

3.9 INTERACTIONS WITH OTHER CHEMICALS......................................................................87
 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE ................................................87
 

3.11 METHODS FOR REDUCING TOXIC EFFECTS....................................................................88
 

3.11.1 Reducing Peak Absorption Following Exposure ................................................................88
 

3.11.2 Reducing Body Burden.......................................................................................................88
 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects..............................................89
 

3.12 ADEQUACY OF THE DATABASE.........................................................................................90
 

3.12.1 Existing Information on Health Effects of Vanadium ........................................................90
 

3.12.2 Identification of Data Needs...............................................................................................92
 

3.12.3 Ongoing Studies..................................................................................................................99
 

4. CHEMICAL AND PHYSICAL INFORMATION..............................................................................101
 

4.1 CHEMICAL IDENTITY..........................................................................................................101
 

4.2 PHYSICAL AND CHEMICAL PROPERTIES .......................................................................101
 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL..........................................................107
 

5.1 PRODUCTION.........................................................................................................................107
 

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5.2 IMPORT/EXPORT...................................................................................................................113
 

5.3 USE...........................................................................................................................................113
 

5.4 DISPOSAL ...............................................................................................................................113
 

6. POTENTIAL FOR HUMAN EXPOSURE .........................................................................................115
 

6.1 OVERVIEW .............................................................................................................................115
 

6.2 RELEASES TO THE ENVIRONMENT .................................................................................117
 

6.2.1 Air .....................................................................................................................................118
 

6.2.2 Water.................................................................................................................................123
 

6.2.3 Soil....................................................................................................................................123
 

6.3 ENVIRONMENTAL FATE.....................................................................................................124
 

6.3.1 Transport and Partitioning ................................................................................................124
 

6.3.2 Transformation and Degradation ......................................................................................127
 

6.3.2.1 Air .................................................................................................................................127
 

6.3.2.2 Water.............................................................................................................................128
 

6.3.2.3 Sediment and Soil .........................................................................................................128
 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT ................................129
 

6.4.1 Air .....................................................................................................................................129
 

6.4.2 Water.................................................................................................................................131
 

6.4.3 Sediment and Soil .............................................................................................................133
 

6.4.4 Other Environmental Media..............................................................................................136
 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE.......................................139
 

6.6 EXPOSURES OF CHILDREN ................................................................................................142
 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES.............................................144
 

6.8 ADEQUACY OF THE DATABASE.......................................................................................145
 

6.8.1 Identification of Data Needs .............................................................................................145
 

6.8.2 Ongoing Studies................................................................................................................148
 

7. ANALYTICAL METHODS................................................................................................................149
 

7.1 BIOLOGICAL MATERIALS ..................................................................................................151
 

7.2 ENVIRONMENTAL SAMPLES.............................................................................................153
 

7.3 ADEQUACY OF THE DATABASE.......................................................................................153
 

7.3.1 Identification of Data Needs .............................................................................................157
 

7.3.2 Ongoing Studies................................................................................................................157
 

8. REGULATIONS, ADVISORIES, AND GUIDELINES.....................................................................159
 

9. REFERENCES ....................................................................................................................................165
 

10. GLOSSARY ......................................................................................................................................201
 

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
 

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LIST OF FIGURES
 

3-1. Levels of Significant Exposure to Vanadium and Compounds - Inhalation ...................................... 34
 

3-2. Levels of Significant Exposure to Vanadium and Compounds - Oral................................................ 56
 

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

Hypothetical Chemical Substance ......................................................................................................81
 

3-4. Existing Information on Health Effects of Vanadium and Compounds.............................................91
 

6-1. Frequency of NPL Sites with Vanadium Contamination .................................................................116
 

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LIST OF TABLES
 

2-1. Lung Effects Observed in Rats Exposed to Vanadium Pentoxide 6 Hours/day, 5 Days/week for 

6 or 13 Days, 3 Months, or 2 Years....................................................................................................17
 

2-2. Hematological Effects in Rats Exposed to Ammonium Metavanadate for 4 Weeks.........................23
 

3-1. Levels of Significant Exposure to Vanadium and Compounds - Inhalation ...................................... 28
 

3-2. Incidence of Lung Tumors in Rats and Mice Exposed to Vanadium Pentoxide for 2 Years.............43
 

3-3. Levels of Significant Exposure to Vanadium and Compounds - Oral................................................ 45
 

3-4. Genotoxicity of Vanadium and Compounds In Vitro.........................................................................67
 

3-5. Genotoxicity of Vanadium and Compounds In Vivo..........................................................................70
 

3-6. Vanadium Elimination Half-Times in Various Organs in Rats Exposed to 8.2 mg
 

Vanadium/kg/day for 1 Week.............................................................................................................76
 

4-1. Chemical Identity of Vanadium and Compounds.............................................................................102
 

4-2. Physical and Chemical Properties of Vanadium and Compounds ...................................................104
 

5-1. Facilities that Produce, Process, or Use Vanadium (Except When Contained in an Alloy).............108
 

5-2. Facilities that Produce, Process, or Use Vanadium Compounds......................................................110
 

5-3. Current U.S. Manufacturers of Vanadium and Selected Vanadium Compounds.............................112
 

6-1. Releases to the Environment from Facilities that Produce, Process, or Use Vanadium (Except
 

When Contained in an Alloy)...........................................................................................................119
 

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

Compounds.......................................................................................................................................121
 

6-3. Vanadium Levels in Food.................................................................................................................137
 

6-4. Estimated Daily Vanadium Intake....................................................................................................140
 

7-1. Analytical Methods for Determining Vanadium in Biological Materials ........................................152
 

7-2. Analytical Methods for Determining Vanadium in Environmental Samples...................................154
 

8-1. Regulations, Advisories, and Guidelines Applicable to Vanadium and Compounds.......................161
 

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VANADIUM 1 

1. PUBLIC HEALTH STATEMENT 

This public health statement tells you about vanadium 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. Vanadium has been found in at least 319 of the 1,699 current or former NPL 

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

exists that the number of sites at which vanadium 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 vanadium, 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. 

1.1 WHAT IS VANADIUM? 

Description Vanadium is a naturally occurring element. It is 

widely distributed in the earth’s crust at an 

average concentration of approximately 

100 mg/kg. Vanadium is found in about 

65 different minerals. 

Depending on its form, vanadium can be a 

gray-white metal or light gray or white lustrous 

powder. Pure vanadium is a bright white, soft, 

and ductile metal. 

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VANADIUM 2 

1. PUBLIC HEALTH STATEMENT 

Uses 

• Vanadium metal 

• Vanadium pentoxide 

• Vanadyl sulfate and sodium metavanadate 

Vanadium is used in producing rust-resistant, 

spring, and high-speed tool steels. It is an 

important carbide stabilizer in making steels. 

Vanadium pentoxide is used in ceramics and 

as a catalyst as well as in the production of 

superconductive magnets. 

Vanadyl sulfate and sodium metavanadate 

have been used in dietary supplements. 

For more information on the physical and chemical properties of vanadium and its production, disposal 

and use, see Chapters 4 and 5. 

1.2 WHAT HAPPENS TO VANADIUM WHEN IT ENTERS THE ENVIRONMENT? 

Sources Vanadium occurs naturally in soil, water, and 

air. Natural sources of atmospheric vanadium 

include continental dust, marine aerosol, and 

volcanic emissions. 

Releases of vanadium to the environment are 

mainly associated with industrial sources, 

especially oil refineries and power plants using 

vanadium rich fuel oil and coal. Global humanmade atmospheric releases of vanadium has 

been estimated to be greater than vanadium 

releases due to natural sources. Natural 

releases to water and soil are far greater overall 

than human-made releases to the atmosphere. 

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VANADIUM 3 

1. PUBLIC HEALTH STATEMENT 

Break down 

• Air 

• Water and soil 

Vanadium cannot be destroyed in the 

environment. It can only change its form or 

become attached or separated from airborne 

particulate, soil, particulate in water, and 

sediment. 

Vanadium particles in the air settle to the 

ground or are washed out of the air by rain. 

Smaller particles, such as those emitted from 

oil-fueled power plants, may stay in the air for 

longer times and are more likely to be 

transported farther away from the site of 

release. 

The transport and partitioning of vanadium in 

water and soil is influenced by many factors 

including acidity of the water or soil and the 

presence of particulates. Vanadium can either 

be dissolved in water as dissolved ions or may 

become adsorbed to particulate matter. 

1.3 HOW MIGHT I BE EXPOSED TO VANADIUM?
 

Food–primary source of exposure Most foods have naturally occurring low 

concentrations of vanadium. Seafood generally 

contains higher concentrations of vanadium than 

meat from land animals. 

Daily intakes of vanadium from food ranging from 

0.01 to 0.02 mg have been reported. Average 

vanadium concentrations in tap water are 

approximately 0.001 mg/L. Assuming that you 

drink approximately 2 L of water a day, a daily 

intake of approximately 0.002 mg of vanadium 

from tap water can be estimated for adults. 

Vanadium also may be found in various 

commercial nutritional supplements and 

multivitamins in amounts ranging from 0.0004 to 

12.5 mg, depending on the serving size 

recommended by the manufacturer. 

Consumption of some vanadium-containing 

supplements may result in intakes of vanadium 

that would exceed intakes from food and water. 

Populations in areas with high levels of residual 

fuel oil consumption may also be exposed to 

above-background levels of vanadium, both from 

increased particulate deposition upon food crops 

and soil in the vicinity of power plants. 

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VANADIUM 4 

1. PUBLIC HEALTH STATEMENT 

Air Most people take in very little vanadium from 

breathing. The general population may also be 

exposed to airborne vanadium through 

inhalation, particularly in areas where use of 

residual fuel oils for energy production is high. 

Individuals exposed to cigarette smoke may also 

be exposed to higher than background levels of 

vanadium. Approximately 0.0004 mg of 

vanadium is given off by in the smoke of one 

cigarette. 

Water and soil Vanadium concentrations in surface water can 

range from approximately 0.04 to 220 μg/L 

depending on geographical location. 

For more information on how you might be exposed to vanadium, see Chapter 6. 

1.4 HOW CAN VANADIUM ENTER AND LEAVE MY BODY? 

Enter your body 

• Inhalation 

• Ingestion 

• Dermal contact 

Some of the vanadium you breathe will enter 

your body through your lungs; however, we do 

not know how much will enter. 

A small amount of vanadium in food and water 

(3–20%) will enter your body through the 

digestive tract. The vanadium compounds you 

are exposed to will determine how much is 

absorbed. 

We do not know how much vanadium will enter 

your body through your skin. It is likely that 

very little will pass through the skin. 

For more information about how vanadium enters and leaves your body, see Chapter 3. 

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VANADIUM 5 

1. PUBLIC HEALTH STATEMENT 

1.5 HOW CAN VANADIUM AFFECT MY HEALTH? 

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

Workers 

• Inhalation 

Breathing air with vanadium pentoxide can 

result in coughing which can last a number of 

days after exposure. 

Laboratory animals 

• Inhalation 

Damage to the lungs, throat, and nose have 

been observed in rats and mice exposed to 

vanadium pentoxide. 

Humans Nausea, mild diarrhea, and stomach cramps 

• Oral have been reported in people taking sodium 

metavanadate or vanadyl sulfate for the 

experimental treatment of diabetes. 

Stomach cramps were also reported in a study 

of people taking about 13 mg vanadium/day. 

Laboratory animals 

• Oral 

A number of effects have been found in rats 

and mice ingesting several vanadium 

compounds. The effects include: 

• Decreases in number of red blood cells 

• Increased blood pressure 

• Mild neurological effects 

Cancer Lung cancer has been found in mice exposed 

to vanadium pentoxide. 

The International Agency for Research on 

Cancer (IARC) has determined that vanadium 

is possibly carcinogenic to humans. 

For more information on health effects in people and animals after breathing, eating, or touching 

vanadium, see Chapter 3. 

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VANADIUM 6 

1. PUBLIC HEALTH STATEMENT 

1.6 HOW CAN VANADIUM AFFECT CHILDREN? 

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

conception to maturity at 18 years of age. 

Effects in children The health effects seen in children from 

exposure to toxic levels of vanadium are 

expected to be similar to the effects seen in 

adults. We do not know if children will be more 

sensitive to vanadium toxicity than adults. 

Birth defects We do not know whether vanadium can cause 

birth defects in people. 

Studies in animals exposed during pregnancy 

have shown that vanadium can cause 

decreases in growth and increases in the 

occurrence of birth defects. These effects are 

usually observed at levels which cause effects 

in the mother. 

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

Food Vanadium is a naturally occurring element that 

is widely distributed in the environment. It is 

found in many foods, typically in small amounts. 

You cannot avoid exposure to vanadium. 

Exposure to the levels of vanadium that are 

naturally present in food and water are not 

considered to be harmful. 

Consumer products Consumption of some vanadium-containing 

supplements may result in intakes of vanadium 

that would exceed intakes from food and water. 

You should check with your physician before 

taking supplements containing vanadium to 

determine if such supplements are appropriate 

for you. 

As a precaution, such products should have 

child-proof caps or should be kept out of reach 

of children so that children will not accidentally 

ingest them. 

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VANADIUM 7 

1. PUBLIC HEALTH STATEMENT 

Air Individuals exposed to cigarette smoke may 

also be exposed to higher-than-background 

levels of vanadium. Avoiding exposure to 

cigarette smoke may reduce exposure of you 

and your family to vanadium. 

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

VANADIUM? 

Detecting exposure All people have small amounts of vanadium in 

their bodies. It can be measured in many 

tissues and fluids including blood, urine, and 

hair. 

Measuring exposure Measurements of vanadium concentrations in 

blood and urine can tell you whether you have 

been exposed to larger-than-normal amounts of 

vanadium. Blood and urinary vanadium levels 

are considered the most reliable indicators of 

occupational exposure to vanadium. 

Measuring the concentration of vanadium in 

breathing air, drinking water, and food can help 

in determining how much vananium you are 

exposed to. 

Measuring vanadium levels in hair is not a good 

indicator of occupational or environmental 

exposure to vanadium. 

For more information on ways to tell whether you have been exposed to vanadium see 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. 

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VANADIUM 8 

1. PUBLIC HEALTH STATEMENT 

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

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

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

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

(an 8-hour workday or a 24-hour day), different animal studies, or other factors. 

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

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

Some regulations and recommendations for vanadium include the following: 

Workplace air OSHA set a legal limit of 0.5 mg/m3 for 

vanadium pentoxide respirable dust averaged 

over an 8-hour work day. A limit of 0.1 mg/m3 

for vanadium pentoxide fume has also been 

established. 

1.10 WHERE CAN I GET MORE INFORMATION? 

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

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

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

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

substances. 

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

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

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

to: 

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology and Environmental Medicine
 

1600 Clifton Road NE
 

Mailstop F-62
 

Atlanta, GA 30333
 

Fax: 1-770-488-4178
 

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VANADIUM 9 

1. PUBLIC HEALTH STATEMENT 

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

National Technical Information Service (NTIS) 

5285 Port Royal Road 

Springfield, VA 22161 

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

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

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VANADIUM 10 

1. PUBLIC HEALTH STATEMENT 

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VANADIUM 11 

2. RELEVANCE TO PUBLIC HEALTH 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO VANADIUM IN THE 

UNITED STATES 

Vanadium is the 22nd most abundant element in the earth’s crust with an average concentration of 

100 ppm. It exists in oxidation states ranging from -1 to +5 with 3+, 4+, and 5+ being the most common 

oxidation states. Vanadium is primarily used in the production of rust-resistant, spring, and high-speed 

tool steels; vanadium pentoxide is used in ceramics. Vanadium is released to the environment by 

continental dust, marine aerosols, volcanic emissions, and the combustion of coal and petroleum crude 

oils. It is naturally released into water and soil as a result of weathering of rock and soil erosion. 

Ambient air concentrations of vanadium are low, with urban areas having higher concentrations. Average 

vanadium concentrations were 3.0–3.7 ng/m3 in urban areas of Illinois; in rural areas, the vanadium 

concentrations were 0.8–1.2 ng/m3

. Higher vanadium levels have been measured in the eastern United 

States due to the high density of oil fired power plants using vanadium-rich residual fuel oil. An average 

vanadium air concentration of 620 ng/m3 was measured in Eastern cities compared to 11 ng/m3 in cities 

throughout the United States. Vanadium residence time in the environment is inversely related to the 

particle size. In water, vanadium is converted from trivalent forms to pentavalent forms. The levels of 

vanadium in surface water range from 0.04 to 104 μg/L. Vanadium levels of 1.2–1.0 μg/L were 

measured in tap water samples collected in several U.S. states. 

Food is the primary route of exposure for the general population; foods with the highest vanadium content 

include ground parsley, freeze-dried spinach, wild mushrooms, and oysters. Vanadium in food is mainly 

ingested as VO2+ (vanadyl, V4+) or HVO4

2- (vanadate, V5+). Estimates of dietary vanadium intake range 

from 0.09 to 0.34 μg/kg/day in adults. Humans are potentially exposed to a variety of vanadium 

compounds, the most common being vanadium pentoxide, sodium metavanadate, sodium orthovanadate, 

vanadyl sulfate, and ammonium metavanadate. Organic anthropogenic vanadium compounds, such as 

bis(maltolato)oxyvanadium (IV) or vanadyl acetyl acetonate, are used in the treatment of diabetes and 

cancer; these compounds have different toxicokinetic properties than inorganic vanadium compounds and 

are not discussed in this toxicological profile. 

Although there is some evidence to suggest that vanadium is an essential nutrient, a functional role for 

vanadium in humans has not been established; increases in abortion rates and decreased milk production 

have been observed in vanadium-deprived goats. Vanadium mimics insulin and stimulates cell 

proliferation and differentiation. In animal models, particularly streptozotoxin-induced diabetes in rats, 

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VANADIUM 12 

2. RELEVANCE TO PUBLIC HEALTH 

vanadium has been shown to normalize blood glucose and lipid levels, improve insulin sensitivity, and 

prevent or reverse secondary complications such as cardiomyopathy, cataract development, and impaired 

antioxidant status. 

2.2 SUMMARY OF HEALTH EFFECTS 

The general population can be exposed to vanadium primarily through oral (ingestion of vanadium in 

food) and inhalation routes of exposure. Based on occupational exposure studies, human experimental 

studies, and studies in laboratory animals, the respiratory tract following inhalation exposure and the 

gastrointestinal tract, hematological system, and developing organism following oral exposure are the 

primary targets of toxicity. 

Adverse respiratory effects have been reported in humans and animals exposed to vanadium compounds 

at concentrations much higher than those typically found in the environment. Although the available data 

in humans are limited, signs of airway irritation (e.g., coughing, wheezing, sore throat) have been 

reported in subjects acutely exposed to 0.6 mg vanadium/m3 and in workers exposed to vanadium 

pentoxide dust. These effects have persisted for days to weeks after exposure termination and are often 

not associated with alterations in lung function. Studies in laboratory animals provide strong support that 

the respiratory tract is the most sensitive target following inhalation exposure to vanadium. A variety of 

lung lesions including alveolar/bronchiolar hyperplasia, inflammation, and fibrosis have been observed in 

rats and mice exposed to vanadium pentoxide; the severity of the lesions is related to concentration and 

duration. The lung effects have been observed following acute exposure to 0.56 mg vanadium/m3 and 

chronic exposures to 0.28 mg vanadium/m3 and have been observed after 2 days of exposure. Longer 

duration exposures also result in inflammation and hyperplasia in the larynx and hyperplasia in nasal 

goblet cells. These histological alterations result in restrictive impairments in lung function; respiratory 

distress is observed at vanadium pentoxide concentrations of ≥4.5 mg vanadium/m3

. 

Other sensitive targets of vanadium toxicity include the gastrointestinal system following oral exposure 

and hematological system following inhalation or oral exposure. Symptoms of gastrointestinal irritation 

(diarrhea, cramps, nausea) have been observed in humans following bolus administration of sodium 

metavanadate or vanadyl sulfate; it appears that with repeated exposure, humans develop a tolerance to 

these effects. Diarrhea has also been observed in rats and mice orally exposed to lethal doses of 

vanadium. Microcytic erythrocytosis (evidenced by decreases in hematocrit, hemoglobin, and mean cell 

volume and increases in reticulocytes and nucleated erythrocytes) has been observed in rats exposed to 

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VANADIUM 13 

2. RELEVANCE TO PUBLIC HEALTH 

1.1 mg vanadium/m3 as vanadium pentoxide for at least 4 days. Hematological effects, including 

decreases in erythrocyte levels, decreases in hemoglobin, and increases in reticulocytes have also been 

observed in rats orally exposed to 1.18 mg vanadium/kg/day as ammonium metavanadate for 4 weeks. 

Information on the potential of vanadium to induce developmental effects in humans is limited, but 

developmental effects have been observed in laboratory animals. Decreases in pup growth have been 

observed at maternal doses of ≥2.1 mg vanadium/kg/day. At higher doses, decreases in pup survival and 

gross, skeletal, and visceral malformations and anomalies have been reported; marked decreases in 

maternal body weight are also observed at these dose levels. 

No studies have examined the carcinogenic potential of vanadium in humans. An increase in lung 

carcinoma incidence has been observed in mice chronically exposed to vanadium pentoxide; there is also 

marginal evidence for lung cancer in male rats (incidence of carcinoma was higher than historical controls 

but not concurrent controls). Carcinogenicity has not been adequately assessed in laboratory animals 

following oral exposure. One study classified vanadium pentoxide in group 2B (possibly carcinogenic to 

humans) based on inadequate evidence in humans and sufficient evidence in animals. The Department of 

Health and Human Services and EPA have not classified carcinogenicity of vanadium. 

2.3 MINIMAL RISK LEVELS (MRLs) 

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

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VANADIUM 14 

2. RELEVANCE TO PUBLIC HEALTH 

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 

Acute-Duration Inhalation MRL 

•	 An MRL of 0.0008 mg vanadium/m3 has been derived for acute-duration inhalation exposure 

(14 days or less) to vanadium pentoxide dust. 

Data on acute toxicity of vanadium in humans are limited to an experimental study in which a small 

number of subjects were exposed to vanadium pentoxide dust for 8 hours (Zenz and Berg 1967). A 

persistent cough lasting for 8 days developed in two subjects exposed to 0.6 mg vanadium/m3

; at 0.1 mg 

vanadium/m3

, a productive cough without any subjective complaints or impact on work or home activities 

were observed in five subjects. The available studies in laboratory animals focused on potential 

respiratory tract effects. Impaired lung function, characterized as airway obstructive changes (increased 

resistance and decreased airflow), was observed in monkeys exposed to 2.5 or 1.7 mg vanadium/m3 as 

vanadium pentoxide for 6 hours (Knecht et al. 1985, 1992); the highest no-observed-adverse-effect level 

(NOAEL) for this effect was 0.34 mg vanadium/m3

. In female rats exposed to 0.56 mg vanadium/m3 

6 hours/day, 5 days/week for 13 days, minimal inflammation and histiocytic infiltration were observed 

(NTP 2002). Alveolar and bronchiolar epithelial hyperplasia and inflammation were observed in the 

lungs of mice similarly exposed to 1.1 mg vanadium/m3 as vanadium pentoxide (NTP 2002). Although 

the Knecht et al. (1985, 1992) or NTP (2002) studies did not include examination of potential end points 

outside of the respiratory tract, longer-duration studies have identified the respiratory tract as the most 

sensitive target of toxicity (NTP 2002). The NTP (2002) rat study was selected as the basis of the acuteduration inhalation MRL. 

In the NTP (2002) study, groups of male and female F344 rats received whole-body exposure to 0, 1, 2, 

or 4 mg vanadium pentoxide/m3 (0, 0.56, 1.1, or 2.2 mg vanadium/m3

) as particulate aerosols 6 hours/day, 

5 days/week. On days 6 and 13, 10 rats/group were killed and a histopathological examination of the 

lungs was conducted. Four rats per group were killed for examination of the onset and extent of lung 

lesions after 1, 2, 5, 10, or 16 days of exposure. Hyperplasia of alveolar epithelium and bronchiole 

epithelium were observed in 100% of the female rats exposed to 1.1 or 2.2 mg vanadium/m3 for 6 or 

13 days. Significant increases in the incidence of histiocytic infiltrate and inflammation were observed in 

rats exposed to 1.1 or 2.2 mg vanadium/m3 for 6 or 13 days and in rats exposed to 0.56 mg vanadium/m3 

for 13 days. A significant increase in fibrosis was observed in rats exposed to 2.2 mg vanadium/m3 for 

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VANADIUM 15 

2. RELEVANCE TO PUBLIC HEALTH 

13 days. No histopathological alterations were observed in the four female rats killed after 1 day of 

exposure; by day 2, inflammation and histiocytic infiltrates (increased number of alveolar macrophages) 

were observed in the rats exposed to 2.2 mg vanadium/m3

. Hyperplasia of the alveolar and bronchiolar 

epidthelium was first observed on day 5 in rats exposed to 1.1 or 2.2 mg vanadium/m3

. 

A benchmark dose (BMD) approach was considered for derivation of the acute-duration inhalation MRL; 

however, the fit was not considered adequate due to the limited amount of information from the study on 

the shape of the exposure-response curve for lung inflammation; more information regarding the BMD 

analysis is presented in Appendix A. A NOAEL/lowest-observed-adverse-effect level (LOAEL) 

approach was used to derive the MRL. The LOAEL of 0.56 mg vanadium/m3 for lung inflammation was 

selected as the point of departure for the MRL. This LOAEL was converted to a human equivalent 

concentration (LOAELHEC) of 0.073 mg vanadium/m3 (see Appendix A for more information on the 

calculation of the LOAELHEC) and divided by an uncertainty factor of 90 (3 for use of a minimal LOAEL, 

3 for animal to human extrapolation using dosimetric adjustments, and 10 for human variability), 

resulting in an acute-duration inhalation MRL of 0.0008 mg vanadium/m3

. 

Intermediate-Duration Inhalation MRL 

The available data on the toxicity of vanadium following intermediate-duration inhalation exposure are 

limited to several rat and mouse studies (NTP 2002) involving exposure to vanadium pentoxide for 

6 hours/day, 5 days/week. These studies demonstrate that the respiratory tract is the most sensitive target 

of toxicity. Signs of respiratory distress (rapid respiration, difficulty breathing) have been observed in 

rats exposed to 4.4 mg vanadium/m3 as vanadium pentoxide for at least 4 weeks (NTP 2002). A 3-month 

exposure resulted in increased incidences of lung lesions in rats and mice and nasal lesions in rats. Lung 

effects included alveolar and bronchiolar epithelial hyperplasia, histiocytic infiltrates, inflammation, and 

fibrosis. A NOAEL of 0.56 mg vanadium/m3 was identified in both species. At 1.1 mg vanadium/m3

, 

epithelial hyperplasia and inflammation (male rats and female mice only) were observed. In mice, the 

severity of the lesions was graded as minimal. In rats, the epithelial hyperplasia was graded as mild in 

males and minimal to mild in females and the inflammation was graded as mild. These data suggest that 

at a given air concentration, rats are more sensitive than mice based on the severity of the lesions. In both 

species, the severity of the lesions increased with increasing concentrations. Significant alterations in 

pulmonary function suggestive of a restrictive disease were observed in rats exposed to 2.2 or 4.4 mg 

vanadium/m3

; lung function tests were not performed in mice. Nasal effects in rats included hyperplasia 

and squamous metaplasia of the respiratory epithelium and inflammation. The NOAEL and LOAEL for 

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VANADIUM 16 

2. RELEVANCE TO PUBLIC HEALTH 

nasal effects were 2.2 and 4.5 mg vanadium/m3 in males and 1.1 and 2.2 mg vanadium/m3 in females. In 

addition to the respiratory tract effects, mild microcytic erythrocytosis was observed in rats exposed to 

≥1.1 mg vanadium/m3

. 

The lowest LOAEL identified in intermediate-duration studies is 1.1 mg vanadium/m3 for lung epithelial 

hyperplasia and inflammation in rats exposed 6 hours/day, 5 days/week for 13 weeks (NTP 2002); the 

NOAEL for these effects is 0.56 mg vanadium/m3

. However, this NOAEL is the same as the LOAEL for 

lung inflammation in rats exposed for 13 days (NTP 2002). As summarized in Table 2-1, lung 

inflammation was observed in rats exposed to 0.56 mg vanadium/m3 for 6 days (not significant), 13 days, 

and 2 years. Although the three studies were conducted for the National Toxicology Program (NTP), the 

13-week study was conducted at a different laboratory using the same strain of rats and vanadium 

pentoxide dusts with similar particles sizes as the acute and chronic studies. An explanation for the 

inconsistent findings is not apparent from the available data. Because an intermediate-duration inhalation 

MRL based on the NOAEL identified in the 13-week study would be higher than the acute-duration 

inhalation MRL, the database is not considered adequate for derivation of an intermediate-duration 

inhalation MRL. However, it would be expected that the acute-duration inhalation MRL would be 

protective of intermediate-duration exposure to vanadium. 

Chronic-Duration Inhalation MRL 

•	 An MRL of 0.0001 mg vanadium/m3 has been derived for chronic-duration inhalation exposure 

(1 year or longer) to vanadium pentoxide dust. 

Two-year rat and mouse studies conducted by NTP (2002) examined the chronic toxicity of inhaled 

vanadium pentoxide 6 hours/day, 5 days/week for 2 years. At the lowest concentration tested in rats 

(0.28 mg vanadium/m3

), lung (increases in the incidence of alveolar and bronchiolar epithelial 

hyperplasia), larynx (degeneration and hyperplasia of the epiglottis epithelium), and nasal (goblet cell 

hyperplasia in respiratory epithelium) effects were observed. Similar lung and larynx effects were 

observed in mice at the lowest concentration tested (0.56 mg vanadium/m3

). The nasal effects observed 

in mice exposed to 0.56 mg vanadium/m3 included goblet cell hyperplasia in the respiratory epithelium 

and nasal olfactory epithelial atrophy and hyaline degeneration. In addition to these effects, a significant 

increase in alveolar/bronchiolar carcinoma incidence was also observed in mice exposed to ≥0.56 mg 

vanadium/m3

. In male rats, an increased combined incidence of alveolar/bronchiolar adenoma or 

carcinoma was also observed; however, the incidence was not significantly higher than concurrent 

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VANADIUM 17 

2. RELEVANCE TO PUBLIC HEALTH 

Table 2-1. Lung Effects Observed in Rats Exposed to Vanadium
 

Pentoxide 6 Hours/day, 5 Days/week for 6 or
 

13 Days, 3 Months, or 2 Years
 

mg vanadium/m3 

Air concentration 0 0.28 0.56 1.1 2.2 4.5 9.0 

6-Day study 

Alveolar hyperplasia 0/10 0/10 10/10a 8/10a (1.4) 

(1.1)b 

Bronchiole 1/10 (1.0) 0/10 10/10a (1.7) 10/10a 

hyperplasia (1.8) 

Histiocytic infiltrate 2/10 (1.0) 6/10 (1.3) 10/10a (1.4) 10/10a 

(1.8) 

Inflammation 0/10 3/10 (1.0) 10/10a (1.5) 10/10a 

(2.5) 

13-Day study 

Alveolar hyperplasia 0/10 3/10 (1.0) 10/10a (1.0) 10/10a 

(2.0) 

Bronchiole 0/10 0/10 10/10a (1.0) 10/10a 

hyperplasia (1.8) 

Histiocytic infiltrate 0/10 10/10a 10/10a (1.9) 10/10a 

(1.3) (2.2) 

Inflammation 0/10 8/10 (1.3) 10/10a (1.7) 10/10a 

(2.0) 

Fibrosis 0/10 0/10 0/10 6/10a (1.5) 

3-Month study (males) 

Epithelial hyperplasia 0/10 0/10 10/10a (2.0) 10/10a 10/10a 10/10a 

(3.0) (3.6) (3.3) 

Inflammation 0/10 0/10 9/10a (1.0) 10/10a 10/10 (1.6) 10/10a 

(1.0) (2.1) 

Fibrosis 0/10 0/10 2/10 (1.0) 10/10a 10/10a 10/10 (3.1) 

(1.9) (3.2) 

3-Month study (females) 

Epithelial hyperplasia 0/10 0/10 10/10a (1.3) 10/10a 10/10a 10/10a 

(2.9) (3.5) (3.2) 

Inflammation 0/10 0/10 0/10 10/10a 10/10a 10/10a 

(1.0) (1.9) (1.2) 

Fibrosis 0/10 0/10 0/10 10/10a 10/10a 10/10a 

(1.0) (2.9) (3.2) 

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VANADIUM 18 

2. RELEVANCE TO PUBLIC HEALTH 

Table 2-1. Lung Effects Observed in Rats Exposed to Vanadium
 

Pentoxide 6 Hours/day, 5 Days/week for 6 or
 

13 Days, 3 Months, or 2 Years
 

mg vanadium/m3 

Air concentration 0 0.28 0.56 1.1 2.2 4.5 9.0 

Alveolar hyperplasia 

Bronchiole 

hyperplasia 

Inflammation 

Fibrosis 

Histiocyte infiltration 

Alveolar hyperplasia 

Bronchiole 

hyperplasia 

Inflammation 

Fibrosis 

Histiocyte infiltration 

2-Year study (males) 

7/50 (2.3) 24/49a 34/48a 49/50a (3.3) 

(2.0) (2.0) 

3/50 (2.3) 17/49a 31/48a 49/50a (3.3) 

(2.2) (1.8) 

5/50 (1.6) 8/49 (1.8) 24/48a 42/50a (2.4) 

(1.3) 

7/50 (1.4) 7/49 (2.0) 16/48a 38/50a (2.1) 

(1.6) 

22/50 40/49a 45/48a 50/50a (3.3) 

(1.3) (2.0) (2.3) 

2-Year study (females) 

4/49 (1.0) 8/49 (1.8) 21/50a 50/50a (3.1) 

(1.2) 

6/49 (1.5) 5/49 (1.6) 14/50a 48/50a (3.0) 

(1.3) 

10/49 10/49 (1.1) 14/50 (1.2) 40/50a (1.7) 

(1.5)
 

19/49 7/49a (1.3) 12/50 (1.6) 32/50a (1.4)
 

(1.4)
 

26/49 35/49a 44/50a 50/50a (1.9)
 

(1.4) (1.3) (2.0) 

a

p≤0.05 b

Average severity grade of lesions in affected animals: 1=minimal; 2=mild, 3=moderate; 4=marked 

Source: NTP 2002 

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VANADIUM 19 

2. RELEVANCE TO PUBLIC HEALTH 

controls, but was higher than historical controls. Because the rat study identified a lower LOAEL for 

lung, larynx, and nasal effects, it was selected as the basis of a chronic-duration inhalation MRL. 

In the NTP (2002) study, groups of 50 male and 50 female F344 rats were exposed to 0, 0.5, 1, or 2 mg 

vanadium pentoxide/m3 (0, 0.28, 0.56, and 1.1 mg vanadium/m3

) 6 hours/day, 5 days/week for 104 weeks. 

No significant alterations in survival or body weight gain were observed in the vanadium-exposed rats. 

Alveolar histiocytic infiltrates were observed in males and females exposed to ≥0.28 mg vanadium/m3

. 

Significant increases in the incidence of hyperplasia of the alveolar and bronchiolar epithelium were 

observed in males exposed to ≥0.28 mg vanadium/m3 and females exposed to ≥0.56 mg vanadium/m3

. 

Squamous metaplasia was observed in alveolar epithelium of males and females exposed to 1.1 mg 

vanadium/m3 and in the bronchiolar epithelium of males exposed to 1.1 mg vanadium/m3

. Chronic 

inflammation was observed in males exposed to 0.56 or 1.1 mg vanadium/m3 and females exposed to 

1.1 mg vanadium/m3 and interstitial fibrosis was observed in males exposed to 1.1 mg vanadium/m3 and 

females exposed to 0.28 or 1.1 mg vanadium/m3

. An increased incidence of brownish pigment in alveolar 

macrophages was observed in males exposed to 1.1 mg vanadium/m3 and females exposed to 0.56 or 

1.1 mg vanadium/m3

; this effect was considered to be of little biological relevance. Chronic 

inflammation, degeneration and hyperplasia of the epiglottis were observed in the larynx of males and 

females exposed to ≥0.28 mg vanadium/m3

; squamous metaplasia of the epiglottis respiratory epithelium 

was also observed in males exposed to ≥0.28 mg vanadium/m3 and in females exposed to 1.1 mg 

vanadium/m3

. Goblet cell hyperplasia of the nasal respiratory epithelium was observed in males exposed 

to ≥0.28 mg vanadium/m3 and in females exposed to 1.1 mg vanadium/m3

. 

BMD analyses of the incidence data for alveolar and bronchiolar epithelial hyperplasia, chronic 

inflammation of the larynx, degeneration of epiglottis respiratory epithelium, and hyperplasia of nasal 

respiratory epithelial goblet cells in male rats were used to determine the point of departure for the MRL. 

As described in greater detail in Appendix A, the BMCL10 values for these effects were 0.09, 0.10, 0.07, 

0.04, and 0.16 mg vanadium/m3

, respectively. 

These BMCL10 values were converted to a human equivalent concentrations (as described in detail in 

Appendix A); the BMCLHEC values were 0.008, 0.017, 0.005, 0.003, and 0.012 mg vanadium/m3 for 

alveolar epithelial hyperplasia, bronchiolar epithelial hyperplasia, chronic inflammation of the larynx, 

degeneration of epiglottis respiratory epithelium, and hyperplasia of nasal respiratory epithelial goblet 

cells, respectively. The BMCLHEC of 0.003 mg vanadium/m3 for degeneration of epiglottis respiratory 

epithelium was selected as the point of departure. This value was divided by an uncertainty factor of 

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VANADIUM 20 

2. RELEVANCE TO PUBLIC HEALTH 

30 (3 for animal to human extrapolation with dosimetric adjustment and 10 for human variability), 

resulting in a chronic-duration inhalation MRL of 0.0001 mg vanadium/m3

. 

Oral MRLs 

Acute-Duration Oral MRL 

Gastrointestinal effects (diarrhea, cramps, nausea, and vomiting) have been observed in diabetic patients 

administered vanadyl sulfate or sodium metavanadate capsules as a supplement to their diabetes treatment 

(Boden et al. 1996; Cusi et al. 2001; Goldfine et al. 1995). The gastrointestinal effects subsided within 

the first couple of weeks of exposure. The concentrations in the capsules ranged from 16 to 24 mg and 

daily doses ranged from 0.35 to 0.66 mg vanadium/kg/day. A small number of studies in laboratory 

animals have examined the acute toxicity of vanadium following oral exposure. Significant increases in 

reticulocyte levels in peripheral blood and polychromatophilic erythroblasts in the bone marrow were 

observed in rats exposed to 27.72 mg vanadium/kg/day as ammonium metavanadate in drinking water for 

2 weeks (Zaporowska and Wasilewski 1989). The remaining nonlethality studies reported developmental 

effects in the offspring of rats and mice administered 7.5–8.4 mg vanadium/kg/day via gavage during 

gestation (Paternain et al. 1987, 1990; Sanchez et al. 1991). The observed developmental effects included 

decreases in fetal growth, increases in resorptions, and gross, visceral, and skeletal malformations and 

anomalies. 

Although the human studies identified the lowest LOAEL values, they were not considered suitable as the 

basis of an MRL. These studies used a small number of diabetic subjects (5–10 subjects per study) and 

no control group. The lowest LOAEL identified in an animal study is 7.5 mg vanadium/kg/day for 

developmental effects (Paternain et al. 1990). In this study, significant increases in early resorptions, 

decreases in fetal body weight and length, and increases in the incidence of soft tissue anomalies/ 

malformations (hematomas in facial area, neck, and dorsal area, cleft palate), and skeletal defects 

(delayed ossification of supraoccipital bone, carpus, tarsus, and sternebrae) were observed in the offspring 

of Swiss mice administered via gavage 7.5 mg vanadium/kg/day as vanadyl sulfate on gestation days 6– 

15. This dose was also associated with significant decreases in maternal body weight gain (during 

gestation days 6–15, the dams gained 46% less weight than controls); no significant alterations in food 

intake were observed. Because 7.5 mg vanadium/kg/day is a serious LOAEL in the dams (ATSDR 

defines serious effects as those that evoke failure in a biological system and can lead to morbidity or 

mortality), this study is not suitable for derivation of an acute-duration oral MRL. It is ATSDR’s policy 

to not use a LOAEL for serious health effects as the basis of an MRL. 

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VANADIUM 21 

2. RELEVANCE TO PUBLIC HEALTH 

Intermediate-Duration Oral MRL 

•	 An MRL of 0.01 mg vanadium/kg/day has been derived for intermediate-duration oral exposure 

(15–364 days) to vanadium. 

Two human studies have examined the oral toxicity of vanadium. No significant alterations in 

hematological parameters, liver function (as measured by serum enzymes), cholesterol and triglyceride 

levels, kidney function (as measured by blood urea nitrogen), body weight, or blood pressure were 

observed in subjects administered via capsule 0.12 or 0.19 mg vanadium as ammonium vanadyl tartrate or 

vanadyl sulfate for 6–12 weeks (Dimond et al. 1963; Fawcett et al. 1997). Studies in laboratory animals 

have identified several sensitive effects including alterations in erythrocyte and reticulocyte levels, 

increased blood pressure, neurobehavioral alterations, and developmental toxicity. The lowest LOAEL 

identified in an intermediate-duration study was 0.12 mg vanadium/kg/day for increases in blood pressure 

observed in rats exposed to sodium metavanadate in drinking water for 210 days (Boscolo et al. 1994); 

several other studies by these investigators have reported similar effects at higher doses (Carmagnani et 

al. 1991, 1992). However, other studies have not found significant alterations in blood pressure at higher 

doses (Bursztyn and Mekler 1993; Sušić and Kentera 1986, 1988). Significant decreases in erythrocyte 

levels have been observed in rats exposed to 1.18 mg vanadium/kg/day as ammonium metavanadate in 

drinking water for 4 weeks (Zaporowska et al. 1993); at higher concentrations, decreases in hemoglobin 

and increases in reticulocyte levels have been observed (Ścibior 2005; Ścibior et al. 2006; Zaporowska 

and Wasilewski 1990, 1991, 1992a, 1992b; Zaporowska et al. 1993). However, other intermediateduration studies have not found significant alterations at doses as high as 9.7 mg vanadium/kg/day (Dai et 

al. 1995; Mountain et al. 1953). At 1.72 mg vanadium/kg/day, impaired performance on neurobehavioral 

tests (open field and active avoidance tests) was observed in rats exposed to administered sodium 

metavanadate for 8 weeks (Sanchez et al. 1998). No other studies have examined the neurotoxic potential 

of vanadium. As with acute-duration exposure, the developing organism is a sensitive target of vanadium 

toxicity. Decreases in pup body weight and length were observed in the offspring of rats administered 

2.1 mg vanadium/kg/day as sodium metavanadate for 14 days prior to mating and throughout gestation 

and lactation (Domingo et al. 1986). At higher doses (6, 10, or 12 mg vanadium/kg/day), decreases in 

pup survival, and increases in the occurrence of gross, visceral, or skeletal malformations and anomalies 

were observed (Elfant and Keen 1987; Morgan and El-Tawil 2003; Poggioli et al. 2001). 

The animal database suggests that the most sensitive targets of vanadium toxicity are blood pressure, 

erythroctyes, nervous system, and the developing organism with LOAEL values of 0.12, 1.18, 1.72, and 

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VANADIUM 22 

2. RELEVANCE TO PUBLIC HEALTH 

2.1 mg vanadium/kg/day, respectively. Two approaches for derivation of an intermediate-duration oral 

MRL were considered. In the first approach, the NOAEL of 0.12 mg vanadium/kg/day identified in the 

Fawcett et al. (1997) study was used as the point of departure for the MRL. The Fawcett et al. (1997) 

study was selected over the Dimond et al. (1963) study, which identified a slightly higher NOAEL 

(0.19 mg vanadium/kg/day) because more subjects (six subjects in Dimond study compared to 15– 

16 subjects in Fawcett study) were examined and the results of the study are described in greater detail. 

In the Fawcett et al. (1997) study, groups of men and women enrolled in a weight training program for at 

least 1 year were administered capsules containing 0 (11 men and 4 women) or 0.12 mg vanadium/kg/day 

as vanadyl sulfate trihydrate (12 men and 4 women) for 12 weeks. Fasting blood samples were collected 

at 0 and 12 weeks and analyzed for hematological (erythrocyte count, hemoglobin, hematocrit, mean cell 

volume, mean cell hemoglobin, platelet count, and total and differential leukocyte count) and serum 

chemistry (cholesterol, high density lipoprotein, triglycerides, albumin, total protein, total and direct 

bilirubin, alkaline phosphatase, alanine amino-transferase) parameters. Body weight and blood pressure 

were measured at weeks 4, 8, and 12. No significant alterations in blood pressure, body weight, or 

hematological or clinical chemistry parameters were found. Using the NOAEL of 0.12 mg vanadium/kg/ 

day and an uncertainty factor of 10 for human variability, the MRL would be 0.01 mg vanadium/kg/day. 

Several animal studies were also considered as the basis of an MRL. Although an increase in blood 

pressure was observed at the lowest adverse effect level (0.12 mg vanadium/kg/day; Boscolo et al. 1994), 

this end point was not selected as the basis for an intermediate-duration oral MRL. This effect has not 

been consistently observed among rat studies and no alterations in blood pressure were observed in a 

study of healthy adults exposed to 0.12 mg vanadium/kg/day for 12 weeks (Fawcett et al. 1997). The 

next highest LOAEL of 1.18 mg vanadium/kg/day for a decrease in erythrocyte levels in rats (Zaporowski 

et al. 1993) was considered as the principal study for the MRL. In the Zaporowski et al. (1993) study, 

groups of 2-month-old male and female Wistar rats (15–16/sex/group) were exposed to ammonium 

metavanadate in drinking water for 4 weeks at doses of 0, 1.18, and 4.93 mg vanadium/kg/day (males) or 

1.50 and 6.65 mg vanadium/kg/day (females). No alterations in behavior or motor activity were 

observed. A significant decrease in water consumption (14% less than controls) was observed in males 

exposed to 4.93 mg vanadium/kg/day. No significant alterations in body weight gain were observed. As 

summarized in Table 2-2, alterations in erythrocyte, hemoglobin, hematocrit, and reticulocyte levels were 

observed. This study identified a minimal LOAEL of 1.18 mg vanadium/kg/day for decreases in 

erythrocyte and hematocrit levels in male rats. The alteration in erythrocyte levels was considered 

minimally adverse because the magnitude of the change was small (approximately 11%). Dividing this 

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VANADIUM 23 

2. RELEVANCE TO PUBLIC HEALTH 

Table 2-2. Hematological Effects in Rats Exposed to Ammonium Metavanadate 

for 4 Weeks 

Dose (mg vanadium/kg/day) 

Males 0 1.18 4.93 

Erythrocytes (x1012/dm3) 8.32 7.38a 7.47b 

Hemoglobin (mmol/L) 9.37 8.94 8.65a 

Hematocrit (L) 0.48 0.47b 0.47a 

Reticulocytes (%) 2.55 2.64 3.82b 

Females 0 1.50 6.65 

Erythrocytes (x1012/dm3) 8.24 7.38c 7.12c 

Hemoglobin (mmol/L) 9.41 8.76 8.72a 

Hematocrit (L) 0.48 0.47 0.47 

Reticulocytes (%) 2.55 2.91 3.64b 

a

Significantly different from control group (p<0.01) b

Significantly different from control group (p<0.05) c

Significantly different from control group (p<0.001) 

Source: Zaporowska et al. 1993 

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VANADIUM 24 

2. RELEVANCE TO PUBLIC HEALTH 

minimal LOAEL by an uncertainty factor of 300 (3 for the use of a minimal LOAEL, 10 for animal to 

human extrapolation, and 10 for human variability) results in an MRL of 0.004 mg vanadium/kg/day. 

Although an MRL based on the Zaporwska et al. (1993) rat study would be approximately 3 times lower 

than an MRL based on the Fawcett et al. (1997) human study, the Fawcett et al. (1997) study was selected 

as the basis of the intermediate-duration oral MRL because greater confidence was given to an MRL 

based on a reliable human study. Thus, the intermediate-duration oral MRL is 0.01 mg vanadium/kg/day. 

Chronic-Duration Oral MRL 

No studies examining the chronic toxicity of vanadium in humans were identified. Although several 

laboratory animal studies have examined chronic toxicity, most tested low doses and did not find effects. 

No adverse effects were observed in rats and mice exposed to 0.7 or 4.1 mg vanadium/kg/day, 

respectively, as vanadyl sulfate in drinking water for 2–2.5 years (Schroeder et al. 1970; Schroeder and 

Balassa 1967). In rats exposed to 28 mg vanadium/kg/day as vanadyl sulfate in drinking water, a 20% 

decrease in body weight gain was observed; no alterations in lungs, heart, liver, or kidneys 

histopathology, hematological parameters, or blood pressure were observed at 19 mg vanadium/kg/day 

(Dai and McNeill 1994; Dai et al. 1994a, 1994b). Because the most sensitive target of vanadium toxicity 

following chronic-duration oral exposure have not been identified, the animal studies that mostly 

identified free-standing NOAEL values were not considered suitable for derivation of an MRL. 

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VANADIUM 25 

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 vanadium. 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. 

Elemental vanadium does not occur in nature; however, vanadium compounds exist in over 50 different 

mineral ores and in association with fossil fuels. It has six oxidation states (1-, 0, 2+, 3+, 4+, and 5+) of 

which 3+, 4+, and 5+ are the most common. The toxicologically significant compounds are vanadium 

pentoxide (V2O5), sodium metavanadate (NaVO3), sodium orthovanadate (Na3VO4), vanadyl sulfate 

(VOSO4), and ammonium vanadate (NH4VO3). Vanadium pentoxide dust is usually encountered in 

occupational settings, and humans would be exposed via the inhalation route. Organic vanadium 

compounds, such as bis(maltolato)oxyvanadium (IV), bis(ethylmaltolato)oxyvanadium (IV), and vanadyl 

acetyl acetonate, have been synthesized for use in the treatment of diabetes and cancer. Because these 

compounds likely have different toxicokinetic properties from inorganic vanadium compounds, they are 

not included in this toxicological profile. 

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 

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VANADIUM 26 

3. HEALTH EFFECTS 

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

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

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

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

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

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

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

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

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

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

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

effects to human health. 

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

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

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

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

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

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

3.2.1.1 Death 

No studies were located regarding death in humans after inhalation exposure to vanadium. 

Increases in mortality have been observed in several studies of laboratory animals exposed to vanadium 

pentoxide. Deaths occurred in rabbits exposed to 114 mg vanadium/m3 for 1 hour, but not in rabbits 

exposed to 43 mg vanadium/m3 (Sjöberg 1950). Exposure to 18 mg vanadium/m3 as vanadium pentoxide 

resulted in death in three of five rats exposed for 6 days (NTP 2002). Intermediate-duration exposure 

resulted in deaths in rats exposed to 9 mg vanadium/m3 and mice exposed to 18 mg vanadium/m3 (NTP 

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VANADIUM 27 

3. HEALTH EFFECTS 

2002). A decrease in survival was observed in mice chronically exposed to 2.2 mg vanadium/m3 (NTP 

2002). The LOAEL values are recorded in Table 3-1 and plotted in Figure 3-1. 

3.2.1.2 Systemic Effects 

The highest NOAEL values and all reliable LOAEL values for each species and duration category are 

recorded in Table 3-1 and plotted in Figure 3-1. 

Respiratory Effects. Although a number of studies have reported respiratory effects in humans 

exposed to vanadium, in particular vanadium pentoxide, very few provide reliable quantitative exposure 

data. In an experimental study, persistent coughing lasting 8 days after exposure termination was 

observed in two subjects exposed to 0.6 mg vanadium/m3 for 8 hours; no alterations in lung function 

(lung function parameters assessed: forced vital capacity, 0.5 and 1 second forced expiratory volume, 

maximal expiratory flow, 200–1,200 cc flow rate, maximal midexpiratory time, and forced inspiratory 

vital capacity) were observed (Zenz and Berg 1967). At 0.1 mg vanadium/m3

, five subjects reported 

productive coughing without other subjective complaints, alterations in lung function, or changes in daily 

activities; this concentration level was considered a NOAEL. Workers exposed to a range of vanadium 

pentoxide dust levels for as little as 1 day (Levy et al. 1984; Musk and Tees 1982; Thomas and Stiebris 

1956; Zenz et al. 1962) or as long as ≥6 years (Irsigler et al. 1999; Lewis 1959; NIOSH 1983; Sjöberg 

1956; Vintinner et al. 1955; Wyers 1946), show mild respiratory distress, such as cough, wheezing, chest 

pain, runny nose, or sore throat. One study of chronically-exposed workers showed increased neutrophils 

in the nasal mucosa (Kiviluoto 1980; Kiviluoto et al. 1979b, 1981a). More severe pathology has not been 

reported. Symptoms are reversible within days or weeks after exposure ceases. Data were not located to 

assess the relationship of exposure level or duration to severity of response. Chest x-rays and pulmonary 

function tests were normal in most cases. Chronic effects were infrequently reported. In a study of 

40 vanadium pentoxide workers with persistent respiratory symptoms (Irsigler et al. 1999), 12 were found 

to have bronchial hyperresponsiveness to inhaled histamine or exercise challenge. No significant 

alterations in baseline lung function were found. The mean urine vanadium level (assessed via spot urine 

samples) in the hyperresponsive group was 52.7 μg/g creatinine compared to 30.7 μg/g creatinine in 

12 matched subjects with persistent respiratory symptoms and without bronchial hyperreactivity; 

statistical comparisons of the two groups were not made. Five to 23 months after removal from exposure, 

bronchial hyperreactivity was still present in nine of the subjects, although the response was less severe in 

five of them and more severe in one subject. 

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8

114

12

0.34 2.5

130

0.28 1.7

107

0.56

123

1.1

109

18

115

9

Table 3-1 Levels of Significant Exposure to Vanadium - Inhalation 

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Exposure/ LOAEL

Duration/

a Frequency Reference Key to Species NOAEL Less Serious Serious (Route) Figure (Strain) System (mg V/m3) (mg V/m3) (mg V/m3) Chemical Form 

ACUTE EXPOSURE Death 

1 Rabbit 1 d 114 (2/4 died) Sjoberg 1950 7 hr/d 

VANADIUM PENTOXID

(NS) 

Systemic 

2 Monkey 6 hr Resp 0.34 M 2.5 M (impaired lung function) Knecht et al. 1985 (Cynomolgus) (NS) VANADIUM PENTOXID

3 Monkey 6 hr Resp 0.28 M 1.7 M (impaired lung function) Knecht et al. 1992 (Cynomolgus) VANADIUM PENTOXID

4 Rat 6 hr/d b Resp 0.56 F (histiocytic infiltrate and NTP 2002 5 d/wk (Fischer- 344) 6 or 13 d inflammation in lungs) VANADIUM PENTOXID

5 Mouse 6 hr/d Resp 1.1 F (hyperplasia of alveolar NTP 2002 5 d/wk (B6C3F1) and bronchiole 

epithelium and inflammation in lungs) 

6 or 13 d VANADIUM PENTOXID

INTERMEDIATE EXPOSURE Death 

6 Rat 6 hr/d 18 M (3/5 males died) NTP 2002 5 d/wk (Fischer- 344) 16 d VANADIUM PENTOXID

7 Rat 6 hr/d 9 (7/10 males and 3/10 NTP 2002 5 d/wk (Fischer- 344) 3 mo females died) VANADIUM PENTOXID
118

18

129

0.62

108

1.1

2.2

4.5

9 9

112

0.56

1.1

4.54.54.54.54.54.54.5

9

Table 3-1 Levels of Significant Exposure to Vanadium - Inhalation (continued) 

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Exposure/ 

Duration/ 

a Frequency Key to Species (Route) Figure (Strain) 

8 Mouse 

(B6C3F1) 

Systemic 

9 Monkey 

(Cynomolgus) 

10 Rat 

(Fischer- 344) 

11 Rat 

(Fischer- 344) 

6 hr/d 5 d/wk 16 d 6 hr/d 5 d/wk 26 wk 6 hr/d 5 d/wk 16 d 6 hr/d 5 d/wk 3 mo 

System 

Resp Resp Bd Wt Resp Cardio Gastro Musc/skel Hepatic Renal Dermal Bd Wt 

LOAEL 

NOAEL Less Serious Serious Reference

(mg V/m3) (mg V/m3) (mg V/m3) Chemical Form 

18 M (5/5 males died) NTP 2002 

VANADIUM PENTOXID

0.62 M (audible wheezing and Knecht et al. 1992 

coughing in 3/8 VANADIUM PENTOXIDmonkeys) 

1.1 2.2 (localized inflammatory NTP 2002

response) VANADIUM PENTOXID

4.5 9 (12-13% decreased body 9 (25-40% decreased body

weight gain) weight gain)

0.56 1.1 (epithelial hyperplasia NTP 2002

and inflammation in VANADIUM PENTOXIDlungs) 

4.5 

4.5 4.5 4.5 4.5 4.5 

4.5 9 (30-60% decreased body

weight gain)
117

1.1 2.29

18

120

0.56

1.1

99994.5

9

110

2.2

119

18

114

92.2

4.5

Table 3-1 Levels of Significant Exposure to Vanadium - Inhalation (continued) 

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Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg V/m3) (mg V/m3) (mg V/m3) Chemical Form 

12 Mouse 6 hr/d Resp 1.1 2.2 (lung inflammation) NTP 2002 5 d/wk (B6C3F1) 16 d VANADIUM PENTOXID

Bd Wt 9 18 (28% decreased body 

weight gain) 

13 Mouse 6 hr/d Resp 0.56 1.1 (lung inflammation and NTP 2002 5 d/wk (B6C3F1) epithelial hyperplasia) 3 mo VANADIUM PENTOXID

Cardio 9 Gastro 9 Hepatic 9 Renal 9 

Bd Wt 4.5 F 9 F (12% decreased body

weight gain)

Immuno/ Lymphoret 

14 Rat 6 hr/d 2.2 (decr phagocytosis and NTP 2002 5 d/wk (Fischer- 344) 16 d incr bactericidal activity) VANADIUM PENTOXID

15 Mouse 6 hr/d 18 NTP 2002 5 d/wk (B6C3F1) 16 d VANADIUM PENTOXID

Reproductive 

16 Rat 6 hr/d 9 M 4.5 F (increased estrous cycle NTP 2002 5 d/wk (Fischer- 344) 3 mo length) VANADIUM PENTOXID

2.2 F 
124

2.29

4.5

126

2.2

116

0.28

1.11.11.11.11.11.1

Table 3-1 Levels of Significant Exposure to Vanadium - Inhalation (continued) 

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Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg V/m3) (mg V/m3) (mg V/m3) Chemical Form 

17 Mouse 6 hr/d 2.2 M 4.5 M (decreased epididymal NTP 2002 5 d/wk (B6C3F1) 3 mo spermatozoa motility) VANADIUM PENTOXID

9 F 

CHRONIC EXPOSURE Death 

18 Mouse 6 hr/d 2.2 M (decreased survival in NTP 2002 5 d/wk (B6C3F1) 2 yr males) VANADIUM PENTOXID

Systemic 

19 Rat 6 hr/d c Resp 0.28 (hyperplasia of alveolar NTP 2002 5 d/wk (Fischer- 344) 2 yr and bronchiolar VANADIUM PENTOXID

epithelium, degeneration and hyperplasia of epiglottis epithelium, and goblet cell hyperplasia in nasal respiratory epithelium) 

Cardio 1.1 Gastro 1.1 Musc/skel 1.1 Hepatic 1.1 Renal 1.1 Bd Wt 1.1 
125

0.56

2.22.22.22.22.20.56

1.1 2.2

128

0.28

Table 3-1 Levels of Significant Exposure to Vanadium - Inhalation (continued) 

***DRAFT FOR PUBLIC COMMENT***

LOAEL 

NOAEL Less Serious Serious Reference

System (mg V/m3) (mg V/m3) (mg V/m3) Chemical Form 

Resp 0.56 (hyperplasia and chronic NTP 2002 

inflammation in lungs; VANADIUM PENTOXIDsquamous metaplasia of epiglottis epithelium and nasal respiratory epithelium; atrophy and degeneration of nasal olfactory epithelium) 

Cardio 2.2 Gastro 2.2 Hepatic 2.2 Renal 2.2 Dermal 2.2 Bd Wt 0.56 1.1 (15-20% decreased body 2.2 (20-29% decreased body 

weight gain) weight gain) 

0.28 M (lung tumor incidence NTP 2002 

higher than historical VANADIUM PENTOXIDcontrols) 

Exposure/ 

Duration/ 

a Frequency Key to Species (Route) Figure (Strain) 

20 Mouse 6 hr/d 

5 d/wk (B6C3F1) 2 yr 

Cancer 

21 Rat 6 hr/d 

5 d/wk (Fischer- 344) 2 yr 
127

0.56

22 

Table 3-1 Levels of Significant Exposure to Vanadium - Inhalation (continued) 

Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg V/m3) (mg V/m3) (mg V/m3) Chemical Form 

***DRAFT FOR PUBLIC COMMENT***

Mouse 6 hr/d 0.56 (alveolar/bronchiolar NTP 2002 5 d/wk (B6C3F1) 2 yr carcinoma) VANADIUM PENTOXID

a The number corresponds to entries in Figure 3-1 b Used to derive an acute-duration inhalation minimal risk level (MRL) of 0.0008 mg vanadium/m3; concentration adjusted for intermittent exposure (6 hours/24 hodays), multiplied by the Regional Deposited Dose Ratio (RDDR) of 0.732 for the thoracic region, and divided by an uncertainty factor of 90 (3 for the use of a minimextrapolation from animals to human with dosimetric adjustment, and 10 for human variability). c Used to derive a chronic-duration inhalation MRL of 0.0001 mg vanadium/m3 calculated using benchmark dose analysis. The BMCL10 of 0.04 mg vanadium/mintermittent exposure (6 hours/24 hours, 5 days/7 days), multiplied by the RDDR of 0.423 for the extrathoracic region, and divided by an uncertainty factor of 30 (3 ffrom animals to humans with dosimetric adjustment and 10 for human variability). Bd Wt = body weight; Cardio = cardiovascular; d = day(s); F = Female; Gastro = gastrointestinal hr = hour(s); Immuno/Lymphoret = immunological/lymphoreticular; lowest-observed-adverse-effect level; M = male; mo = month(s); Musc/skel = musculoskeletal; NOAEL = no-observed-adverse-effect level; NS = not specified; Res= week(s); yr = year(s) 
0.0001

0.001

0.01

0.1

1

10

100

1000

Death

1h

Respiratory

2k

2k 3k

3k

5m

4r

mg V/m3

Figure 3-1 Levels of Significant Exposure to Vanadium - Inhalation

Acute (≤14 days)

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

Systemic

VANADIUM

3. HEALTH EFFECTS 

34

***DRAFT FOR PUBLIC COMMENT***
0.1

1

10

100

Death

8m 6r

7r

Respiratory

9k

12m

12m

13m

13m

10r

10r

11r

11r

Cardiovascular

13m

11r

Gastrointestinal

13m

11r

Musculoskeletal

11r

Hepatic

13m

11r

Renal

13m

11r

Dermal

11r

Body Weight

12m

12m

13m

13m 10r 10r

10r

11r

11r

Immuno/Lymphor

15m

14r

Reproductive

17m

17m

17m

16r

16r

16r

mg V/m3

Figure 3-1 Levels of Significant Exposure to Vanadium - Inhalation (Continued)

Intermediate (15-364 days)

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

Systemic

VANADIUM

3. HEALTH EFFECTS 

35

***DRAFT FOR PUBLIC COMMENT***
0.0001

0.001

0.01

0.1

1

10

Death

18m

Respiratory

20m

19r

Cardiovascular

20m

19r

Gastrointestinal

20m

19r

Musculoskeletal

19r

Hepatic

20m

19r

Renal

20m

19r

Dermal

20m

Body Weight

20m

20m

20m 19r

Cancer *

22m

21r

mg V/m3

Figure 3-1 Levels of Significant Exposure to Vanadium - Inhalation (Continued)

Chronic (≥365 days)

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

Systemic

*Doses represent the lowest dose tested per study that produced a tumorigenic 

response and do not imply the existence of a threshold for the cancer endpoint. 

VANADIUM

3. HEALTH EFFECTS 

36

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VANADIUM 37 

3. HEALTH EFFECTS 

Animal data support the human findings and provide additional evidence that vanadium compounds are 

respiratory toxicants. Signs of respiratory distress, impaired lung function, increased pulmonary 

reactivity, and histological alterations in the lungs, larynx, and nasal cavity have been observed in 

laboratory animals. Rapid respiration during the exposure period was observed in rats exposed to 9.0 mg 

vanadium/m3 as vanadium pentoxide for 16 days or 4.5 mg vanadium/m3 for 4 weeks. In rats exposed to 

9.0 mg vanadium/m3 for 9 weeks, abnormal respiration was also observed during periods between 

vanadium exposures (NTP 2002). Audible wheezing and coughing were observed in monkeys exposed to 

0.62 mg vanadium/m3 for 6 hours; respiratory symptoms were not observed at 0.14 or 0.028 mg 

vanadium/m3 as vanadium pentoxide (Knecht et al. 1992). 

Decreases in pulmonary function were observed in rats exposed to ≥2.2 mg vanadium/m3 6 hours/day, 

5 days/week for 13 weeks (NTP 2002). Exposure to 2.2 or 4.5 mg vanadium/m3 resulted in alterations 

characterized as restrictive based on reduced lung compliance, changes in breathing measurements, 

impaired capacity to diffuse carbon monoxide, reduced static and dynamic lung volumes, and exaggerated 

airflow. The changes in breathing mechanics, static lung volumes, and forced expiratory maneuvers 

observed at 9.0 mg vanadium/m3 were suggestive of an obstructive lung disease; however, the 

investigators noted that these alterations may have been due to the deteriorating condition of the rats 

rather than an obstructive disease. Increased pulmonary resistance was observed in monkeys 1 day after a 

6-hour exposure to 2.8 mg vanadium/m3 (Knecht et al. 1985). Pulmonary reactivity, as evidenced by an 

obstructive pattern of impaired pulmonary function, was also observed in monkeys following a 6-hour 

exposure to 1.7 mg vanadium/m3 as vanadium pentoxide (Knecht et al. 1992); an increase in the total 

number of inflammatory cells present in the lungs was also observed. A similar degree of pulmonary 

reactivity was observed when the monkeys were re-challenged with methacholine following a 26-week 

exposure to 0.28 mg vanadium/m3 (6 hours/day, 5 days/week). Pulmonary reactivity was not 

significantly affected by a provocation challenge with 0.28 mg vanadium/m3 before or after the 26-week 

exposure (Knecht et al. 1992). 

NTP (2002) conducted a series of studies to evaluate the toxicity of vanadium pentoxide in rats and mice 

exposed 6 hours/day, 5 days/week for acute, intermediate, and chronic durations. Histological alterations 

were observed in the lungs, larynx, and nose. In the lungs, hyperplasia of alveolar and bronchiolar 

epithelium occurred at 1.1 mg vanadium/m3 in rats and mice exposed for 6, 13, or 90 days, 0.28 mg 

vanadium/m3 in rats exposed for 2 years, and 0.56 mg vanadium/m3 in mice exposed for 2 years. Lung 

inflammation and histiocytic infiltration (alveolar macrophages) were observed at similar concentrations 

in the acute, intermediate, and chronic duration studies. Fibrosis was also observed in rats exposed to 

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VANADIUM 38 

3. HEALTH EFFECTS 

2.2 mg vanadium/m3 for 13 or 90 days or 0.28 mg vanadium/m3 for 2 years and in mice exposed to 1.1 mg 

vanadium/m3 for 2 years. In both species, the severity of the lung lesions increased with increasing 

exposure duration and vanadium pentoxide exposure level. NTP (2002) also conducted several studies to 

examine the time course of the lung lesions. In rats exposed to 2.2 mg vanadium/m3

, histiocytic infiltrates 

and inflammation were observed after 2 days of exposure and alveolar and bronchiolar epithelial 

hyperplasia were first observed after 5 days of exposure to 1.1 or 2.2 mg vanadium/m3

. In rats exposed to 

0.56 mg vanadium/m3

, hyperplasia was only observed in a few animals after 542 days of exposure; 

however, at the end of the 2-year study, there was a significant increase in the incidence at this exposure 

level. In mice, lung lesions were not observed after 1 or 2 days of exposure. Bronchiolar epithelial 

hyperplasia and inflammation were observed after 5 days of exposure to 2.2 mg vanadium/m3

. At the 

lower exposure levels, lung lesions were observed after 12 days of exposure to 1.1 mg vanadium/m3 and 

54 days of exposure to 0.56 mg vanadium/m3

. 

The nasal effects observed in rats consisted of hyperplasia and squamous metaplasia of respiratory 

epithelium at 2.2 mg vanadium/m3 for 13 weeks, inflammation at 9.0 mg vanadium/m3 for 13 weeks, and 

goblet cell hyperplasia of the respiratory epithelium at 0.28 mg vanadium/m3 for 2 years. In mice exposed 

to vanadium pentoxide for 2 years, the nasal effects included suppurative inflammation at 1.1 mg 

vanadium/m3

, olfactory epithelium atrophy at 0.56 mg vanadium/m3, hyaline degeneration of olfactory 

and respiratory epithelium at 0.56 mg vanadium/m3

, and squamous metaplasia of respiratory epithelium at 

0.56 mg vanadium/m3

. Chronic exposure also resulted in damage to the larynx; degeneration and 

hyperplasia of the epiglottis epithelium were observed in rats exposed to 0.28 mg vanadium/m3 and 

squamous metaplasia of epiglottis epithelium was observed in rats exposed to 1.1 mg vanadium/m3 and 

mice exposed to 0.56 mg vanadium/m3

. 

Cardiovascular Effects. Workers exposed chronically to vanadium pentoxide dusts at incompletely 

documented exposure levels had normal blood pressure values (Vintinner et al. 1955). No other 

cardiovascular parameters were investigated in this study, but another study revealed normal 

electrocardiograms in vanadium workers (Sjöberg 1950). 

No significant alterations in heart rate, blood pressure, or electrocardiogram readings were observed in 

rats exposed to 4.5 mg vanadium/m3 as vanadium pentoxide 6 hours/day, 5 days/week for 13 weeks (NTP 

2002). Decreases in heart rate and blood pressure were found in rats exposed to 9.0 mg vanadium/m3

; 

however, this was attributed to the poor condition of the animals rather than a direct cardiotoxic effect. 

No histological alterations were observed in the hearts of rats exposed to 4.5 or 1.1 mg vanadium/m3 

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VANADIUM 39 

3. HEALTH EFFECTS 

6 hours/day, 5 days/week for 13 weeks or 2 years, respectively, or mice exposed to 9.0 or 2.2 mg 

vanadium/m3 for 13 weeks or 2 years, respectively (NTP 2002). 

Gastrointestinal Effects. No gastrointestinal complaints were reported by subjects exposed to 0.6 or 

0.1 mg vanadium/m3 vanadium pentoxide dusts for 8 hours (Zenz and Berg 1967). Workers exposed to 

vanadium in oil-burner ashes also did not show gastrointestinal symptoms (Sjöberg 1950). One study 

found that workers exposed chronically to vanadium dusts in factories sometimes complained of nausea 

and vomiting (Levy et al. 1984), but these symptoms can have a number of causes (such as exposure to 

other substances) and cannot be directly attributed to the vanadium. No histological alterations were 

observed in the gastrointestinal tract of rats exposed to 4.5 or 1.1 mg vanadium/m3 as vanadium pentoxide 

6 hours/day, 5 days/week for 13 weeks or 2 years, respectively, or mice exposed to 9.0 or 2.2 mg 

vanadium/m3 for 13 weeks or 2 years, respectively, (NTP 2002). 

Hematological Effects. No hematological alterations were observed in humans following acute 

(Zenz and Berg 1967) or occupational exposure (Kiviluoto et al. 1981a; Sjöberg 1950; Vintinner et al. 

1955) to vanadium dusts. 

During the first 23 days of a 13-week study, minimal erythrocyte microcytosis (as evidenced by decreases 

in hematocrit values, hemoglobin, mean cell volume, and mean cell hemoglobin) was observed in rats 

exposed to vanadium pentoxide 6 hours/day, 5 days/week (NTP 2002). The alterations in hematocrit and 

hemoglobin were observed after 4 days of exposure to 1.1 mg vanadium/m3

, mean cell volume and mean 

cell hemoglobin were decreased after 23 or 90 days of exposure to 2.2 mg vanadium/m3

. At 13 weeks, 

the microcytosis was replaced by erythrocytosis (as evidenced by increases in hemoglobin, hematocrit, 

nucleated erythrocytes, and reticulocytes) in rats exposed to 4.5 or 9.0 mg vanadium/m3

. 

Musculoskeletal Effects. Muscular strength was not altered in one study of workers exposed to 

vanadium pentoxide (Vintinner et al. 1955). No significant histological alterations were observed in the 

bone or muscle following a 13-week or 2-year exposure of rats to 9.0 or 1.1 mg vanadium/m3 as 

vanadium pentoxide, respectively, or mice to 9.0 or 2.2 mg vanadium/m3

, respectively. 

Hepatic Effects. Workers exposed chronically to 0.01–0.5 mg/m3 of vanadium dusts had normal 

serum levels of four enzymes (serum alkaline phosphatase, alanine aminotransferase (ALT), aspartate 

aminotransferase (AST), and lactate dehydrogenase) that are commonly used to detect possible liver 

damage (Kiviluoto et al. 1981a). 

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VANADIUM 40 

3. HEALTH EFFECTS 

Significant increases in serum ALT levels were observed in rats exposed to 4.5 mg vanadium/m3 

6 hours/day, 5 days/week for 13 weeks (NTP 2002). However, this alteration was not considered to be 

biologically relevant because it was not associated with histological alterations in the liver. No 

histological alterations were observed in the livers of rats exposed to 4.5 or 1.1 mg vanadium/m3 as 

vanadium pentoxide 6 hours/day, 5 days/week for 13 weeks or 2 years, respectively, or mice exposed to 

9.0 or 2.2 mg vanadium/m3 for 13 weeks or 2 years, respectively (NTP 2002). 

Renal Effects. Workers exposed chronically to 0.01–0.5 mg/m3 of vanadium dusts had normal serum 

levels of electrolytes, creatinine, and urea, suggesting no alterations in renal function (Kiviluoto et al. 

1981b). Workers in other studies of chronic exposure to vanadium had normal urine levels of substances 

used to detect kidney disease (casts, protein levels, urea) (Sjöberg 1950; Vintinner et al. 1955). 

Significant increases in serum urea nitrogen concentration were observed in male rats exposed to 4.5 mg 

vanadium/m3 for 13 weeks and females exposed to 2.2 mg vanadium/m3 for 23 days (but not after 

13 weeks of exposure) (NTP 2002). However, because decreases in total protein and creatinine 

concentration were also observed, the urea nitrogen alteration was attributed to decreased body weight 

rather than an effect on renal clearance. A decrease in overnight urine volumes and increase in urine 

specific gravity were observed in rats exposed to 2.2 mg vanadium/m3 for 13 weeks (NTP 2002). No 

alterations in urine volume or specific gravity were observed in urine samples collected after a 16-hour 

water deprivation period, suggesting that the alterations observed in the overnight urine sample were 

reflective of dehydration rather than altered kidney function. No histological alterations were observed in 

the kidneys of rats exposed to 4.5 or 1.1 mg vanadium/m3 as vanadium pentoxide 6 hours/day, 

5 days/week for 13 weeks or 2 years, respectively, or mice exposed to 9.0 or 2.2 mg vanadium/m3 for 

13 weeks or 2 years, respectively (NTP 2002). 

Dermal Effects. No increases in the occurrence of dermatitis were observed in vanadium pentoxide 

workers (Vintinner et al. 1955); increases in skin rashes were observed in some workers (NIOSH 1983). 

No histological alterations of the skin were observed in rats and mice following intermediate- or chronicduration exposure to vanadium pentoxide (NTP 2002). 

Ocular Effects. Workers chronically exposed to vanadium dusts in factories had slight to moderate 

eye irritation (Levy et al. 1984; Lewis 1959; Sjöberg 1950; Thomas and Stiebris 1956; Vintinner et al. 

1955). Brief exposure to vanadium dust can also cause conjunctivitis (Zenz et al. 1962). 

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VANADIUM 41 

3. HEALTH EFFECTS 

Body Weight Effects. Workers exposed to vanadium ore dust reported weight loss (Vintinner et al. 

1955). Significant decreases in body weight gain have been observed in rats and mice exposed to 

vanadium pentoxide (6 hours/day, 5 days/week) for intermediate or chronic durations (NTP 2002). The 

LOAELs were 9.0 mg vanadium/m3 for rats exposed for 16 or 90 days, 18 mg vanadium/m3 for mice 

exposed for 16 days, 9.0 mg vanadium/m3 for mice exposed for 90 days, and 1.1 mg vanadium/m3 for 

mice exposed for 2 years. At lower concentrations, the decreases were within 10% of the controls. 

Marked decreases in body weight gain (approximately 30% or higher) were observed at lethal 

concentrations. 

3.2.1.3 Immunological and Lymphoreticular Effects 

The only human data located found that workers chronically exposed to unspecified levels of vanadium 

dusts in factories showed no significant signs of allergic reactions on the skin or in the respiratory system 

(Sjöberg 1950). This, however, cannot be considered to be an adequate evaluation of immunological 

function. Systemic immunity was evaluated in rats and mice exposed to vanadium pentoxide 6 hours/day, 

5 days/week for 16 days (NTP 2002). Significant decreases in in vitro phagocytosis and increases in vivo 

bactericidal activity were observed in rats exposed to ≥2.2 mg vanadium/m3

. No adverse effect on the 

response to Klebsiella pneumoniae or to the influenza virus were observed in mice exposed to 18 mg 

vanadium/m3

. 

3.2.1.4 Neurological Effects 

Most workers exposed to vanadium dusts did not report major adverse neurological signs (Sjöberg 1956; 

Vintinner et al. 1955). However, some workers complained of dizziness, depression, headache, or 

tremors of the fingers and arms (Levy et al. 1984; Vintinner et al. 1955), which may or may not have been 

specifically due to vanadium exposure. No histological alterations were observed in the nervous system 

following a 13-week or 2-year exposure of rats to 4.5 or 1.1 mg vanadium/m3

, respectively, or mice to 

9.0 or 2.2 mg vanadium/m3

, respectively (NTP 2002). Because the NTP (2002) study did not assess 

neurological function, these NOAELs are not listed in Table 3-1 or Figure 3-1. 

3.2.1.5 Reproductive Effects 

No studies were located regarding the reproductive effects in humans after inhalation exposure to 

vanadium. There are limited data on the potential reproductive toxicity of vanadium in animals following 

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VANADIUM 42 

3. HEALTH EFFECTS 

inhalation exposure. No histological alterations were observed in rats exposed to 9.0 mg vanadium/m3 as 

vanadium pentoxide for 3 months or 1.1 mg vanadium/m3 for 2 years or in mice exposed to 9.0 mg 

vanadium/m3 for 3 months or 2.2 mg vanadium/m3 for 2 years (NTP 2002). No significant alterations in 

sperm count, motility, or concentration were observed in rats exposed to 9.0 mg vanadium/m3 for 

3 months (NTP 2002). In females exposed to 4.5 mg vanadium/m3 as vanadium pentoxide for 3 months, 

significant increases in estrous cycle length were observed (NTP 2002); at 9.0 mg vanadium/m3

, the 

number of cycling females was significantly reduced. No studies examined reproductive function. 

3.2.1.6 Developmental Effects 

No studies were located regarding the developmental effects in humans or animals after inhalation 

exposure to vanadium. 

3.2.1.7 Cancer 

No studies were located regarding the carcinogenicity in humans after inhalation exposure to vanadium. 

NTP (2002) examined the carcinogenic potential of vanadium in rats and mice exposed to vanadium 

pentoxide 6 hours/day, 5 days/week for 2 years. Increases in the incidence of alveolar/bronchiolar 

adenoma, carcinoma, or the combined incidences of adenoma and carcinoma were observed in male rats. 

As indicated in Table 3-2, the incidences of these tumors were not statistically different from controls; 

however, the incidence of adenomas at 0.28 mg vanadium/m3 and combined incidence of adenoma and 

carcinoma at 0.56 or 1.1 mg vanadium/m3 were greater than historical control levels. Due to the rarity of 

these tumors, NTP considered the increases in adenoma and carcinoma observed in male rats to be related 

to vanadium pentoxide exposure. In female rats, no significant increases in lung tumors were observed. 

In the 0.28 mg vanadium/m3 group, the incidence of alveolar/bronchiolar adenoma exceeded the historical 

control range. NTP (2002) noted that this may be related to vanadium pentoxide exposure; however, 

because it was only observed at the lowest vanadium pentoxide concentration, a clear relationship 

between lung neoplasms and vanadium pentoxide could not be determined in female rats. In male mice, 

significant increases in the incidence of alveolar/bronchiolar carcinoma and the combined incidence of 

alveolar/bronchiolar adenoma and carcinoma were observed at 0.56, 1.1, and 2.2 mg vanadium/m3

; an 

increased incidence of alveolar/bronchiolar adenoma was observed at 1.1 mg vanadium/m3

. In female 

mice, the incidences of alveolar/bronchiolar adenoma or carcinoma and the combined incidence of 

adenoma and carcinoma were significantly elevated in the 0.56, 1.1, and 2.2 mg vanadium/m3 groups. As 

presented in Table 3-2, the tumor incidences in the male and female mice were not concentration-related. 

Based on vanadium lung burden studies in female rats and mice exposed to vanadium pentoxide, NTP 

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VANADIUM 43 

3. HEALTH EFFECTS 

Table 3-2. Incidence of Lung Tumors in Rats and Mice Exposed to Vanadium
 

Pentoxide for 2 Yearsa
 

Concentration (mg vanadium/m3) 

0 0.28 0.56 1.1 

Rats 

Male 

Alveolar/bronchiolar adenoma, multiple 0/50 2/49 0/48 0/50 

Alveolar/bronchiolar adenoma (includes 

multiple)b 

4/50 8/49 5/48 6/50 

Alveolar/bronchiolar carcinoma, multiple 0/50 1/49 0/48 0/50 

Alveolar/bronchiolar carcinoma (includes 

multiple)c 

0/50 3/49 1/48 3/50 

Alveolar/bronchiolar adenoma or 

carcinomad 

4/50 10/49 6/48 9/50 

Female 

Alveolar/bronchiolar adenoma 0/49 3/49 1/50 0/50 

Alveolar/bronchiolar carcinoma 0/49 0/49 0/50 1/50 

Alveolar/bronchiolar adenoma or carcinoma 0/49 3/49 1/50 1/50 

Mice 0 0.56 1.1 2.2 

Male 

Alveolar/bronchiolar adenoma, multiple 1/50 1/50 11/50e 5/50 

Alveolar/bronchiolar adenoma (includes 13/50 16/50 26/50e 15/50 

multiple) 

Alveolar/bronchiolar carcinoma, multiple 1/50 10/50e 16/50e 13/50e 

Alveolar/bronchiolar carcinoma (includes 12/50 29/50 30/50 35/50 

multiple) 

Alveolar/bronchiolar adenoma or carcinoma 22/50 42/50e 43/50e 43/50e 

Female 0 0.28 0.56 1.1 

Alveolar/bronchiolar adenoma, multiple 0/50 3/50 5/50e 6/50e 

alveolar/bronchiolar adenoma (includes 1/50 17/50e 23/50e 19/50e 

multiple) 

Alveolar/bronchiolar carcinoma, multiple 0/50 9/50e 5/50e 5/50e 

Alveolar/bronchiolar carcinoma (includes 0/50 23/50e 18/50e 22/50e 

multiple) 

Alveolar/bronchiolar adenoma or carcinoma 1/50 32/50e 35/50e 32/50e 

a

Animals were exposed for 6 hours/day, 5 days/week

b

Historical incidence for 2-year studies with controls given NTP-2000 diet (mean ±standard deviation): 4.2±3.5%,
 

range 0–12%; with inhalation chamber controls given NIH-07 diet: 1.7±2.4%, range 0–10%
 c

Historical incidence for NTP-2000: diet 0.4±0.8%, range 0–2%; NIH-07 diet: 0.8±1.2%, range 0–10%
 d

Historical incidence for NTP-2000: diet 4.5±3.9%, range 0–14%; NIH-07 diet: 2.5±2.6%, range 0–10%
 e

p≤0.01
 

Source: NTP 2002 

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VANADIUM 44 

3. HEALTH EFFECTS 

(2002) estimated that the total vanadium lung “doses” were 130, 175, and 308 μg vanadium in rats 

exposed to 0.28, 0.56, or 1.1 mg vanadium/m3 for 540 days and 153, 162, and 225 μg vanadium in mice 

exposed to 0.56, 1.1, or 2.2 mg vanadium/m3 for 553 days. In both species, the similarity of the total dose 

at the two lower concentrations (total lung doses of 130 and 175 μg vanadium in rats exposed to 0.28 and 

0.56 mg vanadium/m3 and 153 and 162 μg vanadium in mice exposed to 0.56 and 1.1 mg vanadium/m3

) 

provides a partial explanation for the flat dose-response curve for lung tumors. NTP (2002) also 

suggested that the differences in lung tumor responses between the rats and mice may be due to finding 

that mice received considerably more vanadium on a body weight basis than rats. 

3.2.2 Oral Exposure 

3.2.2.1 Death 

No studies were located regarding death in humans after oral exposure to vanadium. 

The 14-day LD50 values for sodium metavanadate are 41 mg vanadium/kg in rats and 31.2 mg vanadium/ 

kg in mice (Llobet and Domingo 1984). Deaths have been reported in rat dams exposed to 17 mg 

vanadium/kg/day as sodium orthovanadate on gestation days 6–15 (Sanchez et al. 1991) and in rats 

exposed to 22.06 or 24.47 mg vanadium/kg/day as ammonium metavanadate for 4 weeks (Zaporowska 

and Wasilewski 1989, 1990). Although the cause of death was not determined, marked decreases in body 

weight, food intake, and water consumption and increases in the occurrence of diarrhea were observed in 

animals dying early. Chronic exposures of up to 19 mg vanadium/kg as vanadyl sulfate in food or water 

did not affect mortality in rats or mice (Dai et al. 1994a, 1994b; Schroeder and Balassa 1967; Schroeder et 

al. 1970). 

3.2.2.2 Systemic Effects 

The highest NOAEL values and all reliable LOAEL values for systemic effects in each species and 

duration category are recorded in Table 3-3 and plotted in Figure 3-2. 

No studies were located regarding musculoskeletal or dermal/ocular effects in humans or animals 

following oral exposure to vanadium. 

Respiratory Effects. No studies were located regarding respiratory effects in humans after oral 

exposure to vanadium. Rats receiving sodium metavanadate in the drinking water for 3 months had 

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26

41

25

31

69

17

87

27.72

27.65

103

7.5

24

4.2 8.4

Table 3-3 Levels of Significant Exposure to Vanadium - Oral 

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Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg V/kg/day) (mg V/kg/day) (mg V/kg/day) Chemical Form 

ACUTE EXPOSURE Death 

1 Rat 1 d 41 (LD50) Llobet and Domingo 19

1 x/d 

SODIUM METAVANAD

(GW) 

2 Mouse once 31 (LD50) Llobet and Domingo 19

(GW) SODIUM METAVANAD

3 Mouse Gd 6-15 17 F (17/19 dams died) Sanchez et al. 1991 (Swiss) (G) SODIUM ORTHOVANA

Systemic 

4 Rat 2 wk Hemato 27.72 M (increased reticulocytes, Zaporowska and Wasile

(Wistar) (W) increased 1989

polychromatophilic AMMONIUM 

erythroblasts in bone METAVANADATE marrow) 

Bd Wt 27.65 F 

5 Mouse Gd 6-15 Bd Wt 7.5 F (46% decrease in Paternain et al. 1990 (Swiss) (G) maternal weight gain) VANADYL SULFATE 

Developmental 

6 Rat Gd 6-14 4.2 8.4 (facial hemorrhages) Paternain et al. 1987 (G) SODIUM METAVANAD
68

7.5

70

4.2

8.3

89

24.47

91

22.06

30

0.190.190.19

Table 3-3 Levels of Significant Exposure to Vanadium - Oral (continued) 

***DRAFT FOR PUBLIC COMMENT***

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 

7 Mouse Gd 6-15 7.5 F (increased early Paternain et al. 1990 (Swiss) (G) resorptions, decreased VANADYL SULFATE 

fetal growth, increased soft tissue and skeletal defects) 

8 Mouse Gd 6-15 4.2 8.3 (decreased number of Sanchez et al. 1991 (Swiss) (G) ossified sacrococcygeal SODIUM ORTHOVANA

vertebrae) 

INTERMEDIATE EXPOSURE Death 

9 Rat 4 or 8 wk 24.47 M (10/32 animals died by Zaporowska and Wasile

(Wistar) (W) week 4) 1989

AMMONIUM METAVANADATE 

10 Rat 4 wk 22.06 M (12/20 rats died) Zaporowska and Wasile

(Wistar) (W) 1990

AMMONIUM METAVANADATE 

Systemic 

11 Human 45-68 d Hemato 0.19 Dimond et al. 1963 (C) AMMONIUM VANADYL 

TARTRATE 

Hepatic 0.19 Renal 0.19 
79

0.120.120.120.12

93

1

2.1

2.1

76

31

31

72

4.7

0.12

4.7

Table 3-3 Levels of Significant Exposure to Vanadium - Oral (continued) 

***DRAFT FOR PUBLIC COMMENT***

Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg V/kg/day) (mg V/kg/day) (mg V/kg/day) Chemical Form 

12 Human daily Cardio 0.12 Fawcett et al. 1997 12 wk 

VANADYL SULFATE (C) 

b

Hemato 0.12 Hepatic 0.12 Bd Wt 0.12 

13 Rat 10 wk Hemato 1 F 2.1 F (decreased hemoglobin Adachi et al. 2000 (Wistar) (F) and hematocrit, SODIUM METAVANAD

increased reticulocyte) 

Bd Wt 2.1 F 

14 Rat 60 d Cardio 31 M (decreased aorta Akgun-Dar et al. 2007 (Swiss) (G) diameter) VANADYL SULFATE 

Metab 31 M

d

15 Rat 210 d Resp 4.7 M Boscolo et al. 1994 (Sprague- (W) SODIUM METAVANAD

Dawley) 

Cardio 0.12 M (increased blood

pressure)

Hepatic 4.7 M 
75

2222

73

12

74

1.2

77

9.79.7

78

7.67.6

102

6

104

31

Table 3-3 Levels of Significant Exposure to Vanadium - Oral (continued) 

***DRAFT FOR PUBLIC COMMENT***

LOAEL 

NOAEL Less Serious Serious Reference

System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

Cardio 22 M Bursztyn and Mekler 19

SODIUM METAVANAD

Metab 22 M Cardio 12 M (increased blood Carmagnani et al. 1991 

pressure and heart rate) SODIUM METAVANAD

Cardio 1.2 M (increased blood Carmagnani et al. 1992 

pressure) SODIUM METAVANAD

Hemato 9.7 M Dai et al. 1995 

AMMONIUM METAVANADATE 

Bd Wt 9.7 M Hemato 7.6 M Dai et al. 1995 

VANADYL SULFATE 

Bd Wt 7.6 M Bd Wt 6 F (19% decrease in Elefant and Keen 1987 

maternal body weight SODIUM METAVANADgain) 

Bd Wt 31 M Jain et al. 2007 

VANADYL SULFATE 

a 

Key to 

Figure 

16 17 18 19 20 21 22 

Species 

(Strain) 

Rat (Sabra) Rat (SpragueDawley) Rat (SpragueDawley) Rat (Wistar) Rat (Wistar) Rat (SpragueDawley) Rat (Wistar) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

4 wk (W) 7 mo (W) 7 mo (W) 12 wk (W) 12 wk (W) Gd 0- Ld 21 (F) 60 d (G) 
21

6.66.6

30

106

3.42

6.84

81

8.35

8.35

82

10.69

20

10

101

13

Table 3-3 Levels of Significant Exposure to Vanadium - Oral (continued) 

***DRAFT FOR PUBLIC COMMENT***

Exposure/ LOAEL

Duration/

a Frequency Reference Key to Species NOAEL Less Serious Serious (Route) Figure (Strain) System (mg V/kg/day) (mg V/kg/day) (mg V/kg/day) Chemical Form 

23 Rat 75 or 103 d Hemato 6.6 M Mountain et al. 1953 (Wistar) (F) VANADIUM PENTOXID

Bd Wt 6.6 M 30 M (53% decrease in body 

weight gain) 

24 Rat 8 wk Bd Wt 3.42 M 6.84 M (10% decrease in body Sanchez et al. 1998 (Sprague- (G) weight gain) SODIUM METAVANAD

Dawley) 

25 Rat 6 wk Hemato 8.35 M (increased erythrocyte Scibior 2005 (Wistar) (W) levels) SODIUM METAVANAD

Bd Wt 8.35 M 

26 Rat 6 wk Hemato 10.69 M (decreased erythrocyte Scibior et al. 2006 (Wistar) (W) and hemoglobin levels) SODIUM METAVANAD

27 Rat 2 mo Cardio 10 M (increased ventricular Susic and Kentera 1986 (Long- Evans) (F) pressure) AMMONIUM 

METAVANADATE 

28 Rat 7.4 wk Metab 13 M Yao et al. 1997 (Sprague- (W) VANADYL SULFATE Dawley) 
88

24.47

90

22.06

83

19.73

84

19.7319.73

85

12.99

Table 3-3 Levels of Significant Exposure to Vanadium - Oral (continued) 

***DRAFT FOR PUBLIC COMMENT***

Exposure/ LOAEL 

Duration/ 

Frequency NOAEL Less Serious Serious Reference (Route) System (mg V/kg/day) (mg V/kg/day) (mg V/kg/day) Chemical Form 

4 or 8 wk Hemato 24.47 M (decreased erythroctyes, Zaporowska and Wasile

(W) increased reticulocytes) 1989

AMMONIUMMETAVANADATE

4 wk Hemato 22.06 M (decreased erythrocyte, Zaporowska and Wasile

(W) increased reticulocyte) 1990 

AMMONIUM METAVANADATE 

4 wk Hemato 19.73 M (decreased hemoglobin Zaporowska and Wasile

(W) and erythrocyte and 1991

increased reticulocyte) AMMONIUM 

METAVANADATE 

4 wk Gastro 19.73 (diarrhea) Zaporowska and Wasile

(W) 1992a 

AMMONIUM METAVANADATE 

Hemato 19.73 M (decreased hemoglobin

and erythrocyte andincreased reticulocyte)

4 wk Hemato 12.99 M (decreased hemoglobin Zaporowska and Wasile

(W) and erythrocyte and 1992b

increased reticulocyte) AMMONIUM

METAVANADATE

a 

Key to Species 

Figure (Strain) 

29 Rat 

(Wistar) 

30 Rat 

(Wistar) 

31 Rat 

(Wistar) 

32 Rat 

(Wistar) 

33 Rat 

(Wistar) 
86

1.18

4.93

80

1.8

94

1

2.1

100

1.72

134

6.84

14

8.4

Table 3-3 Levels of Significant Exposure to Vanadium - Oral (continued) 

***DRAFT FOR PUBLIC COMMENT***

Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg V/kg/day) (mg V/kg/day) (mg V/kg/day) Chemical Form 

34 Rat 4 wk Hemato 1.18 M (decreased erythrocyte Zaporowska et al. 1993 (Wistar) (W) levels) AMMONIUM 

METAVANADATE 

Bd Wt 4.93 M 

35 Rabbit 24, 129, Hemato 1.8 (decreased erythrocyte Kasibhatla and Rai 199

or 171 d (NS) levels) Not Reported (W) 

Immuno/ Lymphoret 

36 Rat 10 wk 1 F 2.1 F (decreased B-cell, IgG, Adachi et al. 2000 (Wistar) (F) and IgM levels) SODIUM METAVANAD

Neurological 

37 Rat 8 wk 1.72 M (impaired performance Sanchez et al. 1998 (Sprague- (G) on neurobehavioral tests) SODIUM METAVANAD

Dawley) 

38 Rat daily 6.84 M (impaired response in Sanchez et al. 1999 8 wk (Sprague- active avoidance tests) SODIUM METAVANAD

Dawley) (GW) 

Reproductive 

39 Rat 60 d 8.4 Domingo et al. 1986 (Sprague- (GW) SODIUM METAVANAD

Dawley) 
96

31

98

1012

97

17

25

13

2.1

66

6

Table 3-3 Levels of Significant Exposure to Vanadium - Oral (continued) 

***DRAFT FOR PUBLIC COMMENT***

Exposure/ LOAEL 

Duration/ 

Frequency NOAEL Less Serious Serious Reference (Route) System (mg V/kg/day) (mg V/kg/day) (mg V/kg/day) Chemical Form 

60 d 31 M (decreased fertility, Jain et al. 2007 (G) sperm count, and VANADYL SULFATE 

motility) 

M: 70 d F:14 d 10 M (decreased fertility) Morgan and El-Tawil 20

premating,mating, AMMONIUMgestation, 12 F (decreased fertility) METAVANADATE 

lactation (W) 64 d 17 M 25 M (decreased fertility and Llobet et al. 1993 (W) spermatozoa count) SODIUM METAVANAD

60 d 2.1 (reduced pup weight and Domingo et al. 1986 (G) length) SODIUM METAVANAD

Gd 0- Ld 21 6 (decreased pup survival Elefant and Keen 1987 (F) and body weight) SODIUM METAVANAD

a 

Key to Species 

Figure (Strain) 

40 Rat 

(Wistar) 

41 Rat 

(SpragueDawley) 

42 Mouse 

(Swiss) 

Developmental 

43 Rat 

(SpragueDawley) 

44 Rat 

(SpragueDawley) 
99

1012

71

10

48

0.7

50

4.1

49

0.54

Table 3-3 Levels of Significant Exposure to Vanadium - Oral (continued) 

***DRAFT FOR PUBLIC COMMENT***

Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg V/kg/day) (mg V/kg/day) (mg V/kg/day) Chemical Form 

45 Rat M: 70 d F:14 d 10 M (decreased viability, Morgan and El-Tawil 20

premating, (Sprague- mating, increased gross, skeletal AMMONIUM Dawley) gestation, and visceral anomalies, METAVANADATE decreased pup body lactation weight) (W) 

12 F (decreased viability, 

increased gross, skeletal and visceral anomalies, decreased pup body weight) 

46 Rat Gd 19- Ld 25, 10 (decreased pup survival) Poggioli et al. 2001 pups exposed (Wistar) until pnd 100 VANADYL SULFATE 

(W) 

CHRONIC EXPOSURE Death 

47 Rat 2.5 yr 0.7 Schroeder et al. 1970 (W) VANADYL SULFATE 

48 Mouse 2 yr 4.1 Schroeder and Balassa 

(F) VANADYL SULFATE 

49 Mouse 2.5 yr 0.54 Schroeder and Mitchne

(W) VANADYL SULFATE 
92

191919191917

28

19

15

0.70.7

16

4.14.14.14.14.1

17

0.54

Table 3-3 Levels of Significant Exposure to Vanadium - Oral (continued) 

***DRAFT FOR PUBLIC COMMENT***

Exposure/ LOAEL

Duration/

a Frequency Reference Key to Species NOAEL Less Serious Serious (Route) Figure (Strain) System (mg V/kg/day) (mg V/kg/day) (mg V/kg/day) Chemical Form 

Systemic 

50 Rat 52 wk Resp 19 M Dai and McNeill 1994; D

(Wistar) (W) al. 1994a, 1994b

VANADYL SULFATE

Cardio 19 MHemato 19 M Hepatic 19 M 

Renal 19 M (

df

Bd Wt 17 M 28 M (20% decrease in body

weight gain)

Metab 19 M 

51 Rat 2.5 yr Renal 0.7 Schroeder et al. 1970 (W) VANADYL SULFATE 

Bd Wt 0.7 

52 Mouse 2 yr Resp 4.1 Schroeder and Balassa 

(F) VANADYL SULFATE 

Cardio 4.1 Hemato 4.1 Renal 4.1 Bd Wt 4.1 

53 Mouse 2.5 yr Bd Wt 0.54 Schroeder and Mitchne

(W) VANADYL SULFATE 
52

4.1

Table 3-3 Levels of Significant Exposure to Vanadium - Oral (continued) 

Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg V/kg/day) (mg V/kg/day) (mg V/kg/day) Chemical Form 

***DRAFT FOR PUBLIC COMMENT***

Immuno/ Lymphoret 

54 Mouse 2 yr 4.1 Schroeder and Balassa 

(F) VANADYL SULFATE 

a The number corresponds to entries in Figure 3-2 b Used to derive an intermediate-duration oral MRL of 0.01 mg vanadium/kg/day; dose divided by an uncertainty factor of 10 for human variability. Bd Wt = body weight; (C) = capsule; Cardio = cardiovascular; d = day(s); (F) = feed; F = Female; (G) = gavage; Gastro = gastrointestinal; Gd = gestation day; (GW) water; Hemato = hematological; Immuno/Lymphoret = immunological/lymphoreticular; Ld = lactation day; LD50 = lethal dose, 50% kill; LOAEL = lowest-observed-aM = male; Metab = metabolic; mo = month(s); NOAEL = no-observed-adverse-effect level; NS = not specified; pnd = post-natal day; Resp = respiratory; (W) = drinweek(s); x = time(s); yr = year(s) 
1

10

100

Death

2m

3m

1r

Hematological

4r

Body Weight

5m

4r

Developmental

7m

8m

8m

6r

6r

mg V/kg/day

Figure 3-2 Levels of Significant Exposure to Vanadium - Oral

Acute (≤14 days)

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

Systemic

VANADIUM

3. HEALTH EFFECTS

56

***DRAFT FOR PUBLIC COMMENT***
0.01

0.1

1

10

100

Death

9r 10r

Respiratory

15r

Cardiovascular

12

14r

15r

16r

17r

18r

27r

Gastrointestinal

32r

Hematological

11

12

13r

13r

19r

20r 23r

25r

26r

29r 30r 31r 32r

33r

34r

35h

Hepatic

11

12

15r

Renal

11

Body Weight

12

13r

19r

20r

21r

22r 23r

23r

24r

24r

25r

34r

Metabolic

14r

16r

28r

Immuno/Lymphor

36r

36r

Neurological

37r

38r

Reproductive

42m

42m

39r

40r

41r

41r

mg V/kg/day

Figure 3-2 Levels of Significant Exposure to Vanadium - Oral (Continued)

Intermediate (15-364 days)

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

Developmental

43r

44r

45r

45r 46r

Systemic

VANADIUM

3. HEALTH EFFECTS

57

***DRAFT FOR PUBLIC COMMENT***
0.1

1

10

100

Death

48m

49m

47r

Respiratory

52m

50r

Cardiovascular

52m

50r

Hematological

52m

50r

Hepatic

50r

Renal

52m

50r

51r

Body Weight

52m

53m

50r

50r

51r

Metabolic

50r

Immuno/Lymphor

54m

mg V/kg/day

Figure 3-2 Levels of Significant Exposure to Vanadium - Oral (Continued)

Chronic (≥365 days)

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

Systemic

VANADIUM

3. HEALTH EFFECTS

58

***DRAFT FOR PUBLIC COMMENT***
 

 

 

 

 

 

 

 

 

VANADIUM 59 

3. HEALTH EFFECTS 

mononuclear cell infiltration, mostly perivascular, in the lungs; the investigators noted that the effects 

were more evident at the highest dose level (3.5 mg vanadium/kg/day), but incidence data were not 

reported (Domingo et al. 1985). 

Cardiovascular Effects. No significant alterations in systolic or diastolic blood pressure were 

observed in adults exposed to 0.12 mg vanadium/kg/day as vanadyl sulfate for 4, 8, or 12 weeks via 

capsules taken at mealtime (Fawcett et al. 1997). 

Several studies have examined the effects of vanadium on blood pressure in laboratory animals. The 

results are inconsistent; however, differences in the methods used to measure blood pressure and the 

strains of rats tested complicate cross study comparisons. Significant increases in systolic, diastolic, 

and/or mean blood pressure were observed in Sprague-Dawley rats exposed to 0.12–12 mg vanadium/ 

kg/day as sodium metavanadate in drinking water for 180–210 days (measured in femoral artery of 

anesthetized rats; Boscolo et al. 1994), in Sprague-Dawley rats exposed to 1.2–12 mg vanadium/kg/day as 

sodium metavanadate in drinking water for 7 months (measured in the aorta of anesthetized rats; 

Carmagnani et al. 1991, 1992), and Long-Evans rats exposed to 10 mg vanadium/kg/day as ammonium 

vanadate in the diet for 60 days (measured in ventricle of anesthetized rats; Sušić and Kentera 1986). In 

contrast, no alterations in blood pressure were observed in rats exposed to 10 mg vanadium/kg/day as 

ammonium vanadate in the diet for 60 days (Long-Evans rats, measured in femoral artery; Sušić and 

Kentera 1986), 22 mg vanadium/kg/day as sodium metavanadate in drinking water for 4 weeks (Sabra 

rats, measured via tail cuff; Bursztyn and Mekler 1993), 32 mg vanadium/kg/day as vanadyl sulfate in 

drinking water for 52 weeks (Wistar rats, measured via tail cuff; Dai and McNeill 1994), or 63 mg 

vanadium/kg/day as sodium metavanadate in the diet for 24 weeks (Long-Evans rats, measured via tail 

cuff or femoral artery; Sušić and Kentera 1988). Studies in compromised animals have also found 

alterations in blood pressure. Increases in arterial blood pressure (measured via tail cuff) were observed 

in salt-induced hypertensive rats exposed to 22 mg vanadium/kg/day as sodium metavanadate in drinking 

water for 4 weeks compared to hypertensive controls (Bursztyn and Mekler 1993). Similar increases in 

blood pressure (measured via tail cuff) were observed in uninephrectomized rats exposed to 6 mg 

vanadium/kg/day as sodium metavanadate in the diet for 18 weeks (Sušić and Kentera 1988) or 5 mg 

vanadium/kg/day as sodium orthovanadate in the diet (Steffen et al. 1981). Alterations in the reninangiotensin-aldosterone system and alterations in urinary excretion of electrolytes observed in the 

Boscolo et al. (1994) study provide suggestive evidence that altered renal function may play a role in 

vanadium-induced hypertension. Significant increases in plasma renin activity, plasma aldosterone 

levels, and increases in kallikrein (enzyme that releases vasodilating kinins from plasma proteins), and 

***DRAFT FOR PUBLIC COMMENT*** 
 

 

 

 

 

 

 

 

 

 

 

 

VANADIUM 60 

3. HEALTH EFFECTS 

kininases I and II activities were observed in rats exposed to 1.2 or 4.7 mg vanadium/kg/day as sodium 

metavanadate in the drinking water for 7 months. 

Other alterations in the cardiovascular system included significant decreases in aorta diameter and the 

aorta tunica intima thickness in rats administered 31 mg vanadium/kg/day as vanadyl sulfate via gavage 

for 60 days (Akgün-Dar et al. 2007) and an increase in heart rate in rats exposed to 12 mg vanadium/kg/ 

day as sodium metavanadate in drinking water for 7 months (Carmagnani et al. 1991, 1992), but not in 

rats exposed to ≤4.7 mg vanadium/kg/day as sodium metavanadate in drinking water for 7 months 

(Boscolo et al. 1994; Carmagnani et al. 1992) or 10 mg vanadium/kg/day as ammonium vanadate in the 

diet for 2 months (Sušić and Kentera 1986). 

Gastrointestinal Effects. The limited data available for assessing gastrointestinal effects suggest 

that exposure to vanadium may cause mild gastrointestinal irritation. Intestinal cramping and diarrhea 

were observed in subjects exposed to an average dose of 0.19 mg vanadium/kg/day as ammonium 

vanadyl tartrate administered via capsules for 45–68 days (Dimond et al. 1963). Several clinical studies 

investigating the efficacy and mechanism of action of sodium metavanadate and vanadyl sulfate for the 

treatment of diabetes mellitus have found mild gastrointestinal effects (Boden et al. 1996; Cusi et al. 

2001; Goldfine et al. 1995). Mild diarrhea was reported by 4/10 insulin- and noninsulin-dependent 

diabetes patients administered 0.66 mg vanadium/kg/day as sodium metavanadate as capsules 

administered 3 times/day (0.26 mg vanadium/kg at breakfast and lunch and 0.13 mg vanadium/kg at 

dinner) for 14 days (Goldfine et al. 1995); another subject reported nausea and vomiting that subsided 

when the dose was decreased to 0.13 mg vanadium/kg 3 times/day. In another study of eight noninsulin 

dependent diabetics administered 0.35 mg vanadium/kg/day as vanadyl sulfate as capsules 2 times/day for 

4 weeks, diarrhea and abdominal cramps were reported during the first week of treatment, but not 

reported thereafter (Boden et al. 1996). Similarly, insulin-independent diabetics reported diarrhea and 

abdominal discomfort during the first 2 weeks of exposure to vanadyl sulfate (Cusi et al. 2001). The 

initial dose of 0.2 mg vanadium/kg/day administered presumably as capsules 2 times/day was increased 

every 2–3 days and reached 0.6 mg vanadium/kg/day by week 2. Several animal studies have reported 

diarrhea in rats exposed to ≥8.35 mg vanadium/kg/day as sodium metavanadate or ammonium 

metavanadate (Ścibior 2005; Zaporowska and Wasilewski 1989, 1990, 1992a); the diarrhea was often 

observed at doses associated with marked decreases in food intake and water consumption. 

Hematological Effects. No alterations in reticulocyte or platelet counts (Dimond et al. 1963) or 

erythrocyte, hemoglobin, hematocrit, or platelet levels (Fawcett et al. 1997) were observed in adults 

***DRAFT FOR PUBLIC COMMENT*** 
 

 

 

 

 

 

 

 

VANADIUM 61 

3. HEALTH EFFECTS 

exposed to 0.19 mg vanadium/kg/day as ammonium vanadyl tartrate for 6–10 weeks or 0.12 mg 

vanadium/kg/day as vanadyl sulfate for 12 weeks, respectively. 

A series of studies conducted by Zaporowska and associates examined the hematotoxicity of ammonium 

metavanadate administered in drinking water to rats for acute or intermediate durations. A 2-week 

exposure to 27.72 mg vanadium/kg/day resulted in significant increases in reticulocyte levels and 

increases in the percentage of polychromatophilic erythroblasts in the bone marrow in male rats 

(Zaporowska and Wasilewski 1989); a nonsignificant increase in erythrocytes was also observed at this 

dose level. Exposures to 12.99–24.47 mg vanadium/kg/day for 4 weeks resulted in decreases in 

erythrocyte levels and hemoglobin levels and increases in reticulocyte levels (Zaporowska and 

Wasilewski 1989, 1990, 1991, 1992a, 1992b). However, death and decreases in body weight gain, food 

intake, and water consumption were also observed at these dose levels. Similar effects were observed in 

rats exposed to 8.35 or 10.69 mg vanadium/kg/day as sodium metavanadate for 6 weeks (Ścibior 2005; 

Ścibior et al. 2006). One study in this series tested lower concentrations which did not result in frank 

toxicity. Significant decreases in erythrocyte and hematocrit levels were observed in rats exposed to 

1.18 or 4.93 mg vanadium/kg/day as ammonium metavanadate for 4 weeks (Zaporowska et al. 1993); 

significant increases in reticulocyte levels were observed at 4.93 mg vanadium/kg/day. The decreases in 

erythrocyte levels were small (approximately 11% less than controls) and not dose-related. Decreases in 

hemoglobin and hematocrit and increases in reticulocytes were observed in rats exposed to 2.1 mg 

vanadium/kg/day as sodium metavanadate for 10 weeks (Adachi et al. 2000a) and decreases in 

erythrocyte counts were observed in rabbits exposed to 1.8 mg vanadium/kg/day of an unknown 

metavanadate compound for 24 days (Kasbhatla and Rai 1993). However, other investigators have not 

found hematological alterations in rats exposed to 19 mg vanadium/kg/day as vanadyl sulfate for 1 year 

(Dai and McNeill 1994), 9.7 mg vanadium/kg/day as ammonium metavanadate for 12 weeks (Dai et al. 

1995), 7.6 mg vanadium/kg/day as vanadyl sulfate for 12 weeks (Dai et al. 1995), or 6.6 mg 

vanadium/kg/day as vanadium pentoxide for 10–15 weeks (Mountain et al. 1953). As suggested by 

Ścibior et al. (2006), the differences may be due to the duration of exposure, compound administered, or 

age of the animals. 

Hepatic Effects. No significant alterations in serum AST, cholesterol, triglyceride, phospholipid, 

and/or bilirubin levels were observed in humans administered, via capsules, 0.19 mg vanadium/kg as 

ammonium vanadyl tartrate for 45–68 days (Dimond et al. 1963) or 0.12 mg vanadium/kg/day as vanadyl 

sulfate for 12 weeks (Fawcett et al. 1997). 

***DRAFT FOR PUBLIC COMMENT*** 
 

 

 

 

 

 

 

 

 

 

 

 

VANADIUM 62 

3. HEALTH EFFECTS 

Several studies in laboratory animals examining cholesterol and triglyceride levels (Adachi et al. 2000a; 

Dai et al. 1994a) or serum enzyme levels (ALT or AST) (Adachi et al. 2000a; Dai et al. 1994b; Yao et al. 

1997) have not found biologically relevant alterations. The highest NOAEL values for these effects are 

13 mg vanadium/kg/day (Yao et al. 1997) following intermediate-duration exposure and 19 mg 

vanadium/kg/day following chronic-duration exposure (Dai et al. 1994a, 1994b). No histological 

alterations were observed in the livers of rats exposed to 3.5 mg vanadium/kg/day as sodium 

metavanadate in drinking water for 3 months (Domingo et al. 1985), 4.7 mg vanadium/kg/day as sodium 

metavanadate in drinking water for 210 days (Boscolo et al. 1994), or 19 mg vanadium/kg/day as vandyl 

sulfate in drinking water for 1 year (Dai et al. 1994b). 

Renal Effects. Humans given 0.19 mg vanadium/kg as ammonium vanadyl tartrate capsules for 45– 

68 days did not show any changes in urinalysis for albumin, hemoglobin, or formed elements. Blood urea 

nitrogen levels were also unchanged (Dimond et al. 1963). 

There are limited data on the renal toxicity of vanadium compounds. Narrowing of the lumen of the 

proximal tubules was observed in rats exposed to 4.7 or 12 mg vanadium/kg/day as sodium metavanadate 

in drinking water for 7 months (Boscolo et al. 1994; Carmagnani et al. 1991); however, neither study 

reported the incidence of the lesion or statistical significance. Similarly, corticomedullar microhemorrhagic foci were observed in the kidneys of rats exposed to sodium metavanadate in drinking water 

for 3 months (Domingo et al. 1985); the investigators noted that the effect was more evident at the highest 

dose (3.5 mg vanadium/kg/day), but incidence data or statistical analyses were not included in the paper. 

This study also found significant increases in serum total protein, urea, and uric acid levels in rats 

exposed to 3.5 mg vanadium/kg/day. No statistically significant increases in the incidence of histological 

alterations were observed in rats exposed to 19 mg vanadium/kg/day as vanadyl sulfate in drinking water 

for 1 year (Dai et al. 1994b). No histological alterations were observed in the kidneys of rats exposed to 

0.7 mg vanadium/kg/day (Schroeder et al. 1970) as vanadyl sulfate in drinking water for 2.5 years or in 

mice exposed to 4.1 mg vanadium/kg/day as vanadyl sulfate in the diet for 2 years (Schroeder and Balassa 

1967). 

Body Weight Effects. No significant alterations in body weight were observed in adults exposed to 

0.12 mg vanadium/kg/day as vanadyl sulfate administered via capsules for 12 weeks (Fawcett et al. 

1997). Numerous studies have reported significant decreases in body weight gain in rats or mice exposed 

to vanadium compounds. In general, intermediate-duration exposure to <10 mg vanadium/kg/day did not 

result in >10% decreases in body weight gain (Adachi et al. 2000a; Dai et al. 1995; Sanchez et al. 1998; 

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Ścibior 2005; Zaporwska et al. 1993). At higher concentrations, a considerable amount of variability in 

the magnitude of decreases in body weight gain was observed. Decreases of 12–15% were observed in 

rats or mice exposed to 10.69, 13, 20.93, 22.06, or 33 mg vanadium/kg/day as vanadyl sulfate, 

ammonium metavanadate, or sodium metavanadate in drinking water (Llobet et al. 1993; Ścibior et al. 

2006; Yao et al. 1997; Zaporowski and Wasilewski 1989, 1990). However, decreases of ≥37% were 

observed in rats exposed to 12.99 or 19.73 mg vanadium/kg/day as ammonium vanadate in drinking water 

(Zaporowski and Wasilewski 1991, 1992a, 1992b); these decreases in body weight gain were 

accompanied by marked decreases in food intake and water consumption. A severe decrease in body 

weight gain (54%) and weight loss were observed in rats exposed to 30 or 55 mg vanadium/kg/day, 

respectively, as vanadium pentoxide for 75 days (Mountain et al. 1953). In contrast, no alterations in 

body weight gain were observed in rats exposed to 22 mg vanadium/kg/day as sodium metavanadate in 

drinking water (Bursztyn and Mekler 1993) or administered via gavage at 31 mg vanadium/kg/day as 

vanadyl sulfate (Akgün-Dar et al. 2007; Jain et al. 2007). Significant decreases in maternal weight gain 

have been observed in rats exposed to 6 mg vanadium/kg/day as sodium metavanadate (Elfant and Keen 

1997) and mice administered 7.5 mg vanadium/kg/day as vanadyl sulfate (Paternain et al. 1990). 

Following chronic exposure, a 20% decrease in body weight gain was observed in rats exposed to vanadyl 

sulfate in drinking water for 1 year (Dai et al. 1994a). No alterations in body weight gain were observed 

in mice exposed to 4.1 or 0.54 mg vanadium/kg/day as vanadyl sulfate (Schroeder and Balassa 1967; 

Schroeder and Mitchener 1975) or rats exposed to 0.7 mg vanadium/kg/day as vanadyl sulfate (Schroeder 

et al. 1970). 

It is likely that the decreases in body weight in a number of these studies are secondary to decreases in 

water consumption (possibly due to palatability). Decreases in food intake and body weight gain have 

been observed in rats placed on a water restricted diet (Crampton and Lloyd 1954); young rats were 

particularly sensitive to the effect (2-month-old rats were used in the Zaporowski and Wasilewski 

studies). Thus, LOAELs for decreases in body weight gain in drinking water studies reporting decreases 

in water consumption (possibly due to palatability) are not presented in Table 3-3 or Figure 3-2; similarly, 

LOAELs were not listed for studies that did not report whether there was an effect on drinking water 

consumption. 

Metabolic Effects. No studies were located regarding metabolic effects in healthy humans after oral 

exposure to vanadium. No significant alterations in blood glucose or insulin levels were observed in rats 

exposed to 22 mg vanadium/kg/day as sodium metavanadate in drinking water for 4 weeks (Bursztyn and 

Mekler 1993), rats administered 31 mg vanadium/kg/day as vanadyl sulfate for 60 days (Akgün-Dar et al. 

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2007), or rats exposed to 19 mg vanadium/kg/day as vanadyl sulfate in drinking water for 1 year (Dai et 

al. 1994a). Additionally, no alterations in the response to an oral glucose tolerance test were observed in 

rats exposed to 13 mg vanadium/kg/day as vanadyl sulfate in drinking water for 7.4 weeks (Yao et al. 

1997). 

3.2.2.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological effects in humans after oral exposure to vanadium. 

Minimal information on immunological effects in animals was located. Mice exposed to 0.13, 1.3, or 

6.5 mg vanadium/kg/day as sodium orthovanadate in the drinking water for 6 weeks showed a doserelated, but nonsignificant, decrease in the antibody-forming cells in the spleen when challenged with 

sheep erythrocytes (Sharma et al. 1981). The number of plaques formed was 46, 69, and 78%, 

respectively, lower than the response in the controls; the investigators noted that statistical significance 

was not achieved due to the large variation in the control group. Decreases in B-cell levels and IgG and 

IgM levels were observed in rats exposed to 2.1 mg vanadium/kg/day as sodium metavanadate in the diet 

for 10 weeks (Adachi et al. 2000a). Mild spleen hypertrophy and hyperplasia were seen in rats exposed to 

sodium metavanadate in the drinking water for 3 months (Domingo et al. 1985); the investigators noted 

that the effects were more evident at the highest dose (3.5 mg vanadium/kg/day), but incidence data were 

not reported. The highest NOAEL values and all reliable LOAEL values for immunological effects in 

each species and duration category are recorded in Table 3-3 and plotted in Figure 3-2. 

3.2.2.4 Neurological Effects 

No studies were located regarding neurological effects in humans after oral exposure to vanadium. Data 

on the neurotoxicity of vanadium are limited to two studies in rats. In one study, decreases in travelling 

distance and horizontal movement in an open field test and poorer avoidance performance and higher 

latency period in an active avoidance test were observed in rats administered 1.72 mg vanadium/kg/day as 

sodium metavanadate for 8 weeks (Sanchez et al. 1998). In the second study, no alterations in travelling 

distance or vertical movements were observed in an open field test in rats administered 6.84 mg 

vanadium/kg/day as sodium metavanadate for 8 weeks (Sanchez et al. 1999). A decrease in the number 

of avoidance responses to conditioned stimuli and increases in the latency period were also observed in 

these rats. These LOAEL values are recorded in Table 3-3 and Figure 3-2. 

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3.2.2.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans after oral exposure to vanadium. 

Decreases in fertility have been observed in female rats mated to unexposed males (Ganguli et al. 1994b; 

Morgan and El-Tawil 2003) and in male rats or mice mated with unexposed females (Jain et al. 2007; 

Llobet et al. 1993; Morgan and El-Tawil 2003). The lowest LOAEL values for decreased fertility are 

12 and 10 mg vanadium/kg/day for females and males, respectively (Morgan and El-Tawil 2003). No 

alterations in fertility were observed in male and female rats administered 8.4 mg vanadium/kg/day as 

sodium metavanadate (Domingo et al. 1986). Decreases in sperm count and motility have also been 

observed in rats administered 31 mg vanadium/kg/day as vanadyl sulfate for 60 days (Jain et al. 2007). 

This NOAEL value and reliable LOAEL values are recorded in Table 3-3 and plotted in Figure 3-2. 

3.2.2.6 Developmental Effects 

No studies were located regarding developmental effects in humans after oral exposure to vanadium. A 

variety of fetal malformations/anomalies have been observed in animals following gestational exposure to 

vanadium. Exposure on gestation days 6–14 or 6–15 resulted in increases in facial hemorrhages 

(Paternain et al. 1987), hematomas in facial, neck, and dorsal areas (Paternain et al. 1990), and delayed 

ossification (Paternain et al. 1990; Sanchez et al. 1991); the rat and mouse dams were administered 7.5– 

8.3 mg vanadium/kg/day as vanadyl sulfate, sodium metavanadate, or sodium orthovanadate. One study 

also reported increases in early resorptions and decreases in fetal growth in the offspring of mice 

administered 7.5 mg vanadium/kg/day as vanadyl sulfate (Paternain et al. 1990); marked decreases in 

maternal body weight were also observed at this dose level. Vanadium exposure throughout gestation and 

lactation resulted in decreases in pup body weight and length at ≥2.1 mg vanadium/kg/day (Domingo et 

al. 1986; Elfant and Keen 1987; Morgan and El-Tawil 2003). Increases in stillbirths and decreases in pup 

survival were observed at 6 mg vanadium/kg/day (Elfant and Keen 1987); this dose level was associated 

with decreases in maternal food intake and body weight. Increases in gross, skeletal, and visceral 

anomalies were observed in the offspring of rats exposed to 12 mg vanadium/kg/day as ammonium 

metavanadate (Morgan and El-Tawil 2003); similar effects were observed in unexposed dams mated with 

males exposed to 10 mg vanadium/kg/day (Morgan and El-Tawil 2003). In rats exposed to 10 mg 

vanadium/kg/day as vanadyl sulfate in drinking water during gestation and lactation and exposed until 

postnatal day 100, significant decreases in survival were observed (Poggioli et al. 2001). This study also 

found significant decreases in the number of rearings in an open field test and no alterations in locomotor 

activity or working memory. A two-generation, one-dose study in rats showed altered lung collagen 

metabolism in fetuses of adults with lifetime exposure (Kowalska 1988). The toxicological significance 

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VANADIUM 66 

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of this finding is also not known. Reliable LOAEL values from these studies are recorded in Table 3-3 

and plotted in Figure 3-2. 

3.2.2.7 Cancer 

No studies were located that specifically studied cancer in humans or animals after oral exposure to 

vanadium. However, some studies designed to test other end points noted no increase in tumor frequency 

in rats and mice chronically exposed to 0.5–4.1 mg vanadium/kg as vanadyl sulfate in drinking water 

(Schroeder and Balassa 1967; Schroeder and Mitchener 1975; Schroeder et al. 1970). Although results of 

these oral studies were negative for carcinogenicity, they were inadequate for evaluating carcinogenic 

effects because insufficient numbers of animals were used, it was not determined whether or not a 

maximum tolerated dose was achieved, a complete histological examination was not performed, and only 

one exposure dose per study was evaluated. 

3.2.3 Dermal Exposure 

No studies were located regarding the following health effects in humans or animals after dermal 

exposure to vanadium: 

3.2.3.1 Death 

3.2.3.2 Systemic Effects 

3.2.3.3 Immunological and Lymphoreticular Effects 

3.2.3.4 Neurological Effects 

3.2.3.5 Reproductive Effects 

3.2.3.6 Developmental Effects 

3.2.3.7 Cancer 

3.3 GENOTOXICITY 

The in vitro and in vivo data on the genotoxicity of vanadium compounds are summarized in Tables 3-4 

and 3-5, respectively. In workers exposed to vanadium pentoxide, no alterations in the occurrence of 

sister chromatid exchange (Ivancsits et al. 2002) or deoxyribonucleic acid (DNA) strand breaks (Ehrlich 

et al. 2008; Ivancsits et al. 2002) were observed; however, an increase in micronuclei formation was 

observed in lymphocytes (Ehrlich et al. 2008). Similarly, increases in the micronuclei formation were 

observed in mouse bone marrow cells following oral exposure to vanadyl sulfate (Ciranni et al. 1995; 

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Table 3-4. Genotoxicity of Vanadium and Compounds In Vitro 

Results 

With Without 

Species (test system) End point activation activation Reference Form 

Bacillus subtilis Recombination repair No data	 + Kada et al. 1980 V2O5 

+	 VOCl2 

+	 NH4VO3 

B. subtilis Recombination repair No data	 + Kanematsu et al. V2O5 

+ 1980 VOCl2 

+ NH4VO3 

Escherichia coli Gene mutation No data C Kanematsu et al. V2O5 C 1980 NH4VO3 

Salmonella typhimurium	 Gene mutation No data C Kanematsu et al. V2O5 C 1980 NH4VO 

S. typhimurium Gene mutation C C NTP 2002 V2O5 

Saccharomyces cerevisiae	 Induction of diploid No data + Sora et al. 1986 VOSO4 

spores 

S. cerevisiae	 Reverse point + + Bronzetti et al. NH4VO3 

mutation 1990 

S. cerevisiae Mitotic gene +	 + Bronzetti et al. NH4VO3 

conversion 1990 

Mouse erythroleukemia DNA repair No data + Foresti et al. NaVO3 

cells 2001 

Mouse 3T3 and 3T6 cells DNA synthesis No data	 + Smith 1983 Na3VO4 

VOSO4 

Chinese hamster ovary DNA protein crosslinks No data + Cohen et al. NH4VO3 

cells 1992 

Hamster V79 fetal lung hprt mutation No data + Cohen et al. NH4VO3 

fibroblasts frequency 1992 

Chinese hamster V79 cells hprt mutation No data + Klein et al. 1994 NH4VO3 

frequency 

Chinese hamster V79 cells gpt mutation No data C Klein et al. 1994 NH4VO3 

frequency 

Chinese hamster V79 cells hprt mutation No data C Zhong et al. V2O5 

frequency 1994 

Syrian hamster ovary cells Micronuclei formation No data C Gibson et al. V2O5 

1997 

Chinese hamster V79 cells Micronuclei formation No data + Zhong et al. V2O5 

1994 

Chinese hamster ovary Sister chromatid + + Owusu-Yaw et VOSO4 

cells exchange + + al. 1990 V2O3 

+ + NH4VO3 

Chinese hamster V79 cells Sister chromatid No data C Zhong et al. V2O5 

exchange 1994 

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Table 3-4. Genotoxicity of Vanadium and Compounds In Vitro 

Results 

With Without 

Species (test system) End point activation activation Reference Form 

Chinese hamster V79 cells Chromosomal No data +	 Zhong et al. V2O5 

aberrations 1994 

Chinese hamster ovary Chromosomal + + Owusu-Yaw et VOSO4 

cells aberrations + + al. 1990 V2O3 

+ +	 NH4VO3 

Human tumor cells Colony formation No data +	 Hanauske et al. <0.1 pM V 

1987 

Human tumor cells Colony formation No data C Hanauske et al. >0.1 pM V 

1987 

Human leukocytes DNA strand break No data + Birnboim 1988 Na3VO4 

Human fibroblasts DNA strand break No data + Ivancsits et al. V2O5 

2002 

Human erythrocytes, DNA strand break No data C

C

Ivancsits et al. V2O5 

lymphocytes	 2002 

Human nasal epithelial DNA strand break No data Kleinsasser et al. V2O5 

cells	 2003 

Human lymphocytes DNA strand break No data +	 Kleinsasser et al. V2O5 

2003 

Human lymphocytes DNA strand break No data +	 Wozniak and VOSO4 

Blasiak 2004 

Human cervical cancer DNA strand break No data +	 Wozniak and VOSO4 

cells (HeLa)	 Blasiak 2004 

Human lymphocytes DNA strand break No data ±	 Rojas et al. 1996 V2O5 

Human leukocytes DNA strand break No data +	 Rojas et al. 1996 V2O5 

Human lymphocytes Chromosomal No data +	 Migliore et al. NH4VO3, 

aberrations	 + 1993 NaVO3, +	 Na3VO4, +	 VOSO4 

Human lymphocytes Structural No data C Roldán and V2O5 

chromosomal Altamirano 1990 

aberrations 

Human lymphocytes	 Numerical No data + Roldán and V2O5 

chromosomal Altamirano 1990 

aberrations 

Human lymphocytes Sister chromatid No data C

C

C

C

C

Roldán and V2O5 

exchange	 Altamirano 1990 

Human lymphocytes Sister chromatid No data 

exchange 

Migliore et al. NH4VO3, 

1993	 NaVO3, 

Na3VO4, 

VOSO4 

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Table 3-4. Genotoxicity of Vanadium and Compounds In Vitro 

Results 

With Without 

Species (test system) End point activation activation Reference Form 

Human lymphocytes Micronuclei formation No data + Migliore et al. Na3VO4, + 1995 VOSO4 

Human lymphocytes Micronuclei formation No data + Migliore et al. NH4VO3, + 1993 NaVO3, + Na3VO4, + VOSO4 

C = negative result; + = positive result; ± = weakly positive; DNA = deoxyribonucleic acid; hprt = hypoxanthine 

phosphoribosyltransferase; NaVO3= sodium metavanadate; Na3VO4 = sodium orthovanadate; NH4VO3 = ammonium 

metavanadate; V2O5 = vanadium pentoxide; V2O3 = vanadium trioxide; VOSO4 = vanadyl sulfate; VOCl2 = vanadyl 

dichloride 

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Table 3-5. Genotoxicity of Vanadium and Compounds In Vivo 

Exposure 

Species (test system) End point Route Result Reference Form 

Human leukocytes Sister chromatid Inhalation C Ivancsits et al. V2O5 

exchange (occupational) 2002 

Human lymphocytes Sister chromatid Inhalation C Ivancsits et al. V2O5 

exchange (occupational) 2002 

Human lymphocytes Micronuclei formation Inhalation + Ehrlich et al. V2O5 

(occupational) 2008 

Human leukocytes DNA strand breaks Inhalation C Ivancsits et al. V2O5 

(occupational) 2002 

Human lymphocytes DNA strand breaks Inhalation C Ivancsits et al. V2O5 

(occupational) 2002 

Human lymphocytes DNA strand breaks Inhalation C Ehrlich et al. V2O5 

(occupational) 2008 

CD-1 mouse bone marrow Micronuclei formation Drinking water C Villani et al. 2007 VOSO4 

CD-1 mouse blood Micronuclei formation Drinking water ± Villani et al. 2007 VOSO4 

reticulocytes 

CD-1 mouse bone marrow Micronuclei formation Gavage + Ciranni et al. VOSO4 

+ 1995 Na3VO4 

+ NH4VO3 

B6C3F1 mouse Micronuclei formation Inhalation C NTP 2002 V2O5 

erythrocytes 

CD-1 mouse bone marrow Chromosome Gavage + Ciranni et al. VOSO4 

aberrations + 1995 Na3VO4 

+ NH4VO3 

CD-1 mouse bone marrow DNA damage Drinking water C Villani et al. 2007 VOSO4 

CD-1 mouse testis cells DNA damage Drinking water C Villani et al. 2007 VOSO4 

C = negative result; + = positive result; ± = weakly positive; DNA = deoxyribonucleic acid; V2O5 = vanadium pentoxide; 

VOSO4 = vanadyl sulfate; Na3VO4 = sodium orthovanadate; NH4VO3 = ammonium metavanadate 

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Villani et al. 2007), sodium orthovanadate (Ciranni et al. 1995), or ammonium metavanadate (Ciranni et 

al. 1995); however no increases in micronuclei formation were observed in mouse erythrocytes following 

intermediate duration inhalation exposure to vanadium pentoxide (NTP 2002). Increases in chromosomal 

aberrations were also observed in mouse bone marrow following a single gavage exposure to vanadyl 

sulfate, sodium orthovanadate, or ammonium metavanadate (Ciranni et al. 1995). As with the vanadium 

workers, DNA damage was not observed in mouse bone marrow or testis cells following intermediate 

duration exposure to vanadyl sulfate in drinking water. 

Conflicting results have been found for genotoxicity tests in prokaryote assays. Impaired recombination 

repair were found in Bacillus subtilis following exposure to vanadium pentoxide, vanadyl dichloride, or 

ammonium metavanadate (Kada et al. 1980; Kanematsu et al. 1980). No alterations in gene mutation 

frequency were found in Escherichia coli or Salmonella typhimurium for vanadium pentoxide 

(Kanematsu et al. 1980; NTP 2002) or ammonium metavanadate (Kanematsu et al. 1980). In 

nonmammalian eukaryotes, increases in reverse point mutations and mitotic gene conversion were found 

in Saccharomyces cerevisiae (Bronzetti et al. 1990). In general, alterations in DNA repair, synthesis, 

formation of cross links or strand breaks, and gene mutation frequency were observed in mammalian cells 

for vanadium pentoxide, ammonium metavanadate, vanadyl sulfate, sodium orthovanadate (Birnboim 

1988; Cohen et al. 1992; Foresti et al. 2001; Ivancsits et al. 2002; Klein et al. 1994; Kleinsasser et al. 

2003; Rojas et al. 1996; Smith 1983; Wozniak and Blasiak 2004; Zhong et al. 1994). In vitro human data 

suggest cell-specific differences in the ability of vanadium compounds to induce DNA strand breaks. 

DNA strand breaks were found in fibroblasts and lymphocytes (Ivancsits et al. 2002; Kleinsasser et al. 

2003; Wozniak and Blasiak 2004) but not in erythrocytes or nasal epithelial cells (Ivancsits et al. 2002; 

Kleinsasser et al. 2003). Increases in the occurrence of chromosomal aberrations were observed in 

Chinese hamster V79 cells exposed to vanadium pentoxide (Zhong et al. 1994), Chinese hamster ovary 

cells exposed to vanadyl sulfate, vanadium trioxide, or ammonium metavanadate (Owusu-Yaw et al. 

1990), and human lymphocytes exposed to ammonium metavanadate, sodium metavanadate, sodium 

orthovanadate, vanadium pentoxide, or vanadyl sulfate (Migliore et al. 1993; Roldán and Altamirano 

1990). An increase in sister chromatid exchange was found in Chinese hamster ovary cells exposed to 

vanadyl sulfate, vanadium trioxide, or ammonium metavanadate (Owusu-Yaw et al. 1990), but not in 

Chinese hamster V79 cells exposed to vanadium pentoxide (Zhong et al. 1994) or human lymphocytes 

exposed to vanadium pentoxide, ammonium metavanadate, sodium metavanadate, sodium orthovanadate, 

or vanadyl sulfate (Migliore et al. 1993; Roldán and Altamirano 1990). Increases in micronuclei 

formation were also found in Chinese hamster V79 cells exposed to vanadium pentoxide (Zhong et al. 

1994) and in human lymphocytes exposed to sodium orthovanadate, vanadyl sulfate, ammonium 

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metavanadate, or sodium metavanadate (Migliore et al. 1993, 1995), but not in Syrian hamster ovary cells 

exposed to vanadium pentoxide (Gibson et al. 1997). Thus, the available data provide evidence that 

vanadium compounds are genotoxic, both clastogenic effects and DNA damage have been observed in in 

vitro and in vivo studies. 

3.4 TOXICOKINETICS 

3.4.1 Absorption 

3.4.1.1 Inhalation Exposure 

Several occupational studies indicate that absorption can occur in humans following inhalation exposure. 

An increase in urinary vanadium levels was found in workers exposed to <1 ppm of vanadium (Gylseth et 

al. 1979; Kiviluoto et al. 1981b; Lewis 1959; NIOSH 1983). The vanadium concentration in serum was 

also reported to be higher than the nonoccupationally exposed controls following exposure to vanadium 

pentoxide dust (Kiviluoto et al. 1981b). 

Indirect evidence of absorption after inhalation of vanadium in animals is indicated in studies involving 

inhalation exposure or intratracheal administration. In rats and mice exposed to 0.28–2.2 mg 

vanadium/m3 as vanadium pentoxide for 14 days or 2 years (6 hours/day, 5 days/week), marginal 

increases in blood vanadium levels were observed, suggesting that vanadium pentoxide was poorly 

absorbed or rapidly cleared from the blood (NTP 2002); in the 2-year studies, the increase in blood 

vanadium levels were somewhat concentration-related. Intratracheal studies suggest that soluble 

vanadium compounds are readily absorbed through the lungs. Initial pulmonary clearance is rapid in rats. 

There was rapid 100% absorption of vanadium in rats receiving radiolabeled vanadyl chloride (Conklin et 

al. 1982). The greatest absorption of a radioactive dose, 48V, was found to occur 5 minutes after 

administration (Roshchin et al. 1980). Most of the vanadium, 80 and 85% of the tetravalent (V4+) and 

pentavalent (V5+) forms of vanadium, respectively, cleared from the lungs 3 hours after intratracheal 

exposure (Edel and Sabbioni 1988). After 24 hours, >50% of vanadyl oxychloride was cleared from the 

lungs of male rats (Oberg et al. 1978), and at 3 days, 90% of vanadium pentoxide was eliminated from the 

lungs of female rats (Conklin et al. 1982). In another study 50% was cleared in 18 minutes, and the rest 

within a few days (Rhoads and Sanders 1985). 

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3.4.1.2 Oral Exposure 

No studies were located regarding the rate and extent of absorption in humans after oral exposure to 

vanadium. 

The absorption of vanadium through the gastrointestinal tract of animals is low. Less than 0.1% of an 

intragastric dose was detectable in the blood of rats at 15 minutes postexposure, and less than 1% at 

1 hour (Roshchin et al. 1980). Similarly, only 2.6% of an orally administered radiolabeled dose of 

vanadium pentoxide was absorbed 3 days after exposure in rats (Conklin et al. 1982). In contrast, 16.5% 

of vanadium was absorbed in rats exposed to sodium metavanadate in the diet for 7 days (Adachi et al. 

2000b). Vanadium was reported in tissues and urine within hours after a single (Edel and Sabbioni 1988) 

and repeated oral exposure in rats (Bogden et al. 1982; Parker and Sharma 1978), suggesting that it is 

rapidly absorbed. Young rats that consumed vanadium in the drinking water and feed were found to have 

higher tissue vanadium levels 21 days after birth than they did 115 days after birth (Edel et al. 1984). The 

data suggest that there is a higher absorption of vanadium in these young animals due to a greater 

nonselective permeability of the undeveloped gastrointestinal barrier. 

3.4.1.3 Dermal Exposure 

No specific studies were located regarding absorption in humans or animals after dermal exposure to 

vanadium, although absorption by this route is generally considered to be very low (WHO 1988). 

Absorption through the skin is thought to be quite minimal due to its low lipid/water solubility. 

3.4.2 Distribution 

Vanadium has been detected in the lungs (in 52% of the cases) and intestines (in 16% of the cases) of 

humans with no known occupational exposure, collected from autopsy data (Schroeder et al. 1963). In 

the gastrointestinal tract, it was primarily found in the ileum (37%), cecum (45.1%), sigmoid colon 

(15.9%), and rectum (26.2%). The heart, aorta, brain, kidney, muscle, ovary, and testes were found to 

have no detectable vanadium concentrations. Bone was not tested. 

3.4.2.1 Inhalation Exposure 

There are limited data on the distribution of vanadium in workers; serum vanadium levels in workers 

were highest within a day after exposure followed by a rapid decline in levels upon cessation of exposure 

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(Gylseth et al. 1979; Kiviluoto et al. 1981b). Analytical studies have shown low levels of vanadium in 

human kidneys and liver, with even less in brain, heart, and milk. Higher levels were detected in hair, 

bone, and teeth (Byrne and Kosta 1978). Inhalation exposure and intratracheal administration studies in 

laboratory animals have examined the distribution of vanadium. In rats chronically exposed to 0.56 or 

1.1 mg vanadium/m3 as vanadium pentoxide (6 hours/day, 5 days/week), vanadium lung burdens peaked 

after 173 days of exposure and declined for the remainder of the study (day 542); lung burden levels 

never reached steady state (NTP 2002). In contrast, lung burdens appeared to reach steady state by 

exposure day 173 in rats exposed to 0.28 mg vanadium/m3 (NTP 2002). Similarly, lung burdens did not 

reach steady state in mice exposed to 1.1 or 2.2 mg vanadium/m3 as vanadium pentoxide, 6 hours/day, 

5 days/week for 542 days (NTP 2002). Rather, lung burdens peaked near day 54 and declined through 

day 535. Steady state was achieved in mice exposed to 0.56 mg vanadium/m3 during the first 26 days of 

exposure. These data suggest that vanadium is cleared more rapidly from the lungs of mice compared to 

rats. 

Vanadium is rapidly distributed in tissues of rats after acute intratracheal administration. Within 

15 minutes after exposure to 0.36 mg/kg vanadium oxychloride, radiolabeled vanadium was detectable in 

all organs except the brain. The highest concentration was in the lungs, followed by the heart and kidney. 

The other organs had low levels. Maximum concentrations were reached in most tissues between 4 and 

24 hours (Oberg et al. 1978). Vanadium is found to have a two-phase lung clearance after a single acute 

exposure (Oberg et al. 1978; Rhoads and Sanders 1985). The initial phase is rapid with a large percentage 

of the absorbed dose distributed to most organs and blood 24 hours postexposure, followed by a slower 

clearance phase. Vanadium is transported mainly in the plasma. It is found in appreciable amounts in the 

blood initially and only at trace levels 2 days after exposure (Roshchin et al. 1980). The pentavalent and 

tetravalent forms of vanadium compounds were found to have similar distribution patterns (Edel and 

Sabbioni 1988). Three hours after intratracheal exposure to the pentavalent or tetravalent form, 15–17% 

of the absorbed dose was found in the lung, 2.8% in the liver, and 2% in the kidney (Edel and Sabbioni 

1988). Although levels in the kidney are high after exposure, the bone had greater retention of vanadium. 

Skeletal levels of vanadium peaked 1–3 days postexposure (Conklin et al. 1982; Rhoads and Sanders 

1985; Roshchin et al. 1980) and have been reported to persist after 63 days (Oberg et al. 1978). 

3.4.2.2 Oral Exposure 

No studies were located regarding distribution in humans after oral exposure to vanadium. 

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Acute studies with rats showed the highest vanadium concentration to be located in the skeleton. Male 

rats had approximately 0.05% of the administered 48V in bones, 0.01% in the liver, and <0.01% in the 

kidney, blood, testis, or spleen after 24 hours (Edel and Sabbioni 1988). Similar findings were noted by 

other authors who found that the bone had the greatest concentration of radiolabeled vanadium, followed 

by the kidney (Roshchin et al. 1980). Conklin et al. (1982) reported that after 3 days, 25% of the 

absorbed vanadium pentoxide was detectable in the skeleton and blood of female rats. In female rats 

exposed to sodium metavanadate in the diet for 7 days, the highest concentrations of vanadium were 

found in bone, followed by the spleen and kidney (Adachi et al. 2000b); the lowest concentration was 

found in the brain. As summarized in Table 3-6, vanadium elimination half-times in various tissues were 

3.57–15.95 or 3.18–13.50 days following a 1-week exposure to 8.2 mg vanadium/kg/day as sodium 

metavanadate or vanadyl sulfate, respectively, administered in a liquid diet (Hamel and Duckworth 1995). 

Although the elimination half-times were longer in rats administered sodium metavanadate compared to 

vanadyl sulfate, no statistical comparisons were made. 

Oral exposure for an intermediate duration produced the highest accumulation of vanadium in the kidney. 

Adult rats exposed to 5 or 50 ppm vanadium in the drinking water for 3 months had the highest vanadium 

levels in the kidney, followed by bone, liver, and muscle (Parker and Sharma 1978). The retention in 

bone may have been due to phosphate displacement. All tissue levels plateaued at the third week of 

exposure. A possible explanation for the initially higher levels in the kidney during intermediate-duration 

exposure is the daily excretion of vanadium in the urine. When the treatment is stopped, levels decrease 

in the kidney. At the cessation of treatment, vanadium mobilized rapidly from the liver and slowly from 

the bones. Other tissue levels decreased rapidly after oral exposure was discontinued. Thus, retention of 

vanadium was much longer in the bones (Edel et al. 1984; Parker and Sharma 1978). 

In rats exposed to approximately 100 mg/L vanadium in drinking water as vanadyl sulfate or ammonium 

metavanadate for 12 weeks, significant increases, as compared to controls, in bone, kidney, and liver 

vanadium levels were observed; no alterations in vanadium muscle levels were found (Thompson et al. 

2002). The highest concentration of vanadium was found in the bone, followed by the kidney and liver. 

Tissue vanadium concentrations were significantly higher in rats exposed to ammonium metavanadate as 

compared to animals exposed to vanadyl sulfate. 

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Table 3-6. Vanadium Elimination Half-Times in Various Organs in Rats Exposed 

to 8.2 mg Vanadium/kg/day for 1 Week 

Half-time (days) 

Organ Sodium metavanadate Vanadyl sulfate 

Liver 3.57 3.18 

Kidney 3.92 3.27 

Fat 4.06 5.04 

Lung 5.52 4.45 

Muscle 6.11 4.49 

Heart 7.03 5.05 

Spleen 9.13 5.15 

Brain 11.17 9.17 

Testes 15.95 13.50 

Source: Hamel and Duckworth 1995 

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3.4.2.3 Dermal Exposure 

No studies were located regarding distribution in humans and animals after dermal exposure to vanadium. 

3.4.2.4 Other Routes of Exposure 

After intraperitoneal administration to rats, vanadium is distributed to all organs. After 24 hours, the 

highest concentrations were found in the bones and kidney, although initial levels were highest in the 

kidney (Roshchin et al. 1980; Sharma et al. 1980). This is similar to the distribution seen following 

inhalation and oral exposure. 

3.4.3 Metabolism 

Vanadium is an element, and as such, is not metabolized. In the oxygenated blood, it circulates as a 

polyvanadate (isopolyanions containing pentavalent vanadium) but in tissues, it is retained mainly as the 

vanadyl cation (cationic form of tetravalent vanadium). Depending on the availability of reducing 

equivalents (such as reduced glutathione-SH, NADPH, NADH) and oxygen, vanadium may be reduced, 

reoxidized, and/or undergo redox cycling (Byczkowski and Kulkarni 1998). 

3.4.4 Elimination and Excretion 

3.4.4.1 Inhalation Exposure 

Occupational studies showed that urinary vanadium levels significantly increased in exposed workers 

(Gylseth et al. 1979; Kiviluoto et al. 1981b; Lewis 1959; NIOSH 1983; Zenz et al. 1962). Male and 

female workers exposed to 0.1–0.19 mg/m3 vanadium in a manufacturing company, had significantly 

higher urinary levels (20.6 μg/L) than the nonoccupationally exposed control subjects (2.7 μg/L) (NIOSH 

1983). The correlation between ambient vanadium levels and urinary levels of vanadium is difficult to 

determine from these epidemiological studies (Kiviluoto et al. 1981b). In most instances, no other 

excretion routes were monitored. Analytical studies have shown very low levels in human milk (Byrne 

and Kosta 1978). Evidence from animal studies supports the occupational findings. Vanadium 

administered intratracheally to rats was reported to be excreted predominantly in the urine (Oberg et al. 

1978) at levels twice that found in the feces (Rhoads and Sanders 1985). Three days after exposure to 

vanadium pentoxide, 40% of the 48V dose was excreted, mostly in the urine while 30% remained in the 

skeleton (5 days after exposure) (Conklin et al. 1982). 

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In female rats exposed to 0.56 or 1.1 mg vanadium/m3 as vanadium pentoxide for 16 days (6 hours/day, 

5 days/week), lung clearance half-times during an 8-day recovery period were 4.42 and 4.96 days, 

respectively (NTP 2002). In mice similarly exposed to 1.1 or 2.2 mg vanadium/m3

, lung clearance halftimes were 2.55 and 2.40 days, respectively (NTP 2002). In contrast to the 16-day exposure data, the 

lung clearance half-times in female rats exposed to 0.28, 0.56, or 1.1 mg vanadium/m3 for 2 years 

(6 hours/day, 5 days/week) were 37.3, 58.6, and 61.4 days, respectively (NTP 2002). In mice, the halftimes were 6.26, 10.7, and 13.9 days at 0.56, 1.1, and 2.2 mg vanadium/m3 exposure levels (NTP 2002). 

These data suggest that vanadium is more rapidly cleared from the lungs following a short exposure 

period compared to longer periods. 

3.4.4.2 Oral Exposure 

No studies were located regarding excretion in humans after oral exposure to vanadium. 

Since vanadium is poorly absorbed in the gastrointestinal tract, a large percentage of vanadium is excreted 

unabsorbed in the feces in rats following oral exposure. More than 80% of the administered dose of 

ammonium metavanadate or sodium metavanadate accumulated in the feces after 6 or 7 days (Adachi et 

al. 2000b; Patterson et al. 1986). After 2 weeks of exposure, 59.1±18.8% of sodium metavanadate was 

found in the feces (Bogden et al. 1982). However, the principal route of excretion of absorbed vanadium 

is through the kidney in animals. Approximately 0.9% of ingested vanadium was excreted in the urine of 

rats exposed to sodium metavanadate in the diet for 7 days (Adachi et al. 2000b). An elimination halftime of 11.7 days was estimated in rats exposed to vanadyl sulfate in drinking water for 3 weeks 

(Ramanadham et al. 1991). 

3.4.4.3 Dermal Exposure 

No studies were located regarding excretion in humans or animals after dermal exposure to vanadium. 

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 

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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 

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 

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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 vanadium 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. 

No PBPK models for vanadium were located. 

3.5 MECHANISMS OF ACTION 

3.5.1 Pharmacokinetic Mechanisms 

In the body, there is an interconversion of two oxidation states of vanadium, the tetravalent form, vanadyl 

(V+4), and the pentavalent form, vanadate (V+5). Vanadium can reversibly bind to transferrin protein in 

the blood and then be taken up into erythrocytes. Vanadate is considered more toxic than vanadyl 

because vanadate is reactive with a number of enzymes and is a potent inhibitor of the Na+K+-ATPase of 

plasma membranes (Harris et al. 1984; Patterson et al. 1986). There is a slower uptake of vanadyl into 

erythrocytes compared to the vanadate form. Five minutes after an intravenous administration of 

radiolabeled vanadate or vanadyl in dogs, 30% of the vanadate dose and 12% of the vanadyl dose is found 

in erythrocytes (Harris et al. 1984). It is suggested that this difference in uptake is due to the time 

required for the vanadyl form to be oxidized to vanadate. When V+4 or V+5 is administered intravenously, 

a balance is reached in which vanadium moves in and out of the cells at a rate that is comparable to the 

rate of vanadium removal from the blood (Harris et al. 1984). Initially, vanadyl leaves the blood more 

rapidly than vanadate, possibly due to the slower uptake of vanadyl into cells (Harris et al. 1984). Five 

hours after administration, blood clearance is essentially identical for the two forms. A decrease in 

glutathione-SH, NADPH, and NADH occurs within an hour after intraperitoneal injection of sodium 

vanadate in mice (Bruech et al. 1984). It is believed that the redox cycling of vanadium V+5/V+4, 

depending on the local availability of oxygen in tissues, depletes reducing equivalents that are necessary 

for activity of cytochrome P-450. 

Vanadium in the plasma can exist in a bound or unbound form (Bruech et al. 1984). Vanadium as 

vanadyl (Patterson et al. 1986) or vanadate (Harris and Carrano 1984) reversibly binds to human serum 

transferrin at two metal-binding sites on the protein. With intravenous administration of vanadate or 

vanadyl, there is a short lag time for vanadate binding to transferrin, but at 30 hours, the association is 

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Figure 3-3. Conceptual Representation of a Physiologically Based
 

Pharmacokinetic (PBPK) Model for a 

Hypothetical Chemical Substance
 

Inhaled chemical Exhaled chemical 

Ingestion 

Lungs 

Liver 

Vmax 

Km 

A 

V R 

E Fat T 

N E 

O R 

U Slowly I 

S perfused A 

tissues L 

Richly B perfused L B tissues O L Feces O O 

D O Kidney D 

Urine 

Skin 

Chemicals 

contacting skin 

Note: This is a conceptual representation of a physiologically based pharmacokinetic (PBPK) model for a 

hypothetical chemical substance. The chemical substance is shown to be absorbed via the skin, by inhalation, or by 

ingestion, metabolized in the liver, and excreted in the urine or by exhalation. 

Source: adapted from Krishnan and Andersen 1994 

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identical for the two vanadium forms (Harris et al. 1984). The vanadium-transferrin binding is most 

likely to occur with the vanadyl form as this complex is more stable (Harris et al. 1984). The transferrinbound vanadium is cleared from the blood at a slower rate than unbound vanadium in rats, which explains 

a biphasic clearance pattern (Sabbioni and Marafante 1978). The metabolic pathway appears to be 

independent of route of exposure (Edel and Sabbioni 1988). 

3.5.2 Mechanisms of Toxicity 

In vitro studies (as reviewed by Barceloux 1999; Etcheverry and Cortizo 1998; Harland and HardenWilliams 1994; Léonard and Gerber 1994; Mukherjee et al. 2004) have shown that vanadium acts as a 

phosphate analog and, as such, interferes with various ATPases, phosphatases, and phosphate-transfer 

enzymes. Vanadium has been shown to inhibit Na+K+ATPase, Ca2+ATPase, H+K+ATPase, 

K+ATPase, Ca+Mg+ATPase, dynein ATPase, actomyosin ATPase, acid and alkaline phosphatases, 

glucose-6-phosphatase, ribonuclease, phosphodiesterase, and phosphotryosyl-phosphatase. It has also 

been shown to stimulate tyrosine kinase phosphorylase, NADPH oxidase, and adenylate cyclase. 

Additionally, vanadium has been shown to have insulin-mimetic properties, particularly the ability to 

stimulate glucose uptake and oxidation and glycogen synthesis, and the ability to induce cell proliferation. 

The effect of vanadium on various enzymes may be responsible for the diverse effects observed in 

animals exposed to vanadium. However, little information is available regarding the mechanism of 

vanadium toxicity in vivo. 

3.5.3 Animal-to-Human Extrapolations 

There are little data available to evaluate potential toxicokinetic differences between humans and 

laboratory animals. Similar effects have been reported in humans and animals following inhalation or 

oral exposure to vanadium; however, this conclusion is based on the limited human toxicity data. In 

absence of data to the contrary, rats or mice appear to be valid models for extrapolation 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 

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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, 

development, and/or behavior (EPA 1997b). 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 in vivo or in vitro studies were located regarding endocrine disruption in humans and/or animals after 

exposure to vanadium. 

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. 

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Children are not small adults. They differ from adults in their exposures and may differ in their 

susceptibility to hazardous chemicals. Children’s unique physiology and behavior can influence the 

extent of their exposure. Exposures of children are discussed in Section 6.6, Exposures of Children. 

Children sometimes differ from adults in their susceptibility to hazardous chemicals, but whether there is 

a difference depends on the chemical (Guzelian et al. 1992; NRC 1993). Children may be more or less 

susceptible than adults to health effects, and the relationship may change with developmental age 

(Guzelian et al. 1992; NRC 1993). Vulnerability often depends on developmental stage. There are 

critical periods of structural and functional development during both prenatal and postnatal life, and a 

particular structure or function will be most sensitive to disruption during its critical period(s). Damage 

may not be evident until a later stage of development. There are often differences in pharmacokinetics 

and metabolism between children and adults. For example, absorption may be different in neonates 

because of the immaturity of their gastrointestinal tract and their larger skin surface area in proportion to 

body weight (Morselli et al. 1980; NRC 1993); the gastrointestinal absorption of lead is greatest in infants 

and young children (Ziegler et al. 1978). Distribution of xenobiotics may be different; for example, 

infants have a larger proportion of their bodies as extracellular water, and their brains and livers are 

proportionately larger (Altman and Dittmer 1974; Fomon 1966; Fomon et al. 1982; Owen and Brozek 

1966; Widdowson and Dickerson 1964). The infant also has an immature blood-brain barrier (Adinolfi 

1985; Johanson 1980) and probably an immature blood-testis barrier (Setchell and Waites 1975). Many 

xenobiotic metabolizing enzymes have distinctive developmental patterns. At various stages of growth 

and development, levels of particular enzymes may be higher or lower than those of adults, and 

sometimes unique enzymes may exist at particular developmental stages (Komori et al. 1990; Leeder and 

Kearns 1997; NRC 1993; Vieira et al. 1996). Whether differences in xenobiotic metabolism make the 

child more or less susceptible also depends on whether the relevant enzymes are involved in activation of 

the parent compound to its toxic form or in detoxification. There may also be differences in excretion, 

particularly in newborns who all have a low glomerular filtration rate and have not developed efficient 

tubular secretion and resorption capacities (Altman and Dittmer 1974; NRC 1993; West et al. 1948). 

Children and adults may differ in their capacity to repair damage from chemical insults. Children also 

have a longer remaining lifetime in which to express damage from chemicals; this potential is particularly 

relevant to cancer. 

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 

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alveoli being less developed, which results in a disproportionately smaller surface area for alveolar 

absorption (NRC 1993). 

There are limited data on the toxicity of vanadium in children. One study examined the influence of age 

on the renal toxicity of vanadium in male rats administered 10 mg/kg/day sodium orthovanadate via 

intraperitoneal injection for 8 days. Similar morphological effects were observed in the kidneys of 

22-day-old rats and 62-day-old rats; however, the effects were more severe in the older rats (de la Torre et 

al. 1999). The difference in lesion severity is likely due to the significantly lower renal vanadium 

concentration in the young rats. 

Edel et al. (1984) examined age-related changes in the distribution of vanadium in rats exposed to 

background levels of vanadium. At 21 days of age, the highest concentrations of vanadium (ng 

vanadium/g wet weight) were found in the kidney, heart, lung, brain, and liver. By 115 days of age, the 

highest concentration was in the femur; levels in the heart, lung, brain, spleen, and muscle were 

approximately 3–4 times lower. The concentrations of vanadium in the kidney, liver, and lungs 

significantly decreased with increasing age of the rat. The investigators suggested several mechanisms 

that may be responsible for the age-related changes in vanadium tissue concentration, including higher 

gastrointestinal absorption of vanadium in young rats, which may be due to increased bioavailability of 

vanadium in breast milk compared to the diet, or a higher vanadium retention capacity in undeveloped 

tissue due to a greater affinity or lower elimination rate. 

As discussed in Section 3.2, a number of developmental effects including decreases in growth, increases 

in malformation and anomalies, and death have been observed in developmental toxicity studies 

(Domingo et al. 1986; Elfant and Keen 1987; Morgan and El-Tawil 2003; Paternain et al. 1990); however 

most of these effects occurred at doses associated with significant maternal toxicity. 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT 

Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility (NAS/NRC 

1989). 

The National Report on Human Exposure to Environmental Chemicals provides an ongoing assessment 

of the exposure of the U.S. population to environmental chemicals using biomonitoring. This report is 

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available at http://www.cdc.gov/exposurereport/. The biomonitoring data for vanadium from this report 

is discussed in Section 6.5. A biomarker of exposure is a xenobiotic substance or its metabolite(s) or the 

product of an interaction between a xenobiotic agent and some target molecule(s) or cell(s) that is 

measured within a compartment of an organism (NAS/NRC 1989). The preferred biomarkers of exposure 

are generally the substance itself, substance-specific metabolites in readily obtainable body fluid(s), or 

excreta. However, several factors can confound the use and interpretation of biomarkers of exposure. 

The body burden of a substance may be the result of exposures from more than one source. The 

substance being measured may be a metabolite of another xenobiotic substance (e.g., high urinary levels 

of phenol can result from exposure to several different aromatic compounds). Depending on the 

properties of the substance (e.g., biologic half-life) and environmental conditions (e.g., duration and route 

of exposure), the substance and all of its metabolites may have left the body by the time samples can be 

taken. It may be difficult to identify individuals exposed to hazardous substances that are commonly 

found in body tissues and fluids (e.g., essential mineral nutrients such as copper, zinc, and selenium). 

Biomarkers of exposure to vanadium 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 

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 vanadium 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 Vanadium 

Several biomarkers of exposure have been identified for vanadium but none of them can be used to 

quantitatively determine exposure levels. Elevated levels of vanadium have been found in the serum 

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(Gylseth et al. 1979; Kiviluoto et al. 1981b) and urine (Gylseth et al. 1979; Kiviluoto et al. 1981b; Lewis 

1959; NIOSH 1983; Zenz et al. 1962) of exposed workers. However, relationships between exposure 

levels and serum or urine vanadium levels have not been established. Some vanadium workers develop a 

characteristic green tongue, as a result of direct accumulation of the vanadium dusts on the tongue (Lewis 

1959). One report from the 1950s states that vanadium exposure was associated with decreased cystine 

content in the fingernails of vanadium workers (Mountain et al. 1955). However, alterations in cystine 

levels can also be associated with dietary changes and with other disease states, so this is not specific for 

vanadium exposure. No other commonly measured cellular changes have been identified with vanadium 

exposure. 

3.8.2 Biomarkers Used to Characterize Effects Caused by Vanadium 

The primary effects of inhalation exposure to vanadium dusts are coughing, wheezing, and other 

respiratory difficulties. These effects, however, are not specific to vanadium and can be found following 

inhalation of many types of dusts. 

3.9 INTERACTIONS WITH OTHER CHEMICALS 

Vanadium in the drinking water of mice had no influence on tumor induction by the known carcinogen 

1,2-dimethylhydrazine given by subcutaneous injection (Kingsnorth et al. 1986), but dietary vanadium 

did decrease mammary tumors in mice caused by 1-methyl-1-nitrosourea administered concurrently 

(Thompson et al. 1984). The latter effect may have been due to interaction with DNA. 

The combination of manganese and vanadium or of nickel and vanadium administered to pregnant mice 

caused some alterations in behavioral development of the pups as compared to either element 

administered alone (Hoshishima et al. 1983). Oral administration of vanadium in rats interfered with 

copper metabolism, probably by inhibiting the intestinal absorption of copper (Witkowska et al. 1988). 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to vanadium than will most persons 

exposed to the same level of vanadium 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 vanadium, or compromised function of organs 

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affected by vanadium. Populations who are at greater risk due to their unusually high exposure to 

vanadium are discussed in Section 6.7, Populations with Potentially High Exposures. 

No unusually susceptible populations have been identified, but persons with pre-existing respiratory 

disorders such as asthma or chronic obstructive pulmonary disease (COPD) may be expected to have 

increased adverse effects from breathing vanadium dusts. Due to the insulin-mimetic effects of 

vanadium, individuals with hypoglycemia may be unusually susceptible to exposure to high levels of 

vanadium. 

3.11 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to vanadium. 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 vanadium. 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 vanadium: 

Haddad LM, Winchester JF. 1990. Clinical management of poisoning and drug overdose. 2nd ed. 

Philadelphia, PA: W.B. Saunders Company, 1033. 

Stutz DR, Janusz SJ. 1988. Hazardous materials injuries: A handbook for pre-hospital care. 2nd ed. 

Beltsville, MD: Bradford Communications Corporation, 406-407. 

3.11.1 Reducing Peak Absorption Following Exposure 

There is no known treatment to decrease absorption after inhaling vanadium and/or its compounds. 

Following oral exposure, dilution with water or milk is one way to decrease overall absorption (Stutz and 

Janusz 1988). To decrease gastrointestinal absorption, especially for organic vanadium compounds, it has 

been suggested that activated charcoal be ingested. If vanadium gets onto the skin, washing the 

contaminated area with soapy water has been advised. For ocular exposure, it is suggested that the eyes 

be flushed with large amounts of saline or water (Stutz and Janusz 1988). 

3.11.2 Reducing Body Burden 

Several studies have evaluated the effectiveness of chelating agents in reducing vanadium body burden. 

Significant increases in urinary excretion of vanadium were observed in rodents treated with ascorbic acid 

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(Domingo et al. 1990), tiron (sodium 4,5-dihydroxybenzene-1,3-disulfonate) (Domingo et al. 1990; 

Gomez et al. 1991), deferoxamine mesylate (Gomez et al. 1988, 1991), or 2-mercaptosuccinic (Domingo 

et al. 1990) following intramuscular injection of vanadyl sulfate (Domingo et al. 1990) or 6-week oral 

exposure to sodium metavanadate or vanadyl sulfate (Gomez et al. 1991). Administration of EDTA, 

2-mercaptosuccinic or tiron also significantly reduced kidney vanadium levels (Domingo et al. 1990) and 

tiron reduced spleen and kidney vanadium levels (Gomez et al. 1991). Administration of calcium 

disodium EDTA resulted in increases in urinary excretion of vanadium in calves exposed to high levels of 

dietary vanadium (Gummow et al. 2006); however, no difference in vanadium excretion was observed 

after vanadium exposure was terminated. Other studies have examined the potential of chelating agents 

to reduce toxicity. Humans or animals with vanadium poisoning have not been helped by the chelating 

agent dimercaprol (BAL), which is often effective in lessening the toxicity of other metals (Lusky et al. 

1949). Intraperitoneal injections of ascorbic acid and of ethylene diamine tetraacetate (EDTA) reduced 

vanadium-induced morbidity in mice and rats (Jones and Basinger 1983; Mitchell and Floyd 1954). 

Administration of tiron 0, 24, 48, or 72 hours after pregnant mice received a 25 mg/kg sodium 

metavanadate intraperitoneal injection on gestation day 12 resulted in significant reductions in vanadiuminduced abortions, early deliveries, fetal deaths, and incidence of reduced ossification (Domingo et al. 

1993a). Administration of tiron after a 6-week exposure to sodium metavanadate reverted the vanadiuminduced impairment in performance on neurobehavioral tests (Sanchez et al. 1999). Co-exposure to 

calcium disodium EDTA did not significantly alter the toxicity of ingested vanadium in calves (Gummow 

et al. 2006). 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects 

There are limited data on treatments which interfere with the mechanism of action for vanadium toxicity. 

Moderate to severe morphological alterations (average severity score of 3.0) were observed in the kidneys 

25 days after rats were administered 1 mg vanadium/kg/day as ammonium metavanadate via 

subcutaneous injection (Al-Bayati et al. 2002). Administration of the antifibrotic agent, pirfenidone, for 

41 days after exposure termination resulted in a decrease in the severity of the kidney lesions; the lesions 

were scored as very mild with a severity score of 1.42. Although the mechanism associated with the 

reduction in toxicity was not determined, it is possible that the pirfenidone-induced reduction in collagendeposition in the kidney may have contributed to the diminished toxicity. Chandra et al. (2007a) 

demonstrated a reduction in testes toxicity in rats administered 0.4 mg vanadium/kg/day as sodium 

metavanadate via intraperitoneal injection for 26 days and 50 or 100 mg/kg vitamin E acetate 

simultaneously in the diet compared to rats administered vanadium only. The likely mechanism is that 

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vitamin E interrupts the chain reactions of lipid peroxidation and scavenges ROS generated during the 

univalent reduction of molecular oxygen and normal activity of oxidative enzymes; thus its prevents the 

detrimental effect of vanadium on testis by inhibiting the oxidative stress. 

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 vanadium 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 vanadium. 

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. 

3.12.1 Existing Information on Health Effects of Vanadium 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

vanadium are summarized in Figure 3-4. The purpose of this figure is to illustrate the existing 

information concerning the health effects of vanadium. 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. 

Data are available from humans regarding acute, intermediate, and chronic inhalation exposure to 

vanadium pentoxide and on immunologic and neurologic effects, primarily from case studies of factory 

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Figure 3-4. Existing Information on Health Effects of Vanadium and Compounds 

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VANADIUM 92 

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workers. Data regarding acute effects are available from volunteers who ingested ammonium vanadyl 

tartrate in capsules for intermediate periods. No human dermal data were located. 

Data are available regarding the effects of inhalation of vanadium pentoxide in rats, mice, and monkeys 

following acute, intermediate, and chronic exposures. Data are available in humans orally exposed to 

vanadyl sulfate or ammonium metavanadate. Data are available following acute, intermediate, and 

chronic oral exposures in animals, including information on death (from ammonium metavanadate, 

sodium metavanadate, or vanadyl sulfate), systemic toxicity (from vanadyl sulfate, sodium metavanadate, 

sodium orthovanadate, or ammonium metavanadate), immunological (from sodium orthovanadate), 

neurological (from vanadium pentoxide), developmental (from vandyl sulfate, sodium orthovanadate, 

ammonium metavanadate, or sodium metavanadate), and reproductive effects (from sodium 

metavanadate, ammonium metavanadate, or vanadyl sulfate). No animal dermal data were located. 

3.12.2 Identification of Data Needs 

Acute-Duration Exposure. Information on the acute toxicity of inhaled vanadium in humans is 

limited to the finding of symptoms of respiratory irritation (persistent coughing) in a small number of 

subjects exposed to vanadium pentoxide dust for 8 hours (Zenz and Berg 1967). Several animal studies 

confirm that the respiratory tract is the most sensitive target of vanadium toxicity (Knecht et al. 1985, 

1992; NTP 2002). These studies only examined the respiratory tract; however, longer duration studies 

have confirmed the respiratory tract as the most sensitive target following inhalation exposure. At lower 

concentrations, the observed effects included lung inflammation and alveolar and bronchiolar epithelial 

hyperplasia in rats and mice exposed to vanadium pentoxide for 6 or 13 days (NTP 2002); the severity of 

the lung effects increased with increasing vanadium concentrations. Impaired lung function was reported 

in monkeys exposed to fairly low concentrations of vanadium pentoxide for 6 hours (Knecht et al. 1985, 

1992). The animal data were sufficient to derive an acute-duration inhalation MRL for vanadium based 

on lung inflammation in rats (NTP 2002). 

There are limited data on human toxicity following ingestion of vanadium; gastrointestinal effects 

(diarrhea, cramps, nausea, vomiting) have been reported in patients given vanadium supplement as part of 

a diabetes treatment plan (Boden et al. 1996; Cusi et al. 2001; Goldfine et al. 1995). However, these 

studies are limited by the small number of subjects and the lack of control groups. A small number of 

studies in laboratory animals have examined the acute toxicity of vanadium following oral exposure. At 

the lowest doses tested, marked developmental toxicity (decreases in fetal growth, increases in resorptions 

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and gross, visceral, and skeletal malformations and anomalies) was observed in rat and mouse offspring 

(Paternain et al. 1987, 1990; Sanchez et al. 1991). In adult rats, hematological effects (including 

increases in reticulocyte levels and polychromatophilic erythroblasts in bone marrow) were observed at 

higher doses than the developmental effects (Zaporowska and Wasilewski 1989). The database was 

considered inadequate for derivation of an acute-duration oral MRL due to the limitations in the human 

studies and the serious effects observed at the lowest animal dose tested. At the lowest adverse effect 

level, a 46% decrease in weight gain (considered a serious health effect) was observed in the rat dams 

(Paternain et al. 1990); it is ATSDR policy to not use serious LOAELs as the basis of an MRL. 

Additional studies which examine a variety of end points are needed to identify the most sensitive effect 

following acute oral exposure. These additional studies might provide a suitable basis for an acuteduration oral MRL. 

No dermal exposure studies were identified in humans or animals. Studies are needed to establish the 

potential toxicity of vanadium compounds applied to the skin. 

Intermediate-Duration Exposure. No human studies examined the toxicity of vanadium following 

intermediate-duration inhalation exposure. Animal data come from 16-day and 13-week exposure studies 

in rats and mice (NTP 2002). These studies clearly identify the respiratory tract as the most sensitive 

target of toxicity. At low concentrations of vanadium pentoxide, alveolar and bronchiolar epithelial 

hyperplasia were observed in both species. At higher concentrations, nasal effects were also observed. 

Although the NTP (2002) study is a high quality study which identified NOAEL and LOAEL values for a 

sensitive end point, an intermediate-duration inhalation MRL was not derived because the NOAEL value 

was the same as the LOAEL for lung inflammation in rats exposed to vanadium pentoxide for 13 days 

(NTP 2002). An explanation for the inconsistent findings is not apparent from the available data. An 

additional study designed to examine respiratory effects after various exposure durations may provide 

insight into the inconsistent findings of the NTP study and may be useful for derivation of an MRL. 

Data on the toxicity of vanadium following intermediate-duration oral exposure come from two human 

studies and a number of animal studies. The human studies examined a number of potential end points in 

subjects exposed to relatively low doses of vanadium for 6–12 weeks; no adverse effects were observed 

(Dimond et al. 1963; Fawcett et al. 1997). Animal studies have identified several sensitive effects 

including hematological alterations (decreased erythrocyte levels and increased reticulocyte levels) 

(Ścibior 2005; Ścibior et al. 2006; Zaporowska and Wasilewski 1990, 1991, 1992a, 1992b; Zaporowska 

et al. 1993), increased blood pressure (Boscolo et al. 1994; Carmagnani et al. 1991, 1992), alterations in 

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neurobehavioral performance tests (Sanchez et al. 1998), and developmental toxicity (Domingo et al. 

1986; Elfant and Keen 1987; Morgan and El-Tawil 2003; Poggioli et al. 2001). However, the findings 

are inconsistent and a cause of the conflicting results has not been identified. Additional animal studies 

examining hematological, blood pressure, and neurological end points are needed to support the findings 

of the animal studies. An intermediate-duration oral MRL based on the NOAEL identified in one of the 

human studies (Fawcett et al. 1997) was derived. 

No dermal exposure studies were identified in humans or animals. Studies utilizing several vanadium 

compounds would be useful for assessing the potential dermal toxicity of vanadium. 

Chronic-Duration Exposure and Cancer. Sufficient information is available in occupationally 

exposed humans to identify the respiratory system as a target organ following chronic inhalation exposure 

(Lewis 1959; NIOSH 1983; Sjöberg 1956; Vintinner et al. 1955; Wyers 1946). Two-year rat and mouse 

studies (NTP 2002) confirm the identification of the respiratory tract as the most sensitive target of 

inhaled vanadium pentoxide. At the lowest concentrations tested, histological alterations in the lungs 

(alveolar and bronchiolar epithelial hyperplasia), larynx (degeneration and hyperplasia of epiglottis 

epithelium), and nasal cavity (goblet cell hyperplasia) were observed. The NTP (2002) rat study was used 

as the basis of a chronic-duration inhalation MRL for vanadium. 

No studies examining the chronic oral toxicity of vanadium in humans were identified. Several studies 

have examined chronic oral toxicity in rats and mice (Dai and McNeill 1994; Dai et al. 1994a, 1994b; 

Schroeder and Balassa 1967; Schroeder et al. 1970); however, the doses tested did not result in adverse 

effects, with the exception of a decrease in body weight gain, and the most sensitive targets of vanadium 

toxicity following chronic exposure have not been identified. Additional studies examining a variety of 

end points, including potential hematological and cardiovascular effects (sensitive targets following 

intermediate-duration exposure), are needed to identify sensitive targets and establish dose-response 

relationships. 

Data are not available to determine target organs in humans from chronic dermal exposure. Dermal 

exposure studies which could be used to identify targets of toxicity and dose-response relationships are 

needed. 

No studies were located regarding the carcinogenicity in humans after inhalation, oral, or dermal exposure 

to vanadium. Significant increases in the incidence of lung tumors (alveolar/bronchiolar adenoma and/or 

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carcinoma) were observed in mice exposed to airborne vanadium pentoxide for 2 years (NTP 2002). 

Suggestive evidence of lung carcinogenicity was also observed in male rats chronically exposed to 

vanadium pentoxide (NTP 2002). Although several oral studies did not find increases in tumor frequency 

in rats or mice exposed to vanadyl sulfate in drinking water (Schroeder and Balassa 1967; Schroeder and 

Mitchener 1975; Schroeder et al. 1970), these studies were considered inadequate for carcinogenicity 

assessment due to the small number of animals tested, low doses (maximum tolerated dose was not 

achieved), incomplete histological examination, and the use of one exposure dose per study. No studies 

examined the potential carcinogenicity of vanadium following dermal exposure. Additional studies are 

needed to evaluate the potential carcinogenicity of vanadium following oral and dermal exposure. 

Genotoxicity. In vivo genotoxicity assays have been conducted in vanadium pentoxide workers 

(Ehrlich et al. 2008; Ivancsits et al. 2002), in mice exposed to airborne vanadium pentoxide (NTP 2002), 

in mice exposed to vanadyl sulfate in drinking water (Villani et al. 2007), and in mice administered a 

gavage dose of vanadyl sulfate, ammonium metavanadate, or sodium orthovanadate (Ciranni et al. 1995). 

Most of the in vitro genotoxicity assays have been conducted in mammalian systems, although there are 

also mutagenicity assays in cultured bacteria (Kada et al. 1980; Kanematsu et al. 1980; NTP 2002) and 

yeast (Bronzetti et al. 1990; Sora et al. 1986). In mammalian systems, mutagenicity (Cohen et al. 1992), 

DNA damage (Birnboim 1988; Foresti et al. 2001; Ivancsits et al. 2002; Kleinsasser et al. 2003; Rojas et 

al. 1996; Smith 1983; Wozniak and Blasiak 2004), and clastogenicity (Gibson et al. 1997; Migliore et al. 

1993, 1995; Owusu-Yaw et al. 1990; Roldán and Altamirano 1990; Zhong et al. 1994) have been 

observed. In general these studies provide evidence that vanadium compounds damage DNA and induce 

clastogenic alterations. However, there are a number of inconsistencies in the results and additional 

studies are needed. 

Reproductive Toxicity. No studies were located regarding the reproductive effects in humans after 

inhalation, oral, or dermal exposure to vanadium. Following inhalation exposure, alterations in estrous 

cycle were observed in female rats exposed to vanadium pentoxide for 3 months (NTP 2002); no 

alterations in sperm characteristics were observed. Studies examining reproductive function are needed to 

evaluate whether the alterations observed in female rats would result in impaired fertility. Decreases in 

male and/or female fertility were observed in rats and mice orally exposed to vanadium (Ganguli et al. 

1994b; Jain et al. 2007; Llobet et al. 1993; Morgan and El-Tawil 2003). Dermal exposure studies are 

needed to evaluate whether the reproductive system is also a target of toxicity for this route. 

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Developmental Toxicity. The potential developmental toxicity of vanadium has not been assessed in 

humans. Oral exposure studies in animals provide evidence that developmental toxicity is a sensitive end 

point. The observed effects include decreases in fetal/pup growth, increased mortality, and increases in 

gross, skeletal, and visceral malformations and anomalies (Domingo et al. 1986; Elfant and Keen 1987; 

Morgan and El-Tawil 2003; Paternain et al. 1987, 1990; Poggioli et al. 2001). Most of these effects 

occurred at doses associated with decreases in maternal food intake and body weight. Additional studies 

utilizing doses not associated with maternal toxicity would be useful in determining whether the observed 

effects are secondary to maternal toxicity or whether the developing organism is a primary target. No 

studies were located regarding the developmental effects in animals after inhalation or dermal exposure to 

vanadium. Studies are needed to determine whether developmental toxicity would also be a sensitive 

target following inhalation or dermal exposure. 

Immunotoxicity. Data regarding the immunotoxicity of vanadium in humans are limited to a study of 

vanadium workers which did not find signs of allergic reactions on the skin or in the respiratory tract 

(Sjöberg 1950). No alterations in immune response to bacteria and/or viruses were observed in mice 

exposed to airborne vanadium pentoxide for 16 days (NTP 2002); an altered response was observed in 

rats. An altered response to sheep red blood cells in mice exposed to sodium orthovanadate in drinking 

water for 6 weeks (Sharma et al. 1981) and decreases in B-cell, IgG, and IgM levels in rats exposed to 

sodium metavanadate in the diet for 10 weeks (Adachi et al. 2000a) were observed. No dermal exposure 

studies examining immunological end points were identified. Although the animal data provide some 

suggestive evidence of immunotoxicity, additional inhalation and oral exposure studies testing a full 

immunology battery are needed to establish the potential of vanadium to induce immunotoxicity. 

Neurotoxicity. Some workers exposed to vanadium dust complained of dizziness, depression, 

headache, or tremors of the fingers and arms (Levy et al. 1984; Vintinner et al. 1955); however, these 

effects may not have been specifically due to vanadium exposure. Neurotoxicity was not evaluated in 

humans following oral or dermal exposure. In animals, alterations in performance on neurobehavioral 

tests were observed in rats orally exposed to sodium metavanadate (Sanchez et al. 1998, 1999). No 

histological alterations in the nervous system were observed in rats or mice exposed to airborne vanadium 

pentoxide (NTP 2002). Neurotoxicity potential was not assessed in animals following dermal exposure. 

Additional studies performing a complete neurological battery of tests are needed to fully evaluate the 

potential of vanadium to induce neurotoxicity, particularly since the Sanchez et al. (1998) study provides 

suggestive evidence that this may be a sensitive target following oral exposure. 

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Epidemiological and Human Dosimetry Studies. Studies of health effects on people who have 

inhaled vanadium in the workplace clearly show that the target organ is the respiratory system (Domingo 

et al. 1985; Levy et al. 1984; Lewis 1959; Musk and Tees 1982; NIOSH 1983; Sjöberg 1950, 1956; 

Thomas and Stiebris 1956; Vintinner et al. 1955; Wyers 1946; Zenz and Berg 1967; Zenz et al. 1962). 

The dose-response relationship is not known, because exposure levels are not well quantified. Further 

information on exposure levels associated with respiratory effects would be useful. However, people 

living near hazardous waste sites are unlikely to come in contact with amounts of vanadium dusts large 

enough to cause adverse health effects. Further epidemiological studies may be useful in revealing 

adverse health effects in people living near boiler ash dumps. Additional information on potentially 

susceptible populations, such as those people with asthma or other respiratory problems, would be useful. 

There are limited data regarding the oral toxicity of vanadium in humans. Studies in diabetics have 

shown that bolus administration can result in symptoms of gastrointestinal irritation (Boden et al. 1996; 

Cusi et al. 2001; Goldfine et al. 1995). Two studies in healthy individuals (Dimond et al. 1963; Fawcett 

et al. 1997) examined a wide variety of potential targets of vanadium toxicity. However, both studies 

used a small number of subjects and additional studies are needed to evaluate the long-term toxicity of 

vanadium in humans, particularly since vanadium is present in a number of nutritional supplements and 

there is a potential for human exposure. An intermediate-duration oral study (Fawcett et al. 1997) which 

found no adverse effects in subjects administered vanadyl sulfate via capsules was used as the basis of an 

MRL. 

Biomarkers of Exposure and Effect. 

Exposure. Biomarkers specific for exposure to vanadium include the presence of vanadium in the urine 

(Gylseth et al. 1979; Kiviluoto et al. 1981b; Lewis 1959; NIOSH 1983; Zenz et al. 1962) and serum 

(Gylseth et al. 1979) and a green discoloration of the tongue (Lewis 1959), the latter resulting from the 

direct accumulation of vanadium pentoxide. Further studies would be helpful in correlating urinary or 

serum vanadium levels with exposure levels. Vanadium can also be measured in the hair (Stokinger et al. 

1953), and studies could be performed to determine if a correlation exists between levels of vanadium in 

hair and exposure levels. In the 1950s, decreased cystine content of the hair or fingernails was described 

as a possible biomarker of exposure (Mountain et al. 1955). However, this is not specific for vanadium 

since other factors, such as diet or disease, can also affect cystine content. 

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Effect. There are no specific biomarkers of effects. It is possible that further biochemical studies might 

show specific effects. For example, it is possible that specific effects may be seen on lung cells, which 

can be examined by lavage. 

Absorption, Distribution, Metabolism, and Excretion. Data are available from human and 

animal studies regarding the kinetics of vanadium following inhalation and oral exposure. Specific data 

from dermal exposure are lacking; although significant absorption of vanadium by this route in humans is 

unlikely (WHO 1988), data are needed to confirm this hypothesis. No animal studies were located that 

evaluated absorption efficiency following inhalation exposure, although NTP (2002) reported marginal, 

but concentration-related, increases in blood vanadium in rats exposed to vanadium pentoxide for 14 days 

or 2 years. Additionally, information is available from intratracheal exposures (Conklin et al. 1982; Edel 

and Sabbioni 1988; Oberg et al. 1978; Rhoads and Sanders 1985). Oral exposure studies suggest that 

approximately 3–17% of ingested vanadium is absorbed and that absorption efficiency may vary among 

vanadium compounds (Adachi et al. 2000b; Conklin et al. 1982). Intratracheal administration and oral 

exposure suggest similar patterns of distribution and excretion (Adachi et al. 2000b; Conklin et al. 1982; 

Ramanadham et al. 1991; Rhoads and Sanders 1985) for the two routes of exposure. Additional studies 

are needed to provide information on the toxicokinetic properties of vanadium following inhalation and 

dermal exposure. Additionally, there are limited data comparing the absorption and distribution of 

various vanadium compounds; inhalation, oral, and dermal exposure studies are needed to evaluate 

whether there are compound-specific differences. 

Comparative Toxicokinetics. Animal data (Conklin et al. 1982; Oberg et al. 1978; Rhoads and 

Sanders 1985; Roshchin et al. 1980) and limited human (Dimond et al. 1963; Gylseth et al. 1979; 

Schroeder et al. 1963) data are available on the kinetics of vanadium. There is little reason to believe that 

vanadium toxicokinetics would differ between animals and humans. The data indicate that the kinetics 

are similar in both. However, as with any particulate substance, extrapolations on inhalation absorption 

rates from animals to humans would be difficult. Studies are available in humans, rats, mice, and dogs. 

Methods for Reducing Toxic Effects. No vanadium-specific information on reducing the 

absorption of vanadium following inhalation, oral, or dermal exposure were identified; such information 

would be useful in the treatment of persons who may have been exposed to vanadium and/or its 

compounds near hazardous waste sites. Several animal studies have explored the use of chelating agents 

for reducing the vanadium body burden. Administration of ascorbic acid, tiron, deferoxamine mesylate, 

or 2-mercaptosuccinic have been shown to increase urinary excretion of vanadium or reduce kidney levels 

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(Domingo et al. 1990; Gomez et al. 1988, 1991), and EDTA and tiron have been shown to reduce toxicity 

(Domingo et al. 1993a; Jones and Basinger 1983; Mitchell and Floyd 1954; Sanchez et al. 1999), 

presumably by reducing the body burden. There is some evidence that pirfenidone (an antifibrotic agent) 

(Al-Bayati et al. 2002) and vitamin E (Chandra et al. 2007a) may interfere with the mechanism of 

vanadium toxicity. Additional data are needed, particularly studies examining methods for reducing the 

toxicity of inhaled vanadium. 

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. 

There are limited data on the susceptibility of children to vanadium toxicity. No human or animal studies 

examined possible age-related differences in toxicity following inhalation, oral, or dermal exposure. An 

intraperitoneal study found decreases in the severity of renal lesions in young rats (22 days of age) 

compared to older rats (62 days of age) (de la Torre et al. 1999). Additional studies are needed to 

evaluate if there are age-related differences in vanadium toxicity or toxicokinetic properties. 

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 

No ongoing studies examining the toxicity or toxicokinetics of vanadium were identified. 

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4. CHEMICAL AND PHYSICAL INFORMATION 

4.1 CHEMICAL IDENTITY 

Vanadium is a naturally occurring element that appears in group 5(B5) of the periodic table (Lide 2008). 

Vanadium is widely distributed in the earth’s crust at an average concentration of 100 ppm 

(approximately 100 mg/kg), similar to that of zinc and nickel (Byerrum 1991). Vanadium is the 22nd most 

abundant element in the earth’s crust (Baroch 2006). Vanadium is found in about 65 different minerals; 

carnotite, roscoelite, vanadinite, and patronite are important sources of this metal along with bravoite and 

davidite (Baroch 2006, Lide 2008). It is also found in phosphate rock and certain ores and is present in 

some crude oils as organic complexes (Lide 2008). Table 4-1 lists common synonyms and other pertinent 

identification information for vanadium and representative vanadium compounds. 

4.2 PHYSICAL AND CHEMICAL PROPERTIES 

Vanadium is a gray metal with a body-centered cubic crystal system. It is a member of the first transition 

series. Because of its high melting point, it is referred to as a refractory metal (Baroch 2006). When 

highly pure, it is a bright white metal that is soft and ductile. It has good structural strength and a lowfission neutron cross section. Vanadium has good corrosion resistance to alkalis, sulfuric and 

hydrochloric acid, and salt water; however, the metal oxidizes readily above 660 °C (Lide 2008). The 

chemistry of vanadium compounds is related to the oxidation state of the vanadium (Woolery 2005). 

Vanadium has oxidation states of +2, +3, +4, and +5. When heated in air at different temperatures, it 

oxidizes to a brownish black trioxide, a blue black tetraoxide, or a reddish orange pentoxide. It reacts 

with chlorine at fairly low temperatures (180 °C) forming vanadium tetrachloride and with carbon and 

nitrogen at high temperatures forming VC and VN, respectively. The pure metal in massive form is 

relatively inert toward oxygen, nitrogen, and hydrogen at room temperature (HSDB 2009). Vanadium 

pentoxide is an industrially important vanadium compound (Lide 2008). Table 4-2 lists important 

physical and chemical properties of vanadium and vanadium compounds. 

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VANADIUM 102 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Vanadium and Compoundsa 

Characteristic Vanadium Vanadium pentoxide Vanadyl sulfate 

Synonym(s) Vanadium, elemental Vanadium oxide; Vanadic sulfate; 

vanadium(V) oxide; vanadium oxide 

vanadic anhydride; sulfate 

divanadium pentoxide 

Registered trade name(s) 

Chemical formula V V2O5 VOSO4 

Identification numbers: 

CAS registry 7440-62-2 1314-62-1 27774-13-6 

EINECS 231-171-1 215-239-8 248-652-7 

RTECSb YW1355000 YW2450000 YW1925000 

EPA hazardous waste No data P120 No data 

OHM/TADS No data No data No data 

DOT/UN/NA/IMDG shipping No data UN2862 UN2931 

HSDB 1022 1024 1026 

NCI No data No data No data 

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VANADIUM 103 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Vanadium and Compoundsa 

Sodium Ammonium 

Characteristic metavanadate Sodium orthovanadate metavanadate 

Synonym(s) Sodium vanadate(V); Sodium o-vanadate; Ammonium 

vanadic acid, sodium pervanadate; vanadate(V); 

monosodium sodium vanadium oxide; ammonium 

vanadic(II) acid, trisodium monovanadate; 

salt ammonium vanadium 

oxide; ammonium 

vanadium trioxide; 

vanadic acid, 

ammonium salt 

Registered trade name(s) 

Chemical formula NaVO3 Na3VO4 NH4VO3 

Identification numbers: 

CAS registry 13718-26-8 13721-39-6 7803-55-6 

EINECS 237-272-7 237-287-9 232-261-3 

RTECSb YW1050000 YW1120000 YW0875000 

EPA hazardous waste No data No data P119 

OHM/TADS No data No data No data 

DOT/UN/NA/IMDG shipping No data No data UN2859 

HSDB No data No data 6310 

NCI No data No data No data 

a

All information obtained from ChemIDPlus 2009 and HSDB 2009, except where noted. b

RTECS 2009 

CAS = Chemical Abstracts Service; DOT/UN/NA/IMDG = Department of Transportation/United Nations/North 

America/International Maritime Dangerous Goods Code; EPA = Environmental Protection Agency; 

HSDB = Hazardous Substances Data Bank; NCI = National Cancer Institute; NIOSH = National Institute for 

Occupational Safety and Health; OHM/TADS = Oil and Hazardous Materials/Technical Assistance Data System; 

RTECS = Registry of Toxic Effects of Chemical Substances 

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VANADIUM 104 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Vanadium and Compoundsa 

Vanadyl sulfate 

Property Vanadium Vanadium pentoxide dihydrate 

Molecular weight 50.9415 181.88 199.035c 

Color Light gray or white 

lustrous powder, fused 

Yellow to rust-brown 

orthorhombic crystals. 

Blue crystalline 

powderc 

hard lumps or body- Yellow-orange powder or 

centered cubic crystals. dark-gray flakes dispersed 

Pure vanadium is bright in air. Yellow to red 

white, soft and ductile. crystalline powder. 

Physical state Solidb Solidb Solid 

Melting point 1,910 °C 690 °C 

Boiling point 3,407 °C 1,750 °C (decomposes) 

Density at 18.7 °C 6.11 3.357 No data 

Odor No data Odorless No data 

Odor threshold: 

Water No data No data No data 

Air No data No data No data 

Solubility: 

Water Insoluble 1 g dissolves in Soluble in waterc 

approximately 125 mL 

water 

Other solvents Soluble in nitric, Soluble in concentrated No data 

hydrofluoric, and acids, alkalies; insoluble in 

concentrated sulfuric alcohol 

acids; attacked by 

alkali, forming water 

soluble vanadates 

Partition coefficients: 

Log Kow No data No data No data 

Log Koc No data No data No data 

Vapor pressure 2.34x10-2 mm Hg at No data No data 

1,916 °C (extrapolated) 

Henry's law constant No data No data No data 

Autoignition temperature No data No data No data 

Flashpoint No data No data No data 

Flammability limits No data No data No data 

Conversion factors No data No data No data 

Explosive limits No data No data No data 

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VANADIUM 105 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Vanadium and Compoundsa 

Sodium Ammonium 

Property metavanadate Sodium orthovanadate metavanadate 

Molecular weight 121.830c 183.909c 116.98 

Color Colorless, monoclinic, 

prismatic crystals or 

pale-green crystalline 

powderb 

Colorless, hexagonal 

prismsb 

White or slightly 

yellow, crystalline 

powder 

Physical state Solid Solid Solid 

Melting point 630°Cb 850–866 °Cb 200 °C 

Boiling point No data No data No data 

Density No data No data 2.326 g/cm3 

Odor No data No data No data 

Odor threshold: 

Water No data No data No data 

Air No data No data No data 

Solubility: 

Water 21 g/100 g water at 

25 °Cc 

Soluble in waterc Slightly soluble in cold 

water 

Other Solvents No data Insoluble in ethanolc Insoluble in alcohol, 

ether, ammonium 

chloride 

Partition coefficients: 

Log Kow No data No data No data 

Log Koc No data No data No data 

Vapor pressure No data No data No data 

Henry's law constant No data No data No data 

Autoignition temperature No data No data No data 

Flashpoint No data No data No data 

Flammability limits Noncombustibleb No data Nonflammableb 

Conversion factors No data No data No data 

Explosive limits No data No data No data 

a

All information obtained from HSDB 2009, except where noted. b

Lewis 2007 

c

Lide 2008 

d

Vanadyl sulfate pentahydrate - Ethereal blue solid; readily soluble in water 

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VANADIUM 106 

4. CHEMICAL AND PHYSICAL INFORMATION 

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VANADIUM 107 

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

5.1 PRODUCTION 

TRI information is available in the TRI database on facilities that manufacture or process vanadium 

(except when contained in an alloy) and vanadium compounds for Release Year 2007, in accordance with 

Section 313 of the Emergency Planning and Community Right-to-Know Act (Title III of the Superfund 

Amendments and Reauthorization Act of 1986) (TRI07 2009). 

Seven U.S. firms produced ferrovanadium, vanadium pentoxide, vanadium metal, and vanadium-bearing 

chemicals or specialty alloys by processing materials such as petroleum residues, spent catalysts, utility 

ash, and vanadium-bearing pig iron slag (USGS 2009a). 

Vanadium occurs in uranium-bearing minerals of Colorado, in the copper, lead, and zinc vanadates of 

Africa, and with certain phosphatic shales and phosphate rocks in the western United States. Commercial 

production from petroleum ash holds promise as an important source of vanadium. It is a constituent of 

titaniferous magnetites that are widely distributed in Russia, South Africa, Finland, People’s Republic of 

China, eastern and western United Sates, and Australia. The vanadium deposits from sulfide and 

vanadate ores in the Peruvian Andes have been depleted. Most reserves are in deposits where vanadium 

would be a by-product or co-product with other minerals, including phosphate, titanium, iron, and 

petroleum (Baroch 2006). High-purity ductile vanadium can be obtained by reduction of vanadium 

chloride with magnesium or with magnesium-sodium mixtures. Much of the vanadium metal now being 

produced is made by calcium reduction of V2O5 in a pressure vessel (Lide 2008). 

World mine production reported for 2008 (in metric tons) was: China, 20,000; Russia, 16,000; South 

Africa, 23,000; and other countries, 1,000, or about 60,000 metric tons for the world (USGS 2009a). 

Table 5-1 lists the facilities in each state that manufacture or process vanadium (except when contained in 

an alloy), the intended use, and the range of maximum amounts of this material that are stored on site. 

Table 5-2 lists the facilities in each state that manufacture or process vanadium compounds, the intended 

use, and the range of maximum amounts of this material that are stored on site. The data listed in 

Tables 5-1 and 5-2 are derived from the Toxics Release Inventory (TRI07 2009). Only certain types of 

facilities were required to report (EPA 2005b). Therefore, this is not an exhaustive list. 

Current U.S. manufacturers of vanadium and selected vanadium compounds are given in Table 5-3. 

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VANADIUM 108 

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

Table 5-1. Facilities that Produce, Process, or Use Vanadium (Except When 

Contained in an Alloy)
 

Minimum Maximum 

Number of amount on site amount on site 

Statea facilities in poundsb in poundsb Activities and usesc 

AL 7 100 49,999,999 1, 2, 3, 5, 7, 12, 13, 14 

AR 4 0 99,999 1, 5, 13, 14 

AZ 5 10,000 9,999,999 1, 2, 3, 4, 5, 6, 12, 13, 14 

CA 12 0 999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13, 14 

CT 2 10,000 999,999 1, 4, 5, 9, 12 

FL 8 0 999,999 1, 4, 5, 9, 10, 12, 13, 14 

GA 1 1,000,000 9,999,999 1, 11, 13 

ID 3 100,000 999,999 1, 3, 5, 12 

IL 9 0 999,999 1, 5, 7, 12, 13 

IN 3 0 999,999 8, 10, 14 

KS 4 100 999,999 1, 5, 11, 12, 14 

KY 6 0 99,999 1, 5, 7, 8, 11, 12 

LA 7 0 999,999 1, 2, 3, 6, 7, 10, 12, 13, 14 

MD 3 0 99,999 1, 5 

MI 2 1,000 99,999 2, 5, 7, 8, 11, 14 

MO 1 1,000 9,999 12 

MS 3 10,000 999,999 2, 3, 8, 10 

NC 1 1,000 9,999 8 

ND 1 100,000 999,999 1, 5, 12 

NE 3 10,000 99,999 1, 3, 4, 5, 9, 12, 13 

NJ 1 10,000 99,999 2, 13 

NM 2 10,000 9,999,999 12 

NY 3 100 999,999 1, 5, 6 

OH 14 0 9,999,999 1, 3, 4, 5, 7, 8, 11, 12, 13, 14 

OK 2 10,000 99,999 1, 5, 11, 14 

PA 8 0 999,999 1, 2, 3, 4, 5, 6, 7, 8, 12 

PR 1 0 0 0 

SC 10 0 999,999 1, 3, 4, 5, 6, 9, 12, 13 

TN 4 100 9,999 1, 2, 3, 5, 9, 13, 14 

TX 24 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

VA 3 0 99,999 1, 2, 5, 12, 13, 14 

WI 1 1,000 9,999 7, 8 

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VANADIUM 109 

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

Table 5-1. Facilities that Produce, Process, or Use Vanadium (Except When 

Contained in an Alloy)
 

Minimum Maximum 

Number of amount on site amount on site 

Statea facilities in poundsb in poundsb Activities and usesc 

WV 2 1,000 99,999 10, 12
 

WY 2 10,000 99,999 10, 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) 

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VANADIUM 110 

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

Table 5-2. Facilities that Produce, Process, or Use Vanadium Compounds 

Minimum Maximum 

Number of amount on site amount on site 

Statea facilities in poundsb in poundsb Activities and usesc 

AL 25 0 999,999 1, 3, 4, 5, 7, 8, 9, 12, 13, 14 

AR 16 0 999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14 

AZ 19 1,000 99,999,999 1, 3, 4, 5, 6, 9, 10, 12, 13, 14 

CA 28 0 49,999,999 1, 2, 3, 4, 5, 6, 9, 10, 11, 12, 13, 14 

CO 21 100 999,999 1, 4, 5, 9, 12, 13, 14 

CT 5 100 9,999 1, 4, 5, 9, 12, 13 

DE 10 0 999,999 1, 2, 5, 9, 10, 12, 13 

FL 51 0 9,999,999 1, 2, 3, 4, 5, 8, 9, 10, 11, 12, 13, 14 

GA 27 0 49,999,999 1, 3, 4, 5, 7, 9, 10, 12, 13, 14 

HI 1 100 999 1, 5 

IA 14 0 999,999 1, 3, 4, 5, 9, 12, 13, 14 

ID 11 0 49,999,999 1, 2, 3, 5, 6, 10, 14 

IL 45 0 999,999 1, 2, 3, 5, 6, 7, 8, 9, 10, 12, 13, 14 

IN 52 0 9,999,999 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14 

KS 19 0 999,999 1, 3, 4, 5, 9, 10, 12, 13, 14 

KY 23 0 999,999 1, 2, 3, 4, 5, 7, 8, 9, 10, 12, 13, 14 

LA 50 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

MA 10 1,000 99,999 1, 2, 5, 9, 11, 12, 13, 14 

MD 16 0 999,999 1, 4, 5, 6, 7, 9, 12, 13, 14 

ME 7 0 99,999 1, 5, 12, 13 

MI 37 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 13, 14 

MN 10 100 999,999 1, 2, 3, 4, 5, 7, 8, 9, 10, 12, 13, 14 

MO 21 0 999,999 1, 3, 5, 9, 10, 12, 13, 14 

MS 14 0 9,999,999 1, 2, 3, 4, 5, 8, 9, 10, 13, 14 

MT 5 100 999,999 1, 5, 9, 12, 14 

NC 32 0 9,999,999 1, 2, 3, 4, 5, 7, 9, 12, 13, 14 

ND 6 10,000 999,999 1, 5, 9, 12, 13, 14 

NE 9 10,000 999,999 1, 3, 4, 5, 9, 12, 13 

NH 7 0 999,999 1, 5, 9 

NJ 20 100 999,999 1, 2, 3, 4, 5, 6, 7, 9, 10, 12, 13, 14 

NM 8 1,000 999,999 1, 3, 4, 5, 9, 12, 13, 14 

NV 22 0 499,999,999 1, 2, 3, 5, 6, 9, 10, 12, 13, 14 

NY 21 0 999,999 1, 2, 3, 4, 5, 6, 7, 9, 12, 13, 14 

OH 46 0 9,999,999 1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

OK 14 1,000 99,999 1, 3, 4, 5, 8, 9, 10, 11, 12, 13, 14 

OR 3 1,000 99,999 1, 3, 4, 5, 9, 14 

PA 59 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

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VANADIUM 111 

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

Table 5-2. Facilities that Produce, Process, or Use Vanadium Compounds 

Minimum Maximum 

Number of amount on site amount on site 

Statea facilities in poundsb in poundsb Activities and usesc 

PR 8 0 99,999 1, 2, 5, 10, 13 

SC 18 0 9,999,999 1, 3, 4, 5, 7, 8, 9, 12, 13, 14 

SD 2 10,000 99,999 1, 5, 9, 13, 14 

TN 25 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14 

TX 69 0 9,999,999 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14 

UT 26 100 49,999,999 1, 2, 3, 4, 5, 7, 9, 10, 11, 12, 13, 14 

VA 21 0 999,999 1, 3, 4, 5, 8, 9, 10, 12, 13, 14 

VI 1 100,000 999,999 10, 14 

WA 3 10,000 999,999 1, 3, 4, 5, 9, 12, 13 

WI 17 0 999,999 1, 3, 4, 5, 9, 12, 13, 14 

WV 26 0 999,999 1, 2, 3, 4, 5, 6, 7, 9, 11, 12, 13, 14 

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) 

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VANADIUM 112 

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

Table 5-3. Current U.S. Manufacturers of Vanadium and Selected Vanadium
 

Compoundsa
 

Company Location 

Vanadium 

International Specialty Alloys New Castle, Pennsylvania 

Vanadium pentoxide 

Denison Mines (USA) Corp. Blanding, Utah 

Gulf Chemical & Metallurgical Corp. Freeport, Texas 

Stratcor, Inc. Hot Springs, Arizona 

Vanadyl sulfate 

The Shepherd Chemical Co. Cincinnati, Ohio 

Shieldalloy Metallurgical Corp.; Specialty Products Division Cambridge, Ohio 

Stratcor, Inc. Hot Springs, Arizona 

Sodium metavanadate 

Denison Mines (USA) Corp. Blanding, Utah 

Shieldalloy Metallurgical Corp.; Specialty Products Division Cambridge, Ohio 

Sodium orthovanadate 

Shieldalloy Metallurgical Corp.; Specialty Products Division Cambridge, Ohio 

Ammonium metavanadate 

Denison Mines (USA) Corp. Blanding, Utah 

Shieldalloy Metallurgical Corp.; Specialty Products Division Cambridge, Ohio 

Stratcor, Inc. Hot Springs, Arizona 

a

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.

b

USGS 2009b 

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VANADIUM 113 

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

5.2 IMPORT/EXPORT 

Import sources of ferrovanadium from 2004 to 2007 were 76% of the Czech Republic, 7% from 

Swaziland, 6% from Canada, 6% from the Republic of Korea and 5% from other sources. Vanadium 

pentoxide import sources in this same time period were 59% from South Africa, 20% from China, 18% 

from Russia, and 3% from other sources (USGS 2009a). 

5.3 USE 

Vanadium is used in producing rust-resistant, spring, and high-speed tool steels. It is an important 

carbide stabilizer in making steels. About 80% of the vanadium produced is used as ferrovanadium as a 

steel additive. Vanadium foil is used as a bonding agent in cladding titanium to steel. Vanadium 

pentoxide is used in ceramics and as a catalyst as well as in producing a superconductive magnet with a 

field of 175,000 gauss (Lide 2008). Metallurgical use as an alloying agent for iron and steel accounted 

for approximately 92% of domestic vanadium consumption in 2008 (USGS 2009a). 

Vanadium, as elemental vanadium or vanadyl sulfate, also may be found in various commercial 

nutritional supplements and multivitamins (NLM 2009). Vanadyl sulfate and sodium metavanadate have 

been used in supplements for individuals with diabetes, as well by weight training athletes (Barceloux 

1999; IOM 2001; Smith et al. 2008). 

5.4 DISPOSAL 

Waste material contaminated with vanadium should be disposed of in a manner not hazardous to 

employees. The disposal method must conform to applicable local, state, and federal regulations and 

must not constitute a hazard to the surrounding population or environment. Chemical precipitation has 

been investigated as a possible wastewater treatment technology for vanadium (EPA 1982). 

Approximately 8.8x105 and 7.0x105 pounds of vanadium (except when contained in an alloy) and 

vanadium compounds, respectively, were reported for on-site disposal and other releases in 2007. On-site 

disposal or other releases include emissions to the air, discharges to bodies of water, disposal at the 

facility to land, and disposal in underground injection wells. Approximately 1.2x106 and 9.6x106 pounds 

of vanadium (except when contained in an alloy) and vanadium compounds, respectively, were reported 

for off-site disposal and other releases in 2007. An off-site disposal or other release is a discharge of a 

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VANADIUM 114 

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

toxic chemical to the environment that occurs as a result of a facility’s transferring a waste containing a 

TRI chemical off-site for disposal or other release (TRI07 2009). The TRI data should be used with 

caution because only certain types of facilities are required to report (EPA 2005b). This is not an 

exhaustive list. 

Some tool steel scrap was recycled mainly for its vanadium content, and vanadium was recycled from 

spent chemical process catalysts; however, these two sources together accounted for only a small 

percentage (USGS 2009a). 

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VANADIUM 115 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.1 OVERVIEW 

Vanadium has been identified in at least 319 of the 1,699 hazardous waste sites that have been proposed 

for inclusion on the EPA National Priorities List (NPL) (HazDat 2007). However, the number of sites 

evaluated for vanadium is not known. The frequency of these sites can be seen in Figure 6-1. All of 

these sites are located within the United States. 

Vanadium is widely distributed in the earth’s crust at an average concentration of 100 ppm 

(approximately 100 mg/kg), similar to that of zinc and nickel (Byerrum 1991). Vanadium is the 22nd most 

abundant element in the earth’s crust (Baroch 2006). There are about 65 different vanadium-containing 

minerals; carnotite, roscoelite, vanadinite, and patronite are important sources of this metal along with 

bravoite and davidite (Baroch 2006; Lide 2008). It is also found in phosphate rock and certain ores and is 

present in some crude oils as organic complexes (Lide 2008). 

Vanadium is released naturally to the atmosphere by the formation of continental dust, marine aerosols, 

and volcanic emissions. Vanadium is a constituent of nearly all coal and petroleum crude oils. Eastern 

U.S. coal has an average vanadium content of approximately 30 ppm, while coal from western states has 

average content of 15 ppm, and coal from the interior portion of the United States contains an average 

vanadium concentration of 34 ppm (Byerrum et al. 1974). The average vanadium content of bituminous 

and anthracite coal is 30 and 125 ppm, respectively (Byerrum et al. 1974). The most important 

anthropogenic sources of vanadium include the combustion of fossil fuels, particularly residual fuel oils, 

which constitute the single largest overall release of vanadium to the atmosphere. While the levels of 

vanadium in residual fuel oil vary by source, levels of 1–1,400 ppm have been reported (Byerrum et al. 

1974). Natural gas and distillate fuel oils contain very low or undetectable levels (<0.05 ppm) of 

vanadium and are not considered a significant source of vanadium to the environment, except in the case 

of large accidental spills. The natural release of vanadium to water and soils occurs primarily as a result 

of weathering of rocks and soil erosion. This process usually involves the conversion of the less-soluble 

trivalent form to the more soluble pentavalent form. Deposition of atmospheric vanadium is also an 

important source both near and far from industrial plants burning residual fuel oils rich in vanadium. 

Other anthropogenic sources include leachates from mining tailings, vanadium-enriched slag heaps, 

municipal sewage sludge, and certain fertilizers. Natural releases to water and soil are far greater overall 

than anthropogenic releases to the atmosphere. 

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VANADIUM 116 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-1. Frequency of NPL Sites with Vanadium Contamination 

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VANADIUM 117 

6. POTENTIAL FOR HUMAN EXPOSURE 

Ambient atmospheric levels of vanadium are generally low (parts per trillion range) in rural and remote 

areas and greater in urban locations; however, vanadium levels in both rural and urban locations in the 

eastern United States tend to be significantly higher than in other areas throughout the country, 

particularly during winter months. A high density of oil fired power plants that consume vanadium-rich 

residual fuel oil stretching from southern New York to North Carolina are likely to be the greatest 

potential source of the high vanadium levels observed in the eastern United States (Polissar et al. 2001). 

In 2007, the Department of Energy reported that nearly 80% of the residual fuel oil consumed for power 

generation was purchased in the East Coast districts (DOE 2008). 

The general population is exposed to background levels of vanadium primarily through ingestion of food. 

Vanadium in food is mainly ingested as VO2+ (vanadyl, V4+) or HVO4

2- (vanadate) (Sepe et al. 2003). 

Vanadium, as elemental vanadium or vanadyl sulfate, is also found in some dietary supplements and 

multivitamins; consumption of some vanadium-containing supplements may result in intakes of vanadium 

that would exceed those from food. Workers in industries processing or using vanadium compounds are 

commonly exposed to higher than background levels of vanadium as vanadium oxides via the inhalation 

pathway. Exposure to vanadium oxides through inhalation may also be of importance in urban areas, 

particularly in the northeastern United States where large amounts of residual fuel oil are burned. Other 

populations possibly exposed to higher-than-background levels, include those ingesting foodstuffs 

contaminated by vanadium-enriched soil, fertilizers, or sludge. Populations in the vicinity of vanadiumcontaining hazardous waste sites may also be exposed to higher than background levels. Individuals 

exposed to cigarette smoke may also be exposed to higher-than-background levels of vanadium. 

6.2 RELEASES TO THE ENVIRONMENT 

The Toxics Release Inventory (TRI) data should be used with caution because only certain types of 

facilities are required to report (EPA 2005b). This is not an exhaustive list. Manufacturing and 

processing facilities are required to report information to the TRI only if they employ 10 or more full-time 

employees; if their facility is included in Standard Industrial Classification (SIC) Codes 10 (except 1011, 

1081, and 1094), 12 (except 1241), 20–39, 4911 (limited to facilities that combust coal and/or oil for the 

purpose of generating electricity for distribution in commerce), 4931 (limited to facilities that combust 

coal and/or oil for the purpose of generating electricity for distribution in commerce), 4939 (limited to 

facilities that combust coal and/or oil for the purpose of generating electricity for distribution in 

commerce), 4953 (limited to facilities regulated under RCRA Subtitle C, 42 U.S.C. section 6921 et seq.), 

5169, 5171, and 7389 (limited S.C. section 6921 et seq.), 5169, 5171, and 7389 (limited to facilities 

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VANADIUM 118 

6. POTENTIAL FOR HUMAN EXPOSURE 

primarily engaged in solvents recovery services on a contract or fee basis); and if their facility produces, 

imports, or processes ≥25,000 pounds of any TRI chemical or otherwise uses >10,000 pounds of a TRI 

chemical in a calendar year (EPA 2005b). 

6.2.1 Air 

Estimated releases of 8.1x104 pounds (~37 metric tons) of vanadium (except when contained in an alloy) 

to the atmosphere from 49 domestic manufacturing and processing facilities in 2007, accounted for about 

3.8% of the estimated total environmental releases from facilities required to report to the TRI (TRI07 

2009). Estimated releases of 6.0x105 pounds (~270 metric tons) of vanadium compounds to the 

atmosphere from 520 domestic manufacturing and processing facilities in 2007, accounted for about 1.4% 

of the estimated total environmental releases from facilities required to report to the TRI (TRI07 2009). 

These releases are summarized in Tables 6-1 and 6-2. 

Natural sources of atmospheric vanadium include continental dust, marine aerosol, and volcanic 

emissions (Byerrum et al. 1974; Van Zinderen Bakker and Jaworski 1980; Zoller et al. 1973). The 

quantities entering the atmosphere from each of these sources are uncertain; however, continental dust is 

believed to account for the largest portion of naturally emitted atmospheric vanadium followed by marine 

aerosols. Contributions from volcanic emissions are believed to be negligible when compared with the 

other two sources (Zoller et al. 1973). 

Combustion of heavy fuels, especially in oil-fired power plants, refineries, and industrial boilers, and coal 

are the major source of anthropogenic emissions of vanadium into the atmosphere (Mamane and Pirrone 

1998; Sepe et al. 2003). Global anthropogenic atmospheric emission of vanadium as been estimated to be 

2.1x105 metric tons (MT)/year, 3 times higher than vanadium releases due to natural sources. However, 

other estimates indicated that anthropogenic releases of particulate-bound vanadium (9x104 MT/year) 

were more similar to releases due natural sources, such as continental or volcanic dusts, which have 

releases of 7x104 and 1x104 MT/year, respectively) (Mamane and Pirrone 1998). 

Fuel oils may contain vanadium in concentrations ranging from 1 to 1,400 ppm, depending on their origin 

(Byerrum et al. 1974). During the combustion of residual oils organovanadium compounds found in fuel 

oils are oxidized and transformed into various compounds (e.g., vanadium pentoxide, vanadium tetroxide, 

vanadium trioxide, and vanadium dioxide). These compounds are emitted as fly ash into the atmosphere 

(Mamane and Pirrone 1998). 

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6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Releases to the Environment from Facilities that Produce, Process, or
 

Use Vanadium (Except When Contained in an Alloy)a
 

Reported amounts released in pounds per yearb 

Total release 

On- and 

Statec RFd Aire Waterf UIg Landh Otheri On-sitej Off-sitek off-site 

AL 1 17,181 0 0 3,436 0 20,617 0 20,617 

AR 2 6 0 0 0 1,739 6 1,739 1,745 

AZ 2 77 0 0 187,092 0 187,167 2 187,169 

CA 4 252 310 0 127,011 5 76,332 51,246 127,578 

ID 1 38 0 0 244,713 0 244,751 0 244,751 

IL 1 0 0 0 3,068 0 0 3,068 3,068 

KS 3 5,709 0 0 102,300 608,717 11,009 705,717 716,726 

KY 1 14 0 0 0 0 14 0 14 

LA 2 140 5,152 0 56,388 0 5,292 56,388 61,680 

MO 1 0 0 0 0 20 0 20 20 

MS 1 0 0 0 131,300 0 0 131,300 131,300 

ND 1 48,088 0 0 86,381 0 90,782 43,687 134,469 

NE 1 140 0 0 13,000 0 13,140 0 13,140 

NY 1 0 0 0 949 64,880 0 65,828 65,828 

OH 6 1,614 1,674 2 138,507 26,328 48,265 119,860 168,125 

PA 3 3,279 0 0 5 35,104 3,284 35,104 38,388 

PR 1 0 0 0 0 0 0 0 0 

SC 1 1,000 1,972 0 107 0 3,079 0 3,079 

TN 1 10 0 0 1,512 274 10 1,786 1,796 

TX 12 3,212 19,799 0 17,938 5 25,004 15,950 40,954 

VA 1 83 15 0 4,108 4 98 4,112 4,210 

WV 1 0 0 0 52,255 0 52,255 0 52,255 

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VANADIUM 120 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Releases to the Environment from Facilities that Produce, Process, or
 

Use Vanadium (Except When Contained in an Alloy)a
 

Reported amounts released in pounds per yearb 

Total release 

Statec RFd Aire Waterf UIg Landh Otheri On-sitej Off-sitek 

On- and 

off-site 

WY 

Total 

1 

49 

201 

81,043 

0 

28,922 

0 

2 

100,057 

1,270,126 

0 

737,076 

100,258 

881,362 

0 

1,235,808 

100,258 

2,117,170 

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) 

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VANADIUM 121 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-2. Releases to the Environment from Facilities that Produce, Process, or
 

Use Vanadium Compoundsa
 

Reported amounts released in pounds per yearb 

Total release 

On- and 

Statec RFd Aire Waterf UIg Landh Otheri On-sitej Off-sitek off-site 

AL 21 14,224 9,379 0 1,694,971 27 1,711,492 7,109 1,718,601 

AR 8 16,188 169,170 0 1,709,832 1,858 1,895,125 1,923 1,897,048 

AZ 7 1,099 0 0 244,363 0 245,462 0 245,462 

CA 13 187 1,052 0 86,238 15 994 86,498 87,492 

CO 10 1,375 119 0 303,890 7,052 163,631 148,805 312,436 

CT 2 0 0 0 20,009 0 0 20,009 20,009 

DE 4 1,743 17,501 0 428,513 179,436 56,244 570,949 627,193 

FL 21 54,752 1,481 33,315 4,958,132 28,031 1,785,451 3,290,260 5,075,711 

GA 15 27,261 20,059 0 1,873,231 0 1,881,251 39,300 1,920,551 

IA 7 1,571 5 0 173,500 12,644 168,976 18,744 187,720 

ID 2 3,819 1,405 0 616,407 1,620 621,632 1,620 623,252 

IL 22 28,755 10,927 0 418,991 321 341,886 117,108 458,994 

IN 29 19,920 12,250 0 3,311,659 18,648 2,693,285 669,192 3,362,477 

KS 8 11,820 1 0 259,993 0 271,382 432 271,814 

KY 23 20,580 21,751 0 3,198,893 124,137 3,054,104 311,257 3,365,361 

LA 24 147,927 55,994 0 332,235 6,722 436,791 106,087 542,878 

MA 4 4,938 2,491 0 64,314 0 38,274 33,469 71,743 

MD 8 5,704 1,597 0 159,347 260,048 56,863 369,833 426,697 

ME 2 1,500 4,662 0 21,274 0 27,436 0 27,436 

MI 17 6,036 7,869 0 832,882 2,358 622,845 226,300 849,145 

MN 5 2,070 863 0 392,039 3,182 277,956 120,198 398,154 

MO 11 6,124 25 0 262,566 0 268,310 405 268,715 

MS 8 1,037 67,469 1,261,497 2,701,215 0 4,030,172 1,046 4,031,218 

MT 2 2,832 10 0 215,880 12,930 218,722 12,930 231,652 

NC 20 15,186 8,878 0 1,373,808 15,355 1,350,201 63,027 1,413,228 

ND 3 1,115 0 0 143,171 679 136,742 8,223 144,965 

NE 3 2,615 0 0 78,511 0 81,126 0 81,126 

NH 3 1,075 0 0 10,380 0 2,975 8,480 11,455 

NJ 7 1,638 16,250 0 5,018 6,300 17,638 11,568 29,206 

NM 5 1,971 830 0 490,597 0 493,398 0 493,398 

NV 5 17 0 0 2,201,622 0 2,201,639 0 2,201,639 

NY 9 20,512 3,276 0 585,147 247,051 551,640 304,346 855,986 

OH 26 106,896 1,139 1,810 2,159,259 162,350 1,793,794 637,660 2,431,454 

OK 10 2,842 11 0 126,270 0 77,723 51,400 129,123 

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6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-2. Releases to the Environment from Facilities that Produce, Process, or
 

Use Vanadium Compoundsa
 

Reported amounts released in pounds per yearb 

Total release 

On- and 

Statec RFd Aire Waterf UIg Landh Otheri On-sitej Off-sitek off-site 

OR 1 305 0 0 9,900 0 10,205 0 10,205 

PA 29 13,634 1,127 0 1,499,090 550 936,936 577,465 1,514,401 

PR 1 0 0 0 0 0 0 0 0 

SC 16 4,754 4,227 0 276,695 322 263,725 22,274 285,999 

SD 1 104 0 0 17,100 0 13,104 4,100 17,204 

TN 15 3,931 30,351 0 1,508,290 0 1,268,104 274,468 1,542,572 

TX 33 25,734 6,258 11,292 1,652,925 120,018 1,642,602 173,625 1,816,227 

UT 9 1,021 1,000 0 284,148 28,151 285,391 28,929 314,320 

VA 16 4,059 5,687 0 693,368 38,974 632,757 109,331 742,088 

VI 1 37 8,387 0 24,878 0 11,990 21,312 33,302 

WA 1 387 182 0 96,659 0 97,228 0 97,228 

WI 14 4,914 868 0 577,355 131,721 106,054 608,803 714,857 

WV 15 4,775 991 0 2,085,660 38,000 1,681,804 447,622 2,129,425 

WY 4 1,913 0 0 244,462 0 176,966 69,409 246,375 

Total 520 600,897 495,542 1,307,914 40,424,686 1,448,501 34,702,024 9,575,516 44,277,540 

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) 

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VANADIUM 123 

6. POTENTIAL FOR HUMAN EXPOSURE 

Vanadium has not been identified in air collected at current or former NPL hazardous waste sites where 

vanadium was detected in some environmental media (HazDat 2007). 

6.2.2 Water 

Estimated releases of 2.9x104 pounds (~13 metric tons) of vanadium (except when contained in an alloy) 

to surface water from 49 domestic manufacturing and processing facilities in 2007, accounted for about 

1.4% of the estimated total environmental releases from facilities required to report to the TRI (TRI07 

2009). Estimated releases of 5.0x105 pounds (~230 metric tons) of vanadium compounds to surface water 

from 520 domestic manufacturing and processing facilities in 2007, accounted for about 1.1% of the 

estimated total environmental releases from facilities required to report to the TRI (TRI07 2009). These 

releases are summarized in Tables 6-1 and 6-2. 

Natural sources of vanadium release to water include wet and dry deposition, soil erosion, and leaching 

from rocks and soils. The largest amount of vanadium release occurs naturally through water erosion of 

land surfaces. It has been estimated that approximately 32,300 tons of vanadium are dissolved and 

transported to the oceans by water, and an additional 308,650 tons are thought to be transported in the 

form of particulate and suspended sediment (Van Zinderen Bakker and Jaworski 1980). 

Anthropogenic releases to water and sediments are far smaller than natural sources (Van Zinderen Bakker 

and Jaworski 1980). Such sources of vanadium in water may include leaching from the residue of ores 

and clays, vanadium-enriched slags, urban sewage sludge, and certain fertilizers, all of which are 

subjected to rain and groundwater drainage, as well as leachate from ash ponds and coal preparation 

wastes (Byerrum et al. 1974; Van Zinderen Bakker and Jaworski 1980). Leaching may potentially occur 

from landfills and from the airborne particulate matter that is deposited in areas with high residual fuel oil 

combustion, although neither of these release sources is documented. 

Vanadium has been identified in groundwater and surface water at 224 and 129 sites, respectively, of the 

319 NPL hazardous waste sites where it was detected in some environmental media (HazDat 2007). 

6.2.3 Soil 

Estimated releases of 1.3 million pounds (~580 metric tons) of vanadium (except when contained in an 

alloy) to soils from 49 domestic manufacturing and processing facilities in 2007, accounted for about 60% 

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VANADIUM 124 

6. POTENTIAL FOR HUMAN EXPOSURE 

of the estimated total environmental releases from facilities required to report to the TRI (TRI07 2009). 

An additional 2 pounds (~0.9 kilograms) of vanadium were released via underground injection (TRI07 

2009). Estimated releases of 40 million pounds (~1.8x104 metric tons) of vanadium compounds to soils 

from 520 domestic manufacturing and processing facilities in 2007, accounted for about 91% of the 

estimated total environmental releases from facilities required to report to the TRI (TRI07 2009). An 

estimated 1.3 million pounds (~590 metric tons) of vanadium compounds were released via underground 

injection from 520 domestic manufacturing and processing facilities in 2007, accounted for about 3.0% of 

the estimated total environmental releases from facilities required to report to the TRI (TRI07 2009). 

These releases are summarized in Tables 6-1 and 6-2. 

Natural releases of vanadium to soil result from weathering of rock-bearing vanadium minerals, 

precipitation of vanadium particulate from the atmosphere, deposition of suspended particulate from 

water, and plant and animal wastes. The largest amount of vanadium released to soil occurs through the 

natural weathering of geological formations (Byerrum et al. 1974; Van Zinderen Bakker and Jaworski 

1980). 

Anthropogenic releases of vanadium to soil are less widespread than natural releases and occur on a 

smaller scale. These include the use of certain fertilizers containing materials with a high vanadium 

content such as rock phosphate (10–1,000 mg/kg vanadium), superphosphate (50–2,000 mg/kg 

vanadium), and basic slag (1,000–5,000 mg/kg vanadium) (Van Zinderen Bakker and Jaworski 1980) as 

well as disposal of industrial wastes such as slag heaps and mine tailings. Additional release to the 

environment may also result from the disposal of vanadium-containing wastes in landfills, although this 

has not been specifically documented, and from wet and dry deposition of airborne particulate, 

particularly in areas with high levels of residual fuel oil combustion (Byerrum et al. 1974). 

Vanadium has been identified in soil at 172 sites and in sediment at 44 sites collected from 319 NPL 

hazardous waste sites, where vanadium was detected in some environmental media (HazDat 2007). 

6.3 ENVIRONMENTAL FATE 

6.3.1 Transport and Partitioning 

The global biogeochemical cycling of vanadium is characterized by releases to the atmosphere, water, and 

land by natural and anthropogenic sources, long-range transportation of particles in both air and water, 

wet and dry deposition, adsorption, and complexing. Vanadium generally enters the atmosphere as an 

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6. POTENTIAL FOR HUMAN EXPOSURE 

aerosol. From natural sources, vanadium is probably in the form of mineral particles; it has been 

suggested that these may frequently be in the less-soluble trivalent form (Byerrum et al. 1974; Zoller et al. 

1973). From human-made sources, almost all of the vanadium released to the atmosphere is in the form 

of simple or complex vanadium oxides (Byerrum et al. 1974). 

The size distribution of vanadium-bearing particles in the atmosphere is substantially altered during longrange transportation (Zoller et al. 1973). Natural sources of vanadium, as well as man-made sources such 

as ore-processing dust, tend to release large particles that are more likely to settle near the source. 

Smaller particles, such as those emitted from oil-fueled power plants, have a longer residence time in the 

atmosphere and are more likely to be transported farther away from the site of release (Zoller et al. 1973). 

Vanadium transported within the atmosphere is eventually transferred to soil and water on the earth's 

surface by wet and dry deposition and dissolution in sea water (Duce and Hoffman 1976; Van Zinderen 

Bakker and Jaworski 1980). Eventually, in the course of biogeochemical movement between soil and 

water, these particulates are adsorbed to hydroxides or associated with organic compounds and are 

deposited on the sea bed (WHO 1988). 

Deposition rates ranging from 20.5 to 84.9 μg/cm2

/day of vanadium were reported in urban dust collected 

between March and September 2002 from six locations Adapazarí, Turkey (Dundar 2006). Vanadium is 

considered a marker of air pollution emitted from residual oil and coal combustion (Mamane and Pirrone 

1998). 

The transport and partitioning of vanadium in water and soil is influenced by pH, redox potential, and the 

presence of particulate. In fresh water, vanadium generally exists in solution as the vanadyl ion (V4+) 

under reducing conditions and the vanadate ion (V5+) under oxidizing conditions, or as an integral part of, 

or adsorbed onto, particulate matter (Wehrli and Stumm 1989). The chemical formulas of the vanadyl 

species most commonly reported in fresh water are VO2+ and VO(OH)+

, and the vanadate species are 

- H2VO4 and HVO4

2- (Wehrli and Stumm 1989). The partitioning of vanadium between water and 

sediment is strongly influenced by the presence of particulate in the water. Both vanadate and vanadyl 

species are known to bind strongly to mineral or biogenic surfaces by adsorption or complexing (Wehrli 

and Stumm 1989). Thus, vanadium is transported in water in one of two ways: solution or suspension. It 

has been estimated that only 13% is transported in solution, while the remaining 87% is in suspension 

(WHO 1988). 

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Upon entering the ocean, vanadium in suspension or adsorbed and/or absorbed onto particulate is 

deposited upon the sea bed (WHO 1988). The fate of the remaining dissolved vanadium is more 

complex. Only about 0.001% of vanadium entering the oceans is estimated to persist in soluble form 

(Byerrum et al. 1974). Adsorption/absorption and biochemical processes are thought to contribute to the 

extraction of vanadium from sea water (WHO 1988). Adsorption to organic matter as well as to 

manganese oxide and ferric hydroxide, demonstrated by the high particle-water partition coefficient of 

5.7x105 L/kg for the adsorption of manganese oxide in sea water, results in the precipitation of the 

dissolved vanadium (Wehrli and Stumm 1989; WHO 1988). Biochemical processes are also of 

importance in the partitioning from sea water to sediment (WHO 1988). Some marine organisms, in 

particular the ascidians (sea squirts), bioconcentrate vanadium very efficiently, attaining body 

concentrations approximately 10,000 times greater than the ambient sea water (Byerrum et al. 1974). 

Upon the death of the organism, the body burden adds to the accumulation of vanadium in silt (WHO 

1988). The extent to which either bioconcentration or adsorption dominates is uncertain (WHO 1988). 

In general, marine plants and invertebrates contain higher levels of vanadium than terrestrial plants and 

animals. In the terrestrial environment, bioconcentration is more commonly observed amongst the lower 

plant phyla than in the higher, seed-producing phyla. The vanadium levels in terrestrial plants are 

dependent upon the amount of water-soluble vanadium available in the soil, pH, and growing conditions. 

It has been found that the uptake of vanadium into the above-ground parts of many plants is low, although 

root concentrations have shown some correlation with levels in the soil (Byerrum et al. 1974). Certain 

legumes, such as Astralagus preussi, have been shown to be vanadium accumulators. Vanadium is 

believed to replace molybdenum as a specific catalyst in nitrogen fixation (Cannon 1963), and the root 

nodules of these plants may contain vanadium levels three times greater than those of the surrounding soil 

(Byerrum et al. 1974). Of the few plants known to actively accumulate vanadium, Amanita muscaria, a 

poisonous mushroom, has been demonstrated to contain levels up to 112 ppm (dry weight). Vanadium 

appears to be present in all terrestrial animals, but, in vertebrates, tissue concentrations are often so low 

that detection is difficult. The highest levels of vanadium in terrestrial mammals are generally found in 

the liver and skeletal tissues (Van Zinderen Bakker and Jaworski 1980; WHO 1988). No data are 

available regarding biomagnification of vanadium within the food chain, but human studies suggest that it 

is unlikely; most of the 1–2% vanadium that appears to be absorbed by humans following ingestion is 

rapidly excreted in the urine with no evidence of long-term accumulation (Fox 1987). 

The form of vanadium present in the soil is determined largely by the parent rock. Ferric hydroxides and 

solid bitumens (organic) constitute the main carriers of vanadium in the sedimentation process. Iron acts 

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VANADIUM 127 

6. POTENTIAL FOR HUMAN EXPOSURE 

as a carrier for trivalent vanadium due to the high affinity between trivalent vanadium and trivalent iron, 

and is responsible for its diffusion through molten rocks where it becomes trapped during crystallization. 

The mobility of vanadium in soils is affected by the pH of the soil. Relative to other metals, vanadium is 

fairly mobile in neutral or alkaline soils, but its mobility decreases in acidic soils (Van Zinderen Bakker 

and Jaworski 1980). Similarly, under oxidizing, unsaturated conditions, some mobility is observed, but 

under reducing, saturated conditions, vanadium is immobile (Van Zinderen Bakker and Jaworski 1980). 

In a 30-month field study to examine the movement of metal ions through a profile of an acidic loamy 

sand soil from the Upper Coastal Plain (South Carolina), <3% of the applied vanadium, as dissolved salt 

(vanadyl sulfate), was found to move below the surface 7.5 cm region (Martin and Kaplan 1998). 

Buchter et al. (1989) reported log Kd values for various metal ions in 11 soils from 7 states in the U.S. 

(Louisiana, South Carolina, Hawaii, Iowa, New Hampshire, New Mexico, and Florida). Log Kd values 

for vanadium (applied as ammonium vanadate) ranged from 1.035 in Calciorthid soil from New Mexico 

(pH 8.5, 0.44% total organic carbon [TOC], 70.0% sand, 19.3% silt, 10.7% clay) to 3.347 in Kula soil 

from Hawaii (pH 5.9, 6.62% TOC, 73.7% sand, 25.4% silt, 0.9% clay). 

6.3.2 Transformation and Degradation 

As an element, vanadium cannot be degraded in the environment, but may undergo various precipitation 

or ligand exchange reactions. Vanadium in compounds may undergo oxidation-reduction reactions under 

various environmental conditions. Vanadium can be complexed by various ligands present in the 

environment (e.g., fulvic and humic acids). Despite forming complexes with organic matter, it is 

generally not incorporated into organic compounds. Thus, transformation occurs primarily between 

various inorganic compounds during its movement through the environment, and biotransformation is not 

considered to be an important environmental fate process. Vanadium can exist in many different 

oxidation states, ranging from -2 to +5; however, under environmental conditions, vanadium can exist in 

the +3, +4, or +5 oxidation states, with the +5 oxidation state being the most prevalent under most 

environmental conditions (Crans et al. 1998). 

6.3.2.1 Air 

Vanadium-containing particulates emitted to the atmosphere from anthropogenic sources are frequently 

simple or complex oxides (Byerrum et al. 1974) or may be associated with sulfates (Zoller et al. 1973). 

Generally, lower oxides formed during combustion of coal and residual fuel oils, such as vanadium 

trioxide, undergo further oxidation to the pentoxide form, often before leaving the stacks (EPA 1985a). 

The average residence time for vanadium in the atmosphere is unknown as the particle size varies 

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VANADIUM 128 

6. POTENTIAL FOR HUMAN EXPOSURE 

considerably. An estimated residence time of about 1 day has been proposed for the settling of fly ash 

vanadium pentoxide when associated with hydrogen sulfate (EPA 1985a). 

6.3.2.2 Water 

Vanadium entering water by leaching from vanadium-containing rocks is rapidly oxidized from lesssoluble vanadium(III) to more-soluble vanadium(V), which is the most common oxidation state of 

vanadium found in surface waters (Byerrum et al. 1974; Crans et al. 1998). In water, vanadium can 

undergo hydrolytic reactions, forming oligomeric anionic species. The equilibrium of vanadium(V) in 

solution is sensitive to vanadium concentration, pH, ionic strength, and oxidation-reduction potential 

(Crans et al. 1998). The species of vanadium most likely to be found in sea water are (H2V4O13)

4-, 

HVO4

2-, and VO3- (Van Zinderen Bakker and Jaworski 1980). Vanadium(III) is only found in very 

reducing environments or is complexed to organic ligands (Crans et al. 1998). Vanadium is continuously 

precipitated from sea water by ferric hydroxides and organic matter (WHO 1988) and forms sediments on 

the seabed. 

6.3.2.3 Sediment and Soil 

There are about 65 different vanadium-containing minerals (Baroch 2006; Lide 2008). The main 

vanadium-containing minerals include carnotite, cuprodescloizite, descloizite, mottramite, patronite, 

roscoelite, and vanadinite (Crans et al. 1998). Vanadium exists in its +3 to +5 oxidation states in these 

minerals. Vanadium(V) is more soluble and is easily leached from soils into water. The vanadium 

oxides, carnotite, cuprodescloizite, descloizite, mottramite, and vanadinite, are mostly vanadium(V) 

minerals and comprise most of the vanadium-containing minerals. Roscoelite contains vanadium(III), 

and the exact chemical composition of patronite is not known (Crans et al. 1998). Weathering of rocks 

and minerals during soil formation may extract vanadium in the form of a complex anion that may remain 

in the soil or enter the hydrosphere. Vanadium remains in the soil after being precipitated from the 

weathering solution. This can be brought about by precipitation with polyvalent cations such as divalent 

calcium and divalent copper, by binding with organic complexing agents, adsorbing onto anion 

exchangers such as clay particles in the soil, and coprecipitating and adsorbing to hydrous ferric oxide in 

the soil (Van Zinderen Bakker and Jaworski 1980). In the presence of humic acids, mobile metavanadate 

anions can be converted to the immobile vanadyl cations resulting in local accumulation of vanadium 

(Van Zinderen Bakker and Jaworski 1980). 

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6. POTENTIAL FOR HUMAN EXPOSURE 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

Reliable evaluation of the potential for human exposure to vanadium depends in part on the reliability of 

supporting analytical data from environmental samples and biological specimens. Concentrations of 

vanadium 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 vanadium 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 vanadium 

in a variety of environmental media are detailed in Chapter 7. 

6.4.1 Air 

Levels of vanadium measured in ambient air vary widely between rural and urban locations, time of 

season, and geographical location. In general, urban locations often tend to have greater atmospheric 

levels of vanadium as compared to rural sites since there is a larger density of combustion sources capable 

of emitting particulate matter containing vanadium to the environment. Sweet et al. (1993) reported 

average vanadium concentrations of 3.0 and 3.0 ng/m3 (fine particles, <2.5 μm) and 3.7 and 3.0 ng/m3 

(coarse particles, 2.5–10 μm) in samples of inhalable particulate matter collected over a 3-year sampling 

period in southeast Chicago and East St. Louis Illinois, respectively. Average vanadium concentrations in 

fine and coarse particulate matter collected from a rural site in Bondville, Illinois were 0.8 and 1.2 ng/m3

, 

respectively (Sweet et al. 1993). Aerosol sampling (PM2.5 fraction) was conducted from 1988 to 1995 at a 

rural location in Underhill, Vermont (Polissar et al. 2001). A geometric mean concentration of 

0.82 ng/m3 was reported for vanadium, with seasonal maxima occurring during the winter and spring 

months and minimum concentrations observed during the summer months. A factor analysis method 

applied to the data determined that the most likely sources of the vanadium were oil fired power plants 

predominantly located in eastern Virginia, Pennsylvania, southern New York, New Jersey, Maryland, and 

Delaware (Polissar et al. 2001). Measurements obtained at five different rural sites in northwestern 

Canada were found have average vanadium concentrations of 0.72 ng/m3 (range 0.21–1.9 ng/m3

) (Zoller 

et al. 1973). Between the years 1965 and 1969, average ambient vanadium concentrations in rural air in 

the United States ranged from <1 to 40 ng/m3 (Byerrum et al. 1974), although some rural areas may have 

levels as high as 64 ng/m3 due to localized burning of fuel oils with a high vanadium content (WHO 

1988). Vanadium concentrations in air samples collected from a rural forest in Denmark that received 

heavy deposition from European cities were 11.5 and 4.4 ng/m3 in samples from 1979 to 1980 and 2002 

to 2005, respectively (Hovmand et al. 2008). 

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Northeastern locations in the United States typically have higher atmospheric levels of vanadium as 

compared to other regions of the country. U.S. cities were divided into two groups based on the levels of 

vanadium present in the atmosphere and geographic location (Zoller et al. 1973). The first group of cities 

is widely distributed throughout the United States and is characterized by ambient air vanadium 

concentrations that range from 3 to 22 ng/m3

, with an average concentration of 11 ng/m3 (approximately 

20 times that of remote areas). Cities in the second group, primarily located in the northeastern United 

States, had vanadium concentrations in air that ranged from 150 to 1,400 ng/m3 with an average of 

620 ng/m3 (Zoller et al. 1973). The variation is attributed to the use of large quantities of residual fuel oil 

for the generation of heat and electricity, particularly during winter months 

Atmospheric levels of vanadium at remote sites tend to be lower since both natural and anthropogenic 

emissions are typically negligible. Vanadium concentrations measured over the South Pole ranged from 

0.001 to 0.002 ng/m3 (WHO 1988) and are frequently 2 orders of magnitude smaller than those over the 

ocean at middle latitudes (WHO 1988). For example, vanadium concentrations in air measurements taken 

at nine rural sites located in the Eastern Pacific averaged 0.1 ng/m3 (range 0.02–0.8 ng/m3

). Atmospheric 

aerosols were collected from Mt. Everest in May–June, 2005; vanadium concentrations ranged from 

0.9 to 3.8 ng/m3

, with a mean of 1.4 ng/m3 (Cong et al. 2008). Vanadium concentrations at other remote 

locations of 0.044 and 0.0039 ng/m3 were reported for Greenland, 1988–1989 and Terra Nova Bay, 

Antarctica, 2000–2001, respectively (Cong et al. 2008; Mosher et al. 1993). 

Vanadium was detected in exhaust aerosol collected from the Elbtunnel, a major highway tunnel in 

Hamburg, Germany, at an average concentration of 14.8 ng/m3 (range: 7.6–36.9 ng/m3

) (Dannecker et al. 

1990). Fine atmospheric particulate PM2.5 (particles with diameters of <2.5 μm) were collected from 

November 2000 to September 2001 in Guaynabo, Puerto Rico, an urban industrialized area, and in 

Fajardo, Puerto Rico, a less polluted reference site (Figueroa et al. 2006). Vanadium concentrations in the 

PM2.5 were 40 and 1.4 ng/m3 for Guaynabo and Fajardo, respectively. Mean urban vanadium 

concentrations in winter and summer air (fine and course particulate combined) collected from the 

Birmingham University campus, Edgbaston, United Kingdom in January-February 1992 and July-August 

1992 were 11.2 and 3.5 ng/m3

, respectively. Vanadium concentrations were higher in the fine particle 

fraction, 7.6 and 2.3 ng/m3 (winter and summer), as compared to the coarse particle samples, 3.6 and 

1.2 ng/m3 (winter and summer) (Harrison et al. 1996). Mean vanadium concentrations in air samples 

from a central Copenhagen street (January–March 1992 and February–March 1993) and a city park 

(January–March 1992) were reported to be 12 and 10 ng/m3

, respectively (Nielsen 1996). Smith et al. 

(1996) reported mean vanadium concentrations in air samples collected from a city site, a rural site, and 

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6. POTENTIAL FOR HUMAN EXPOSURE 

an industrial site in Lahore, Pakistan in 1992–1993 of 127, 161, and 253 ng/m3, respectively. Mean 

vanadium concentrations in air samples of 10, 180, and 110 ng/m3 were reported in Karachi, Pakistan; 

Calcutta, India; and Bombay, India, respectively (Smith et al. 1996). Schroeder et al. (1987) reported 

concentration ranges of vanadium associated with particulate matter in the atmosphere: 0.001–14 ng/m3 

(remote areas); 2.7–97 ng/m3 (rural); 10–130 ng/m3 (urban Canada); 0.4–1,460 ng/m3 (urban United 

States); 11–73 ng/m3 (urban Europe); and 1.7–180 ng/m3 (urban other). 

Vanadium and nickel were measured in air particulate samples collected during and after the Kuwait oil 

fires (from March 1991 to July 1992) at Dhahran, Saudi Arabia (Sadiq and Mian 1994). Vanadium 

concentrations ranged from not detected to 1,165.8 ng/m3 in the inhalable (PM10, <10 μm) and from not 

detected to 160.26 ng/m3 in the total suspended particulate. The minimum vanadium concentration was 

found in samples collected in December 1991 and gradually increased through May 1992. 

Air sampling in homes in two New York counties in the winter of 1986 measured various contaminants in 

the indoor air (Koutrakis et al. 1992). Mean vanadium concentrations in indoor air of non-source homes 

(no kerosene heaters, wood stoves, or cigarette smokers), wood-burning homes, kerosene heater homes, 

and smoking homes were 5, 4, 6, and 6 ng/m3

, respectively. Miguel et al. (1995) reported vanadium 

concentrations in samples of indoor air from non-industrial office workplaces and restaurants in the cities 

of Sao Paulo and Rio de Janeiro, Brazil in the summer of 1993 ranging from less than the detection limit 

to 0.360 μg/m3

. Kinney et al. (2002) reported mean winter and summer vanadium concentrations of 

9.49 and 4.17 ng/m3 in indoor air (particle-associated) in 38 homes sampled in 1999 in the West Central 

Harlem section of New York City. A mean vanadium concentration of 0.8 ng/m3 was reported inside 

patrol cars of ten nonsmoking North Carolina State Highway Patrol troopers during 25 work days (3 pm 

to midnight shift) during August–October of 2001 (Riediker et al. 2003). 

6.4.2 Water 

Levels of vanadium in fresh water illustrate geographic variations produced by differences in effluents 

and leachates, from both anthropogenic and natural sources, entering the water table. Vanadium 

concentrations in water can range from approximately 0.2 to >100 μg/L depending on geographical 

location (Sepe et al. 2003). Vanadium was detected in 3,387 of 3,625 surface water samples recorded in 

the STORET database for 2007–2008 at concentrations ranging from 0.04 to 104 μg/L in samples where 

vanadium was detected (EPA 2009a). Measurements of vanadium in such natural fresh waters as the 

Animas, Colorado, Green, Sacramento, San Joaquin, and San Juan Rivers, as well as some fresh water 

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supplies in Wyoming, range from 0.3 to 200 μg/L (Byerrum et al. 1974; Van Zinderen Bakker and 

Jaworski 1980). The presence of naturally occurring uranium ores resulted in rivers in the Colorado 

Plateau containing vanadium concentrations of up to 70 μg/L, and in Wyoming, vanadium concentrations 

in water were found to range from 30 to 220 μg/L (Byerrum et al. 1974). 

Taylor et al. (2001) reported vanadium concentrations of <0.05 μg/L in water collected in June and 

September 1994 from the Alamosa River, Colorado and 6.2 μg/L in water collected in September 1992 

from Big Arsenic Spring, New Mexico. Saleh and Wilson (1999) reported various metal concentrations 

in surface water from the Houston Ship Channel, Texas; vanadium concentrations ranged from 4.062 to 

115.600 μg/L in samples from Buffalo Bayou and the Washburn Tunnel, respectively. Coal mining 

activity in the west-central region of Indiana has resulted in a number of sites where surface waters are 

contaminated with acidic mine drainage. Surface water samples collected from 12 locations in westcentral Indiana that have been contaminated with acidic mine drainage were reported to contain vanadium 

at concentrations ranging from 0.17 to 0.66 mg/L (Allen et al. 1996). Kennish (1998) reported vanadium 

concentrations ranging from 1.0 to 38 nmol/L (0.05–1.9 μg/L) in waters from U.S. estuaries and 

32 nmol/L (1.6 μg/L) in U.S. coastal marine waters. 

Levels in sea water are considerably lower than those in fresh water because much of the vanadium is 

precipitated (Byerrum et al. 1974; Van Zinderen Bakker and Jaworski 1980). Vanadium concentrations 

measured usually average 1–3 μg/L (Sepe et al. 2003; Van Zinderen Bakker and Jaworski 1980), although 

levels as high as 29 μg/L have been reported (Byerrum et al. 1974). The total content of vanadium in sea 

water has been estimated to be 7.5x1012 kg (7.5x109 metric tons) (Byerrum et al. 1974). Mean vanadium 

concentrations ranging from 2.08 to 2.60 μg/L were reported in seawater samples collected along the 

Saudi coast of the Arabian Gulf (Sadiq et al. 1992b). 

Fiorentino et al. (2007) measured vanadium concentrations in groundwater collected from the southwest 

of the Province of Buenos Aires, Argentina; all samples contained vanadium, and concentrations ranged 

from 0.05 to 2.47 mg/L. Groundwater samples collected from 104 monitoring wells from shallow 

aquifers beneath an industrial city in the Eastern Province of Saudi Arabia contained vanadium 

concentrations that ranged from 0.04 to 55.69 μg/L, with a mean concentration of 7.46 μg/L (Sadiq and 

Alam 1997). 

Vanadium is on the EPA Drinking Water Contaminant Candidate List (CCL). The contaminants on this 

list are known or anticipated to occur in public water systems; however, they are currently not regulated 

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VANADIUM 133 

6. POTENTIAL FOR HUMAN EXPOSURE 

by existing national primary drinking water regulation. Research in ongoing to determine whether 

regulations are needed (EPA 2008b). 

Mean vanadium concentrations in tap water collected from homes participating a dietary study in EPA 

Region V (Indiana, Illinois, Michigan, Minnesota, Ohio, and Wisconsin) for the National Human 

Exposure Assessment Survey (NHEXAS) were 1.2 and 1.0 μg/L, respectively, in samples collected after 

running the water at high velocity for 3 minutes (flushed tap water) and after there had been no usage of 

any tap water or toilet in the home for the previous 4 hours (standing tap water) (Thomas et al. 1999). 

As part of the National Water-Quality Assessment Program of the U.S. Geological Survey (USGS), water 

samples were collected during 1991–2004 from domestic wells (private wells used for household drinking 

water) for analysis of drinking-water contaminants. Vanadium was detected in 452 of 662 samples, with 

a median concentration of 1.29 μg/L (USGS 2009c). 

Lagerkvist et al. (1986) summarized older reports from the 1960s and 1970s regarding vanadium 

concentrations in drinking water. One report stated that 91% of drinking water samples analyzed from 

U.S. sources had vanadium concentrations below 10 μg/L, with an average concentration of 4.3 μg/L. In 

another report, the typical vanadium concentrations in drinking water were about 1 μg/L. 

6.4.3 Sediment and Soil 

Vanadium is widely distributed in the earth’s crust at an average concentration of 100 ppm 

(approximately 100 mg/kg) (Byerrum 1991). The level of vanadium measured in soil is closely related to 

the parent rock type (Van Zinderen Bakker and Jaworski 1980; Waters 1977). A range of 3–310 mg/kg 

has been observed, with tundra podsols and clays exhibiting the highest concentration, 100 and 

300 mg/kg, respectively (Byerrum et al. 1974). The average vanadium content of soils in the United 

States is 200 mg/kg (Byerrum et al. 1974) and seems to be most abundant in the western United States, 

especially the Colorado Plateau (Cannon 1963; Grayson 1983). 

Gallagher et al. (2008) measured various metal concentrations in soils collected during the summer of 

2005 from a site in Jersey City, New Jersey on the west bank of Upper New York Bay. This land was 

originally an intertidal mud flat and a salt marsh that was filled during 1860–1919 with material 

consisting of mostly debris from construction projects and refuse from New York City. It was used as a 

railroad yard until 1967. The site was then transferred to the New Jersey Division of Parks and Forestry 

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in 1970. Vanadium concentrations in soil collected from this site ranged from below the detection limit 

(<0.01 μg/g) to 317 μg/g, with a median value of 56.4 μg/g (Gallagher et al. 2008). Metal concentrations 

were measured in two alluvial soils from the lower Mississippi River Delta. Median vanadium 

concentrations of 3.2 and 3.8 μg/g were reported in freshly deposited alluvium soil from Bonnet Carré 

Spillway and in urban soil samples from New Orleans, respectively (Mielke at el. 2000). 

Various trace elements were measured in 13 surface soils collected from southwestern Saskatchewan, 

Canada (Mermut et al. 1996). Fertilizers and pesticides are the two major anthropogenic sources of trace 

elements in the Canadian Prairies. Vanadium concentrations ranged from 31.75 mg/kg in Hatton soil (0– 

13 cm, pH 6.2, 1.32% organic content [OC], 6% clay) to 180.06 mg/kg in Sceptre soil (90–105 cm, pH 

8.0, 0.85% OC, 73% clay). Clay soils were found to contain more vanadium that other soils (Mermut et 

al. 1996). Vanadium concentrations in 16 soil samples collected in May 2000 in the vicinity of a cement 

plant in Catalonia, Spain ranged from 5.6 to 12.4 mg/kg dry weight. These values were generally lower 

than vanadium levels found in urban areas (Schuhmacher et al. 2002). The geometric mean vanadium 

concentrations in 112 samples street dust and 40 samples of urban soil collected in Aviles, Northern Spain 

were 28.1 (range 25.0–34.0) and 34.1 (22.0–67.0) μg/g, respectively (Ordóñez et al. 2003). 

Metal contamination was determined in soil samples collected from 10 locations in the Hafr Al Batin 

Area (Saudi Arabia) near the Saudi/Kuwaiti border following the Gulf War (1990–1991) (Sadiq et al. 

1992a). Oil burning in Kuwait, atmospheric fallout of particulates form the use of explosives in the Gulf 

War, and other war-related ground activities created air pollution problems in the countries neighboring 

Kuwait. Vanadium concentrations in soil ranged from 2 mg/kg collected at the most distant sampling site 

from the Kuwaiti border (15–25 cm depth) to 59 mg/kg collected from a sampling site near the border (0– 

5 cm depth). Vanadium concentrations in soil samples were found to decrease with increasing distance 

from the border (Sadiq et al. 1992a). Various metal concentrations were determined in 25 surface soil 

samples from Surat, India, an industrial area. Vanadium concentrations ranged from 141.9 to 

380.6 mg/kg with a mean 284.8 mg/kg (Krishna and Govil 2007). 

Mean vanadium concentration of 44 and 82 mg/kg were reported in the sediments of Lake Huron and 

Lake Superior. Vanadium was detected in sediment samples from the Georgian Bay and North Channel 

(Lake Huron) at mean concentrations of 67 and 66 mg/kg, respectively (International Joint Commission 

1978). Heit et al. (1984) reported vanadium concentrations in Rocky Mountain Lake sediments of 

27.3 and 15 mg/kg dry weight in Lake Husted surface (0–2 cm) and subsurface sediments, respectively, 

and 35 and 32.8 mg/kg dry weight in Lake Louise surface and subsurface sediments, respectively. 

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6. POTENTIAL FOR HUMAN EXPOSURE 

Vanadium concentrations of 55 and 43 mg/kg dry weight were reported in surface sediments from Lake 

Haiyaha and The Loch, two other Rocky Mountain lakes. Total vanadium concentrations of 136 and 

222 mg/kg dry weight were reported in sediment samples from the Texas City channel and Ashtabula 

River, Ohio (Engler 1979). 

Four sediment cores collected January 1996 from Central Park Lake New York City, New York were 

analyzed for various metals including vanadium; average vanadium concentrations ranged from 87 μg/g 

at a depth of 44–47 cm to 665 μg/g at a depth of 12–14 cm (Chillrud et al. 1999). In 1966, approximately 

35% of the residual fuel oil used in New York City was from Venezuela. Vanadium is enriched in the 

sulfur-rich petroleum from Venezuela. Comparison of the approximate year of deposition to vanadium 

concentration in the sediment for Central Park Lake showed that vanadium levels in sediments from 

Central Park Lake were found to decrease after restrictions on sulfur content of fuel oils used in New 

York City were introduced starting in 1966. The average vanadium concentration peaks at 665 μg/g in 

sediments from 12 to 14 cm depth, which correlates with approximately with the mid 1960s (Chillrud et 

al. 1999). Trace metal concentrations were measured in sediment cores collected in February 1992 from 

the Gulf of Mexico; the average vanadium concentration was 47.78 μg/g and ranged from 15.6 to 

117.5 μg/g (Macias-Zamora et al. 1999). Metal concentrations were measured in sediment collected 

during early and late autumn of 1993 and 1994 from 16 locations in Lake Erie, the Niagara River, and 

Lake Ontario; vanadium concentrations ranged from 6.0 to 31.1 μg/kg dry weight in these sediment 

samples (Lowe and Day 2002). 

Vanadium concentrations in surface sediments collected during 1988–1991 from the Great Astrolabe 

Lagoon, Fiji ranged from 2 to 726 mg/kg dry weight. This lagoon, which encompasses a number of small 

volcanic islands, is considered to be a pristine marine environment with minimal human impact in this 

study (Morrison et al. 1997). 

A diesel oil spill occurred in April 2002 from a pipeline on the Pacific side of Mexico, in Salina Cruz into 

the San Pedro stream, Xadani estuary, and the Superior Lagoon mouth (Salazar-Coria et al. 2007). 

Vanadium concentrations in sediment collected after the spill during the dry and rainy seasons were 

110.5 and 123.0 mg/kg dry weight at the San Pedro site, 95.4 and 148.9 mg/kg dry weight at the Piedra 

Estuary, 113.3 and 107.7 mg/kg dry weight at the Xadani estuary, and <5.0 mg/kg dry weight at Superior 

Lagoon, respectively. Vanadium concentrations in a reference site, upstream from the spill were below 

the limit of detection, <5.0 mg/kg dry weight. 

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Chemical contamination was measured in sediment from the Shuaiba Industrial Area (SIA), a coastal area 

in Kuwait that receives industrial effluent (Beg et al. 2001). The SIA contains a petrochemical company, 

three refineries, two power desalination plants, a melamine company, an industrial gas corporation, a 

paper products company, and other smaller industrial plants, as well as a large harbor. Vanadium 

concentrations were reported to range from 9.8 to 146.0 mg/kg dry weight in sediment from Shuaiba 

coastal area (Beg et al. 2001). 

6.4.4 Other Environmental Media 

The majority of foods have naturally occurring low concentrations of vanadium, many of them ≤1 ng/g 

(Byrne and Kosta 1978). Food items containing the highest levels of vanadium include ground parsley 

(1,800 ng/g dry weight), freeze-dried spinach (533–840 ng/g), wild mushrooms (50–2,000 ng/g dry 

weight), and oysters (455 ng/g wet weight) (Byrne and Kosta 1978). Intermediate levels are found in food 

types such as certain cereals (ranging from 0.7 ng/g in maize to 30 ng/g in Macedonian rice), fish (ranging 

from 3.5 ng/g in mackerel to 28 ng/g in freeze-dried tuna), and liver (ranging from 7.3 ng/g in beef to 

38 ng/g in chicken) (Byrne and Kosta 1978). In general, seafoods have been found to be higher in 

vanadium than terrestrial animal tissues (WHO 1988). Vanadium concentrations in cow milk ranging 

from about 0.2 to 10 μg/kg also have been reported in older reports from the late 1970s and early 1960s, 

respectively (Lagerkvist et al. 1986). Pennington and Jones (1987) surveyed 234 foods from a 1984 

collection of the FDA’s Total Diet Study for various trace elements including vanadium. Sixty-four 

percent of the Total Diet Foods had vanadium concentrations of <0.5 μg/100 g and 88% had vanadium 

concentrations of <2 μg/100 g. Foods with the highest vanadium concentrations included breakfast 

cereals, canned fruit juices, fish sticks, several vegetables, sweeteners, wine, and beer. The data from this 

survey are summarized in Table 6-3. 

Vanadium, as elemental vanadium or vanadyl sulfate, also may be found in various commercial nutritional 

supplements and multivitamins; vanadium concentration can range from 0.0004 to 12.5 mg in these 

supplements depending on the serving size recommended by the manufacturer (NLM 2009). Vanadium 

has been used in supplements for individuals with diabetes; intakes of 30–150 mg/day for vanadyl sulfate 

(9–47 mg V/day) and 125 mg/day for sodium metavanadate (52 mg V/day) have been reported (IOM 

2001; Smith et al. 2008). 

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Table 6-3. Vanadium Levels in Food 

Mean Range 

Food item (μg/100 g) 

Adult foods 

Milk, yogurt, and cheese 0.1 0–0.6 

Meat, fish, and poultry 1.0 0–11.9 

Eggs 0.3 0.2–0.4 

Nuts 0.6 0.2–1.0 

Legumes 0.1 0–0.3 

Grains and grain products 2.3 0–14.7 

Fruits and fruit juices 0.6 0–7.1 

Vegetables 0.6 0–7.2 

Mixed dishes and soups 0.6 0–2.0 

Desserts 0.9 0–2.9 

Sweeteners 2.3 0.4–4.7 

Fats and sauces 0.3 0–0.6 

Beverages 0.7 0–3.3 

Infant foods 

Formulas 0.1 0–0.2 

Meat and poultry 0.5 0–0.8 

Cereals 1.6 1.2–2.0 

Fruit and juices 1.6 0–13.4 

Vegetables 0.4 0–1.1 

Mixed dishes 0.2 0–0.6 

Custard 0.2 No data 

Source: Pennington and Jones 1987 

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Gummow et al. (2005) reported a study that looked at the commonly consumed tissues and milk 

concentrations of vanadium in cattle in South Africa that were extensively farmed over a 5-year period 

(1999–2004) in an area adjacent to a vanadium processing plant that was known to have higher-thannormal background levels of vanadium. The group of cattle included two groups, one group of 10 cattle 

that was farmed adjacent to the mine, with an average exposure of 1,229 mg V/day, and another group of 

20 cattle that was farmed 2–3 km from the first group with an exposure about half that of the high 

exposure group (mean=532 mg V/day). Cattle in the trial were monitored over a 5-year period and six 

cohorts of animals were slaughtered over this period. Concentrations of vanadium in commonly 

consumed tissues (liver, kidney, fillet, and triceps) ranged from <0.05 to 11.51 mg/kg (wet-weight) in 

triceps and liver, respectively, over both groups. The median concentration of vanadium in milk was 

0.23 mg/kg (range: <0.05–1.92 mg/kg) over both groups. Concentrations of vanadium in tissues from the 

group raised adjacent to the mine and those raised 2–3 km away were not differentiated in the 

presentation of the data. 

Concentrations of various metals, including vanadium, were measured in samples of six fish species 

collected during 1997 and 1998 along the coast of the Adriatic Sea. Vanadium concentrations (μg/kg 

fresh weight) were 45.3–74.4 (anchovy), <4.0–4.8 (angler), <4.0 (hake), 6.7–29.8 (mackerel), 11.8– 

32.4 (red mullet), and <4.0–2.9 (sole) (Sepe et al. 2003). 

Vanadium is found in almost all coals used in the United States, with levels ranging from extremely low 

to 10 g/kg (Byerrum et al. 1974; WHO 1988). Eastern U.S. coal has an average content of 30 ppm, 

western coal has an average content of 15 ppm, and coal from the interior contains an average of 34 ppm 

(Byerrum et al. 1974). The average vanadium content of bituminous and anthracite coal is 30 and 

125 ppm, respectively (Byerrum et al. 1974). 

Vanadium is usually the most abundant trace metal found in petroleum samples (Amorim et al. 2007). 

Vanadium concentrations in petroleum may be as high as 1,500 mg/kg, while some crude oils contain 

<0.1 mg/kg. Vanadium occurs predominantly as the vanadyl ion (VO2+) in the form of organometallic 

complexes with porphyrins. Vanadyl porphyrins originated from the formation of crude oil; the vanadyl 

ion was substituted for magnesium ion (Mg2+) in the chlorophylls of plants. Other vanadium complexes 

in petroleum include non-porphyrin and organic acid complexes (Hovmand et al. 2008). Mamane and 

Pirrone (1998) reported that residual fuel oils manufactured from U.S. crude oils contain 25–50 ppm of 

vanadium. Venezuelan, Middle Eastern, and North African residual oils have vanadium concentrations of 

200–300, 10–20, and 50–90 ppm, respectively. Vanadium is highly enriched relative to other elements in 

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heavy fuel oils due to vanadium porphyrins. Because of this, vanadium is used as a marker for emissions 

from fuel oil combustion (Mamane and Pirrone 1998). 

Vanadium concentrations ranging from 0.49 to 5.33 μg/g in were measured in 45 different brands of 

whole unsmoked cigarettes. Mean vanadium concentrations of 1.11, 0.67, 0.09, and 0.33 μg/cigarette in 

whole unsmoked cigarettes, ash, filter, and smoke of six different brands of cigarettes, respectively 

(Adachi et al. 1998a). 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

Food is the main source of vanadium intake for humans (Lagerkvist et al. 1986). Higher dietary intake 

levels are possible when food is grown in soil contaminated with greater than background levels of 

vanadium. Vanadium in food is mainly ingested as VO2+ (vanadyl, V4+) or HVO4

2- (vanadate) (Sepe et al. 

2003). Byrne and Kučera (1991) reported a daily intake of vanadium of 10–20 μg. The dietary intake of 

vanadium estimated from the combined total intake of solids and liquids from a dietary study in EPA 

Region V (Indiana, Illinois, Michigan, Minnesota, Ohio, and Wisconsin) for the NHEXAS was 

0.34 μg/kg of body weight/day (Thomas et al. 1999). Pennington and Jones (1987) surveyed 234 foods 

from a 1984 collection of the FDA’s Total Diet Study for various trace elements including vanadium. 

Based on this survey, estimated daily intakes of vanadium ranged from 6.2 μg/day for 60–65-year-old 

females to 18.3 μg/day for 25–30-year-old males. Table 6-4 summarizes the estimated daily intakes of 

vanadium for the various age groups in this study. 

Various metal concentrations were determined in foods (meat, fish and seafood, pulses [lentil, bean], 

cereals, vegetables, fruits, tubers, whole milk, yogurt, eggs, and sugar) purchased from local markets, 

supermarkets, and grocery stores in zones of Tarragona County (Catalonia, Spain) near a hazardous waste 

incinerator, which has been operating since 1999 (Bocio et al. 2005). A dietary intake for vanadium of 

28.9 μg/day was estimated for an average adult man (70 kg body weight) in Tarragona County (Catalonia, 

Spain). Fish and seafood (hake, sardine, and mussels) were the only foods that contributed to this value; 

vanadium was not detected in any other foods that were surveyed. The detection limit for vanadium in 

this study was 0.25 μg/g (Bocio et al. 2005). Sepe et al. (2003) reported an 11–34% contribution to the 

daily vanadium ingestion from fish collected during 1997 and 1998 along the coast of the Adriatic Sea for 

the population in this area. 

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Table 6-4. Estimated Daily Vanadium Intake 

Age group Intake (μg/day) 

6–11 Months 6.7 

2 Years 6.5 

14–16 Years, female 7.1 

14–16 Years, male 11.0 

25–30 Years, female 8.1 

25–30 Years, male 18.3 

60–65 Years, female 6.2 

60–65 Years, male 10.6 

Source: Pennington and Jones 1987 

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Gummow et al. (2005) estimated dietary intakes of vanadium from the consumption of cattle in South 

Africa that were raised over a 5-year period (1999–2004) in an area adjacent to a vanadium processing 

plant that was known to have higher-than-normal background levels of vanadium. The median potential 

daily intakes of vanadium in the diet of humans consuming beef from these cattle were estimated to be 

1.9, 1.8, 2.9, and 1.2 μg/kg body weight/day for consuming fillet, triceps, liver, and kidney, respectively. 

The median potential daily intake of vanadium from drinking milk of these cattle was estimated to be 

4.6 μg/kg body weight/day (Gummow et al. 2005). 

As compared to food, drinking water is a less important source of vanadium exposure for the general 

population. Thomas et al. (1999) reported mean vanadium concentrations of 1.2 and 1.0 μg/L in flushed 

tap water and standing tap water samples from Indiana, Illinois, Michigan, Minnesota, Ohio, and 

Wisconsin, respectively. Assuming a daily intake of 2 L of water (EPA 1988), a daily intake of 

approximately 2 μg of vanadium from tap water can be estimated. 

Vanadium is present in many dietary supplements, including multivitamin and mineral supplement 

formulations, as well as products marketed for weight control, bodybuilding, and diabetes control (NTP 

2008). The National Library of Medicine’s (NLM’s) Dietary Supplements Label Database lists 

>100 products containing vanadium (NLM 2009). Many of these products contain <10 μg of vanadium. 

Some of these products contain up to 12.5 mg of vanadium depending on the serving size recommended 

by the manufacturer. Three containing vanadyl sulfate are also listed on the NLM’s Dietary Supplements 

Label Database, containing 0.01–1.66 mg of vanadyl sulfate (0.003–0.52 mg vanadium) depending on the 

serving size recommended by the manufacturer (NLM 2009). According to the Third National Health 

and Nutrition Examination Survey on supplement use of vanadium, the median intake of supplement 

vanadium by adults was approximately 9 μg/day (IOM 2001). Vanadium has been used in supplements 

for individuals with diabetes. Intakes of 30–150 mg/day for vanadyl sulfate (9–47 mg V/day) and 

125 mg/day for sodium metavanadate (52 mg V/day) have been reported (IOM 2001; Smith et al. 2008). 

Vanadyl sulfate supplements have been used as well by weight training athletes at levels up to 60 mg/day 

(18.6 mg V/day) (Barceloux 1999). Consumption of some vanadium-containing supplements may result 

in intakes of vanadium that would exceed those from food and water. 

The general population may also be exposed to airborne vanadium through inhalation, particularly in 

areas where use of residual fuel oils for energy production is high (Zoller et al. 1973). Assuming air 

concentrations of approximately 50 ng/m3

, Byrne and Kosta (1978) estimated a daily intake of 1 μg 

vanadium, assuming an average inhalation rate of 20 m3

/day. In addition, cigarette smoke can contribute 

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6. POTENTIAL FOR HUMAN EXPOSURE 

vanadium exposure. Koutrakis et al. (1992) estimated an emission rate for vanadium from cigarette 

smoke of 373 ng/cigarette; approximately 0.04 μg of vanadium is given off by in the smoke of one 

cigarette. 

Lin et al. (2004) reported vanadium concentrations in the blood of 52 Taiwanese college students (19– 

42 years old). None of these students had occupational exposure to vanadium and five of the students (all 

male) were smokers. The average vanadium concentration in was 0.42 ng/mL in all students, with a 

range of 0.01–1.20 ng/mL. The average vanadium concentration in blood for the female students was 

0.37 ng/L and the average concentration for nonsmoking male students was 0.44 ng/L; the average for the 

five smokers was 0.47 ng/mL. Concentrations of vanadium in human blood reported in the literature 

range from 0.032 to 0.095 ng/mL (Kučera et al. 1992; Lin et al. 2004; Sabbioni et al. 1996). The average 

vanadium concentration in blood of individuals that have occupational exposure is 33.2 (3.10–217) 

ng/mL (Lin et al. 2004). Sabbioni et al. (1996) surveyed the literature for reports on vanadium 

determination in human blood, serum, and urine and reported that vanadium concentrations in blood 

and/or serum ranged from 0.45–18.4 nmol/L (0.022–0.937 μg/L) and concentrations in urine ranged from 

4.16–15.7 nmol/L (0.212–0.800 μg/L). Normal concentrations of vanadium in blood and serum were 

reported to be around 1 nmol/L (0.05 μg/L) and around 10 nmol/L (0.5 μg/L) for urine. Nixon et al. 

(2002) reported similar values for vanadium concentrations of 0.05 and 0.24 μg/L in serum and urine, 

respectively, in healthy individuals from a literature survey. Vanadium concentrations ranging from 30 to 

160 μg/kg have been reported in hair (Fernandes et al. 2007; Kučera et al. 1992). No functional role for 

vanadium in higher animals or humans has been identified (IOM 2001). 

6.6 EXPOSURES OF CHILDREN 

This section focuses on exposures from conception to maturity at 18 years in humans. Differences from 

adults in susceptibility to hazardous substances are discussed in Section 3.7, Children’s Susceptibility. 

Children are not small adults. A child’s exposure may differ from an adult’s exposure in many ways. 

Children drink more fluids, eat more food, breathe more air per kilogram of body weight, and have a 

larger skin surface in proportion to their body volume. A child’s diet often differs from that of adults. 

The developing human’s source of nutrition changes with age: from placental nourishment to breast milk 

or formula to the diet of older children who eat more of certain types of foods than adults. A child’s 

behavior and lifestyle also influence exposure. Children crawl on the floor, put things in their mouths, 

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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). 

Similar to adults, dietary intake of vanadium through the ingestion of food is the primary exposure route 

for children. This route of exposure is particularly relevant when the food is contaminated with soil 

because soil contains an average of about 10,000 times as much vanadium as is found in many biological 

materials (Byrne and Kosta 1978). Since young children tend to ingest soil and dust during daily 

activities, children may be exposed to vanadium through the ingestion of soil or dust. Cigarette smoke 

can contribute vanadium exposure of children. Approximately 0.04 μg of vanadium is given off by in the 

smoke of one cigarette (Koutrakis et al. 1992). 

Blood and hair samples were collected from 23 children living in the vicinity of a metallurgical plant 

producing vanadium pentoxide (V2O5) approximately 20 km from Prague, Czechoslovakia (Kučera et al. 

1992). These children may have been exposed to vanadium due to contamination of well water. A 

control group consisted of 17 children from a nonpolluted rural area about 30 km from Prague. Median 

vanadium concentrations in hair samples from the exposed and control groups did not differ significantly, 

and were 98 and 88 μg/kg, respectively. The median vanadium concentration in the blood of the exposed 

children and the children in the control group were 0.078 and 0.042 μg/L, respectively, and were 

considered significantly different (Kučera et al. 1992). 

Concentrations of vanadium in human breast milk of 0.46, 0.27, 0.21, 0.11, 0.69, and 0.13 μg/g have been 

reported in samples from Nigeria, Zaire, Guatemala, Hungary, Philippines, and Sweden, respectively 

(Nriagu et al. 1992). Ikem et al. (2002) reported mean vanadium concentrations of 0.001, 0.002, and 

0.003 μg/mL in milk-based liquid formulas from the United Kingdom, milk based powdered formulas 

from the United States, and soy-based powder formulas from the United States, respectively. Vanadium 

was not detected in milk-based powdered formulas from Nigeria and the United Kingdom. Daily intakes 

of vanadium for infants in the United States were estimated to be 0.05, 3.5, and 2.8 μg/day for milk-based 

powder formulas, soy-based powder formulas, and hypoallergenic powder formulas from the United 

States, respectively (Ikem et al. 2002). 

Pennington and Jones (1987) reported concentrations in infant foods that ranged from 0.1 μg/100 g in 

formulas to 1.6 μg/100 g in cereals, fruits, and juices. Daily intakes of vanadium of 6.7, 6.5, 7.1, and 

11.6 μg/day for children aged 6–11 months, 2 years, 14–16 years (female), and 14–16 years (male), 

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respectively, were estimated based on this food survey. A summary of these data are found in Tables 6-3 

and 6-4. 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

Populations consuming foods grown in soils supplemented with fertilizers or sludge containing vanadium 

or in soils naturally high in vanadium content may be exposed to concentrations higher than background 

levels. This is due primarily to surface deposition. 

Populations in areas with high levels of residual fuel oil consumption may also be exposed to abovebackground levels of vanadium, both from increased particulate deposition upon food crops and soil in 

the vicinity of power plants and higher ambient air levels (Zoller et al. 1973). Cities in the northeastern 

United States frequently fall into this category, where ambient air levels often range from 150 to 

1,400 ng/m3 (Zoller et al. 1973). 

Personal exposure measurements were conducted on 18 boilermakers and 11 utility workers before and 

during a 3-week overhaul of a large oil-fired power plant (Liu et al. 2005). Utility workers included 

mechanics, welders, laborers, painters, precipitator operators, work crew supervisors, and laboratory 

workers. During the overhaul, boilermakers worked both inside and outside the boiler and were more 

likely to be exposed to ash. Utility workers worked outside the boiler in adjacent areas and had little 

direct contact with the ash. Time-weighted average exposures for the boilermakers and the utility 

workers were 1.20 and 1.10 μg/m3

, respectively, before the overhaul work and 8.9 and 1.4 μg/m3, 

respectively, during the overhaul work (Liu et al. 2005). 

Full-shift, personal breathing sampling was conducted on nine employees working in the finishing and 

cut-off areas (torch cutting, pneumatic hammer, water blast, and the five finishing workstations) of a 

titanium investment casting plant in Redmond, Oregon during July 7–10, 2003. Respirable vanadium 

pentoxide concentrations ranged from 0.0005 to 0.0089 mg/m3

, with the highest measurement of 

0.123 mg/m3 in the torch cutting area (NIOSH 2004). 

Vanadium, as elemental vanadium or vanadyl sulfate, may be found in various commercial nutritional 

supplements and multivitamins; vanadium concentration can range from 0.0004 to 12.5 mg in these 

supplements depending on the serving size recommended by the manufacturer (NLM 2009). Vanadium 

supplements have be used and studied as supplements for diabetic individuals. Intakes of 30–150 mg/day 

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for vanadyl sulfate (9–47 mg V/day) and 125 mg/day for sodium metavanadate (52 mg V/day) have been 

reported (IOM 2001; Smith et al. 2008). Vanadyl sulfate supplements have been used as well by weight 

training athletes at levels up to 60 mg/day (18.6 mg V/day) (Barceloux 1999). Consumption of some 

vanadium containing supplements may result in intakes of vanadium that would exceed that from food 

and water. 

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 vanadium 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 vanadium. 

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. The physical and chemical properties of vanadium and its 

compounds are reasonably well documented (see Tables 4-1 and 4-2). No data needs are indentified. 

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 2007, became available in March of 2009. This database is updated yearly and should 

provide a list of industrial production facilities and emissions. 

Companies involved in the vanadium production industry (see Table 5-3), uses of vanadium and various 

vanadium compounds (Lide 2008; USGS 2009a), and various sources of release are also available (see 

Table 6-1). There is little information available describing the amounts of vanadium consumed in each 

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6. POTENTIAL FOR HUMAN EXPOSURE 

use category or the quantities recycled and disposed of within the United States. Few details were found 

regarding the specific disposal methods used (HSDB 2009; USGS 2009a). Information in each of these 

areas would provide an indication of the potential for human exposure as a result of disposal practices. 

Environmental Fate. The relative contributions of natural (Byerrum et al. 1974; Zoller et al. 1973) 

and anthropogenic sources (Byerrum et al. 1974; TRI07 2009) of vanadium to the different environmental 

media are available. Partitioning between the various media is described, in particular from soil to water 

and from water to sediment (Wehrli and Stumm 1989; WHO 1988), but specific coefficients are not 

available in many studies. Information on the transport of vanadium within each media is available (Duce 

and Hoffman 1976; Martin and Kaplan 1998; Wehrli and Stumm 1989; WHO 1988; Zoller et al. 1973). 

Bioavailability from Environmental Media. Occupational studies on the uptake of vanadium via 

the inhalation route exist; however, data suggesting that this route is relevant with regard to hazardous 

waste sites are lacking. Dermal absorption data are limited; however, it is likely that absorption via this 

route is low since vanadium, like other metals, has low solubility in lipids (WHO 1988). The daily 

intakes of vanadium from air, food, and water are generally small (Bocio et al. 2005; Thomas et al. 1999; 

Zoller et al. 1973). Seafood or milk from cows raised in an area with vanadium contamination can be a 

more significant dietary contribution of vanadium (Gummow et al. 2005; Sepe et al. 2003). No data 

needs are identified. 

Food Chain Bioaccumulation. The uptake of vanadium in aquatic plants and animals is reasonably 

well documented; levels of vanadium present in different species have been established (Byerrum et al. 

1974; WHO 1988). Levels present in terrestrial plants (Byerrum et al. 1974; Cannon 1963) and animals 

(Van Zinderen Bakker and Jaworski 1980; WHO 1988) have been established for several species. Uptake 

of vanadium by terrestrial plants grown on sludge-amended, or vanadium-containing fertilized fields has 

been studied. Vanadium does not appear to concentrate in above-ground portions of terrestrial plants 

(Byerrum et al. 1974). No data needs are identified. 

Exposure Levels in Environmental Media. Reliable monitoring data for the levels of vanadium 

in contaminated media at hazardous waste sites are needed so that the information obtained on levels of 

vanadium in the environment can be used in combination with the known body burden of vanadium to 

assess the potential risk of adverse health effects in populations living in the vicinity of hazardous waste 

sites. 

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Estimates of human exposure to vanadium from food (Bocio et al. 2005; Byrne and Kosta 1978; Byrne 

and Kučera 1991; Gummow et al. 2005; Pennington and Jones 1987; Sepe et al. 2003; Thomas et al. 

1999; WHO 1988), drinking water (USGS 2009c; Lagerkvist et al. 1986; Thomas et al. 1999), and air 

(Byrne and Kosta 1978) are limited. Current information on emission levels from the combustion of 

residual fuel oil would enable a more complete picture of populations potentially exposed to higher than 

background ambient air levels. A data need is identified regarding vanadium levels found in 

environmental media in the vicinity of hazardous waste sites. 

Exposure Levels in Humans. Limited information was located describing levels of vanadium 

present in human tissues for the general population (Byrne and Kosta 1978; Fernandes et al. 2007; Kučera 

et al. 1992; Lin et al. 2004; Nixon et al. 2002; Sabbioni et al. 1996). Little information is available on 

tissue levels found in populations near hazardous waste sites. A data need for vanadium levels in blood 

samples of the general population and those residing near hazardous waste sites is identified. 

This information is necessary for assessing the need to conduct health studies on these populations. 

Exposures of Children. Measurements of the vanadium in blood and hair of children who have been 

exposed to vanadium, as well as unexposed children, are limited (Kučera et al. 1992). Additional 

information monitoring vanadium concentrations in children are needed. Specific data on the intake of 

vanadium from food eaten by children and from their diet are also limited (Ikem et al. 2002; Pennington 

and Jones 1987). 

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 vanadium 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 subregistries to be established. The information that is amassed in the National Exposure Registry facilitates 

the epidemiological research needed to assess adverse health outcomes that may be related to exposure to 

this substance. 

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6. POTENTIAL FOR HUMAN EXPOSURE 

6.8.2 Ongoing Studies 

No long-term research studies on the environmental fate of vanadium were identified. No ongoing 

studies or long-term research concerning occupational or general population exposures to vanadium were 

identified (FEDRIP 2009). 

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VANADIUM 149 

7. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting, 

measuring, and/or monitoring vanadium, its metabolites, and other biomarkers of exposure and effect to 

vanadium. 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. 

Vanadium can be determined as the total metal, as well as in its different oxidation states (species). The 

various oxidation states of vanadium can interconvert between the oxidation state depending on 

conditions such as, oxidation-reduction potential, pH, and salinity. In natural waters, dissolved vanadium 

exists as vanadium(IV) or vanadium(V) and these species have different toxic properties; therefore, 

determination of the vanadium species present in a sample can be more important than the total vanadium 

content of the sample in order to best evaluate human exposure (Pyrzyńska and Wierzbicki 2004). 

Analytical techniques for the determination of species of vanadium include standard atomic spectroscopic 

techniques and separations methods coupled with sensitive detectors. Separation methods include 

capillary electrophoresis (CE) and liquid chromatography (LC). Atomic spectroscopic methods used for 

the determination of vanadium include atomic absorption spectroscopy (AAS) with flame and graphite 

tube atomizers, inductively coupled plasma optical emission spectrometry (ICP-OES), inductively 

coupled plasma mass spectrometry (ICP-MS), x-ray fluorescence spectrometry (XRF), and 

spectrophotometric methods (Chen and Owens 2008). 

Sample preparation is one of the most important steps in the analysis of vanadium in biological and 

environmental samples. Direct analysis of vanadium species using atomic spectroscopic or separation 

techniques is generally not feasible due to the relatively low concentrations of vanadium found in samples 

as compared to other metals. In addition, the complexity of the matrices of biological and environmental 

samples can interfere with the determination of vanadium species, and it is often necessary to remove the 

matrices prior to vanadium analysis (Pyrzyńska and Wierzbicki 2004; Chen and Owens 2008). 

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7. ANALYTICAL METHODS 

The main methods for matrix removal are liquid-liquid extraction (LLE) and solid phase extraction (SPE). 

LLE is based on the distribution of the analyte between two immiscible solvents and involves the 

formation of an uncharged chemical species in the aqueous phase by chelation or ion-association of the 

vanadium ion, followed by extraction into an organic solvent. Example of complexing reagents (chelates) 

used to bind vanadium species include, vanadium(IV) with bis(salicylaldehyde) tetramethylethylenediimine in a chloroform/water mixture, vanadium(V) with N-benzoyl-N-phenylhydroxylamine (BPHA) in 

a chloroform/water mixture, and vanadium(V) with 2-(5-bromo-2-pyridylazo)-5-(N-propyl-N-sulfopropylamino)-phenol (5-Br-PAPS) in a xylene/water mixture. Each of these LLE steps was followed by 

separation using liquid chromatography with UV detection. Other complexing agents that have been 

studied include dibenzo-18-crown-6 and N-phenyl-(1,2-methanofullerene)-formohydroxamic acid 

(PMFFA) (Chen and Owens 2008; Pyrzyńska and Wierzbicki 2004). 

SPE is based on the transfer of metal ions from an aqueous phase to the active sites of a solid phase. 

Compared to LLE, SPE is simpler and more convenient to automate. It also uses less solvent and requires 

fewer manipulations. Several ion-exchange resins, functionalized cellulose sorbents, and chelating resins 

have been studied for the selective preconcentration and separation of vanadium species. Cellulose 

sorbent with phosphonic acid exchange groups gives excellent enrichment of vanadium(IV) and 

vanadium(V) and can be simultaneously eluted using an ethylenediamine tetraacetic acid (EDTA) 

solution. Other solid phases used to separate and preconcentrate vanadium species include Sephadex 

DEAE A-25 with Eriochrome Cyanide R complexation, C18 microcolumn or XAD-7 resin with 

complexation using 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol or dithizone or 8-hydroxyquinoline 

(8-HQ), and Chelex 100 (Chen and Owens 2008; Pyrzyńska and Wierzbicki 2004). 

Vanadium concentrations in biological and environmental samples are typically very low, and vanadium 

analysis requires powerful analytical methods. Analytical methods with sufficient sensitivity include 

neutron activation analysis (NAA), electrothermal atomic absorption spectrometry (ETAAS), inductively 

coupled plasma atomic emission spectrometry (ICP-AES), ICP-MS, and some UV-vis spectrophotometric 

methods (Pyrzyńska and Wierzbicki 2004). ETAAS is routinely used for the determination of trace 

concentrations of vanadium. ICP-MS has better sensitivity than ETAAS; however, interference from the 

sample matrix can complicate the analysis. The species 16O35Cl+ and 34S16OH+ from the sample matrix 

can overlap with the most abundant isotope of vanadium at m/z=51 (Nixon et al. 2002; Pyrzyńska and 

Wierzbicki 2004). 

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Due to the low levels of vanadium that are typically found in biological and environmental samples, care 

must be exercised during sample handling in order to avoid contamination. Vanadium may be found in 

disposable steel needles, collection vials, storage containers, and chemicals and reagents (Kučera and 

Sabbioni 1998). 

7.1 BIOLOGICAL MATERIALS 

Methods for determination of vanadium in biological samples are summarized in Table 7-1. 

NAA has been widely used to measure trace elements (including vanadium) in biological samples (Allen 

and Steinnes 1978; Lavi and Alfassi 1988; Martin and Chasteen 1988; Mousty et al. 1984). 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. When 51V is bombarded with neutrons, it becomes 52V (half-life 3.75 minutes and 

γ emission of 1.433 MeV). The resultant γ emission is detected with an efficient detector with high 

spectral resolution such as a well-type germanium detector combined with a multichannel analyzer. The 

concentration of vanadium is determined through its short-lived half-life of 52V (Seiler 1995). Detection 

limits of low- to sub-ppb (μg/L) levels of vanadium in blood and urine samples have been obtained (Allen 

and Steinnes 1978; Lavi and Alfassi 1988; Mousty et al. 1984). The advantages of the NAA technique 

are its sensitivity and multi-elemental capability. The disadvantages of this technique include its high 

cost and the limited availability of nuclear facilities for NAA analysis (Seiler 1995). 

Sabbioni et al. (1996) surveyed the literature for reports on vanadium determination in human blood, 

serum, and urine. Many analytical methods have been used to determine vanadium concentrations in 

blood, serum, and urine samples, including spectrography, colorimetry, catalytic reactions, XRF, particle 

induced x-ray emission (PIXE), ICP-AES, isotope dilution mass spectrometry (ID-MS), graphite furnace 

AAS (GF-AAS), and NAA. Only ID-MS, NAA, and GF-AAS can determine vanadium concentrations at 

levels of a few picograms (pg) of vanadium; GF-AAS and NAA are used most frequently (Kučera and 

Sabbioni 1998; Nixon et al. 2002; Sabbioni et al. 1996). 

Nixon et al. (2002) reported the use of a Dynamic Reaction CellTM ICP-MS (DRC-ICP-MS) for the 

analysis of vanadium in serum and urine. Generally, Zeeman graphite furnace atomic absorption 

spectrometry (ZGFAAS) and NAA are routinely used for the determination of vanadium in urine and 

serum. While ICP-MS as been routinely used to determine heavy metal concentrations in blood, serum, 

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Table 7-1. Analytical Methods for Determining Vanadium in Biological Materials 

Sample 

matrix Preparation method 

Analytical 

method 

Sample 

detection limit 

Percent 

recovery Reference 

Blood/urine Digest sample and 

evaporate; redissolve 

in acid; extract with 

MIBK; evaporate; 

redissolve in acid 

NAA ~1 μg/L (blood); 

2–4 μg/L (urine) 

No data Allen and Steinnes 

1978 

Urine Wet ashing with HNO3; 

chelation with 

GFAAS 1 μg/L 96–100% Buchet et al. 1982 

cupferron; extraction 

into MIBK 

Serum/urine Digestion in 

H2SO4/HClO4/HNO3 

add KMnO4, sulfamic 

acid, and HCl; extract 

with BTA in benzene 

ETAAS 0.008 μg/L 90.3% 

(serum); 

90.8% (urine) 

Ishida et al. 1989 

Serum Coprecipitate sample 

with lead nitrate or 

NAA 0.7 μg/L No data Lavi and Alfassi 

1988 

bismuth nitrate; dry 

and irradiate 

Blood Microwave digestion 

with HNO3 

ICP-MS 0.0078 μg/L No data Lin et al. 2004 

Serum/urine Dilution with 1% HNO3 

and addition of internal 

DRC-ICPMS 

0.028 μg/L No data Nixon et al. 2002 

standard 

Hair Washing and drying of 

hair samples, followed 

by cryogenic grinding; 

powdered hair samples 

prepared as slurries in 

mixtures of HNO3 and 

a slurry stabilizer 

ETAAS 0.28–0.34 μg/L No data Fernandes et al. 

2007 

BTA = N-benzoyl-N-(o-tolyl)hydroxylamine; DRC-ICP-MS = Dynamic Reaction CellTM inductively coupled mass 

spectrometry; MIBK = methyl isobutyl ketone; NAA = neutron activation analysis 

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and urine, and ICP-MS quantitation is at least an order of magnitude better than ZGFAAS for elements 

such as arsenic, lead, selenium, and cadmium, interference from 16O35Cl+

, which is produced in the argon 

plasma of the instrument, has limited the use of ICP-MS for the determination of vanadium. In this study 

it was found that with proper dynamic reaction cell conditions, OCl+ interference can be eliminated. The 

detection limit for vanadium (0.028 μg/L) was also found to be superior to that of ZGFAAS (1.9 μg/L) 

(Nixon et al. 2002). 

Fernandes et al. (2007) reported on a method to analyze hair samples using ETAAS. Samples were 

powdered using cryogenic grinding and hair slurries contained nitric acid, Triton X-100 (a nonionic 

surfactant), and water soluble tertiary amines. Limits of detection of 0.28 and 0.34 μg/L were reported 

using longitudinal heating and transversal heating graphite furnace atomizers, respectively. 

7.2 ENVIRONMENTAL SAMPLES 

Standard methods are available to measure vanadium concentrations in air, surfaces, water, soil, sediment, 

and plant and animal tissue (EPA 1983a, 1983b, 1983c, 1994a, 1994b, 1997a, 2003a; NIOSH 2003a, 

2003b, 2003c, 2003d; OSHA 2002; USGS 1987, 1993, 1996, 1998, 2006, 2007). Atomic spectroscopic 

methods are generally used in these methods as well as ICP-MS and spectrophotometric methods. 

NIOSH Method 7504 (1994) and OSHA Method ID-185 (1991) can be used to measure vanadium oxides 

in air samples using XRF. Methods for determination of vanadium in environmental samples are 

summarized in Table 7-2. 

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 vanadium 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 vanadium. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

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7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Vanadium in Environmental
 

Samples
 

Sample 

Preparation Analytical detection Percent 

Sample matrix method method limit recovery Reference 

Vanadium 

Air	 Collect sample on ICP-AES 

MCE or PVC 

filter, followed by 

HNO3/HClO4 

ashing 

Air	 Collect sample on ICP-AES 

MCE or PVC 

filter, followed by 

aqua regia ashing 

Air	 Collect sample on ICP-AES 

MCE filter, 

followed by hot 

block/HCl/HNO3 

digestion 

Wipes	 Wipe surface; ash ICP-AES 

wipe with 

HNO3/HClO4 

Air, wipe, or bulk	 Digestion of filters ICAP-AES 

with HNO3/ 

H2SO4/H2O2 

Water	 Acid solubilization ICP-MS 

Water	 Sample is mixed AVICP-AES 

with HNO3/HCl 

and heated 

Water	 Acidified with FAAS
 

HNO3
 

Water	 Acidified with GFAAS
 

HNO3
 

Water	 Filter and ICP-AES 

acidified samples 

Water	 Filter and ICP-MS 

acidified samples 

0.028 μg/filter 

0.028 μg/filter 

0.003 μg/mL 

0.01 μg/wipe 

1.9 μg 

0.014 μg/L 

0.2 μg/L 

200 μg/L 

4 μg/L 

6 μg/L 

0.08 mg/L 

98.3–103.2% NIOSH 2003a 

(MCE) (Method 7300)
 

102.5–
 

108.3%
 

(PVC)
 

101.3– NIOSH 2003b 

106.0% (Method 7301)
 

(MCE)
 

77.8–96.1%
 

(PVC)
 

No data	 NIOSH 2003c 

(Method 7303) 

No data	 NIOSH 2003d 

(Method 9102) 

No data	 OSHA 2002 

(Method ID-125G) 

97–109.2%	 EPA 1997a (EPA 

Method 200.10) 

93%	 EPA 2003 (EPA 

Method 200.5) 

95–100%	 EPA 1983a, 1983b 

(EPA Method 

286.1) 

No data	 EPA 1983a, 1983c 

(EPA Method 

286.2) 

No data	 USGS 1987 (USGS 

Method I-1472-87) 

64–105%	 USGS 1998 (USGS 

Method I-2477-92) 

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VANADIUM	 155 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Vanadium in Environmental
 

Samples
 

Sample 

Preparation Analytical detection Percent 

Sample matrix method method limit recovery Reference 

Water	 Treatment with an 

ammonium 

persulfate 

phosphoric acid 

reagent and gallic 

acid solution 

Water	 Filter and 

acidified samples 

Water (filtered)	 Filtered 

(0.045 μm 

membrane); 

preserved with 

HNO3 

Water Preserved with 

(unfiltered) HNO3 followed by 

digestion 

Water/waste Digestion with 

water/solid nitric and 

wastes hydrochloric acid 

Water/wastes	 Digestion with 

nitric and 

hydrochloric acid 

Water/waste Acid digestion
 

water/solid
 

wastes
 

Soil/sediment	 Air-dried and 

sieved; digestion 

with HNO3 using 

a closed-vessel 

microwave 

digestion 

procedure 

Animal tissue	 Acid digestion 

Animal tissue	 Acid digestion 

Colorimetric 

ICP-OES
 

ICP-MS
 

ICP-MS 

ICP-AES 

ICP-MS 

ICP-AES 

ICP-MS 

ICP-MS 

ICP-AES 

1 μg/L 

5 μg/L 

0.05 μg/L 

0.05 μg/L 

3 μg/L 

2.5 μg/L 

5 μg/L 

0.01 μg/L 

0.06 μg/g 

Not 

calculatable 

No data	 USGS 1993 (USGS 

Method I-2880) 

98%	 USGS 1998 (USGS 

Method I-4471-97) 

No data	 USGS 2006 (USGS 

Method I-2020-05) 

No data	 USGS 2006 (USGS 

Method I-4020-05) 

84–104%	 EPA 1994a (EPA 

Method 200.7) 

74.9–113.4%	 EPA 1994b (EPA 

Method 200.8) 

No data	 EPA 2007 (EPA 

Method 6010 C) 

No data	 USGS 2006 (USGS 

Method I-5020-05) 

101%	 USGS 1996 (USGS 

Method B-9001-95 

[ICP-MS]) 

96%	 USGS 1996 (USGS 

Method B-9001-95 

[ICP-AES]) 

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VANADIUM	 156 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Vanadium in Environmental
 

Samples
 

Sample 

Preparation Analytical detection Percent 

Sample matrix method method limit recovery Reference 

Biota	 Digestion with ICP-MS 0.01 μg/L No data USGS 2006 (USGS 

HNO3 using a Method I-9020-05) 

closed-vessel 

microwave 

digestion 

procedure 

Vanadium oxides 

Air	 Collect sample on XRD 4–28 μg No data NIOSH 1994
 

PVC filter, (V2O5), 5– (Method 7504)
 

dissolve filter in 62 μg (V2O3), 

THF; redeposit on 7–50.3 μg
 

silver filter (NH4VO3)
 

Vanadium pentoxide 

Air	 Collect sample on XRD 25 μg at 65 s 163.4– OSHA 1991 

PVC filter, 190.2% (Method ID-185)
 

dissolve filter in (respirable 

THF; suspension dust); 85.9–
 

is produced with 91.1% (finethe collected respirable
 

dust, which is dust)
 

transferred to 

silver membrane
 

AVICP-AES = axially viewed inductively coupled plasma-atomic emission spectrometry; EPA = Environmental 

Protection Agency; FAAS = flame atomic absorption spectrometry; GFAAS : graphite furnace atomic absorption 

spectrometry; ICAP-AES = inductively coupled argon plasma-atomic emission spectroscopy; ICP-AES = inductively 

coupled plasma-atomic emission spectroscopy; ICP-MS = inductively couples plasma-mass spectrometry; 

ICP-OES = inductively coupled plasma-optical emission spectroscopy; MCE = mixed cellulose ester; 

NIOSH = National Institute for Occupational Safety and Health; OSHA = Occupational Safety and Health 

Administration; PVC = polyvinyl chloride; THF = tetrahydrofuran; USGS = United States Geological Survey; 

XRD = X-ray diffraction 

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7. ANALYTICAL METHODS 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

7.3.1 Identification of Data Needs 

Methods for Determining Biomarkers of Exposure and Effect. Sensitive and selective 

methods are available for the detection and quantitative measurement of vanadium after the sample matrix 

in which it is contained as been properly treated. Atomic spectroscopic methods used for the 

determination of vanadium include AAS with flame and graphite tube atomizers, ICP-OES, ICP-MS, 

XRF, and spectrophotometric methods (Chen and Owens 2008). No data needs are identified. 

Exposure. Methods exist to determine vanadium levels in environmental samples and human tissues. 

While several biomarkers of exposure have been indentified, none of them can be used to quantitatively 

determine exposure levels (Rydzynski 2001). Kučera et al. (1998) reported that blood and urinary 

vanadium levels are considered the most reliable indicators of occupational exposure to vanadium. No 

data needs are identified. 

Effect. No well-documented biomarkers of effect specific for vanadium have been report (Rydzynski 

2001). The primary effects of exposure to vanadium dusts are coughing, wheezing, and other respiratory 

difficulties; however, these effects are not specific to vanadium and can be found following inhalation of 

many types of dusts (Rydzynski 2001). No data needs are identified. 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. Methods for determining vanadium in water, air, and waste samples with adequate selectivity 

and sensitivity are well developed and undergoing constant improvement. No data needs are identified. 

7.3.2 Ongoing Studies 

No ongoing studies regarding methods for measuring vanadium in biological and environmental samples 

were located (FEDRIP 2009). 

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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 0.0008 mg vanadium/m3 based on a LOAEL of 

0.56 mg vanadium/m3 for lung inflammation in rats exposed to vanadium pentoxide 6 hours/day, 

5 days/week for 13 days (NTP 2002). The MRL was derived by dividing the human equivalent 

concentration of the LOAEL (0.073 mg vanadium/m3

) by an uncertainty factor of 90 (3 for use of a 

minimal LOAEL, 3 for animal to human extrapolation with dosimetric adjustments, and 10 for human 

variability). 

ATSDR has derived a chronic-duration inhalation MRL of 0.0001 mg vanadium/m3 based on a BMCL10 

of 0.04 mg vanadium/m3 for degeneration of epiglottis respiratory epithelium of rats exposed to vanadium 

pentoxide 6 hours/day, 5 days/week for 2 years (NTP 2002). The MRL was derived by dividing the 

human equivalent concentration of the BMCL10 (0.003 mg vanadium/m3

) by an uncertainty factor of 30 

(3 for animal to human extrapolation with dosimetric adjustments and 10 for human variability). 

ATSDR has derived an intermediate-duration oral MRL of 0.01 mg vanadium/kg/day based on a NOAEL 

of 0.12 mg vanadium/kg/day for hematological and blood pressure effects in humans exposed to vanadyl 

sulfate for 12 weeks (Fawcett et al. 1997) and an uncertainty factor of 10 for human variability. 

IRIS (2009) has derived an oral reference dose (RfD) of 0.009 mg/kg/day for vanadium pentoxide based 

on a NOAEL of 0.89 mg/kg/day for decreased hair cysteine levels in rats exposed to vanadium pentoxide 

for 2.5 years (Stokinger et al. 1953) and an uncertainty factor of 100 (10 for extrapolation from animals to 

humans and 10 to protect against unusually susceptible individuals). 

EPA has not derived an inhalation reference concentration (RfC) for vanadium and vanadium compounds. 

OSHA has required employers of workers who are occupationally exposed to vanadium peroxide to 

institute engineering controls and work practices to reduce and maintain employee exposure at or below 

permissible exposure limits (PELs) (OSHA 2009). The employer must use engineering and work practice 

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VANADIUM 160 

8. REGULATIONS AND ADVISORIES 

controls to reduce exposures to not exceed 0.5 mg/m3 for vanadium peroxide as respirable dust (as V2O5) 

and 0.1 mg/m3 as fume (as V2O5) at any time (OSHA 2009). 

Vanadium pentoxide, vanadyl sulfate dehydrate, and ammonium metavanadate are on the list of 

chemicals appearing in “Toxic Chemicals Subject to Section 313 of the Emergency Planning and 

Community Right-to-Know Act of 1986" and has been assigned a reportable quantity (RQ) limit of 

1,000 pounds each (EPA 2009d). Vanadium pentoxide is also considered to be an extremely hazardous 

substance (EPA 2009e). The RQ represents the amount of a designated hazardous substance which, when 

released to the environment, must be reported to the appropriate authority. 

The international and national regulations, advisories, and guidelines regarding vanadium and compounds 

in air, water, and other media are summarized in Table 8-1. 

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Table 8-1. Regulations, Advisories, and Guidelines Applicable to Vanadium and
 

Compounds
 

Agency Description Information Reference 

INTERNATIONAL 

Guidelines: 

IARC Carcinogenicity classification IARC 2009 

Vanadium pentoxide Group 2Ba 

WHO Air quality guidelines WHO 2000 

Vanadium 

TWA based on effects other than 

cancer or odor/annoyance using 

an averaging time of 24 hours 

1 μg/m3 

Drinking water quality guidelines No data WHO 2006 

NATIONAL 

Regulations and 

Guidelines: 

a. Air 

ACGIH TLV (8-hour TWA)b 

Vanadium pentoxide (respirable 

fraction of dust or fume, as V2O5) 

0.05 mg/m3 

ACGIH 2008 

TLV Basis Irritation and lung 

AIHA ERPG values No AIHA 2008 

EPA Second AEGL chemical priority list EPA 2008a 

Vanadium and compounds Yesc 

Hazardous air pollutant No EPA 2009b 

42 USC 7412 

NIOSH REL (15-minute ceiling) 

Vanadium pentoxided 

IDLH 

0.05 mg/m3 

35 mg/m3 

NIOSH 2005 

Target organ Eyes, skin, and 

respiratory system 

OSHA PEL (ceiling limit) for general industry 

Vanadium pentoxide 

Respirable dust (as V2O5) 

Fume (as V2O5) 

0.5 mg/m3 

0.1 mg/m3 

OSHA 2009 

29 CFR 1910.1000, 

Table Z-1 

b. Water 

EPA Designated as hazardous substances 

in accordance with Section 311(b)(2)(A) 

of the Clean Water Act 

EPA 2009h 

40 CFR 116.4 

Vanadium pentoxide Yes 

Vanadyl sulfate dehydrate Yes 

Drinking water contaminant candidate 

list 

EPA 1998b 

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8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations, Advisories, and Guidelines Applicable to Vanadium and
 

Compounds
 

Agency Description Information Reference 

Vanadium Yes 63 FR 10274 

NATIONAL (cont.) 

EPA Drinking water standards and health 

advisories 

No EPA 2006a 

National primary drinking water 

standards 

No EPA 2003b 

National recommended water quality 

criteria 

No EPA 2006b 

Reportable quantities of hazardous 

substances designated pursuant to 

Section 311 of the Clean Water Act 

EPA 2009c 

40 CFR 117.3 

Vanadium pentoxide 1,000 pounds 

Vanadyl sulfate dehydrate 1,000 pounds 

c. Food 

FDA EAFUSe No FDA 2008 

d. Other 

ACGIH Carcinogenicity classification A4f ACGIH 2008 

Biological exposure indices (end of shift 

at end of workweek) 

Vanadium in urine 50 μg/g creatinine 

EPA Carcinogenicity classification No IRIS 2009 

RfC No 

RfD 

Vanadium pentoxide 9x10-3 mg/kg/day 

Superfund, emergency planning, and 

community right-to-know 

Designated CERCLA hazardous 

substance and their reportable 

quantities 

EPA 2009d 

40 CFR 302.4 

Vanadium pentoxideg 

Vanadyl sulfate dehydrateh 

Ammonium metavanadatei 

1,000 pounds 

1,000 pounds 

1,000 pounds 

Effective date of toxic chemical EPA 2009f 

release reporting 40 CFR 372.65 

Vanadium (except when 

contained in an alloy) 

01/01/2000 

Extremely hazardous substance and 

its threshold planning quantity 

Vanadium pentoxide 100/10,000 pounds 

EPA 2009e 

40 CFR 355, 

Appendix A 

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VANADIUM 163 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations, Advisories, and Guidelines Applicable to Vanadium and
 

Compounds
 

Agency Description Information Reference 

NATIONAL (cont.) 

TSCA chemical lists and reporting EPA 2009g 

periods 40 CFR 712.30 

Vanadium, vanadium pentoxide, 

vanadyl sulfate dehydrate, sodium 

metavanadate, sodium 

orthovanadate, and ammonium 

metavanadate 

Effective date 07/11/2003 

Reporting date 09/09/2003 

DHHS Carcinogenicity classification No data NTP 2005 

IOM Upper Tolerable Limit 1.8 mg/day IOM 2001 

a

Group 2B: possibly carcinogenic to humans

b

Vanadium peroxide is included in the 2008 Notice of Intended Changes in which the substance and its
 

corresponding values and notations for which the withdrawal of the Documentation and adopted TLV are proposed.
 c

Vanadium and compounds are included on the list of 371 priority chemicals that are acutely toxic and represent the 

selection of chemicals for AEGL development by the NAC/AEGL committee during the next several years.

d

The REL applies to all vanadium compounds except vanadium metal and vanadium carbide.
 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

Designated CERCLA hazardous substance pursuant to Section 311(b)(2) of the Clean Water Act and Section 3001 

of the Resource Conservation and Recovery Act.

h

Designated CERCLA hazardous substance pursuant to Section 311(b)(2) of the Clean Water Act.
 i

Designated CERCLA hazardous substance pursuant to Section 3001 of the Resource Conservation and Recovery
 

Act.
 

ACGIH = American Conference of Governmental Industrial Hygienists; AEGL = acute exposure guideline levels;
 

AIHA = American Industrial Hygiene Association; CERCLA = Comprehensive Environmental Response,
 

Compensation, and Liability Act; CFR = Code of Federal Regulations; DHHS = Department of Health and Human 

Services; 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; IOM = Institute of Medicien; NAC = National
 

Advisory Council; 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;
 

TLV = threshold limit values; TSCA = Toxic Substances Control Act; TWA = time-weighted average; USC = United 

States Code; WHO = World Health Organization
 

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VANADIUM 196 

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9. REFERENCES 

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VANADIUM 201 

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)—Usually defined as the lower confidence limit on the dose that produces a 

specified magnitude of changes in a specified adverse response. For example, a BMD10 would be the 

dose at the 95% lower confidence limit on a 10% response, and the benchmark response (BMR) would be 

10%. The BMD is determined by modeling the dose response curve in the region of the dose response 

relationship where biologically observable data are feasible. 

Benchmark Dose Model—A statistical dose-response model applied to either experimental toxicological 

or epidemiological data to calculate a BMD. 

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. 

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. 

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VANADIUM 202 

10. GLOSSARY 

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. 

Immunologic Toxicity—The occurrence of adverse effects on the immune system that may result from 

exposure to environmental agents such as chemicals. 

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VANADIUM 203 

10. GLOSSARY 

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. 

Mortality—Death; mortality rate is a measure of the number of deaths in a population during a specified 

interval of time. 

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VANADIUM 204 

10. GLOSSARY 

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. 

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 

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VANADIUM 205 

10. GLOSSARY 

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. 

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. 

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VANADIUM 206 

10. GLOSSARY 

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. 

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. 

Xenobiotic—Any chemical that is foreign to the biological system. 

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VANADIUM 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 

***DRAFT FOR PUBLIC COMMENT*** 
 

 

VANADIUM A-2 

APPENDIX A 

are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of 

the lack of precise toxicological information on the people who might be most sensitive (e.g., infants, 

elderly, nutritionally or immunologically compromised) to the effects of hazardous substances. ATSDR 

uses a conservative (i.e., protective) approach to address this uncertainty consistent with the public health 

principle of prevention. Although human data are preferred, MRLs often must be based on animal studies 

because relevant human studies are lacking. In the absence of evidence to the contrary, ATSDR assumes 

that humans are more sensitive to the effects of hazardous substance than animals and that certain persons 

may be particularly sensitive. Thus, the resulting MRL may be as much as 100-fold below levels that 

have been shown to be nontoxic in laboratory animals. 

Proposed MRLs undergo a rigorous review process: Health Effects/MRL Workgroup reviews within the 

Division of Toxicology and Environmental Medicine, expert panel peer reviews, and agency-wide MRL 

Workgroup reviews, with participation from other federal agencies and comments from the public. They 

are subject to change as new information becomes available concomitant with updating the toxicological 

profiles. Thus, MRLs in the most recent toxicological profiles supersede previously published levels. 

For additional information regarding MRLs, please contact the Division of Toxicology and 

Environmental Medicine, Agency for Toxic Substances and Disease Registry, 1600 Clifton Road NE, 

Mailstop F-62, Atlanta, Georgia 30333. 

***DRAFT FOR PUBLIC COMMENT*** 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

VANADIUM A-3 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Vanadium compounds 

CAS Numbers: 7440-62-2 

Date: August 2009 

Profile Status: Pre-Public Comment, Final Draft 

Route: [X] Inhalation [ ] Oral 

Duration: [X] Acute [ ] Intermediate [ ] Chronic 

Graph Key: 4 

Species: Rat 

Minimal Risk Level: 0.0008 [ ] mg/kg/day [X] mg vanadium/m3 

Reference: NTP. 2002. NTP toxicology and carcinogenesis studies of vanadium pentoxide (CAS No. 

1314-62-1) in F344/N rats and B6C3F1 mice (inhalation). Natl Toxicol Program Tech Rep Ser (507):1-

343. 

Experimental design: Groups of 40–60 female F344 rats were exposed to 0, 1, 2, or 4 mg vanadium 

pentoxide/m3 (0, 0.56, 1.1, and 2.2 mg vanadium/m3

) 6 hours/day, 5 days/week for 16 days. On days 6 

and 13, 10 rats/group were killed and a histopathological examination of the lungs was conducted. Four 

animals per group were killed for examination of onset and extent of lung lesions on days 1, 2, 5, 10, and 

16. The remaining animals were used to measure blood and lung concentrations of vanadium, lung 

clearance half-times, and cell proliferation rates. 

Effect noted in study and corresponding doses: Hyperplasia of alveolar epithelium and bronchiole 

epithelium were observed in 100% of the female rats exposed to 1.1 or 2.2 mg vanadium/m3 for 6 or 

13 days. Significant increases in the incidence of histiocytic infiltrate and inflammation were observed in 

rats exposed to 1.1 or 2.2 mg vanadium/m3 for 6 or 13 days and in rats exposed to 0.56 mg vanadium/m3 

for 13 days. A significant increase in fibrosis was observed in rats exposed to 2.2 mg vanadium/m3 for 

13 days. No histopathological alterations were observed in the four female rats killed after 1 day of 

exposure; by day 2, inflammation and histiocytic infiltrates (increased number of alveolar macrophages) 

were observed in the rats exposed to 2.2 mg vanadium/m3

. Hyperplasia of the alveolar and bronchiolar 

epidthelium was first observed on day 5 in rats exposed to 1.1 or 2.2 mg vanadium/m3

. 

Dose and end point used for MRL derivation: Increase in the incidence of lung inflammation in rats 

exposed to 0.56 mg vanadium/m3 as vanadium pentoxide for 13 days. 

[ ] NOAEL [X] LOAEL 

A BMD analysis was considered for determining the point of departure for the inflammation in female 

rats exposed to vanadium pentoxide for 13 days. All available dichotomous models in the EPA 

benchmark dose software ([BMDS] version 2.1) were fit to the incidence data for lung inflammation 

(0/10, 8/10, 10/10, and 10/10 in rats exposed to 0, 0.56, 1.1, or 2.2 mg vanadium/m3

) using the extra risk 

option. The multistage model was run for all polynomial degrees up to n-1 (where n is the number of 

dose groups including control). Adequate model fit is judged by three criteria: goodness-of-fit p-value 

(p>0.1), visual inspection of the dose-response curve, and scaled residual at the data point (except the 

control) closest to the predefined benchmark response (BMR). Among all the models providing adequate 

fit to the data, the lowest lower bound on the BMC (BMCL) is selected as the point of departure when the 

difference between the BMDLs estimated from these models are more three-fold; otherwise, the BMCL 

from the model with the lowest AIC is chosen. In accordance with U.S. EPA (2000) guidance, 

***DRAFT FOR PUBLIC COMMENT*** 

 


 

VANADIUM A-4 

APPENDIX A 

benchmark concentrations (BMCs) and BMCLs associated with an extra risk of 10% are calculated for all 

models. 

Table A-1. Model Predictions for the Incidence of Inflammation in Female Rats
 

Exposed to Vanadium Pentoxide 6 Hours/Day, 5 Days/Week for 13 Days
 

Model 

Gammab 

χ2 Goodness of 

fit p-valuea 

1.00 

AIC 

12.01 

BMC10 

(mg V/m3) 

0.33 

BMCL10 

(mg V/m3) 

0.02 

Logistic 1.00 14.01 0.46 0.10 

LogLogistic 1.00 12.01 0.46 0.01 

LogProbit 

Multistagec 

1.00 

0.93 

14.01 

12.69 

0.42 

0.03 

0.03 

0.02 

Probit 1.00 14.01 0.38 0.09 

Weibullb 1.00 14.01 0.25 0.02 

Quantal-linear 0.93 12.69 0.03 0.02 

a

Values <0.10 fail to meet conventional goodness-of-fit criteria b

Power restricted to ≥1 c

Betas restricted to ≥0; 1-degree polynomial 

AIC = Akaike Information Criterion; BMC = maximum likelihood estimate of the concentration associated with the 

selected benchmark response; BMCL = 95% lower confidence limit on the BMC 

Source: NTP 2002 

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VANADIUM A-5 

APPENDIX A 

Figure A-1. Fit of Gamma Model to Data on the Incidence of Inflammation in 

Female Rats Exposed to Vanadium Pentoxide for 13 Days
 

Gamma Multi-Hit Model with 0.95 Confidence Level 

Gamma Multi-Hit 

1 

0.8 

ed

0.6 

ectfon Afiract

0.4 

F 

0.2 

0 

BMDL BMD 

0 0.5 1 1.5 2 

dose 

22:23 05/24 2009 

BMCs and BMCLs indicated are associated with an extra risk of 10%, and are in units of mg vanadium/m3 

Source: NTP 2002 

Although the data provide an adequate statistical fit, the estimated BMCL10 of 0.02 mg vanadium/m3 

appears to be an overly conservative estimate of a no-adverse-effect level, which may be a reflection of 

the limited amount of information from the study on the shape of the exposure-response relationship 

(incidences of lung inflammation were 0/10 in controls and 8/10 at the lowest vanadium concentration). 

In a chronic-duration study conducted by NTP (2002), no significant alterations in the incidence of lung 

inflammation were observed in male and female rats exposed to 0.28 mg vanadium/m3

; the LOAEL for 

lung inflammation was 0.56 mg vanadium/m3 in males and 1.1 mg vanadium/m3 in females. 

Due to the low confidence in the BMCL10, a NOAEL/LOAEL approach was used to determine the point 

of departure for the acute MRL. 

Uncertainty Factors used in MRL derivation: 

[X] 3 for use of a minimal LOAEL 

[X] 3 for extrapolation from animals to humans with dosimetric adjustment 

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VANADIUM A-6 

APPENDIX A 

[X] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? Not applicable. 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: 

The duration-adjusted LOAEL of 0.1 mg vanadium/m3 was converted to a human equivalent 

concentration (LOAELHEC) using the following equation: 

LOAELHEC = LOAELADJ x RDDRTH
 

LOAELHEC = 0.1 mg vanadium/m3 x 0.732
 

LOAELHEC = 0.073 mg vanadium/m3
 

where: 

The RDDR is a multiplicative factor used to adjust an observed inhalation particulate exposure 

concentration of an animal to the predicted inhalation particulate exposure concentration for a human. 

The RDDR program (EPA 1990) was used to calculate a multiplier of 0.732 for the thoracic region was 

determined using a default body weight of 0.124 kg (EPA 1994c) and a particle size MMAD of 1.2 μm 

with a geometric standard deviation of 1.9 

Was a conversion used from intermittent to continuous exposure? The LOAEL was adjusted for 

intermittent exposure as follows: 

LOAELADJ = LOAEL x 6 hours/day x 5 days/week 

LOAELADJ = 0.56 mg vanadium/m3 x 6 hours/24 hours x 5 days/7 days 

LOAELADJ = 0.1 mg vanadium/m3 

Other additional studies or pertinent information that lend support to this MRL: Data on acute toxicity of 

vanadium in humans are limited to an experimental study in which a small number of subjects were 

exposed to vanadium pentoxide dust for 8 hours (Zenz and Berg 1967). A persistent cough lasting for 

8 days developed in two subjects exposed to 0.6 mg vanadium/m3

; at 0.1 mg vanadium/m3, a productive 

cough without any subjective complaints or impact on work or home activities were observed in 

5 subjects. The available studies in laboratory animals focused on potential respiratory tract effects. 

Impaired lung function characterized as airway obstructive changes (increased resistance and decreased 

airflow) were observed in monkeys exposed to 2.5 or 1.7 mg vanadium/m3 as vanadium pentoxide for 

6 hours (Knecht et al. 1985, 1992); the highest NOAEL for this effect was 0.34 mg vanadium/m3

. 

Alveolar and bronchiolar epithelial hyperplasia and inflammation were observed in the lungs of mice 

exposed to 1.1 mg vanadium/m3 6 hours/day, 5 days/week for 13 days (NTP 2002). Although the Knecht 

et al. (1985, 1992) or NTP (2002) studies did not include examination of potential end points outside of 

the respiratory tract, longer-duration studies have identified the respiratory tract as the most sensitive 

target of toxicity (NTP 2002). 

Agency Contacts (Chemical Managers): Jessilynn Taylor, Sam Keith, Larry Cseh 

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VANADIUM A-7 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Vanadium compounds 

CAS Numbers: 7440-62-2 

Date: August 2009 

Profile Status: Pre-Public Comment, Final Draft 

Route: [X] Inhalation [ ] Oral 

Duration: [ ] Acute [ ] Intermediate [X] Chronic 

Graph Key: 19 

Species: Rat 

Minimal Risk Level: 0.0001 [ ] mg/kg/day [X] mg vanadium/m3 

Reference: NTP. 2002. NTP toxicology and carcinogenesis studies of vanadium pentoxide (CAS No. 

1314-62-1) in F344/N rats and B6C3F1 mice (inhalation). Natl Toxicol Program Tech Rep Ser (507):1-

343. 

Experimental design: Groups of 50 male and 50 female F344 rats were exposed to 0, 0.5, 1, or 2 mg 

vanadium pentoxide/m3 (0, 0.28, 0.56, and 1.1 mg vanadium/m3

) 6 hours/day, 5 days/week for 104 weeks. 

The following parameters were used to assess toxicity: clinical observations, body weights (every 

4 weeks from week 5 to 89 and every 2 weeks from week 92 to 104), complete necropsy, and microscopic 

examination of major tissues and organs. 

Effect noted in study and corresponding doses: No significant alterations in survival or body weight gain 

were observed in the vanadium-exposed rats. A summary of selected non-neoplastic respiratory tract 

lesions is presented in Table A-2. Alveolar histiocytic infiltrates were observed in males and females 

exposed to ≥0.28 mg vanadium/m3

. Significant increases in the incidence of hyperplasia of the alveolar 

and bronchiolar epithelium were observed in males exposed to ≥0.28 mg vanadium/m3 and females 

exposed to ≥0.56 mg vanadium/m3

. Squamous metaplasia was observed in alveolar epithelium of males 

and females exposed to 1.1 mg vanadium/m3 and in the bronchiolar epithelium of males exposed to 

1.1 mg vanadium/m3

. Chronic inflammation was observed in males exposed to 0.56 or 1.1 mg 

vanadium/m3 and females exposed to 1.1 mg vanadium/m3 and interstitial fibrosis was observed in males 

exposed to 1.1 mg vanadium/m3 and females exposed to 0.28 or 1.1 mg vanadium/m3

. An increased 

incidence of brownish pigment in alveolar macrophages was observed in males exposed to 1.1 mg 

vanadium/m3 and females exposed to 0.56 or 1.1 mg vanadium/m3

; this effect was considered to be of 

little biological relevance. Chronic inflammation, degeneration, and hyperplasia of the epiglottis were 

observed in the larynx of males and females exposed to ≥0.28 mg vanadium/m3

; squamous metaplasia of 

the epiglottis respiratory epithelium was also observed in males exposed to ≥0.28 mg vanadium/m3 and in 

females exposed to 1.1 mg vanadium/m3

. Goblet cell hyperplasia of the nasal respiratory epithelium was 

observed in males exposed to ≥0.28 mg vanadium/m3 and in females exposed to 1.1 mg vanadium/m3

. A 

positive trend for increased incidences of uterine stromal polyp was observed; NTP did not consider it to 

be related to vanadium pentoxide exposure. An increased incidence of nephropathy was observed in male 

rats exposed to 0.56 or 1.1 mg vanadium/m3

; NTP considered the finding to be of marginal biological 

significance because there was a lack of increase in severity, as compared to controls, and significant 

findings in female rats. No significant increases in the incidence of lung neoplasms were observed; 

however, the incidence of alveolar/bronchiolar adenoma in males exposed to 0.28 mg vanadium/m3 and 

alveolar/bronchiolar carcinoma or combined incidence of adenoma and carcinoma in males exposed to 

0.28 or 1.1 mg vanadium/m3 were higher than historical controls. These increases in lung tumors were 

considered to be related to vanadium pentoxide exposure. 

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VANADIUM A-8
 

APPENDIX A
 

Table A-2. Selected Respiratory Tract Effects Observed in Rats Exposed to
 

Vanadium Pentoxide 6 Hours/Day, 5 Days/Week for 2 Years
 

Air concentration (mg vanadium/m3) 0 0.28 0.56 1.1 

Males 

Lungs 

Alveolar hyperplasia 7/50 (2.3) 24/49b (2.0) 34/48b (2.0) 49/50b (3.3) 

Bronchiole hyperplasia 3/50 (2.3) 17/49b (2.2) 31/48b (1.8) 49/50b (3.3) 

Inflammation 5/50 (1.6) 8/49 (1.8) 24/48b (1.3) 42/50b (2.4) 

Fibrosis 7/50 (1.4) 7/49 (2.0) 16/48c (1.6) 38/50b (2.1) 

Histiocyte infiltration 22/50 (1.3) 40/49b (2.0) 45/48b (2.3) 50/50b (3.3) 

Larynx 

Chronic inflammation 3/49 (1.0) 20/50b (1.1) 17/50b (1.5) 28/49b (1.6) 

Degeneration of epiglottis respiratory 0/49 22/50b (1.1) 23/50b (1.1) 33/50b (1.5) 

epithelium 

Hyperplasia of epiglottis respiratory 0/49 22/50b (1.1) 23/50b (1.1) 33/49b (1.5)
 

epithelium
 

Squamous metaplasia of epiglottis 0/49 18/50b (1.5) 34/50b (1.5) 32/49b (1.9)
 

respiratory epithelium 

Nose 

Hyperplasia of respiratory epithelium 4/49 (1.8) 15/50b (1.8) 12/49c (2.0) 17/48b (2.1) 

goblet cell 

Female 

Lung 

Alveolar hyperplasia 4/49 (1.0) 8/49 (1.8) 21/50b (1.2) 50/50b (3.1) 

Bronchiole hyperplasia 6/49 (1.5) 5/49 (1.6) 14/50c (1.3) 48/50b (3.0) 

Inflammation 10/49 (1.5) 10/49 (1.1) 14/50 (1.2) 40/50c (1.7) 

Fibrosis 19/49 (1.4) 7/49 (1.3) 12/50 (1.6) 32/50b (1.4) 

Histiocyte infiltration 26/49 (1.4) 35/49c (1.3) 44/50b (2.0) 50/50b (1.9) 

Larynx 

Chronic inflammation 8/50 (1.8) 26/49b (1.5) 27/49b (1.3) 37/50b (1.4) 

Degeneration of epiglottis respiratory 2/50 (1.0) 33/49b (1.2) 26/49b (1.2) 40/50b (1.5) 

epithelium 

Hyperplasia of epiglottis respiratory 0/50 25/49b (1.4) 26/49b (1.3) 33/50b (1.5)
 

epithelium
 

Squamous metaplasia of epiglottis 2/50 (2.0) 7/49 (1.9) 7/40 (1/7) 16/50b (1.4)
 

respiratory epithelium 

Nose 

Hyperplasia of respiratory epithelium 13/50 (2.0) 18/50 (2.0) 16/50 (1.9) 30/50b (2.0) 

goblet cell 

a

Average severity grade of lesions in affected animals: 1=minimal; 2=mild, 3=moderate; 4=marked

b

p≤0.01 c

p≤0.05

Source: NTP 2002 

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VANADIUM A-9 

APPENDIX A 

Dose and end point used for MRL derivation: The human equivalent concentration of the BMCL10 for 

degeneration of respiratory epithelium of the epiglottis, 0.003 mg vanadium/m3

, was used as the point of 

departure for the chronic-duration inhalation MRL. 

[ ] NOAEL [ ] LOAEL [X] BMCL10 

BMD analysis was used to determine the point of departure for select respiratory tract lesions in rats 

exposed to vanadium pentoxide for 2 years. A number of lesions were observed in male and female rats 

exposed to 0.28 mg vanadium/m3 including hyperplasia of the alveolar and bronchiolar epithelium, 

chronic inflammation of the larynx, degeneration of the epiglottis, and hyperplasia of respiratory 

epithelial goblet cells. The incidence of these lesions in male rats were modeled using all available 

dichotomous models in the EPA BMDS (version 2.1) that were fit to the incidence data for alveolar 

hyperplasia, bronchial hyperplasia, using the extra risk option. The multistage model was run for all 

polynomial degrees up to n-1 (where n is the number of dose groups including control). Adequate model 

fit is judged by three criteria: goodness-of-fit p-value (p>0.1), visual inspection of the dose-response 

curve, and scaled residual at the data point (except the control) closest to the predefined BMR. Among all 

the models providing adequate fit to the data, the lowest BMCL is selected as the point of departure when 

the difference between the BMCLs estimated from these models are more three-fold; otherwise, the 

BMCL from the model with the lowest AIC is chosen. In accordance with U.S. EPA (2000) guidance, 

BMCs and BMCLs associated with an extra risk of 10% are calculated for all models. 

The results of the BMD analyses are presented in Table A-3 and Figures A-2 through A-6. 

Table A-3. Model Predictions for Respiratory Effects in Rats Exposed to
 

Vanadium Pentoxide for 2 Years
 

Model 

χ2 Goodness 

of fit p-valuea AIC 

BMC10 

(mg V/m3) 

BMCL10 

(mg V/m3) 

Alveolar hyperplasia in male rats 

Gammab 0.25 183.50 0.12 0.04 

Logistic 0.52 181.44 0.11 0.09 

Log-Logistic 0.08 185.40 NA NA 

Log-Probit 0.13 184.60 0.15 0.08 

Multistagec 0.21 184.00 0.05 0.04 

Probit 0.57 181.29 0.10 0.09 

Weibullb 0.33 183.11 0.10 0.05 

Quantal-Linear 0.21 184.00 0.05 0.04 

Bronchiolar hyperplasia in male rats 

Gammab 0.28 165.38 0.17 0.10 

Logistic 0.60 163.19 0.15 0.12 

Log-Logistic 0.08 167.58 NA NA 

Log-Probit 0.12 166.67 0.19 0.13 

Multistagec 0.56 164.51 0.13 0.07 

Probit 0.71 162.87 0.14 0.12 

Weibullb 0.45 164.73 0.15 0.09 

Quantal-linear 0.03 170.74 

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VANADIUM A-10
 

APPENDIX A
 

Table A-3. Model Predictions for Respiratory Effects in Rats Exposed to
 

Vanadium Pentoxide for 2 Years
 

χ2 Goodness BMC10 BMCL10 

Model of fit p-valuea AIC (mg V/m3) (mg V/m3) 

Chronic inflammation in larynx of male rats 

Gammab 0.04 230.93 NA NA 

Logistic 0.01 235.47 NA NA 

Log-Logistic 0.11 229.28 0.10 0.07 

Log-Probit 0.00 235.73 NA NA 

Multistagec 0.04 230.93 NA NA 

Probit 0.01 235.09 NA NA 

Weibullb 0.04 230.93 NA NA 

Quantal-linear 0.04 230.93 NA NA 

Degeneration of epiglottis respiratory epithelium in male rats 

Gammab 0.06 210.55 NA NA 

Logistic 0.00 230.64 NA NA 

Log-Logistic 0.47 206.17 0.06 0.04 

Log-Probit 0.01 214.79 NA NA 

Multistagec 0.06 210.55 NA NA 

Probit 0.00 229.81 NA NA 

Weibullb 0.06 210.55 NA NA 

Quantal-linear 0.06 210.55 NA NA 

Hyperplasia of nasal respiratory epithelial goblet cells in male rats 

Gammab 0.12 213.84 0.32 0.20 

Logistic 0.07 215.11 NA NA 

Log-Logistic 0.15 213.35 0.27 0.16 

Log-Probit 0.03 216.79 NA NA 

Multistagec 0.12 213.84 0.32 0.20 

Probit 0.07 214.97 NA NA 

Weibullb 0.12 213.84 0.32 0.20 

Quantal-linear 0.12 213.84 0.32 0.20 

a

Values <0.10 fail to meet conventional goodness-of-fit criteria b

Power restricted to ≥1 c

Betas restricted to ≥0; 1-degree polynomial 

AIC = Akaike Information Criterion; BMD = maximum likelihood estimate of the dose/concentration associated with 

the selected benchmark response; BMDL = 95% lower confidence limit on the BMD; NA = not applicable 

Source: NTP 2002 

***DRAFT FOR PUBLIC COMMENT*** 
 

VANADIUM A-11 

APPENDIX A 

Figure A-2. Fit of Probit Model to Data on the Incidence of Alveolar Hyperplasia in 

Male Rats Exposed to Vanadium Pentoxide for 2 Years 

Probit Model with 0.95 Confidence Level 

Probit 

1 

0.8 

edect

0.6 

fon AfractiF

0.4 

0.2 

0 BMDL BMD 

0 0.2 0.4 0.6 0.8 1 

dose 

23:03 05/24 2009 

BMCs and BMCLs indicated are associated with an extra risk of 10%, and are in units of mg vanadium/m3 

Source: NTP 2002 

***DRAFT FOR PUBLIC COMMENT*** 

 


 

 

VANADIUM A-12 

APPENDIX A 

Figure A-3. Fit of Probit Model to Data on the Incidence of Bronchiolar
 

Hyperplasia in Male Rats Exposed to Vanadium Pentoxide for 2 Years
 

Probit Model with 0.95 Confidence Level 

Probit 

1 

0.8 

ed

0.6 

ectfon Afracti

0.4 

F 

0.2 

0 

BMDL BMD 

0 0.2 0.4 0.6 0.8 1 

dose 

23:18 05/24 2009 

BMCs and BMCLs indicated are associated with an extra risk of 10%, and are in units of mg vanadium/m3 

Source: NTP 2002 

***DRAFT FOR PUBLIC COMMENT*** 
 


 


 

 
 

Figure A-4. Fit of Log-logistic Model to Data on the Incidence
 

Chronic Inflammation in Larynx of Male Rats Exposed to
 

Vanadium Pentoxide for 2 Years
 

Log-Logistic Model with 0.95 Confidence Level 

Log-Logistic 

0.7 

0.6 

0.5 

edectf

0.4 

on Af 

0.3 

racti F

0.2 

0.1 

0 

BMDL BMD 

VANADIUM A-13 

APPENDIX A 

0 0.2 0.4 0.6 0.8 1 

dose 

09:24 05/26 2009 

BMCs and BMCLs indicated are associated with an extra risk of 10%, and are in units of mg vanadium/m3 

Source: NTP 2002 

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VANADIUM A-14 

APPENDIX A 

Figure A-5. Fit of Log-logistic Model to Data on the Incidence of Degeneration of
 

Epiglottis Respiratory Epithelium in Male Rats Exposed to Vanadium
 

Pentoxide for 2 Years
 

Log-Logistic Model with 0.95 Confidence Level 

Log-Logistic 

0.8 

0.7 

0.6 

0.5 

edectf

0.4 

on Af iactr

0.3 

F 

0.2 

0.1 

0 

BMDL BMD 

0 0.2 0.4 0.6 0.8 1 

dose 

09:53 05/26 2009 

BMCs and BMCLs indicated are associated with an extra risk of 10%, and are in units of mg vanadium/m3 

Source: NTP 2002 

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VANADIUM A-15 

APPENDIX A 

Figure A-6. Fit of Log-logistic Model to Data on the Incidence of Hyperplasia of
 

Nasal Respiratory Epithelial Goblet Cells in Male Rats Exposed to Vanadium
 

Pentoxide for 2 Years
 

Log-Logistic Model with 0.95 Confidence Level 

Log-Logistic 

0.5 

0.4 

edect

0.3 

fon AfiractF

0.2 

0.1 

0 BMDL BMD 

0 0.2 0.4 0.6 0.8 1 

dose 

10:00 05/26 2009 

BMCs and BMCLs indicated are associated with an extra risk of 10%, and are in units of mg vanadium/m3 

Source: NTP 2002 

In summary, the lowest BMCL10 values for alveolar epithelial hyperplasia, bronchiolar epithelial 

hyperplasia, laryngeal chronic inflammation, degeneration of epiglottis epithelium, and hyperplasia of 

nasal goblet cells were 0.09, 0.10, 0.07, 0.04, 0.16 mg vanadium/m3

, respectively. 

Uncertainty Factors used in MRL derivation: 

[ ] 10 for use of a LOAEL 

[X] 3 for extrapolation from animals to humans with dosimetric adjustments 

[X] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? Not applicable. 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: 

Human equivalent concentrations were calculated for each BMCL10 using the following equation: 

BMCLHEC = BMCLADJ x RDDR 

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VANADIUM A-16 

APPENDIX A 

where: 

The RDDR is a multiplicative factor used to adjust an observed inhalation particulate exposure 

concentration of an animal to the predicted inhalation particulate exposure concentration for a human. 

The RDDR program (EPA 1994c) was used to calculate a multiplier for the different regions of the 

respiratory tract was determined using a default body weight of 0.380 kg (EPA 1994c) and a particle size 

MMAD of 1.2 μm with a geometric standard deviation of 1.9. The BMDLHEC values are presented in 

Table A-4 

Table A-4. Summary of Human Equivalent Concentrations of BMCL Values for 

Rats Exposed to Vanadium Pentoxide for 2 Years 

BMCL10 BMCLADJ a BMCLHEC 

Effect (mg vanadium/m3) (mg vanadium/m3) RDDR (mg vanadium/m3) 

Alveolar epithelial 0.09 0.016 0.502b 0.008 

hyperplasia 

Bronchiolar epithelial 0.10 0.018 0.971c 0.017 

hyperplasia 

Laryngeal chronic 0.07 0.012 0.423d 0.005 

inflammation 

Degeneration of epiglottis 0.04 0.0071 0.423d 0.003 

epithelium 

Hyperplasia of nasal 0.16 0.029 0.423d 0.012 

goblet cells 

a

BMCLADJ= BMCL10 x 6 hours/24 hours x 5 days/7 days b

Pulmonary region 

c

Thoracic region

d

Extrathoracic region 

BMCL = benchmark concentration, lower confidence limit RDDR = regional deposited dose ratio 

Source: NTP 2002 

Was a conversion used from intermittent to continuous exposure? The BMCL10 was adjusted for 

intermittent exposure, as noted in Table A-4. 

Other additional studies or pertinent information that lend support to this MRL: An increased combined 

incidence of alveolar/bronchiolar adenoma or carcinoma was observed in male rats (NTP 2002). 

Although the incidence was not significantly higher than concurrent controls, it was higher than historical 

controls and NTP considered it to be a vanadium-related effect. 

In mice exposed to ≥0.56 mg vanadium/m3 for 6 hours/day, 5 days/week for 2 years, significant increases 

in the incidence of alveolar and bronchiolar hyperplasia, chronic lung inflammation, squamous metaplasia 

of the respiratory epithelium of the epiglottis, goblet cell hyperplasia in the nasal respiratory epithelium 

and nasal olfactory epithelial atrophy, and hyaline degeneration were observed (NTP 2002). In addition 

to these effects, a significant increase in alveolar/bronchiolar carcinoma incidence was also observed in 

mice exposed to ≥0.56 mg vanadium/m3

. 

Agency Contacts (Chemical Managers): Jessilynn Taylor, Sam Keith, Larry Cseh 

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VANADIUM A-17 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Vanadium compounds 

CAS Numbers: 7440-62-6 

Date: August 2009 

Profile Status: Pre-Public Comment, Final Draft 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [X] Intermediate [ ] Chronic 

Graph Key: 12 

Species: Human 

Minimal Risk Level: 0.01 [X] mg vanadium/kg/day [ ] mg vanadium/m3 

Reference: Fawcett JP, Farquhar SJ, Thou T, et al. 1997. Oral vanadyl sulphate does not affect blood 

cells, viscosity or biochemistry in humans. Pharmacol Toxicol 80:202-206. 

Experimental design: Groups of men and women enrolled in a weight training program for at least 1 year 

were administered capsules containing 0 (11 men and 4 women) or 0.5 mg/kg/day vanadyl sulfate 

trihydrate (0.12 mg vanadium/kg/day) (12 men and 4 women) for 12 weeks. Fasting blood samples were 

collected at 0 and 12 weeks and analyzed for hematological (erthyroctye count, hemoglobin, hematocrit, 

mean cell volume, mean cell hemoglobin, platelet count, and total and differential leukocyte count) and 

serum chemistry (cholesterol, high density lipoprotein, triglycerides, albumin, total protein, total and 

direct bilirubin, alkaline phosphatase, ALT) parameters. Body weight and blood pressure were measured 

at weeks 4, 8, and 12. 

Effect noted in study and corresponding doses: No significant alterations in blood pressure, body weight, 

or hematological or clinical chemistry parameters were found. 

Dose and end point used for MRL derivation: NOAEL of 0.12 mg vanadium/kg/day for hematological 

alterations and blood pressure. 

[X] NOAEL [ ] LOAEL 

Uncertainty Factors used in MRL derivation: 

[ ] 10 for use of a LOAEL 

[ ] 10 for extrapolation from animals to humans 

[X] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? No. 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: Not 

applicable. 

Was a conversion used from intermittent to continuous exposure? Not applicable. 

Other additional studies or pertinent information that lend support to this MRL: Studies in laboratory 

animals have identified several sensitive effects including alterations in erythrocyte and reticulocyte 

levels, increased blood pressure, neurobehavioral alterations, and developmental toxicity. Significant 

increases in blood pressure have been observed in rats exposed to 0.12 mg vanadium/kg/day for 210 days 

(Boscolo et al. 1994); increases in blood pressure have been observed at higher doses in several other 

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VANADIUM A-18 

APPENDIX A 

studies by these investigators (Carmagnani et al. 1991, 1992). In general, other studies have not found 

increases in blood pressure in rats exposed to doses as high as 31 mg vanadium/kg/day (Bursztyn and 

Mekler 1993; Sušić and Kentera 1986, 1988). Decreases in erythrocyte levels have been observed in rats 

exposed to 1.18 mg vanadium/kg/day as ammonium metavanadate in drinking water for 4 weeks 

(Zaporowska et al. 1993); at higher concentrations, decreases in hemoglobin and increases in reticulocyte 

levels have been observed (Ścibior 2005; Ścibior et al. 2006; Zaporowska and Wasilewski 1990, 1991, 

1992a, 1992b; Zaporowska et al. 1993). Decreases in pup body weight and length have been observed in 

the offspring of rats administered 2.1 mg vanadium/kg/day as sodium metavanadate for 14 days prior to 

mating and throughout gestation and lactation (Domingo et al. 1986). At higher doses (6, 10, or 12 mg 

vanadium/kg/day), decreases in pup survival, and increases in the occurrence of gross, visceral, or skeletal 

malformations and anomalies were observed (Elfant and Keen 1987; Morgan and El-Tawil 2003; 

Poggioli et al. 2001). 

Agency Contacts (Chemical Managers): Jessilynn Taylor, Sam Keith, Larry Cseh 

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VANADIUM	 B-1 

APPENDIX B. USER'S GUIDE 

Chapter 1 

Public Health Statement 

This chapter of the profile is a health effects summary written in non-technical language. Its intended 

audience is the general public, especially people living in the vicinity of a hazardous waste site or 

chemical release. If the Public Health Statement were removed from the rest of the document, it would 

still communicate to the lay public essential information about the chemical. 

The major headings in the Public Health Statement are useful to find specific topics of concern. The 

topics are written in a question and answer format. The answer to each question includes a sentence that 

will direct the reader to chapters in the profile that will provide more information on the given topic. 

Chapter 2 

Relevance to Public Health 

This chapter provides a health effects summary based on evaluations of existing toxicologic, 

epidemiologic, and toxicokinetic information. This summary is designed to present interpretive, weightof-evidence discussions for human health end points by addressing the following questions: 

1.	 What effects are known to occur in humans? 

2.	 What effects observed in animals are likely to be of concern to humans? 

3.	 What exposure conditions are likely to be of concern to humans, especially around hazardous 

waste sites? 

The chapter covers end points in the same order that they appear within the Discussion of Health Effects 

by Route of Exposure section, by route (inhalation, oral, and dermal) and within route by effect. Human 

data are presented first, then animal data. Both are organized by duration (acute, intermediate, chronic). 

In vitro data and data from parenteral routes (intramuscular, intravenous, subcutaneous, etc.) are also 

considered in this chapter. 

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using 

existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer 

potency or perform cancer risk assessments. Minimal Risk Levels (MRLs) for noncancer end points (if 

derived) and the end points from which they were derived are indicated and discussed. 

Limitations to existing scientific literature that prevent a satisfactory evaluation of the relevance to public 

health are identified in the Chapter 3 Data Needs section. 

Interpretation of Minimal Risk Levels 

Where sufficient toxicologic information is available, ATSDR has derived MRLs for inhalation and oral 

routes of entry at each duration of exposure (acute, intermediate, and chronic). These MRLs are not 

meant to support regulatory action, but to acquaint health professionals with exposure levels at which 

adverse health effects are not expected to occur in humans. 

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VANADIUM B-2 

APPENDIX B 

MRLs should help physicians and public health officials determine the safety of a community living near 

a chemical emission, given the concentration of a contaminant in air or the estimated daily dose in water. 

MRLs are based largely on toxicological studies in animals and on reports of human occupational 

exposure. 

MRL users should be familiar with the toxicologic information on which the number is based. Chapter 2, 

"Relevance to Public Health," contains basic information known about the substance. Other sections such 

as Chapter 3 Section 3.9, "Interactions with Other Substances,” and Section 3.10, "Populations that are 

Unusually Susceptible" provide important supplemental information. 

MRL users should also understand the MRL derivation methodology. MRLs are derived using a 

modified version of the risk assessment methodology that the Environmental Protection Agency (EPA) 

provides (Barnes and Dourson 1988) to determine reference doses (RfDs) for lifetime exposure. 

To derive an MRL, ATSDR generally selects the most sensitive end point which, in its best judgement, 

represents the most sensitive human health effect for a given exposure route and duration. ATSDR 

cannot make this judgement or derive an MRL unless information (quantitative or qualitative) is available 

for all potential systemic, neurological, and developmental effects. If this information and reliable 

quantitative data on the chosen end point are available, ATSDR derives an MRL using the most sensitive 

species (when information from multiple species is available) with the highest no-observed-adverse-effect 

level (NOAEL) that does not exceed any adverse effect levels. When a NOAEL is not available, a 

lowest-observed-adverse-effect level (LOAEL) can be used to derive an MRL, and an uncertainty factor 

(UF) of 10 must be employed. Additional uncertainty factors of 10 must be used both for human 

variability to protect sensitive subpopulations (people who are most susceptible to the health effects 

caused by the substance) and for interspecies variability (extrapolation from animals to humans). In 

deriving an MRL, these individual uncertainty factors are multiplied together. The product is then 

divided into the inhalation concentration or oral dosage selected from the study. Uncertainty factors used 

in developing a substance-specific MRL are provided in the footnotes of the levels of significant exposure 

(LSE) tables. 

Chapter 3 

Health Effects 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables and figures are used to summarize health effects and illustrate graphically levels of exposure 

associated with those effects. These levels cover health effects observed at increasing dose 

concentrations and durations, differences in response by species, MRLs to humans for noncancer end 

points, and EPA's estimated range associated with an upper- bound individual lifetime cancer risk of 1 in 

10,000 to 1 in 10,000,000. Use the LSE tables and figures for a quick review of the health effects and to 

locate data for a specific exposure scenario. The LSE tables and figures should always be used in 

conjunction with the text. All entries in these tables and figures represent studies that provide reliable, 

quantitative estimates of NOAELs, LOAELs, or Cancer Effect Levels (CELs). 

The legends presented below demonstrate the application of these tables and figures. Representative 

examples of LSE Table 3-1 and Figure 3-1 are shown. The numbers in the left column of the legends 

correspond to the numbers in the example table and figure. 

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VANADIUM	 B-3 

APPENDIX B 

LEGEND 

See Sample LSE Table 3-1 (page B-6) 

(1)	 Route of Exposure. One of the first considerations when reviewing the toxicity of a substance 

using these tables and figures should be the relevant and appropriate route of exposure. Typically 

when sufficient data exist, three LSE tables and two LSE figures are presented in the document. 

The three LSE tables present data on the three principal routes of exposure, i.e., inhalation, oral, 

and dermal (LSE Tables 3-1, 3-2, and 3-3, respectively). LSE figures are limited to the inhalation 

(LSE Figure 3-1) and oral (LSE Figure 3-2) routes. Not all substances will have data on each 

route of exposure and will not, therefore, have all five of the tables and figures. 

(2)	 Exposure Period. Three exposure periods—acute (less than 15 days), intermediate (15– 

364 days), and chronic (365 days or more)—are presented within each relevant route of exposure. 

In this example, an inhalation study of intermediate exposure duration is reported. For quick 

reference to health effects occurring from a known length of exposure, locate the applicable 

exposure period within the LSE table and figure. 

(3)	 Health Effect. The major categories of health effects included in LSE tables and figures are 

death, systemic, immunological, neurological, developmental, reproductive, and cancer. 

NOAELs and LOAELs can be reported in the tables and figures for all effects but cancer. 

Systemic effects are further defined in the "System" column of the LSE table (see key number 

18). 

(4)	 Key to Figure. Each key number in the LSE table links study information to one or more data 

points using the same key number in the corresponding LSE figure. In this example, the study 

represented by key number 18 has been used to derive a NOAEL and a Less Serious LOAEL 

(also see the two "18r" data points in sample Figure 3-1). 

(5)	 Species. The test species, whether animal or human, are identified in this column. Chapter 2, 

"Relevance to Public Health," covers the relevance of animal data to human toxicity and 

Section 3.4, "Toxicokinetics," contains any available information on comparative toxicokinetics. 

Although NOAELs and LOAELs are species specific, the levels are extrapolated to equivalent 

human doses to derive an MRL. 

(6)	 Exposure Frequency/Duration. The duration of the study and the weekly and daily exposure 

regimens are provided in this column. This permits comparison of NOAELs and LOAELs from 

different studies. In this case (key number 18), rats were exposed to “Chemical x” via inhalation 

for 6 hours/day, 5 days/week, for 13 weeks. For a more complete review of the dosing regimen, 

refer to the appropriate sections of the text or the original reference paper (i.e., Nitschke et al. 

1981). 

(7)	 System. This column further defines the systemic effects. These systems include respiratory, 

cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, and 

dermal/ocular. "Other" refers to any systemic effect (e.g., a decrease in body weight) not covered 

in these systems. In the example of key number 18, one systemic effect (respiratory) was 

investigated. 

(8)	 NOAEL. A NOAEL is the highest exposure level at which no harmful effects were seen in the 

organ system studied. Key number 18 reports a NOAEL of 3 ppm for the respiratory system, 

which was used to derive an intermediate exposure, inhalation MRL of 0.005 ppm (see 

footnote "b"). 

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VANADIUM	 B-4 

APPENDIX B 

(9)	 LOAEL. A LOAEL is the lowest dose used in the study that caused a harmful health effect. 

LOAELs have been classified into "Less Serious" and "Serious" effects. These distinctions help 

readers identify the levels of exposure at which adverse health effects first appear and the 

gradation of effects with increasing dose. A brief description of the specific end point used to 

quantify the adverse effect accompanies the LOAEL. The respiratory effect reported in key 

number 18 (hyperplasia) is a Less Serious LOAEL of 10 ppm. MRLs are not derived from 

Serious LOAELs. 

(10)	 Reference. The complete reference citation is given in Chapter 9 of the profile. 

(11)	 CEL. A CEL is the lowest exposure level associated with the onset of carcinogenesis in 

experimental or epidemiologic studies. CELs are always considered serious effects. The LSE 

tables and figures do not contain NOAELs for cancer, but the text may report doses not causing 

measurable cancer increases. 

(12)	 Footnotes. Explanations of abbreviations or reference notes for data in the LSE tables are found 

in the footnotes. Footnote "b" indicates that the NOAEL of 3 ppm in key number 18 was used to 

derive an MRL of 0.005 ppm. 

LEGEND 

See Sample Figure 3-1 (page B-7) 

LSE figures graphically illustrate the data presented in the corresponding LSE tables. Figures help the 

reader quickly compare health effects according to exposure concentrations for particular exposure 

periods. 

(13)	 Exposure Period. The same exposure periods appear as in the LSE table. In this example, health 

effects observed within the acute and intermediate exposure periods are illustrated. 

(14)	 Health Effect. These are the categories of health effects for which reliable quantitative data 

exists. The same health effects appear in the LSE table. 

(15)	 Levels of Exposure. Concentrations or doses for each health effect in the LSE tables are 

graphically displayed in the LSE figures. Exposure concentration or dose is measured on the log 

scale "y" axis. Inhalation exposure is reported in mg/m3 or ppm and oral exposure is reported in 

mg/kg/day. 

(16)	 NOAEL. In this example, the open circle designated 18r identifies a NOAEL critical end point in 

the rat upon which an intermediate inhalation exposure MRL is based. The key number 18 

corresponds to the entry in the LSE table. The dashed descending arrow indicates the 

extrapolation from the exposure level of 3 ppm (see entry 18 in the table) to the MRL of 

0.005 ppm (see footnote "b" in the LSE table). 

(17)	 CEL. Key number 38m is one of three studies for which CELs were derived. The diamond 

symbol refers to a CEL for the test species-mouse. The number 38 corresponds to the entry in the 

LSE table. 

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VANADIUM	 B-5 

APPENDIX B 

(18)	 Estimated Upper-Bound Human Cancer Risk Levels. This is the range associated with the upperbound for lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. These risk levels are derived 

from the EPA's Human Health Assessment Group's upper-bound estimates of the slope of the 

cancer dose response curve at low dose levels (q1*). 

(19)	 Key to LSE Figure. The Key explains the abbreviations and symbols used in the figure. 

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1 2 3 4 

→

SAMPLE 

Table 3-1. Levels of Significant Exposure to [Chemical x] – Inhalation 

→→

Exposure 

Key to frequency/ figurea Species duration 

INTERMEDIATE EXPOSURE 

5 6 

Systemic ↓ ↓

NOAEL 

System (ppm) 

7 8 ↓ ↓

LOAEL (effect) Less serious (ppm) 

9 

↓

Serious (ppm) 

Re

10 

↓

→→

18 Rat 13 wk Resp 3b 10 (hyperplasia) 

5 d/wk Nit6 hr/d 

CHRONIC EXPOSURE 

Cancer 11 

↓

38 Rat 18 mo 20 (CEL, multiple Wo

5 d/wk organs) 7 hr/d 

39 Rat 89–104 wk 10 (CEL, lung tumors, NT

5 d/wk nasal tumors) 6 hr/d 

40 Mouse 79–103 wk 10 (CEL, lung tumors, NT

5 d/wk hemangiosarcomas) 6 hr/d 

a The number corresponds to entries in Figure 3-1. b Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5x10-3 ppm; dose adjusted for intermittent ex

by an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability). 

12 
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VANADIUM B-8 

APPENDIX B 

This page is intentionally blank. 

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VANADIUM 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 

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VANADIUM C-2 

APPENDIX C 

DOT 

DOT/UN/ 

NA/IMDG 

DWEL 

ECD 

ECG/EKG 

EEG 

EEGL 

EPA 

F 

F1 

FAO 

FDA 

FEMA 

FIFRA 

FPD 

fpm 

FR 

FSH 

g 

GC 

gd 

GLC 

GPC 

HPLC 

HRGC 

HSDB 

IARC 

IDLH 

ILO 

IRIS 

Kd 

kg 

kkg 

Koc 

Kow 

L 

LC 

LC50 

LCLo 

LD50 

LDLo 

LDH 

LH 

LOAEL 

LSE 

LT50 

m 

MA 

MAL 

mCi 

Department of Transportation 

Department of Transportation/United Nations/ 

North America/Intergovernmental Maritime Dangerous Goods Code 

drinking water exposure level 

electron capture detection 

electrocardiogram 

electroencephalogram 

Emergency Exposure Guidance Level 

Environmental Protection Agency 

Fahrenheit 

first-filial generation 

Food and Agricultural Organization of the United Nations 

Food and Drug Administration 

Federal Emergency Management Agency 

Federal Insecticide, Fungicide, and Rodenticide Act 

flame photometric detection 

feet per minute 

Federal Register 

follicle stimulating hormone 

gram 

gas chromatography 

gestational day 

gas liquid chromatography 

gel permeation chromatography 

high-performance liquid chromatography 

high resolution gas chromatography 

Hazardous Substance Data Bank 

International Agency for Research on Cancer 

immediately dangerous to life and health 

International Labor Organization 

Integrated Risk Information System 

adsorption ratio 

kilogram 

metric ton 

organic carbon partition coefficient 

octanol-water partition coefficient 

liter 

liquid chromatography 

lethal concentration, 50% kill 

lethal concentration, low 

lethal dose, 50% kill 

lethal dose, low 

lactic dehydrogenase 

luteinizing hormone 

lowest-observed-adverse-effect level 

Levels of Significant Exposure 

lethal time, 50% kill 

meter 

trans,trans-muconic acid 

maximum allowable level 

millicurie 

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VANADIUM 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 

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VANADIUM 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 

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VANADIUM C-5 

APPENDIX C 

> greater than 

≥ greater than or equal to 

= equal to 

< less than 

≤ less than or equal to 

% percent 

α alpha 

β beta 

γ gamma 

δ delta 

μm micrometer 

μg microgram 

q1

* cancer slope factor 

– negative 

+ positive 

(+) weakly positive result 

(–) weakly negative result 

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VANADIUM C-6 

APPENDIX C 

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VANADIUM D-1 

APPENDIX D. INDEX
 

absorbed dose ........................................................................................................................................................74, 86
 

adsorbed.............................................................................................................................................................125, 126
 

adsorption ..................................................................................................................................................124, 125, 126
 

alanine aminotransferase (see ALT)............................................................................................................................39
 

ALT (see alanine aminotransferase)................................................................................................................39, 40, 61
 

ambient air.....................................................................................................................................4, 129, 130, 144, 147
 

aspartate aminotransferase (see AST)..........................................................................................................................39
 

AST (see aspartate aminotransferase)....................................................................................................................39, 61
 

bioavailability ..............................................................................................................................................................85
 

bioconcentration ........................................................................................................................................................126
 

biomarker.........................................................................................................................................85, 86, 97, 149, 157
 

body weight effects................................................................................................................................................41, 62
 

breast milk ...................................................................................................................................................85, 142, 143
 

cancer.................................................................................................................................5, 11, 13, 25, 65, 68, 84, 161
 

carcinogen............................................................................................................................................................87, 163
 

carcinogenic...................................................................................................................................5, 13, 25, 42, 66, 163
 

carcinogenicity ..........................................................................................................................................13, 42, 66, 94
 

carcinoma ............................................................................................................................................13, 16, 42, 43, 94
 

cardiovascular..................................................................................................................................................38, 60, 94
 

cardiovascular effects ......................................................................................................................................38, 59, 94
 

chromosomal aberrations.................................................................................................................................66, 68, 71
 

clearance ..............................................................................................................................................40, 72, 74, 77, 81
 

death ......................................................................................................................................25, 26, 44, 61, 85, 90, 126
 

deoxyribonucleic acid (see DNA)................................................................................................................................66
 

dermal effects ..............................................................................................................................................................40
 

developmental effects .................................................................................................. 13, 20, 42, 65, 66, 85, 92, 95, 98
 

diabetes.................................................................................................................... 5, 11, 20, 25, 60, 92, 113, 136, 141
 

DNA (see deoxyribonucleic acid) ............................................................................... 66, 67, 68, 69, 70, 71, 86, 87, 95
 

elimination half-time .............................................................................................................................................75, 78
 

elimination rate............................................................................................................................................................85
 

endocrine ...............................................................................................................................................................82, 83
 

fetus .............................................................................................................................................................................83
 

gastrointestinal effects ...............................................................................................................................20, 39, 60, 92
 

general population .............................................................................................................4, 11, 12, 117, 141, 147, 148
 

genotoxic ...............................................................................................................................................................25, 71
 

genotoxicity .....................................................................................................................................................66, 71, 95
 

groundwater .......................................................................................................................................................123, 132
 

half-life ................................................................................................................................................................86, 151
 

hematological effects.................................................................................................................................23, 39, 60, 92
 

hepatic effects........................................................................................................................................................39, 61
 

immunological.....................................................................................................................................25, 41, 64, 90, 96
 

immunological effects .................................................................................................................................................64
 

Kow .....................................................................................................................................................................104, 105
 

LD50 .............................................................................................................................................................................44
 

metabolic effects..........................................................................................................................................................63
 

micronuclei ............................................................................................................................................................66, 71
 

milk............................................................................................................ 11, 73, 77, 88, 136, 138, 139, 141, 143, 146
 

musculoskeletal effects................................................................................................................................................39
 

neurobehavioral ...................................................................................................................................21, 83, 89, 93, 96
 

neurological effects......................................................................................................................................5, 41, 64, 66
 

nuclear .......................................................................................................................................................................151
 

ocular effects .........................................................................................................................................................40, 44
 

pharmacodynamic........................................................................................................................................................78
 

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VANADIUM D-2 

APPENDIX D 

pharmacokinetic.........................................................................................................................................78, 79, 80, 84
 

renal effects ...........................................................................................................................................................40, 62
 

reproductive effects .............................................................................................................................41, 64, 66, 92, 95
 

respiratory effects................................................................................................................................12, 27, 44, 93, 96
 

retention...........................................................................................................................................................74, 75, 85
 

solubility..............................................................................................................................................................73, 146
 

systemic effects ...............................................................................................................................................27, 44, 66
 

toxicokinetic ........................................................................................................................................11, 25, 82, 98, 99
 

tremors...................................................................................................................................................................41, 96
 

tumors........................................................................................................................................................42, 44, 87, 94
 

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